bluuebunny/crossref_metadata_2025_split huggingface dataset:
A single center phase II study of ixazomib in patients with relapsed or refractory cutaneous or peripheral T‐cell lymphomas
Authors: Boonstra Philip S. , Polk Avery , Brown Noah , Hristov Alexandra C. , Bailey Nathanael G. , Kaminski Mark S. , Phillips Tycel , Devata Sumana , Mayer Tera , Wilcox Ryan A. 
Published: August 2017

AbstractThe transcription factor GATA‐3, highly expressed in many cutaneous T‐cell lymphoma (CTCL) and peripheral T‐cell lymphomas (PTCL), confers resistance to chemotherapy in a cell‐autonomous manner. As GATA‐3 is transcriptionally regulated by NF‐κB, we sought to determine the extent to which proteasomal inhibition impairs NF‐κB activation and GATA‐3 expression and cell viability in malignant T cells. Proteasome inhibition, NF‐κB activity, GATA‐3 expression, and cell viability were examined in patient‐derived cell lines and primary T‐cell lymphoma specimens ex vivo treated with the oral proteasome inhibitor ixazomib. Significant reductions in cell viability, NF‐κB activation, and GATA‐3 expression were observed preclinically in ixazomib‐treated cells. Therefore, an investigator‐initiated, single‐center, phase II study with this agent in patients with relapsed/refractory CTCL/PTCL was conducted. Concordant with our preclinical observations, a significant reduction in NF‐κB activation and GATA‐3 expression was observed in an exceptional responder following one month of treatment with ixazomib. While ixazomib had limited activity in this small and heterogeneous cohort of patients, inhibition of the NF‐κB/GATA‐3 axis in a single exceptional responder suggests that ixazomib may have utility in appropriately selected patients or in combination with other agents.
A retrospective analysis of 538 sinonasal fungus ball cases treated at a single tertiary medical center in Korea (1996‐2015)
Authors: Yoon Young Hoon , Xu Jun , Park Soo Kyoung , Heo Jae Hyung , Kim Yong Min , Rha Ki‐Sang 
Published: August 2017

BackgroundSinonasal fungus ball (FB) is a type of noninvasive fungal rhinosinusitis affecting immunocompetent hosts. FB, previously considered rare, has been reported with increasing frequency. We reviewed our experience of 538 cases over the past 20 years.MethodsWe retrospectively examined clinical records including clinical presentations, radiological findings, management, and outcomes of FB patients who have undergone surgery for treatment. The number of FB patients who underwent endoscopic sinus surgery (ESS) was calculated annually. Causal relationships between structural variations and FB were also investigated.ResultsThe number of FB patients who underwent sinus surgery has increased. The mean age was 58.3 years, and the gender ratio was approximately 2 (female): 1 (male). While the most common presenting symptoms of maxillary sinus FB patients were nasal symptoms, such as postnasal drip and nasal obstruction, sphenoid sinus FB patients presented with headache mostly. On computed tomography (CT) scans, the most common finding was intralesional hyperdensity (77.3%). There was no significant correlation between the presence of FB and structural variations (nasal septal deviation, concha bullosa, Haller cell). Median follow‐up period of the patients was 11 months. Recurrence or residual disease occurred in only 6 (1.1%) cases.ConclusionThe number of FB patients who underwent surgery has increased steadily over the past 20 years. FB should be considered in patients with unilateral nasal symptoms and unexplained headaches. A preoperative CT scan is an essential tool in making diagnosis easier and faster. Endoscopic surgery is the treatment of choice, with a low morbidity and recurrence rate.
Dysregulation of LIMK‐1/cofilin‐1 pathway: A possible basis for alteration of neuronal morphology in experimental cerebral malaria
Authors: Simhadri Praveen Kumar , Malwade Ruchi , Vanka Ravisankar , Nakka Venkata Prasuja , Kuppusamy Gowthamarajan , Babu Phanithi Prakash 
Published: August 2017

