bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment patterns, adverse events, and economic burden in a privately insured population of patients with chronic lymphocytic leukemia in the United States
Authors: Kabadi Shaum M. , Goyal Ravi K. , Nagar Saurabh P. , Kaye James A. , Davis Keith L. 
Published: May 2019

AbstractIntroductionContemporary data describing treatment patterns, adverse events (AEs), and outcomes in patients with chronic lymphocytic leukemia (CLL) in clinical practice are lacking. We conducted a retrospective cohort study and assessed treatment patterns, AEs, health‐care resource use (HCRU), and costs in patients with diagnosis of CLL.MethodsUsing a nationally representative population of privately insured patients in the US, adult patients with CLL diagnosis (July 2012‐June 2015) were selected if they had continuous health plan enrollment for ≥12 months before the first CLL diagnosis without any evidence of any CLL‐directed treatment. Treatment patterns up to four lines of therapy (LOT) and occurrence of AEs during CLL therapies were assessed. Mean per‐patient monthly HCRU and costs were assessed overall and by number of unique AEs.ResultsOf all patients meeting the selection criteria (n = 7,639; median age, 66 years), 18% (n = 1,379) received a systemic therapy during study follow‐up. Of these, bendamustine/rituximab (BR) was the most common first observed regimen (28.1%), while ibrutinib was the most common therapy in the second (20.8%) and third (25.5%) observed regimens. The mean monthly all‐cause and CLL‐related costs, among patients treated with a systemic therapy, were $7,943 (SD = $15,757) and $5,185 (SD = $9,935), respectively. Mean monthly all‐cause costs increased by the number of AEs (from $905 [SD = $1,865] among those with no AEs to $6,032 [SD = $13,290] among those with ≥6 AEs).ConclusionsChemoimmunotherapy, particularly BR, was the most common first observed therapy for CLL, whereas ibrutinib was most preferred in the second and third observed lines of therapy during the study period. Findings demonstrate that the economic burden of AEs in CLL is substantial.
Oxoborane Formation Turns on Formazanate‐Based Photoluminescence
Authors: Maar Ryan R. , Hoffman Nicholas A. , Staroverov Viktor N. , Gilroy Joe B. 
Published: May 2019

AbstractThe synthesis of compounds containing multiple bonds to boron has challenged main‐group chemists for decades. Despite significant progress, the possibility that the formation of such bonds can turn on photoluminescence has received minimal attention. We report an oxoborane (B=O) complex that is electronically stabilized by a formazanate ligand in the absence of significant steric bulk and, unlike the common BX2 (X=F, Cl) formazanate adducts, exhibits intense photoluminescence. The latter property was rationalized through density‐functional calculations which indicated that the B=O bond enhances photoluminescence by drastically reducing differences between the ligand's geometries in the ground and excited states. The title oxoborane compound was synthesized from an air‐ and moisture‐stable BCl2 formazanate complex and subsequently converted to a redox‐active boroxine. Each of these species may also serve as a precursor to functional materials.
Effects of Sublethal Doses of Herbicides on the Competitive Interactions Between 2 Nontarget Plants, Centaurea cyanus L. and Silene noctiflora L.
Authors: Boutin Céline , Montroy Kaitlyn , Mathiassen Solvejg K. , Carpenter David J. , Strandberg Beate , Damgaard Christian 
Published: May 2019

Abstract
Plant competitive interactions influence the effect of herbicides, and the effect of competitive interactions on plant responses may be important to include in the ecological risk assessment of herbicides. In the present study the effect of competitive interactions and sublethal doses of 2 herbicides on plant species was investigated in competition experiments and fitted to empirical competition models. Two nontarget species commonly found in agroecosystems (Centaurea cyanus L. and Silene noctiflora L.) and 2 herbicides (glyphosate and metsulfuron methyl) were used in separate experiments. Plants were sprayed at the 6- to 8-leaf stage. Effects of herbicide treatments and plant density were modeled by generalization of a discrete hyperbolic competition model. The 10% effective dose (ED10) was calculated for C. cyanus. All experiments showed that as density increased, plants were negatively affected. Furthermore, in all cases, C. cyanus remained a better competitor than S. noctiflora. Nevertheless, the density of S. noctiflora (competitor) was an influential element in determining the ED10 of C. cyanus measured at the mature stage. With herbicide exposure, the competitive interactions were further altered; C. cyanus was less affected by glyphosate when S. noctiflora increased to high density. In contrast, at the young stage, conspecific density was important in determining the sensitivity of C. cyanus to metsulfuron methyl, whereas the density of the competitor S. noctiflora had a limited influence. Overall, the results demonstrate the importance of integrating the effect of herbicide and species interactions measured at the reproductive stage into the ecological risk assessments of pesticides. Environ Toxicol Chem 2019;38:2053–2064. © 2019 SETAC.
Overcoming Challenges of Incorporating Higher Tier Data in Ecological Risk Assessments and Risk Management of Pesticides in the United States: Findings and Recommendations from the 2017 Workshop on Regulation and Innovation in Agriculture
Authors: Levine Steven L , Giddings Jeffrey , Valenti Theodore , Cobb George P , Carley Danesha Seth , McConnell Laura L 
Published: May 2019

