bluuebunny/crossref_metadata_2025 huggingface dataset:
Natural and Designed Toxins for Precise Therapy: Modern Approaches in Experimental Oncology
Authors: Shilova Olga , Shramova Elena , Proshkina Galina , Deyev Sergey
Published: May 2021

Cancer cells frequently overexpress specific surface receptors providing tumor growth and survival which can be used for precise therapy. Targeting cancer cell receptors with protein toxins is an attractive approach widely used in contemporary experimental oncology and preclinical studies. Methods of targeted delivery of toxins to cancer cells, different drug carriers based on nanosized materials (liposomes, nanoparticles, polymers), the most promising designed light-activated toxins, as well as mechanisms of the cytotoxic action of the main natural toxins used in modern experimental oncology, are discussed in this review. The prospects of the combined therapy of tumors based on multimodal nanostructures are also discussed.
The Relevance of Amyloid β-Calmodulin Complexation in Neurons and Brain Degeneration in Alzheimer’s Disease
Authors: Poejo Joana , Salazar Jairo , Mata Ana M. , Gutierrez-Merino Carlos
Published: May 2021

Intraneuronal amyloid β (Aβ) oligomer accumulation precedes the appearance of amyloid plaques or neurofibrillary tangles and is neurotoxic. In Alzheimer’s disease (AD)-affected brains, intraneuronal Aβ oligomers can derive from Aβ peptide production within the neuron and, also, from vicinal neurons or reactive glial cells. Calcium homeostasis dysregulation and neuronal excitability alterations are widely accepted to play a key role in Aβ neurotoxicity in AD. However, the identification of primary Aβ-target proteins, in which functional impairment initiating cytosolic calcium homeostasis dysregulation and the critical point of no return are still pending issues. The micromolar concentration of calmodulin (CaM) in neurons and its high affinity for neurotoxic Aβ peptides (dissociation constant ≈ 1 nM) highlight a novel function of CaM, i.e., the buffering of free Aβ concentrations in the low nanomolar range. In turn, the concentration of Aβ-CaM complexes within neurons will increase as a function of time after the induction of Aβ production, and free Aβ will rise sharply when accumulated Aβ exceeds all available CaM. Thus, Aβ-CaM complexation could also play a major role in neuronal calcium signaling mediated by calmodulin-binding proteins by Aβ; a point that has been overlooked until now. In this review, we address the implications of Aβ-CaM complexation in the formation of neurotoxic Aβ oligomers, in the alteration of intracellular calcium homeostasis induced by Aβ, and of dysregulation of the calcium-dependent neuronal activity and excitability induced by Aβ.
The Effect of Non-Thermal Plasma on the Structural and Functional Characteristics of Human Spermatozoa
Authors: Tvrdá Eva , Lovíšek Daniel , Kyzek Stanislav , Kováčik Dušan , Gálová Eliška
Published: May 2021

Significant antibacterial properties of non-thermal plasma (NTP) have converted this technology into a promising alternative to the widespread use of antibiotics in assisted reproduction. As substantial data available on the specific in vitro effects of NTP on male reproductive cells are currently missing, this study was designed to investigate selected quality parameters of human spermatozoa (n = 51) exposed to diffuse coplanar surface barrier discharge NTP for 0 s, 15 s, 30 s, 60 s and 90 s. Sperm motility characteristics, membrane integrity, mitochondrial activity, production of reactive oxygen species (ROS), DNA fragmentation and lipid peroxidation (LPO) were investigated immediately following exposure to NTP and 2 h post-NTP treatment. Exposure to NTP with a power input of 40 W for 15 s or 30 s was found to have no negative effects on the sperm structure or function. However, a prolonged NTP treatment impaired all the sperm quality markers in a time- and dose-dependent manner. The most likely mechanism of action of high NTP doses may be connected to ROS overproduction, leading to plasma membrane destabilization, LPO, mitochondrial failure and a subsequent loss of motility as well as DNA integrity. As such, our findings indicate that appropriate plasma exposure conditions need to be carefully selected in order to preserve the sperm vitality, should NTP be used in the practical management of bacteriospermia in the future.
Scaling up Metal Hydrides for Real-Scale Applications: Achievements, Challenges and Outlook
Authors: Jensen Emil H. , Dornheim Martin , Sartori Sabrina
Published: May 2021

As the world evolves, so does the energy demand. The storage of hydrogen using metal hydrides shows great promise due to the ability to store and deliver energy on demand while achieving higher volumetric density and safer storage conditions compared with traditional storage options such as compressed gas or liquid hydrogen. Research is typically performed on lab-sized samples and tanks and shows great potential for large scale applications. However, the effects of scale-up on the metal hydride’s performance are relatively less investigated. Studies performed so far on both materials, and hydride-based storage tanks show that the scale-up can significantly impact the system’s capacity, kinetics, and sorption properties. The findings presented in this review suggest areas of further investigation in order to implement metal hydrides in real scale applications.
Computed Tomographic Changes in Patients with Cystic Fibrosis Treated by Combination Therapy with Lumacaftor and Ivacaftor
Authors: Arnaud François , Stremler-Le Bel Nathalie , Reynaud-Gaubert Martine , Mancini Julien , Gaubert Jean-Yves , Gorincour Guillaume
Published: May 2021

