bluuebunny/crossref_metadata_2025_split huggingface dataset:
Polymersomes as Nanoreactors Enabling the Application of Solvent‐Sensitive Enzymes in Different Biphasic Reaction Setups
Authors: Golombek Florian , Castiglione Kathrin 
Published: July 2020

AbstractThere is an increasing interest in biocatalysis to perform chemical reactions in biphasic systems, consisting of an aqueous phase and a water‐immiscible organic solvent or ionic liquid. In most cases, the hydrophobic phase is used as reservoir for poorly water‐soluble substrates or for in situ product removal. However, many enzymes are solvent‐sensitive and cannot be used in such systems. In this study, the solvent‐sensitive enzyme mandelate racemase is exemplarily protected from the organic phase by its entrapment in (crosslinked) polymersomes. The covalent crosslinking of the individual chains of the block copolymer poly(2‐methyloxazoline)15‐poly(dimethylsiloxane)68‐poly(2‐methyloxazoline)15 via terminal methacrylates leads to enhanced membrane stability. This effect is especially pronounced for long‐time incubation in the presence of organic solvents and ionic liquids. By using a gentle polymerization initiator at its minimal necessary concentration, the prior encapsulated enzymes remain intact during crosslinking. Although the insertion of natural channel proteins into the membrane improves the mass transport into the vesicles, it is non‐essential. Mandelate racemase in (crosslinked) polymersomes remains active in different highly dispersed biphasic systems for more than 24 h. The free enzyme, on the other hand, gets completely inactivated within 1 h, thus illustrating the potential of polymersomes as nanoreactors in biphasic reaction setups.
Exon 11 homozygous mutations and intron 10/exon 11 junction deletions in the KIT gene are associated with poor prognosis of patients with gastrointestinal stromal tumors
Authors: Shen Yan‐Ying , Ma Xin‐Li , Wang Ming , Zhuang Chun , Ni Bo , Tu Lin , Liu Qiang , Zhao Wen‐Yi , Cao Hui 
Published: July 2020

AbstractBackgroundGastrointestinal stromal tumors (GISTs) with different types of mutations exhibit different clinical characteristics and prognosis. This study aimed to evaluate the prognostic value of mutations in KIT and PDGFRA in a large‐scale cohort of GIST patients with current therapy including surgery and imatinib.MethodsA total of 1163 patients diagnosed with GISTs between January 2006 and December 2018 were enrolled in this study. Mutation analysis was performed for exons 9, 11, 13, and 17 of KIT and exons 12 and 18 of PDGFRA. Mutations were grouped into 12 categories according to the gene, exon, and involved codons; they were analyzed considering the clinical characteristics, disease‐free survival (DFS), and overall survival (OS) of patients with GISTs.ResultsIn low‐risk GISTs, we identified two predictors of worse DFS: tumor origin in the rectum and KIT exon 11 deletion involving two or more codons. In high‐risk GISTs treated with R0 resection and imatinib, patients with KIT exon 11 homozygous mutations and KIT intron 10/exon 11 junction deletions demonstrated the highest recurrence rate, indicating that these mutations can be independent prognostic factors of DFS. The presence of KIT exon 11 homozygous mutations also independently influenced OS.ConclusionLow‐incidence mutations such as KIT exon 11 homozygous mutations or intron 10/exon 11 junction deletions in GISTs should be carefully evaluated to explore novel treatment strategies, as tumors with these mutations have a high recurrence rate and a very poor prognosis after surgery followed by imatinib adjuvant treatment.
A phase 2 trial of consolidation pembrolizumab following concurrent chemoradiation for patients with unresectable stage III non–small cell lung cancer: Hoosier Cancer Research Network LUN 14‐179
Authors: Durm Greg A. , Jabbour Salma K. , Althouse Sandra K. , Liu Ziyue , Sadiq Ahad A. , Zon Robin T. , Jalal Shadia I. , Kloecker Goetz H. , Williamson Michael J. , Reckamp Karen L. , Langdon Robert M. , Kio Ebenezer A. , Gentzler Ryan D. , Adesunloye Bamidele A. , Harb Wael A. , Walling Radhika V. , Titzer Michael L. , Hanna Nasser H. 
Published: July 2020

