bluuebunny/crossref_metadata_2025 huggingface dataset:
The Role of an Industrial Alkaline Wastewater in the Alkali Activation of Biomass Fly Ash
Authors: Novo Catarina C. , Senff Luciano , Seabra Maria P. , Novais Rui M. , Labrincha João A.
Published: April 2022

Alkali-activated materials are generally considered a more sustainable alternative to Portland cement binders. This derives not only from the use of solid wastes as precursors, but also from the low temperatures required for their synthesis. However, to increase the environmental advantages of these materials, alternative activators should be explored, as the common route involves the use of commercial activators such as sodium silicate or sodium hydroxide solutions. In this work, the possibility of using an alkaline industrial wastewater, coming from a Portuguese paper and pulp industry, as a partial replacement of the commercial sodium hydroxide solution was studied. The results show that the use of the industrial wastewater decreased the workability of the pastes and their setting times, higher incorporations inducing a stronger reduction. Despite this, the results demonstrate the feasibility of replacing up to 25 vol.% of the sodium hydroxide solution with the industrial wastewater without compromising the mechanical performance of the binder. The compressive strength of this composition reached 22.7 MPa, this being slightly higher than the value seen in the reference (20.0 MPa). The use of a waste-containing activator, as reported here, might be a key driver to foster the wider use of this technology.
Enrichment in a Fish Polyculture: Does it Affect Fish Behaviour and Development of Only One Species or Both?
Authors: Thomas Marielle , Reynaud Jean-Gabriel , Ledoré Yannick , Pasquet Alain , Lecocq Thomas
Published: April 2022

Physical enrichment of structures has been used for the last decades in aquaculture to improve fish production and welfare. Until now, this enrichment has been practiced in fish monoculture but not in fish polyculture. In this study, we developed a polyculture of two freshwater species (pikeperch and sterlet) in recirculated systems (tank of 2.4 m3) with or without physical structures for enrichment. Two types of structures were used: a cover plank on a part of the tank decreasing the light intensity and vertical pipes modifying the water flow. The experiment was conducted in triplicate for a three-month period with juvenile fishes (143 ± 41 g and 27.3 ± 2.2 cm for pikeperch and 133 ± 21 g and 32.8 ± 1.6 cm for sterlet). Behavioural (space occupation and abnormal behaviours) and morphological (total length, final weight, Fulton condition factor, coefficient of variation of the final weight, percentage of biomass gain and specific growth rate) traits were measured. The pikeperch changed their space occupation and showed a preference for low light areas. Sterlet also changed their space occupation: they did not use the cover and occurred mainly in the part of the tank without enrichment. There was no difference for the frequency of abnormal behaviours for pikeperch and sterlet between the two sets (with or without enrichment). There was no statistical difference between the two sets for all the morphological and growth parameters no matter the species and the rearing modality.
Novel MIMO Antenna System for Ultra Wideband Applications
Authors: Alharbi Abdullah G. , Rafique Umair , Ullah Shakir , Khan Salahuddin , Abbas Syed Muzahir , Ali Esraa Mousa , Alibakhshikenari Mohammad , Dalarsson Mariana
Published: April 2022

The design of a 4 × 4 MIMO antenna for UWB communication systems is presented in this study. The single antenna element is comprised of a fractal circular ring structure backed by a modified partial ground plane having dimensions of 30 × 30 mm2. The single antenna element has a wide impedance bandwidth of 9.33 GHz and operates from 2.67 GHz to 12 GHz. Furthermore, the gain of a single antenna element increases as the frequency increases, with a peak realized gain and antenna efficiency of 5 dBi and >75%, respectively. For MIMO applications, a 4 × 4 array is designed and analyzed. The antenna elements are positioned in a plus-shaped configuration to provide pattern as well as polarization diversity. It is worth mentioning that good isolation characteristics are achieved without the utilization of any isolation enhancement network. The proposed MIMO antenna was fabricated and tested, and the results show that it provides UWB response from 2.77 GHz to over 12 GHz. The isolation between the antenna elements is more than 15 dB. Based on performance attributes, it can be said that the proposed design is suitable for UWB MIMO applications.
Clinical Mass Spectrometry in Immunosuppressant Analysis: Toward a Full Automation?
Authors: Fania Chiara , Bagnati Marco , Albertario Marina , Ferraris Carlotta , Lamonaca Marta , Dianzani Umberto
Published: April 2022

The analysis of immunosuppressive drugs allows the physician to monitor, and eventually correct, immunosuppressive therapy. The panel of molecules under evaluation includes cyclosporine A (CsA), tacrolimus, sirolimus, and everolimus. Initially, assays were performed by immunometric methods, but in the past few years this methodology has been largely superseded by a more accurate and specific technique, liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS), which is now considered the “gold standard” for immunosuppressant analysis. Both LC-MS/MS and often also immunoassays require a preanalytical manual sample preparation, which involves time-consuming sequential operations whose traceability is often hampered and adds up to the probability of gross errors. The aim of this work was to compare an “open” LC-MS/MS with a fully automated system, consisting of LC instrumentation combined with a triple quadrupole MS, named Thermo ScientificTM CascadionTM SM Clinical Analyzer (Cascadion). Such automated systems suit the requirements of the reference method and are designed to completely eliminate all of the manual procedures. More than 2000 immunosuppressant samples were analyzed both with the open LC-MS/MS and with Cascadion. Statistics allowed the evaluation of linearity, intra- and inter-assay CV%, bias %, limit of detection and of quantitation, and Passing–Bablok and Bland–Altman plots. Results indicated a good correlation between the two methods. In both cases, methods confirmed their suitability for diagnostic settings. Cascadion could provide support when the presence of specialized personnel is lacking, and/or when great productivity and continuous workflow are required.
‘An Element of Perfection’: The Transductive Art of Robert Mallary
Authors: Mason Catherine
Published: April 2022

