bluuebunny/crossref_metadata_2025 huggingface dataset:
Retrofit Strategies for Energy Efficiency of Historic Urban Fabric in Mediterranean Climate
Authors: Ulu Meltem , Durmuş Arsan Zeynep
Published: July 2020

Energy-efficient retrofitting of historic housing stock requires methodical approach, in-depth analysis and case-specific regulatory system, yet only limited efforts have been realized. In large scale rehabilitation projects, it is essential to develop a retrofit strategy on how to decide energy-efficient solutions for buildings providing the most energy saving in a short time. This paper presents a pilot study conducted at a neighborhood scale, consisting of 22 pre-, early-republican and contemporary residential buildings in a historic urban fabric in the Mediterranean climate. This study aims to develop an integrated approach to describe case-specific solutions for larger scale historic urban fabric. It covers the building performance simulation (BPS) model and numerical analysis to determine the most related design parameters affecting annual energy consumption. All the case buildings were classified into three main groups to propose appropriate retrofit solutions in different impact categories. Retrofit solutions were gathered into two retrofit packages, Package 1 and 2, and separately, three individual operational solutions were determined, considering a five-levelled assessment criteria of EN 16883:2017 Standard. Energy classes of case buildings were calculated based on National Building Energy Regulations. Changes in building classes were evaluated considering pre- and post-retrofit status of the buildings. For the integrated approach, the most related design parameters on annual energy consumption were specified through Pearson correlation analysis. The approach indicated that three buildings, representing each building group, can initially be retrofitted. For all buildings, while maximum energy saving was provided by Package 2 with 48.57%, minimum energy saving was obtained from Package 1 with 19.8%.
Use of Electronic UV Dosimeters in Measuring Personal UV Exposures and Public Health Education
Authors: Allen Martin W. , Swift Neil , Nield Kathryn M. , Liley Ben , McKenzie Richard L.
Published: July 2020

The performance limits of electronic ultraviolet (EUV) dosimeters, which use AlGaN Schottky photodiodes as the ultraviolet radiation (UVR) sensing element to measure personal erythemally weighted UVR exposures, were investigated via a direct comparison with meteorological-grade reference instruments. EUV dosimeters with two types of AlGaN Schottky photodiode were compared to second-generation ‘Robertson–Berger type’ broadband erythemal radiometers. This comparison was done by calculating correction factors for the deviations of the spectral responsivity of each instrument from the CIE erythemal action spectrum and for deviations in their angular response from the ideal cosine response of flat surfaces and human skin. Correction factors were also calculated to convert the output of these instruments to vitamin D-weighted UV irradiances. These comparisons showed that EUV dosimeters can be engineered with spectral responsivities and cosine response errors approaching those of Robertson–Berger type radiometers, making them very acceptable for use in human UVR exposure and sun safety behaviour studies, provided appropriate side-by-side calibrations are performed. Examples of these calibrations and the effect of EUV dosimeter sampling rates on the calculation of received erythemal UVR doses and erythemal UVR dose rates are provided, as well as brief descriptions of their use in primary skin cancer prevention programmes, handheld meters, and public health displays.
Modelling the Present Global Terrestrial Climatic Response Due to a Chicxulub-Type Asteroid Impact
Authors: Mendoza Víctor M. , Mendoza Blanca , Garduño René , Pazos Marni
Published: July 2020

A Chicxulub-like asteroid event occurs, on average, approximately every ~27 to 200 million years. Therefore, such an event could happen presently. Here, we simulate the climatic anomalies it may cause with respect to the current conditions, assuming the same target geology of carbonates and evaporates and a 1 Gt release of sulphate gases. We used a thermodynamic model, including water vapor, cloudiness (by greenhouse and albedo effects), and cryosphere feedback to calculate aerosol cooling. We found that it took nearly 4.5 years for solar radiation to recover its preimpact value—during the first year practically no solar radiation reached the surface. Recovery of the temperature took more than 45 years. The lowest temperatures occurred between 1.5 and 5 years after the impact, being the coldest at −14 °C below the preimpact temperature. July surface temperature anomalies occurred 1.5 years after the impact, becoming one of the largest, compared to preimpact temperatures. Most continents showed temperature anomalies of −45 °C. The least cold places were the polar regions with temperature anomalies between approximately −5 and 0 °C. As for the most remarkable climatic effect, we found that, for ~6 years, the ice extended over almost all the ocean surface and, after ~25 years, it covered nearly half of the surface, remaining so for beyond 45 years. The continental ice remained without reduction beyond 45 years. Sixty years after the impact, the surface oceanic and continental fractions covered by ice were 0.52 and 0.98, respectively. We also modeled the effect of smaller quantities of sulfur released after asteroid impacts, concluding that an instantaneous, large climatic perturbation attributed to a loading range may lead to a semi-permanent shift in the climate system.
Cobalt-Hydrogen Atomic and Ionic Collisional Data
Authors: Yakovleva Svetlana A. , Belyaev Andrey K. , Bergemann Maria
Published: July 2020

Rate coefficients for inelastic processes in low-energy Co + H,

Co

+

+

H

−

,

Co

+

+
H

, and

Co

2
+

+

H

−

collisions are estimated using the quantum simplified model. Considerations include 44 triplet and 55 quintet molecular states of CoH, as well as 91 molecular states of CoH

