Brazilian law requires that treatment for breast cancer begin within 60 days of diagnosis. This waiting time is an indicator of accessibility to health services. The aim of this study was to analyze which factors are associated with waiting times between diagnosis and treatment of breast cancer in women in Brazil between 1998 and 2012. Information from Brazilian women diagnosed with breast cancer between 1998 and 2012 was collected through the Hospital Registry of Cancer (HRC), developed by the National Cancer Institute (INCA). We performed a secondary data analysis, and found that the majority of women (81.3%) waited for ≤60 days to start treatment after being diagnosed. Those referred by the public health system, aged ≥50 years, of nonwhite race, diagnosed at stage I or II, and with low levels of education waited longer for treatment to start. We observed that only 18.7% experienced a delay in starting treatment, which is a positive reflection of the quality of the care network for the diagnosis and treatment of breast cancer. We also observed inequalities in access to health services related to age, region of residence, stage of the disease, race, and origin of referral to the health service. Full article

In this paper, fly ash is used to inhibit the alkali-carbonate reaction (ACR). The experimental results suggest that when the alkali equivalent (equivalent Na₂Oeq) of the cement is 1.0%, the adding of 30% fly ash can significantly inhibit the expansion in low-reactivity aggregates. For moderately reactive aggregates, the expansion rate can also be reduced by adding 30% of fly ash. According to a polarizing microscope analysis, the cracks are expansion cracks mainly due to the ACR. The main mechanisms of fly ash inhibiting the ACR are that it refines the pore structure of the cement paste, and that the alkali migration rate in the curing solution to the interior of the concrete microbars is reduced. As the content of fly ash increases, the concentrations of K⁺ and Na⁺ and the pH value in the pore solution gradually decrease. This makes the ACR in the rocks slower, such that the cracks are reduced, and the expansion due to the ACR is inhibited. Full article

Severe plastic deformation (SPD) techniques are known to promote exceptional mechanical properties due to their ability to induce significant grain and cell size refinement. Cell and grain refinement are driven by continuous newly introduced dislocations and their evolution can be followed at the earliest stages of plastic deformation. Pure metals are the most appropriate to study the early deformation processes as they can only strengthen by dislocation rearrangement and cell-to-grain evolution. However, pure metals harden also depend on texture evolution and on the metal stacking fault energy (SFE). Low SFE metals (i.e., copper) strengthen by plastic deformation not only by dislocation rearrangements but also by twinning formation within the grains. While, high SFE metals, (i.e., aluminium) strengthen predominantly by dislocation accumulation and rearrangement with plastic strain. Thence, in the present study, the early stages of plastic deformation were characterized by transmission electron microscopy on pure low SFE Oxygen-Free High Conductivity (OFHC) 99.99% pure Cu and on a high SFE 6N-Al. To induce an almost continuous rise from very-low to low plastic deformation, the two pure metals were subjected to high-pressure torsion (HPT). The resulting strengthening mechanisms were modelled by microstructure quantitative analyses carried out on TEM and then validated through nanoindentation measurements. Full article

Our societies rely on the quality and availability of natural resources. Driven by population growth, economic development, and innovation, future demand for natural resources is expected to further increase in coming decades. Raw materials will be an important part of society’s future material mix as countries increasingly transition towards resource-efficient and greenhouse-gas neutral economies. Raw materials are also fundamental to meet ecological and socio-economic targets within the UN Sustainable Development Agenda. For instance, they have a fundamental role in renewable energy technologies, new building materials and infrastructure, communication systems, and low-carbon transportation. However, some materials are largely supplied from countries with poor governance. The future availability of these materials and associated impacts are of increasing concern going forward. Recent raw material criticality studies have explored economic, geo-political, and technological factors that affect materials’ supply. However, environmental and social pressures also play a role in their security of supply. For instance, conflicts can prevent access to mineral deposits; accidents and environmental damage compromise public acceptance and can hinder future extraction operations. This article will introduce this Special Issue with a focus on material requirements and responsible sourcing of materials for a low-carbon society, and provides an overview of the subsequent research papers. Full article

Breast cancer is the most frequent cancer diagnosed in women and the second most common cancer-causing death worldwide. The major problem around the management of breast cancer is its high heterogeneity and the development of therapeutic resistance. Therefore, understanding the fundamental breast cancer biology is crucial for better diagnosis and therapy. Protein sialylation is a key posttranslational modification of glycoproteins, which is also involved in tumor progression and metastasis. Increased expression of sialic acids (Sia) can interfere in receptor–ligand interactions and might protect tumor cells from the immune system. Furthermore, Sia content on the cell membrane plays a role in cancer resistance towards chemo- and radiation therapy. In this study, we glycoengineered MCF-7 breast cancer cells using a series of non-natural Sia precursors, which are prolonged in their acyl side chain. We observed a significant reduction in the natural Sia (N-Acetylneuraminic acid) expression after cultivation of MCF-7 cells with these Sia precursors. In addition, the expression of polySia, a unique glycosylation of the neural cell adhesion molecule NCAM, which interferes with cell adhesion, was decreased. We conclude that sialic acid engineering i) opens up novel opportunities to study the biological role of Sia in breast cancer and ii) provides a toolbox to examine the sialic acid-dependent complex cellular alterations in breast cancer cell biology. Full article