In 1969, American artist Robert Mallary (1917–1997) coined the term ‘transductive art’ to describe an approach to art based on the notion of receiving energy from one system and retransmitting it, often in a different form, to another. Long before the realm of techno-art became a recognizable construct, Mallary was interested in a system of relationships, seeking in his words, ‘an element of perfection’ in combinations of materials and technologies to make ‘a beautiful whole’. From his experiments with the Mexican Muralists to assemblage and Neo-Dada sculpture, and finally, his synergistic relationship with the computer, Mallary’s work addressed the place of the human in a technological world. He instigated one of the first American computer art curriculums within a fine art department, developing early examples of software created by artists for use by artists. His espousal of the digital to become a ‘Supermedium’, led him to conceptualise a ‘spatial-synesthetic art’, a multi-media immersive environment combining three-dimensional projected visual elements, motion, and sound. Although unrealised, this system anticipated future VR/virtual reality developments such as the ‘Cave Automatic Virtual Environment’ (CAVE™) system developed at the University of Illinois, Chicago, in 1992. The current review will therefore argue, by example, that Mallary deserves a prominent position in the history of techno-art, and by virtue of both the several emerging influences he had the insight to recognise and bring together and his numerous subsequent contributions as simultaneously an artist, a theorist, and an educator.
Characteristics of Lightning Electromagnetic Fields Produced by Antarctica Storms
Authors: Mohammad Sulaiman Ali , Ahmad Mohd Riduan , Abdullah Mardina , Sangjong Park , Shamsul Baharin Shamsul Ammar , Yusop Norbayah , Lu Gaopeng , Cooray Vernon
Published: April 2022

This paper presents the temporal characteristics of electromagnetic fields produced by cloud-to-ground (CG) lightning flashes associated with Antarctica storms. A total of 51 positive CG (+CG) and 103 negative CG (−CG) flashes have been recorded by a magnetic direction finder (MDF) sensor in King Sejong Station, King George Island. In total, 47 positive and 107 negative return strokes were located, ranges from 32 to 569 km. All CG flashes were detected to occur over the ocean. The return strokes characteristics include the observations of slow front, fast rising, rise time, and pulse duration with geometric mean values of 3.2, 0.53, 3.21, 13.12, and 67.09 µs for +CG flashes, while 3.9, 0.57, 3.72, 20.75, and 69.86 µs for −CG flashes, respectively. Additionally, the average peak currents of +CG and −CG flashes were 4.13 kA and 3.14 kA, respectively. The temporal characteristics of the return strokes of Antarctica storms are comparable to other geographical regions. The smaller peak currents might be due to small magnitude of Antarctica cloud charges when compared to other geographical regions.
Condensed Phase Kinetic Studies of Hydroxynitrates Derived from the Photooxidation of Carene, Limonene, trans-Carveol, and Perillic Alcohol
Authors: Vesto James I. , McAlister Addison B. , Wright Kathryn A. , Huang Aaron , Baldwin Petra R. , McLaughlin Sta. Maria Emily J. , LaLonde Rebecca Lyn , Carrasquillo Anthony J.
Published: April 2022

Organic hydroxynitrates (HNs) are key products of hydrocarbon oxidation in the atmosphere. Understanding the fate and processing of these molecules is critical due to their function in the sequestration of NOx species from the atmosphere and in the formation of secondary organic aerosol. However, the direct study of individual HNs’ reactivity has been largely hindered by the lack of authentic standards which has further limited the ability to deconvolute the role of structural features. Herein, we report the kinetic stabilities of six biogenic volatile organic compound-derived HN in acidified single-phase organic/water matrices. Lifetimes for tertiary HNs ranged from 15 min to 6.4 h, whereas secondary HN varied from 56 days to 2.1 years. Product analysis highlights the role that additional non-hydrolysis reactions have in the condensed phase conversion of HNs. This work provides the first evidence for the structural dependence of HN stability in bulk mixed media.
Positive Solutions for a System of Fractional Boundary Value Problems with r-Laplacian Operators, Uncoupled Nonlocal Conditions and Positive Parameters
Authors: Tudorache Alexandru , Luca Rodica
Published: April 2022

In this paper, we investigate the existence and nonexistence of positive solutions for a system of Riemann–Liouville fractional differential equations with r-Laplacian operators, subject to nonlocal uncoupled boundary conditions that contain Riemann–Stieltjes integrals, various fractional derivatives and positive parameters. We first change the unknown functions such that the new boundary conditions have no positive parameters, and then, by using the corresponding Green functions, we equivalently write this new problem as a system of nonlinear integral equations. By constructing an appropriate operator A, the solutions of the integral system are the fixed points of A. Following some assumptions regarding the nonlinearities of the system, we show (by applying the Schauder fixed-point theorem) that operator A has at least one fixed point, which is a positive solution of our problem, when the positive parameters belong to some intervals. Then, we present intervals for the parameters for which our problem has no positive solution.
Galacto-Oligosaccharide (GOS) Synthesis during Enzymatic Lactose-Free Milk Production: State of the Art and Emerging Opportunities
Authors: Liburdi Katia , Esti Marco
Published: April 2022