+

. The estimations provide the rate coefficients for the 4862 partial processes (mutual neutralization, ion-pair formation, excitation, and de-excitation) in the neutral CoH system, and for the

8190

partial processes in the ionized CoH

+

system,

13
,
052

processes in total. At

T
=
6000

K, the rate coefficients with the largest values around

6
×

10

−
8

cm

3

s

−
1

correspond to the mutual neutralization processes into the

Co
(

e
2

F
)
+
H

and

Co
+

(

g
5

F
)

+
H

final channels in the neutral and ionized systems, respectively. Among the excitation and de-excitation processes in Co + H and in Co

+

+ H collisions, at

T
=
6000

K, the largest rate coefficients have values around

7
×

10

−
9

cm

3

s

−
1

and correspond to the processes

Co
(

y
2

S
∘

)
+
H

→

Co
(

e
2

F
;

v
4

D
∘

)
+
H

and

Co
+

(

h
3

P
)

+
H

→

Co
+

(

g
3

P
;

g
5

P
;

g
5

F
)

+
H

, respectively. The calculations single out inelastic processes important for non-local thermodynamic equilibrium (NLTE) modelling of Co I and Co II spectra in stellar atmospheres. The test NLTE calculations are carried out, and it is found that the new collision rates have a strong effect on the line formation and NLTE abundance corrections.
Development of an LDL Receptor-Targeted Peptide Susceptible to Facilitate the Brain Access of Diagnostic or Therapeutic Agents
Authors: André Séverine , Larbanoix Lionel , Verteneuil Sébastien , Stanicki Dimitri , Nonclercq Denis , Vander Elst Luce , Laurent Sophie , Muller Robert N. , Burtea Carmen
Published: July 2020

Blood-brain barrier (BBB) crossing and brain penetration are really challenging for the delivery of therapeutic agents and imaging probes. The development of new crossing strategies is needed, and a wide range of approaches (invasive or not) have been proposed so far. The receptor-mediated transcytosis is an attractive mechanism, allowing the non-invasive penetration of the BBB. Among available targets, the low-density lipoprotein (LDL) receptor (LDLR) shows favorable characteristics mainly because of the lysosome-bypassed pathway of LDL delivery to the brain, allowing an intact discharge of the carried ligand to the brain targets. The phage display technology was employed to identify a dodecapeptide targeted to the extracellular domain of LDLR (ED-LDLR). This peptide was able to bind the ED-LDLR in the presence of natural ligands and dissociated at acidic pH and in the absence of calcium, in a similar manner as the LDL. In vitro, our peptide was endocytosed by endothelial cells through the caveolae-dependent pathway, proper to the LDLR route in BBB, suggesting the prevention of its lysosomal degradation. The in vivo studies performed by magnetic resonance imaging and fluorescent lifetime imaging suggested the brain penetration of this ED-LDLR-targeted peptide.
On the Risks of Phylogeny-Based Strain Prioritization for Drug Discovery: Streptomyces lunaelactis as a Case Study
Authors: Martinet Loïc , Naômé Aymeric , Baiwir Dominique , De Pauw Edwin , Mazzucchelli Gabriel , Rigali Sébastien
Published: July 2020

Strain prioritization for drug discovery aims at excluding redundant strains of a collection in order to limit the repetitive identification of the same molecules. In this work, we wanted to estimate what can be unexploited in terms of the amount, diversity, and novelty of compounds if the search is focused on only one single representative strain of a species, taking Streptomyces lunaelactis as a model. For this purpose, we selected 18 S. lunaelactis strains taxonomically clustered with the archetype strain S. lunaelactis MM109T. Genome mining of all S. lunaelactis isolated from the same cave revealed that 54% of the 42 biosynthetic gene clusters (BGCs) are strain specific, and five BGCs are not present in the reference strain MM109T. In addition, even when a BGC is conserved in all strains such as the bag/fev cluster involved in bagremycin and ferroverdin production, the compounds produced highly differ between the strains and previously unreported compounds are not produced by the archetype MM109T. Moreover, metabolomic pattern analysis uncovered important profile heterogeneity, confirming that identical BGC predisposition between two strains does not automatically imply chemical uniformity. In conclusion, trying to avoid strain redundancy based on phylogeny and genome mining information alone can compromise the discovery of new natural products and might prevent the exploitation of the best naturally engineered producers of specific molecules.
Ginsenoside Compound K: Insights into Recent Studies on Pharmacokinetics and Health-Promoting Activities
Authors: Sharma Anshul , Lee Hae-Jeung
Published: July 2020

Ginseng (Panax ginseng) is an herb popular for its medicinal and health properties. Compound K (CK) is a secondary ginsenoside biotransformed from major ginsenosides. Compound K is more bioavailable and soluble than its parent ginsenosides and hence of immense importance. The review summarizes health-promoting in vitro and in vivo studies of CK between 2015 and 2020, including hepatoprotective, anti-inflammatory, anti-atherosclerosis, anti-diabetic, anti-cancer, neuroprotective, anti-aging/skin protective, and others. Clinical trial data are minimal and are primarily based on CK-rich fermented ginseng. Besides, numerous preclinical and clinical studies indicating the pharmacokinetic behavior of CK, its parent compound (Rb1), and processed ginseng extracts are also summarized. With the limited evidence available from animal and clinical studies, it can be stated that CK is safe and well-tolerated. However, lower water solubility, membrane permeability, and efflux significantly diminish the efficacy of CK and restrict its clinical application. We found that the use of nanocarriers and cyclodextrin for CK delivery could overcome these limitations as well as improve the health benefits associated with them. However, these derivatives have not been clinically evaluated, thus requiring a safety assessment for human therapy application. Future studies should be aimed at investigating clinical evidence of CK.
Mapping the Interactome of the Nuclear Heparan Sulfate Proteoglycan Syndecan-1 in Mesothelioma Cells
Authors: Kumar-Singh Ashish , Shrinet Jatin , Parniewska Malgorzata Maria , Fuxe Jonas , Dobra Katalin , Hjerpe Anders
Published: July 2020