Background: As Cystic Fibrosis (CF) treatments drastically improved in recent years, tools to assess their efficiency need to be properly evaluated, especially cross-sectional imaging techniques. High-resolution computed tomography (HRCT) scan response to combined lumacaftor- ivacaftor therapy (Orkambi®) in patients with homozygous for F508del CFTR has not yet been assessed. Methods: We conducted a retrospective observational study in two French reference centers in CF in Marseille hospitals, including teenagers (>12 years old) and adults (>18 years) who had received lumacaftor–ivacaftor and for whom we had at disposal at least two CT scans, one at before therapy and one at least six months after therapy start. CT scoring was performed by using the modified version of the Brody score. Results: 34 patients have been included. The mean age was 26 years (12–56 years). There was a significant decrease in the total CT score (65.5 to 60.3, p = 0.049) and mucous plugging subscore (12.3 to 8.7, p = 0.009). Peribronchial wall thickening (PWT) was significantly improved only in the adult group (29.1 to 27.0, p = 0.04). Improvements in total score, peribronchial thickening, and mucous pluggings were significantly correlated with improvement in FEV1 (forced expiratory volume in 1 s). Conclusions: Treatment with lumacaftor–ivacaftor was associated with a significant improvement in the total CT score, which was mainly related to an improvement in mucous pluggings.
Exosomes Derived from Non-Classic Sources for Treatment of Post-Traumatic Osteoarthritis and Cartilage Injury of the Knee: In Vivo Review
Authors: Li Dan , Gupta Puneet , Sgaglione Nicholas A. , Grande Daniel A.
Published: May 2021

Osteoarthritis of the knee is one of the most common chronic, debilitating musculoskeletal conditions. Current conservative treatment modalities such as weight loss, non-steroidal anti-inflammatory drugs, and intra-articular steroid injections often only provide temporary pain relief and are unsatisfactory for long-term management. Though end stage osteoarthritis of the knee can be managed with total knee arthroplasty (TKA), finding alternative non-surgical options to delay or prevent the need for TKA are needed due to the increased healthcare costs and expenditures associated with TKA. Exosomes have been of particular interest given recent findings highlighting that stem cells may at least partially mediate some of their effects through the release of extracellular vesicles, such as exosomes. As such, better understanding the biological mechanisms and potential therapeutic effects of these exosomes is necessary. Here, we review in vivo studies that highlight the potential clinical use of exosomes derived from non-classical sources (not bone marrow or adipose derived MSCs derived MSCs) for osteoarthritis of the knee.
Physical Laws Shape Up HOX Gene Collinearity
Authors: Papageorgiou Spyros
Published: May 2021

Hox gene collinearity (HGC) is a multi-scalar property of many animal phyla particularly important in embryogenesis. It relates entities and events occurring in Hox clusters inside the chromosome DNA and in embryonic tissues. These two entities differ in linear size by more than four orders of magnitude. HGC is observed as spatial collinearity (SC), where the Hox genes are located in the order (Hox1, Hox2, Hox3 …) along the 3′ to 5′ direction of DNA in the genome and a corresponding sequence of ontogenetic units (E1, E2, E3, …) located along the Anterior—Posterior axis of the embryo. Expression of Hox1 occurs in E1, Hox2 in E2, Hox3 in E3, etc. Besides SC, a temporal collinearity (TC) has been also observed in many vertebrates. According to TC, first Hox1 is expressed in E1; later, Hox2 is expressed in E2, followed by Hox3 in E3, etc. Lately, doubt has been raised about whether TC really exists. A biophysical model (BM) was formulated and tested during the last 20 years. According to BM, physical forces are created which pull the Hox genes one after the other, driving them to a transcription factory domain where they are transcribed. The existing experimental data support this BM description. Symmetry is a physical–mathematical property of matter that was explored in depth by Noether who formulated a ground-breaking theory (NT) that applies to all sizes of matter. NT may be applied to biology in order to explain the origin of HGC in animals developing not only along the A/P axis, but also to animals with circular symmetry.
Identification of the Ricin-B-Lectin LdRBLk in the Colorado Potato Beetle and an Analysis of Its Expression in Response to Fungal Infections
Authors: Rotskaya Ulyana N. , Kryukov Vadim Yu. , Kosman Elena , Tyurin Maksim , Glupov Viktor V.
Published: May 2021

Ricin-B-lectins (RBLs) have been identified in many groups of organisms, including coleopterans insects, particularly the Colorado potato beetle Leptinotarsa decemlineata (LdRBLs). We hypothesized that one of these LdRBLs (LdRBLk) may be involved in the immune response to fungal infections. We performed a theoretical analysis of the structure of this protein. Additionally, the expression levels of the LdRBlk gene were measured in L. decemlineata in response to infections with the fungi Metarhizium robertsii and Beauveria bassiana. The expression levels of LdRBlk in the L. decemlineata cuticle and fat body were increased in response to both infections. The induction of LdRBlk expression was dependent on the susceptibility of larvae to the fungi. Upregulation of the LdRBlk gene was also observed in response to other stresses, particularly thermal burns. Elevation of LdRBlk expression was frequently observed to be correlated with the expression of the antimicrobial peptide attacin but was not correlated with hsp90 regulation. Commercially available β-lectin of ricin from Ricinuscommunis was observed to inhibit the germination of conidia of the fungi. We suggest that LdRBLk is involved in antifungal immune responses in the Colorado potato beetle, either exerting fungicidal properties directly or acting as a modulator of the immune response.
The Consequences of Our Changing Environment on Life Threatening and Debilitating Fungal Diseases in Humans
Authors: van Rhijn Norman , Bromley Michael
Published: May 2021

