bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synthesis, in vitro, and in vivo evaluation of novel N-phenylindazolyl diarylureas as potential anti-cancer agents
Authors: Solano Lucas N. , Nelson Grady L. , Ronayne Conor T. , Jonnalagadda Shirisha , Jonnalagadda Sravan K. , Kottke Kaija , Chitren Robert , Johnson Joseph L. , Pandey Manoj K. , Jonnalagadda Subash C. , Mereddy Venkatram R. 
Published: October 2020

AbstractNovel N-phenylindazole based diarylureas have been designed, synthesized and evaluated as potential anticancer agents. In vitro cell viability studies of these derivatives illustrate good potency with IC50 values in the range of 0.4–50 μM in several cancer cell lines including murine metastatic breast cancer 4T1, murine glioblastoma GL261, human triple negative breast cancer MDA-MB-231, human pancreatic cancer MIAPaCa-2, and human colorectal cancer cell line WiDr. The ester group in the lead compound 8i was modified to incorporate amino-amides to increase solubility and stability while retaining biological activity. Further in vitro studies reveal that lead candidates inhibit tube length in HUVEC cells. In vivo systemic toxicity studies indicate that these candidate compounds are well tolerated in mice without any significant side effects. Anticancer efficacy studies in WiDr tumor xenograft and 4T1 tumor syngraft models demonstrate that the lead candidate 11 exhibits significant antitumor properties as a single agent in these tumor models.
Computational pipeline to probe NaV1.7 gain-of-function variants in neuropathic painful syndromes
Authors: Toffano Alberto A. , Chiarot Giacomo , Zamuner Stefano , Marchi Margherita , Salvi Erika , Waxman Stephen G. , Faber Catharina G. , Lauria Giuseppe , Giacometti Achille , Simeoni Marta 
Published: October 2020

AbstractApplications of machine learning and graph theory techniques to neuroscience have witnessed an increased interest in the last decade due to the large data availability and unprecedented technology developments. Their employment to investigate the effect of mutational changes in genes encoding for proteins modulating the membrane of excitable cells, whose biological correlates are assessed at electrophysiological level, could provide useful predictive clues. We apply this concept to the analysis of variants in sodium channel NaV1.7 subunit found in patients with chronic painful syndromes, by the implementation of a dedicated computational pipeline empowering different and complementary techniques including homology modeling, network theory, and machine learning. By testing three templates of different origin and sequence identities, we provide an optimal condition for its use. Our findings reveal the usefulness of our computational pipeline in supporting the selection of candidates for cell electrophysiology assay and with potential clinical applications.
Alcohol use in severely injured trauma patients
Authors: Riuttanen Antti , Jäntti Saara J. , Mattila Ville M. 
Published: October 2020

AbstractAlcohol is a major risk factor for several types of injuries, and it is associated with almost all types and mechanisms of injury. The focus of the study was to evaluate alcohol use in severely injured trauma patients with New Injury Severity Score (NISS) of 16 or over, and to compare mortality, injury severity scores and mechanisms and patterns of injury between patients with positive and negative blood alcohol levels (BAL). Medical histories of all severely injured trauma patients (n = 347 patients) enrolled prospectively in Trauma Register of Tampere University Hospital (TAUH) between January 2016 to December 2017 were evaluated for alcohol/substance use, injury mechanism, mortality and length of stay in Intensive Care Unit (ICU). A total of 252 of 347 patients (72.6%) were tested for alcohol with either direct blood test (50.1%, 174/347), breathalyser (11.2%, 39/347), or both (11.2%, 39/347). After untested patients were excluded, 53.5% of adult patients (18–64 years), 20.5% of elderly patients (above 65 years) and 13.3% of paediatric patients (0–17 years) tested BAL positive. The mean measured BAL for the study population was 1.9 g/L. The incidence of injuries was elevated in the early evenings and the relative proportion of BAL positive patients was highest (67.7%) during the night. Injury severity scores (ISS or NISS) and length of stay in ICU were not adversely affected by alcohol use. Mortality was higher in patients with negative BAL (18.2% vs. 7.7%, p = 0.0019). Falls from stairs, and assaults were more common in patients with positive BAL (15.4% vs. 5.4% and 8.7% vs. 2.7%, p < 0.006, respectively). There were no notable differences in injury patterns between the two groups. Alcohol use among severely injured trauma patients is common. Injury mechanisms between patients with positive and negative BAL have differences, but alcohol use will not increase mortality or prolong length of stay in ICU. This study supports the previously reported findings that BAL is not a suitable marker to assess patient mortality in trauma setting.
Biomarker-estimated flavan-3-ol intake is associated with lower blood pressure in cross-sectional analysis in EPIC Norfolk
Authors: Ottaviani Javier I. , Britten Abigail , Lucarelli Debora , Luben Robert , Mulligan Angela A. , Lentjes Marleen A. , Fong Reedmond , Gray Nicola , Grace Philip B. , Mawson Deborah H. , Tym Amy , Wierzbicki Antonia , Forouhi Nita G. , Khaw Kay-Tee , Schroeter Hagen , Kuhnle Gunter G. C. 
Published: October 2020

