bluuebunny/crossref_metadata_2025_split huggingface dataset:
Design, synthesis, antileishmanial, and antifungal biological evaluation of novel 3,5‐disubstituted isoxazole compounds based on 5‐nitrofuran scaffolds
Authors: Trefzger Ozildéia S. , Barbosa Natália V. , Scapolatempo Renata L. , das Neves Amarith R. , Ortale Maria L. F. S. , Carvalho Diego B. , Honorato Antônio M. , Fragoso Mariana R. , Shuiguemoto Cristiane Y. K. , Perdomo Renata T. , Matos Maria F. C. , Chang Marilene R. , Arruda Carla C. P. , Baroni Adriano C. M. 
Published: December 2019

AbstractNineteen 3,5‐disubstituted‐isoxazole analogs were synthesized based on nitrofuran scaffolds, by a [3 + 2] cycloaddition reaction between terminal acetylenes and 5‐nitrofuran chloro‐oxime. The compounds were obtained in moderate to very good yields (45–91%). The antileishmanial activity was assayed against the promastigote and amastigote forms of Leishmania (Leishmania) amazonensis. Alkylchlorinated compounds 14p–r were active on both the promastigote and amastigote forms, with emphasis on compound 14p, which showed strong activity against the amastigote form (IC50 = 0.6 μM and selectivity index [SI] = 5.2). In the alkyl series, compound 14o stands out with an IC50 = 8.5 μM and SI = 8.0 on the amastigote form. In the aromatic series, the most active compounds were those containing electron‐donor groups, such as trimethoxy isoxazole 14g (IC50 = 1.2 μM and SI = 20.2); compound 14h, with IC50 = 7.0 μM and SI = 6.1; and compound 14j containing the 4‐SCH3 group, with IC50 = 5.7 μM and SI = 10.2. In addition, the antifungal activity of 19 nitrofuran isoxazoles was evaluated against five strains of Candida (C. albicans, C. parapsilosis, C. krusei, C. tropicalis, and C. glabrata). Eleven isoxazole derivatives were active against C. parapsilosis, and compound 14o was found to be the most active (minimal inhibitory concentration [MIC] = 3.4 μM) for this strain. Compound 14p was active against all the strains tested, with an MIC = 17.5 μM for C. glabrata, lower than that of the fluconazole used as the reference drug.
Insulin‐Resistant Pathways Are Associated With Disease Activity in Rheumatoid Arthritis and Are Subject to Disease Modification Through Metabolic Reprogramming: A Potential Novel Therapeutic Approach
Authors: Gallagher Lorna , Cregan Sian , Biniecka Monika , Cunningham Clare , Veale Douglas J. , Kane David J. , Fearon Ursula , Mullan Ronan H. 
Published: December 2019

ObjectiveTo investigate a role for insulin‐resistant pathways in inflammation and therapeutic targeting for disease modification in rheumatoid arthritis (RA).MethodsRA disease activity and cardiovascular risk factors, including insulin resistance and body mass index (BMI), were assessed in an Irish RA cohort. Glucose transporter 1 (GLUT‐1) and GLUT‐4 activity in RA and osteoarthritis (OA) synovial tissue was examined using immunohistochemistry. Spontaneous release of proinflammatory mediators from ex vivo RA synovial explants and primary synovial fibroblast (SF) cell culture supernatants was quantified by enzyme‐linked immunosorbent assay. Phosphorylated AMP‐activated protein kinase (p‐AMPK) and GLUT‐1 protein expression was analyzed by Western blotting. Cellular glycolytic and oxidative phosphorylation was assessed using extracellular flux analysis.ResultsInsulin resistance was independently associated with both BMI (unstandardized coefficient B 0.113 [95% confidence interval (95% CI) 0.059–0.167]; P < 0.001) (n = 61) and swollen joint count in 28 joints (SJC28) (B 0.114 [95% CI 0.032–0.197]; P = 0.008) (n = 61). Increased GLUT‐1 expression in RA synovium (n = 26) versus OA synovium (n = 16) was demonstrated (P = 0.0003), with increased expression in the lining, sublining, and vascular regions. In contrast, decreased GLUT‐4 expression in the RA lining layer (n = 21) versus the OA lining layer (n = 8) was observed (P = 0.0358). Decreased GLUT‐1 protein expression was observed in parallel with increased p‐AMPK protein expression in SFs in the presence of metformin (n = 4). Metformin increased glycolytic activity and decreased oxidative phosphorylation in RASFs (n = 7) (P < 0.05 for both). Metformin or aminoimidazole carboxamide ribonucleotide presence decreased spontaneous production of interleukin‐6 (IL‐6), IL‐8, and monocyte chemotactic protein 1 in RA synovial explants and SFs (n = 5–7).ConclusionInsulin resistance is significantly associated with BMI and synovitis in RA, suggesting distinct interplay between glucose availability and inflammation in RA. Furthermore, the effect of metformin on proinflammatory mechanisms suggests a role for AMPK‐modifying compounds in the treatment of RA.
Dynamic analysis of a novel time‐lag four‐dimensional fractional‐order financial system
Authors: Zhang Zhe , Zhang Jing , Cheng Fanyong , Liu Feng , Ding Can 
Published: December 2019

