bluuebunny/crossref_metadata_2025_split huggingface dataset:
The efficacy of first-line tyrosine kinase inhibitors combined with co-medications in Asian patients with EGFR mutation non-small cell lung cancer
Authors: Su Vincent Yi-Fong , Yang Kuang-Yao , Huang Ting-Yu , Hsu Chia-Chen , Chen Yuh-Min , Yen Jiin-Cherng , Chou Yueh-Ching , Chang Yuh-Lih , He Chien-Hui 
Published: September 2020

AbstractThe real-world efficacy of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) in patients with advanced non-small cell lung cancer (NSCLC) harboring EGFR-activating mutations remains unclear. We conducted a retrospective cohort study using data from the claims database of Taipei Veterans General Hospital to perform direct comparisons of these three EGFR-TKIs (gefitinib, erlotinib, and afatinib) combined with co-medications (metformin, statins, antacids, and steroids). Stage IIIB and IV NSCLC patients with EGFR mutations receiving EGFR-TKIs as first-line treatment for > 3 months between 2011 and 2016 were enrolled. The primary endpoint was time to treatment failure (TTF). Patients who had received co-medications (≥ 28 defined daily doses) in the first 3 months of EGFR-TKI therapy were assigned to co-medications groups. A total of 853 patients treated with gefitinib (n = 534), erlotinib (n = 220), and afatinib (n = 99) were enrolled. The median duration of TTF was 11.5 months in the gefitinib arm, 11.7 months in the erlotinib arm, and 16.1 months in the afatinib arm (log-rank test, P < 0.001). After adjustments, afatinib showed lower risk of treatment failure compared with gefitinib (hazard ratio [HR] 0.54, 95% confidence interval [CI] 0.41–0.71) and erlotinib (HR 0.62, 95% CI 0.46–0.83). The risk of treatment failure in patients treated with EGFR-TKIs who received concomitant systemic glucocorticoid therapy was higher than in those treated with EGFR-TKI monotherapy (HR 1.47, 95% CI 1.08–2.01). Afatinib or erlotinib use was associated with a lower risk of treatment failure in patients with advanced NSCLC harboring EGFR mutations compared to gefitinib use. Concurrent use of systemic glucocorticoids was linked to higher risk of treatment failure.
Slippery liquid infused fluoropolymer coating for central lines to reduce catheter associated clotting and infections
Authors: Bandyopadhyay Saibal , Jones Andrew , McLean Andrew , Sterner Matthew , Robbins Carolyn , Cunningham Matthew , Walters Mark , Doddapaneni Kiran , Keitel Isaac , Gallagher Colin 
Published: September 2020

AbstractThrombosis and infections are two grave, interrelated problems associated with the use of central venous catheters (CVL). Currently used antibiotic coated CVL has limited clinical success in resisting blood stream infection and may increase the risk of emerging antibiotic resistant strains. We report an antibiotic-free, fluoropolymer-immobilized, liquid perfluorocarbon-coated peripherally inserted central catheter (PICC) line and its effectiveness in reducing catheter associated thrombosis and pathogen colonization, as an alternative to antibiotic coated CVL. Commercially available polyurethane PICC catheter was modified by a three-step lamination process, with thin fluoropolymer layers to yield fluoropolymer–polyurethane–fluoropolymer composite structure before applying the liquid perfluorocarbon (LP). This high throughput process of modifying commercial PICC catheters with fluoropolymer is quicker, safer and shows higher thromboresistance than fluorinated, omniphobic catheter surfaces, produced by previously reported self-assembled monolayer deposition techniques. The LP immobilized on the fluoropolymer is highly durable in physiological flow conditions for over 60 days and continue to resist Staphylococcus colonization.
Fast responses to images of animate and inanimate objects in the nonhuman primate amygdala
Authors: Cleeren E. , Popivanov I. D. , Van Paesschen W. , Janssen Peter 
Published: September 2020

AbstractVisual information reaches the amygdala through the various stages of the ventral visual stream. There is, however, evidence that a fast subcortical pathway for the processing of emotional visual input exists. To explore the presence of this pathway in primates, we recorded local field potentials in the amygdala of four rhesus monkeys during a passive fixation task showing images of ten object categories. Additionally, in one of the monkeys we also obtained multi-unit spiking activity during the same task. We observed remarkably fast medium and high gamma responses in the amygdala of the four monkeys. These responses were selective for the different stimulus categories, showed within-category selectivity, and peaked as early as 60 ms after stimulus onset. Multi-unit responses in the amygdala were lagging the gamma responses by about 40 ms. Thus, these observations add further evidence that selective visual information reaches the amygdala of nonhuman primates through a very fast route.
A general method for analyzing arbitrary planar negative-refractive-index multilayer slab optical waveguide structures
Authors: Wu Yaw-Dong 
Published: September 2020