Syndecan-1 (SDC1) is a cell surface heparan sulfate proteoglycan (HSPG), which regulates various signaling pathways controlling the proliferation and migration of malignant mesothelioma and other types of cancer. We have previously shown that SDC1 can translocate to the nucleus in mesothelioma cells through a tubulin-dependent transport mechanism. However, the role of nuclear SDC1 is largely unknown. Here, we performed co-immunoprecipitation (Co-IP) of SDC1 in a mesothelioma cell line to identify SDC1 interacting proteins. The precipitates contained a large number of proteins, indicating the recovery of protein networks. Proteomic analysis with a focus on nuclear proteins revealed an association with pathways related to cell proliferation and RNA synthesis, splicing and transport. In support of this, the top RNA splicing candidates were verified to interact with SDC1 by Co-IP and subsequent Western blot analysis. Further loss- and gain-of-function experiments showed that SDC1 influences RNA levels in mesothelioma cells. The results identify a proteomic map of SDC1 nuclear interactors in a mesothelioma cell line and suggest a previously unknown role for SDC1 in RNA biogenesis. The results should serve as a fundament for further studies to discover the role of nuclear SDC1 in normal and cancer cells of different origin.
A Novel C1-Esterase Inhibitor Oxygenator Coating Prevents FXII Activation in Human Blood
Authors: Gerling Katharina , Ölschläger Sabrina , Avci-Adali Meltem , Neumann Bernd , Schweizer Ernst , Schlensak Christian , Wendel Hans-Peter , Stoppelkamp Sandra
Published: July 2020

The limited hemocompatibility of currently used oxygenator membranes prevents long-term use of artificial lungs in patients with lung failure. To improve hemocompatibility, we developed a novel covalent C1-esterase inhibitor (C1-INH) coating. Besides complement inhibition, C1-INH also prevents FXII activation, a very early event of contact phase activation at the crossroads of coagulation and inflammation. Covalently coated heparin, as the current anticoagulation gold standard, served as control. Additionally, a combination of both coatings (C1-INH/heparin) was established. The coatings were tested for their hemocompatibility by dynamic incubation with freshly drawn human whole blood. The analysis of various blood and plasma parameters revealed that C1-INH-containing coatings were able to markedly reduce FXIIa activity compared to heparin coating. Combined C1-INH/heparin coatings yielded similarly low levels of thrombin-antithrombin III complex formation as heparin coating. In particular, adhesion of monocytes and platelets as well as the diminished formation of fibrin networks were observed for combined coatings. We could show for the first time that a covalent coating with complement inhibitor C1-INH was able to ameliorate hemocompatibility. Thus, the early inhibition of the coagulation cascade is likely to have far-reaching consequences for the other cross-reacting plasma protein pathways.
Aggregate Removal Nanofiltration of Human Serum Albumin Solution Using Nanocellulose-Based Filter Paper
Authors: Wu Lulu , Mantas Athanasios , Gustafsson Simon , Manukyan Levon , Mihranyan Albert
Published: July 2020

This study is dedicated to the rapid removal of protein aggregates and viruses from plasma-derived human serum albumin (HSA) product to reduce the risk of viral contamination and increase biosafety. A two-step filtration approach was implemented to first remove HSA aggregates and then achieve high model virus clearance using a nanocellulose-based filter paper of different thicknesses, i.e., 11 μm (prefilter) and 22 μm (virus filter) at pH 7.4 and room temperature. The pore size distribution of these filters was characterized by nitrogen gas sorption analysis. Dynamic light scattering (DLS) and size-exclusion high performance liquid chromatography (SE-HPLC) were performed to analyze the presence of HSA aggregates in process intermediates. The virus filter showed high clearance of a small-size model virus, i.e., log10 reduction value (LRV) > 5, when operated at 3 and 5 bar, but a distinct decrease in LRV was detected at 1 bar, i.e., LRV 2.65–3.75. The throughput of HSA was also dependent on applied transmembrane pressure as was seen by Vmax values of 110 ± 2.5 L m−2 and 63.6 ± 5.8 L m−2 at 3 bar and 5 bar, respectively. Protein loss was low, i.e., recovery > 90%. A distribution of pore sizes between 40 nm and 60 nm, which was present in the prefilter and absent in the virus filter, played a crucial part in removing the HSA aggregates and minimizing the risk of virus filter fouling. The presented results enable the application of virus removal nanofiltration of HSA in bioprocessing as an alternative to virus inactivation methods based, e.g., on heat treatment.
Endoplasmic Reticulum Stress in Macrophages: The Vicious Circle of Lipid Accumulation and Pro-Inflammatory Response
Authors: Sukhorukov Vasily N. , Khotina Victoria A. , Bagheri Ekta Mariam , Ivanova Ekaterina A. , Sobenin Igor A. , Orekhov Alexander N.
Published: July 2020

