bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synthesis and In Vitro Biological Evaluation of New Pyrido[2,3‐b]pyrazinone‐Based Cytotoxic Agents and Molecular Docking as BRAF Inhibitors
Authors: Amin Kamelia , El‐Badry Ossama , Abdel Rahman Doaa , Ammar Usama 
Published: August 2019

AbstractIn this study, synthesis of new pyrido[2,3‐b]pyrazinone derivatives were identified. The in vitro cytotoxic activity of synthesized compounds against human colon cancer cell line (HCT 116) and kinase assay (V600EBRAF) were investigated. The results revealed that compounds 4 b and 4 c (4‐nitro and 4‐methoxy benzylidene acid hydrazide substitution, respectively) were the most active compounds among the synthesized derivatives (IC50 12.120 and 13.103 μM, respectively). Moreover, they exhibited inhibitory activity against V600EBRAF (Inh % 79.23 and 81.33, respectively). In addition, the designed derivatives were subjected to be simulated with the active site of mutated BRAF kinase domain using a suitable molecular docking protocol. Docking results coincided with good activity of compound 4 c and showed high docking score with BRAF protein kinase domain −21.85171 kcal/mol better than native ligand. The results of this study consider pyridopyrazinone scaffold (with substituted phenyl ring through a spacer) a key nucleus for further molecular and structural optimization.
Ultraminiature and Flexible Sensor Based on Interior Corner Flow for Direct Pressure Sensing in Biofluids
Authors: Tang Longjun , Hong Wen , Wang Xiaolin , Sun Wenxi , Yang Bin , Wei Meng , Pan Jingwei , Liu Jingquan 
Published: August 2019

AbstractConventional pressure sensing devices are well developed for either indirect evaluation or internal measuring of fluid pressure over millimeter scale. Whereas, specialized pressure sensors that can directly work in various liquid environments at micrometer scale remain challenging and rarely explored, but are of great importance in many biomedical applications. Here, pressure sensor technology that utilizes capillary action to self‐assemble the pressure‐sensitive element is introduced. Sophisticated control of capillary flow, tunable sensitivity to liquid pressure in various mediums, and multiple transduction modes are realized in a polymer device, which is also flexible (thickness of 8 µm), ultraminiature (effective volume of 18 × 100 × 580 µm3), and transparent, enabling the sensor to work in some extreme situations, such as in narrow inner spaces (e.g., a microchannel of 220 µm in width and 100 µm in height), or on the surface of small objects (e.g., a 380 µm diameter needle). Potential applications of this sensor include disposables for in vivo and short‐term measurements.
Photocatalytic Micromotors Activated by UV to Visible Light for Environmental Remediation, Micropumps, Reversible Assembly, Transportation, and Biomimicry
Authors: Kong Lei , Mayorga‐Martinez Carmen C. , Guan Jianguo , Pumera Martin 
Published: August 2019

AbstractPhotocatalytic micromotors are light‐induced, chemically powered micromachines based on photocatalytic materials, activated by light illumination, and have redox reactions with environmental solutions to produce chemical gradients and bubbles that propel the micromachines through self‐diffusiophoresis, self‐electrophoresis, and bubble recoil. Due to the fact that excitation light relates largely to the bandgaps of selected materials, the development of photocatalytic micromotors has experienced an evolution from ultraviolet‐light‐activated to visible‐light‐activated and potentially biocompatible systems. Furthermore, due to the strong redox capacity and physical effects caused by the products or product gradients, photocatalytic micromotors have applications in environmental remediation, micropumps, reversible assembly, transportation, and biomimicry.
Trends in Demographics and Surgical Treatment of Weapon‐Related Limb Injuries Over Two Decades in a Resource‐Scarce Setting
Authors: Muhrbeck Måns , Holmgren Kaspar , Osman Zaher , von Schreeb Johan , Wladis Andreas , Andersson Peter 
Published: August 2019