AbstractIn this paper, a general method for analyzing arbitrary planar negative-refractive-index (NRI) multilayer slab optical waveguide structures was proposed. Some degenerated examples were introduced to prove the accuracy of the proposed method. The analytical and numerical results show excellent agreement. The method can also be degenerated to analyze arbitrary planar conventional optical waveguide structures. Based on this general method, the analysis and calculation of any kinds of planar NRI slab optical waveguide structures and planar conventional optical waveguide structures can be achieved easily.
Iron deficiency markers in patients undergoing iron replacement therapy: a 9-year retrospective real-world evidence study using healthcare databases
Authors: Cacoub Patrice , Nicolas Gael , Peoc’h Katell 
Published: September 2020

AbstractThe diagnosis and treatment of iron deficiency is a primary public health goal. This study aimed to make an inventory of the use of biomarkers to assess the iron supply in patients given iron replacement therapy. A retrospective longitudinal real-world study of a cohort of patients receiving iron replacement therapy was conducted using data from healthcare coverage databases between January 2006 and December 2015 in France. The frequency of oral or intravenous iron treatment episodes preceded and/or followed by a biological assessment of iron deficiency was described. We then differentiate patients with or without chronic inflammatory diseases, which could impact the prescription. The evolution between 2006 and 2015 was also studied. The 96,724 patients received an average of 4.9 administrations of iron per patient, corresponding to 1.7 treatment episodes. In one-third of treatment episodes (34.6%), patients had a pre-treatment biological assessment, 15.5% a post-treatment assessment, and 7.3% both. The post-treatment measure of iron supply markers (i.e., Ferritin and transferrin saturation) was more frequent in patients suffering from chronic inflammatory diseases than in those without underlying chronic condition (22.6% to 41.0% vs. 3.1%; p < 0.0001). Serum ferritin was measured 30 times more than transferrin saturation measurements. The use of both tests increased steadily during the study period, although remaining low. Despite the recommendations, biological assessments of iron status are seldom prescribed and/or performed in the context of a pre- or post-treatment assessment, although more frequently realized in patients with chronic inflammatory diseases.
A central role for the transcriptional regulator VtlR in small RNA-mediated gene regulation in Agrobacterium tumefaciens
Authors: Budnick James A. , Sheehan Lauren M. , Ginder Miranda. J. , Failor Kevin C. , Perkowski Julia. M. , Pinto John. F. , Kohl Kirsten A. , Kang Lin , Michalak Pawel , Luo Li , Heindl Jason E. , Caswell Clayton C. 
Published: September 2020

AbstractLysR-type transcriptional regulators (LTTRs) are the most common type of transcriptional regulators in prokaryotes and function by altering gene expression in response to environmental stimuli. In the class Alphaproteobacteria, a conserved LTTR named VtlR is critical to the establishment of host-microbe interactions. In the mammalian pathogen Brucella abortus, VtlR is required for full virulence in a mouse model of infection, and VtlR activates the expression of abcR2, which encodes a small regulatory RNA (sRNA). In the plant symbiont Sinorhizobium meliloti, the ortholog of VtlR, named LsrB, is involved in the symbiosis of the bacterium with alfalfa. Agrobacterium tumefaciens is a close relative of both B. abortus and S. meliloti, and this bacterium is the causative agent of crown gall disease in plants. In the present study, we demonstrate that VtlR is involved in the ability of A. tumefaciens to grow appropriately in artificial medium, and an A. tumefaciens vtlR deletion strain is defective in motility, biofilm formation, and tumorigenesis of potato discs. RNA-sequencing analyses revealed that more than 250 genes are dysregulated in the ∆vtlR strain, and importantly, VtlR directly controls the expression of three sRNAs in A. tumefaciens. Taken together, these data support a model in which VtlR indirectly regulates hundreds of genes via manipulation of sRNA pathways in A. tumefaciens, and moreover, while the VtlR/LsrB protein is present and structurally conserved in many members of the Alphaproteobacteria, the VtlR/LsrB regulatory circuitry has diverged in order to accommodate the unique environmental niche of each organism.
A flavin-dependent monooxygenase catalyzes the initial step in cyanogenic glycoside synthesis in ferns
Authors: Thodberg Sara , Sørensen Mette , Bellucci Matteo , Crocoll Christoph , Bendtsen Amalie Kofoed , Nelson David Ralph , Motawia Mohammed Saddik , Møller Birger Lindberg , Neilson Elizabeth Heather Jakobsen 
Published: September 2020

