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Given the link between visual stimuli and memory, children with dyslexia could benefit from research discovering what visual stimuli they find more pleasing and memorable. People like natural landscapes (e.g.,forests) more than human-made (e.g.,cityscapes) or "combined" landscapes (i.e.,combination of human-made and natural components, e.g.,tires in a meadow). The purpose was to determine if the greater likability for natural generalized to children with dyslexia and age-equivalent controls and if photograph type impacted recognition rates after the short and long term. All children liked natural landscape photographs the most but paid longer attention to combined landscape photographs. Both groups recognized all photograph types at a high rate after the short retention interval, but after the long interval, the children with dyslexia had better memory, especially for combined photographs. On the basis of these results, we advise educators to incorporate images of natural landscapes into the learning context in order to create a more aesthetically pleasing environment or to infuse combined images for a more engaging and memorable environment. [ABSTRACT FROM AUTHOR]

Background: Psoriasis is a common chronic inflammatory skin disease associated with a heavy burden of morbidity, disability and cost. The occurrence of the disease in Israel has not been previously investigated. Objectives: To provide standardized estimates of trends in psoriasis incidence, prevalence and mortality among patients in Israel between 2011 and 2017. Methods: Using electronic health records from Clalit Health Services, the largest nationwide public health provider in Israel, we conducted a population‐based study investigating trends in the annual incidence and prevalence of psoriasis between the years 2011 and 2017. We report age‐ and sex‐adjusted rates, using the standard European population as a reference. Results: We identified 71 094 incident psoriasis cases. The mean (SD) age of onset was 42.4 (21.0) years with a bimodal distribution, peaking in the early '30s and early '60s. Late‐onset psoriasis, occurring after 40 years of age, accounted for 51.1% of incident cases. The annual psoriasis incidence rate was constant throughout the study period (280/100 000 person‐years). Psoriasis prevalence rose from 2.5% in 2011 to 3.8% in 2017. Conclusions: Psoriasis prevalence is increasing in Israel, although its incidence is stable. Clinicians and policymakers should plan to address the growing demands in the clinical, economic and societal burden of psoriasis. [ABSTRACT FROM AUTHOR]

Sport is an integral and enduring part of many societies, such as Australia. Participation in outdoor sports, such as tennis, comes with a very real risk of dangerous solar ultraviolet exposure which can result in erythema (sunburn), serious conditions such as skin cancer, including melanoma, and eye conditions such as cataracts and pterygium. This study remotely assesses the effective ultraviolet exposures in response to the increased sun safety awareness at a major summertime tennis tournament in Australia. The assessment only uses publicly accessible data and information. It was found that tournament organizers have effectively adopted sun‐safe protocols into the uniform policy that the court officials (judges and ball kids) are mandated to follow. The combination of sun‐participant geometry and the photoprotection provided by uniforms significantly reduced the ambient ultraviolet exposure, which was recorded to be as high as 9.9 SED h−1, to just 1.0 and 0.5 SED h−1 for ball kids and judges, respectively, compared to up to 2.0 SED h−1 for players. Even though caution is needed against complacency with sun safety, with the need for the court officials and the players to still apply sunscreen, the court officials provided persistent visual role modeling of sun‐safe behaviors. [ABSTRACT FROM AUTHOR]

Summary: Background: Patients with IBD are at risk of excess corticosteroids. Aims: To assess steroid excess in a large IBD cohort and test associations with quality improvement and prescribing. Methods: Steroid exposure was recorded for outpatients attending 19 centres and associated factors analysed. Measures taken to avoid excess were assessed. Results: Of 2385 patients, 28% received steroids in the preceding 12 months. 14.8% had steroid excess or dependency. Steroid use was significantly lower at 'intervention centres' which participated in a quality improvement programme (exposure: 23.8% vs 31.0%, P < .001; excess 11.5% vs 17.1%, P < .001). At intervention centres, steroid use fell from 2015 to 2017 (steroid exposure 30.0%‐23.8%, P = .003; steroid excess 13.8%‐11.5%, P = .17). Steroid excess was judged avoidable in 50.7%. Factors independently associated with reduced steroid excess in Crohn's disease included maintenance with anti‐TNF agents (OR 0.61 [95% CI 0.24‐0.95]), treatment in a centre with a multi‐disciplinary team (OR 0.54 [95% CI 0.20‐0.86]) and treatment at an intervention centre (OR 0.72 [95% CI 0.46‐0.97]). Treatment with 5‐ASA in CD was associated with higher rates of steroid excess (OR 1.72 [95% CI 1.24‐2.09]). In ulcerative colitis (UC), thiopurine monotherapy was associated with steroid excess (OR 1.97 [95% CI 1.19‐3.01]) and treatment at an intervention centre with less steroid excess (OR 0.72 [95% CI 0.45‐0.95]). Conclusions: This study validates steroid assessment as a meaningful quality measure and provides a benchmark for this performance indicator in a large cohort. A programme of quality improvement was associated with lower steroid use. [ABSTRACT FROM AUTHOR]

A study of three isomeric compounds containing a phenolic moiety attached to the nitrogen‐rich triazolo–triazole bicycle is presented. In the three isomers, the phenolic OH group is in the ortho, meta and para positions. The crystal structure analysis of the meta isomer (C10H9N5O) shows that the 2H‐tautomer is present in the crystal and that the molecule adopts a substantially planar geometry. However, the conformation found in the crystal is different compared to the monoprotonated cation of the same compound previously investigated in several salts. The packing of the meta isomer is driven by the formation of strong hydrogen bonds and shows the formation of infinite planar ribbons, parallel to a, formed around 21 crystallographic axes. The three isomers were tested against some cancer cell lines and also against normal cell lines. The ortho isomer shows a weak antiproliferative activity, the meta isomer shows significant antiproliferative activity against some cancer lines and no activity against healthy cell lines, and the para isomer is active against all the tested cell lines. [ABSTRACT FROM AUTHOR]

