bluuebunny/crossref_metadata_2025_split huggingface dataset:
PD-L1 strong expressions affect the clinical outcomes of osimertinib in treatment naïve advanced EGFR-mutant non-small cell lung cancer patients
Authors: Hsu Kuo-Hsuan , Tseng Jeng-Sen , Yang Tsung-Ying , Chen Kun-Chieh , Su Kang-Yi , Yu Sung-Liang , Chen Jeremy J. W. , Huang Yen-Hsiang , Chang Gee-Chen 
Published: June 2022

AbstractThe impact of strong Programmed Death-ligand 1 (PD-L1) expression on the clinical outcomes of osimertinib in treatment naïve advanced Epidermal Growth Factor Receptor (EGFR)-mutant Non-small Cell Lung Cancer (NSCLC) patients remains uncertain. We enrolled advanced NSCLC patients who harbored sensitizing EGFR mutation and were treated first-line with osimertinib between 2017 and 2021. The PD-L1 expression level was also tested. A total of 85 patients were included. The objective response rate to osimertinib was 78.9%, with the disease control rate being 90.8%. Median Progression-free Survival (PFS) was 22.1 months, while median Overall Survival (OS) was not reached (NR). Patients with the exon 19 deletion experienced better PFS than those with the exon 21 L858R mutation (NR vs 12.4 months, aHR 0.24 (95% CI, 0.10 to 0.57); p = 0.001). Seventy-one of these 85 patients had reported on their PD-L1 expression. Patients with a PD-L1 < 50% experienced longer PFS than patients with a PD-L1 ≧50% (26.5 vs 9.7 months, aHR 0.19 (95% CI, 0.06 to 0.67); p = 0.009). Additionally, patients with a PD-L1 < 50% experienced better OS than those with a PD-L1 ≧50% (NR vs 25.4 months, aHR 0.09 (95% CI, 0.01 to 0.70); p = 0.021). Strong expressions of PD-L1 in treatment naïve advanced EGFR-mutant NSCLC patients were associated with poor prognoses in those undergoing treatment with osimertinib as first-line therapy.
Using directional OCT to analyze photoreceptor visibility over AMD-related drusen
Authors: Marsh-Armstrong Brennan , Murrell Kelly S. , Valente Denise , Jonnal Ravi S. 
Published: June 2022

AbstractInvestigators have reported reduced visibility of the cone photoreceptors overlying drusen using adaptive optics (AO) imaging techniques. Two hypotheses have been proposed to explain this phenomenon. First, the disease-related deformation of the photoreceptor outer segment (OS) may reduce its ability to act as a wave guide, thus decreasing the cell’s familiar reflectance pattern. Second, drusen could disorient the photoreceptors away from the eye’s pupil, reducing the amount of light reflected back out the pupil. In this work, we use directional OCT (dOCT) images of drusen in AMD patients to measure the respective contributions of these deforming and disorienting factors.
Association of FXI activity with thrombo-inflammation, extracellular matrix, lipid metabolism and apoptosis in venous thrombosis
Authors: Pallares Robles Alejandro , ten Cate Vincent , Schulz Andreas , Prochaska Jürgen H. , Rapp Steffen , Koeck Thomas , Panova-Noeva Marina , Heitmeier Stefan , Schwers Stephan , Leineweber Kirsten , Seyfarth Hans-Jürgen , Opitz Christian F. , Spronk Henri , Espinola-Klein Christine , Lackner Karl J. , Münzel Thomas , Andrade-Navarro Miguel A. , Konstantinides Stavros V. , ten Cate Hugo , Wild Philipp S. 
Published: June 2022