Hurricanes cause landscape-scale disturbances that affect biogeochemical cycling and water quality in coastal ecosystems. During Hurricane Irma’s passage through northern Florida, water movements driven by wind velocities up to 105 km h⁻¹ caused a salinity peak in an estuary/blackwater river complex. Water quality was monitored across the 15 km site to detect the magnitude and duration of disturbance. Saline water intruded 15 km inland into a freshwater portion of the river that peaked at a salinity of 2 psu. Due to the volume of precipitation from the hurricane, significant runoff of freshwater and dissolved organic matter (DOM) caused a decrease in salinity, dissolved oxygen (DO), and Chlorophyll-a concentrations while increasing turbidity and fluorescent dissolved organic matter (fDOM). The disturbance caused rapid changes observed by in-situ water quality monitors over a 3-week period, but some effects persisted for longer periods as shown by 3-month weekly water sampling. This disturbance caused shifts in DOM loading, altered salinity dynamics, and reshaped landscapes due to wind and wave surge both in upland marsh and downstream estuary. Hurricane disturbance temporarily and abruptly alters the aquatic continuum, and observations of system response can help us understand the mechanisms associated with ecosystem resilience and recovery. Full article

Diabetes mellitus-related morbidity and mortality is a rapidly growing healthcare problem, globally. Several nutraceuticals exhibit potency to target the pathogenesis of diabetes mellitus. The antidiabetic effects of compounds of garlic have been extensively studied, however, limited data are available on the biological effects of a certain garlic component, allithiamine. In this study, allithiamine was tested using human umbilical cord vein endothelial cells (HUVECs) as a hyperglycaemic model. HUVECs were isolated by enzymatic digestion and characterized by flow cytometric analysis using antibodies against specific marker proteins including CD31, CD45, CD54, and CD106. The non-cytotoxic concentration of allithiamine was determined based on MTT, apoptosis, and necrosis assays. Subsequently, cells were divided into three groups: incubating with M199 medium as the control; or with 30 mMol/L glucose; or with 30 mMol/L glucose plus allithiamine. The effect of allithiamine on the levels of advanced glycation end-products (AGEs), activation of NF-κB, release of pro-inflammatory cytokines including IL-6, IL-8, and TNF-α, and H₂O₂-induced oxidative stress was investigated. We found that in the hyperglycaemia-induced increase in the level of AGEs, pro-inflammatory changes were significantly suppressed by allithiamine. However, allithiamine could not enhance the activity of transketolase, but it exerts a potent antioxidant effect. Collectively, our data suggest that allithiamine could alleviate the hyperglycaemia-induced endothelial dysfunction due to its potent antioxidant and anti-inflammatory effect by a mechanism unrelated to the transketolase activity. Full article

Background. Meningiomas constitute one-third of all primary brain tumors. Although typically benign, about 20% of these tumors recur despite surgery and radiation, and may ultimately prove fatal. There are currently no effective chemotherapies for meningioma. We, therefore, set out to develop patient-derived orthotopic xenograft (PDOX) mouse models of human meningioma using tumor. Method. Of nine patients, four had World Health Organization (WHO) grade I tumors, five had WHO grade II tumors, and in this second group two patients also had recurrent (WHO grade III) meningioma. We also classified the tumors according to our recently developed molecular classification system (Types A, B, and C, with C being the most aggressive). We transplanted all 11 surgical samples into the skull base of immunodeficient (SCID) mice. Only the primary and recurrent tumor cells from one patient—both molecular Type C, despite being WHO grades II and III, respectively—led to the formation of meningioma in the resulting mouse models. We characterized the xenografts by histopathology and RNA-seq and compared them with the original tumors. We performed an in vitro drug screen using 60 anti-cancer drugs followed by in vivo validation. Results. The PDOX models established from the primary and recurrent tumors from patient K29 (K29P-PDOX and K29R-PDOX, respectively) replicated the histopathology and key gene expression profiles of the original samples. Although these xenografts could not be subtransplanted, the cryopreserved primary tumor cells were able to reliably generate PDOX tumors. Drug screening in K29P and K29R tumor cell lines revealed eight compounds that were active on both tumors, including three histone deacetylase (HDAC) inhibitors. We tested the HDAC inhibitor Panobinostat in K29R-PDOX mice, and it significantly prolonged mouse survival (p < 0.05) by inducing histone H3 acetylation and apoptosis. Conclusion. Meningiomas are not very amenable to PDOX modeling, for reasons that remain unclear. Yet at least some of the most malignant tumors can be modeled, and cryopreserved primary tumor cells can create large panels of tumors that can be used for preclinical drug testing. Full article