In internally post‐tensioned (PT) prestressed concrete (PC) structures, the prestressing system is usually made of high‐strength steel tendons embedded within concrete through either metallic or plastic ducts filled with cement grout or grease. Construction defects or degradation phenomena may lead to insufficient covering, exposing the prestressing steel to a harmful environment, potentially compromising the durability and load‐bearing capacity of the structure. Based on experimental tests on six 1:5 scaled PT specimens, this study presents accurate numerical simulations of four‐point bending tests on girders with unbonded and partially bonded tendons having different levels of initial prestress. Nonlinear finite element analyses (FEAs) were developed to reflect the friction‐type interaction mechanism between unbonded tendons and external ducts under increasing external load up to failure. Both global and local response parameters of the girders were studied validating numerical results against experimental findings. The numerical simulations provide insights on the stress pattern of unbonded and partially bonded strands, shedding light on the lower bearing capacity of defective girders compared to those with bonded tendons. Such findings contribute to a multi‐scale assessment and decision‐making framework for existing PT girders with defective grouting and low residual prestress levels, enhancing the understanding of their structural behavior and informing maintenance or retrofitting decisions. [ABSTRACT FROM AUTHOR]

Trials including drug further approved by health authorities involved 84/447 (18.8%) of patients and had an overall response rate of 32.9% (26/79 evaluable pts). B Introduction: b Previous reviews of phase 1 trials in oncology have reported a treatment response rate of 4%-6% and a toxicity-related mortality rate of 0.5%. All patients were assessed for toxicity and 382/447 (85%) for treatment response. [Extracted from the article]

Two distinct genomic disorders have been linked to Xq28‐gains, namely Xq28‐duplications including MECP2 and Int22h1/Int22h2‐mediated duplications involving RAB39B. Here, we describe six unrelated patients, five males and one female, with Xq28‐gains distal to MECP2 and proximal to the Int22h1/Int22h2 low copy repeats. Comparison with patients carrying overlapping duplications in the literature defined the MidXq28‐duplication syndrome featuring intellectual disability, language impairment, structural brain malformations, microcephaly, seizures and minor craniofacial features. The duplications overlapped for 108 kb including FLNA, RPL10 and GDI1 genes, highly expressed in brain and candidates for the neurologic phenotype. [ABSTRACT FROM AUTHOR]

Pseudomonas syringae is described as a species complex, containing P. syringae‐related species classified into 13 phylogroups and 23 clades. Pseudomonas syringae is one of the main pathogens of fruit trees, affecting nut trees, hazelnut and kiwi, pome and stone fruits. Bacterial canker of apricots is an important disease in regions of production with cold winters and conducive soils. This work characterizes the bacteria able to induce canker in apricots isolated in different French orchards. Bacteria from four phylogroups were able to induce canker. The pathogenicity to apricot was not linked to the pathogenicity to the three herbaceous species and cherry fruits tested, and was not always related to hypersensitive reaction on tobacco and ice nucleation activity. Bacteria pathogenic to apricot belong to phylogroups 01, 02, 03 and 07. The bacteria of phylogroups 01a and 07a (Pseudomonas viridiflava) characterized in this work have not previously been described as pathogenic to apricot. [ABSTRACT FROM AUTHOR]

In a minority of relapsed myeloma, patient's disease may spread into extramedullary sites, associated with high degrees of heterogeneity. The breadth of myeloma therapeutic armamentarium allows clinicians to manage its heterogeneous presentation, including intracranial relapses, with fair success resulting in a significant prolongation of survival. [ABSTRACT FROM AUTHOR]

Introduction: Sempervivum tectorum L. (Crassulaceae), is a succulent perennial plant widespread in Mediterranean countries and commonly used in traditional medicine for ear inflammation, ulcers and skin rashes as a refrigerant and astringent. Objective: To demonstrate the therapeutic effects of the plant, various fractions were purified and characterised. The potential wound healing activity, proliferation rate and intracellular signalling cascades were investigated by using human epithelial colorectal carcinoma (HCT 116) cells. Methodology: An extraction method without organic solvents was applied for the first time. The purification was carried out by droplet counter current chromatography (DCCC) coupled with high‐performance liquid chromatography (HPLC) and electrospray ionisation mass spectrometry (ESI‐MS) data. By nuclear magnetic resonance (NMR) [1H, 13C and two‐dimensional (2D) experiments] pure components were identified. Wound healing and cell proliferation assays were utilised to determine the role of the isolated S. tectorum (SVT) fraction on cellular migration and proliferation. The signalling pathways elicited from the SVT fractions, were analysed by Western blot analysis. Results: In this study two rare natural components were identified, namely monosaccharide sedoheptulose and polyalcohol 2‐C‐methyl‐D‐erythritol, along with known organic acids and flavonoids. The fractions with high level of sedoheptulose enhance the proliferation and the cellular migration of epithelial HCT 116 cells. The intracellular signalling cascades elicited from the purified fractions induce the c‐Src‐mediated transactivation of EGFR and the activation of the STAT3 pathway which, in turn, are crucially involved in the cellular proliferation and migration. Conclusions: Our study demonstrates the efficacy of purified fractions of S. tectorum L. in enhancing cellular proliferation and migration, suggesting their potential role as topical therapeutic treatments for wound healing. Sempervivum tectorum L. known as houseleek, is a wild‐growing succulent perennial plant known to have therapeutic benefits. A solvent free extraction, followed by DCCC fractionation coupled with HPLC was applied to isolate the rare monosaccharide sedoheptulose and the polyalcohol 2‐C‐Methyl‐D‐erythritol beside the known organic acids and flavonoid glycosides. In HCT‐116 cells, exposure to S. tectorum extracts enhance cellular migration and proliferation, by promoting EGFR transactivation. [ABSTRACT FROM AUTHOR]