AbstractAnimal experiments and early phase human trials suggest that inhibition of factor XIa (FXIa) safely prevents venous thromboembolism (VTE), and specific murine models of sepsis have shown potential efficacy in alleviating cytokine storm. These latter findings support the role of FXI beyond coagulation. Here, we combine targeted proteomics, machine learning and bioinformatics, to discover associations between FXI activity (FXI:C) and the plasma protein profile of patients with VTE. FXI:C was measured with a modified activated partial prothrombin time (APTT) clotting time assay. Proximity extension assay-based protein profiling was performed on plasma collected from subjects from the Genotyping and Molecular Phenotyping of Venous Thromboembolism (GMP-VTE) Project, collected during an acute VTE event (n = 549) and 12-months after (n = 187). Among 444 proteins investigated, N = 21 and N = 66 were associated with FXI:C during the acute VTE event and at 12 months follow-up, respectively. Seven proteins were identified as FXI:C-associated at both time points. These FXI-related proteins were enriched in immune pathways related to causes of thrombo-inflammation, extracellular matrix interaction, lipid metabolism, and apoptosis. The results of this study offer important new avenues for future research into the multiple properties of FXI, which are of high clinical interest given the current development of FXI inhibitors.
The Glasgow Prognostic Score and stricture site can predict prognosis after endoscopic duodenal stent placement for malignant gastric outlet obstruction
Authors: Takamatsu Yu , Fujimori Nao , Miyagahara Tsukasa , Suehiro Yuta , Kaku Toyoma , Kawabe Ken , Ohno Akihisa , Matsumoto Kazuhide , Murakami Masatoshi , Teramatsu Katsuhito , Takeno Ayumu , Oono Takamasa , Ogawa Yoshihiro 
Published: June 2022

AbstractEndoscopic duodenal stent (DS) placement for malignant gastric outlet obstruction (GOO) is rapidly increasing in clinical practice; however, the most suitable patient candidates for DS placement have not been determined. One hundred and thirty-five patients with GOO who underwent DS placement in three Japanese referral centers between January 2010 and October 2019 were retrospectively evaluated. Overall survival (OS) after DS placement, technical/clinical success rates, adverse events, and predictive factors affecting OS after DS placement were also analyzed. The median OS after DS placement of all patients was 81 (7–901) days. Technical and clinical success rates were 99.3% and 83.7%, respectively. The GOO Scoring System score significantly increased before and after DS placement (0.9 vs. 2.7, P < 0.001). The procedure-related complication rate was 6.0%. All 19 patients (14.1%) with stent occlusion underwent endoscopic re-intervention successfully. Multivariate analyses revealed chemotherapy after DS placement (P = 0.01), stricture site in D3 (distal part of the papilla) (P = 0.01), and a Glasgow Prognostic Score (GPS) of 0–1 before duodenal stent placement (P < 0.001) were factors significantly associated with prolonged OS. In conclusion, patients with a GPS of 0–1 and D3 stricture who are tolerant of chemotherapy are suitable candidates for DS placement.
Prevalence and factors associated with overweight, obesity, and hypertension in a large clinical sample of adults with autism spectrum disorder
Authors: Thom Robyn P. , Palumbo Michelle L. , Keary Christopher J. , Hooker Jacob M. , McDougle Christopher J. , Ravichandran Caitlin T. 
Published: June 2022

AbstractAdults with autism spectrum disorder (ASD) are at risk for excess bodyweight and hypertension, yet the prevalence of and clinical predictors for these health conditions remain unknown. The objective of this study was to assess the prevalence of overweight, obesity, and hypertension in a large clinical sample of adults with a confirmed diagnosis of ASD and to examine potential clinical predictors. This retrospective chart review study included adult subjects (≥ 20 years) with ASD who had been seen within the past 5 years at a multidisciplinary developmental disorders clinic. Data collected from the electronic health record included age, sex, race and ethnicity, cognitive ability, language ability, body mass index (BMI), hypertension, and use of second generation antipsychotic medications (SGAs). Of 622 adults with a confirmed diagnosis of ASD potentially eligible for the study, 483 (78%) had one or more notes in their records from the past 5 years. Those with recent notes were 23% female, 89% White, and had a mean (SD) age of 28.1 (7.1) years. Overall prevalence estimates for adults represented by this predominantly male, White, and young clinical sample were 28% (95% CI 24%, 32%) for overweight (BMI 25–29.9 kg/m2), 35% (95% CI 31%, 40%) for obesity (≥ 30 kg/m2), and 11% (95% CI 9%, 15%) for hypertension. Controlling for age and sex, intellectual disability (ID) was significantly associated with BMI (p = 0.003) but not hypertension (p = 0.69); those with moderate or more severe ID had a mean BMI that was 2.26 kg/m2 (95% CI 0.96, 3.57) lower than those with no ID. Controlling for age and sex, neither language ability, Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) subtype of autism, nor past or current use of SGAs were significantly associated with BMI or hypertension. The study identified a high prevalence of overweight and obesity in adults with ASD consistent with the prevalence of these medical comorbidities in the U.S. population.
Aspergillus tamarii mediated green synthesis of magnetic chitosan beads for sustainable remediation of wastewater contaminants
Authors: El-Sharkawy Reyad M. , Swelim Mahmoud A. , Hamdy Ghada B. 
Published: June 2022