AbstractCyanogenic glycosides form part of a binary plant defense system that, upon catabolism, detonates a toxic hydrogen cyanide bomb. In seed plants, the initial step of cyanogenic glycoside biosynthesis—the conversion of an amino acid to the corresponding aldoxime—is catalyzed by a cytochrome P450 from the CYP79 family. An evolutionary conundrum arises, as no CYP79s have been identified in ferns, despite cyanogenic glycoside occurrence in several fern species. Here, we report that a flavin-dependent monooxygenase (fern oxime synthase; FOS1), catalyzes the first step of cyanogenic glycoside biosynthesis in two fern species (Phlebodium aureum and Pteridium aquilinum), demonstrating convergent evolution of biosynthesis across the plant kingdom. The FOS1 sequence from the two species is near identical (98%), despite diversifying 140 MYA. Recombinant FOS1 was isolated as a catalytic active dimer, and in planta, catalyzes formation of an N-hydroxylated primary amino acid; a class of metabolite not previously observed in plants.
Synthesis of new pyrazolone and pyrazole-based adamantyl chalcones and antimicrobial activity
Authors: Al-Saheb Rawan , Makharza Sami , Al-battah Feras , Abu-El-Halawa Rajab , Kaimari Tawfeq , Abu Abed Omar S. 
Published: September 2020

Abstract
Chalcones and their derivatives are becoming increasingly popular due to their various pharmacological effects. Chalcone molecules may be extracted from natural resources, entirely synthesised, or biosynthesised by modifying the natural ones. In the present study, five pyrazole-based adamantyl heterocyclic compounds were synthesised by condensation of 1-adamantyl chalcone with substituted phenylhydrazine. The products were characterised by using ¹H NMR, ¹³C NMR and FT-IR spectroscopy. The microbiological activity of these compounds was investigated against bacteria and fungi. The new compounds showed good to moderate activity against the microbial species used for screening. All developed molecules showed antibacterial activity against Gram-negative and Gram-positive. These molecules showed antifungal activities against Fusarium oxysporum fungus and in a dose-dependent manner, apart from RS-1 molecules which showed compromised antifungal activity and even at a high dose.
Vieira Natividade Experimental Plots at Mata Nacional do Vimeiro, Portugal
Authors: Carrasquinho Isabel , Nóbrega Filomena , Gonçalves Jorge , Costeira Isabel 
Published: September 2020

In 1933, Joaquim Vieira Natividade established an experimental field with oaks and related genera at Mata Nacional do Vimeiro, Portugal. This experimental area includes the only Portuguese plots with the hybrid Quercus x hispanica hybrid ‘Lucombeana’ (Quercus cerris x suber) with seeds obtained from the Cambridge Botanic Gardens.In 1962-1965, their offspring were included in this area.
Those plots integrate an ex situ forest genetic resources, representing a unique population for understanding the structure, function and evolution of the genome (genomics) and its gene expression (transcriptomics). In all progenies, with approximately 60 years, it is evident the segregation for several phenotypic characteristics, specifically in the cork formation and in the leaf shape. Based on that, two projects were developed with this plant material. The first was focused on finding out the molecular basis responsible for the variation in cork and the other on association genetic studies.
The aim of this work is to allow access and sharing of knowledge about this genetic material in accordance with the established by FAO in the State of the World’s Forest Genetic Resources report. Information about these hybridsis available at PANGAEA repository.
Psychotherapie in der interdisziplinären multimodalen Schmerztherapie: Update
Authors: Müller Maike , Bräscher Anne-Kathrin 
Published: September 2020

ZusammenfassungPsychotherapie bei chronischen Schmerzen? Was auf den ersten Blick unpassend erscheint, entpuppt sich als hilfreiche und wirksame Intervention für Störungsbilder, bei denen rein somatisch orientierte Behandlungsversuche scheitern. Eingebettet in die interdisziplinäre multimodale Schmerztherapie stellt die Schmerzpsychotherapie heutzutage einen essenziellen Bestandteil der Behandlung chronischer Schmerzen dar.
Hyperfibrinolyse nach Reanimation bei akuter Lungenarterienembolie
Authors: Weber Christian F. , Wesselly Ariane , Held Thomas , Anheuser Petra , Schönwälder Jürgen , Weischer Willem 
Published: September 2020