Two novel NO photodonors (NOPDs) based on BODIPY and Rhodamine antennae activatable with the highly biocompatible green light are reported. Both NOPDs exhibit considerable fluorescence emission and release NO with remarkable quantum efficiencies. The combination of the photoreleasing and emissive performance for both compounds is superior to those exhibited by other NOPDs based on similar light‐harvesting centres, making them very intriguing for image‐guided phototherapeutic applications. Preliminary biological data prove their easy visualization in cell environment due to the intense green and orange‐red fluorescence and their photodynamic action on cancer cells due to the NO photo‐liberated. [ABSTRACT FROM AUTHOR]

Empowering obstetricians to assess and improve their own practices of screening brief intervention and referral to treatment (SBIRT) in treating alcohol use disorders (AUDs) and preventing fetal alcohol spectrum disorder (FASD) is the goal of the American College of Obstetricians and Gynecologist (ACOG) FASD Prevention Program. The FASD Prevention Program is a CDC funded initiative of the ACOG which is the largest specialty professional membership organization in the United States. Obstetrics and gynecology as a specialty is dedicated to the broad, integrated medical and surgical care of women's health throughout their lifespan. Understanding of reproductive physiology, including the physiologic, social, cultural, environmental, and genetic factors that influence disease in women, is a major priority for ACOG. Preventive counseling and health education are essential and integral parts of the practice of obstetricians and gynecologists as they advance the individual and community‐based health of women of all ages. The FASD Prevention Program aims to provide obstetrician‐gynecologists with the resources and tools needed to communicate with patients and the communities they serve about alcohol use during pregnancy. This review describes activities to empower and educate providers to address alcohol use disorder in pregnancy and the effect of FASD. [ABSTRACT FROM AUTHOR]

Aims/Introduction: Epigenetics participate in the pathogenesis of metabolic memory, a situation in which hyperglycemia exerts prolonged deleterious effects even after its normalization. We tested the hypothesis that genetic variants in an epigenetic gene could predispose to diabetes complications. Material and Methods: We assessed the frequency of five single‐nucleotide polymorphisms in the gene encoding deoxyribonucleic acid methytransferase 1 (DNMT1; rs8112895, rs7254567, rs11085721, rs17291414 and rs10854076), and their associations with diabetic kidney disease, retinopathy, distal polyneuropathy and autonomic cardiovascular neuropathy in 359 individuals with long‐term type 1 diabetes. Results: None of the single‐nucleotide polymorphisms studied was significantly associated with the presence of chronic complications in the overall population. However, after sex stratification, the minor allele C of rs11085721 conferred risk for cardiovascular neuropathy in women after adjustment for confounding variables (odds ratio 2.32; 95% confidence interval 1.26–4.33; P = 0.006). Conclusions: The fact that heterozygous mutations in DNMT1 are associated with hereditary sensory autonomic neuropathy provides plausibility to the present finding. If confirmed in independent samples, it suggests that genetic variants in epigenetic genes might predispose to more or fewer epigenetic changes in the face of similar metabolic derangements triggered by hyperglycemia, constituting the "genetics of epigenetics" for microvascular diabetes complications. [ABSTRACT FROM AUTHOR]

The risk of keratinocyte skin cancer, malignant melanoma and ultraviolet radiation (UVR)‐induced eye disease is disproportionately higher in Australia and New Zealand compared to equivalent northern hemisphere latitudes. While many teachers are aware of the importance of reinforcing sun safety messages to students, many may not be aware of the considerable personal exposure risk while performing outdoor duties in locations experiencing high to extreme ambient UVR year‐round. Personal erythemally effective exposure of classroom teachers in tropical Townsville (19.3°S) was measured to establish seasonal extremes in exposure behavior. Mean daily personal exposure was higher in winter (91.2 J m‐2, 0.91 Standard Erythema Dose [SED]) than summer (63.3 J m−2, 0.63 SED). The range of exposures represents personal exposures that approximate current national guidelines for Australian workers at the study latitude of approximately 1.2 SED (30 J m−2 effective to the International Commission on Non‐Ionizing Radiation Protection). Similar proportions of teachers spent more than 1 h outdoors per day in winter (28.6%) and summer (23.6%) as part of their teaching duties with seasonal differences having little effect on the time of exposure. Personal exposures for teachers peaked during both seasons near school meal break times at 11:00 am and 1:00 pm, respectively. [ABSTRACT FROM AUTHOR]

The atmosphere of the Jovian satellite Io is constantly being lost to the surrounding magnetosphere of Jupiter. The material is ionized and then distributed by Jupiter's magnetic field into a torus around Jupiter called the Io plasma torus. This plasma affects radio signals as they propagate from the Juno spacecraft to Earth during the spacecraft's perijove passes. During Perijoves 3, 6, and 8 we determine the total electron content in the Io plasma torus using two‐way tracking data from Juno. We find that the location of the torus is displaced from predictions that use the VIP4 offset tilted dipole approximation. The displacements are consistent with those found in ground‐based observations. The peak total electron content and scale height are found for two different regions of the torus, the cold inner torus and a warmer torus beyond 5.5 RJ. Properties of the cold torus vary appreciably with System III longitude, but properties of the torus beyond 5.5 RJ do not. Key Points: Io plasma torus total electron content profiles are derived from Juno Perijoves 3, 6, and 8Torus locations are displaced from nominal centrifugal equatorPeak total electron content and scale height vary with System III longitude [ABSTRACT FROM AUTHOR]