Much attention has recently been paid to β-Galactosidases (β-D-galactoside galactohidrolase; EC 3.2.1.23), commonly known as lactases, due to the lactose intolerance of the human population and the importance of dairy products in the human diet. This enzyme, produced by microorganisms, is being used in the dairy industry for hydrolyzing the lactose found in milk to produce lactose-free milk (LFM). Conventionally, β-galactosidases catalyze the hydrolysis of lactose to produce glucose and galactose in LFM; however, they can also catalyze transgalactosylation reactions that produce a wide range of galactooligosaccharides (GOS), which are functional prebiotic molecules that confer health benefits to human health. In this field, different works aims to identify novel microbial sources of β-galactosidase for removing lactose from milk with the relative GOS production. Lactase extracted from thermophilic microorganisms seems to be more suitable for the transgalactosylation process at relatively high temperatures, as it inhibits microbial contamination. Different immobilization methods, such as adsorption, covalent attachment, chemical aggregation, entrapment and micro-encapsulation, have been used to synthesize lactose-derived oligosaccharides with immobilized β-galactosidases. In this mini-review, particular emphasis has been given to the immobilization techniques and bioreactor configurations developed for GOS synthesis in milk, in order to provide a more detailed overview of the biocatalytic production of milk oligosaccharides at industrial level.
Assessing Climate Change Impacts on Island Bees: The Aegean Archipelago
Authors: Kougioumoutzis Konstantinos , Kaloveloni Aggeliki , Petanidou Theodora
Published: April 2022

Pollinators’ climate change impact assessments focus mainly on mainland regions. Thus, we are unaware how island species might fare in a rapidly changing world. This is even more pressing in the Mediterranean Basin, a global biodiversity hotspot. In Greece, a regional pollinator hotspot, climate change research is in its infancy and the insect Wallacean shortfall still remains unaddressed. In a species distribution modelling framework, we used the most comprehensive occurrence database for bees in Greece to locate the bee species richness hotspots in the Aegean, and investigated whether these might shift in the future due to climate change and assessed the Natura 2000 protected areas network effectiveness. Range contractions are anticipated for most taxa, becoming more prominent over time. Species richness hotspots are currently located in the NE Aegean and in highly disturbed sites. They will shift both altitudinally and latitudinally in the future. A small proportion of these hotspots are currently included in the Natura 2000 protected areas network and this proportion is projected to decrease in the coming decades. There is likely an extinction debt present in the Aegean bee communities that could result to pollination network collapse. There is a substantial conservation gap in Greece regarding bees and a critical re-assessment of the established Greek protected areas network is needed, focusing on areas identified as bee diversity hotspots over time.
Assessment of Physicochemical and Rheological Properties of Xylo-Oligosaccharides and Glucose-Enriched Doughs Fermented with BB-12
Authors: Precup Gabriela , Teleky Bernadette-Emőke , Ranga Floricuța , Vodnar Dan Cristian
Published: April 2022

Xylo-oligosaccharides (XOS) are considered non-digestible fibers produced mainly from agricultural biomass and are classified as “emerging prebiotic” compounds. Since XOS were shown to promote the growth of bifidobacteria in the gut with potential effects on one’s health, scientists used them as food ingredients. For example, the addition of XOS in bakery products could improve their physicochemical characteristics. The current work aimed to investigate the effect of XOS and glucose addition on wheat flour sourdough fermented with Bifidobacterium animalis subsp. lactis (BB-12) strain in terms of organic acid production. The effect on viscoelastic changes during frozen storage and after the thawing process was also studied. The results showed that the viability of BB-12 increased slightly with the increase in XOS and glucose concentrations, which determined dough acidification due to accumulation of organic acids, that positively influenced the dough’s rheological properties such as a higher elasticity before and after frozen storage. With 10% XOS-addition, the acetic acid quantity reached 0.87 ± 0.03 mg/L, and the highest lactic acid concentration was found in the 10% XOS-enriched doughs, the glucose-enriched doughs and in the control sample (100% wheat dough). The quantity of glucose, maltose, XOS, and xylose decreased until the end of fermentation.
The CpG Island-Binding Protein SAMD1 Contributes to an Unfavorable Gene Signature in HepG2 Hepatocellular Carcinoma Cells
Authors: Simon Clara , Stielow Bastian , Nist Andrea , Rohner Iris , Weber Lisa Marie , Geller Merle , Fischer Sabrina , Stiewe Thorsten , Liefke Robert
Published: April 2022