AbstractThe release of different hazardous substances into the water bodies during the industrial and textile processing stages is a serious problem in recent decades. This study focuses on the potentiality of Fe3O4-NPs-based polymer in sustainable bioremediation of toxic substances from contaminated water. The biosynthesis of Fe3O4-NPs by A. tamarii was performed for the first time. The effect of different independent variables on the Fe3O4-NPs production were optimized using Plackett–Burman design and central composite design (CCD) of Response Surface Methodology. The optimum Fe3O4-NPs production was determined using incubation period (24 h), temperature (30 °C), pH (12), stirring speed (100 rpm) and stirring time (1 h). The incorporation of Fe3O4-NPs into chitosan beads was successfully performed using sol–gel method. The modified nanocomposite exhibited remarkable removal capability with improved stability and regeneration, compared to control beads. The optimal decolorization was 94.7% at 1.5 g/l after 90 min of treatment process. The reusability of biosorbent beads displayed 75.35% decolorization after the 7th cycle. The results showed a highly significant reduction of physico-chemical parameters (pH, TDS, TSS, COD, EC, and PO4) of contaminated wastewater. The sorption trials marked Fe3O4-NPs-based biopolymer as efficient and sustainable biosorbent for the elimination of hazardous toxic pollutants of wastewater in a high-speed rate.
Audience effect on domestic dogs’ behavioural displays and facial expressions
Authors: Pedretti Giulia , Canori Chiara , Marshall-Pescini Sarah , Palme Rupert , Pelosi Annalisa , Valsecchi Paola 
Published: June 2022

AbstractIn the present study we investigated the influence of positive and negative arousal situations and the presence of an audience on dogs’ behavioural displays and facial expressions. We exposed dogs to positive anticipation, non-social frustration and social frustration evoking test sessions and measured pre and post-test salivary cortisol concentrations. Cortisol concentration did not increase during the tests and there was no difference in pre or post-test concentrations in the different test conditions, excluding a different level of arousal. Displacement behaviours of “looking away” and “sniffing the environment” occurred more in the frustration-evoking situations compared to the positive anticipation and were correlated with cortisol concentrations. “Ears forward” occurred more in the positive anticipation condition compared to the frustration-evoking conditions, was positively influenced by the presence of an audience, and negatively correlated to the pre-test cortisol concentrations, suggesting it may be a good indicator of dogs’ level of attention. “Ears flattener”, “blink”, “nose lick”, “tail wagging” and “whining” were associated with the presence of an audience but were not correlated to cortisol concentrations, suggesting a communicative component of these visual displays. These findings are a first step to systematically test which subtle cues could be considered communicative signals in domestic dogs.
Modeling and simulation of high energy density lithium-ion battery for multiple fault detection
Authors: Sadhukhan Chandrani , Mitra Swarup Kumar , Bhattacharyya Suvanjan , Almatrafi Eydhah , Saleh Bahaa , Naskar Mrinal Kanti 
Published: June 2022

AbstractLithium-ion battery, a high energy density storage device has extensive applications in electrical and electronic gadgets, computers, hybrid electric vehicles, and electric vehicles. This paper presents multiple fault detection of lithium-ion battery using two non-linear Kalman filters. A discrete non-linear mathematical model of lithium ion battery has been developed and Unscented Kalman filter (UKF) is employed to estimate the model parameter. Occurrences of multiple faults such as over-charge, over-discharge and short circuit faults between inter cell power batteries, affects the parameter variation of system model. Parallel combinations of some UKF (bank of filters) compare the model parameter variation between the normal and faulty situation and generates residual signal indicating different fault. Simulation results of multiple numbers of statistical tests have been performed for residual based fault diagnosis and threshold calculation. The performance of UKF is then compared with Extended Kalman filter (EKF) with same battery model and fault scenario. The simulation result proves that UKF model responses better and quicker than that of EKF for fault diagnosis.
Transcriptional response of Meloidogyne incognita to non-fumigant nematicides
Authors: Wram Catherine L. , Hesse Cedar N. , Zasada Inga A. 
Published: June 2022