Human activities have significantly impacted the environment and are changing our climate in ways that will have major consequences for ourselves, and endanger animal, plant and microbial life on Earth. Rising global temperatures and pollution have been highlighted as potential drivers for increases in infectious diseases. Although infrequently highlighted, fungi are amongst the leading causes of infectious disease mortality, resulting in more than 1.5 million deaths every year. In this review we evaluate the evidence linking anthropomorphic impacts with changing epidemiology of fungal disease. We highlight how the geographic footprint of endemic mycosis has expanded, how populations susceptible to fungal infection and fungal allergy may increase and how climate change may select for pathogenic traits and indirectly contribute to the emergence of drug resistance.
The Equitable Implementation of Cystic Fibrosis Personalized Medicines in Canada
Authors: Shemie Genevieve , Nguyen Minh Thu , Wallenburg John , Ratjen Felix , Knoppers Bartha Maria
Published: May 2021

This article identifies the potential sources of inequity in three stages of integrating cystic fibrosis personalized medicines into the Canadian healthcare system and proposes mitigating strategies: (1) clinical research and diagnostic testing; (2) regulatory oversight and market authorization; and (3) implementation into the healthcare system. There is concern that differential access will cast a dark shadow over personalized medicine by stratifying the care that groups of patients will receive—not only based on their genetic profiles, but also on the basis of their socioeconomic status. Furthermore, there is a need to re-evaluate regulatory and market approval mechanisms to accommodate the unique nature of personalized medicines. Physical and financial accessibility ought to be remedied before personalized medicines can be equitably delivered to patients. This article identifies the socio–ethical and legal challenges at each stage and recommends mitigating policy solutions.
Insights into Public Visual Behaviors through Eye-Tracking Tests: A Study Based on National Park System Pilot Area Landscapes
Authors: Wang Peng , Yang Wenjuan , Wang Dengju , He Youjun
Published: May 2021

National parks are important natural reserves of high ecological value, and the visual perception of national park landscapes is closely tied to the degree of protection that the natural resources within national parks receive. Visual cognition has a direct impact on public consciousness and plays an increasingly important role in national park management. Most techniques and methods previously used to study visual behaviors are subjective and qualitative; objective and quantitative studies are rare. Here, we used the eye-tracking method to study the visual behaviors of individuals viewing landscapes within the Qianjiangyuan National Park System Pilot Area to assess the visual and psychological mechanisms underlying public perception of different landscapes. The effect of landscape type on visual behaviors was greater than that of color diversity and degree of spatial confinement and was mainly related to the characteristics of landscape elements. The public preferred recreational and forest landscapes with high ornamental value, whereas rural and wetland landscapes tended to be neglected given that perception of these landscapes required additional information to facilitate interpretation. When landscape colors were uniform and landscape spaces were more confined, the fixation duration was longer, and instant attractiveness was stronger. The effects of subject background on behavioral preferences were examined. Females were more interested in the whole landscape, whereas males focused more on the parts of the landscapes with prominent humanistic architectural features, complex colors, and open space. Art students generally preferred landscapes with strong humanistic attributes, whereas students majoring in forestry preferred landscapes with strong natural attributes.
Exploring Phonological Aspects of Australian Indigenous Sign Languages
Authors: Jorgensen Eleanor , Green Jennifer , Bauer Anastasia
Published: May 2021

Spoken languages make up only one aspect of the communicative landscape of Indigenous Australia—sign languages are also an important part of their rich and diverse language ecologies. Australian Indigenous sign languages are predominantly used by hearing people as a replacement for speech in certain cultural contexts. Deaf or hard-of-hearing people are also known to make use of these sign languages. In some circumstances, sign may be used alongside speech, and in others it may replace speech altogether. Alternate sign languages such as those found in Australia occupy a particular place in the diversity of the world’s sign languages. However, the focus of research on sign language phonology has almost exclusively been on sign languages used in deaf communities. This paper takes steps towards deepening understandings of signed language phonology by examining the articulatory features of handshape and body locations in the signing practices of three communities in Central and Northern Australia. We demonstrate that, while Australian Indigenous sign languages have some typologically unusual features, they exhibit the same ‘fundamental’ structural characteristics as other sign languages.
An Analytical Approach for Facility Location for Truck Platooning—A Case Study of an Unmanned Following Truck Platooning System in Japan
Authors: Watanabe Daisuke , Kenmochi Takeshi , Sasa Keiju
Published: May 2021