The unmethylated CpG island-binding protein SAMD1 is upregulated in many human cancer types, but its cancer-related role has not yet been investigated. Here, we used the hepatocellular carcinoma cell line HepG2 as a cancer model and investigated the cellular and transcriptional roles of SAMD1 using ChIP-Seq and RNA-Seq. SAMD1 targets several thousand gene promoters, where it acts predominantly as a transcriptional repressor. HepG2 cells with SAMD1 deletion showed slightly reduced proliferation, but strongly impaired clonogenicity. This phenotype was accompanied by the decreased expression of pro-proliferative genes, including MYC target genes. Consistently, we observed a decrease in the active H3K4me2 histone mark at most promoters, irrespective of SAMD1 binding. Conversely, we noticed an increase in interferon response pathways and a gain of H3K4me2 at a subset of enhancers that were enriched for IFN-stimulated response elements (ISREs). We identified key transcription factor genes, such as IRF1, STAT2, and FOSL2, that were directly repressed by SAMD1. Moreover, SAMD1 deletion also led to the derepression of the PI3K-inhibitor PIK3IP1, contributing to diminished mTOR signaling and ribosome biogenesis pathways. Our work suggests that SAMD1 is involved in establishing a pro-proliferative setting in hepatocellular carcinoma cells. Inhibiting SAMD1’s function in liver cancer cells may therefore lead to a more favorable gene signature.
Regulatory Crosstalk between Physiological Low O2 Concentration and Notch Pathway in Early Erythropoiesis
Authors: Labat Véronique , Bayard Eva Nguyen van Thanh dit , Refeyton Alice , Huart Mathilde , Avalon Maryse , Debeissat Christelle , Rodriguez Laura , de la Grange Philippe Brunet , Ivanovic Zoran , Vlaski-Lafarge Marija
Published: April 2022

Physiological low oxygen (O2) concentration (<5%) favors erythroid development ex vivo. It is known that low O2 concentration, via the stabilization of hypoxia-induced transcription factors (HIFs), intervenes with Notch signaling in the control of cell fate. In addition, Notch activation is implicated in the regulation of erythroid differentiation. We test here if the favorable effects of a physiological O2 concentration (3%) on the amplification of erythroid progenitors implies a cooperation between HIFs and the Notch pathway. To this end, we utilized a model of early erythropoiesis ex vivo generated from cord blood CD34+ cells transduced with shHIF1α and shHIF2α at 3% O2 and 20% O2 in the presence or absence of the Notch pathway inhibitor. We observed that Notch signalization was activated by Notch2R–Jagged1 ligand interaction among progenitors. The inhibition of the Notch pathway provoked a modest reduction in erythroid cell expansion and promoted erythroid differentiation. ShHIF1α and particularly shHIF2α strongly impaired erythroid progenitors’ amplification and differentiation. Additionally, HIF/NOTCH signaling intersects at the level of multipotent progenitor erythroid commitment and amplification of BFU-E. In that, both HIFs contribute to the expression of Notch2R and Notch target gene HES1. Our study shows that HIF, particularly HIF2, has a determining role in the early erythroid development program, which includes Notch signaling.
Transient Receptor Potential (TRP) Channels: Markers and Therapeutic Targets for Cancer?
Authors: Morelli Maria Beatrice , Amantini Consuelo
Published: April 2022

This Special Issue in Biomolecules explores the roles of Transient Receptor Potential channels (TRPs) in cancer [...]
Factors Influencing Gallstone Formation: A Review of the Literature
Authors: Sun Hao , Warren Jonathan , Yip James , Ji Yu , Hao Shaolong , Han Wei , Ding Yuchuan
Published: April 2022

Gallstone disease is a common pathology of the digestive system with nearly a 10–20% incidence rate among adults. The mainstay of treatment is cholecystectomy, which is commonly associated with physical pain and may also seriously affect a patient’s quality of life. Clinical research suggests that cholelithiasis is closely related to the age, gender, body mass index, and other basic physical characteristics of patients. Clinical research further suggests that the occurrence of cholelithiasis is related to obesity, diabetes, non-alcoholic fatty liver, and other diseases. For this reason, we reviewed the following: genetic factors; excessive liver cholesterol secretion (causing cholesterol supersaturation in gallbladder bile); accelerated growth of cholesterol crystals and solid cholesterol crystals; gallbladder motility impairment; and cardiovascular factors. Herein, we summarize and analyze the causes and mechanisms of cholelithiasis, discuss its correlation with the pathogenesis of related diseases, and discuss possible mechanisms.
Treatment of Painful Palmoplantar Keratoderma Related to Pachyonychia Congenita Using EGFR Inhibitors
Authors: Greco Céline , Ponsen Anne-Charlotte , Leclerc-Mercier Stéphanie , Schlatter Joël , Cisternino Salvatore , Boucheix Claude , Bodemer Christine
Published: April 2022

Pachyonychia congenita (PC) is a genodermatosis associated with severe painful palmoplantar keratoderma (PPK) and thickened dystrophic nails caused by autosomal dominant-negative mutations in five genes encoding keratins 6A-B-C, 16, and 17. The mechanical, surgical, or medical options for painful PC are inefficient. Given ErbB/Her family members’ role in epidermal homeostasis, this study sought to investigate the possibility of treating PC patients with PPK by blocking signaling either with EGFR (Her1) inhibitor erlotinib or lapatinib, a dual EGFR(Her1)/Her2. After 1 month of therapy with oral erlotinib treatment at 75 mg/day, the pain disappeared for patient #1, with partially reduced hyperkeratosis, while increasing the dose to 100 mg/day resulted in painful skin fissures. Therapy replacement with erlotinib cream at 0.2% was inconclusive, and substitution with oral lapatinib at alternating doses of 500 and 750 mg/day achieved a good compromise between pain reduction, symptom improvements, and side effects. Patient #2′s treatment with erlotinib cream failed to display significant improvements. Oral erlotinib started at 75 mg/day then reduced to 25 mg/day because of the formation of an acneiform rash. Treatment considerably improved the patient’s condition, with an almost complete disappearance of pain. Oral Her1 or 1/2 inhibitors reduced pain, improved two PC patients’ quality of life, and offered promising therapeutic perspectives.
Induced and Evoked Brain Activation Related to the Processing of Onomatopoetic Verbs
Authors: Röders Dorian , Klepp Anne , Schnitzler Alfons , Biermann-Ruben Katja , Niccolai Valentina
Published: April 2022