ObjectiveLoss of cognition even after survival is the salient feature of cerebral malaria (CM). Currently, the fate of neuronal morphology is not studied at the ultrastructural level in CM. Recent studies suggest that maintenance of neuronal morphology and dendritic spine density (actin dynamics in particular) are essential for proper cognitive function. LIMK‐1/cofilin‐1 signaling pathway is known to be involved in the maintenance of actin dynamics through regulation of cofilin‐1, and in executing learning and memory functions.MethodsUsing an experimental mouse model, we analyzed the behavioral parameters of asymptomatic mice with CM by performing a rapid murine coma and behavior scale experiment. We performed Golgi–Cox staining to assess neuronal morphology, dendritic spine density, and arborization in brain cortex subjected to Plasmodium berghei ANKA infection compared to asymptomatic, anemic, and control groups. We studied the neural gene expression pattern of LIMK‐1, cofilin‐1, and β‐actin in all the experimental groups by semiquantitative and quantitative polymerase chain reaction followed by immunoblotting and immunofluorescence.ResultsWe observed significant loss of dendritic spine density, abnormal spine morphology, reduced dendritic arborization, and extensive dendritic varicosities in the cortical neurons of CM‐infected brain. Furthermore, these observations correlated with diminished protein levels of LIMK‐1, cofilin‐1, phospho‐cofilin‐1, and β‐actin in the whole brain lysates as well as formation of actin–cofilin rods in the brain sections of symptomatic mice with CM.InterpretationOverall, our findings suggest that the altered neuronal morphology and dysregulation of LIMK‐1/cofilin‐1 pathway could affect the cognitive outcome after experimental CM. Therefore, this study could help to establish newer therapeutic strategies addressing long‐term cognitive impairment after CM. Ann Neurol 2017;82:429–443
One‐Step Reforming of CO2 and CH4 into High‐Value Liquid Chemicals and Fuels at Room Temperature by Plasma‐Driven Catalysis
Authors: Wang Li , Yi Yanhui , Wu Chunfei , Guo Hongchen , Tu Xin 
Published: August 2017

AbstractThe conversion of CO2 with CH4 into liquid fuels and chemicals in a single‐step catalytic process that bypasses the production of syngas remains a challenge. In this study, liquid fuels and chemicals (e.g., acetic acid, methanol, ethanol, and formaldehyde) were synthesized in a one‐step process from CO2 and CH4 at room temperature (30 °C) and atmospheric pressure for the first time by using a novel plasma reactor with a water electrode. The total selectivity to oxygenates was approximately 50–60 %, with acetic acid being the major component at 40.2 % selectivity, the highest value reported for acetic acid thus far. Interestingly, the direct plasma synthesis of acetic acid from CH4 and CO2 is an ideal reaction with 100 % atom economy, but it is almost impossible by thermal catalysis owing to the significant thermodynamic barrier. The combination of plasma and catalyst in this process shows great potential for manipulating the distribution of liquid chemical products in a given process.
Thiourea modified hyper‐crosslinked polystyrene resin for heavy metal ions removal from aqueous solutions
Authors: Yang Zujin , Huang Xiaonan , Yao Xingdong , Ji Hongbing 
Published: August 2017

ABSTRACTA hyper‐crosslinked resin chemically modified with thiourea (TM‐HPS) was synthesized, characterized, and evaluated for the removal of heavy metal ions (Pb2+, Cd2+, and Cu2+) from aqueous solutions. The structural characterization results showed that a few thiourea groups were grafted on the surface of the resin with a big BET surface area and a large number of narrow micropores. Various experimental conditions such as pH, contact time, temperature, and initial metal concentration of the three heavy metal ions onto TM‐HPS were investigated systematically. The results indicated that the prepared resin was effective for the removal of the heavy metal ions from aqueous solutions. The isotherm data could be better fitted by Langmuir model, yielding maximum adsorption capacities of 689.65, 432.90, and 290.69 mg/g for Pd2+, Cd2+, and Cu2+, respectively. And the adsorption kinetics of the three metal ions followed the pseudo‐second‐order equation. FTIR and XPS analysis of TM‐HPS before and after adsorption further revealed that the adsorption mechanism could be a synergistic effect between functional groups and metal ions and electrostatic attraction, which may provide a new insight into the design of highly effective adsorbents and their potential technological applications for the removal of heavy metal ions from aqueous solutions. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 45568.
Preparation of amidoxime‐modified polyacrylonitrile nanofibrous adsorbents for the extraction of copper(II) and lead(II) ions and dye from aqueous media
Authors: Ren Jing , Yan Chunqiu , Liu Qingwen , Yang Qingbiao , Lu Guanxiu , Song Yan , Li Yaoxian 
Published: August 2017