Abstract
Pesticide regulation requires regulatory authorities to assess the potential ecological risk of pesticides submitted for registration, and most risk assessment schemes use a tiered testing and assessment approach. Standardized ecotoxicity tests, environmental fate studies, and exposure models are used at lower tiers and follow well-defined methods for assessing risk. If a lower tier assessment indicates that the pesticide may pose an ecological risk, higher tier studies using more environmentally realistic conditions or assumptions can be performed to refine the risk assessment and inform risk management options. However, there is limited guidance in the United States on options to refine an assessment and how the data will be incorporated into the risk assessment and risk management processes. To overcome challenges to incorporation of higher tier data into ecological risk assessments and risk management of pesticides, a workshop was held in Raleigh, North Carolina. Attendees included representatives from the United States Environmental Protection Agency, United States Department of Agriculture, National Oceanic and Atmospheric Administration, universities, commodity groups, consultants, nonprofit organizations, and the crop protection industry. Key recommendations emphasized the need for 1) more effective, timely, open communication among registrants, risk assessors, and risk managers earlier in the registration process to identify specific protection goals, address areas of potential concern where higher tier studies or assessments may be required, and if a higher tier study is necessary that there is agreement on study design; 2) minimizing the complexity of study designs while retaining high value to the risk assessment and risk management process; 3) greater transparency regarding critical factors utilized in risk management decisions with clearly defined protection goals that are operational; and 4) retrospective analyses of success–failure learnings on the acceptability of higher tier studies to help inform registrants on how to improve the application of such studies to risk assessments and the risk management process. Integr Environ Assess Manag 2019;15:714–725. © 2019 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals, Inc. on behalf of Society of Environmental Toxicology & Chemistry (SETAC).
Retracted: PRC1 gene silencing inhibits proliferation, invasion, and angiogenesis of retinoblastoma cells through the inhibition of the Wnt/β‐catenin signaling pathway
Authors: Liao Yu‐Jun , Yin Xiao‐Long , Deng Yan , Peng Xiao‐Wei 
Published: May 2019

AbstractRetinoblastoma is an ocular malignancy occurring in childhood. The current study evaluates the ability of silenced PRC1 on retinoblastoma cell proliferation, and angiogenesis via the Wnt/β‐catenin signaling pathway. A total of 36 cases of retinoblastoma tissues (n = 36) and normal retinal tissues (n = 10) were selected in the current study. Retinoblastoma cells presenting with the high PRC1 messenger RNA (mRNA) expression were selected among the WERI‐Rb‐1, HXO‐RB44, Y79, SO‐Rb50, and SO‐Rb70 cells lines, and were transfected with siRNA‐PRC1 and LiCl (the activator of the Wnt/β‐catenin pathway). The expressions of PRC1, VEGF, Wnt1, β‐catenin, CyclinD1, extent of β‐catenin, and GSK‐3β phosphorylation were evaluated. Cell proliferation, cell‐cycle distribution, and cell invasion of retinoblastoma cells were evaluated by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay, flow cytometry, and Transwell assay. The angiogenesis of retinoblastoma cells was detected by tube formation assay. HXO‐RB44 and WERI‐Rb‐1 cells were selected owing to the highest PRC1 mRNA expression. Meanwhile, PRC2 gene silencing presented lower expression levels of PRC1, VEGF, Wnt1, β‐catenin, CyclinD1, extent of β‐catenin and GSK‐3β phosphorylation, decreased proliferation and invasion abilities, extended G0/G1 phase, and shortened S and G2/M phases of HXO‐RB44 and WERI‐Rb‐1 cells, suggesting the silenced PRC2 inactivated Wnt/β‐catenin pathway, so as to further restrain the retinoblastoma cell proliferation, invasion, and angiogenesis. These results support the view that PRC1 gene silencing could suppress the proliferation, and angiogenesis of retinoblastoma cells by repressing the Wnt/β‐catenin pathway.
Recombinant human growth hormone treatment of mice suppresses inflammation and apoptosis caused by skin flap ischemia–reperfusion injury
Authors: Liu Ben , Xu Qingjia , Wang Juntao , Lin Junhao , Pei Yantao , Cui Yidong , Wang Gang , Zhu Lei 
Published: May 2019