Grounded cognition theory postulates that cognitive processes related to motor or sensory content are processed by brain networks involved in motor execution and perception, respectively. Processing words with auditory features was shown to activate the auditory cortex. Our study aimed at determining whether onomatopoetic verbs (e.g., “tröpfeln”—to dripple), whose articulation reproduces the sound of respective actions, engage the auditory cortex more than non-onomatopoetic verbs. Alpha and beta brain frequencies as well as evoked-related fields (ERFs) were targeted as potential neurophysiological correlates of this linguistic auditory quality. Twenty participants were measured with magnetoencephalography (MEG) while semantically processing visually presented onomatopoetic and non-onomatopoetic German verbs. While a descriptively stronger left temporal alpha desynchronization for onomatopoetic verbs did not reach statistical significance, a larger ERF for onomatopoetic verbs emerged at about 240 ms in the centro-parietal area. Findings suggest increased cortical activation related to onomatopoeias in linguistically relevant areas.
Smart Maintenance and Health Monitoring of Buildings and Infrastructure Using High-Resolution Laser Scanners
Authors: Ozbek Muammer
Published: April 2022

An integrated structural health monitoring system was proposed for the rapid assessment of damage on large structures such as high-rise buildings, industrial chimneys, long-span bridges, and similar facilities. The system used ground-based high-resolution IR (infrared) laser vibrometers to measure the dynamic response of structures. To utilize these devices as automated scanners in a fast and efficient way, a new targeting and control mechanism was developed. Different aspects of the proposed system, such as targeting precision and scanning efficiency, were discussed by presenting the results of laboratory experiments and outdoor vibration tests. In addition to the enhancements made in the measurement system, a new methodology was introduced to analyze the recorded vibration response. A novel data processing approach, based on a comparison of the mode shapes calculated on the healthy reference and damaged structures, made it possible to determine the location of the flaw. If available, a finite element model of the analyzed structure also enables the degree of the damage to be calculated very accurately. The reliability of the identification algorithm was demonstrated by conducting extensive numerical simulations and vibration tests on scale building models.
Germline Variants in Angiogenesis-Related Genes Contribute to Clinical Outcome in Head and Neck Squamous Cell Carcinoma
Authors: Butkiewicz Dorota , Gdowicz-Kłosok Agnieszka , Krześniak Małgorzata , Rutkowski Tomasz , Łasut-Szyszka Barbara , Składowski Krzysztof
Published: April 2022

Fibroblast growth factor (FGF)/FGF receptor (FGFR), and platelet-derived growth factor (PDGF)/PDGF receptor (PDGFR) systems, as well as some matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs), are involved in various steps of angiogenesis. Data indicate that common germline variations in angiogenesis-regulating genes may modulate therapy results and cancer progression. However, whether these variants affect clinical outcome in head and neck squamous cell carcinoma (HNSCC) is unclear. Hence, we assessed the relationship between FGF/FGFR, PDGF/PDGFR, MMP, and TIMP genetic variants and treatment outcomes in HNSCC patients receiving radiotherapy (RT) alone or combined with cisplatin-based chemotherapy. In multivariate analysis, FGF2 rs1048201 CC homozygotes showed a higher risk of death (p = 0.039), while PDGFRA rs2228230 T was strongly associated with an increased risk of locoregional relapse (HR 2.49, p = 0.001) in the combination treatment subgroup. In the RT alone subset, MMP2 rs243865 TT carriers had a higher risk of locoregional recurrence (HR 2.92, p = 0.019), whereas PDGFRB rs246395 CC homozygotes were at increased risk of metastasis (HR 3.06, p = 0.041). The MMP2 rs7201 C and TIMP2 rs7501477 T were associated with a risk of locoregional failure in the entire cohort (p = 0.032 and 0.045, respectively). Furthermore, rs1048201, rs2228230, rs246395, rs243865, rs7201, and rs7201/rs7501477 were independent indicators of an unfavorable outcome. This study demonstrates that the FGF2, PDGFRA, PDGFRB, MMP2, and TIMP2 variants may contribute to treatment failure and poor prognosis in HNSCC.
MMP9: A Tough Target for Targeted Therapy for Cancer
Authors: Augoff Katarzyna , Hryniewicz-Jankowska Anita , Tabola Renata , Stach Kamilla
Published: April 2022

Having the capability to proteolyze diverse structural and signaling proteins, matrix metalloproteinase 9 (MMP9), one of the best-studied secretory endopeptidases, has been identified as a crucial mediator of processes closely associated with tumorigenesis, such as the extracellular matrix reorganization, epithelial to mesenchymal transition, cell migration, new blood vessel formation, and immune response. In this review, we present the current state of knowledge on MMP9 and its role in cancer growth in the context of cell adhesion/migration, cancer-related inflammation, and tumor microenvironment formation. We also summarize recent achievements in the development of selective MMP9 inhibitors and the limitations of using them as anticancer drugs.
Anticancer Potential of Post-Fermentation Media and Cell Extracts of Probiotic Strains: An In Vitro Study
Authors: Nowak Adriana , Zakłos-Szyda Małgorzata , Rosicka-Kaczmarek Justyna , Motyl Ilona
Published: April 2022