Truck platooning involves a small convoy of freight vehicles using electronic coupling as an application in automated driving technology, and it is expected to represent a major solution for improving efficiency in truck transportation in the near future. Recently, there have been several trials regarding truck platooning with major truck manufacturers and logistics companies on public roads in the United States, European countries and Japan. There is a need to locate a facility for the formation of truck platooning to realize the unmanned operation of trucks following in a platoon. In this study, we introduce the current status of truck platooning in Japan and present the optimal location model for truck platooning using the continuous approximation model with a numerical experiment, considering the case in Japan. We derived the optimal locational strategy for the combination of the long-haul ratio and the cost factor of platooning. With parameters estimated for several scenarios for the deployment of truck platooning in Japan, the numerical results show that the optimal locational strategy for a platoon of manned vehicles and a platoon with unmanned following vehicles is the edge of the local region, and that for a platoon of fully automated vehicles is the center of the region.
Tribocorrosion Influenced Pitting of a Duplex Stainless Steel
Authors: Renner Peter , Chen Yan , Huang Zhihao , Raut Ajinkya , Liang Hong
Published: May 2021

Due to its accelerated, uncontrollable, and unpredictable nature, pitting is one of the most common failure modes in pipelines used for oil and gas exploration. A comprehensive understanding of the mechanisms of pitting under conditions involving both abrasion and corrosion is currently lacking. This research investigated the effects of mechanical rubbing on the development of pitting of a widely used Type 2205 duplex stainless steel. Tribocorrosion experiments were conducted under mildly abrasive conditions where there is pitting but no significant material loss. Results showed that passivation was accelerated by rubbing, even though pitting was simultaneously formed. The length-to-width aspect ratio of the pits increased exponentially when the normal load during corrosive wear tests was increased. This phenomenon could lead to catastrophic failure in industrial applications such as underground and deep ocean pipes in the oil and gas industry.
Exploring the Effect of Status Quo, Innovativeness, and Involvement Tendencies on Luxury Fashion Innovations: The Mediation Role of Status Consumption
Authors: Puiu Andreea-Ionela , Ardeleanu Anca Monica , Cojocaru Camelia , Bratu Anca
Published: May 2021

The article explores the mechanisms that affect consumers’ interest in luxury clothing innovations. The actual research aims to investigate the effect of status quo and clothing involvement on consumer brand loyalty. More, it was intended to quantify the influence of the level of engagement concerning clothing acquisition and the status quo tendency on the consumers’ level of interest toward innovative luxury fashion products. The models were analyzed through the partial-least square-path modeling method. The results revealed that status quo bias and consumers’ involvement in fashion influence their loyalty to brands and level of innovativeness. The novelty of the present research comes from the analysis of the impact of the status quo manifest variables on consumers’ innovative tendencies. Moreover, it was found that status consumption fully mediates the relationships among the investigated predictors and considered outcome variables. The mediator manifests the highest effect size of all investigated predictors. The actual paper advances research in a direction that was not sufficiently addressed in the past, introducing the status quo construct as the main predictor of peoples’ inclination to be loyal to a brand or to manifest a tendency toward innovativeness. Moreover, the article emphasizes the essential role manifested by social status in foreseeing a behavioral response.
Current Status of Amino Acid-Based Permeation Enhancers in Transdermal Drug Delivery
Authors: Pereira Rui , Silva Sandra G. , Pinheiro Marina , Reis Salette , Vale M. Luísa do
Published: May 2021

Transdermal drug delivery (TDD) presents many advantages compared to other conventional routes of drug administration, yet its full potential has not been achieved. The administration of drugs through the skin is hampered by the natural barrier properties of the skin, which results in poor permeation of most drugs. Several methods have been developed to overcome this limitation. One of the approaches to increase drug permeation and thus to enable TDD for a wider range of drugs consists in the use of chemical permeation enhancers (CPEs), compounds that interact with skin to ultimately increase drug flux. Amino acid derivatives show great potential as permeation enhancers, as they exhibit high biodegradability and low toxicity. Here we present an overview of amino acid derivatives investigated so far as CPEs for the delivery of hydrophilic and lipophilic drugs across the skin, focusing on the structural features which promote their enhancement capacity.
Hot Deformation Constitutive Equation and Plastic Instability of 30Cr4MoNiV Ultra-High-Strength Steel
Authors: Chen Gang , Yao Yuanchao , Jia Yuzhen , Su Bin , Liu Guoyue , Zeng Bin
Published: May 2021

In this work, the hot deformation behavior of 30Cr4MoNiV ultra-high-strength steel is investigated by isothermal compression tests using the Gleeble-3500 thermal simulation machine (Dynamic Systems Inc., New York, NY, USA) at a temperature range of 1173–1373 K under the strain rate of 0.01–10 s−1. A constitutive equation with strain-dependent constants and processing maps suitable for 30Cr4MoNiV ultra-high-strength steel are established. The results show that the combination of the hyperbolic sine function and the Zener-Hollomon parameter can accurately represent the influences of deformation temperature, strain rate, and strain on the flow stress of the 30Cr4MoNiV ultra-high-strength steel. The applicability of plastic instability criteria such as m, m˙, S, S˙ and the instability parameter ξ are analyzed, the stability and instability regions are clarified accurately, and the optimized processing regions are given in the stability regions. The optimized regions are verified by the uniform equiaxed grains, and the plastic instability is validated by dynamic strain aging and the microstructure of the voids.
Recent Advances and Future Perspectives on Microfluidic Mix-and-Jet Sample Delivery Devices
Authors: Hejazian Majid , Balaur Eugeniu , Abbey Brian
Published: May 2021