The endoplasmic reticulum (ER) stress is an important event in the pathogenesis of different human disorders, including atherosclerosis. ER stress leads to disturbance of cellular homeostasis, apoptosis, and in the case of macrophages, to foam cell formation and pro-inflammatory cytokines production. In atherosclerosis, several cell types can be affected by ER stress, including endothelial cells, vascular smooth muscular cells, and macrophages. Modified low-density lipoproteins (LDL) and cytokines, in turn, can provoke ER stress through different processes. The signaling cascades involved in ER stress initiation are complex and linked to other cellular processes, such as lysosomal biogenesis and functioning, autophagy, mitochondrial homeostasis, and energy production. In this review, we discuss the underlying mechanisms of ER stress formation and the interplay of lipid accumulation and pro-inflammatory response. We will specifically focus on macrophages, which are the key players in maintaining chronic inflammatory milieu in atherosclerotic lesions, and also a major source of lipid-accumulating foam cells.
Specific and Non-Invasive Fluorescent Labelling of Extracellular Vesicles for Evaluation of Intracellular Processing by Intestinal Epithelial Cells
Authors: Hansen Maria S. , Gadegaard Ida S. E. , Arnspang Eva C. , Blans Kristine , Nejsum Lene N. , Rasmussen Jan T.
Published: July 2020

The presence of extracellular vesicles (EVs) in milk has gained interest due to their capacity to modulate the infant’s intestinal and immune system. Studies suggest that milk EVs are enriched in immune-modulating proteins and miRNA, highlighting their possible health benefits to infants. To assess uptake of milk EVs by intestinal epithelial cells, a method was developed using labelling of isolated EVs with fluorophore-conjugated lactadherin. Lactadherin is a generic and validated EV marker, which enables an effective labelling of phosphatidylserine (PS) exposing EVs. Labelled EVs could effectively be used to describe a dose- and time-dependent uptake into the intestinal epithelial Caco-2 cell line. Additionally, fluorescence microscopy was employed to show that EVs colocalize with endosomal markers and lysosomes, indicating that EVs are taken up via general endocytotic mechanisms. Collectively, a method to specifically label isolated EVs is presented and employed to study the uptake of milk EVs by intestinal epithelial cells.
Neuronal-Specific Inhibition of Endoplasmic Reticulum Mg2+/Ca2+ ATPase Ca2+ Uptake in a Mixed Primary Hippocampal Culture Model of Status Epilepticus
Authors: Deshpande Laxmikant S. , DeLorenzo Robert J. , Churn Severn B. , Parsons J. Travis
Published: July 2020

Loss of intracellular calcium homeostasis is an established mechanism associated with neuronal dysfunction and status epilepticus. Sequestration of free cytosolic calcium into endoplasmic reticulum by Mg2+/Ca2+ adenosinetriphosphatase (ATPase) is critical for maintenance of intracellular calcium homeostasis. Exposing hippocampal cultures to low-magnesium media is a well-accepted in vitro model of status epilepticus. Using this model, it was shown that endoplasmic reticulum Ca2+ uptake was significantly inhibited in homogenates from cultures demonstrating electrophysiological seizure phenotypes. Calcium uptake was mainly neuronal. However, glial Ca2+ uptake was also significantly inhibited. Viability of neurons exposed to low magnesium was similar to neurons exposed to control solutions. Finally, it was demonstrated that Ca2+ uptake inhibition and intracellular free Ca2+ levels increased in parallel with increasing incubation in low magnesium. The results suggest that inhibition of Mg2+/Ca2+ ATPase-mediated endoplasmic reticulum Ca2+ sequestration contributes to loss of intracellular Ca2+ homeostasis associated with status epilepticus. This study describes for the first time inhibition of endoplasmic reticulum Mg2+/Ca2+ ATPase in a mixed primary hippocampal model of status epilepticus. In combination with animal models of status epilepticus, the cell culture model provides a powerful tool to further elucidate mechanisms that result in inhibition of Mg2+/Ca2+ ATPase and downstream consequences of decreased enzyme activity.
Brain Abscess Masquerading as Brain Infarction
Authors: Jeong Da-Eun , Lee Jun
Published: July 2020

Occasionally, acute ischemic stroke can be difficult to differentiate from acute intracranial infection. We describe a patient who presented with sudden onset of right hemiparesis and fever. Magnetic resonance imaging (MRI) was consistent with an acute stroke, showing multiple lesions with restricted diffusion in the left middle cerebral artery territory. These lesions were not enhancing and were not associated with vasogenic edema. A diagnosis of acute stroke was made based on the clinical and radiographic data. Follow-up MRI obtained eleven days later showed interval development of ring enhancement and vasogenic edema surrounding the previously noted core of restricted diffusion. Based on these findings, the diagnosis was revised to cerebral abscesses and the patient was treated successfully with antibiotics. In retrospect, the largest diffusion-weighted lesion on baseline MRI demonstrated two characteristics that were atypical for stroke: it had an ovoid shape and a subtle T2 hypointense core. This case demonstrates that acute clinical and radiographic presentation of cerebral abscess and ischemic stroke can be strikingly similar. Follow-up imaging can be instrumental in arriving at an accurate diagnosis.
Explaining Age at Autism Spectrum Diagnosis in Children with Migrant and Non-Migrant Background in Austria
Authors: Garcia Primo Patricia , Weber Christoph , Posada de la Paz Manuel , Fellinger Johannes , Dirmhirn Anna , Holzinger Daniel
Published: July 2020