AbstractBackgroundIn the past decades, surgical management of limb injuries in high‐resource settings has improved. The possibility of limb salvage has increased. It is not known whether similar changes have transpired in resource‐scarce conflict settings.MethodsRetrospective cohort study using routinely collected patient data from the International Committee of the Red Cross hospitals in Pakistan was conducted. Consecutive data from 2009 to 2012 (535 patients) and randomly selected data from 1992 to 1995 (463 patients) were used. Only patients with weapon‐related limb injuries were included. Differences in surgical procedures were assessed with logistic regression to adjust for confounding factors.ResultsLess injuries were related to mines in 2009–2012 than in 1992–1995 (3.7% vs. 20.3%, p < 0.0001), but injuries from bombs, shells and fragments were more frequent (38.5% vs. 19.4%, p  < 0.0001) as were injuries with only a small degree of tissue damage (42.0% vs. 31.1%, p  = 0.0004). In the logistic regression, the time period did not affect the risk of amputation, debridement, length of hospital stay or in‐hospital mortality. The use of external fixation (OR 0.56, 95% CI 0.33–0.96, p  = 0.04), split skin grafts (OR 0.31, 95% CI 0.21–0.45, p  < 0.0001) and blood transfusion (OR 0.43, 95% CI 0.28–0.66, p  = 0.0001) was less frequent in 2009–2012.ConclusionIn this resource‐scarce conflict setting, the risk of amputation appears unchanged over time, while the use of external fixation and split skin grafts was less common in 2009–2012 than in 1992–1995. These results contrast with the improved limb salvage results seen in high‐resource settings. It likely reflects the challenges of providing advanced limb‐preserving techniques in a resource‐scarce setting.
Outcomes After Urgent Thyroidectomy Following Rapid Control of Thyrotoxicosis in Graves’ Disease are Similar to Those After Elective Surgery in Well‐Controlled Disease
Authors: Ali Adibah , Debono Miguel , Balasubramanian Sabapathy P. 
Published: August 2019

AbstractBackgroundSurgery for Graves’ disease (GD) is usually performed after adequate control with medical treatment. Occasionally, rapid pre‐operative optimization is required. The primary objective was to compare the outcomes of patients undergoing elective surgery for well‐controlled GD with those undergoing rapid pre‐operative treatment. We also propose a formal treatment protocol for future use.MethodsA retrospective cohort study in a tertiary referral centre included 247 patients with well‐controlled GD undergoing elective surgery and 19 patients with poorly controlled disease undergoing surgery after rapid optimization. The latter group did not respond well to thionamides (carbimazole and/or propylthiouracil) or had intolerance or side effects to thionamides and were treated with a range of non‐thionamide drugs, including Lugol's iodine, cholestyramine, beta blockers and steroids (with or without thionamides), and closely monitored for 1–2 weeks before surgery. Outcome measures included thyroid storm, hypoparathyroidism and recurrent laryngeal nerve palsy.ResultsIn total, 266 patients with male‐to‐female ratio of 1:6 and median (interquartile range) age of 39 (31–51) were included. Overall, long‐term recurrent laryngeal palsy and hypoparathyroidism occurred in 1 (0.38%) and 13 (4.9%) patients, respectively. No patient had thyroid storm. There was no significant difference in hypoparathyroidism (p = 1), vocal cord palsy (p = 0.803) and post‐operative bleeding (p = 0.362), between elective surgery and rapid optimization groups.ConclusionRapid pre‐operative treatment is effective, safe and is associated with similar outcomes compared to usual treatment. A rapid pre‐operative optimization protocol is proposed.
Solid-State Electrolytes for Lithium-Ion Batteries: Fundamentals, Challenges and Perspectives
Authors: Zhao Wenjia , Yi Jin , He Ping , Zhou Haoshen 
Published: August 2019

Abstract
With the rapid popularization and development of lithium-ion batteries, associated safety issues caused by the use of flammable organic electrolytes have drawn increasing attention. To address this, solid-state electrolytes have become the focus of research for both scientific and industrial communities due to high safety and energy density. Despite these promising prospects, however, solid-state electrolytes face several formidable obstacles that hinder commercialization, including insufficient lithium-ion conduction and surge transfer impedance at the interface between solid-state electrolytes and electrodes. Based on this, this review will provide an introduction into typical lithium-ion conductors involving inorganic, organic and inorganic–organic hybrid electrolytes as well as the mechanisms of lithium-ion conduction and corresponding factors affecting performance. Furthermore, this review will comprehensively discuss emerging and advanced characterization techniques and propose underlying strategies to enhance ionic conduction along with future development trends.