AbstractBackgroundThis study was to investigate the effects of recombinant human growth hormone (rhGh) on ischemia‐reperfusion (I/R) injury of mouse flaps.MethodsHealthy mice were randomly divided into four groups as follows: sham group, the IR group, the sham+rhGH group and the IR+rhGH group, with 12 mice in each group. Skin pathology was tested by hematoxylin and eosin staining. The flap survival of each group was measured after 7 days. The levels of superoxide dismutase (SOD) and malondialdehyde (MDA) were determined using corresponding kit. The levels of interleukin (IL)‐6 and tumor necrosis factor (TNF)‐α in serum and flap were respectively measured by performing enzyme‐linked immunosorbent assay and quantitative real‐time (qRT)‐PCR. The expressions of cleaved caspase‐3, B cell lymphoma/leukemia‐2 (Bcl‐2), Bcl‐2‐associated X protein (Bax), vascular endothelial growth factor (VEGF), MnSOD, toll‐like receptor 4 (TLR4), and galectin‐3 and (p)‐p65 were analyzed by RT‐PCR or/and Western blot.ResultsProphylactic systemic application of recombinant human GH reduced the pathological damage of skin IR and significantly improved the flap survival of IR in mice, accompanied by elevation of VEGF. After administration of recombinant human GH, the activity of SOD/MnSOD in the flap was significantly increased, while the content of MDA was decreased. Cleaved caspase‐3 and Bax were downregulated and Bcl‐2 was upregulated in IR+rhGH group, compared to IR group. The levels of TLR4, Galectin‐3 and p‐p65 were decreased by rhGH.ConclusionrhGH had protective effects on flap IR injury, and can be used as a drug intervention target for the treatment of skin flap IR injury.
Biosynthesis of Fe3O4‐magnetic nanoparticles using clover leaf aqueous extract: Green synthesis of 1,3‐benzoxazole derivatives
Authors: Shafaei Faezeh , Babaei Seyyed Ebrahim , Shahvelayati Ashraf Sadat , Honarmand Janatabadi Fatemeh 
Published: May 2019

AbstractIn this research, magnetic Fe3O4‐NP nanoparticles were synthesized employing a green biosynthetic procedure by reduction of ferric chloride solution with clover leaf water extract. The nanoparticles prepared via this biosynthesis method can potentially be valuable for different purposes such as organic synthesis. In this research, 1,3‐benzoxazole derivatives were generated via a multicomponent reaction of α‐bromo ketones, isothiocyanate, and propiolate in the presence of a catalytic amount of bio‐Fe3O4 MNPs and sodium hydride in water at 50°C in good yields. The catalyst was reused five times with a minor decrease in its catalytic activity.
Microbial‐induced synthesis of mineralization products based on the capture of carbon dioxide: Characteristics, reaction kinetics, interfacial adhesion properties, and mechanism of action
Authors: Yi Haihe , Zhan Qiwei , Qian Chunxiang 
Published: May 2019