Introduction: Neuroimaging biomarkers are important for early diagnosis of Alzheimer's disease, and comparing multimodality neuroimaging to autopsy data is essential. Methods: We compared the pathologic findings from a prospective autopsy cohort (n = 100) to Pittsburgh compound B PET (PiB‐PET), 18F‐fluorodeoxyglucose PET (FDG‐PET), and MRI. Correlations between neuroimaging biomarkers and neuropathologic schemes were assessed. Results: PiB‐PET showed strong correlations with Thal amyloid phase and Consortium to Establish a Registry for Alzheimer's Disease score and categorized 44% of Thal phase 1 participants as positive. FDG‐PET and MRI correlated modestly with Braak tangle stage in Alzheimer's type pathology. A subset of participants with "none" or "sparse" neuritic plaque scores had elevated PiB‐PET signal due to diffuse amyloid plaque. Participants with findings characterized as "suspected non‐Alzheimer's pathophysiology" represented 15% of the group. Discussion: PiB‐PET is associated with Alzheimer's disease, neuritic plaques, and diffuse plaques. FDG‐PET and MRI have modest correlation with neuropathologic schemes. Participants with findings characterized as suspected non‐Alzheimer's pathophysiology most commonly had primary age‐related tauopathy. [ABSTRACT FROM AUTHOR]

Background: To date, the quantification of the anticoagulant (ACD-A) in plasma units has been based on theoretical calculations. An accurate quantification could help minimize the risks associated with plasmapheresis, given that the total ACD-A used during the procedure is distributed between the donor and the plasma unit. Our aim was to experimentally quantify the volume of ACD-A in units collected by plasmapheresis.Study Design and Methods: We used proton nuclear magnetic resonance spectroscopy to measure the ACD-A volume in 295 plasma units collected by the Azienda USL-IRCCS of Reggio Emilia, Italy. We analyzed the determinants of the differences between estimated and measured ACD-A through multivariate regression models.Results: The experimentally measured ACD-A in plasma units was variable, with 45% of the samples showing a discrepancy of more than 15 mL compared to the manufacturer's estimate. ACD-A was underestimated for higher density of the units (p < 0.0005); a weak association was also observed with triglycerides (underestimated for higher levels, p = 0.015) and sex (overestimated in females, p = 0.008), but our model explained only 35% of the individual variability.Conclusion: The manufacturer's algorithms do not accurately estimate the ACD-A in units collected by plasmapheresis. Donor-related characteristics may affect ACD-A distribution between donor and plasma unit, thereby explaining the discrepancies between estimate and measurement. Errors in the estimate of the ACD-A actually received by donors could hamper studies on dose-response relationship between anticoagulant and adverse reactions. Our work should stimulate research on tailored procedures aimed at minimizing the anticoagulant received by donors and increasing plasmapheresis safety. [ABSTRACT FROM AUTHOR]

Aim: This study determined cardiovascular impairment in young children with obstructive respiratory disease who were assessed using the opening interrupter technique (RINT).Methods: This pilot study enrolled 41 children who had been referred to pulmonology and allergology specialists at the University of Catania, Italy, from March to July 2017: 23 (mean age 4.13 ± 0.62 years) had chronic coughs and wheezing and 18 controls (mean age 4.27 ± 0.66 years) had obstructive chest disease, but were otherwise healthy. Airway resistance was evaluated using RINT and cardiac function by studying the ejection fraction, pulmonary artery systolic pressure (PASP), tricuspid annular plane systolic excursion and tricuspid flow propagation velocity (TFPV).Results: The RINT and PASP values were significantly higher in the patient group when compared to the controls, but the TFPV values were lower. A direct and significant Spearman's correlation coefficient (r) between RINT and PASP values was observed (r = 0.81). We found a significant inverse correlation between RINT and TFPV (r = -0.83), as well as TFPV and PASP (r = -0.78).Conclusion: This study showed that children with obstructive respiratory diseases had a major risk of cardiovascular impairment. Impaired diastolic function of the right ventricle occurred very early when airway resistance was abnormally increased. [ABSTRACT FROM AUTHOR]

Summary: Four 'clean label' formulations for fish burgers made with mechanically separated fish meat were characterised in sensory, textural and chemical terms. The formulations differed in the ratios of European sea bass to rainbow trout (50:50 and 30:70) and the ratios of fish to potato flakes (dry matter ratio, DMR: 2.5:1 and 1.5:1). The sensory profile was mainly influenced by DMR. Recipes with the higher DMR were positively correlated with sandy, dry and crusty attributes, salty taste and overall flavour. Soft texture was perceived for recipes with the lower DMR, although no differences in texture were detected by a texturometer. Lowering DMR increased ash and water content and decreased protein content, as expected. The results indicated that 100 g of burger provided more essential fatty acids than the recommended daily intake, irrespective of formulation. In conclusion, multiple factor analysis indicated that the main changes detected and perceived were due to DMR. The different steps approached during the trial: from waste recovering to high added value fish burgers. [ABSTRACT FROM AUTHOR]

The present work reports on the synthesis of a molecularly imprinted polymer (MIP) based on methacrylic acid and ethylene glycol dimethacrylate for sunitinib delivery. Sunitinib (SUT) is a tyrosine kinase inhibitor used in many cancer diseases. Like the majority of the anticancer drugs, SUT suffers of a low bioavailability, and at the same time, it is characterized by a narrow therapeutic window. In order to reduce drug systemic toxicity, we synthesized a MIP‐based drug delivery system for SUT‐controlled release. MIP was obtained by bulk polymerization through the so‐called noncovalent approach. Rebinding experiments were performed to evaluate the success of the imprinting process and the ability of MIP to bind in a specific and selective fashion the template molecule. Resulting data showed that sunitinib rebinding percentage was 70%, while nonimprinted polymer (NIP) rebinding percentage was 46%. A not significant difference was observed between MIP and NIP in semaxanib binding experiments. Moreover, the drug release profiles were studied for both MIP and NIP. A sustained release was observed from sunitinib‐loaded MIP during 24 hours, reaching 58% after 6 hours and 76% at the end‐point. NIP, on the contrary, released almost 90% of the loaded drug within 6 hours. Furthermore, the drug carrier was tested in vitro against MCF‐7 cells, in which the cytotoxic effect of sunitinib released from MIP reached the maximum after 72 hours, while NIP completed its effect within 48 hours. These results demonstrated that molecularly imprinted polymers are suitable systems for SUT release. [ABSTRACT FROM AUTHOR]