AbstractIn this paper, a novel four‐dimensional fractional‐order financial system (FFS) with time delay is presented. Unlike traditional bifurcation analysis of financial systems, the selection rules of two bifurcation points within the system are discussed. In addition, the motion state of the system in the vicinity of two bifurcation points are analyzed separately, such that the dynamic analysis of this novel nonlinear fourth‐dimensional FFS is more comprehensive. The detailed dynamical behaviors of this financial system, such as oscillation, stability, and bifurcation points, are deduced via rigorous mathematical analysis. Finally, some simulations are performed to verify the dynamic characteristics of the FFS around the two bifurcation points which satisfy the selection conditions of the bifurcation point.
Maternal surgery and anesthesia during pregnancy and risk of birth defects in the National Birth Defects Prevention Study, 1997–2011
Authors: Fisher Sarah C. , Siag Kamalnain , Howley Meredith M. , Van Zutphen Alissa R. , Reefhuis Jennita , Browne Marilyn L. ,   the National Birth Defects Prevention Study
Published: December 2019

AbstractBackgroundThere is little recent research on the teratogenicity of maternal anesthesia exposure. We used National Birth Defects Prevention Study data to describe surgical procedures conducted during pregnancy and to estimate the risk of birth defects associated with periconceptional anesthesia exposure.MethodsWe used logistic regression to assess associations between general and local anesthesia for surgery during the periconceptional period and specific birth defects. We calculated odds ratios and 95% confidence intervals for 25 birth defects with at least five exposed cases (11,501 controls, 24,337 cases), adjusted for maternal race/ethnicity, age, body mass index, periconceptional exposure to X‐ray, CT, or radionuclide scans, and study site.ResultsThe most commonly reported procedures were dental, dermatologic, and cervical cerclage procedures, regardless of gestational timing. Overall, 226 case and 73 control women reported periconceptional general anesthesia; 230 case and 89 control women reported periconceptional local anesthesia. Women who reported general or local anesthesia were disproportionately non‐Hispanic white and were more likely to report periconceptional opioid use and at least one periconceptional X‐ray/CT/radionuclide scan. Women who reported general anesthesia were also more likely to report periconceptional injury. We did not observe any significant associations between either type of anesthesia exposure and the birth defects studied. Odds ratios were generally close to null and imprecise.ConclusionsOur study population reported a wide range of surgical procedures during pregnancy, requiring both general and local anesthesia. Our findings suggest that periconceptional anesthesia is not strongly associated with the birth defects assessed in this study.
Exploration of highly selective fluorogenic ‘on–off' chemosensor for H2PO4− ions: ICT‐based sensing and ATPase activity profiling
Authors: Wagh Yogesh B. , Tayade Kundan C. , Kuwar Anil , Sahoo Suban K. , Mayank  , Singh Narinder , Dalal Dipak S. 
Published: December 2019

AbstractAbstractIn this study, the recognition contour of Chemosensor 1 was investigated using semiaqueous methanol (XH, mole fraction = 0.31) for a range of anions and bioactive species. Host–receptor signalling based on the internal charge transfer mechanism for Chemosensor 1 was explored and reported. Structure of Chemosensor 1 and its plausible anion coordination based on hydrogen bonding is complemented with density functional theory. Consequently, we investigated the applicability of the synthesized probe in blood plasma, urine, tap water samples, and for monitoring of ATP in lysosomes by apyrase enzyme.
Methods for Estimating the Probability of Clonality in Cell Line Development
Authors: Chen Chun , Le Kim , Le Huong , Daris Kristi , Soice Neil , Stevens Jennitte , Goudar Chetan T. 
Published: December 2019