This study explored (i) differences in age at Autism Spectrum Disorder (ASD) diagnosis between children with and without a migrant background in the main diagnostic centre for ASD in Upper Austria (ii) factors related to the age at diagnosis and (iii) whether specific factors differed between the two groups. A retrospective chart analysis included all children who received their first diagnosis before the age of 10 years (n = 211) between 2013 and 2018. Children with a migrant background were diagnosed 13 months earlier than those without (r = 0.278, p < 0.001), and had more severe delays in language, more severe autism, no Asperger’s syndrome, lower parental educational level and more frequent referrals by paediatricians. For the total sample, expressive language delay, severity of restricted and repetitive behaviours, higher nonverbal development, and paediatric referrals explained earlier diagnoses. There was a stronger effect of parental education and weaker effect of language impairment on age at ASD diagnosis in children with a migrant background. In conclusion, no delay in diagnosing ASD in children with a migrant background in a country with universal health care and an established system of paediatric developmental surveillance was found. Awareness of ASD, including Asperger’s syndrome, should be raised among families and healthcare professionals.
Treatment of Dystonia Using Trihexyphenidyl in Costello Syndrome
Authors: Romeo Domenico M. , Specchia Alessandro , Fasano Alfonso , Leoni Chiara , Onesimo Roberta , Brogna Claudia , Veltri Stefania , Zampino Giuseppe
Published: July 2020

Costello syndrome (CS), a rare syndrome with multisystemic involvement inherited as a dominant trait, is characterized by developmental delay, coarse facial appearance, cardiac defects including hypertrophic cardiomyopathy, skin abnormalities, brain complications, and a predisposition to certain malignancies. The musculoskeletal system is particularly affected in CS, with peculiar orthopedic anomalies that impact posture and gait. Dystonia has been recently documented to contribute to abnormal postures and musculoskeletal anomalies characterizing CS, suggesting the possible use of pharmacological treatments to treat these complications. We report the case of a child affected by CS displaying a particularly severe musculoskeletal involvement with dystonic posture especially in the arms and legs. The Movement Disorder-Childhood Rating Scale (MD-CRS) and a gait analysis were used to assess clinical patterns of hyperkinetic movement disorder and dystonia. The child was further treated with trihexyphenidyl for six months with a final dosage of 14 mg. MD-CRS and gait analysis assessments provided evidence for a significant improvement of posture and the related musculoskeletal problems with no side effects. Our preliminary study report provides first evidence that pharmacological anti-dystonia treatment significantly improves movement and posture disorders in patients with CS. Further studies enrolling larger cohorts of patients should be performed to validate these preliminary observations.
The Relationship Benefits of Auto Maintenance and Repair Service: A Case Study of Korea
Authors: Hong Jinpyo , Kim Boyoung , Oh Sungho
Published: July 2020

This study aimed to empirically examine what effects confidence, social, and economic benefit factors have on continuous relationship orientation through the mediation of service trust, service satisfaction, and customer engagement factors in the auto maintenance and repair service sector. This study carried out a questionnaire survey with 319 customers using auto maintenance and repair service and verified hypotheses. As a result of the analysis, the confidence and social benefits of auto maintenance and repair service affected service trust, while the confidence and economic benefits affected service satisfaction. Service trust did not affect customer engagement or long-term relationship continuity but affected them when it mediated service satisfaction. Consequently, it was revealed that confidence benefit should be consolidated and that professionalism or service quality excellence in maintenance or repair becomes the most important factors to produce customer engagement or long-term relationship continuity in the auto maintenance and repair service. Although it is vital to improve trust or service, it is confirmed that a relationship can be maintained only if the auto maintenance or repair service is satisfactory.
A Systematic Approach to Calculate Unit Emergy Values of Cement Manufacturing in China Using Consumption Quota of Dry and Wet Raw Materials
Authors: Zhang Junxue , S. Srinivasan Ravi , Peng Changhai
Published: July 2020

The Chinese cement industry produced 2150 million metric tons of cement in 2014, accounting for 58.1% of the world’s total. This industry has a hugely destructive effect on the environment owing to its pollution. The environmental impact of cement manufacturing is a major concern for China. Although researchers have attempted to estimate impacts using life cycle assessment approaches, it lacks the ability to provide a holistic evaluation of the impacts on the environment. Emergy analysis, through ecological accounting, offers environmental decision making using elaborate book keeping. In spite of the high environmental impact of the cement industry, there has only been a handful of research work done to compute the unit emergy values (UEVs) of cement manufacturing in China. A thorough study of existing UEVs of cement manufacturing in China showed pitfalls that may lead to inaccurate estimations if used in emergy analysis. There is a strong need for a new, updated UEV for cement manufacturing in China, particularly reflecting both the dry and wet raw materials in the manufacturing process. This paper develops a methodology to calculate the nonrenewable resources used in cement manufacturing, particularly using mainstream cement production line. Our systematic approach-based UEV estimates of cement manufacturing in China using the quota method are 2.56 × 1012 sej/kg (wet material) and 2.46 × 1012 sej/kg (dry material). Emergy indicators such as environmental loading ratios which were calculated at 2390 (wet material) and 2300 (dry material); emergy yield ratios at 15.7 and 15.8; and emergy sustainability indices at 0.0066 and 0.0069 for dry and wet materials used in cement manufacturing, respectively; these show the immense impact on the environment in China.
Development of Antibody Immuno-PET/SPECT Radiopharmaceuticals for Imaging of Oncological Disorders—An Update
Authors: Dewulf Jonatan , Adhikari Karuna , Vangestel Christel , Wyngaert Tim Van Den , Elvas Filipe
Published: July 2020