ABSTRACTAmidoxime‐modified polyacrylonitrile nanofibrous films (AOPAN NFs) were prepared via an electrospinning technique. The traditional preparation methods for amidoximated polyacrylonitrile (AOPAN) solution were changed and improved. First, the PAN solution was modified by hydroxylamine hydrochloride to produce an AOPAN solution, and then, a small amount of inhibitor was added to the AOPAN solution for electrospinning. We found that the crosslinking of the AOPAN solution was inhibited by the addition of a small amount of inhibitor; at the same time, the storage time of the AOPAN solution was prolonged. In addition, the prepared AOPAN solution was electrospun into nanofibrous films, which could be used as excellent adsorption materials for Cu(II), Pb(II), and methyl orange (MO) after drying. The maximal adsorption capacities for Cu(II), Pb(II), and MO were 143.47, 178.57, and 68.07 mg/g, respectively. The adsorption capacities of the nanofibrous films were more than 50% that of the first adsorption after four recycling runs; this indicated the reusability of the nanofibrous films for water treatment. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 45697.
Escherichia coli “TatExpress” strains super‐secrete human growth hormone into the bacterial periplasm by the Tat pathway
Authors: Browning Douglas F. , Richards Kirsty L. , Peswani Amber R. , Roobol Jo , Busby Stephen J.W. , Robinson Colin 
Published: August 2017

AbstractNumerous high‐value proteins are secreted into the Escherichia coli periplasm by the General Secretory (Sec) pathway, but Sec‐based production chassis cannot handle many potential target proteins. The Tat pathway offers a promising alternative because it transports fully folded proteins; however, yields have been too low for commercial use. To facilitate Tat export, we have engineered the TatExpress series of super‐secreting strains by introducing the strong inducible bacterial promoter, ptac, upstream of the chromosomal tatABCD operon, to drive its expression in E. coli strains commonly used by industry (e.g., W3110 and BL21). This modification significantly improves the Tat‐dependent secretion of human growth hormone (hGH) into the bacterial periplasm, to the extent that secreted hGH is the dominant periplasmic protein after only 1 hr induction. TatExpress strains accumulate in excess of 30 mg L−1 periplasmic recombinant hGH, even in shake flask cultures. A second target protein, an scFv, is also shown to be exported at much higher rates in TatExpress strains.
Recombinant RNA Polymerase from Geobacillus sp. GHH01 as tool for rapid generation of metagenomic RNAs using in vitro technologies
Authors: Kinfu Birhanu M. , Jahnke Maike , Janus Mareike , Besirlioglu Volkan , Roggenbuck Michael , Meurer Richard , Vojcic Ljubica , Borchert Martin , Schwaneberg Ulrich , Chow Jennifer , Streit Wolfgang R. 
Published: August 2017

AbstractThe exciting promises of functional metagenomics for the efficient discovery of novel biomolecules from nature are often hindered by factors associated with expression hosts. Aiming to shift functional metagenomics to a host independent innovative system, we here report on the cloning, heterologous expression, and reconstitution of an RNA polymerase (RNAP) from the thermophilic Geobacillus sp. GHH01 and in vitro transcription thereafter. The five genes coding for RNAP subunits, a house keeping sigma factor and two transcription elongation factors were cloned and over expressed as His6‐tagged and/ or tag‐free proteins. Purified subunits were reconstituted into a functional polymerase through either the classical method of denaturation and subsequent renaturation or through a new resource and time efficient thermo‐reconstitution method which takes advantage of the subunits’ temperature stability. Additionally, all subunits were cloned into a single vector system for a co‐expression and in vivo reconstitution to the RNAP core enzyme. Both the core and holoenzyme form of the RNAP exhibited a robust transcription activity and were stable up to a temperature of 55°C close to their fullest activity. The Geobacillus RNAP showed a remarkable in vitro transcription profile recognizing DNA template sequences of diverse bacteria and archaea as well as metagenomic samples. Coupled with a subsequent in vitro translation step, this recombinant transcription system could allow a new, clone‐free, and functional metagenomic screening approach.
Cascading effect in bioprocessing—The impact of mild hypothermia on CHO cell behavior and host cell protein composition
Authors: Goey Cher H. , Tsang Joshua M.H. , Bell David , Kontoravdi Cleo 
Published: August 2017