The integration of the Gas Dynamic Virtual Nozzle (GDVN) and microfluidic technologies has proven to be a promising sample delivery solution for biomolecular imaging studies and has the potential to be transformative for a range of applications in physics, biology, and chemistry. Here, we review the recent advances in the emerging field of microfluidic mix-and-jet sample delivery devices for the study of biomolecular reaction dynamics. First, we introduce the key parameters and dimensionless numbers involved in their design and characterisation. Then we critically review the techniques used to fabricate these integrated devices and discuss their advantages and disadvantages. We then summarise the most common experimental methods used for the characterisation of both the mixing and jetting components. Finally, we discuss future perspectives on the emerging field of microfluidic mix-and-jet sample delivery devices. In summary, this review aims to introduce this exciting new topic to the wider microfluidics community and to help guide future research in the field.
Editorial for the Special Issue on Analysis, Design and Fabrication of Micromixers
Authors: Kim Kwang-Yong
Published: May 2021

During the last couple of decades, there have been rapid developments in analysis, design, and fabrication of micromixers [...]
Effect of Co-Inoculation of Bacillus sp. Strain with Bacterial Endophytes on Plant Growth and Colonization in Tomato Plant (Solanum lycopersicum)
Authors: Salehin Ahsanul , Puri Ramesh Raj , Hafiz Md Hafizur Rahman , Itoh Kazuhito
Published: May 2021

Colonization of a biofertilizer Bacillus sp. OYK strain, which was isolated from a soil, was compared with three rhizospheric and endophytic Bacillus sp. strains to evaluate the colonization potential of the Bacillus sp. strains with a different origin. Surface-sterilized seeds of tomato (Solanum lycopersicum L. cv. Chika) were sown in the sterilized vermiculite, and four Bacillus sp. strains were each inoculated onto the seed zone. After cultivation in a phytotron, plant growth parameters and populations of the inoculants in the root, shoot, and rhizosphere were determined. In addition, effects of co-inoculation and time interval inoculation of Bacillus sp. F-33 with the other endophytes were examined. All Bacillus sp. strains promoted plant growth except for Bacillus sp. RF-37, and populations of the rhizospheric and endophytic Bacillus sp. strains were 1.4–2.8 orders higher in the tomato plant than that of Bacillus sp. OYK. The plant growth promotion by Bacillus sp. F-33 was reduced by co-inoculation with the other endophytic strains: Klebsiella sp. Sal 1, Enterobacter sp. Sal 3, and Herbaspirillum sp. Sal 6., though the population of Bacillus sp. F-33 maintained or slightly decreased. When Klebsiella sp. Sal 1 was inoculated after Bacillus sp. F-33, the plant growth-promoting effects by Bacillus sp. F-33 were reduced without a reduction of its population, while when Bacillus sp. F-33 was inoculated after Klebsiella sp. Sal 1, the effects were increased in spite of the reduction of its population. Klebsiella sp. Sal 1 colonized dominantly under both conditions. The higher population of rhizospheric and endophytic Bacillus sp. in the plant suggests the importance of the origin of the strains for their colonization. The plant growth promotion and colonization potentials were independently affected by the co-existing microorganisms.
Occurrence and Release of Trace Elements in Pyrite-Rich Waste Rock
Authors: Nyström Elsa , Thomas Helen , Wanhainen Christina , Alakangas Lena
Published: May 2021

Waste rock can contain high concentrations of deleterious trace elements, which upon oxidation can be released, having a significant impact on water quality. Therefore, knowledge about their occurrence and overall mobility is crucial to ensure suitable environmental protection measures. Sulfide-rich waste rock was characterized and quantified using automated mineralogy (QEMSCAN). Selected pyrite grains were analyzed for trace element occurrence using LA-ICP-MS before, during, and after leaching the waste rock in 10 L small-scale test cells for two years to assess trace element occurrence and mobility. Sequential extraction was used to estimate elemental sequestration during the experiment. The high abundance of pyrite (66%) and scarcity of buffering minerals resulted in low pH (<1.3) leachate with high concentrations of trace elements such as As (21 mg/L), Cu (20 mg/L), Hg (13 µg/L, Pb (856 µg/L), Sb (967 µg/L), Tl (317 µg/L ), and Zn (23 mg/L) in solution with limited retention in secondary minerals, primarily due to these elements’ association with pyrite either as inclusions or impurities showing an average abundance of 193 ppm As, 15 ppm Cu, 13 ppm Hg, 20 ppm Pb, 24 ppm Sb, 26 ppm Tl, and 74 ppm Zn in the waste rock. The occurrence of Cu and Zn as inclusions associated with the pyrite led to their extensive mobilization of 79% and 72%, respectively, despite their low abundance in the waste rock. Provided the overall leachability of S (11%) and limited formation of secondary minerals, the average oxidation rate suggests depletion of the pyrite within approximately 18 years. In conclusion, this study shows the importance of detailed mineralogical investigations and early preventive measures of waste rock to ensure sustainable mine waste and water management.
Most Important Factors for Deciding Rehabilitation Provision for Severe Stroke Survivors Post Hospital Discharge: A Study Protocol for a Best–Worst Scaling Experiment
Authors: Mohapatra Sushmita , Cheung Kei-Long , Hiligsmann Mickaël , Anokye Nana
Published: May 2021