Positron emission tomography (PET) and single-photon emission computed tomography (SPECT) are molecular imaging strategies that typically use radioactively labeled ligands to selectively visualize molecular targets. The nanomolar sensitivity of PET and SPECT combined with the high specificity and affinity of monoclonal antibodies have shown great potential in oncology imaging. Over the past decades a wide range of radio-isotopes have been developed into immuno-SPECT/PET imaging agents, made possible by novel conjugation strategies (e.g., site-specific labeling, click chemistry) and optimization and development of novel radiochemistry procedures. In addition, new strategies such as pretargeting and the use of antibody fragments have entered the field of immuno-PET/SPECT expanding the range of imaging applications. Non-invasive imaging techniques revealing tumor antigen biodistribution, expression and heterogeneity have the potential to contribute to disease diagnosis, therapy selection, patient stratification and therapy response prediction achieving personalized treatments for each patient and therefore assisting in clinical decision making.
SNAIL Promotes Metastatic Behavior of Rhabdomyosarcoma by Increasing EZRIN and AKT Expression and Regulating MicroRNA Networks
Authors: Skrzypek Klaudia , Kot Marta , Konieczny Paweł , Nieszporek Artur , Kusienicka Anna , Lasota Małgorzata , Bobela Wojciech , Jankowska Urszula , Kędracka-Krok Sylwia , Majka Marcin
Published: July 2020

Rhabdomyosarcoma (RMS) is a predominant soft tissue tumor in children and adolescents. For high-grade RMS with metastatic involvement, the 3-year overall survival rate is only 25 to 30%. Thus, understanding the regulatory mechanisms involved in promoting the metastasis of RMS is important. Here, we demonstrate for the first time that the SNAIL transcription factor regulates the metastatic behavior of RMS both in vitro and in vivo. SNAIL upregulates the protein expression of EZRIN and AKT, known to promote metastatic behavior, by direct interaction with their promoters. Our data suggest that SNAIL promotes RMS cell motility, invasion and chemotaxis towards the prometastatic factors: HGF and SDF-1 by regulating RHO, AKT and GSK3β activity. In addition, miRNA transcriptome analysis revealed that SNAIL-miRNA axis regulates processes associated with actin cytoskeleton reorganization. Our data show a novel role of SNAIL in regulating RMS cell metastasis that may also be important in other mesenchymal tumor types and clearly suggests SNAIL as a promising new target for future RMS therapies.
Nitric Oxide (NO) and NO Synthases (NOS)-Based Targeted Therapy for Colon Cancer
Authors: Wang Hao , Wang Liye , Xie Zuoxu , Zhou Shuang , Li Yan , Zhou Yue , Sun Meiyan
Published: July 2020

Colorectal cancer (CRC) is one of the most lethal malignancies worldwide and CRC therapy remains unsatisfactory. In recent decades, nitric oxide (NO)—a free-radical gas—plus its endogenous producer NO synthases (NOS), have attracted considerable attention. NO exerts dual effects (pro- and anti-tumor) in cancers. Endogenous levels of NO promote colon neoplasms, whereas exogenously sustained doses lead to cytotoxic functions. Importantly, NO has been implicated as an essential mediator in many signaling pathways in CRC, such as the Wnt/β-catenin and extracellular-signal-regulated kinase (ERK) pathways, which are closely associated with cancer initiation, metastasis, inflammation, and chemo-/radio-resistance. Therefore, NO/NOS have been proposed as promising targets in the regulation of CRC carcinogenesis. Clinically relevant NO-donating agents have been developed for CRC therapy to deliver a high level of NO to tumor sites. Notably, inducible NOS (iNOS) is ubiquitously over-expressed in inflammatory-associated colon cancer. The development of iNOS inhibitors contributes to targeted therapies for CRC with clinical benefits. In this review, we summarize the multifaceted mechanisms of NO-mediated networks in several hallmarks of CRC. We review the clinical manifestation and limitations of NO donors and NOS inhibitors in clinical trials. We also discuss the possible directions of NO/NOS therapies in the immediate future.
Current Trends of Artificial Intelligence for Colorectal Cancer Pathology Image Analysis: A Systematic Review
Authors: Thakur Nishant , Yoon Hongjun , Chong Yosep
Published: July 2020

