bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quality of patient‐reported outcomes in oncology clinical trials using immune checkpoint inhibitors: A systematic review
Authors: Malone Eoghan , Barua Reeta , Meti Nicholas , Li Xuan , Fazelzad Rouhi , Hansen Aaron R. 
Published: June 2021

AbstractBackgroundThere are limited data regarding the quality of patient‐reported outcome (PRO) data in immune checkpoint inhibitor (ICI) clinical trial publications.MethodsA systematic search of citations from various databases was conducted to identify prospective clinical trials involving ICI in advanced tumors from 2003 to 2020. A 30‐point score was adapted from the CONSORT PRO extension statement to assess adherence to CONSORT PRO reporting. Linear regression was used to identify factors associated with quality reporting.ResultsAfter the review of 8058 articles, 33 trials were included with ICIs as either monotherapy (91%) or part of a combination regimen (9%). The median score was 23.5 points (range 15–29). In the majority of cases (82%), PROs were reported in a separate publication from the original study. Most of the trials were conducted in the metastatic setting and predominantly in melanoma, lung, and renal cell carcinoma (RCC) (73%). Univariate analysis revealed that trials with greater than 250 patients were associated with a higher score. The score was more likely to be lower in disease sites other than melanoma, lung, and RCC and was higher in the KEYNOTE than in the CHECKMATE trial series. There was no significant correlation between the score and whether a trial met its primary end‐point or if the trial improved or worsened the quality of life. In the multivariate analysis, the number of patients enrolled to the trial, disease site, and trial series remained significant.ConclusionsThe quality of reporting of PROs in ICI phase II and III clinical trials is heterogeneous across various cancer sites. As PRO data are increasingly used to counsel patients and complement clinical decision making, innovative and collaborative efforts are required to improve the reporting of these essential data.
Comparing the frequency of CD33+ pSTAT3+ myeloid‐derived suppressor cells and IL‐17+ lymphocytes in patients with prostate cancer and benign prostatic hyperplasia
Authors: Sanaei Mohammad‐Javad , Taheri Fatemeh , Heshmati Masoud , Bashash Davood , Nazmabadi Roya , Mohammad‐Alibeigi Faramarz , Nahid‐Samiei Mahboobeh , Shirzad Hedayatollah , Bagheri Nader 
Published: June 2021

AbstractProstate cancer (PCa) is one of the most epidemic types of cancer in men. The tumor microenvironment (TME) of PCa is involved in the emergence of immunosuppressive factors such as myeloid‐derived suppressor cells (MDSC), which regulate the immune system by several mechanisms, including interleukin (IL)‐10 production. On the other hand, IL‐17+ helper T cells (Th17) induce MDSCs and chronic inflammation in TME by producing IL‐17. This study demonstrated that the frequency of CD33+ pSTAT3+ MDSC and IL‐17+ lymphocyte as well as IL‐10 messenger RNA (mRNA) expression were significantly higher in the PCa patients than in the benign prostatic hyperplasia (BPH) group. Moreover, there was no significant relationship between the frequency of CD33+ pSTAT3+ MDSC, and IL‐17+ lymphocyte with Gleason scores in the PCa group. We suggested that the higher frequency of CD33+ pSTAT3+ MDSC and IL‐17+ lymphocyte and the more frequent expression of IL‐10 mRNA in PCa patients may play roles in tumor progression from BPH to PCa.
Kinetics and catalytic distillation simulation for the heterogeneously catalytic synthesis of imine
Authors: Chen Jian , Zhu Mengjing , Xiang Fuwei , Li Junfeng , Yang Hongjun , Mao Zhipeng , Chang Ganggang , Li Shaoping 
Published: June 2021

Abstract(2‐methyl‐6‐ethylphenyl)‐1‐methoxypropyl‐2‐imine (MEMI) is an important intermediate for the synthesis of commercial pesticide S‐metolachlor. However, the research on heterogeneously catalytic kinetics of MEMI, and further the catalytic distillation simulation aiming at continuous operation, have never been reported. Herein, the catalytic kinetics for the synthesis of MEMI by HPW/Al‐MCM‐41 have been systematically investigated, and further fitted by using a pseudo‐homogeneous kinetic model, based on which, the reaction equilibrium constant, activation energy, and rate constant are obtained. Furthermore, simulation of the continuous process of MEMI synthesis was carried out using the software Aspen Plus V10. Sensitivity analysis of operating parameters such as feed stage, distillation rate, number of reactive theoretical stages, and the best operating conditions were also obtained. An excellent product purity (>98.9%) of MEMI could be achieved when operated at the optimum conditions. Compared with the batch method, catalytic distillation provided continuous synthesis of MEMI, and the reaction was more thorough, achieving process integration and optimization. Our results provide substantial theoretical and empirical supports for the industrial synthesis of MEMI.
Severity of arterial and/or arteriolar sclerosis in IgA nephropathy and the effects of renin–angiotensin system inhibitors on its prognosis
Authors: Sugiura Naoko , Moriyama Takahito , Miyabe Yoei , Karasawa Kazunori , Nitta Kosaku 
Published: June 2021