AbstractThere is limited research about the impacts of new nematicides, including fluazaindolizine, fluopyram, and fluensulfone, on the plant-parasitic nematode Meloidogyne incognita, despite it being a pervasive agricultural pest. In this study, M. incognita second-stage juveniles were exposed for 24-h to fluensulfone, fluazaindolizine, fluopyram, and oxamyl and total RNA was extracted and sequenced using next-generation sequencing to determine gene expression. The effects of nematicide exposure on cellular detoxification pathways, common differentially expressed (DE) genes, and fatty acid and retinol-binding genes were examined. Fluopyram and oxamyl had the smallest impacts on the M. incognita transcriptome with 48 and 151 genes that were DE, respectively. These compounds also elicited a weak response in the cellular detoxification pathway and fatty acid and retinol-binding (FAR) genes. Fluensulfone and fluazaindolizine produced robust transcriptional responses with 1208 and 2611 DE genes, respectively. These compounds had strong impacts on cellular detoxification, causing differential regulation of transcription factors and genes in the detox pathway. These compounds strongly down-regulated FAR genes between 52–85%. Having a greater understanding of how these compounds function at a molecular level will help to promote proper stewardship, aid with nematicide discovery, and help to stay a step ahead of nematicide resistance.
Intranasal immunization with a proteosome-adjuvanted SARS-CoV-2 spike protein-based vaccine is immunogenic and efficacious in mice and hamsters
Authors: Stark Felicity C. , Akache Bassel , Deschatelets Lise , Tran Anh , Stuible Matthew , Durocher Yves , McCluskie Michael J. , Agbayani Gerard , Dudani Renu , Harrison Blair A. , Renner Tyler M. , Makinen Shawn R. , Bavananthasivam Jegarubee , Duque Diana , Gagne Martin , Zimmermann Joseph , Zarley C. David , Cochrane Terrence R. , Handfield Martin 
Published: June 2022

AbstractWith the persistence of the SARS-CoV-2 pandemic and the emergence of novel variants, the development of novel vaccine formulations with enhanced immunogenicity profiles could help reduce disease burden in the future. Intranasally delivered vaccines offer a new modality to prevent SARS-CoV-2 infections through the induction of protective immune responses at the mucosal surface where viral entry occurs. Herein, we evaluated a novel protein subunit vaccine formulation containing a resistin-trimerized prefusion Spike antigen (SmT1v3) and a proteosome-based mucosal adjuvant (BDX301) formulated to enable intranasal immunization. In mice, the formulation induced robust antigen-specific IgG and IgA titers, in the blood and lungs, respectively. In addition, the formulations were highly efficacious in a hamster challenge model, reducing viral load and body weight loss. In both models, the serum antibodies had strong neutralizing activity, preventing the cellular binding of the viral Spike protein based on the ancestral reference strain, the Beta (B.1.351) and Delta (B.1.617.2) variants of concern. As such, this intranasal vaccine formulation warrants further development as a novel SARS-CoV-2 vaccine.
Quantification and characterisation of commensal wild birds and their interactions with domestic ducks on a free-range farm in southwest France
Authors: Le Gall-Ladevèze Chloé , Guinat Claire , Fievet Pierre , Vollot Benjamin , Guérin Jean-Luc , Cappelle Julien , Le Loc’h Guillaume 
Published: June 2022

AbstractThe role of commensal birds in the epidemiology of pathogens in poultry farms remains unclear. Our study aimed to identify potential key species for interactions with domestic ducks on one free-range duck farm in southwest France. Methods combined direct individual observations on duck outdoor foraging areas, network analysis, and general linear mixed models of abundances. Results showed a wide diversity of wild bird species visiting foraging areas, heavily dominated in frequency by White wagtails (Motacilla alba) and Sparrows (Passer domesticus and Passer montanus). These also were the only species seen entering duck premises or perching on drinkers in the presence of ducks. Moreover, White wagtails were the species most frequently observed on the ground and in close proximity to ducks. Network analysis suggested the role of White wagtails and Sparrows in linking ducks to other wild birds on the farm. The abundance of White wagtails was positively associated with open vegetation, with the presence of ducks and particularly in the afternoon, while the abundance of Sparrows was positively associated only with the fall-winter season. By precisely characterising interactions, the study was able to identify few wild bird species which should be prioritized in infectious investigations at the interface with poultry.
Impact of GST thickness on GST-loaded silicon waveguides for optimal optical switching
Authors: Parra Jorge , Navarro-Arenas Juan , Kovylina Miroslavna , Sanchis Pablo 
Published: June 2022