Background: Lactic acid bacteria (LAB), many of which are probiotics, can produce health-promoting metabolites (postbiotics). Purpose: To assess the mechanism of antiproliferative action of postbiotics, post-fermentation media (PFM) and cell extracts (CEs) of several strains of LAB were studied against colon (Caco-2), and cervix (HeLa) cancer cell lines, as well as normal intestine (IEC-6) cells, were used as a comparison. Methods: Postbiotics of various LAB (n = 39) were screened for their antiproliferative activity. The effect of PFM and CEs on reactive oxygen species (ROS), mitochondrial membrane potential (MMP), ATP production, phosphatidylserine (PS) externalisation, and apoptosis-related caspases 3/7 and 9 activation was assayed. Results: PFM and CEs showed strong dose-dependent antiproliferative activity against Caco-2 cells, up to 77.8 ± 0.8% and 58.4 ± 1.6% for PFM and CEs, respectively. Stronger inhibitory activity against cancerous (Caco-2 and HeLa) cells than against normal (IEC-6) cells was observed. PFM were more inhibitory than CEs, and both generated oxidative stress in Caco-2 cells. PFM of L. plantarum 0991 and L. brevis 0983 induced apoptosis in Caco-2 cells by the mitochondrial signalling pathway. Conclusions: Anticancer activity of PFM and CEs of LAB, as well as the ability of apoptosis induction, is strain-specific.
Catalytic Hydrogenation of CO2 to Methanol: A Review
Authors: Ren Menghao , Zhang Yanmin , Wang Xuan , Qiu Hengshan
Published: April 2022

High-efficiency utilization of CO2 facilitates the reduction of CO2 concentration in the global atmosphere and hence the alleviation of the greenhouse effect. The catalytic hydrogenation of CO2 to produce value-added chemicals exhibits attractive prospects by potentially building energy recycling loops. Particularly, methanol is one of the practically important objective products, and the catalytic hydrogenation of CO2 to synthesize methanol has been extensively studied. In this review, we focus on some basic concepts on CO2 activation, the recent research advances in the catalytic hydrogenation of CO2 to methanol, the development of high-performance catalysts, and microscopic insight into the reaction mechanisms. Finally, some thinking on the present research and possible future trend is presented.
Continuous Production of DHA and EPA Ethyl Esters via Lipase-Catalyzed Transesterification in an Ultrasonic Packed-Bed Bioreactor
Authors: Kuo Chia-Hung , Tsai Mei-Ling , Wang Hui-Min David , Liu Yung-Chuan , Hsieh Chienyan , Tsai Yung-Hsiang , Dong Cheng-Di , Huang Chun-Yung , Shieh Chwen-Jen
Published: April 2022

Ethyl esters of omega-3 fatty acids are active pharmaceutical ingredients used for the reduction in triglycerides in the treatment of hyperlipidemia. Herein, an ultrasonic packed-bed bioreactor was developed for continuous production of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) ethyl esters from DHA+EPA concentrate and ethyl acetate (EA) using an immobilized lipase, Novozym® 435, as a biocatalyst. A three-level–two-factor central composite design combined with a response surface methodology (RSM) was employed to evaluate the packed-bed bioreactor with or without ultrasonication on the conversion of DHA + EPA ethyl ester. The highest conversion of 99% was achieved with ultrasonication at the condition of 1 mL min−1 flow rate and 100 mM DHA + EPA concentration. Our results also showed that the ultrasonic packed-bed bioreactor has a higher external mass transfer coefficient and a lower external substrate concentration on the surface of the immobilized enzyme. The effect of ultrasound was also demonstrated by a kinetic model in the batch reaction that the specificity constant (V′max/K2) in the ultrasonic bath was 8.9 times higher than that of the shaking bath, indicating the ultrasonication increased the affinity between enzymes and substrates and, therefore, increasing reaction rate. An experiment performed under the highest conversion conditions showed that the enzyme in the bioreactor remained stable at least for 5 days and maintained a 98% conversion.
High-Throughput Screening to Identify Inhibitors of Plasmodium falciparum Importin α
Authors: Walunj Sujata B. , Dias Manisha M. , Kaur Chhaminder , Wagstaff Kylie M. , Dey Vishakha , Hick Caroline , Patankar Swati , Jans David A.
Published: April 2022

The global burden of malaria and toxoplasmosis has been limited by the use of efficacious anti-parasitic agents, however, emerging resistance in Plasmodium species and Toxoplasma gondii threatens disease control worldwide, implying that new agents/therapeutic targets are urgently needed. Nuclear localization signal (NLS)-dependent transport into the nucleus, mediated by members of the importin (IMP) superfamily of nuclear transporters, has shown potential as a target for intervention to limit viral infection. Here, we show for the first time that IMPα from P. falciparum and T. gondii have promise as targets for small molecule inhibitors. We use high-throughput screening to identify agents able to inhibit P. falciparum IMPα binding to a P. falciparum NLS, identifying a number of compounds that inhibit binding in the µM-nM range, through direct binding to P. falciparum IMPα, as shown in thermostability assays. Of these, BAY 11-7085 is shown to be a specific inhibitor of P. falciparum IMPα-NLS recognition. Importantly, a number of the inhibitors limited growth by both P. falciparum and T. gondii. The results strengthen the hypothesis that apicomplexan IMPα proteins have potential as therapeutic targets to aid in identifying novel agents for two important, yet neglected, parasitic diseases.
Plasma Metabolomic Alterations Induced by COVID-19 Vaccination Reveal Putative Biomarkers Reflecting the Immune Response
Authors: Dagla Ioanna , Iliou Aikaterini , Benaki Dimitra , Gikas Evagelos , Mikros Emmanuel , Bagratuni Tina , Kastritis Efstathios , Dimopoulos Meletios A. , Terpos Evangelos , Tsarbopoulos Anthony
Published: April 2022

