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Mark Carroll opublikował 1 rok, 3 miesiące temu
BACKGROUND Malignant neoplasms of the salivary glands are rare, and therapeutic options are limited. Results from recently published studies indicate a possible use for checkpoint inhibition in a subset of patients, but there are no established criteria for programme cell death ligand 1 (PD-L1) scoring in salivary gland carcinomas (SGCs). METHODS In this retrospective study, we present a cohort of 94 SGC patients with full clinical follow-up. We included 41 adenoid cystic carcinomas (AdCC), 21 mucoepidermoid carcinomas (MEC), 16 acinic cell carcinomas (ACC), 12 adenocarcinomas, not otherwise specified (AC, NOS), 2 epithelial-myoepithelial carcinomas (EMC), one salivary duct carcinoma (SDC), and one carcinoma ex pleomorphic adenoma (CA ex PA). Subsequent histopathological analysis was performed with special emphasis on the composition of the immune cell infiltrate (B-/T-lymphocytes). We assessed PD-L1 (SP263) on full slides by established scoring criteria tumor proportion score (TPS), combined positivity score (CPS) and immune cell (IC) score. RESULTS We identified significantly elevated CD3+, TP, CP, and IC scores in AC, NOS compared to AdCC, MEC, and ACC. CPS correlated with node-positive disease. Moreover, AC, NOS displayed IC scores of 2 or 3 in the majority (67%) of cases (p = 0.0031), and was associated with poor prognosis regarding progression-free (PFS) (p less then 0.0001) and overall survival (OS) (p less then 0.0001). CPS correlated with strong nuclear or null p53 staining in AC, NOS but not in other SGCs. Long-lasting partial remission could be achieved in one AC, NOS patient who received Pembrolizumab as third-line therapy. CONCLUSIONS The current study is the first to investigate the use of established scoring criteria for PD-L1 expression in malignant salivary gland tumors. Our findings identify unique characteristics for AC, NOS among the family of SGCs, as it is associated with poor prognosis and might represent a valuable target for immune checkpoint inhibition.Air pollution is one of the world’s leading environmental causes of death. The epidemiological relationship between outdoor air pollution and the onset of health diseases associated with death is now well established. Relevant toxicological proofs are now dissecting the molecular processes that cause inflammation, reactive species generation, and DNA damage. In addition, new data are pointing out the role of airborne particulates in the modulation of genes and microRNAs potentially involved in the onset of human diseases. In the present review we collect the relevant findings on airborne particulates of one of the biggest hot spots of air pollution in Europe (i.e., the Po Valley), in the largest urban area of this region, Milan. The different aerodynamic fractions are discussed separately with a specific focus on fine and ultrafine particles that are now the main focus of several studies. Results are compared with more recent international findings. Possible future perspectives of research are proposed to create a new discussion among scientists working on the toxicological effects of airborne particles.Migration to the U.S. has been associated with increased body size and obesity risk in Latinas, but results for Caribbean immigrant women are limited and inconclusive. Emerging evidence also suggests that early-life environment associations with women’s midlife body mass index (BMI) may be different for larger and smaller women, but this has not been tested within migration life-course history. We examined the associations of nativity and migration timing with midlife body size in a sample of majority Caribbean Latinas and whether these associations varied across the body size distribution. We used interview data from 787 self-identified Latinas (ages 40-65 years) and assessed overall obesity using BMI (kg/m2) and central obesity based on waist circumference (WC, cm). We used linear and quantile regression to examine the association of migration history with BMI and WC and logistic regression for the probability of obesity. Foreign birthplace, later migration age, and lower percent of life in the U.S. were associated with lower BMI and WC means and lower odds of overall and central obesity. Quantile regression showed only inverse associations in the upper quantiles of BMI and WC. For example, relative to U.S.-born women, women living less then 50% of their lives in the U.S. had lower BMI in the 75th BMI percentile (β = -4.10, 95% CI -6.75, -0.81), with minimal differences in the 25th (β = 0.04, 95% CI -1.01, 0.96) and 50th BMI percentiles (β = -1.54, 95% CI -2.90, 0.30). Our results support that migration to and increasing time in the U.S. are associated with greater body size in midlife Latina women, with stronger influences at higher body size distribution.Background Tacrolimus is routinely monitored using trough concentrations, however, recent data have suggested that area under the curve (AUC) provides better correlation with toxicity and efficacy. Area under the curve is cumbersome to measure, but studies have demonstrated that surrogate time points such as 2-hour concentrations are well correlated with AUC. Methods This is a single center, retrospective study of adult kidney transplant recipients with 2-hour tacrolimus concentrations measured over three years post-transplant. The primary outcome was to determine the difference in serum creatinine (Scr) in those with 2-hour tacrolimus concentrations greater than 20 ng/mL versus those less than or equal to 20 ng/mL. Results A total of 150 kidney transplant recipients were included. The mean Scr and glomerular filtration rate were 1.49 ± 1.01 mg/dL and 59 ± 23.2 ml/min/1.73 m2, respectively, for the entire cohort. The rate of donor specific antibody formation was 2% and 8% experienced biopsy-proven rejection. The rate of cytomegalovirus viremia was 2% and BK viremia was 13%. There was no significant difference in kidney function over 36 months for the groups specified a priori. Conclusions Long-term outcomes of maintaining tacrolimus 2-hour concentrations over 20 ng/mL is favorable with minimal opportunistic infections.A detailed comparison of the gas permeability of four Polymers of Intrinsic Microporosity containing Tröger’s base (TB-PIMs) is reported. In particular, we