AbstractA major challenge in downstream purification of monoclonal antibodies (mAb) is the removal of host cell proteins (HCPs). Previous studies have shown that cell culture conditions significantly impact the HCP content at harvest. However, it is currently unclear how process conditions affect physiological changes in the host cell population, and how these changes, in turn, cascade down to change the HCP profile. We examined how temperature downshift (TDS) to mild hypothermia affects key upstream performance indicators, that is antibody titre, HCP concentration and HCP species, across the cell culture decline phase and at harvest through the lens of changes in cellular behavior. Mild hypothermic conditions introduced on day 5 of fed‐batch Chinese hamster ovary (CHO) cell bioreactors resulted in a lower cell proliferation rate but larger percentages of healthier cells across the cell culture decline phase compared to bioreactors maintained at standard physiological temperature. Moreover, the onset of apoptosis was less evident in mild hypothermic cultures. Consequently, mild hypothermic cultures took an extra 5 days to reach an integral viable cell concentration (IVCC) and antibody yield similar to that of the control at standard physiological temperature. When cell viability dropped below 80%, mild hypothermic cell cultures had a reduced variety of HCP species by 36%, including approximately 44% and 27% lower proteases and chaperones, respectively, despite having similar HCP concentration. This study suggests that TDS may be a good strategy to provide cleaner downstream feedstocks by reducing the variety of HCPs and to maintain product integrity by reducing the number of proteases and chaperones.
Cell‐free production of a therapeutic protein: Expression, purification, and characterization of recombinant streptokinase using a CHO lysate
Authors: Tran Kevin , Gurramkonda Chandrasekhar , Cooper Merideth A. , Pilli Manohar , Taris Joseph E. , Selock Nicholas , Han Tzu‐Chiang , Tolosa Michael , Zuber Adil , Peñalber‐Johnstone Chariz , Dinkins Christina , Pezeshk Niloufar , Kostov Yordan , Frey Douglas D. , Tolosa Leah , Wood David W. , Rao Govind 
Published: August 2017

AbstractThe use of cell‐free systems to produce recombinant proteins has grown rapidly over the past decade. In particular, cell‐free protein synthesis (CFPS) systems based on mammalian cells provide alternative methods for the production of many proteins, including those that contain disulfide bonds, glycosylation, and complex structures such as monoclonal antibodies. In the present study, we show robust production of turbo green fluorescent protein (tGFP) and streptokinase in a cell‐free system using instrumented mini‐bioreactors for highly reproducible protein production. We achieved recombinant protein production (∼600 μg/ml of tGFP and 500 μg/ml streptokinase) in 2.5 hr of expression time, comparable to previously reported yields for cell‐free protein expression. Also, we demonstrate the use of two different affinity tags for product capture and compare those to a tag‐free self‐cleaving intein capture technology. The intein purification method provided a product recovery of 86%, compared with 52% for conventionally tagged proteins, while resulting in a 30% increase in total units of activity of purified recombinant streptokinase compared with conventionally tagged proteins. These promising beneficial features combined with the intein technology makes feasible the development of dose‐level production of therapeutic proteins at the point‐of‐care.
Deletion of Fmr1 results in sex‐specific changes in behavior
Authors: Nolan Suzanne O. , Reynolds Conner D. , Smith Gregory D. , Holley Andrew J. , Escobar Brianna , Chandler Matthew A. , Volquardsen Megan , Jefferson Taylor , Pandian Ashvini , Smith Tileena , Huebschman Jessica , Lugo Joaquin N. 
Published: August 2017

AbstractObjectiveIn this study, we used a systemic Fmr1 knockout in order to investigate both genotype‐ and sex‐specific differences across multiple measures of sociability, repetitive behaviors, activity levels, anxiety, and fear‐related learning and memory.BackgroundFragile X syndrome is the most common monogenic cause of intellectual disability and autism. Few studies to date have examined sex differences in a mouse model of Fragile X syndrome, though clinical data support the idea of differences in both overall prevalence and phenotype between the sexes.MethodsUsing wild‐type and systemic homozygous Fmr1 knockout mice, we assessed a variety of behavioral paradigms in adult animals, including the open field test, elevated plus maze, nose‐poke assay, accelerating rotarod, social partition task, three‐chambered social task, and two different fear conditioning paradigms. Tests were ordered such that the most invasive tests were performed last in the sequence, and testing paradigms for similar behaviors were performed in separate cohorts to minimize testing effects.ResultsOur results indicate several sex‐specific changes in Fmr1 knockout mice, including male‐specific increases in activity levels, and female‐specific increases in repetitive behaviors on both the nose‐poke assay and motor coordination on the accelerating rotarod task. The results also indicated that Fmr1 deletion results in deficits in fear learning and memory across both sexes, and no changes in social behavior across two tasks.ConclusionThese findings highlight the importance of including female subjects in preclinical studies, as simply studying the impact of genetic mutations in males does not yield a complete picture of the phenotype. Further research should explore these marked phenotypic differences among the sexes. Moreover, given that treatment strategies are typically equivalent between the sexes, the results highlight a potential need for sex‐specific therapeutics.
Concomitant coronary artery disease and its management in patients referred to transcatheter aortic valve implantation: Insights from the POL‐TAVI Registry
Authors: Huczek Zenon , Zbroński Karol , Grodecki Kajetan , Scisło Piotr , Rymuza Bartosz , Kochman Janusz , Dąbrowski Maciej , Witkowski Adam , Wojakowski Wojciech , Parma Radosław , Ochała Andrzej , Grygier Marek , Olasińska‐Wiśniewska Anna , Araszkiewicz Aleksander , Jagielak Dariusz , Ciećwierz Dariusz , Puchta Dominika , Paczwa Katarzyna , Filipiak Krzysztof J. , Wilimski Radosław , Zembala Marian , Opolski Grzegorz 
Published: August 2017