Efficient decision-making is crucial to ensure adequate rehabilitation with optimal use of healthcare resources. Establishing the factors associated with making decisions concerning rehabilitation provision is important to guide clinical staff towards person-centred decisions for rehabilitation after severe stroke. In this study we conduct a best–worst scaling (BWS) experiment to identify the most important factors and their relative weight of importance for deciding the type of ongoing rehabilitation services a person with severe stroke might receive post hospital discharge. Fractional, efficient designs are applied regarding the survey design. Key multidisciplinary staff regularly involved in making decisions for rehabilitation in a stroke unit will be recruited to participate in an online BWS survey. Hierarchical Bayes estimation will be used as the main analysis method, with the best–worst count analysis as a secondary analysis. The survey is currently being piloted prior to commencing the process of data collection. Results are expected by the end of September 2021. The research will add to the current literature on clinical decision-making in stroke rehabilitation. Findings will quantify the preferences of factors among key multi-disciplinary clinicians working in stroke units in the UK, involved in decision-making concerning rehabilitation after stroke.
Remodeling of the Posterior Cerebral Artery P1-Segment after Pipeline Flow Diverter Treatment of Posterior Communicating Artery Aneurysms
Authors: Litao Miguel S. , Burkhardt Jan-Karl , Tanweer Omar , Raz Eytan , Huang Paul , Becske Tibor , Shapiro Maksim , Riina Howard , Nelson Peter K.
Published: May 2021

Introduction: Flow diverters such as the pipeline embolization device (PED) cause hemodynamic changes of the treated vessel segment. In posterior communicating artery (PcomA), aneurysms’ unique anatomic consideration have to be taken in account due to the connection between the anterior and posterior circulation. We hypothesize that in conjunction with PcomA remodeling, there will also be remodeling of the ipsilateral P1 segment of the posterior cerebral artery (PCA) after PED treatment for PcomA aneurysms. Methods: We retrospectively collected radiological as well as clinical data of PcomA aneurysm patients treated with PED including PcomA and P1 vessel diameters before and after treatment as well as patient and aneurysm characteristics. Results: Overall, 14 PcomA aneurysm patients were included for analysis and PED treatment was performed without complications in all patients. In 10 out of 14 patients (71%), a decrease in PcomA diameter was observed and there was a significant mean decrease of 0.78 mm in PcomA diameter on angiographic last follow-up (LFU) (p = 0.003). In the same patient population (10 out of 14 patients), there was meanwhile a significant mean increase of 0.43 mm in the ipsilateral P1 segment diameter observed (p = 0.015). These vessel remodeling effects were in direct correlation with aneurysm occlusion since all of these patients showed aneurysm occlusion at LFU while 29% showed only partial occlusion without vessel remodeling effects. A decrease in PcomA diameter was directly associated with aneurysm occlusion (p = 0.042). There were no neurologic complications on LFU. Conclusion: In the treatment of PcomA aneurysms with PED, the P1 segment of the PCA increases in diameter while the PcomA diameter decreases. Our results suggest that this remodeling effect is associated with aneurysm occlusion and decrease of PcomA is hemodynamically compensated for by an increase in the ipsilateral P1 diameter.
Insights into Nuclear G-Protein-Coupled Receptors as Therapeutic Targets in Non-Communicable Diseases
Authors: Gonçalves-Monteiro Salomé , Ribeiro-Oliveira Rita , Vieira-Rocha Maria Sofia , Vojtek Martin , Sousa Joana B. , Diniz Carmen
Published: May 2021

G-protein-coupled receptors (GPCRs) comprise a large protein superfamily divided into six classes, rhodopsin-like (A), secretin receptor family (B), metabotropic glutamate (C), fungal mating pheromone receptors (D), cyclic AMP receptors (E) and frizzled (F). Until recently, GPCRs signaling was thought to emanate exclusively from the plasma membrane as a response to extracellular stimuli but several studies have challenged this view demonstrating that GPCRs can be present in intracellular localizations, including in the nuclei. A renewed interest in GPCR receptors’ superfamily emerged and intensive research occurred over recent decades, particularly regarding class A GPCRs, but some class B and C have also been explored. Nuclear GPCRs proved to be functional and capable of triggering identical and/or distinct signaling pathways associated with their counterparts on the cell surface bringing new insights into the relevance of nuclear GPCRs and highlighting the nucleus as an autonomous signaling organelle (triggered by GPCRs). Nuclear GPCRs are involved in physiological (namely cell proliferation, transcription, angiogenesis and survival) and disease processes (cancer, cardiovascular diseases, etc.). In this review we summarize emerging evidence on nuclear GPCRs expression/function (with some nuclear GPCRs evidencing atypical/disruptive signaling pathways) in non-communicable disease, thus, bringing nuclear GPCRs as targets to the forefront of debate.
Quantification and Classification of Diclofenac Sodium Content in Dispersed Commercially Available Tablets by Attenuated Total Reflection Infrared Spectroscopy and Multivariate Data Analysis
Authors: Siozou Eirini , Sakkas Vasilios , Kourkoumelis Nikolaos
Published: May 2021