present the results of a systematic study of the differences between four related polymers, highlighting the importance of the role of methyl groups positioned at the bridgehead of ethanoanthracene (EA) and triptycene (Trip) components. The PIMs show BET surface areas between 845-1028 m2 g-1 and complete solubility in chloroform, which allowed for the casting of robust films that provided excellent permselectivities for O2/N2, CO2/N2, CO2/CH4 and H2/CH4 gas pairs so that some data surpass the 2008 Robeson upper bounds. Their interesting gas transport properties were mostly ascribed to a combination of high permeability and very strong size-selectivity of the polymers. Time lag measurements and determination of the gas diffusion coefficient of all polymers revealed that physical ageing strongly increased the size-selectivity, making them suitable for the preparation of thin film composite membranes.Differentiation therapy is an alternative strategy used to induce the differentiation of blast cells toward mature cells and to inhibit tumor cell proliferation for cancer treatment. Nobiletin (NOB), a polymethoxyflavone phytochemical, is present abundantly in citrus peels and has been reported to possess anti-cancer activity. In this study, we investigated the anti-leukemic effects of NOB on cell differentiation and its underlying mechanisms in human chronic myeloid leukemia (CML) K562 cells. NOB (100 μM) treatment for 24 and 48 h significantly decreased viability of K562 cells to 54.4 ± 5.3% and 46.2 ± 9.9%, respectively. NOB (10-100 μM) significantly inhibited cell growth in K562 cells. Flow cytometry analysis and immunoblotting data showed that NOB (40 and 80 μM) could modulate the cell cycle regulators including p21, p27, and cyclin D2, and induce G1 phase arrest. NOB also increased the messenger RNA (mRNA) and protein expression of megakaryocytic differentiation markers, such as CD61, CD41, and CD42 as well as the formation of large cells with multi-lobulated nuclei in K562 cells. These results suggested that NOB facilitated K562 cells toward megakaryocytic differentiation. Furthermore, microarray analysis showed that expression of EGR1, a gene associated with promotion of megakaryocytic differentiation, was markedly elevated in NOB-treated K562 cells. The knockdown of EGR1 expression by small interference RNA (siRNA) could significantly attenuate NOB-mediated cell differentiation. We further elucidated that NOB induced EGR1 expression and CD61 expression through increases in MAPK/ERK phosphorylation in K562 cells. These results indicate that NOB promotes megakaryocytic differentiation through the MAPK/ERK pathway-dependent EGR1 expression in human CML cells. In addition, NOB when combined with imatinib could synergistically reduce the viability of K562 cells. Our findings suggest that NOB may serve as a beneficial anti-leukemic agent for differentiation therapy.Endothelial colony-forming cells (ECFC) are currently considered as a promising cell population for the pre-endothelialization or pre-vascularization of tissue-engineered constructs, including small-diameter biodegradable vascular grafts. However, the extent of heterogeneity between ECFC and mature vascular endothelial cells (EC) is unclear. Here, we performed a transcriptome-wide study to compare gene expression profiles of ECFC, human coronary artery endothelial cells (HCAEC), and human umbilical vein endothelial cells (HUVEC). Characterization of the abovementioned cell populations was carried out by immunophenotyping, tube formation assay, and evaluation of proliferation capability while global gene expression profiling was conducted by means of RNA-seq. ECFC were similar to HUVEC in terms of immunophenotype (CD31+vWF+KDR+CD146+CD34-CD133-CD45-CD90-) and tube formation activity yet had expectedly higher proliferative potential. HCAEC and HUVEC were generally similar to ECFC with regards to their global gene expression profile; nevertheless, ECFC overexpressed specific markers of all endothelial lineages (NRP2, NOTCH4, LYVE1), in particular lymphatic EC (LYVE1), and had upregulated extracellular matrix and basement membrane genes (COL1A1, COL1A2, COL4A1, COL4A2). Proteomic profiling for endothelial lineage markers and angiogenic molecules generally confirmed RNA-seq results, indicating ECFC as an intermediate population between HCAEC and HUVEC. Therefore, gene expression profile and behavior of ECFC suggest their potential to be applied for a pre-endothelialization of bioartificial vascular grafts, whereas in terms of endothelial hierarchy they differ from HCAEC and HUVEC, having a transitional phenotype.Pregnancy is a period in a woman’s life associated with an increased risk of developing lower extremity chronic venous disease (CVD). Pregnancy-associated CVD is associated with changes in placental villi. We investigated angiogenesis and lymphangiogenesis in the placental villi of women with CVD during pregnancy compared with healthy controls with no history of CVD (HC). An observational, analytical, and prospective cohort study was conducted on 114 women in their third trimester of pregnancy (32 weeks). Sixty-two participants were clinically diagnosed with CVD. In parallel, 52 controls with no history of CVD (HC) were studied. Gene and protein expression of CD31, podoplanin (D2-40), Flt-1, and placental growth factor (PIGF) was analysed by real-time polymerase chain reaction (RT-qPCR) and immunohistochemistry. CD31 and D2-40 gene expression was significantly greater in the placental villi of women with CVD, as were the numbers of vessels positive for CD31 and D2-40. Significantly higher gene and protein expression of Flt-1 and PIGF was observed in the placental villi of women with CVD. Histological analysis showed more placental villi with periodic acid of Schiff (PAS)-positive material in women with CVD. Our results show a connection between pregnancy-associated CVD and leading to higher proangiogenic and lymphangiogenic activity in placental villi.With the increasing demands to better the marine environment, environmentally friendly anti-fouling coatings have attracted attention from society. Adding hydrolyzable microcapsules without toxin to paints is a very useful and safe method to get bionic anti-fouling coatings with a micro-nano surface structure. Based on this trend, a form of environment-friendly microcapsules were prepared