AbstractFlavan-3-ols are a group of bioactive compounds that have been shown to improve vascular function in intervention studies. They are therefore of great interest for the development of dietary recommendation for the prevention of cardio-vascular diseases. However, there are currently no reliable data from observational studies, as the high variability in the flavan-3-ol content of food makes it difficult to estimate actual intake without nutritional biomarkers. In this study, we investigated cross-sectional associations between biomarker-estimated flavan-3-ol intake and blood pressure and other CVD risk markers, as well as longitudinal associations with CVD risk in 25,618 participants of the European Prospective Investigation into Cancer (EPIC) Norfolk cohort. High flavan-3-ol intake, achievable as part of an habitual diet, was associated with a significantly lower systolic blood pressure (− 1.9 (− 2.7; − 1.1) mmHg in men and − 2.5 (− 3.3; − 1.8) mmHg in women; lowest vs highest decile of biomarker), comparable to adherence to a Mediterranean Diet or moderate salt reduction. Subgroup analyses showed that hypertensive participants had stronger inverse association between flavan-3-ol biomarker and systolic blood pressure when compared to normotensive participants. Flavanol intake could therefore have a role in the maintenance of cardiovascular health on a population scale.
Intrinsic molecular vibration and rigorous vibrational assignment of benzene by first-principles molecular dynamics
Authors: Wang Shaoqing 
Published: October 2020

AbstractVibrational assignment, which establishes the correspondence between vibrational modes and spectral frequencies, is a key step in any spectroscopic study. Due to the lack of experimental technique to directly observe the thermal vibration of atoms, the assignment is usually done by empirical trial-and-error method with considerable uncertainty. Here we demonstrate a successful study of intrinsic molecular vibration property based on first-principles molecular dynamics trajectory. A unified approach for calculating and assigning vibrational frequencies is developed and applied to solve some historical issues of benzene vibration. As a major achievement, the experimental frequencies of benzene a2g and b2u vibrations are reassigned, which breaks a deadlock in contemporary spectroscopic science and removes a cloud over the application of density-functional theory in organic chemistry. This work paves the way for the comprehensive realization of the first-principles spectroscopic research, and provides crucial clues to solve the century-old problems of Kekule resonance, π-deformation, and aromaticity.
Specificity of the chromatic noise influence on the luminance contrast discrimination to the color vision phenotype
Authors: Sousa Bruna Rafaela Silva , Loureiro Terezinha Medeiros Gonçalves , Goulart Paulo Roney Kilpp , Cortes Maria Izabel Tentes , Costa Marcelo Fernandes , Bonci Daniela Maria Oliveira , Baran Luiz Claudio Portnoi , Hauzman Einat , Ventura Dora Fix , Miquilini Leticia , Souza Givago Silva 
Published: October 2020