AbstractAs a new type of green environment‐friendly cementitious material, microbial‐induced mineralization products have garnered more and more attention. In this paper, the synthesis of mineralization products under microbial inducement was conducted. The composition and microstructure of mineralization products were studied using energy‐dispersive spectrometer (EDS), X‐ray diffraction (XRD), scanning electron microscopy (SEM), and transmission electron microscope (TEM). The results showed that mineralization products were calcite, while the shape was similar to globular type, and particle size was about 5 μm. The effect of microbial culture solution, secretion solution, and concentration on the conductivity of the solution was compared and analyzed. During the formation of mineralization products, bacterial bodies not only played the role of nucleation sites but also accelerated the deposition of mineralization products. Thus, it could be seen that the bacterial bodies had a certain influence on the reaction kinetics. The adhesion force of mineralization products was evaluated by the interfacial adhesion properties between the mineralization products and glass slides. The results of the sonication test and scratch test indicated that the interfacial adhesion strength between mineralization products and glass slides was closely related to the mass of mineralization products deposited. The larger the mass of mineralization products deposited, the greater the interfacial adhesion strength. Based on the above research and analysis, the reaction process and mechanism model of microbial‐induced mineralization were defined.
Orthogonal factor‐pair Latin squares of prime‐power order
Authors: Hammer James , Lorch John 
Published: May 2019

AbstractWe introduce a linear method for constructing factor‐pair Latin squares of prime‐power order and we identify criteria for determining whether two factor‐pair Latin squares constructed using this linear method are orthogonal. Then we show that families of pairwise mutually orthogonal diagonal factor‐pair Latin squares exist in all prime‐power orders.
Toll‐like receptors: A pathway alluding to cancer control
Authors: Ayala‐Cuellar Ana Patricia , Cho Jaejin , Choi Kyung‐Chul 
Published: May 2019

AbstractToll‐like receptors (TLRs) are usually expressed on immune cells such as macrophages, dendritic cells, mast cells, as well as on eosinophils and some epithelial cells. They play a central role in the recognition of harmful molecules that belong to invading microorganisms or internal damaged tissues, which lead to inflammation. Among the hallmarks of cancer, there is immune evasion and inflammation. Summing this with the discovery that a majority of cancers also seem to express TLRs, made researchers realize these receptors might also be linked with cancer progression. This review will cover some of the effects of TLR engagement in cancer cells that might induce the promotion or inhibition of cancer with mechanisms involved. The differences of TLR expression in cancer progression and its possible relation with patient prognosis, TLR genetic disorders found in cancer, and new strategies to cancer therapy will be discussed to target TLRs in cancer cells.
TNF‐α‐induced exosomal miR‐146a mediates mesenchymal stem cell‐dependent suppression of urethral stricture
Authors: Liang Ying‐Chun , Wu Yu‐Peng , Li Xiao‐Dong , Chen Shao‐Hao , Ye Xiao‐Jian , Xue Xue‐Yi , Xu Ning 
Published: May 2019

AbstractThe effective treatment of urethral stricture remains a medical problem. The use of proinflammatory cytokines as stimuli to improve the reparative efficacy of mesenchymal stem cells (MSCs) towards damaged tissues represents an evolving field of investigation. However, the therapeutic benefits of this strategy in the treatment of urethral stricture remain unknown. Here, we enriched exosomes derived from human umbilical cord‐derived MSCs pretreated with or without tumor necrosis factor alpha (TNF‐α) to evaluate their therapeutic effects in an in vivo model of TGFβ1‐induced urethral stricture. Male Sprague‐Dawley rats received sham (saline) or TGFβ1 injections to urethral tissues followed by incisions in the urethra. Animals in the TGFβ1 injection (urethral fibrosis) cohort were subsequently injected with vehicle control, or with exosomes derived from MSCs cultured with or without TNF‐α. After 4 weeks, rats underwent ultrasound evaluation and, following euthanasia, urethral tissues were harvested for histological and molecular analysis. In vitro, the effects of MSC‐derived exosomes on fibroblast secretion of collagen and cytokines were studied by enzyme‐linked immunosorbent assay (ELISA), quantitative real‐time polymerase chain reaction (qRT‐PCR), and western blot analysis. Exosomes derived from MSCs pretreated with TNF‐α were more effective in suppressing urethral fibrosis and stricture than exosomes from untreated MSCs. We found that miR‐146a, an anti‐inflammatory miRNA, was strongly upregulated in TNF‐α‐stimulated MSCs and was selectively packaged into exosomes. Moreover, miR‐146a‐containing exosomes were taken up by fibroblasts and inhibited fibroblast activation and associated inflammatory responses, a finding that may underlie the therapeutic mechanism for suppression of urethral stricture. Inhibition of miR‐146a in TNF‐α‐treated MSCs partially reduced antifibrotic effects and increased the release of proinflammatory factors of exosomes derived from these cells. Together these findings demonstrate that exosomes derived from TNF‐α‐treated MSCs are of therapeutic benefit in urethral fibrosis, suggesting that this strategy may have utility as an adjuvant therapy in the treatment of urethral stricture diseases.
An Evaluation of the Progressive Supranuclear Palsy Speech/Language Variant
Authors: Whitwell Jennifer L. , Stevens Chase A. , Duffy Joseph R. , Clark Heather M. , Machulda Mary M. , Strand Edythe A. , Martin Peter R. , Utianski Rene L. , Botha Hugo , Spychalla Anthony J. , Senjem Matthew L. , Schwarz Christopher G. , Jack Clifford R. , Ali Farwa , Hassan Anhar , Josephs Keith A. 
Published: May 2019