Graphical Abstract
Multiple BACE1 inhibitors abnormally increase the BACE1 protein level in neurons by prolonging its half‐life
Authors: Liu Lei , Lauro Bianca M. , Ding Li , Rovere Matteo , Wolfe Michael S. , Selkoe Dennis J. 
Published: August 2019

AbstractIntroductionThere is keen interest in elucidating the biological mechanisms underlying recent failures of β‐site amyloid precursor protein–cleaving enzyme‐1 (BACE1) inhibitors in Alzheimer's disease trials.MethodsWe developed a highly sensitive and specific immunoassay for BACE1 in cell lines and iPSC‐derived human neurons to systematically analyze the effects of eight clinically relevant BACE1 inhibitors.ResultsSeven of 8 inhibitors elevated BACE1 protein levels. Among protease inhibitors tested, the elevation was specific to BACE1 inhibitors. The inhibitors did not increase BACE1 transcription but extended the protein's half‐life. BACE1 became elevated at concentrations below the IC50 for amyloid β (Aβ).DiscussionElevation of BACE1 by 7 of 8 BACE1 inhibitors raises new concerns about advancing such β‐secretase inhibitors for AD. Chronic elevation could lead to intermittently uninhibited BACE1 when orally dosed inhibitors reach trough levels, abnormally increasing substrate processing. Compounds such as roburic acid that lower Aβ by dissociating β/γ secretase complexes are better candidates because they neither inhibit β‐ and γ‐secretase nor increase BACE1 levels.
AS DROPS IN THEIR SEA: ANGELOLOGY THROUGH ONTOLOGY IN FAḪR AL-DĪN AL-RĀZĪ’S AL-MAṬĀLIB AL-῾ĀLIYA
Authors: Hammed Nora Jacobsen Ben 
Published: August 2019

AbstractIn this article, I examine key passages from the Aš῾arite theologian Faḫr al- Dīn al-Rāzī’s (d. 606/1210) final work, Al-Maṭālib al-῾āliya (“ The lofty inquiries ”), in order to theorize Rāzī’s cosmology and angelology. In his attempt to prove the existence of these beings, Rāzī divides reality into material and intelligible realms. Angels, which signify the celestial intellects and spheres, exist as non-space-occupying beings and represent an aspect of the intelligible world. Of these, some are associated with celestial bodies, and others are entirely unassociated with materiality. I then present evidence for the possibility that Rāzī believed that these celestial spiritual beings are pre-eternal with God. These positions indicate a certain degree of conceptual continuity with the falsafa tradition, and reflect al-Ġazālī’s (d. 505/1111) previous integration of the philosophical structure of reality into some of his texts. Additionally, one may look to other philosophical currents that developed in the Islamic world beyond the falāsifa, and connect Rāzī’s cosmology to both the Hermetic tradition and the Epistles of the Iḫwān al-Ṣafā᾿.
AḤMAD B. AL-ṬAYYIB AL-SARAḪSĪ, RÉVISEUR DE L’INTRODUCTION ARITHMÉTIQUE DE NICOMAQUE DE GÉRASE ET RÉDACTEUR DES RASĀ᾿IL IḪWĀN AL-ṢAFĀ᾿
Authors: de Vaulx D'Arcy Guillaume 
Published: August 2019

AbstractBefore Ṯābit b. Qurra's translation, there was a first Arabic version of Nicomachus’ Introduction to arithmetic. Full of mistakes, it was revised by an anonymous student of al-Kindī. Thanks to the part that Freudenthal and Levy have edited and translated, we are now able to identify this reviser as Aḥmad b. al-Ṭayyib al-Saraḫsī, who we also identified as the author of the Rasā᾿il Iḫwān al-Ṣafā᾿. The comparison of the gloss written by this reviser with a new fragment of Saraḫsī on one part, and with the “ Epistles of the Brethren in Purity ” on the other, corroborate Saraḫsī’s authorship of the epistles. Furthermore, studying the misunderstandings on Nicomachus’ text in this kindianised version gives a new light on al-Kindī’s attempt to unify philosophy and on the specific ontology of the Brethren in Purity.
When Passion Appears, Exercise Addiction Disappears
Authors: Szabo Attila , Kovacsik Rita 
Published: August 2019