This paper exploits an effective approach to overcome the breakdown limitations of traditional galvanic isolators based on chip-scale isolation barriers, thus achieving a very high isolation rating (i.e., compliant with the reinforced isolation requirements). Such an approach is based on radio frequency (RF) planar coupling between two side-by-side co-packaged chips. Standard packaging along with proper assembling techniques can be profitably used to go beyond 20-kV surge voltage without using expensive or exotic isolation components. As a proof of concept, a bidirectional data transfer system based on RF planar coupling able to withstand an isolation rating as high as 25 kV has been designed in a low-cost standard 0.35-µm CMOS technology. Experimental measurements demonstrated a maximum data rate of 40 Mbit/s using a carrier frequency of about 1 GHz. The adopted approach also guarantees a common mode transient immunity (CMTI) of 250 kV/µs, which is a firstrate performance in view of next generation galvanic isolators for wide-bandgap power semiconductor devices, such as gallium nitride high-electron mobility transistors (GaN HEMTs) and silicon carbide (SiC) MOSFETs. Full article

Nonlinear dissipative phenomena are common features of many dynamical systems and engineering applications, and their experimental characterization has always been a challenge among the research community. Within the wide range of nonlinear damping mechanisms, friction is surely one of the most common, and with a high impact on the dynamical behavior of structures. In this paper, the nonlinear identification of friction in a negative stiffness oscillator is pursued. The structure exhibits a strong nonlinear behavior, mainly due to its polynomial elastic restoring force with a negative stiffness region. This leads to an asymmetric double-well potential with two stable equilibrium positions, and the possibility of switching between them in a chaotic way. Friction plays a crucial role in this context, as it derives from the continuous sliding between the central guide and the moving mass. The system is driven through harmonic tests with several input amplitudes, in order to estimate the variations in the energy dissipated per cycle. The identification of the frictional behavior is then pursed by minimizing the errors between the experimental measurements and the model predictions, using the harmonic balance method in conjunction with a continuation technique on the forcing amplitudes. Full article

From an animal health perspective, relatively little is known about the typical or healthy ranges of concentrations for many metabolites in bovine biofluids and tissues. Here, we describe the results of a comprehensive, quantitative metabolomic characterization of six bovine biofluids and tissues, including serum, ruminal fluid, liver, Longissimus thoracis (LT) muscle, semimembranosus (SM) muscle, and testis tissues. Using nuclear magnetic resonance (NMR) spectroscopy, liquid chromatography–tandem mass spectrometry (LC–MS/MS), and inductively coupled plasma–mass spectrometry (ICP–MS), we were able to identify and quantify more than 145 metabolites in each of these biofluids/tissues. Combining these results with previous work done by our team on other bovine biofluids, as well as previously published literature values for other bovine tissues and biofluids, we were able to generate quantitative reference concentration data for 2100 unique metabolites across five different bovine biofluids and seven different tissues. These experimental data were combined with computer-aided, genome-scale metabolite inference techniques to add another 48,628 unique metabolites that are biochemically expected to be in bovine tissues or biofluids. Altogether, 51,801 unique metabolites were identified in this study. Detailed information on these 51,801 unique metabolites has been placed in a publicly available database called the Bovine Metabolome Database. Full article

In this article, poly(ethylene oxide)-based polymer electrolyte films doped with ammonium iodide (NH₄I) and plasticized with glycerol were provided by a solution casting method. In the unplasticized system, the maximum ionic conductivity of 3.96 × 10-5 S cm⁻¹ was achieved by the electrolyte comprised of 70 wt. % PEO:30 wt. % NH₄I. The conductivity was further enhanced up to (1.77×10-4 S cm⁻¹) for the plasticized system when 10 wt. % glycerol was added to the highest conducting unplasticized one at ambient temperature. The films were characterized by various techniques to evaluate their electrochemical performance. The results of impedance spectroscopy revealed that bulk resistance (R_b) considerably decreased for the highest plasticized polymer electrolyte. The dielectric properties and electric modulus parameters were studied in detail. The LSV analysis verified that the plasticized system can be used in energy storage devices with electrochemical stability up to 1.09 V and the TNM data elucidated that the ions were the main charge carrier. The values of the ion transference number (t_ion) and electron transfer number (t_el) were calculated. The nonappearance of any redox peaks in the cyclic voltammograms indicated that the chemical reaction had not occurred at the electrode/electrolyte interface. Full article