through mini-emulsion polymerization. The target microcapsules had a poly(urea-formaldehyde) (PUF) shell and a mixed core of silicone oil and capsaicin. Additionally, the microcapsules were introduced into zinc acrylate resin to obtain bionic anti-fouling coatings with micro-nano morphology. The effects of polyvinyl alcohol (PVA) molecular weight, stirring rate, and temperature on the morphology of the microcapsules were studied by optical microscopy (OM), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). It was found that spherical nanoparticles with smooth surfaces were obtained, and the mean diameter was approximately 1.38 μm when the molecular weight of PVA was 77 K, the stirring rate was 600 rpm and the temperature was 55 °C. Fourier-transform infrared spectra (FTIR) results showed that the silicone oil and capsaicin were successfully encapsulated, the core materials of the microcapsules reached 72.37% and the yield of microcapsules was 68.91% by the Soxhlet method. Furthermore, the hydrophobicity, corrosion resistance and anti-fouling performance of the coatings were evaluated by the water contact angle, electrochemical and real-sea tests. The results indicated that the anti-fouling coatings had excellent hydrophobicity and anti-fouling performance due to the micro-nano convex structure and the release of core materials. Encouragingly, the anti-fouling coatings show excellent and long-term anti-fouling performance, which is expected to be widely applied in marine anti-fouling coatings.Plant cell wall proteins play major roles during plant development and in response to environmental cues. A bioinformatic search for functional domains has allowed identifying the PAC domain (Proline-rich, Arabinogalactan proteins, conserved Cysteines) in several proteins (PDPs) identified in cell wall proteomes. This domain is assumed to interact with pectic polysaccharides and O-glycans and to contribute to non-covalent molecular scaffolds facilitating the remodeling of polysaccharidic networks during rapid cell expansion. In this work, the characteristics of the PAC domain are described in detail, including six conserved Cys residues, their spacing, and the predicted secondary structures. Modeling has been performed based on the crystal structure of a Plantago lanceolata PAC domain. The presence of β-sheets is assumed to ensure the correct folding of the PAC domain as a β-barrel with loop regions. We show that PDPs are present in early divergent organisms from the green lineage and in all land plants. PAC domains are associated with other types of domains Histidine-rich, extensin, Proline-rich, or yet uncharacterized. The earliest divergent organisms having PDPs are Bryophytes. Like the complexity of the cell walls, the number and complexity of PDPs steadily increase during the evolution of the green lineage. The association of PAC domains with other domains suggests a neo-functionalization and different types of interactions with cell wall polymers.The recent global pandemic of COVID-19 highlights the urgent need for practical applications of anti-microbial coatings on touch-surfaces. Nanostructured TiO2 is a promising candidate for the passive reduction of transmission when applied to handles, push-plates and switches in hospitals. Here we report control of the nanostructure dimension of the mille-feuille crystal plates in anatase columnar crystals as a function of the coating thickness. This nanoplate thickness is key to achieving the large aspect ratio of surface area to migration path length. TiO2 solid coatings were prepared by pulsed-pressure metalorganic chemical vapor deposition (pp-MOCVD) under the same deposition temperature and mass flux, with thickness ranging from 1.3-16 mm, by varying the number of precursor pulses. SEM and STEM were used to measure the mille-feuille plate width which is believed to be a key functional nano-dimension for photocatalytic activity. Competitive growth produces a larger columnar crystal diameter with thickness. The question is if the nano-dimension also increases with columnar crystal size. We report that the nano-dimension increases with the film thickness, ranging from 17-42 nm. The results of this study can be used to design a coating which has co-optimized thickness for durability and nano-dimension for enhanced photocatalytic properties.This special issue intends to review and update our understanding of the antimicrobial defense mechanisms of the skin and oral cavity. These two environments are quite different in terms of water, pH, and nutrient availability, but have some common antimicrobial factors. The skin surface supports the growth of a limited range of microorganisms but provides a hostile environment for others. The growth of most microorganisms is prevented or limited by the low pH, scarcity of some nutrients such as phosphorus and the presence of antimicrobial peptides, including defensins and cathelicidins, and antimicrobial lipids, including certain fatty acids and long-chain bases. On the other hand, the oral cavity is a warm, moist, nutrient rich environment which supports the growth of diverse microflora. Saliva coating the oral soft and hard surfaces determines which microorganisms can adhere to these surfaces. Some salivary proteins bind to bacteria and prevent their attachment to surfaces. Other salivary peptides, including defensins, cathelicidins, and histatins are antimicrobial. Antimicrobial salivary proteins include lysozyme, lactoferrin, and lactoperoxidase. There are also antimicrobial fatty acids derived from salivary triglycerides and long-chain bases derived from oral epithelial sphingolipids. The various antimicrobial factors determine the microbiomes of the skin surface and the oral cavity. Alterations of these factors can result in colonization by opportunistic pathogens, and this may lead to infection. Neutrophils and lymphocytes in the connective tissue of skin and mucosa also contribute to innate immunity.Among humans, simply looking at infants can activate affiliative and nurturant behaviors. However, it remains unknown whether mere exposure to infants also activates other aspects of the caregiving motivational system, such as generalized defensiveness in the absence of immediate threats. Here, we demonstrate that simply viewing faces of infants (especially from the ingroup) may heighten vigilance against social threats and