AbstractBackgroundCoronary artery disease (CAD) and degenerative aortic stenosis often coexist. However, the impact of CAD and its management on the prognosis after transcatheter aortic valve implantation (TAVI) remains uncertain. We sought to evaluate the impact of obstructive CAD, SYNTAX score (Ss), and percutaneous coronary intervention (PCI) prior to TAVI on short‐term outcome.MethodsOverall, 896 patients who underwent TAVI after heart team decision was included. Pre‐procedural angiograms were analysed to calculate baseline Ss (bSs) and residual Ss (rSs). Baseline, procedural and follow‐up data up to 30 days was acquired from the national POL‐TAVI registry.ResultsPatients with obstructive CAD at baseline (n = 462, 52%) had higher mortality as compared with the remaining (8.7 vs. 5.1%, log‐rank P = 0.039). Also, after correction for confounding factors obstructive CAD was identified as independent predictor of mortality (hazard ratio [HR] 1.74, 95% confidence intervals [CIs] 1.03–2.94, P = 0.037). In obstructive CAD, neither bSs (AUC 0.47, CI 0.38–0.56, P = 0.47) nor rSs (AUC 0.47, CI 0.30–0.64, P = 0.72 for those undergoing PCI and AUC 0.48, CI 0.37–0.59, P = 0.75 for the remaining) was predictive of mortality. When revascularization status was considered, patients with PCI prior to TAVI had similar outcome as those without obstructive CAD at baseline (7.7 vs. 5.1%, log‐rank P = 0.23) with no negative impact on mortality (HR 1.13, CI 0.62–2.09, P = 0.69).ConclusionsIn conclusion, obstructive CAD at baseline evaluation for TAVI has independent negative impact on short‐term prognosis. However, neither baseline nor residual Ss values have prognostic ability in patients undergoing TAVI. Revascularization prior to TAVI seems to improve survival to levels comparable with patients without obstructive CAD at baseline.
Hemodynamic analysis of a novel bioresorbable scaffold in porcine coronary artery model
Authors: Tenekecioglu Erhan , Torii Ryo , Bourantas Christos V. , Cavalcante Rafael , Sotomi Yohei , Zeng Yaping , Collet Carlos , Crake Tom , Abizaid Alexandre , Onuma Yoshinobu , Su Solomon , Santoso Teguh , Serruys Patrick W. 
Published: August 2017

AbstractBackgroundThe shear stress distribution assessment can provide useful insights for the hemodynamic performance of the implanted stent/scaffold. Our aim was to investigate the effect of a novel bioresorbable scaffold, Mirage on local hemodynamics in animal models.MethodThe main epicardial coronary arteries of 7 healthy mini‐pigs were implanted with 11 Mirage Microfiber sirolimus‐eluting Bioresorbable Scaffolds (MMSES). Optical coherence tomography (OCT) was performed post scaffold implantation and the obtained images were fused with angiographic data to reconstruct the coronary artery anatomy. Blood flow simulation was performed and Endothelial Shear Stress(ESS) distribution was estimated for each of the 11 scaffolds. ESS data were extracted in each circumferential 5‐degree subunit of each cross‐section in the scaffolded segment. The generalized linear mixed‐effect analysis was implemented for the comparison of ESS in two scaffold groups; 150‐µm strut thickness MMSES and 125‐µm strut thickness MMSES.ResultsESS was significantly higher in MMSES (150 µm) [0.85(0.49–1.40) Pa], compared to MMSES (125 µm) [0.68(0.35–1.18) Pa]. Both MMSES (150 µm) and MMSES (125 µm) revealed low recirculation zone percentages per luminal surface area [3.17% ± 1.97% in MMSES (150 µm), 2.71% ± 1.32% in MMSES (125 µm)].ConclusionThinner strut Mirage scaffolds induced lower shear stress due to the small size vessels treated as compared to the thick strut version of the Mirage which was implanted in relatively bigger size vessels. Vessel size should be taken into account in planning BRS implantation. Small vessels may not get benefit from BRS implantation even with a streamlined strut profile. This pilot study warrants comparative assessment with commercially available bioresorbable scaffolds.