This study investigated the leaves of Clinacanthus nutans for its bioactive compounds and acute and subacute toxicity effects of C. nutans ethanolic leaf extract (CELE) on blood, liver and kidneys of ICR mice. A total of 10 8-week-old female mice were divided into groups A (control) and B (2000 mg/kg) for the acute toxicity study. A single dose of 2000 mg/kg was administered to group B through oral gavage and mice were monitored for 14 days. In the subacute toxicity study, mice were divided into five groups: A (control), B (125 mg/kg), C (250 mg/kg), D (500 mg/kg) and E (1000 mg/kg). The extract was administered daily for 28 days via oral gavage. The mice were sacrificed, and samples were collected for analyses. Myricetin, orientin, isoorientin, vitexin, isovitexin, isookanin, apigenin and ferulic acid were identified in the extract. Twenty-eight days of continuous oral administration revealed significant increases (p < 0.05) in creatinine, ALT and moderate hepatic and renal necrosis in groups D and E. The study concluded that the lethal dose (LD₅₀) of CELE in mice is greater than 2000 mg/kg and that repeated oral administrations of CELE for 28 days induced hepatic and renal toxicities at 1000 mg/kg in female ICR mice. Full article

A series of GdCu ${}_2$ nanoparticles with controlled sizes ranging from 7 nm to 40 nm has been produced via high-energy inert-gas ball milling. Rietveld refinements on the X-ray diffraction measurements ensure that the bulk crystalline $Imma$ structure is retained within the nanoparticles, thanks to the employed low milling times ranging from t = 0.5 to t = 5 h. The analysis of the magnetic measurements shows a crossover from Superantiferromagnetism (SAF) to a Super Spin Glass state as the size decreases at NP size of $⟨D⟩\approx$ 18 nm. The microstrain contribution, which is always kept below 1%, together with the increasing surface-to-core ratio of the magnetic moments, trigger the magnetic disorder. Additionally, an extra contribution to the magnetic disorder is revealed within the SAF state, as the oscillating RKKY indirect exchange achieves to couple with the aforementioned contribution that emerges from the size reduction. The combination of both sources of disorder leads to a maximised frustration for $⟨D⟩\approx$ 25 nm sized NPs. Full article

A series of yeast strains was tested in order to evaluate their catalytic potential in biocatalysis of one-pot indolizine’s synthesis. Yeast cultivation was performed in a submerged system at 28 °C for 72 h at 180 rpm. An assessment of the reagents’ toxicity on yeast viability and metabolic functionality concluded that the growth potential of three Yarrowia lipolytica strains were least affected by the reactants compared to the other yeast strains. Further, crude fermentation products (biomass and cell-free supernatant)—obtained by submerged cultivation of these yeasts—were used in multistep cascade reactions for the production of fluorescent indolizine compounds with important biologic activities. A whole–cell catalyzed multicomponent reaction of activated alkynes, α-bromo-carbonyl reagents and 4,4′-bipyridine, at room temperature in buffer solution led to the efficient synthesis of bis-indolizines 4a, 4b and 4c, in good-to-excellent yields (47%–77%). The metabolites of the selected Y. lipolytica strains can be considered effective biocatalysts in cycloaddition reactions and the high purity and bioconversion yields of the synthesized indolizines indicates a great potential of this type of “green” catalysts. Seeds of Triticum estivum L. were used to investigate the impact of the final products on the germination and seedling growth. The most sensitive physiological parameters suggest that indolizines, at the concentrations tested, have non-toxic effect on germination and seedling growth of wheat, fact also confirmed by confocal laser scanning microscopy images. Full article

Bitterness in almonds is controlled by a single gene (Sk dominant for sweet kernel, sk recessive for bitter kernel) and the proportions of the offspring genotypes (SkSk, Sksk, sksk) depend on the progenitors’ genotype. Currently, the latter is deduced after crossing by recording the phenotype of their descendants through kernel tasting. Chemical markers to early identify parental genotypes related to bitter traits can significantly enhance the efficiency of almond breeding programs. On this basis, volatile metabolites related to almond bitterness were investigated by Solid Phase Microextraction-Gas Chromatography-Mass Spectrometry coupled to univariate and multivariate statistics on 244 homo- and heterozygous samples from 42 different cultivars. This study evidenced the association between sweet almonds’ genotype and some volatile metabolites, in particular benzaldehyde, and provided for the first time chemical markers to discriminate between homo- and heterozygous sweet almond genotypes. Furthermore, a multivariate approach based on independent variables was developed to increase the reliability of almond classification. The Partial Least Square-Discriminant Analysis classification model built with selected volatile metabolites that showed discrimination capacity allowed a 98.0% correct classification. The metabolites identified, in particular benzaldehyde, become suitable markers for the early genotype identification in almonds, while a DNA molecular marker is not yet available. Full article