Abstract. There are approximately 1,000 published articles on exercise addiction, which is characterized by exaggerated training yielding adverse effects. In contrast, there are less than 20 identified cases of exercise addiction in the literature. Recently, it was reported that there is an association between exercise addiction and passion. To test the impact of the latter on exercise addiction, we reanalyzed the combined data from two recent studies. High- and low-exercise volume groups differed in exercise addiction even after controlling for age and sex ( p < .001). However, after adding obsessive and harmonious passion as continuous predictor variables, the statistical significance vanished, whereas both predictors emerged as significant ( p < .001). Further, when controlled for the effect of passion, the correlation between exercise addiction and weekly exercise volume turned out to be negative. Therefore, a conceptual confound between the presumed risk of exercise addiction and passion could render the results of several hundreds of published works questionable. The current findings send an important message to scholars in the field: Studying exercise addiction without controlling for passion may yield false results.
The epigenetic factor BORIS (CTCFL) controls the androgen receptor regulatory network in ovarian cancer
Authors: Salgado-Albarrán Marisol , González-Barrios Rodrigo , Guerra-Calderas Lissania , Alcaraz Nicolás , Estefanía Sánchez-Correa Thalía , Castro-Hernández Clementina , Sánchez-Pérez Yesennia , Aréchaga-Ocampo Elena , García-Carrancá Alejandro , Cantú de León David , Herrera Luis A. , Baumbach Jan , Soto-Reyes Ernesto 
Published: August 2019

AbstractThe identification of prognostic biomarkers is a priority for patients suffering from high-grade serous ovarian cancer (SOC), which accounts for >70% of ovarian cancer (OC) deaths. Meanwhile, borderline ovarian cancer (BOC) is a low malignancy tumor and usually patients undergo surgery with low probabilities of recurrence. However, SOC remains the most lethal neoplasm due to the lack of biomarkers for early diagnosis and prognosis. In this regard, BORIS (CTCFL), a CTCF paralog, is a promising cancer biomarker that is overexpressed and controls transcription in several cancer types, mainly in OC. Studies suggest that BORIS has an important function in OC by altering gene expression, but the effect and extent to which BORIS influences transcription in OC from a genome-wide perspective is unclear. Here, we sought to identify BORIS target genes in an OC cell line (OVCAR3) with potential biomarker use in OC tumor samples. To achieve this, we performed in vitro knockout and knockdown experiments of BORIS in OVCAR3 cell line followed by expression microarrays and bioinformatics network enrichment analysis to identify relevant BORIS target genes. In addition, ex vivo expression data analysis of 373 ovarian cancer patients were evaluated to identify the expression patterns of BORIS target genes. In vitro, we uncovered 130 differentially expressed genes and obtained the BORIS-associated regulatory network, in which the androgen receptor (AR) acts as a major transcription factor. Also, FN1, FAM129A, and CD97 genes, which are related to chemoresistance and metastases in OC, were identified. In SOC patients, we observed that malignancy is associated with high levels of BORIS expression while BOC patients show lower levels. Our study suggests that BORIS acts as a main regulator, and has the potential to be used as a prognostic biomarker and to yield novel drug targets among the genes BORIS controls in SOC patients.
Dynamic responses, GPS positions and environmental conditions of two light rail vehicles in Pittsburgh
Authors: Liu Jingxiao , Chen Siheng , Lederman George , Kramer David B. , Noh Hae Young , Bielak Jacobo , Garrett James H. , Kovačević Jelena , Bergés Mario 
Published: August 2019

AbstractWe present DR-Train, the first long-term open-access dataset recording dynamic responses from in-service light rail vehicles. Specifically, the dataset contains measurements from multiple sensor channels mounted on two in-service light rail vehicles that run on a 42.2-km light rail network in the city of Pittsburgh, Pennsylvania. This dataset provides dynamic responses of in-service trains via vibration data collected by accelerometers, which enables a low-cost way of monitoring rail tracks more frequently. Such an approach will result in more reliable and economical ways to monitor rail infrastructure. The dataset also includes corresponding GPS positions of the trains, environmental conditions (including temperature, wind, weather, and precipitation), and track maintenance logs. The data, which is stored in a MAT-file format, can be conveniently loaded for various potential uses, such as validating anomaly detection and data fusion as well as investigating environmental influences on train responses.
GCN250, new global gridded curve numbers for hydrologic modeling and design
Authors: Jaafar Hadi H. , Ahmad Farah A. , El Beyrouthy Naji 
Published: August 2019