support for institutions that purportedly maintain security. Across two studies, participants viewed and rated one among several image types (between-subjects design) Infants, adult males, adult females, and puppies in Study 1, and infants of varying racial/ethnic groups (including one’s ingroup) and puppies in Study 2. Following exposure to one of these image types, participants completed measures of intergroup bias from a range of outgroups that differed in perceived threat, belief in a dangerous world, right-wing authoritarianism and social-political conservatism (relative to liberalism). In Study 1 (United States), stronger affiliative reactions to images of infants (but not adults or puppies) predicted stronger perceptions of a dangerous world, endorsement of right-wing authoritarianism, and support for social-political conservatism (relative to liberalism). Study 2 (Italy) revealed that exposure to images of ingroup infants (compared to outgroup infants) increased intergroup bias against outgroups that are characterized as threatening (immigrants and Arabs) and increased conservatism. These findings suggest a predisposed preparedness for social vigilance in the mere suggested presence of infants (e.g., viewing images) even in the absence of salient external threats.Precision medicine, which includes comprehensive genome sequencing, is a potential therapeutic option for treating high-grade serous carcinoma (HGSC). However, HGSC is a heterogeneous tumor at the architectural, cellular, and molecular levels. Intratumoral molecular heterogeneity currently limits the precision of medical strategies based on the gene mutation status. This study was carried out to analyze the presence of 160 cancer-related genetic alterations in three tissue regions with different pathological features in a patient with HGSC. The patient exhibited histological heterogeneous features with different degrees of large atypical cells and desmoplastic reactions. TP53 mutation, ERBB2 and KRAS amplification, and WT1, CDH1, and KDM6A loss were detected as actionable gene alterations. Interestingly, the ERBB2 and KRAS amplification status gradually changed according to the region examined. The difference was consistent with the differences in pathological features. Our results demonstrate the need for sampling of the appropriate tissue region showing progression of pathological features for molecular analysis to solve issues related to tumor heterogeneity prior to developing precision oncology strategies.Coupling between electrically excited electromechanical resonances of piezoelectric ceramics is undesirable for the purpose of their characterization, since the material models correspond to monomodal resonances. However, coupling takes place quite often and it is unavoidable at the shear resonance of standard in-plane poled and thickness-excited rectangular plates. The piezoelectric coefficient e15, the elastic compliance s55E and the dielectric permittivity component ε11S for a piezoelectric ceramic can be determined, including all losses, using the automatic iterative method of analysis of the complex impedance curves for the shear mode of an appropriated resonator. This is the non-standard, thickness-poled and longitudinally excited, shear plate. In this paper, the automatic iterative method is modified. The purpose is to be able to deal with the analysis of the impedance curves of the non-standard plate as the periodic phenomena of coupling and decoupling of the main shear resonance and other resonances takes place. This happens when the thickness of the plate is reduced, and its aspect ratio (width of the excitation (w)/thickness for poling (t)) is increased. In this process, the frequency of the shear resonance also increases and meets those of other plate modes periodically. We aim to obtain the best approach for the shear properties of near coupling and to reveal both their validity and the limitations of the thus-obtained information. Finally, we use a plate of a Ba0.85Ca0.15Ti0.90Zr0.10O3 eco-piezoceramic as a case study.We report a robust, sidewall transfer metal assistant chemical etching scheme for fabricating Al2O3 nanotube arrays with an ultra-high aspect ratio. Electron beam lithography followed by low-temperature Au metal assisted chemical etching (MacEtch) is used to pattern high resolution, high aspect ratio, and vertical silicon nanostructures, used as a template. This template is subsequently transferred by an atomic layer deposition of the Al2O3 layer, followed by an annealing process, anisotropic dry etching of the Al2O3 layer, and a sacrificial silicon template. The process and characterization of the Al2O3 nanotube arrays are discussed in detail. Vertical Al2O3 nanotube arrays with line widths as small as 50 nm, heights of up to 21 μm, and aspect ratios up to 4201 are fabricated on top of a silicon substrate. More importantly, such a sidewall transfer MacEtch approach is compatible with well-established silicon planar processes, and has the benefits of having a fully controllable linewidth and height, high reproducibility, and flexible design, making it attractive for a broad range of practical applications.Nano-scaled structures, wireless sensing, wearable devices, and wireless communications systems are anticipated to support the development of new next-generation technologies in the near future. Exponential rise in future Radio-Frequency (RF) sensing systems have demonstrated its applications in areas such as wearable consumer electronics, remote healthcare monitoring, wireless implants, and smart buildings. In this paper, we propose a novel, non-wearable, device-free, privacy-preserving Wi-Fi imaging-based occupancy detection system for future smart buildings. The proposed system is developed using off-the-shelf non-wearable devices such as Wi-Fi router, network interface card, and an omnidirectional antenna for future body centric communication. The core idea is to detect presence of person along its activities of daily living without deploying a device on person’s body. The Wi-Fi signals received using non-wearable devices are converted into time-frequency scalograms. The occupancy is detected by classifying the scalogram images using an auto-encoder neural network. In addition to occupancy detection, the deep neural network also identifies the activity performed by the occupant. Moreover, a