Colorectal cancer (CRC) is one of the most common cancers requiring early pathologic diagnosis using colonoscopy biopsy samples. Recently, artificial intelligence (AI) has made significant progress and shown promising results in the field of medicine despite several limitations. We performed a systematic review of AI use in CRC pathology image analysis to visualize the state-of-the-art. Studies published between January 2000 and January 2020 were searched in major online databases including MEDLINE (PubMed, Cochrane Library, and EMBASE). Query terms included “colorectal neoplasm,” “histology,” and “artificial intelligence.” Of 9000 identified studies, only 30 studies consisting of 40 models were selected for review. The algorithm features of the models were gland segmentation (n = 25, 62%), tumor classification (n = 8, 20%), tumor microenvironment characterization (n = 4, 10%), and prognosis prediction (n = 3, 8%). Only 20 gland segmentation models met the criteria for quantitative analysis, and the model proposed by Ding et al. (2019) performed the best. Studies with other features were in the elementary stage, although most showed impressive results. Overall, the state-of-the-art is promising for CRC pathological analysis. However, datasets in most studies had relatively limited scale and quality for clinical application of this technique. Future studies with larger datasets and high-quality annotations are required for routine practice-level validation.
Cancer Nanomedicine Special Issue Review Anticancer Drug Delivery with Nanoparticles: Extracellular Vesicles or Synthetic Nanobeads as Therapeutic Tools for Conventional Treatment or Immunotherapy
Authors: Zocchi Maria Raffaella , Tosetti Francesca , Benelli Roberto , Poggi Alessandro
Published: July 2020

Both natural and synthetic nanoparticles have been proposed as drug carriers in cancer treatment, since they can increase drug accumulation in target tissues, optimizing the therapeutic effect. As an example, extracellular vesicles (EV), including exosomes (Exo), can become drug vehicles through endogenous or exogenous loading, amplifying the anticancer effects at the tumor site. In turn, synthetic nanoparticles (NP) can carry therapeutic molecules inside their core, improving solubility and stability, preventing degradation, and controlling their release. In this review, we summarize the recent advances in nanotechnology applied for theranostic use, distinguishing between passive and active targeting of these vehicles. In addition, examples of these models are reported: EV as transporters of conventional anticancer drugs; Exo or NP as carriers of small molecules that induce an anti-tumor immune response. Finally, we focus on two types of nanoparticles used to stimulate an anticancer immune response: Exo carried with A Disintegrin And Metalloprotease-10 inhibitors and NP loaded with aminobisphosphonates. The former would reduce the release of decoy ligands that impair tumor cell recognition, while the latter would activate the peculiar anti-tumor response exerted by γδ T cells, creating a bridge between innate and adaptive immunity.
Identification of Novel microRNA Prognostic Markers Using Cascaded Wx, a Neural Network-Based Framework, in Lung Adenocarcinoma Patients
Authors: Kim Jeong Seon , Chun Sang Hoon , Park Sungsoo , Lee Sieun , Kim Sae Eun , Hong Ji Hyung , Kang Keunsoo , Ko Yoon Ho , Ahn Young-Ho
Published: July 2020

The evolution of next-generation sequencing technology has resulted in a generation of large amounts of cancer genomic data. Therefore, increasingly complex techniques are required to appropriately analyze this data in order to determine its clinical relevance. In this study, we applied a neural network-based technique to analyze data from The Cancer Genome Atlas and extract useful microRNA (miRNA) features for predicting the prognosis of patients with lung adenocarcinomas (LUAD). Using the Cascaded Wx platform, we identified and ranked miRNAs that affected LUAD patient survival and selected the two top-ranked miRNAs (miR-374a and miR-374b) for measurement of their expression levels in patient tumor tissues and in lung cancer cells exhibiting an altered epithelial-to-mesenchymal transition (EMT) status. Analysis of miRNA expression from tumor samples revealed that high miR-374a/b expression was associated with poor patient survival rates. In lung cancer cells, the EMT signal induced miR-374a/b expression, which, in turn, promoted EMT and invasiveness. These findings demonstrated that this approach enabled effective identification and validation of prognostic miRNA markers in LUAD, suggesting its potential efficacy for clinical use.
Periodontal Diseases as Putative Risk Factors for Head and Neck Cancer: Systematic Review and Meta-Analysis
Authors: Gopinath Divya , Kunnath Menon Rohit , K. Veettil Sajesh , George Botelho Michael , Johnson Newell W.
Published: July 2020

Whether “periodontal disease” can be considered as an independent risk factor for head and neck cancer (HNC) remains controversial. The aim of the current meta-analysis was to quantitatively assess this relationship in order to determine whether this represents a true risk factor, with implications for cancer prevention and management. PubMed, Scopus, and Embase databases were systematically searched. Selective studies were reviewed, and meta-analysis was performed to estimate the pooled odds ratio (OR) with 95% confidence intervals (CIs) on eligible studies using a random effects model. In total, 21 eligible observational studies (4 cohorts and 17 case-controls) were identified for qualitative synthesis after a review of 1051 articles. Significant heterogeneity could be identified in measures utilized for reporting of periodontal disease. Meta-analysis performed on nine studies that employed objective measures for reporting periodontal disease demonstrated a significant association between periodontal disease and HNC [OR 3.17, 95% CI, 1.78–5.64]. A diseased periodontium represents an independent risk marker, and a putative risk factor, for HNC. Prospective studies with standardized measures of periodontal disease severity and extent, integrated with microbiological and host susceptibility facets, are needed to elucidate the mechanisms of this positive association and whether treatment of the former influences the incidence and outcomes for HNC.
Impact of Chemotherapy in the Adjuvant Setting of Early Stage Uterine Leiomyosarcoma: A Systematic Review and Updated Meta-Analysis
Authors: Rizzo Alessandro , Nannini Margherita , Astolfi Annalisa , Indio Valentina , De Iaco Pierandrea , Perrone Anna Myriam , De Leo Antonio , Incorvaia Lorena , Di Scioscio Valerio , Pantaleo Maria Abbondanza
Published: July 2020