A new methodology, based on Fourier transform infrared spectroscopy equipped with an attenuated total reflectance accessory (ATR FT-IR), was developed for the determination of diclofenac sodium (DS) in dispersed commercially available tablets using chemometric tools such as partial least squares (PLS) coupled with discriminant analysis (PLS-DA). The results of PLS-DA depicted a perfect classification of the tablets into three different groups based on their DS concentrations, while the developed model with PLS had a sufficiently low root mean square error (RMSE) for the prediction of the samples’ concentration (~5%) and therefore can be practically used for any tablet with an unknown concentration of DS. Comparison with ultraviolet/visible (UV/Vis) spectrophotometry as the reference method revealed no significant difference between the two methods. The proposed methodology exhibited satisfactory results in terms of both accuracy and precision while being rapid, simple and of low cost.
The Chemistry Behind ADCs
Authors: Kostova Vesela , Désos Patrice , Starck Jérôme-Benoît , Kotschy Andras
Published: May 2021

Combining the selective targeting of tumor cells through antigen-directed recognition and potent cell-killing by cytotoxic payloads, antibody-drug conjugates (ADCs) have emerged in recent years as an efficient therapeutic approach for the treatment of various cancers. Besides a number of approved drugs already on the market, there is a formidable follow-up of ADC candidates in clinical development. While selection of the appropriate antibody (A) and drug payload (D) is dictated by the pharmacology of the targeted disease, one has a broader choice of the conjugating linker (C). In the present paper, we review the chemistry of ADCs with a particular emphasis on the medicinal chemistry perspective, focusing on the chemical methods that enable the efficient assembly of the ADC from its three components and the controlled release of the drug payload.
Continuous Twin Screw Granulation: A Review of Recent Progress and Opportunities in Formulation and Equipment Design
Authors: Portier Christoph , Vervaet Chris , Vanhoorne Valérie
Published: May 2021

Continuous twin screw wet granulation is one of the key continuous manufacturing technologies that have gained significant interest in the pharmaceutical industry as well as in academia over the last ten years. Given its considerable advantages compared to wet granulation techniques operated in batch mode such as high shear granulation and fluid bed granulation, several equipment manufacturers have designed their own manufacturing setup. This has led to a steep increase in the research output in this field. However, most studies still focused on a single (often placebo) formulation, hence making it difficult to assess the general validity of the obtained results. Therefore, current review provides an overview of recent progress in the field of continuous twin screw wet granulation, with special focus on the importance of the formulation aspect and raw material properties. It gives practical guidance for novel and more experienced users of this technique and highlights some of the unmet needs that require further research.
Urea as a Cocrystal Former—Study of 3 Urea Based Pharmaceutical Cocrystals
Authors: Leng Fucheng , Robeyns Koen , Leyssens Tom
Published: May 2021

Cocrystallization is commonly used for its ability to improve the physical properties of APIs, such as solubility, bioavailability, compressibility, etc. The pharmaceutical industry is particularly interested in those cocrystals comprising a GRAS former in connection with the target API. In this work, we focus on the potential of urea as a cocrystal former, identifying three novel pharmaceutical cocrystal systems with catechin, 3-hydroxyl-2-naphthoic and ellagic acid. Interestingly, the stability of catechin under high humidity or high temperature environment is improved upon cocrystallization with urea. Moreover, the solubility of ellagic acid is improved about 17 times. This work displays the latent possibility of urea in improving the physical property of drug molecules using a cocrystallization approach.
Polymer Particles Bearing Recombinant LEL CD81 as Trapping Systems for Hepatitis C Virus
Authors: Polyakov Dmitry , Sinitsyna Ekaterina , Grudinina Natalia , Antipchik Mariia , Sakhabeev Rodion , Korzhikov-Vlakh Viktor , Shavlovsky Mikhail , Korzhikova-Vlakh Evgenia , Tennikova Tatiana
Published: May 2021

Hepatitis C is one of the most common social diseases in the world. The improvements in both the early diagnostics of the hepatitis C and the treatment of acute viremia caused by hepatitis C virus are undoubtedly an urgent task. In present work, we offered the micro- and nanotraps for the capturing of HCV. As a capturing moiety, we designed and synthesized in E. coli a fusion protein consisting of large extracellular loop of CD81 receptor and streptavidin as spacing part. The obtained protein has been immobilized on the surface of PLA-based micro- and nanoparticles. The developed trapping systems were characterized in terms of their physico-chemical properties. In order to illustrate the ability of developed micro- and nanotraps to bind HCV, E2 core protein of HCV was synthesized as a fusion protein with GFP. Interaction of E2 protein and hepatitis C virus-mimicking particles with the developed trapping systems were testified by several methods.
Graphene-Coated Highly Sensitive Photonic Crystal Fiber Surface Plasmon Resonance Sensor for Aqueous Solution: Design and Numerical Analysis
Authors: Paul Alok Kumar , Mollah Md. Aslam , Hassan Md. Zahid , Gomez-Cardona Nelson , Reyes-Vera Erick
Published: May 2021