novel encryption algorithm using Chirikov and Intertwining map-based is also proposed to encrypt the scalogram images. This feature enables secure storage of scalogram images in a database for future analysis. The classification accuracy of the proposed scheme is 91.1%.A pulsed electromagnetic field (PEMF) has been shown to contribute to heightening bone regeneration in a range of clinical areas, including dentistry. Due to the scarcity of studies using PEMF in oral implantology, the present experiment scrutinized the effect of PEMF can lead to improving the stability of the implant. A total of 19 subjects (40 implants in total) were selected to participate in the current study and were randomly allocated to either the PEMF group or control group. Subjects in the PEMF group received an activated miniaturized electromagnetic device (MED) while the control group received a sham healing cup. Implants stability was assessed by resonance frequency analyses (RFA) via implant stability quotient (ISQ) calculations. RFA were recorded as following immediately after procedure, and then 2, 4, 6, 8 and 12 weeks later. Radiographic analysis was performed at baseline, 6 and 12 weeks after implant placement. Proinflammatory cytokines were evaluated in peri-implant crevicular fluid (PICF). The PEMF group presented higher ISQ mean values when compared to the control group. The primary stability time frame (the first 2 weeks) MED group depicted an increase in stability of 6.8%, compared to a decrease of 7.6% in the control group related to the baseline. An overall stability increase of 13% was found in MED treated group (p = 0.02), in contrast, the overall stability in the control group decreased by 2% (p = 0.008). TNF-α concentration during first 4 weeks was lower in the MED treated group. The data strongly suggests that MED generated continuing a PEMF may be considered as a new way to stimulate the stability of the implants at the early healing period.In this study, a climate chamber, as an alternative method, has been used to dry raisins and the sensory profiles of the sweet sherry wines obtained have been evaluated. Other important factors, namely grape variety, vintage, vinification conditions, as well as the ageing method and its length of time, have also been considered. When heavy rainfall had been registered, the musts extracted from grapes dried under controlled conditions in a climate chamber showed a lower intensity of the musty off-odor compared to those elaborated with sun-dried grapes. The wine fermented at low temperature with Saccharomyces bayanus scored the highest in citric and floral notes, and this was preferred over all the other wines that were evaluated. The wines aged in oak barrels were preferred to both, wines aged in the presence of oak chips as well as those aged without any wood contact. The use of climate chambers to dry the grapes that are going to be used for the elaboration of sweet wines appears to be an advantageous alternative to the traditional method, since it allows a more precise control of the process and highly valued sweet wines from a sensory point of view are obtained thereby.The Cactaceae family is an important source of triterpenes and sterols. The wide uses of those plants include food, gathering, medicinal, and live fences. Several studies have led to the isolation and characterization of many bioactive compounds. This review is focused on the chemistry and biological properties of sterols and triterpenes isolated mainly from some species with columnar and arborescent growth forms of Mexican Cactaceae. Regarding the biological properties of those compounds, apart from a few cases, their molecular mechanisms displayed are not still fully understand. To contribute to the above, computational chemistry tools have given a boost to traditional methods used in natural products research, allowing a more comprehensive exploration of chemistry and biological activities of isolated compounds and extracts. From this information an in silico bioprospection was carried out. The results suggest that sterols and triterpenoids present in Cactaceae have interesting substitution patterns that allow them to interact with some bio targets related to inflammation, metabolic diseases, and neurodegenerative processes. Thus, they should be considered as attractive leads for the development of drugs for the management of chronic degenerative diseases.Glioblastoma is an aggressive brain tumour with a patient median survival of approximately 14 months. The development of innovative treatment strategies to increase the life span and quality of life of patients is hence essential. This requires the use of appropriate glioblastoma models for preclinical testing, which faithfully reflect human cancers. The aim of this study was to establish glioblastoma patient-derived xenografts (PDXs) by heterotopic transplantation of tumour pieces in the axillae of NMRI nude mice. Ten out of 22 patients’ samples gave rise to tumours in mice. Their human origin was confirmed by microsatellite analyses, though minor changes were observed. The glioblastoma nature of the PDXs was corroborated by pathological evaluation. Latency times spanned from 48.5 to 370.5 days in the first generation. Growth curve analyses revealed an increase in the growth rate with increasing passages. The methylation status of the MGMT promoter in the primary material was maintained in the PDXs. However, a trend towards a more methylated pattern could be found. A correlation was observed between the take in mice and the proportion of Sox2+ cells (r = 0.49, p = 0.016) and nestin+ cells (r = 0.55, p = 0.007). Our results show that many PDXs maintain key features of the patients’ samples they derive from. They could thus be used as preclinical models to test new therapies and biomarkers.Hybrid sandwich structures are more and more widely used in many industries. This is mainly due to their good properties. One of the limitations regarding the use of sandwich structures is their difficult processing. Therefore, it seems reasonable to determine the influence of cutting parameters and machining configuration on the characteristic defect (phase) formed at the boundary of the materials forming a hybrid sandwich structure. This study investigates the effects of layer orientations during milling and machining parameters such as the cutting speed Vc, the