BackgroundFive‐year overall survival (OS) for patients with unresectable stage III non–small cell lung cancer (NSCLC) is poor. Until recently, a standard of care was concurrent chemoradiation alone. Patients with metastatic NSCLC treated with anti–programmed death 1 antibodies have demonstrated improved OS. This trial evaluated pembrolizumab as consolidation therapy after concurrent chemoradiation in patients with unresectable stage III disease.MethodsPatients with unresectable stage III NSCLC received concurrent chemoradiation with cisplatin and etoposide, cisplatin and pemetrexed, or carboplatin and paclitaxel and 59.4 to 66.6 Gy of radiation. Patients with nonprogression of disease were enrolled and received pembrolizumab (200 mg intravenously every 3 weeks for up to 12 months). The primary endpoint was the time to metastatic disease or death (TMDD). Secondary endpoints included progression‐free survival (PFS) and OS.ResultsThe median follow‐up for 93 patients (92 for efficacy) was 32.2 months (range, 1.2‐46.6 months). The median TMDD was 30.7 months (95% confidence interval [CI], 18.7 months to not reached), which was significantly longer than the historical control of 12 months (P < .0001). The median PFS was 18.7 months (95% CI, 12.4‐33.8 months), and the median OS was 35.8 months (95% CI, 24.2 months to not reached). The 1‐, 2‐, and 3‐year OS estimates were 81.2%, 62.0%, and 48.5%, respectively. Forty patients (43.5%) completed 12 months of treatment (median number of cycles, 13.5). Symptomatic pneumonitis (grade 2 or higher) was noted in 16 patients (17.2%); these cases included 4 grade 3 events (4.3%), 1 grade 4 event (1.1%), and 1 grade 5 event (1.1%).ConclusionsConsolidation pembrolizumab after concurrent chemoradiation improves TMDD, PFS, and OS in comparison with historical controls of chemoradiation alone. Rates of grade 3 to 5 pneumonitis were similar to those reported with chemoradiation alone.
Prognostic value of blasts in peripheral blood in myelofibrosis in the ruxolitinib era
Authors: Masarova Lucia , Bose Prithviraj , Pemmaraju Naveen , Daver Naval G. , Zhou Lingsha , Pierce Sherry , Sasaki Koji , Kantarjian Hagop M. , Estrov Zeev , Verstovsek Srdan 
Published: July 2020

BackgroundCirculating blasts (peripheral blood [PB] blasts) ≥1% have long been considered an unfavorable feature for patients with primary myelofibrosis. Whether further quantification of PB blasts and their correlation with bone marrow (BM) blasts have incremental value with regard to patient prognostication is unclear. Similarly, the role of the JAK1/JAK2 inhibitor ruxolitinib (RUX) is not well defined in patients who have increased blasts.MethodsThe authors retrospectively studied 1316 patients with myelofibrosis who presented at their institution between 1984 and 2018 and had available PB and BM blasts.ResultsThe PB blast percentage influenced overall survival (OS) only among patients who had BM blasts <5%, with a median OS of 64 months for patients with 0% PB blasts, 48 months for those with 1% to 3% PB blasts, and 22 months for those with 4% PB blasts (P < .01). Patients who had 4% PB blasts and 5% to 9% BM/PB blasts had clinical features similar to those of patients who had 10% to 19% blasts. Although the OS of the former patients was longer than in patients who had 10% to 19% blasts, it was not statistically different (median OS: 22, 26, and 13 months, respectively; P > .05). Forty‐four percent of patients received RUX throughout their disease course. All patients who had <10% blasts (PB or BM) and received treatment with RUX had superior OS compared with those who did not receive RUX within the same group. PB blasts ≥4% and BM blasts ≥5% were significant for predicting inferior survival in multivariate analysis.ConclusionsThe current results provide comprehensive insight into the role of peripheral blasts in patients with myelofibrosis and indicates that patients who have PB blasts ≥4% have an unfavorable prognosis. RUX provides a survival benefit to patients who have PB blasts <10%.
A2Cloud‐RF: A random forest based statistical framework to guide resource selection forhigh‐performancescientific computing on the cloud
Authors: Samuel David , Khan Syeduzzaman , Balos Cody J. , Abuelhaj Zachariah , Dutoi Anthony D. , Kari Chadi , Mueller David , Pallipuram Vivek K. 
Published: July 2020