AbstractPhase-change integrated photonics has emerged as a new platform for developing photonic integrated circuits by integrating phase-change materials like GeSbTe (GST) onto the silicon photonics platform. The thickness of the GST patch that is usually placed on top of the waveguide is crucial for ensuring high optical performance. In this work, we investigate the impact of the GST thickness in terms of optical performance through numerical simulation and experiment. We show that higher-order modes can be excited in a GST-loaded silicon waveguide with relatively thin GST thicknesses (<100 nm), resulting in a dramatic reduction in the extinction ratio. Our results would be useful for designing high-performance GST/Si-based photonic devices such as non-volatile memories that could find utility in many emerging applications.
Luseogliflozin preserves the pancreatic beta-cell mass and function in db/db mice by improving mitochondrial function
Authors: Yamauchi Yuki , Nakamura Akinobu , Yokota Takashi , Takahashi Kiyohiko , Kawata Shinichiro , Tsuchida Kazuhisa , Omori Kazuno , Nomoto Hiroshi , Kameda Hiraku , Cho Kyu Yong , Anzai Toshihisa , Tanaka Shinya , Terauchi Yasuo , Miyoshi Hideaki , Atsumi Tatsuya 
Published: June 2022

AbstractWe aimed to determine the mechanism by which the sodium glucose co-transporter 2 inhibitor, luseogliflozin, preserves pancreatic beta-cell mass and function in db/db mice. Six-week-old db/db mice were fed to standard chow or standard chow containing 0.01% luseogliflozin. After 4 weeks, DNA microarray analysis, real-time PCR analysis, and measurement of mitochondrial respiratory capacity and reactive oxygen species (ROS) generation were performed using isolated islets. Immunohistochemistry and electron microscopic analysis were performed using pancreatic tissues. Metabolites extracted from the islets were measured by capillary electrophoresis mass spectrometry. The expression of genes involved in the tricarboxylic acid (TCA) cycle and electron transport chain was upregulated by luseogliflozin. Luseogliflozin improved the mitochondrial complex II-linked oxidative phosphorylation capacity and reduced ROS generation. Mitochondrial morphology was normally maintained by luseogliflozin. Luseogliflozin increased NK6 homeobox 1 (NKX6.1) expression and TCA cycle metabolites. Relief of glucotoxicity by luseogliflozin may involve lower mitochondrial ROS generation and an improvement in complex II-linked mitochondrial respiration. Reducing ROS generation through preventing complex II damage likely increases NKX6.1 expression and ameliorate glucose metabolism in the TCA cycle, contributing to the protection of pancreatic beta-cells. Protection of complex II in pancreatic beta-cells represents a novel therapeutic target for type 2 diabetes.
Mechanisms of Quercetin against atrial fibrillation explored by network pharmacology combined with molecular docking and experimental validation
Authors: Tan Xin , Xian Wei , Li Xiaorong , Chen Yongfeng , Geng Jiayi , Wang Qiyi , Gao Qin , Tang Bi , Wang Hongju , Kang Pinfang 
Published: June 2022

AbstractAtrial fibrillation (AF) is a common atrial arrhythmia for which there is no specific therapeutic drug. Quercetin (Que) has been used to treat cardiovascular diseases such as arrhythmias. In this study, we explored the mechanism of action of Que in AF using network pharmacology and molecular docking. The chemical structure of Que was obtained from Pubchem. TCMSP, Swiss Target Prediction, Drugbank, STITCH, Pharmmapper, CTD, GeneCards, DISGENET and TTD were used to obtain drug component targets and AF-related genes, and extract AF and normal tissue by GEO database differentially expressed genes by GEO database. The top targets were IL6, VEGFA, JUN, MMP9 and EGFR, and Que for AF treatment might involve the role of AGE-RAGE signaling pathway in diabetic complications, MAPK signaling pathway and IL-17 signaling pathway. Molecular docking showed that Que binds strongly to key targets and is differentially expressed in AF. In vivo results showed that Que significantly reduced the duration of AF fibrillation and improved atrial remodeling, reduced p-MAPK protein expression, and inhibited the progression of AF. Combining network pharmacology and molecular docking approaches with in vivo studies advance our understanding of the intensive mechanisms of Quercetin, and provide the targeted basis for clinical Atrial fibrillation treatment.