feed fz and the cutting width ae. The study is conducted on a two-layer sandwich structure composed of two materials 2024 aluminum alloy and epoxy-carbon composite with 60% of high-strength carbon fibers. A statistical analysis is performed using the Statistica program. The results show that the change in the cutting parameters has a greater impact on the formation of a defect on the surface of samples when the machining process starts on the side of the composite rather than the metal. The highest defect value is obtained for the milling from the composite layer when the process is performed with the following cutting parameters Vc = 300 m/min, fz = 0.08 mm/tooth, ae = 5 mm.An adverse reaction of dry skin occurs frequently during treatment with anticancer epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). In this study, we conducted basic research to clarify the mechanism of EGFR-TKI-induced dry skin and propose new treatments or preventative measures. Dermal water content was significantly lower in the erlotinib-treated mice than in the control group. An assessment of the expression levels of functional genes in the skin revealed that only the expression of the water channel aquaporin-3 (AQP3) was significantly decreased in the erlotinib-treated group. When erlotinib was added to epidermal keratinocyte HaCaT cells, the expression levels of both AQP3 mRNA and protein decreased. Erlotinib treatment also significantly decreased the expression levels of phospho-EGFR and phospho-extracellular signal-regulated kinase (ERK), both in HaCaT cells and mouse skin. Dry skin due to erlotinib may be caused by the decreased expression of AQP3 in the skin, thereby limiting water transport from the vascular side to the corneum side. The decrease in AQP3 may also be attributable to ERK suppression via inhibition of EGFR activity by erlotinib. Therefore, substances that increase AQP3 expression may be effective for erlotinib-induced dry skin.Thanks to the rapid advances of technology, we are currently experiencing the fourth industrial revolution, which is introducing several changes in how organizations operate and how people learn and do their work. Many questions arise within this framework about how these transformations may affect workers’ wellbeing, and the Work and Organizational Psychology is called upon to address these open issues. This study aims to investigate personal and organizational antecedents (resilience, goal orientation and opportunities for information and training) and one consequence (work engagement) of technology acceptance within factories, comparing white- and blue-collar workers. The study involved a sample of 598 workers (white-collar = 220, blue-collar = 378) employed at an Italian company who filled in a self-report questionnaire. In both samples, the multi-group structural equation model showed a positive relationship between resilience, opportunities for information and training, and technology acceptance, which in turn showed a positive association with work engagement. All indirect effects were significant. This study investigated the motivational dynamics related to the introduction of new technologies within factories involving the little-studied population of blue-collar workers. Results highlighted the importance of providing information and opportunities for training to all employees, in order to support Industry 4.0 transformations without impacting on workers’ motivation.Catalysts are essential for mediating a controlled polymerization in atom transfer radical polymerization (ATRP). Copper-based catalysts are widely explored in ATRP and are highly efficient, leading to well-controlled polymerization of a variety of functional monomers. In addition to copper, iron-based complexes offer new opportunities in ATRP catalysis to develop environmentally friendly, less toxic, inexpensive, and abundant catalytic systems. Despite the high efficiency of iron catalysts in controlling polymerization of various monomers including methacrylates and styrene, ATRP of acrylate-based monomers by iron catalysts still remains a challenge. In this paper, we review the fundamentals and recent advances of iron-catalyzed ATRP focusing on development of ligands, catalyst design, and techniques used for iron catalysis in ATRP.Libraries are invaluable resources, documenting significant events that have shaped human history. However, the preservation of old books is severely threatened by insects commonly referred to as bookworms. In this study, a sample of infested books in a historic library in Taiwan was randomly selected and examined. An anobiid book-boring beetle, Falsogastrallus sauteri Pic, 1914 (Coleoptera Ptinidae) was identified as the major bookworm species present. To facilitate its identification, both adults and larvae of F. sauteri are redescribed, with emphasis on its ultramorphological characteristics as revealed by scanning electronic microscopy. Furthermore, an undescribed parasitoid wasp in the Bethylidae was discovered in the frass, holes and tunnels created by F. sauteri. The new species, Cephalonomia formosiensis sp. nov. is described, and we suggest that it probably uses F. sauteri as host.The clinical efficacy of a late evening snack (LES) is well documented in patients with cirrhosis, but its effect on survival remains unclear. This cohort study aimed to compare the overall survival between LES-treated patients and untreated patients. We conducted a retrospective cohort study to determine the effect of LES, which is defined as an oral intake of a branched-chain amino acids (BCAA)-enriched nutrient before bedtime, on survival in 523 patients with cirrhosis seen at a tertiary referral center in Japan from March 2004 to April 2019. The association between LES and all-cause mortality was evaluated using propensity score matching and inverse probability of treatment weighting analyses. The median age of the 523 participants was 66 years; 286 (55%) patients were men and 87 (17%) received LES therapy. Of the 231 propensity-matched patients, 20 (26%) LES-treated patients and 72 (47%) untreated patients died during a median follow-up of 2.0 years (interquartile range, 0.5-4.8). Propensity score matching analysis showed that the overall survival was significantly higher in LES-treated patients than in untreated patients (hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.34-0.93). The