AbstractMany studies have examined how color and luminance information are processed in the visual system. It has been observed that chromatic noise masked luminance discrimination in trichromats and that luminance thresholds increased as a function of noise saturation. Here, we aimed to compare chromatic noise inhibition on the luminance thresholds of trichromats and subjects with severe deutan or protan losses. Twenty-two age-matched subjects were evaluated, 12 trichromats and 10 with congenital color vision impairment: 5 protanopes/protanomalous, and 5 deuteranopes/deuteranomalous. We used a mosaic of circles containing chromatic noise consisting of 8 chromaticities around protan, deutan, and tritan confusion lines. A subset of the circles differed in the remaining circles by the luminance arising from a C-shaped central target. All the participants were tested in 4 chromatic noise saturation conditions (0.04, 0.02, 0.01, 0.005 u′v′ units) and 1 condition without chromatic noise. We observed that trichromats had an increasing luminance threshold as a function of chromatic noise saturation under all chromatic noise conditions. The subjects with color vision deficiencies displayed no changes in the luminance threshold across the different chromatic noise saturations when the noise was composed of chromaticities close to their color confusion lines (protan and deutan chromatic noise). However, for tritan chromatic noise, they were found to have similar results to the trichromats. The use of chromatic noise masking on luminance threshold estimates could help to simultaneously examine the processing of luminance and color information. A comparison between luminance contrast discrimination obtained from no chromatic and high-saturated chromatic noise conditions could be initially undertaken in this double-duty test.
Individualized fluid administration for critically ill patients with sepsis with an interpretable dynamic treatment regimen model
Authors: Zhang Zhongheng , Zheng Bin , Liu Nan 
Published: October 2020

AbstractFluid strategy is the key to the successful management of patients with sepsis. However, previous studies failed to consider individualized treatment strategy, and clinical trials typically included patients with sepsis as a homogeneous study population. We aimed to develop sequential decision rules for managing fluid intake in patients with sepsis by using the dynamic treatment regimen (DTR) model. A retrospective analysis of the eICU Collaborative Research Database comprising highly granular data collected from 335 units at 208 hospitals was performed. The DTR model used a backward induction algorithm to estimate the sequence of optimal rules. 22,868 patients who had sepsis according to the Acute Physiology and Chronic Health Evaluation (APACHE) IV diagnosis group were included. Optimal fluid management (liberal [> 40 ml/kg/d] versus restricted [< 40 ml/kg/d]) strategy were developed on the Day 1, 3 and 5 after ICU admission according to current states and treatment history. Important determinants of optimal fluid strategy included mean blood pressure, heart rate, previous urine output, previous fluid strategy, ICU type and mechanical ventilation. Different functional forms such as quadratic function and interaction terms were used at different stages. The proportion of subjects being inappropriately treated with liberal fluid strategy (i.e. those actually received liberal fluid strategy, but could have longer survival time if they received restricted fluid strategy) increased from day 1 to 5 (19.3% to 29.5%). The survival time could be significantly prolonged had all patients been treated with optimal fluid strategy (5.7 [2.0, 5.9] vs. 4.1 [2.0, 5.0] days; p < 0.001). With a large volume of sepsis data, we successfully computed out a sequence of dynamic fluid management strategy for sepsis patients over the first 5 days after ICU admission. The decision rules generated by the DTR model predicted a longer survival time compared to the true observed strategy, which sheds light for improving patient outcome with the aim from computer-assisted algorithm.
Perioperative fluids and complications after pancreatoduodenectomy within an enhanced recovery pathway
Authors: Gilgien Jérôme , Hübner Martin , Halkic Nermin , Demartines Nicolas , Roulin Didier 
Published: October 2020

AbstractOptimized fluid management is a key component of enhanced recovery (ERAS) pathways. Implementation is challenging for pancreatoduodenectomy (PD) and clear guidance is missing in the respective protocol. The aim of this retrospective study was to evaluate the influence of perioperative intravenous (IV) fluid administration on postoperative complications. 164 consecutive patients undergoing PD within ERAS between October 2012 and June 2017 were included. Perioperative IV fluid and morbidity (Clavien classification and comprehensive complication index (CCI)) were assessed. A threshold of more than 4400 ml IV fluid during the first 24 h could be identified to predict occurrence of complications (area under ROC curve 0.71), with a positive and negative predictive value of 93 and 23% respectively. More than 4400 ml intravenous fluids during the first 24 h was an independent predictor of overall postoperative complications (adjusted odds ratio 4.40, 95% CI 1.47–13.19; p value = 0.008). Patients receiving ≥ 4400 ml were associated with increased overall complications (94 vs 77%; p value < 0.001), especially pulmonary complications (31 vs 16%; p value = 0.037), as well as a higher median CCI (33.7 vs 26.2; p value 0.041). This threshold of 4400 ml intravenous fluid might be a useful indicator for the management following pancreatoduodenectomy.
TGF-β1 is a regulator of the pyruvate dehydrogenase complex in fibroblasts
Authors: Smith Edward R. , Hewitson Timothy D. 
Published: October 2020