This paper presents the design and analysis of a surface plasmon resonance (SPR) sensor in a photonic crystal fiber (PCF) platform, where graphene is used externally to attain improved sensing performance for an aqueous solution. The performance of the proposed sensor was analyzed using the finite element method-based simulation tool COMSOL Multiphysics. According to the simulation results, the proposed sensor exhibits identical linear characteristics as well as a very high figure of merit (FOM) of 2310.11 RIU−1 in the very low detection limit of 10−3. The analysis also reveals the maximum amplitude sensitivity of 14,847.03 RIU−1 and 7351.82 RIU−1 for the x and y polarized modes, respectively, which are high compared to several previously reported configurations. In addition, the average wavelength sensitivity is 2000 nm/RIU which is comparatively high for the analyte refractive index (RI) ranging from 1.331 to 1.339. Hence, it is highly expected that the proposed PCF-based SPR sensor can be a suitable candidate in different sensing applications, especially for aqueous solutions.
The Importance of Non-Diffusional Factors in Determining Photosynthesis of Two Contrasting Quinoa Ecotypes (Chenopodium quinoa Willd.) Subjected to Salinity Conditions
Authors: Delatorre-Herrera José , Ruiz Karina B. , Pinto Manuel
Published: May 2021

The broad distribution of quinoa in saline and non-saline environments is reflected in variations in the photosynthesis-associated mechanisms of different ecotypes. The aim of this study was to characterize the photosynthetic response to high salinity (0.4 M NaCl) of two contrasting Chilean genotypes, Amarilla (salt-tolerant, salares ecotype) and Hueque (salt-sensitive, coastal ecotype). Our results show that saline stress induced a significant decrease in the K+/Na+ ratio in roots and an increase in glycine betaine in leaves, particularly in the sensitive genotype (Hueque). Measurement of the photosynthesis-related parameters showed that maximum CO2 assimilation (Amax) in control plants was comparable between genotypes (ca. 9–10 μmol CO2 m−2 s−1). However, salt treatment produced different responses, with Amax values decreasing by 65.1% in the sensitive ecotype and 37.7% in the tolerant one. Although both genotypes maintained mesophyll conductance when stomatal restrictions were removed, the biochemical components of Amarilla were impaired to a lesser extent under salt stress conditions: for example, the maximum rate of ribulose-1,5-bisphosphate carboxylase/oxygenase (RubisCO; Vcmax) was not as affected in Amarilla, revealing that this enzyme has a higher affinity for its substrate in this genotype and, thus, a better carboxylation efficiency. The present results show that the higher salinity tolerance of Amarilla was also due to its ability to control non-diffusional components, indicating its superior photosynthetic capacity compared to Hueque, particularly under salt stress conditions.
Transcriptome Analysis of Light-Regulated Monoterpenes Biosynthesis in Leaves of Mentha canadensis L.
Authors: Yu Xu , Qi Xiwu , Li Shumin , Fang Hailing , Bai Yang , Li Li , Liu Dongmei , Chen Zequn , Li Weilin , Liang Chengyuan
Published: May 2021

Light is a key environmental aspect that regulates secondary metabolic synthesis. The essential oil produced in mint (Mentha canadensis L.) leaves is used widely in the aromatics industry and in medicine. Under low-light treatment, significant reductions in peltate glandular trichome densities were observed. GC-MS analysis showed dramatically reduced essential oil and menthol contents. Light affected the peltate glandular trichomes’ development and essential oil yield production. However, the underlying mechanisms of this regulation were elusive. To identify the critical genes during light-regulated changes in oil content, following a 24 h darkness treatment and a 24 h recovery light treatment, leaves were collected for transcriptome analysis. A total of 95,579 unigenes were obtained, with an average length of 754 bp. About 56.58% of the unigenes were annotated using four public protein databases: 10,977 differentially expressed genes (DEGs) were found to be involved in the light signaling pathway and monoterpene synthesis pathway. Most of the TPs showed a similar expression pattern: downregulation after darkness treatment and upregulation after the return of light. In addition, the genes involved in the light signal transduction pathway were analyzed. A series of responsive transcription factors (TFs) were identified and could be used in metabolic engineering as an effective strategy for increasing essential oil yields.
Abscisic Acid’s Role in the Modulation of Compounds that Contribute to Wine Quality
Authors: Alonso Rodrigo , Berli Federico J. , Fontana Ariel , Piccoli Patricia , Bottini Rubén
Published: May 2021

Abscisic acid (ABA) plays a crucial role in the plant responses to environmental signals, in particular by triggering secondary metabolism. High-altitude vineyards in Mendoza, Argentina, are exposed to elevated solar ultraviolet-B (UV-B) levels and moderate water deficits (WD), thus producing grapevine berries with high enological quality for red winemaking. Volatile organic compounds (VOCs) and phenolic compounds (PCs) accumulate in the berry skins, possess antioxidant activity, and are important attributes for red wine. The aim of the present study was to analyze the role of ABA in the modulation of these compounds in Vitis vinifera L. cv. Malbec wines by comparing the independent and interactive effects of UV-B, WD, and ABA. Two UV-B treatments (ambient solar UV-B or reduced UV-B), two watering treatments (well-watered or moderate water deficit) and two ABA treatments (no ABA and sprayed ABA) were given in a factorial design during one growing season. Sprayed ABA, alone and/or in combination with UV-B (specially) and WD (to a lower degree) increased low molecular weight polyphenols (LMWP), anthocyanins, but most noticeably the stilbenes trans-resveratrol and piceid. Under these treatments, VOCs were scarcely affected, and the antioxidant capacity was influenced by the combination of UV-B and WD. From a technological point of view, ABA applications may be an effective vineyard management tool, considering that it elicited a higher content of compounds beneficial for wine aging, as well compounds related to color.