AbstractIgA nephropathy (IgAN) patients often suffer from arterial and/or arteriolar sclerosis (AAS); however, it is unclear whether these features are associated with a poor prognosis. This retrospective cohort study aimed to analyse the prognosis of IgAN patients with AAS and assess whether treatment with renin–angiotensin system inhibitors (RASI) improved their survival. The study included 678 IgAN patients, who were grouped into AAS0 (n = 340; AAS absent) and AAS1 (n = 338; AAS present) groups. Each patient's clinical, laboratory, and histological backgrounds and 20‐year renal prognosis were analysed. In the AAS1 group, the impact of RASI initiated during the follow‐up period on the renal prognosis was also evaluated after adjustments for background characteristics. IgAN patients with AAS had significantly higher age, blood pressure, body mass index, total cholesterol, uric acid levels, and proteinuria than patients without AAS; they also had more severe histological findings, decreased renal function, and lower survival rates than those without AAS (64.0 versus 84.7%, p < 0.001). Multivariate Cox regression analysis incorporating clinical and histological findings and treatments revealed AAS as an independent factor for disease progression (hazard ratio: 2.23, p = 0.010). Participants in the AAS1 group treated with RASI during follow‐up had a significantly higher renal survival rate than those who were not (75.5 versus 44.3%, p = 0.013). In conclusion, AAS was found to be associated with serious clinical, laboratory, and histological findings and poor prognosis. RASI initiated during the follow‐up period was found to improve renal prognosis.
RhII‐Catalyzed De‐symmetrization of Ethane‐1,2‐dithiol and Propane‐1,3‐dithiol Yields Metallo‐β‐lactamase Inhibitors
Authors: Krasavin Mikhail , Zhukovsky Daniil , Solovyev Igor , Barkhatova Darina , Dar'in Dmitry , Frank Denia , Martinelli Giada , Weizel Lilia , Proschak Anna , Rotter Marco , Kramer Jan S. , Brunst Steffen , Wichelhaus Thomas A. , Proschak Ewgenij 
Published: June 2021

AbstractDiversity‐oriented synthesis (DOS) is a rich source for novel lead structures in Medicinal Chemistry. In this study, we present a DOS‐compatible method for synthesis of compounds bearing a free thiol moiety. The procedure relies on Rh(II)‐catalyzed coupling of dithiols to diazo building blocks. The synthetized library was probed against metallo‐β‐lactamases (MBLs) NDM‐1 and VIM‐1. Biochemical and biological evaluation led to identification of novel potent MBL inhibitors with antibiotic adjuvant activity.
Sociodemographic and hospital‐based predictors of intense end‐of‐life care among children, adolescents, and young adults with hematologic malignancies
Authors: Mun Sophia , Wang Rong , Ma Xiaomei , Ananth Prasanna 
Published: June 2021

BackgroundChildren, adolescents, and young adults with hematologic malignancies tend to receive high‐intensity end‐of‐life care (HI‐EOLC), but sociodemographic and hospital‐based predictors of HI‐EOLC remain unclear.MethodsThe authors conducted a population‐based, retrospective cohort study with the Premier Healthcare Database. They identified individuals with hematologic malignancies who were 0 to 39 years old at death and died between 2010 and 2017. HI‐EOLC was defined as experiencing 2 or more of the following: cardiopulmonary resuscitation, intravenous chemotherapy, hemodialysis, mechanical ventilation, tracheostomy placement, or an emergency department visit within the last 30 days of life and death in the intensive care unit. Multivariable logistic regression models were constructed to identify patient sociodemographic and hospital characteristics associated with HI‐EOLC.ResultsAmong 1454 decedents, more than half (55%) experienced HI‐EOLC. In multivariable models, patients treated in medium (adjusted odds ratio [aOR], 1.63; 95% confidence interval [CI], 1.07‐2.50) or large hospitals (aOR, 2.21; 95% CI, 1.45‐3.39), insured by Medicaid (aOR, 1.40 ; 95% CI, 1.09‐2.06), or receiving cancer‐directed treatment in the Northeast (aOR, 1.50; 95% CI, 1.05‐2.15) were more likely to receive HI‐EOLC.ConclusionsA majority of children, adolescents, and young adults with hematologic malignancies experienced HI‐EOLC, and the likelihood of HI‐EOLC was influenced by the hospital size, type of insurance, and geographic region. Further research is needed to determine how to mitigate these risks.
Antibacterial and antioxidant effect of ethanol extracts of Terminalia chebula on Streptococcus mutans
Authors: Nam Yea Ji , Hwang Young Sun 
Published: June 2021