Melanoma skin cancer rates in Queensland exceed the national Australian incidence rate, which together with New Zealand are recognized as the world's highest. Incidence is especially high among younger members of the population. In this study, the sun‐protective behaviors of urban Queenslanders (n = 752) going about their day‐to‐day activities during a midweek noon time hourly period were observed on a summer's day in central Brisbane (27.47°S, 153.03°E), Australia. Observed sun protection practices were poor, given the time of year and peak solar noon period of the study. More individuals (n = 249; 33.1%) were seen wearing sunglasses than a hat (n = 101; 13.4%). Ninety‐three individuals were actively engaging with mobile phones (phone in hand). A further 231 individuals (30.7%) were observed with a mobile phone on them. Opportunities to modify group behavior based on mobile phone sun protection notifications and to engage with "at risk" members of the Queensland population are considered from the variable codependencies examined in this study, including the influence of social group size, observed sun protection and mobile phone use. Our preliminary findings suggest that mobile phones provide an underutilized opportunity for delivering tailored skin cancer prevention messaging. Sun‐protective behaviours and mobile phone use of urban Queenslanders during a midweek noon time hourly period were observed on a summer's day in central, Brisbane, Australia. Our findings suggest that mobile phones provide an under‐utilized opportunity for delivering tailored skin cancer prevention messaging to young people and suggest that a sizeable proportion of funding for mass media public awareness campaigns should be directed towards this approach in favor of traditional electronic media outlets. [ABSTRACT FROM AUTHOR]

Objectives: Endoscopic ultrasound‐guided fine‐needle aspiration (EUS‐FNA) is the gold standard for the diagnosis of solid pancreatic lesions (SPLs). Cytological samples can also be obtained using touch imprint cytology (TIC) on EUS fine‐needle biopsy (FNB) specimens. We aimed to compare sample quality and diagnostic yield of EUS‐FNA‐standard cytology (EUS‐FNA‐SC) to that of EUS‐FNB‐TIC in a series of patients with SPLs. Methods: Thirty‐two consecutive patients referred for EUS‐tissue acquisition of SPLs who underwent rapid on‐site evaluation of both EUS‐FNA‐SC and paired EUS‐FNB‐TIC during the same endoscopic session were retrospectively identified. Sample quality (evaluated in terms of blood contamination, presence of clots, tissue casts, cellularity, and necrosis) and diagnostic yield were compared between the techniques. Results: The mean number of passes to reach diagnosis at rapid on‐site evaluation was similar between EUS‐FNA‐SC and EUS‐FNB‐TIC (1.09 ± 0.3 vs 1.13 ± 0.34, P =.711). EUS‐FNA‐SC scores of sample quality were comparable to those of EUS‐FNB‐TIC (blood contamination, 2.47 ± 1.11 vs 2.25 ± 1.14, P =.109; clots, 1.25 ± 0.76 vs 1.19 ± 0.69, P =.624; tissue casts, 3.56 ± 0.88 vs 3.59 ± 1.09, P =.872; cellularity, 2.84 ± 1.11 vs 3.09 ± 1.09, P =.244; necrosis, 2.25 ± 1.08 vs 2.53 ± 1.02 P =.059; total score, 12.38 ± 2.88 vs 17.66 ± 2.38, P =.536). Adequacy, sensitivity and diagnostic accuracy of the two sampling techniques were equal (93.7%, 90.6% and 90.6%, respectively). Conclusions: EUS‐FNB‐TIC provides comparable samples to those of EUS‐FNA‐SC and combines the benefits of cytology and histology for the evaluation of SPLs by employing a single needle during the same endoscopic procedure. Cytology and histology present pros and cons in the preoperative evaluation of solid pancreatic lesions, and which one should be preferred is still a matter of debate. The use of the touch imprint cytology on EUS‐fine‐needle‐biopsy specimens allows to combine the benefits by providing cytological and histological samples acquired during the same procedure and with the same needle. In our study sample quality and diagnostic yield of EUS standard cytology and EUS touch imprint cytology were evaluated in patients who underwent EUS‐FNA and paired EUS‐FNB with rapid‐on‐site assessment of the same lesion. [ABSTRACT FROM AUTHOR]

Rationale: Protein dynamics are fundamental for biological activity. Direct surface functionalization with these biomolecules often creates regions presenting non‐homogeneous and altered protein functionality. Aptamers have been shown to be an effective method to enhance the biocompatibility of biomaterials by acting as docking points for biomolecules capable of improving cell responses and the colonization/proliferation processes. Here mass spectrometry (MS) was successfully applied as an analytical approach to study the interactions between a fibronectin fragment (FN) and anti‐fibronectin aptamers in solution and on a chitosan film. Methods: A 30 kDa N‐terminal fibronectin fragment, a ssDNA anti‐fibronectin 40 nucleotide long aptamer and chitosan 95/50 (degree of deacetylation 92.6–97.5%; molecular weight 80–220 kDa) were used. First, the dynamics of the FN in aqueous solution, in the presence or absence of anti‐FN‐specific DNA aptamers, were described. Thus, the same study was carried out on 2% (w/w) chitosan‐based films, functionalized with FN alone or through aptamers as selective spacers. Results: Amide hydrogen/deuterium exchange mass spectrometry (HDX‐MS) analysis identified the SYRIGDTWSKKDNRGNL and YRVGDTYERPKDSMI, YVVGETWEKPYQGWMM and WERTYLGNAL fragments as presumably involved in the interaction of FN with aptamers. MS findings indicated the improved functionality of FN on chitosan when aptamers were used as selective spacer, and this may explain why cells preferentially attached to aptamer‐bound FN rather than on chitosan‐FN films. Conclusions: Aptamers did not affect the amount of adsorbed FN, but influenced its conformation enhancing its biological activity toward adhesion and growth of osteoblasts. HDX‐MS data allowed the identification of the FN/aptamer interaction regions. Differences in FN flexibility on the chitosan film in the presence or absence of the aptamer were established providing insights at the molecular level to better understand the protein biological functionality on cell proliferation. [ABSTRACT FROM AUTHOR]