ZusammenfassungKommt es nach einer Reanimation – z. B. wegen akuter Lungenarterienembolie – im Rahmen eines Post-Cardiac-Arrest-Syndroms (PCAS) zu einer Hyperfibrinolyse, stellt dies eine diagnostische und therapeutische Herausforderung dar. In diesem Fallbericht wird die Pathophysiologie der Koagulopathie bei PCAS beschrieben und der Einsatz antifibrinolytischer Therapie bei Patienten mit thrombotischen Komplikationen wie Lungenarterienembolien diskutiert.
In Silico Hemostasis Modeling and Prediction
Authors: Nechipurenko Dmitry Y. , Shibeko Aleksey M. , Sveshnikova Anastasia N. , Panteleev Mikhail A. 
Published: September 2020

AbstractComputational physiology, i.e., reproduction of physiological (and, by extension, pathophysiological) processes in silico, could be considered one of the major goals in computational biology. One might use computers to simulate molecular interactions, enzyme kinetics, gene expression, or whole networks of biochemical reactions, but it is (patho)physiological meaning that is usually the meaningful goal of the research even when a single enzyme is its subject. Although exponential rise in the use of computational and mathematical models in the field of hemostasis and thrombosis began in the 1980s (first for blood coagulation, then for platelet adhesion, and finally for platelet signal transduction), the majority of their successful applications are still focused on simulating the elements of the hemostatic system rather than the total (patho)physiological response in situ. Here we discuss the state of the art, the state of the progress toward the efficient “virtual thrombus formation,” and what one can already get from the existing models.
Does Rabeprazole Sodium Alleviate the Anti-diabetic Activity of
Linagliptin? Drug-Drug Interaction Analysis by In vitro and In vivo
Methods
Authors: Hossain Md. Jamal , Sultan Md. Zakir , Rashid Mohammad A. , Kuddus Md. Ruhul 
Published: September 2020

AbstractDrug interaction has turned into the preeminent regarding issues for a prescriber
during polypharmacy. The foremost objective of this research was to form a
complex between linagliptin and rabeprazole sodium by in vitro
interactions. The interactions between the drugs have been examined by
monitoring some chromatographic and spectroscopic analyses viz. TLC, HPLC,
FT-IR, UV, Job’s plot, conductometric titrations, and Ardon’s
spectrophotometric strategy. Rabeprazole sodium formed a stable complex with
linagliptin, which was ensured from the insight of these analytical data. The
developed complex’s bright spot was clearly watched in the TLC plate.
The retention time (Rt) of the formed complex was 5.303 min,
where the Rt were 3.364 and 3.103 min for linagliptin and
rabeprazole sodium, respectively, in HPLC chromatograms. In FT-IR and UV spectra
of the formed complex revealed some disappearance of characteristic peaks that
affirmed the complexation. All of the variations of the spectrophotometric and
chromatographic properties from the antecedent drugs indicated the drug-drug
interaction. Another crucial fact for the experimental aim was to affirm the
assumed drug interaction by in vivo model examination. The assessment of
anti-diabetic property on alloxan-induced Swiss albino mice proved significant
in vivo interaction between the drugs. It was outlined from the
animal study that the hypoglycemic activity of linagliptin might be
significantly affected due to the complex formation of the drug with a proton
pump inhibitor (PPI). Nonetheless, it is the primary outcome of the interaction,
which recommends the bigger in vivo study or clinical monitoring on the
human model.
Bouncing back, if not beyond: Challenges for research on resilience
Authors: Hoegl Martin , Hartmann Silja 
Published: September 2020

AbstractSetbacks are a fact of life for individuals and collectives—and resilience is a key concept in explaining why some entities positively adapt (i.e., bounce back) or even emerge stronger (i.e., bounce beyond), while others suffer from such events, sometimes permanently. In this short note, we briefly introduce the concept of resilience before moving to three key challenges for management research in this field. With this, we would like to encourage the international scholarly research community to view any phenomenon of their interest also from a resilience perspective, considering significant setbacks and processes of positive adaptation.
Regulation of hepatic insulin signaling and glucose homeostasis by sphingosine kinase 2
Authors: Aji Gulibositan , Huang Yu , Ng Mei Li , Wang Wei , Lan Tian , Li Min , Li Yufei , Chen Qi , Li Rui , Yan Sishan , Tran Collin , Burchfield James G. , Couttas Timothy A. , Chen Jinbiao , Chung Long Hoa , Liu Da , Wadham Carol , Hogg Philip J. , Gao Xin , Vadas Mathew A. , Gamble Jennifer R. , Don Anthony S. , Xia Pu , Qi Yanfei 
Published: September 2020