AbstractObjectiveDental caries is a high prevalent chronic bacterial infectious disease caused by plaque, a bacterial colony deposited on tooth surfaces and gum tissues. Streptococcus mutans is a primary cariogenic bacterium commonly found in the human oral cavity. Oral hygiene products containing antibacterial ingredients can be helpful in caries management. In this study, we investigated the anticaries mechanism of the ethanol extract of Terminalia chebula (EETC) on S. mutans and suggest its possible application as a functional ingredients for oral hygiene products.Materials and methodsThe EETC was prepared from the Terminalia chebula fruit. Disk diffusion, minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and colony forming unit (CFU) were analyzed to observe the antibacterial activity of EETC. The glucan formation was measured using the filtrate of bacterial culture medium and sucrose. Gene expression was analyzed using RT‐PCR. Cytotoxicity was analyzed using the MTT assay. The radical‐scavenging activities of DPPH and ABTS were also tested to verify the antioxidant activity of EETC.ResultsThe antibacterial activity of the EETC was explored through a disc diffusion analysis and CFU measurement. EETC treatment decreased insoluble glucan formation and gene expression of glycosyltransferase B (gtf B), glycosyltransferase C (gtf C), glycosyltransferase D (gtf D), and fructosyltransferase (ftf). The MIC and MBC of EETC on S. mutans were not cytotoxic to gingival fibroblasts. In addition, we observed DPPH and ABTS‐radical scavenging activities of EETC.ConclusionsThese results indicate that the antibacterial and antioxidant effects of EETC may contribute to oral hygiene products for dental caries management.
Light‐Driven Waste‐To‐Value Upcycling: Bio‐Based Polyols and Polyurethanes from the Photo‐Oxygenation of Cardanols
Authors: Stuhr Robin , Bayer Patrick , Stark Christian B. W. , Jacobi von Wangelin Axel 
Published: June 2021

AbstractThe upcycling of waste biomass into valuable materials by resource‐efficient chemical transformations is a prime objective for sustainable chemistry. This approach is demonstrated in a straightforward light‐driven synthesis of polyols and polyurethane foams from the multi‐ton waste products of cashew nut processing. The photo‐oxygenation of cardanol from nutshell oil results in the formation of synthetically versatile hydroperoxides. The choice of the workup method (i. e., reduction, hydrogenation, epoxidation) enables access to a diverse range of alcohols with tunable alkene and OH functions. Condensation with isocyanates to give rigid polyurethane foams provides a resource‐efficient waste‐to‐value chain that benefits from the availability of cardanol and installation of OH groups from aerial O2.
Coldwater fish in a warm water world: Implications for predation of salmon smolts during estuary transit
Authors: Nobriga Matthew L. , Michel Cyril J. , Johnson Rachel C. , Wikert John D. 
Published: June 2021

Abstract

Predator–prey systems face intensifying pressure from human exploitation and a warming climate with implications for where and how natural resource management can successfully intervene. We hypothesized young salmon migrating to the Pacific Ocean face a seasonally intensifying predator gauntlet when warming water temperature intensifies a multiple predator effect (MPE) from Striped Bass Morone saxatilis and Largemouth Bass Micropterus salmoides. We evaluated this hypothesis using data synthesis and simulation modeling.
Contemporary studies based on acoustically tagged fish reaffirmed older observations that Chinook Salmon smolts must transit the Delta before water temperature reaches 20°C or mortality will be nearly 100%. Striped Bass attack rates on tethered smolts were insensitive to distance from shore and water temperature, whereas Largemouth Bass attack rates were highest near shorelines in warm water, supporting the temporal aspect of the hypothesis. Whether the combined effects of the two predators produce an MPE remains unconfirmed due to limitations on quantifying salmon behavior.
We used multiple simulation models to try to reconstruct the empirical relationship between smolt survival and water temperature. Simulations reinforced attack rate results, but could not recreate the temperature dependence in smolt survival except at higher than observed temperatures. We propose three hypotheses for why and recommend discerning among them should be a focus of research.
We found significant linear relationships between monthly mean inflow to the Delta from each of its two largest tributaries and monthly mean water temperatures along associated salmon migration routes, but these relationships can be nonlinear, with most of the correlation occurring at low inflows when water temperature is largely controlled by air temperature and day length. As the global climate warms, changed circumstances in predator–prey relationships may present important challenges when managing species vulnerable to extinction in addition to presently more abundant species.
Three tips for creating an online course for nontraditional student populations
Authors: Forman M. Rebecca , Chapman John A. 
Published: June 2021