The definition of performance limit states for progressive collapse design and assessment of civil structures is an open issue and deserves special attention in view of future building codes and standards. In this study, the main findings of a multilevel sensitivity analysis are presented to characterize the progressive collapse capacity of a selected class of modern European buildings having a reinforced concrete framed structure. After that a group of capacity model properties are assumed as random variables on the basis of earlier studies, the sensitivity of both ultimate load capacity and corresponding maximum and residual drifts to the ultimate steel strain and location of column‐removal scenario is assessed. Then, the influence of the capacity model properties on maximum drift demand corresponding to a code‐compliant design gravity load is evaluated. Finally, five performance limit states associated with increasing levels of damage are introduced and the corresponding load capacity is quantified under varying capacity model properties. Analysis results indicate a high sensitivity to the ultimate steel strain, column location in plan, beam span and yield steel strength. [ABSTRACT FROM AUTHOR]

The regulation of cytochrome P450 activity is often achieved by structural transitions induced by substrate binding. We describe the conformational transition experienced upon binding by the P450 OleP, an epoxygenase involved in oleandomycin biosynthesis. OleP bound to the substrate analog 6DEB crystallized in 2 forms: one with an ensemble of open and closed conformations in the asymmetric unit and another with only the closed conformation. Characterization of OleP-6DEB binding kinetics, also using the P450 inhibitor clotrimazole, unveiled a complex binding mechanism that involves slow conformational rearrangement with the accumulation of a spectroscopically detectable intermediate where 6DEB is bound to open OleP. Data reported herein provide structural snapshots of key precatalytic steps in the OleP reaction and explain how structural rearrangements induced by substrate binding regulate activity. [ABSTRACT FROM AUTHOR]

Sarcopenia represents one of the hallmarks of all chronic disease, including non‐small cell lung cancer (NSCLC). A computed tomography scan is an easy modality to estimate the skeletal muscle mass through cross‐sectional image analysis at the level of the third lumbar vertebra (L3). Baseline skeletal muscle mass (SMM) was evaluated using gender‐specific cutoffs for skeletal muscle index in NSCLC patients administered immunotherapy with nivolumab to evaluate its possible correlations with clinical outcomes. From April 2015 to August 2018, 23 stage IV NSCLC patients were eligible for image analysis. Nine patients (39.1%) had low SMM. Among patients with baseline low and non‐low SMM, median progression free survival was 3.1 and 3.8 months, respectively (P = 0.0560), while median overall survival was 4.1 and 13 months, respectively (P = 0.2866). This hypothesis‐generating preliminary report offers the opportunity to speculate about the negative influence of sarcopenia on immune response. In our opinion, nutritional status could affect the clinical outcomes of immunotherapy, even if we cannot make definitive conclusions here. Further studies on the topic are required. [ABSTRACT FROM AUTHOR]

BACKGROUND: Electrical stunning (E) and asphyxia in the air (A) are two common stunning/killing methods for fish. However, they can stress the fish and affect flesh quality, so an alternative should be found. The present study aimed to evaluate the effects of carbon monoxide asphyxia (CO) compared to E and A on the evolution of post rigor mortis changes in rainbow trout (Oncorhynchus mykiss) fillets related to chemical, textural, and sensorial properties during storage time. RESULTS: Fish fillets from the E group showed a higher pH (P < 0.05) than the A ones, both at time of rigor resolution (TRR0) and from TRR4 until TRR7 (7 days after rigor resolution, which corresponded to 10 days post mortem), with the CO group being always intermediate. The CO treatment ensured that the fillets showed the lowest yellowness index (b*), even if only at TRR2 and TRR5. Lipid oxidation and texture profile analyses were unaffected. Sensory analysis revealed that the CO fillets had the lowest odor intensity and the highest juiciness scores (P < 0.05). The sensory descriptors resulted the most discriminant variables of the fillets obtained from the differently stunned animals, as resulted by the canonical discriminant analysis. CONCLUSION: The carbon monoxide stunning/slaughtering method could be applied to rainbow trout without detrimental effects on physical, chemical, or sensory characteristics of the fish flesh. © 2018 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

Objective: Subjects with cleft lip and palate (CLP) present high prevalence of dental agenesis. Among candidate genes for these phenotypes is IRF6. However, genetic studies do not analyze dental agenesis as a phenotype associated with cleft. Therefore, we investigated the frequency of rare and novel variations in IRF6 in subjects with non‐syndromic unilateral cleft lip and palate (NSUCLP), with and without dental agenesis. Subjects and Methods: Genomic DNA samples of 100 subjects with NSUCLP with and without dental agenesis and 50 controls were sequenced. IRF6 mutational screening was conducted by direct sequencing. Results: Ten new and rare missense variations were identified, two in the group cleft with agenesis and eight in the group cleft without agenesis, and none were found in control group. In silico analysis revealed four variations as potentially deleterious, being two in the group with cleft and agenesis and two in the group with cleft without agenesis. Conclusion: The study identified novel IFR6 variations in subjects with NSUCLP with or without associated dental agenesis. The hypothesis of a higher frequency of deleterious variations in the subjects with cleft associated with dental agenesis, when compared to the group of cleft without agenesis and control without cleft, was not supported. [ABSTRACT FROM AUTHOR]