survival benefit of LES therapy was most prominent in patients with Child-Pugh C cirrhosis (HR, 0.40; 95% CI, 0.20-0.81). Inverse probability of treatment weighting analysis also revealed that LES significantly improved the prognosis of patients with cirrhosis (HR, 0.57; 95% CI, 0.33-0.99). In this retrospective study of patients with cirrhosis, we found that nocturnal BCAA supplementation was associated with a significant reduction in the risk of death in patients with liver cirrhosis.Most acrylonitrile butadiene styrene (ABS) resin is plagued by an unpleasant odor attributed to the high residual volatile organic compound (VOC) content. This paper primarily aimed to solve the odor issue of ABS resin by effectively reducing the VOC content. To that end, a synthesis of ABS resins was optimized through a supercritical extraction process while evaluating multiple novel chain transfer agents (linear dimer of α-methyl-styrene, methyl 3-mercaptopropionate, and dodecyl mercaptan). ABS resin obtained through a α-methyl-styrene chain transfer agent demonstrated the lowest odor. Moreover, it had the least amount of VOC content which was three times lower than when dodecyl mercaptan was employed. To improve the supercritical extraction process, an orthogonal test was designed to optimize four main process parameters extrusion temperature, residence time, vacuum degree and extractant dosage. The most optimal conditions were found to be 250 °C extrusion temperature, one minute residence time, vacuum degree of minus 99 KPa, and 1.5% CO2 extractant dosage.Nanofiltration (NF) can enable P recovery from waste streams via retaining multivalent impurities from spent pickling acid. However, with the currently available membranes, an economically feasible process is impossible. Layer-by-layer modified NF membranes are a promising solution for the recovery of P from acidic leachate. LbL membranes show a high level of versatility in terms of fine tuning for ion retention, which is necessary to achieve sufficient phosphorus yields. However, the stability of layer-by-layer modified membranes during phosphoric acid (H3PO4) filtration needs to be further investigated. In our study, we show that a polyethersulfone hollow fiber membrane modified with four or eight bi-layers was stable during immersing and filtering of a 15% H3PO4 solution. A sulfonated polyethersulfone (sPES)-based hollow fiber LbL membrane was only stable during filtration. Thus, we show the importance of applying real process conditions to evaluate membranes. Another important aspect is the influence of the high ionic strength of the feed solution on the membrane. We show that a high ionic strength led to a decrease in Mg retention, which could be increased to 85% by adjusting the process parameters.Recalcitrant chestnut seeds are rich in γ-aminobutyric acid (GABA), which negatively regulates adventitious root development by altering carbon/nitrogen metabolism. However, little is known regarding the role of this metabolite in chestnut seeds. In this study, we investigated the effects of GABA changes on the germination of chestnut seeds treated with exogenous GABA and vigabatrin (VGB, which inhibits GABA degradation). Both treatments significantly inhibited seed germination and primary root growth and resulted in the considerable accumulation of H2O2, but the endogenous GABA content decreased before germination at 48 h. Soluble sugar levels increased before germination, but subsequently decreased, whereas starch contents were relatively unchanged. Changes to organic acids were observed at 120 h after sowing, including a decrease and increase in citrate and malate levels, respectively. Similarly, soluble protein contents increased at 120 h, but the abundance of most free amino acids decreased at 48 h. Moreover, the total amino acid levels increased only in response to VGB at 0 h. Accordingly, GABA and VGB altered the balance of carbon and nitrogen metabolism, thereby inhibiting chestnut seed germination. These results suggested that changes to GABA levels in chestnut seeds might prevent seed germination. The study data may also help clarify the dormancy and storage of chestnut seeds, as well as other recalcitrant seeds.There is limited evidence of phenolic compounds acting as protective agents on several cancer types, including breast cancer (BC). Nevertheless, some polyphenol classes have not been investigated and there is a lack of studies assessing the effect on menopausal status and hormone receptor status as influenced by these compounds. The objective of this study is to evaluate the association between the intake of all polyphenol classes in relation to the BC risk by menopausal and hormone receptor status. We used data from a population-based multi-case-control study (MCC-Spain) including 1472 BC cases and 1577 controls from 12 different regions of Spain. The odds ratios (ORs) with 95% CI were calculated using logistic regression of mixed effects by quartiles and log2 of polyphenol intakes (adjusted for the residual method) of overall BC, menopausal and receptor status. No associations were found between total intake of polyphenols and BC risk. However, inverse associations were found between stilbenes and all BC risk (ORQ4 vs. Q1 0.70, 95%CI 0.56-0.89, Ptrend = 0.001), the consumption of hydroxybenzaldehydes (ORQ4 vs. Q1 0.75, 95%CI 0.59-0.93, Ptrend = 0.012) and hydroxycoumarins (ORQ4 vs. Q1 0.73, 95%CI 0.57-0.93; Ptrend = 0.005) were also inversely associated. The intake of stilbenes, hydroxybenzaldehydes and hydroxycoumarins can contribute to BC reduction risk on all menopausal and receptor statuses.Polylactic acid (PLA)/polybutylene succinate (PBS)/wood flour (WF) biocomposites were fabricated by in situ reactive extrusion with coupling agents. Methylenediphenyl 4,4′-diisocyanate (MDI) and maleic anhydride (MA) were used as coupling agents. To evaluate the effects of MDI and MA, various properties (i.e., interfacial adhesion, mechanical, thermal, and viscoelastic properties) were investigated. PLA/PBS/WF biocomposites without coupling agents revealed poor interfacial adhesion leading to deteriorated properties. However, the incorporation of MDI and/or MA into biocomposites showed high performances by increasing interfacial adhesion. For instance, the incorporation of MDI resulted in improved tensile, flexural, and impact strengths and