AbstractThe USDA curve-number (CN) method is fundamental for rainfall-runoff modeling. A global CN database is not currently available for geospatial hydrologic analysis at a resolution higher than 0.1°. We developed a globally consistent, gridded dataset defining CNs at the 250 m spatial resolution from new global land cover (300 m) and soils data (250 m). The resulting data product – GCN250 – represents runoff for a combination of the European space agency global land cover dataset for 2015 (ESA CCI-LC) resampled to 250 m and geo-registered with the hydrologic soil group global data product (HYSOGs250m) released in 2018. Our analysis indicated that medium to high runoff potential currently dominates the globe, with curve numbers ranging between 75 and 85. Global curve numbers were 62, 78, and 90 for dry, average, and wet antecedent runoff conditions, respectively. Australia has the highest runoff potential, while Europe has the lowest. Runoff ratios compare well with GLDAS. The potential application of this data includes hydrologic design, land management applications, flood risk assessment, and groundwater recharge modeling.
The TM6SF2 E167K genetic variant induces lipid biosynthesis and reduces apolipoprotein B secretion in human hepatic 3D spheroids
Authors: Prill Sebastian , Caddeo Andrea , Baselli Guido , Jamialahmadi Oveis , Dongiovanni Paola , Rametta Raffaela , Kanebratt Kajsa P. , Pujia Arturo , Pingitore Piero , Mancina Rosellina Margherita , Lindén Daniel , Whatling Carl , Janefeldt Annika , Kozyra Mikael , Ingelman-Sundberg Magnus , Valenti Luca , Andersson Tommy B. , Romeo Stefano 
Published: August 2019

AbstractThere is a high unmet need for developing treatments for nonalcoholic fatty liver disease (NAFLD), for which there are no approved drugs today. Here, we used a human in vitro disease model to understand mechanisms linked to genetic risk variants associated with NAFLD. The model is based on 3D spheroids from primary human hepatocytes from five different donors. Across these donors, we observed highly reproducible differences in the extent of steatosis induction, demonstrating that inter-donor variability is reflected in the in vitro model. Importantly, our data indicates that the genetic variant TM6SF2 E167K, previously associated with increased risk for NAFLD, induces increased hepatocyte fat content by reducing APOB particle secretion. Finally, differences in gene expression pathways involved in cholesterol, fatty acid and glucose metabolism between wild type and TM6SF2 E167K mutation carriers (N = 125) were confirmed in the in vitro model. Our data suggest that the 3D in vitro spheroids can be used to investigate the mechanisms underlying the association of human genetic variants associated with NAFLD. This model may also be suitable to discover new treatments against NAFLD.
Climate and Soil Characteristics Determine Where No-Till Management Can Store Carbon in Soils and Mitigate Greenhouse Gas Emissions
Authors: Ogle Stephen M. , Alsaker Cody , Baldock Jeff , Bernoux Martial , Breidt F. Jay , McConkey Brian , Regina Kristiina , Vazquez-Amabile Gabriel G. 
Published: August 2019

AbstractAdoption of no-till management on croplands has become a controversial approach for storing carbon in soil due to conflicting findings. Yet, no-till is still promoted as a management practice to stabilize the global climate system from additional change due to anthropogenic greenhouse gas emissions, including the 4 per mille initiative promoted through the UN Framework Convention on Climate Change. We evaluated the body of literature surrounding this practice, and found that SOC storage can be higher under no-till management in some soil types and climatic conditions even with redistribution of SOC, and contribute to reducing net greenhouse gas emissions. However, uncertainties tend to be large, which may make this approach less attractive as a contributor to stabilize the climate system compared to other options. Consequently, no-till may be better viewed as a method for reducing soil erosion, adapting to climate change, and ensuring food security, while any increase in SOC storage is a co-benefit for society in terms of reducing greenhouse gas emissions.
Visual inputs and postural manipulations affect the location of somatosensory percepts elicited by electrical stimulation
Authors: Christie Breanne P. , Charkhkar Hamid , Shell Courtney E. , Marasco Paul D. , Tyler Dustin J. , Triolo Ronald J. 
Published: August 2019

AbstractThe perception of somatosensation requires the integration of multimodal information, yet the effects of vision and posture on somatosensory percepts elicited by neural stimulation are not well established. In this study, we applied electrical stimulation directly to the residual nerves of trans-tibial amputees to elicit sensations referred to their missing feet. We evaluated the influence of congruent and incongruent visual inputs and postural manipulations on the perceived size and location of stimulation-evoked somatosensory percepts. We found that although standing upright may cause percept size to change, congruent visual inputs and/or body posture resulted in better localization. We also observed visual capture: the location of a somatosensory percept shifted toward a visual input when vision was incongruent with stimulation-induced sensation. Visual capture did not occur when an adopted posture was incongruent with somatosensation. Our results suggest that internal model predictions based on postural manipulations reinforce perceived sensations, but do not alter them. These characterizations of multisensory integration are important for the development of somatosensory-enabled prostheses because current neural stimulation paradigms cannot replicate the afferent signals of natural tactile stimuli. Nevertheless, multisensory inputs can improve perceptual precision and highlight regions of the foot important for balance and locomotion.