Importance The contribution of the microvascular supply to the pathogenesis of Leber's hereditary optic neuropathy (LHON) is poorly understood. Background: We aimed at measuring the peripapillary capillary vessel density (VD) using optical coherence tomography angiography (OCT‐A) at different stages of LHON. Design Prospective, cross‐sectional, multicenter, observational study. Participants: Twenty‐two LHON patients divided in four groups: unaffected mutation carriers (LHON‐u); early sub‐acute stage (LHON‐e); late sub‐acute stage (LHON‐l); chronic stage (LHON‐ch). Methods: OCT‐A scans centred on the optic disc were obtained by spectral domain OCT system. Main Outcome Measures: VD, retinal nerve fibre layer (RNFL) and ganglion cell‐inner plexiform layer (GC‐IPL) thickness were compared between groups. Results: Significant VD changes were detected in every sector (P < 0.0001). In LHON‐e, the VD was reduced in the temporal sector compared with LHON‐u and in the temporal and inferotemporal sectors compared with controls. In LHON‐l, VD was reduced in whole, temporal, superotemporal and inferotemporal sectors compared with LHON‐u and controls. In LHON‐ch, the VD was reduced in all sectors compared to the other groups. An asynchronous pattern emerged in the temporal sector with VD changes occurring earlier than RNFL thickness changes and together with GC‐IPL thinning. Conclusions and Relevance: Significant peripapillary miscrovascular changes were detected over the different stages of LHON. Studying the vascular network separately from fibres revealed that microvascular changes in the temporal sector preceded the changes of RNFL and mirrored the GC‐IPL changes. Measurements of the peripapillary vascular network may become a useful biomarker to monitor the disease process, evaluate therapeutic efficacy and elucidate pathophysiology. [ABSTRACT FROM AUTHOR]

Background: Sarcopenia and muscle tissue degradation are hallmarks of the majority of chronic diseases, including non‐small cell lung cancer (NSCLC). A computed tomography scan could be an easy modality to estimate the skeletal muscle mass through cross‐sectional image analysis at the level of the third lumbar vertebra. Methods: Baseline skeletal muscle mass (SMM) was evaluated through the skeletal muscle index (SMI), together with skeletal muscle radiodensity (SMD), in NSCLC patients undergoing first‐line chemotherapy to evaluate correlations with safety and clinical outcomes. When SMIs at different time points were available, further comparison was made between patients with worse and improved SMIs. Results: Among 81 stage IV NSCLC patients, 28 had low SMM and 23 had low SMD. There were no significant differences in univariate analysis of progression‐free survival (PFS) between patients with baseline low and non‐low SMM (P = 0.06388) or between patients with low and non‐low SMD (P = 0.9126). Baseline low SMM, however, proved a significant predictor of shorter PFS in multivariate analysis (hazard ratio 0.54, 95% confidence interval 0.31–0.93; P = 0.0278), but not low SMD. There were no differences in overall survival (OS) between patients with baseline low and non‐low SMM or low and non‐low SMD. No differences in PFS and OS between evaluable patients with worse or improved SMI were found. A significant difference in hematological toxicities between patients with baseline low and non‐low SMM (P = 0.0358) was observed. Conclusions: Low SMM is predictive of shorter PFS, while consecutive changes in muscular mass do not seem to be a predictor of PFS or OS. The role of muscle radiodensity remains a matter of debate. [ABSTRACT FROM AUTHOR]

In this paper, we present our route to fabricate Cu2ZnSnSe4 (CZTSe) thin films, which allows to achieve reproducible processing of kesterite absorber, that leads to efficiencies in the range of 10%. The article mainly focuses on the annealing process and demonstrates that controlling of the reactor pressure for selenization can be reliably used to tune the losses of volatile constituents in the absorber, enabling adjustments on the properties of the film and solar cell. The findings reveal a noteworthy resilience to small changes of the process parameters in the vicinity of optimum conditions. Interestingly, a certain pressure range for optimum Zn and Sn composition exists, which results in a broad and stable process window and enables reproducible processing of CZTSe with high power conversion efficiencies. The established process also allows simple upscaling of the device area and results in a power conversion efficiency of ≈ 8% on a large area of 2.85 cm2. The highest efficiencies achieved by our process are around 11% for smaller lab scale devices. In this paper, we present our route to fabricate Cu2ZnSnSe4 thin films that leads to efficiencies beyond 10%. The paper focuses on the annealing process and demonstrates the existence of a certain pressure region for selenization, which results in a stable and reproducible process window. The presented devices in this work showed a power conversion of 10.7% for 0.33 cm2 and 7.8% for 2.85 cm2 cell areas. [ABSTRACT FROM AUTHOR]

SOX2 is a transcription factor that is essential for maintenance of pluripotency and has several conserved roles in early embryonic development. Heterozygous loss‐of‐function variants in SOX2 are identified in approximately 40% of all cases of bilateral anophthalmia/micropthalmia (A/M). Increasingly SOX2 mutation‐positive patients without major eye findings, but with a range of other developmental disorders including autism, mild to moderate intellectual disability with or without structural brain changes, esophageal atresia, urogenital anomalies, and endocrinopathy are being reported, suggesting that the clinical phenotype associated with SOX2 loss is much broader than previously appreciated. In this report we describe six new cases, four of which carry novel pathogenic SOX2 variants. Four cases presented with bilateral anophthalmia in addition to extraocular involvement. Another individual presented with only unilateral anophthalmia. One individual did not have any eye findings but presented with a suprasellar teratoma in infancy and was found to have the recurrent c.70del20 mutation in SOX2 (c.70_89del, p.Asn24Argfs*65). This is this first time this tumor type has been reported in the context of a de novo SOX2 mutation. Notably, individuals with hypothalamic hamartomas and slow‐growing hypothalamo‐pituitary tumors have been reported previously, but it is still unclear how SOX2 loss contributes to their formation. [ABSTRACT FROM AUTHOR]