AbstractMammalian cell banks for biopharmaceutical production are usually derived from a single progenitor cell. Different methods to estimate the probability that the cell banks are clonally derived, or the probability of clonality (PoC), associated with various cloning workflows have been reported previously. In this review, a systematic analysis and comparison of the methods used to calculate the PoC are provided. As the single cell deposition and high‐resolution imaging technologies continue to advance and the cloning workflow evolves, an aligned understanding and best practice on estimating the PoC is necessary to compare different cloning workflows adopted across the biopharmaceutical industry and it will help to accelerate regulatory acceptance.
Cell‐free protein synthesis: The transition from batch reactions to minimal cells and microfluidic devices
Authors: Ayoubi‐Joshaghani Mohammad H. , Dianat‐Moghadam Hassan , Seidi Khaled , Jahanban‐Esfahalan Ali , Zare Peyman , Jahanban‐Esfahlan Rana 
Published: December 2019

AbstractThanks to the synthetic biology, the laborious and restrictive procedure for producing a target protein in living microorganisms by biotechnological approaches can now experience a robust, pliant yet efficient alternative. The new system combined with lab‐on‐chip microfluidic devices and nanotechnology offers a tremendous potential envisioning novel cell‐free formats such as DNA brushes, hydrogels, vesicular particles, droplets, as well as solid surfaces. Acting as robust microreactors/microcompartments/minimal cells, the new platforms can be tuned to perform various tasks in a parallel and integrated manner encompassing gene expression, protein synthesis, purification, detection, and finally enabling cell‐cell signaling to bring a collective cell behavior, such as directing differentiation process, characteristics of higher order entities, and beyond. In this review, we issue an update on recent cell‐free protein synthesis (CFPS) formats. Furthermore, the latest advances and applications of CFPS for synthetic biology and biotechnology are highlighted. In the end, contemporary challenges and future opportunities of CFPS systems are discussed.
Real‐time dissolved carbon dioxide monitoring II: Surface aeration intensification for efficient CO2 removal in shake flasks and mini‐bioreactors leads to superior growth and recombinant protein yields
Authors: Chopda Viki R. , Holzberg Timothy , Ge Xudong , Folio Brandon , Wong Lynn , Tolosa Michael , Kostov Yordan , Tolosa Leah , Rao Govind 
Published: December 2019

AbstractMass transfer is known to play a critical role in bioprocess performance and henceforth monitoring dissolved O2 (DO) and dissolved CO2 (dCO2) is of paramount importance. At bioreactor level these parameters can be monitored online and can be controlled by sparging air/oxygen or stirrer speed. However, traditional small‐scale systems such as shake flasks lack real time monitoring and also employ only surface aeration with additional diffusion limitations imposed by the culture plug. Here we present implementation of intensifying surface aeration by sparging air in the headspace of the reaction vessel and real‐time monitoring of DO and dCO2 in the bioprocesses to evaluate the impact of intensified surface aeration. We observed that sparging air in the headspace allowed us to keep dCO2 at low level, which significantly improved not only biomass growth but also protein yield. We expect that implementing such controlled smart shake flasks can minimize the process development gap which currently exists in shake flask level and bioreactor level results.
Size, shape, and flexibility influence nanoparticle transport across brain endothelium under flow
Authors: Nowak Maksymilian , Brown Tyler D. , Graham Adam , Helgeson Matthew E. , Mitragotri Samir 
Published: December 2019

AbstractNanoparticle‐based therapeutic formulations are being increasingly explored for the treatment of various ailments. Despite numerous advances, the success of nanoparticle‐based technologies in treating brain diseases has been limited. Translational hurdles of nanoparticle therapies are attributed primarily to their limited ability to cross the blood–brain barrier (BBB), which is one of the body's most exclusive barriers. Several efforts have been focused on developing affinity‐based agents and using them to increase nanoparticle accumulation at the brain endothelium. Very little is known about the role of fundamental physical parameters of nanoparticles such as size, shape, and flexibility in determining their interactions with and penetration across the BBB. Using a three‐dimensional human BBB microfluidic model (μHuB), we investigate the impact of these physical parameters on nanoparticle penetration across the BBB. To gain insights into the dependence of transport on nanoparticle properties, two separate parameters were measured: the number of nanoparticles that fully cross the BBB and the number that remain associated with the endothelium. Association of nanoparticles with the brain endothelium was substantially impacted by their physical characteristics. Hard particles associate more with the endothelium compared to soft particles, as do small particles compared to large particles, and spherical particles compared to rod‐shaped particles. Transport across the BBB also exhibited a dependence on nanoparticle properties. A nonmonotonic dependence on size was observed, where 200 nm particles exhibited higher BBB transport compared to 100 and 500 nm spheres. Rod‐shaped particles exhibited higher BBB transport when normalized by endothelial association and soft particles exhibited comparable transport to hard particles when normalized by endothelial association. Tuning nanoparticles' physical parameters could potentially enhance their ability to cross the BBB for therapeutic applications.
Insurance impacts survival for children, adolescents, and young adults with bone and soft tissue sarcomas
Authors: Penumarthy Neela L. , Goldsby Robert E. , Shiboski Stephen C. , Wustrack Rosanna , Murphy Patricia , Winestone Lena E. 
Published: December 2019