Vaccination is currently the most effective strategy for the mitigation of the COVID-19 pandemic. mRNA vaccines trigger the immune system to produce neutralizing antibodies (NAbs) against SARS-CoV-2 spike proteins. However, the underlying molecular processes affecting immune response after vaccination remain poorly understood, while there is significant heterogeneity in the immune response among individuals. Metabolomics have often been used to provide a deeper understanding of immune cell responses, but in the context of COVID-19 vaccination such data are scarce. Mass spectrometry (LC-MS) and nuclear magnetic resonance (NMR)-based metabolomics were used to provide insights based on the baseline metabolic profile and metabolic alterations induced after mRNA vaccination in paired blood plasma samples collected and analysed before the first and second vaccination and at 3 months post first dose. Based on the level of NAbs just before the second dose, two groups, “low” and “high” responders, were defined. Distinct plasma metabolic profiles were observed in relation to the level of immune response, highlighting the role of amino acid metabolism and the lipid profile as predictive markers of response to vaccination. Furthermore, levels of plasma ceramides along with certain amino acids could emerge as predictive biomarkers of response and severity of inflammation.
Proteomic Analysis of the Role of the Adenylyl Cyclase–cAMP Pathway in Red Blood Cell Mechanical Responses
Authors: Ugurel Elif , Goksel Evrim , Cilek Neslihan , Kaga Elif , Yalcin Ozlem
Published: April 2022

Red blood cell (RBC) deformability is modulated by the phosphorylation status of the cytoskeletal proteins that regulate the interactions of integral transmembrane complexes. Proteomic studies have revealed that receptor-related signaling molecules and regulatory proteins involved in signaling cascades are present in RBCs. In this study, we investigated the roles of the cAMP signaling mechanism in modulating shear-induced RBC deformability and examined changes in the phosphorylation of the RBC proteome. We implemented the inhibitors of adenylyl cyclase (SQ22536), protein kinase A (H89), and phosphodiesterase (PDE) (pentoxifylline) to whole blood samples, applied 5 Pa shear stress (SS) for 300 s with a capillary tubing system, and evaluated RBC deformability using a LORRCA MaxSis. The inhibition of signaling molecules significantly deteriorated shear-induced RBC deformability (p < 0.05). Capillary SS slightly increased the phosphorylation of RBC cytoskeletal proteins. Tyrosine phosphorylation was significantly elevated by the modulation of the cAMP/PKA pathway (p < 0.05), while serine phosphorylation significantly decreased as a result of the inhibition of PDE (p < 0.05). AC is the core element of this signaling pathway, and PDE works as a negative feedback mechanism that could have potential roles in SS-induced RBC deformability. The cAMP/PKA pathway could regulate RBC deformability during capillary transit by triggering significant alterations in the phosphorylation state of RBCs.
The Psychometric Properties and Cutoff Score of the Child and Adolescent Mindfulness Measure (CAMM) in Chinese Primary School Students
Authors: Chen Xin , Liang Kaixin , Huang Liuyue , Mu Wenlong , Dong Wenjing , Chen Shiyun , Chen Sitong , Chi Xinli
Published: April 2022

To date, the Child and Adolescent Mindfulness Measure (CAMM) has been translated into several languages, including Chinese. This study aimed to explore the reliability and validity of the Chinese version of the CAMM and to identify the appropriate cutoff score among Chinese primary school students. A total of 1283 participants (52.2% males; 11.52 ± 0.78 years of age) completed a series of questionnaires to evaluate their mental health, including mindfulness, subjective well-being, positive youth development (PYD), depression, and anxiety. Item analysis, Confirmatory Factor Analysis (CFA), Exploratory Structural Equation Modeling (ESEM), criterion-related validity analysis, Receiver Operating Characteristic (ROC) analysis, and reliability analysis were performed. The results show that the Chinese version of the CAMM had acceptable item–scale correlation (r = 0.405–0.775, p < 0.001) and was the best fit for the two-factor ESEM model (χ2 = 168.251, p < 0.001, df = 26, TLI = 0.910, CFI = 0.948, RMSEA = 0.065, SRMR = 0.033) among Chinese primary school students. Additionally, the total score of the Chinese version of the CAMM was significantly associated with subjective well-being and PYD (r = 0.287–0.381, p < 0.001), and negatively associated with depression, and anxiety (r = −0.612–−0.542, p < 0.001). Moreover, a cutoff score of 22 or higher revealed a significant predictive power for all the included criteria. Finally, the Chinese version of the CAMM had good internal consistency (Cronbach’s α = 0.826, McDonald’s ω = 0.826). Altogether, the Chinese version of the CAMM had satisfactory psychometric properties, and it can be applied to Chinese children.
Dextro-Transposition of Great Arteries and Neurodevelopmental Outcomes: A Review of the Literature
Authors: Kordopati-Zilou Kalliopi , Sergentanis Theodoros , Pervanidou Panagiota , Sofianou-Petraki Danai , Panoulis Konstantinos , Vlahos Nikolaos , Eleftheriades Makarios
Published: April 2022