Objective: In this study, we created the Canine Visual Function Instrument (CVFI) and tested its validity and reliability for assessing the quality of vision of dogs. Methods: We used Cronbach's alpha to test the strength of the consistency of the questions in the instrument and factor analysis to assess whether the questions achieved unidimensionality in the measurement of dogs' vision quality. Results: Our analysis shows that the CVFI is a valid and reliable tool to seek self‐reported observations about dogs' vision quality from owners. Our results also show that the vision quality scale has high empirical validity and therefore can be used to determine whether a dog has normal vision or moderate or serious visual impairments. Conclusion: The CVFI might have important practical applications in the field of veterinary ophthalmology in two important ways. First, it can be used to determine whether the treatment of dogs with visual impairment improves vision quality. Second, it can be used as a warning system to alert owners about their dogs' quality of vision. [ABSTRACT FROM AUTHOR]

This research investigated the influence of cloud on the broadband UVA solar noon irradiances evaluated from the solar noon satellite‐based OMI spectral UV data that were compared to the irradiances of a ground‐based radiometer from 1 October 2004 to 31 December 2016. The correlation between ground‐based radiometer data and the evaluated OMI broadband UVA data evaluated with a model were dependent on whether or not the solar disk was obscured by the presence of cloud and the total sky cloud fraction. For conditions when the sun was not obscured by cloud, the evaluated satellite and the ground‐based UVA irradiance correlation was best for cloud cover between 0 and 2 octa (R2 = 0.77) and the worst for high cloud cover of >4–8 octa (R2 between 0.3 and 0.4). The R2 reduced with increasing cloud amount and showed significantly weaker correlation when the sun was obscured. The correlation between the evaluated satellite broadband UVA and the ground‐based measurements over the twelve years for total cloud cover conditions of 4 or less octa confirmed that the broadband UVA satellite evaluation model for the OMI spectral data is valid for approximately 71% of the days at the Southern Hemisphere subtropical study site. The time series of the evaluated satellite UVA irradiances at solar noon for the Toowoomba study site from October 2004 to December 2016 for all sky conditions. This includes 3861 values over 3861 days from satellite‐based data representing 88% of the available days. The annual cyclical pattern with the changing seasons of high and low solar noon UVA irradiances between approximately 30 W m−2 and 60 W m−2 is superimposed on the variation due to cloud. [ABSTRACT FROM AUTHOR]

Epidermal growth factor receptor (EGFR) is a prototypical cell‐surface receptor that plays a key role in the regulation of cellular signaling, proliferation and differentiation. Mutations of its kinase domain have been associated with the development of a variety of cancers and, therefore, it has been the target of drug design. Single amino acid substitutions (SASs) in this domain have been proven to alter the equilibrium of pre‐existing conformer populations. Despite the advances in structural descriptions of its so‐called active and inactive conformations, the associated dynamics aspects that characterize them have not been thoroughly studied yet. As the dynamic behaviors and molecular motions of proteins are important for a complete understanding of their structure–function relationships we present a novel procedure, using (or based on) normal mode analysis, to identify the collective dynamics shared among different conformers in EGFR kinase. The method allows the comparison of patterns of low‐frequency vibrational modes defining representative directions of motions. Our procedure is able to emphasize the main similarities and differences between the collective dynamics of different conformers. In the case of EGFR kinase, two representative directions of motions have been found as dynamics fingerprints of the active conformers. Protein motion along both directions reveals to have a significant impact on the cavity volume of the main pocket of the active site. Otherwise, the inactive conformers exhibit a more heterogeneous distribution of collective motions. © 2018 Wiley Periodicals, Inc. Mutations of Epidermal growth factor receptor (EGFR) have been associated to different human cancers altering the equilibrium of pre‐existing conformer populations, certain of which can become enzymatically more active than the wild‐type. A comparative analysis of dynamics features shared this active conformers. Two representative directions of motions have been found as dynamics fingerprints. Protein motion along both directions impacts on the cavity volume of the main pocket of the active site. [ABSTRACT FROM AUTHOR]

Riboflavin (Rf) is an endogenous photosensitizer, which can participate in Type I and Type II processes. We have recently shown that the yield of the triplet excited states of Rf is enhanced in the presence of pectin‐coated silver nanoparticles (Pec@AgNP) due to formation of a complex between Rf and Pec@AgNP (Rf‐Pec@AgNP). Consequently, under aerobic conditions, the amounts of singlet molecular oxygen and superoxide radical anion generated are also larger in the presence of the nanoparticles. This result made us suspect that the nanoparticles could have a beneficial effect in Rf‐based PDT. To prove this hypothesis, we here compared the photodamage in HeLa cells incubated with Rf in the presence and in the absence of Pec@AgNP applying several optical assays. We used fluorescence imaging of irradiated HeLa cells incubated with Annexin V and propidium iodide to evaluate the occurrence of apoptosis/necrosis, the reduction of the tetrazolium dye MTT to formazan and neutral red uptake to prove cell viability, as well as synchrotron infrared microscopy of single cells to evaluate possible structural changes of DNA and nuclear proteins. The enhanced photodamage observed in the presence of Pec@AgNP seems to indicate that Rf enters into the cells complexed with the nanoparticles. Here, we employ pectin‐coated silver nanoparticles to enhance the photodamage produced by Riboflavin in HeLa cells. [ABSTRACT FROM AUTHOR]