AbstractBackgroundWhile racial/ethnic survival disparities have been described in pediatric oncology, the impact of income has not been extensively explored. We analyzed how public insurance influences 5‐year overall survival (OS) in young patients with sarcomas.MethodsThe University of California San Francisco Cancer Registry was used to identify patients aged 0‐39 diagnosed with bone or soft tissue sarcomas between 2000 and 2015. Low‐income patients were defined as those with no insurance or Medicaid, a means‐tested form of public insurance. Survival curves were computed using the Kaplan‐Meier method and compared using log‐rank tests and Cox models. Causal mediation was used to assess whether the association between public insurance and mortality is mediated by metastatic disease.ResultsOf 1106 patients, 39% patients were classified as low‐income. Low‐income patients were more likely to be racial/ethnic minorities and to present with metastatic disease (OR 1.96, 95% CI 1.35‐2.86). Low‐income patients had significantly worse OS (61% vs 71%). Age at diagnosis and extent of disease at diagnosis were also independent predictors of OS. When stratified by extent of disease, low‐income patients consistently had significantly worse OS (localized: 78% vs 84%, regional: 64% vs 73%, metastatic: 23% vs 30%, respectively). Mediation analysis indicated that metastatic disease at diagnosis mediated 15% of the effect of public insurance on OS.ConclusionsLow‐income patients with bone and soft tissue sarcomas had decreased OS regardless of disease stage at presentation. The mechanism by which insurance status impacts survival requires additional investigation, but may be through reduced access to care.
Rectal NETs and rectosigmoid junction NETs may need to be treated differently
Authors: Cai Wen , Ge Weiting , Hu Hanguang , Mao Jianshan 
Published: December 2019

AbstractNeuroendocrine tumors (NETs) are heterogeneous, and the incidence of NETs is rapidly increasing. We observed different survival in patients with rectal NETs and rectosigmoid junction NETs, which are treated similarly. We included patients with rectal and rectosigmoid junction NETs from the SEER database. The 5‐year survival was set as the end‐point. 6675 patients with rectal NETs and 329 patients with rectosigmoid junction NETs, were eligible for the analysis. Initially, the survival analyses suggested that the 5‐year survival significantly differed between the patients with rectal and rectosigmoid junction NETs (HR = 0.82, 95% CI 0.70‐0.95; P = .01). Tumor differentiation, an invasion deeper than T2, and lymph node and distant metastases were still important risk factors affecting survival for both location. While, the males showed better survival (HR = 0.69, 95% CI 0.55‐0.88; P < .01) and primary tumor surgery had no benefits (P = .56) for patients with rectosigmoid junction NETs. The factors that predict regional lymph node metastases varied by location. In rectal NETs, invasion deeper than T1 and a tumor larger than 1 cm could significantly increase the risk of regional lymph node metastases (all OR > 5, P < .01). In rectosigmoid junction NETs, the risk of regional lymph node metastases was considered significantly higher with invasion deeper than T1 (all OR > 5, P < .01) and a tumor larger than 2 cm (OR = 31.32, 95% CI 2.53‐387.57; P < .01). We advocate a clear and consistent definition of the rectosigmoid junction for future studies, and more studies are needed to determine the reason underlying differences between rectum and rectosigmoid junction.
Patient expectations of benefit from systemic treatments for metastatic prostate cancer
Authors: Oswald Laura B. , Kasimer Rachel , Rappazzo Katherine , Fought Angela J. , Penson David F. , Morgans Alicia K. 
Published: December 2019