SummaryThis article proposes a random‐forest based A2Cloud framework to match scientific applications with Cloud providers and their instances for high performance. The framework leverages four engines for this task: PERF engine, Cloud trace engine, A2Cloud‐ext engine, and the random forest classifier (RFC) engine. The PERF engine profiles the application to obtain performance characteristics, including the number of single‐precision (SP) floating‐point operations (FLOPs), double‐precision (DP) FLOPs, x87 operations, memory accesses, and disk accesses. The Cloud trace engine obtains the corresponding performance characteristics of the selected Cloud instances including: SP floating point operations per second (FLOPS), DP FLOPS, x87 operations per second, memory bandwidth, and disk bandwidth. The A2Cloud‐ext engine uses the application and Cloud instance characteristics to generate objective scores that represent the application‐to‐Cloud match. The RFC engine uses these objective scores to generate two types of random forests to assist users with rapid analysis: application‐specific random forests (ARF) and application‐class based random forests. The ARF consider only the input application's characteristics to generate a random forest and provide numerical ratings to the selected Cloud instances. To generate the application‐class based random forests, the RFC engine downloads the application profiles and scores of previously tested applications that perform similar to the input application. Using these data, the RFC engine creates a random forest for instance recommendation. We exhaustively test this framework using eight real‐world applications across 12 instances from different Cloud providers. Our tests show significant statistical agreement between the instance ratings given by the framework and the ratings obtained via actual Cloud executions.
Creatinine‐Based Renal Function Assessment in Pediatric Drug Development: An Analysis Using Clinical Data for Renally Eliminated Drugs
Authors: Zhang Yifei , Sherwin Catherine M. , Gonzalez Daniel , Zhang Qunshu , Khurana Mona , Fisher Jeffrey , Burckart Gilbert J. , Wang Yaning , Yao Lynne P. , Ganley Charles J. , Wang Jian 
Published: July 2020

The estimated glomerular filtration rate (eGFR) equations based on serum creatinine (SCR) have been used for pediatric dose adjustment in drug labeling. This study evaluated the performance of those equations in estimating individual clearance of drugs that are predominantly eliminated by glomerular filtration, using clinical data from the renally eliminated drugs gadobutrol, gadoterate, amikacin, and vancomycin. The eGFR was compared with the observed drug clearance (CL) in 352 pediatric patients from birth to 12 years of age. Multiple eGFR equations overestimated the drug CL on average, including the original and bedside Schwartz equations, which showed an average eGFR/CL ratio between 1 and 3. Further analysis with bedside Schwartz equation showed a higher eGFR/CL ratio in the subjects with a lower SCR or CL. Supraphysiological eGFR as high as 380 mL/min/1.73 m2 was obtained using the bedside Schwartz equation for some of the subjects, most of whom are children < 2 years of age with SCR < 0.2 mg/dL. Excluding the subjects with supraphysiological eGFR from the analysis did not change the overall trend of overestimation. In conclusion, Schwartz equations led to an overestimation of drug clearance for the drugs evaluated. When greater precision is required in predicting eGFR for pediatric patients, such as in drug dosing, revised k constants for the Schwartz equation or new methods of glomerular filtration rate estimation may be necessary.
TiO2 Mesocrystals Processed at Low Temperature as the Electron‐Transport Material in Perovskite Solar Cells
Authors: Guo Minghuang , Shen Deli , Li Yafeng , Akram Muhammad Aftab , Wei Mingdeng 
Published: July 2020

AbstractTiO2 is the most widely used material for preparing the electron‐transporting layer (ETL) in perovskite solar cells (PSCs). However, it requires a high‐temperature sintering process. Moreover, the intrinsic defects and low electron mobility of TiO2 ETLs cause instability and hysteresis effects in PSCs. In this study, a mesoporous film composed of anatase TiO2 mesocrystals was facilely fabricated by a low‐temperature route and then used as an ETL in PSCs for the first time. A satisfactory efficiency of 20.26 % can be achieved through delicate control of the entire device fabrication procedure. The optimal device, with an area of 1 cm2, achieves an efficiency of 17.07 %. In comparison to the common TiO2 ETLs, those composed of TiO2 mesocrystals show the enhanced electron extraction and suppression of charge accumulation at the perovskite/ETL interface, resulting in improved photovoltaic performance and reduced hysteresis.
Prevention of heart failure events with intensive versus standard blood pressure lowering across the spectrum of kidney function and albuminuria: a SPRINT substudy
Authors: Vaduganathan Muthiah , Pareek Manan , Kristensen Anna M.D. , Biering‐Sørensen Tor , Byrne Christina , Almarzooq Zaid , Olesen Thomas Bastholm , Olsen Michael H. , Bhatt Deepak L. 
Published: July 2020