SignificanceHepatic insulin resistance is a chief pathogenic determinant in the development of type 2 diabetes, which is often associated with abnormal hepatic lipid regulation. Sphingolipids are a class of essential lipids in the liver, where sphingosine kinase 2 (SphK2) is a key enzyme in their catabolic pathway. However, roles of SphK2 and its related sphingolipids in hepatic insulin resistance remain elusive. Here we generate liver-specific Sphk2 knockout mice, demonstrating that SphK2 in the liver is essential for insulin sensitivity and glucose homeostasis. We also identify sphingosine as a bona fide endogenous inhibitor of hepatic insulin signaling. These findings provide physiological insights into SphK2 and sphingosine, which could be therapeutic targets for the management of insulin resistance and diabetes.
Proline-rich domain of human ALIX contains multiple TSG101-UEV interaction sites and forms phosphorylation-mediated reversible amyloids
Authors: Elias Ruben D. , Ma Wen , Ghirlando Rodolfo , Schwieters Charles D. , Reddy Vijay S. , Deshmukh Lalit 
Published: September 2020

Significance
Human ALIX is involved in many essential cellular processes. The carboxy (C)-terminal proline-rich domain (PRD) of ALIX, which interacts with multiple partners, has eluded analysis owing to the presence of polyproline stretches that hinder recombinant protein production. By dividing it into two fragments, the amino (N)- and the C-terminal portions, we carry out a detailed biophysical investigation of ALIX-PRD. The disordered N-terminal fragment comprises three proline-rich motifs that compete for binding to its partner, TSG101-UEV. In contrast, the C-terminal fragment forms reversible amyloids modulated by tyrosine phosphorylation, the first known example where posttranslational modifications dictate the dissolution of amyloid fibrils. This study illustrates the mechanistic interdependence of multivalency brought out by polymerization of ALIX-PRD and its effect on ALIX function.
Non-Markovian trajectories involving future in semi-classical path integral expression
Authors: Wang Fei 
Published: September 2020

Abstract
Semi-classical path integral expression for a quantum system coupled to a harmonic bath is derived based on the stationary phase condition. It is discovered that the system path is non-Markovian. Most strikingly, the system path not only couples to its past, but also to its future, i.e. the equation of motion for the system is an integro-differential equation that involves all times. Numerical examples are given at the end. Because of the future-non-Markovian nature of the equation, the numerical solution cannot be obtained by iterative methods. Instead, root search algorithms must be employed.
The M waves of the biceps brachii have a stationary (shoulder-like) component in the first phase: implications and recommendations for M-wave analysis
Authors: Rodriguez-Falces Javier , Botter Alberto , Vieira Taian , Place Nicolas 
Published: September 2020

Abstract

Objective. We recently documented that compound muscle action potentials (M waves) recorded over the ‘pennate’ vastus lateralis showed a sharp deflection (named as a shoulder) in the first phase. Here, we investigated whether such a shoulder was also present in M waves evoked in a muscle with different architecture, such as the biceps brachii, with the purpose of elucidating the electrical origin of such afeature. Approach. M waves evoked by maximal single shocks to the brachial plexus were recorded in monopolar and bipolar configurations from 72 individuals using large (10 mm diameter) electrodes and from eight individuals using small (1 mm diameter) electrodes arranged in a linear array. The changes in M-wave features at different locations along the muscle fiber direction were examined. Main results. The shoulder was recognizable in most (87%) monopolar M waves, whereas it was rarely observed (6%) in bipolar derivations. Recordings made along the fiber direction showed that the shoulder was a stationary (non-propagating) feature, with short duration (spiky), which had positive polarity at all locations along the fibers. The latency of the shoulder (9.5 ± 0.5 ms) was significantly shorter than the estimated time taken for the action potentials to reach the biceps tendon (12.8 ms). Significance. The shoulder must be generated by a dipole source, i.e. a source created at a fixed anatomical position, although the exact origin of this dipole is uncertain. Our results suggest that the shoulder may not be due to the end-of-fiber signals formed at the biceps brachii tendon. The shoulder is not related to any specific arrangement of muscle fibers, as it has been observed in both pennate and fusiform muscles. Being a stationary (non-propagating) component, the shoulder is not reliable for studying changes in sarcolemmal excitability, and thus should be excluded from the M-wave analysis.