ABSTRACTBackgroundThe Movement Disorder Society clinical criteria for progressive supranuclear palsy (PSP) provide a framework for assessing the presence/severity of clinical symptoms and define a speech/language variant of PSP.ObjectivesTo evaluate the clinical criteria in a cohort of speech/language patients with longitudinal follow‐up.MethodsA total of 52 patients presenting with progressive apraxia of speech and/or agrammatic aphasia were followed longitudinally for up to 6 visits with clinical assessments and magnetic resonance imaging. We assessed oculomotor, postural instability, and akinesia diagnostic levels and determined whether patients met criteria for possible PSP‐speech/language or probable PSP at each visit. Kaplan‐Meier curves assessed time‐to‐event probabilities according to age. Statistical parametric mapping and midbrain volume were assessed according to disease progression.ResultsFew PSP symptoms were observed early in the disease, with oculomotor abnormalities and falls first observed 2 years after onset. Falls were more common than vertical supranuclear gaze palsy. Bradykinesia and rigidity commonly developed but axial was rarely greater than appendicular rigidity. During follow‐up, 54% met criteria for possible PSP‐speech/language, 38% for probable PSP‐Richardson's syndrome, and 38% for probable PSP‐parkinsonism, most commonly 6 to 6.9 years after onset. The probability of developing PSP was greater when onset was at an age older than 70 years. Patients who progressed to probable PSP had more parkinsonism and oculomotor impairment at baseline and greater midbrain atrophy when compared with those who did not develop probable PSP.ConclusionsSymptoms typical of PSP commonly develop in patients presenting with a progressive speech/language disorder. Older age appears to be an important prognostic factor in these patients.
Influence of common SCN1A promoter variants on the severity of SCN1A‐related phenotypes
Authors: de Lange Iris M. , Weuring Wout , van ‘t Slot Ruben , Gunning Boudewijn , Sonsma Anja C. M. , McCormack Mark , de Kovel Carolien , van Gemert Lisette J. J. M. , Mulder Flip , van Kempen Marjan J. A. , Knoers Nine V. A. M. , Brilstra Eva H. , Koeleman Bobby P. C. 
Published: May 2019

AbstractBackgroundPathogenic variants in SCN1A cause variable epilepsy disorders with different disease severities. We here investigate whether common variation in the promoter region of the unaffected SCN1A allele could reduce normal expression, leading to a decreased residual function of Nav1.1, and therefore to more severe clinical outcomes in patients affected by pathogenic SCN1A variants.MethodsFive different SCN1A promoter‐haplotypes were functionally assessed in SH‐SY5Y cells using Firefly and Renilla luciferase assays. The SCN1A promoter region was analyzed in a cohort of 143 participants with SCN1A pathogenic variants. Differences in clinical features and outcomes between participants with and without common variants in the SCN1A promoter‐region of their unaffected allele were investigated.ResultsAll non‐wildtype haplotypes showed a significant reduction in luciferase expression, compared to the wildtype promoter‐region (65%–80%, p = 0.039–0.0023). No statistically significant differences in clinical outcomes were observed between patients with and without common promoter variants. However, patients with a wildtype promoter‐haplotype on their unaffected SCN1A allele showed a nonsignificant trend for milder phenotypes.ConclusionThe nonsignificant observed trends in our study warrant replication studies in larger cohorts to explore the potential modifying role of these common SCN1A promoter‐haplotypes.