AimsTo determine whether a strategy of intensive blood pressure control reduces the risk of heart failure (HF) events consistently across the spectrum of kidney function and albuminuria.Methods and resultsSPRINT was a randomized clinical trial in which 9361 individuals ≥50 years, at high risk for or with cardiovascular disease, a systolic blood pressure of 130–180 mmHg, but without diabetes, were randomized to intensive (target <120 mmHg) vs. standard (target <140 mmHg) blood pressure control. We assessed whether estimated glomerular filtration rate (eGFR) and urine albumin‐to‐creatinine ratio (UACR) modified the effects of the blood pressure control strategy in reducing HF events (either hospitalization or emergency department visits) and the composite of HF events or cardiovascular death, using Cox proportional hazards regression and restricted cubic splines. Of the 9361 individuals included in SPRINT, eGFR and UACR were available for 9324 (99.6%) and 8913 (95.2%) subjects, respectively, including 2650 (28.4%) with eGFR <60 mL/min/1.73 m2 and 248 (2.8%) with UACR >300 mg/g. During a median follow‐up of 3.2 years (range 0–4.8 years), 160 (1.8%) participants had HF events and 233 (2.6%) had HF events or cardiovascular death. Risks of HF events or cardiovascular death increased from 0.42 (0.34–0.53) per 100 patient‐years in patients with eGFR ≥60 mL/min/1.73 m2 and UACR <30 mg/g to 4.55 (3.00–6.91) per 100 patient‐years in patients with eGFR <60 mL/min/1.73 m2 and UACR >300 mg/g. A similar gradient was observed for HF events alone. Both eGFR and UACR were independently, non‐linearly associated with HF hospitalization and HF hospitalization or cardiovascular death (test for overall trend, P < 0.001). While the effects of intensive blood pressure control on HF event risk appeared to attenuate at lower eGFR and higher UACR, there was no significant interaction between eGFR or UACR and blood pressure control strategy (continuous and categorical interaction P > 0.05).ConclusionIn SPRINT, eGFR and albuminuria were strong and additive determinants in forecasting HF risk. The effect of intensive blood pressure control in decreasing HF risk did not significantly vary across the spectrum of kidney function or albuminuria. Multidisciplinary pathways, incorporating blood pressure control, are needed for at‐risk patients with chronic kidney disease to attenuate HF risk.Trial Registration: ClinicalTrials.gov Identifier NCT01206062.
Geographic patterns of implicit age bias and associations with state‐level health outcomes across the United States
Authors: Giasson Hannah L. , Chopik William J. 
Published: July 2020

AbstractNegative attitudes toward aging are pervasive in society and may be detrimental to people's health as they become older. Older people tend to report feeling significantly younger than their chronological age, often as a way of psychologically distancing themselves from the stigma of old age. However, attitudes and behaviors toward aging may differ across regional contexts. We examined associations among state‐level patterns of bias against older adults and state‐level health outcomes across the United States. Data from 803,009 respondents (ages: 15–94) across 50 U.S. states (and the District of Columbia) revealed geographic variation in implicit age bias. Higher state‐level implicit age bias was associated with poorer state‐level health outcomes among adults ages 65+. Older adults living in states high in implicit age bias showed greater age‐group dissociation compared to older adults living in states low in implicit age bias. Findings highlight potential consequences of implicit age bias and invite further research on the long‐term health implications of individual age‐group dissociation in response to regional age bias.
Diesel and gasoline like fuel production with minimum styrene content from catalytic pyrolysis of polystyrene
Authors: Amjad Um‐e‐Salma , Ishaq Manzar , Rehman Hamood ur , Ahmad Nabeel , Sherin Lubna , Hussain Murid , Mustafa Maria 
Published: July 2020

AbstractPyrolysis of waste polystyrene to generate fuel was carried out to yield pyrolysis oil. For the first time, NiO deposited over ZrO2 carrier as catalyst, was deployed and evaluated in the catalytic pyrolysis. Catalysts based on different loading (2, 5, 10, and 15%) of NiO deposited over ZrO2 carrier were prepared by solution combustion synthesis and tested toward screening of catalytic pyrolysis of PS in semi batch reactor. Based on conversion, yield of oil and low styrene monomer content, the catalytic performance with different loadings was evaluated and optimized. Furthermore, the oil obtained from the best catalysts were analyzed using GC–MS for carbon number distribution, depolymerization reactions, and diesel fuel generation. These catalysts were also characterized using X‐ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), pyridine FTIR, and scanning electron microscopy (SEM) techniques. As compared to thermal pyrolysis, the catalytic pyrolysis process was found to be highly selective toward diesel like fuel generation with minimum styrene monomer formation. Also, 2 and 10% NiO catalyst showed the best catalytic performance in pyrolysis process that could be ascribed to the presence of Lewis and Brönsted acid sites resulting in selectivity for C16 carbon number, diesel fuel generation, and depolymerization reactions.
Enhancement in rice seed germination via improved respiratory metabolism under chilling stress
Authors: Nie Lixiao , Liu Hongyan , Zhang Li , Wang Weiqin 
Published: July 2020