AbstractTGF-β1 reprograms metabolism in renal fibroblasts, inducing a switch from oxidative phosphorylation to aerobic glycolysis. However, molecular events underpinning this are unknown. Here we identify that TGF-β1 downregulates acetyl-CoA biosynthesis via regulation of the pyruvate dehydrogenase complex (PDC). Flow cytometry showed that TGF-β1 reduced the PDC subunit PDH-E1α in fibroblasts derived from injured, but not normal kidneys. An increase in expression of PDH kinase 1 (PDK1), and reduction in the phosphatase PDP1, were commensurate with net phosphorylation and inactivation of PDC. Over-expression of mutant PDH-E1α, resistant to phosphorylation, ameliorated effects of TGF-β1, while inhibition of PDC activity with CPI-613 was sufficient to induce αSMA and pro-collagen I expression, markers of myofibroblast differentiation and fibroblast activation. The effect of TGF-β1 on PDC activity, acetyl-CoA, αSMA and pro-collagen I was also ameliorated by sodium dichloroacetate, a small molecule inhibitor of PDK. A reduction in acetyl-CoA, and therefore acetylation substrate, also resulted in a generalised loss of protein acetylation with TGF-β1. In conclusion, TGF-β1 in part regulates fibroblast activation via effects on PDC activity.
Evaluation of electrode-sample contact impedance under different curing humidity conditions during measurement of AC impedance of cement-based materials
Authors: Wang Ruipan , He Fuqiang , Chen Changping , Dai Lizong 
Published: October 2020

AbstractIn this study, a simple method was proposed to calculate electrode-sample contact impedance in the cases of two-point and four-point measurements. The results indicated that when using the saturated calcium hydroxide solution (SCH) as conductive medium, the contact impedance in the four-point measurement is negligible for the impedance range of cement-based materials. The SCH can be used as a reference for correction of the contact impedance. A reasonable combination of curing humidity and different conductive media is recommended for the two-point measurement, which is suitable for testing the ACIS of cement-based materials. In a case of contact impedance not being precisely known, it is highly recommended that a four-point measurement with two different ratios of the length of the sample and the center spacing of the voltage electrodes (L/a) should be conducted to evaluate the effect of the contact impedance following the procedure proposed in this study.
Automated video-based heart rate tracking for the anesthetized and behaving monkey
Authors: Froesel Mathilda , Goudard Quentin , Hauser Marc , Gacoin Maëva , Ben Hamed Suliann 
Published: October 2020

AbstractHeart rate (HR) is extremely valuable in the study of complex behaviours and their physiological correlates in non-human primates. However, collecting this information is often challenging, involving either invasive implants or tedious behavioural training. In the present study, we implement a Eulerian video magnification (EVM) heart tracking method in the macaque monkey combined with wavelet transform. This is based on a measure of image to image fluctuations in skin reflectance due to changes in blood influx. We show a strong temporal coherence and amplitude match between EVM-based heart tracking and ground truth ECG, from both color (RGB) and infrared (IR) videos, in anesthetized macaques, to a level comparable to what can be achieved in humans. We further show that this method allows to identify consistent HR changes following the presentation of conspecific emotional voices or faces. EVM is used to extract HR in humans but has never been applied to non-human primates. Video photoplethysmography allows to extract awake macaques HR from RGB videos. In contrast, our method allows to extract awake macaques HR from both RGB and IR videos and is particularly resilient to the head motion that can be observed in awake behaving monkeys. Overall, we believe that this method can be generalized as a tool to track HR of the awake behaving monkey, for ethological, behavioural, neuroscience or welfare purposes.
A globally threatened shark, Carcharias taurus, shows no population decline in South Africa
Authors: Klein Juliana D. , der Merwe Aletta E. Bester-van , Dicken Matthew L. , Emami-Khoyi Arsalan , Mmonwa Kolobe L. , Teske Peter R. 
Published: October 2020