AbstractBackgroundMetastatic prostate cancer is incurable, but systemic therapies can improve quality of life and prolong survival. Accurate perceptions of treatment risks and benefits are vital as patients with metastatic disease make treatment decisions. We assessed treatment‐related expectations for benefit among patients with metastatic prostate cancer and explored associated sociodemographic characteristics.MethodsMen with metastatic prostate cancer (N = 100) completed surveys assessing their treatment‐related expectations for cancer cure, symptom relief, and prolonged life expectancy. Frequencies were used to describe the proportions of reported expectations. Fisher's exact tests were used to assess the associations of sociodemographic characteristics with treatment expectations.ResultsOne third (33%) of participants believed treatment was at least a little likely to cure their metastatic cancer. Most participants believed treatment could provide symptom relief (76%) and extend life expectancy (95%). Among participants reporting that cancer cure was at least a little likely vs not at all, more men identified as non‐white (24% vs 5%; P = .01), self‐reported good health (90% vs 58%; P < .01), and had greater optimism (78% vs 47%; P < .01). Among participants reporting that symptom relief was at least a little likely vs not at all, more men were less than 70 years old (62% vs 0%; P = .01).ConclusionA large proportion of patients with metastatic prostate cancer reported beliefs inconsistent with understanding that treatment was not curative. Race, better self‐reported health, and greater optimism were related to unrealistic expectations. Efforts to ensure alignment of patient and clinician expectations may facilitate more effective shared decision‐making for treating metastatic disease.
Considering methodological integrity in counselling and psychotherapy research
Authors: Levitt Heidi M. , Morrill Zenobia , Collins Kathleen M. 
Published: December 2019

AbstractWithin the field of counselling and psychotherapy research, qualitative methods have been a longstanding tradition of inquiry due to the mutual interest of therapists and researchers in both internal experiences and intersubjective processes. Methodological integrity is a conceptual framework that has been advanced to increase the rigor of these methods. In this paper, we consider the value of this concept for counselling and psychotherapy researchers and reviewers. This framework guides investigators and reviewers to consider how procedures can be adapted to meet the goals of specific studies, given their characteristics and approach to inquiry. In this brief article, we exemplify the relevance and application of this concept to this field by describing the decision‐making process within the designing of a qualitative research project to investigate clients' needs within rape crisis counselling. Through this exemplar, we also provide guidance to counselling and psychotherapy researchers on considerations during the process of research review and reporting.
The perception of makeup for the elderly and the makeup behavior of new seniors
Authors: Baek Kyoung J. 
Published: December 2019

AbstractWith the rapid aging of the world population and the tendency to focus on appearances, the demand for cosmetics for the elderly is likely to keep rising. Therefore, it is necessary to develop cosmetics for the elderly. In this study, we aimed at studying the perception and attitude toward makeup of New Seniors at the pre‐elderly stage, assessing a strategy to approach them and evaluating their needs through the analysis of their effective behaviors related to makeup. We conducted in‐depth interviews and participant observation through video recording. The results showed that New Seniors had a prejudice against makeup in the elderly, their generation did not enjoy using makeup, and they tend to wear makeup to look younger rather than prettier. Also, they need training in how to apply makeup and use products that meet their needs, are easy to use, and produce effects that stand out.
Ambient Electrochemical N2 Reduction to NH3 on Nitrogen and Phosphorus Co‐doped Porous Carbon with Trace Iron in Alkaline Electrolytes
Authors: Song Pengfei , Wang Hao , Cao Xuemei , Liu Na , Wang Qian , Wang Rongmin 
Published: December 2019

AbstractThe electrocatalytic N2 reduction reaction (NRR) provides an environmentally benign approach for NH3 production that can be powered by renewable energy. It remains a challenge to understand the NRR mechanism and develop highly chemically active and selective yet low‐cost electrocatalysts. Herein, we report that N, P co‐doped porous carbon (NPC) with trace Fe (0.028 wt%) (Fe‐NPC) can serve as an electrocatalyst for the NRR in NaOH aqueous solution under ambient conditions. The Fe‐NPC catalyst exhibits significantly enhanced NRR activity compared with NPC, owing to the N, P co‐doped effect and trace Fe species active sites in the carbon material. The highest faradaic efficiency and ammonia yield of Fe‐NPC at −0.1 V vs. RHE reached 5.3 % and 4.36 μg h−1 mg−1cat. Furthermore, the electrochemical reaction mechanism on the Fe‐NPC electrode was investigated by electrochemical in situ Fourier transform infrared spectroscopy, and suggested an associative pathway.