AbstractChilling stress is one of the abiotic stresses that severely limited the production of many field crops. The chilling stress during emergence stages of rice severely hampered the process of seed germination and seedling growth and resulted in yield losses. Meanwhile, the development of seed priming has been proved to effectively enhance the seedling establishment of rice under chilling stress. However, the regulating effects of seed priming on the respiratory metabolism during rice seed germination under chilling stress have rarely been explored. In the present study, the effects of two pre‐optimized seed priming treatments, selenium priming (Se) and salicylic priming (SA), were examined under chilling stress. The results revealed that chilling stress significantly reduced the rice seed germination and seedling growth, as well as the respiration rate and ATP contents in rice seeds and seedlings. While seed priming was effective to significantly enhance the respiration rate and ATP levels in rice seeds and seedlings, such positive effects might be induced by the enhanced glycolysis metabolism, as well as the repair and biogenesis of mitochondria. However, the molecular mechanisms in association with the enhanced respiration in primed rice seeds and seedlings under chilling stress still needed to be addressed in future studies.
Common HTR2A variants and 5‐HTTLPR are not associated with human in vivo serotonin 2A receptor levels
Authors: Spies Marie , Nasser Arafat , Ozenne Brice , Jensen Peter S. , Knudsen Gitte M. , Fisher Patrick M. 
Published: July 2020

AbstractThe serotonin 2A receptor (5‐HT2AR) is implicated in the pathophysiology and treatment of various psychiatric disorders. [18F]altanserin and [11C]Cimbi‐36 positron emission tomography (PET) allow for high‐resolution imaging of 5‐HT2AR in the living human brain. Cerebral 5‐HT2AR binding is strongly genetically determined, though the impact of specific variants is poorly understood. Candidate gene studies suggest that HTR2A single nucleotide polymorphisms including rs6311/rs6313, rs6314, and rs7997012 may influence risk for psychiatric disorders and mediate treatment response. Although known to impact in vitro expression of 5‐HT2AR or other serotonin (5‐HT) proteins, their effect on human in vivo brain 5‐HT2AR binding has as of yet been insufficiently studied. We thus assessed the extent to which these variants and the commonly studied 5‐HTTLPR predict neocortex in vivo 5‐HT2AR binding in healthy adult humans. We used linear regression analyses and likelihood ratio tests in 197 subjects scanned with [18F]altanserin or [11C]Cimbi‐36 PET. Although we observed genotype group differences in 5‐HT2AR binding of up to ~10%, no genetic variants were statistically significantly predictive of 5‐HT2AR binding in what is the largest human in vivo 5‐HT2AR imaging genetics study to date. Thus, in vitro and post mortem results suggesting effects on 5‐HT2AR expression did not carry over to the in vivo setting. To any extent these variants might affect clinical risk, our findings do not support that 5‐HT2AR binding mediates such effects. Our observations indicate that these individual variants do not significantly contribute to genetic load on human in vivo 5‐HT2AR binding.
Boardroom gender diversity and dividend payout strategies: Effects of mergers deals
Authors: Trinh Vu Quang , Cao Ngan Duong , Dinh Linh Hai , Nguyen Hong Ngoc 
Published: July 2020

AbstractOur study examines the effects of mergers and acquisitions deals on the relationship between female leadership and dividend strategies for 90 UK listed firms during the period 2006–2016. Results indicate that firms with a larger proportion of female directors serving on the board are more likely to pay higher dividends, but this positive finding is weaker when the firms experienced a higher number of mergers and acquisitions deals. Interestingly, extended analyses on female directors' positions show the opposing effects of female Chairmen and female CEOs on a firm's payout strategies. Although a female Chairman is associated with higher dividend payout levels, a female CEO shows an adverse impact. Yet these results tend to be reversed for firms with more merger and acquisition transactions. Our findings make a significant contribution to a trendy but relatively limited and inconclusive topic that links gender diversity to scrutiny intensity.