AbstractKnowledge about the demographic histories of natural populations helps to evaluate their conservation status, and potential impacts of natural and anthropogenic pressures. In particular, estimates of effective population size obtained through molecular data can provide useful information to guide management decisions for vulnerable populations. The spotted ragged-tooth shark, Carcharias taurus (also known as the sandtiger or grey nurse shark), is widely distributed in warm-temperate and subtropical waters, but has suffered severe population declines across much of its range as a result of overexploitation. Here, we used multilocus genotype data to investigate the demographic history of the South African C. taurus population. Using approximate Bayesian computation and likelihood-based importance sampling, we found that the population underwent a historical range expansion that may have been linked to climatic changes during the late Pleistocene. There was no evidence for a recent anthropogenic decline. Together with census data suggesting a stable population, these results support the idea that fishing pressure and other threats have so far not been detrimental to the local C. taurus population. The results reported here indicate that South Africa could possibly harbour the last remaining, relatively pristine population of this widespread but vulnerable top predator.
Stainless steel weld metal enhanced with carbon nanotubes
Authors: Borges D. J. A. , Cardoso D. C. S. , Braga E. M. , Castro A. A. F. , Dos Reis M. A. L. , Loayza C. R. L. 
Published: October 2020

AbstractThis paper aims to establish the most indicated route to manufacture a nanostructured powder composed of 5 wt% Multi-walled Carbon Nanotubes and 304LSS powder. Four specimens were prepared using Mechanical Alloying and Chemical Treatment (CT) with Hydrogen Peroxide ($${\mathrm{H}}_{2}{\mathrm{O}}_{2}$$H2O2) as the main processes. A thermal treatment post-processing was used in half of the samples to remove the remaining amorphous carbon and to evaluate its effects. Regarding the powder analysis, attachment, amorphous carbon degree, crystallinity, and doping of the CNT throughout the metal matrix were investigated. The nanostructured powders were then inserted as a core in a 304LSS tubular rod to perform the arc welding process. The CT route eliminated the amorphous carbon and generated more refiner grains, which provided a cross-section hardness gain of more than 40% regarding the 304LSS joint. In summary, the CT route, combined with the GTAW process, provided a new method for nanocomposite manufacturing by combining shorter preparation steps, obtaining an improvement in the microstructural and hardness performance.
Bioactive effects of nonthermal argon-oxygen plasma on inorganic bovine bone surface
Authors: Wu Chengzan , Ma Kai , Zhao Hongmei , Zhang Qian , Liu Yanshan , Bai Na 
Published: October 2020

AbstractAs a commonly used bone substitute material in the clinic, inorganic bovine bone has the characteristics of osteoconduction but not osteoinduction. This study aimed to treat inorganic bovine bone using nonthermal argon-oxygen plasma (NTAOP) to obtain greater bioreactivity for enhancing adhesion, proliferation and differentiation of mouse preosteoblast MC3T3-E1 cells. In this study, inorganic bovine bone was activated by NTAOP, and the surface characteristics were analyzed. MC3T3-E1 cells were then seeded onto the surface of inorganic bovine bone. Cell morphology, proliferation and osteogenic differentiation were examined. There was no obvious change in the surface morphology of specimens between the two groups. Regarding the elemental composition of the material, the amount of surface carbon was reduced, whereas oxygen, phosphorus and calcium levels were increased in the NTAOP group. Further studies showed that the NTAOP groups performed better than their untreated counterparts in terms of supporting cell proliferation and differentiation. Inorganic bovine bone treated with NTAOP can promote preosteoblast adhesion, proliferation and differentiation.
Behandlung der allergischen Rhinitis – was gibt es Neues im deutschen Gesundheitssystem?
Authors: Just Maren , Dietz Andreas 
Published: October 2020

ZUSAMMENFASSUNGDie allergische Rhinitis/Rhinokonjunktivitis ist eine der häufigsten chronischen Erkrankungen vor allem im Kindes- und Jugendalter. Aufgrund ihrer Häufigkeit und Chronizität sowie den gesundheitlichen Einschränkungen und den hiermit verbundenen direkten, indirekten und intangiblen Kosten stellt sie ein massives gesellschaftliches Problem dar. Durch strukturierte Versorgungsrichtlinien, wie die ARIA-Leitlinie 2019, sollen wichtige Aspekte der Patientenversorgung, Umsetzung von Leitlinienempfehlungen und deren Anwendung in der Praxis gefördert werden.