an increase in tensile and flexural modulus was observed by the incorporation of MA. Specially, remarkably improved thermal stability was found in the PLA/PBS/WF biocomposites with 1 phr MDI and 1 phr MA. Also, the addition of MDI or MA into biocomposites increased the glass transition temperature and crystallinity, respectively. For viscoelastic property, the PLA/PBS/WF biocomposites with 1 phr MDI and 1 phr MA achieved significant enhancement in storage modulus compared to biocomposites without coupling agents. Therefore, the most balanced performances were evident in the PLA/PBS/WF biocomposites with the hybrid incorporation of small quantities of MDI and MA.The aim of this study was to evaluate the effects of different Se sources on the meat quality and shelf life of fattening pigs. The control diet was supplemented with 0.3 mg/kg of Se from sodium selenite (SS), and experimental diets included 0.3, 0.3 and 0.15 + 0.15 mg/kg of Se from Se-enriched yeast (SY), selenomethionine (Se-Met) and SS + Se-Met, respectively. The results showed that using organic Se or Se + Se-Met in fattening pigs’ diet could increase average daily gain (ADG) (p less then 0.05), decrease F/G (p less then 0.05), reduce (p less then 0.01) moisture, drip loss and cooking loss of longissimus thoracis, as well as increase (p less then 0.05) protein and fat contents of longissimus thoracis. Diet supplementation with SY or Se + Se-Met could increase (p less then 0.01) back fat thickness and skin thickness, and SY could increase (p less then 0.01) belly fat rat. Adding SY or Se + Se-Met could reduce (p less then 0.01) L value (45 min, 24 h). Adding Se-Met could decrease (p less theSe supplementation was more effective than SS supplementation for meat quality and the shelf life of fattening pigs.Adult vaccination is high on the agenda in many countries. Two different vaccines are available for the prevention of pneumococcal disease in adults a 23-valent polysaccharide vaccine (PPV23), and a 13-valent conjugated vaccine (PCV13). The objective of this review is to update the evidence base for vaccine efficacy and effectiveness of PPV23 and PCV13 against invasive pneumococcal disease and pneumonia among an unselected elderly population. We systematically searched for clinical trials and observational studies published between January 1 2016 and April 17 2019 in Pubmed, Embase, Cinahl, Web of Science, Epistemonikos and Cochrane databases. Risk of bias was assessed using Cochrane Risk of Bias tool for and the Newcastle-Ottawa Scale. Results were stratified by vaccine type and outcome. We identified nine studies on PCV13 and six on PPV23. No new randomized clinical trials were identified. Due to different outcomes, it was not possible to do a meta-analysis. New high-quality observational studies indicate protective vaccine effectiveness for both vaccines against vaccine type pneumonia. Our estimates for the protective vaccine efficacy and effectiveness (VE) of PPV23 on pneumonia and pneumococcal pneumonia overlap with results from previously published reviews. Some of the results indicate that the effectiveness of the PPV23 is best in younger age groups, and that it decreases over time.This article presents selected issues related to the workpiece surface quality after machining by the laser sintering of AlSi10MG alloy powder. The surfaces of the workpiece were prepared and machined by longitudinal turning with tools made of sintered carbides. The occurrence of breaches on the machined material surface was found, which negatively influence the values of 3D surface roughness parameters. The occurring phenomena were analyzed and proposals for their explanation were made. Guidelines for the machining of workpieces achieved by the laser sintering of powders were developed. The lowest value of the 3D roughness parameters was obtained for f = 0.06 mm/rev, ap = 0.5-1.0 mm, and for the nose radius of cutting insert rε = 0.8 mm. The results of research on the effect of cutting parameters on the values of parameters describing the surface quality are presented. Topography measurements and 3D surface roughness parameters are presented, as well as the results of a microscopic 3D surface analysis. Taguchi’s method was used in the research methodology.An oscillating piezoresistive microcantilever (MC) coated with an aluminum (Al)-doped zinc oxide (ZnO) nanorods was used to detect carbon monoxide (CO) in air at room temperature. Al-doped ZnO nanorods were grown on the MC surface using the hydrothermal method, and a response to CO gas was observed by measuring a resonant frequency shift of vibrated MC. CO gas response showed a significant increase in resonant frequency, where sensitivity in the order of picogram amounts was obtained. An increase in resonant frequency was also observed with increasing gas flow rate, which was simultaneously followed by a decrease in relative humidity, indicating that the molecular interface between ZnO and H2O plays a key role in CO absorption. The detection of other gases of carbon compounds such as CO2 and CH4 was also performed; the sensitivity of CO was found to be higher than those gases. The results demonstrate the reversibility and reproducibility of the proposed technique, opening up future developments of highly sensitive CO-gas detectors with a fast response and room temperature operation.Roads should deliver appropriate information to drivers and thus induce safer driving behavior. This concept is also known as „self-explaining roads” (SERs). Previous studies have demonstrated that understanding how road characteristics affect drivers’ speed choices is the key to SERs. Thus, in order to reduce traffic casualties via engineering methods, this study aimed to establish a speed decision model based on visual road information and to propose an innovative method of SER design. It was assumed that driving speed is determined by road geometry and modified by the environment. Lane fitting and image semantic segmentation techniques were used to extract road features. Field experiments were conducted in Tibet, China, and 1375 typical road scenarios were picked out. By controlling variables, the driving speed stimulated by each piece of information was evaluated. Prediction models for geometry-determined speed and environment-modified speed were built using the random forest algorithm and convolutional neural network.