Background: Arterial switch operation (ASO) is the gold-standard surgical approach for dextro-transposition of the great arteries (D-TGA). It is performed during the neonatal period and has almost diminished the previously high mortality rate (from 90% if left untreated to <0.5%). Despite the impressively high survival rates, the surgical procedure itself—along with the chronic post-operative complications and the perinatal impaired cerebral oxygen delivery—introduces multiple and cumulative risk factors for neurodevelopmental impairment. Method: This study is a review of English articles, using PUBMED and applying the following search terms, “transposition of the great arteries”, “neurodevelopment”, “autism”, “cerebral palsy”, and “attention-deficit hyperactivity disorder”. Data were extracted by two authors. Results: Even though general IQ is mainly found within the normal range, D-TGA children and adolescents display reduced performance in the assignments of executive functions, fine motor functions, attention, working memory, visual–spatial skills, and higher-order language skills. Moreover, D-TGA survivors may eventually struggle with inferior academic achievements and psychiatric disorders such as depression, anxiety, and ADHD. Conclusions: The existing literature concerning the neurodevelopment of D-TGA patients suggests impairment occurring during their lifespan. These findings underline the importance of close developmental surveillance so that D-TGA patients can better reach their full potential.
Guideline Adherence of Paediatric Urolithiasis: An EAU Members’ Survey and Expert Panel Roundtable Discussion
Authors: Bañuelos Marco Beatriz , Haid Bernhard , Radford Anna , Knoll Thomas , Sultan Sajid , Spinoit Anne-Françoise , Hiess Manuela , Sforza Simone , Lammers Rianne J. M. , ‘t Hoen Lisette Aimée , Bindi Edoardo , O’Kelly Fardod , Silay Mesrur Selçuk ,   on behalf of the EAU Young Academic Urologists (YAU) Paediatric Urology Group
Published: April 2022

Background: Paediatric nephrolithiasis has increased globally, requiring standardized recommendations. This study aims to assess the paediatric urolithiasis care between EAU members along with the statements of three experts in this field. Methods: The results of an electronic survey among EAU members comparing the guideline recommendations to their current practice managing paediatric nephrolithiasis in 74 centres are contrasted with insights from an expert-panel. The survey consisted of 20 questions in four main sections: demographics, instrument availability, surgical preferences and follow-up preferences. Experts were asked to give insights on the same topics. Results: A total of 74 responses were received. Computerised Tomography was predominantly used as the main imaging modality over ultrasound. Lack of gonadal protection during operations was identified as an issue. Adult instruments were used frequently instead of paediatric instruments. Stone and metabolic analysis were performed by 83% and 63% of the respondents respectively. Conclusions: Percutaneous Nephrolithotomy is the recommended standard treatment for stones > 20 mm, 12% of respondents were still performing shockwave lithotripsy despite PNL, mini and micro-PNL being available. Children have a high risk for recurrence yet stone and metabolic analysis was not performed in all patients. Expert recommendations may guide clinicians towards best practice.
Frequency of Winter Coupled North Pacific/North America Circulation Regimes
Authors: Overland James E. , Wang Muyin
Published: April 2022

The jet stream over North America alternates between a more zonal direction and a wavy pattern (a more meridional flow) associated with persistent blocking patterns. To better understand these important patterns, we base our study on the frequency of winter (November–February) events during 1981–2020, based on four circulation regime types: blocking, the Alaskan Ridge, North American Ridge/Pacific Wave-Train; and zonal, the Pacific Trough and the central Pacific High/Arctic Low (Amini and Straus 2019). Increased information on within and between season variability is important, as the impacts of blocking include the California heatwave and mid-continent or east coast cold spells. Rather than extensive pattern duration or significant trends, temporal variability is the major feature. In some years the combination of the Alaskan Ridge and North American Ridge/Pacific Wave-Train patterns represent ~5 major events covering 35 days of the 120-day winter period, with individual events lasting 10 days. Within-season multiple occurrences and short durations dominate the winter meteorology of the continental United States. The characterization of the persistence of these blocking events is relevant for extended range forecasts.
Climate Change Impact on Energy Poverty and Energy Efficiency in the Public Housing Building Stock of Bari, Italy
Authors: Vurro Giandomenico , Santamaria Valentina , Chiarantoni Carla , Fiorito Francesco
Published: April 2022

The public housing stock across the European Union is generally constituted of old buildings (built prior to 1980) with high energy demand and indoor thermal comfort issues, which could be exacerbated by climate change. The aim of this paper was to quantify the impact of climate change on the energy demand of the public housing building stock. A neighbourhood located in Bari (south Italy) is considered as representative of a common construction typology of late 1970s in Italy. Energy models were created and calibrated with real-time data collected from utilities’ bills. The results showed a medium to strong correlation between age and energy consumption (r = 0.358), but no evident correlation between the number of tenants and energy consumption, although a significantly low energy consumption was found in apartments occupied by more than five tenants. An energy penalty of about 7 kWh/m2 of heating energy consumption for every 10 years of increase in the average age of tenants was calculated. Moreover, the impact of future weather scenarios on energy consumptions was analysed and an average annual energy penalty of 0.3 kWh/m2 was found.