Background: Although the use of adjuvant chemotherapy (AC) appears to be increasing over the past few years, several clinical trials and previous meta-analyses failed to determine whether AC could improve clinical outcomes in uterine leiomyosarcoma (uLMS). The aim of this systematic review and meta-analysis was to compare AC (with or without radiotherapy) versus observation (obs) after primary surgery in early stage uLMS. Materials and Methods: Randomized controlled (RCTs) and non-randomized studies (NRSs) were retrieved. Outcomes of interest were as follows: distant recurrence rate, locoregional recurrence rate and overall recurrence rate. Results about distant recurrence rate, locoregional recurrence rate and overall recurrence rate were compared by calculating odds ratios (ORs) with 95% confidence intervals (CIs); ORs were combined with Mantel–Haenszel method. Results: Nine studies were included in the analysis, involving 545 patients (AC: 252, obs: 293). Compared with obs, AC did not reduce locoregional and distant recurrence rate, with a pooled OR of 1.36 and 0.63, respectively. Similarly, administration of AC did not decrease overall recurrence rate in comparison to obs. Conclusion: According to our results, AC (with or without radiotherapy) did not decrease recurrence rate in early stage uLMS; thus, the role of AC in this setting remains unclear.
Role of Telomeres and Telomeric Proteins in Human Malignancies and Their Therapeutic Potential
Authors: Fernandes Stina George , Dsouza Rebecca , Pandya Gouri , Kirtonia Anuradha , Tergaonkar Vinay , Lee Sook Y. , Garg Manoj , Khattar Ekta
Published: July 2020

Telomeres are the ends of linear chromosomes comprised of repetitive nucleotide sequences in humans. Telomeres preserve chromosomal stability and genomic integrity. Telomere length shortens with every cell division in somatic cells, eventually resulting in replicative senescence once telomere length becomes critically short. Telomere shortening can be overcome by telomerase enzyme activity that is undetectable in somatic cells, while being active in germline cells, stem cells, and immune cells. Telomeres are bound by a shelterin complex that regulates telomere lengthening as well as protects them from being identified as DNA damage sites. Telomeres are transcribed by RNA polymerase II, and generate a long noncoding RNA called telomeric repeat-containing RNA (TERRA), which plays a key role in regulating subtelomeric gene expression. Replicative immortality and genome instability are hallmarks of cancer and to attain them cancer cells exploit telomere maintenance and telomere protection mechanisms. Thus, understanding the role of telomeres and their associated proteins in cancer initiation, progression and treatment is very important. The present review highlights the critical role of various telomeric components with recently established functions in cancer. Further, current strategies to target various telomeric components including human telomerase reverse transcriptase (hTERT) as a therapeutic approach in human malignancies are discussed.
Application of Variable Frequency Microwaves in Microwave-Assisted Chemistry: Relevance and Suppression of Arc Discharges on Conductive Catalysts
Authors: Horikoshi Satoshi , Arai Yuuhei , Ahmad Iftikhar , DeCamillis Clayton , Hicks Keith , Schauer Bob , Serpone Nick
Published: July 2020

The application and advantages of variable frequency microwaves (VFM; range, 5.85–6.65 GHz) are reported for the first time in microwave chemistry, particularly when carrying out reactions catalyzed by metallic conductive catalysts so as to avoid the formation of arc discharges, and especially when using a strong microwave absorber such as activated carbon (AC) particulates as supports of metal-based catalysts. Two model reactions performed in low boiling point nonpolar solvents are described wherein arc discharges easily occur under the more conventional fixed frequency microwave (FFM) approach: (i) the synthesis of 4-methylbiphenyl (4MBP) by the Suzuki-Miyaura cross-coupling process catalyzed by Pd particles supported on AC particulates (Pd/AC), and (ii) the synthesis of toluene via the dehydrogenation of methylcyclohexane (MCH) catalyzed by Pt particles dispersed on AC particulates (Pt/AC). Contrary to the usage of fixed frequency microwaves (5.85 GHz and 6.65 GHz), the use of VFM microwaves increased the chemical yields of 4MBP {49% versus 5–8% after 60 min} and toluene {89% versus 24% after 10 min} by suppressing the formation of discharges that otherwise occur on the catalyst/AC surface with FFM microwaves. Consequently, relative to the latter approach, the VFM technology is significantly advantageous, especially in reactions with solid conductive catalysts, not least of which are the reduction in power consumption, thus energy savings, and the prevention of potential mishaps.
Characterization of Electrode Performance in Enzymatic Biofuel Cells Using Cyclic Voltammetry and Electrochemical Impedance Spectroscopy
Authors: Bojang Adama A. , Wu Ho Shing
Published: July 2020

The main objective of this study was to examine the quantitative performance of the electrochemical redox reaction of glucose by glucosidase and oxygen with laccase in a phosphate buffer solution at pH 7.0. The characterization of electrode performance was performed by using electrochemical analysis such as cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The use of such electrochemical analysis (CV and EIS) enables a better understanding of the redox process, the charge transfer resistance, and, hence, the potential mass transfer among the electrode materials in phosphorus buffer solution. The experimental results show that the maximum power densities of the bioanode and the biocathode electrodes were 800 µA/cm2 and 600 µA/cm2, respectively. Both the bioanode and biocathode show high internal resistance. The occurrence of peak-separation shows an excellent mass-transfer mechanism and better chemical reactivity in the electrode.