AbstractIn spring 2020, the University of Minnesota Erosion and Stormwater Management Certification Program temporarily ceased in‐person workshops due to the spread of COVID‐19. Twenty workshops were canceled, and the 1,233 attendees (all adult learners) were moved into asynchronous online course sections. These online workshops were the first remote courses that many of the attendees had ever attempted. Here, we provide tips for successfully creating online classes for nontraditional student populations.
A non‐Newtonian fluidic cellulose‐modified glass microfiber separator for flexible lithium‐ion batteries
Authors: Zhu Ying , Cao Kaiyue , Cheng Wanke , Zeng Suqing , Dou Shuo , Chen Wenshuai , Zhao Dawei , Yu Haipeng 
Published: June 2021

AbstractThe separator is of great importance for regulating ion transmission, maintaining electrode stability, and device safety in lithium‐ion batteries. Despite their many advantages, glass microfiber separators have shortcomings that often give rise to poor cycle performance and fatal short‐circuit risk when used in flexible batteries. Here, we propose the use of a scalable non‐Newtonian fluidic cellulose permeation‐diffusion strategy to develop a cellulose/glass microfiber composite film with an hourglass‐gradient structure. Due to the unique gradient morphology resulting from the presence of cellulose macromolecules, the as‐prepared composite film showed an improved surface mass density, adjustable pore structure, controllable ion transport, ideal mechanical flexibility, and robustness. When used as the separator in an assembled lithium‐ion battery, the composite film exhibited rapid ion diffusion and Li dendrite inhibition, which endowed the battery with excellent cycle stability (specific capacity of 108.5 mAh g−1 after 1000 cycles) and good rate performance. This composite film shows great potential application in flexible lithium‐ion batteries including but not limited to pouch cells.image
Identifying genetic risk variants associated with brain volumetric phenotypes via K‐sample Ball Divergence method
Authors: Hu Yue , Tan Haizhu , Li Cai , Zhang Heping 
Published: June 2021

AbstractRegional human brain volumes including total area, average thickness, and total volume are heritable and associated with neurological disorders. However, the genetic architecture of brain structure and function is still largely unknown and worthy of exploring. The Pediatric Imaging, Neurocognition, and Genetics (PING) data set provides an excellent resource with genome‐wide genetic data and related neuroimaging data. In this study, we perform genome‐wide association studies (GWAS) of 315 brain volumetric phenotypes from the PING data set including 1036 samples with 539,865 single‐nucleotide polymorphisms (SNPs). We introduce a nonparametric test based on K‐sample Ball Divergence (KBD) to identify genetic risk variants that influence regional brain volumes. We carry out simulations to demonstrate that KBD is a powerful test for identifying significant SNPs associated with multivariate phenotypes although controlling the type I error rate. We successfully identify nine SNPs below a significance level of 5 × 10−5 for the PING data. Among the nine identified genetic variants, two SNPs rs486179 and rs562110 are located in the ADRA1A gene that is a well‐known risk factor of mental illness, such as schizophrenia and attention deficit hyperactivity disorder. Our study suggests that the nonparametric test KBD is an effective method for identifying genetic variants associated with complex diseases in large‐scale GWAS of multiple phenotypes.
R2* and quantitative susceptibility mapping in deep gray matter of 498 healthy controls from 5 to 90 years
Authors: Treit Sarah , Naji Nashwan , Seres Peter , Rickard Julia , Stolz Emily , Wilman Alan H. , Beaulieu Christian 
Published: June 2021

AbstractPutative MRI markers of iron in deep gray matter have demonstrated age related changes during discrete periods of healthy childhood or adulthood, but few studies have included subjects across the lifespan. This study reports both transverse relaxation rate (R2*) and quantitative susceptibility mapping (QSM) of four primary deep gray matter regions (thalamus, putamen, caudate, and globus pallidus) in 498 healthy individuals aged 5–90 years. In the caudate, putamen, and globus pallidus, increases of QSM and R2* were steepest during childhood continuing gradually throughout adulthood, except caudate susceptibility which reached a plateau in the late 30s. The thalamus had a unique profile with steeper changes of R2* (reflecting additive effects of myelin and iron) than QSM during childhood, both reaching a plateau in the mid‐30s to early 40s and decreasing thereafter. There were no hemispheric or sex differences for any region. Notably, both R2* and QSM values showed more inter‐subject variability with increasing age from 5 to 90 years, potentially reflecting a common starting point in iron/myelination during childhood that diverges as a result of lifestyle and genetic factors that accumulate with age.
Squeezing flow of Casson hybrid nanofluid between parallel plates with a heat source or sink and thermophoretic particle deposition
Authors: Jyothi A. M. , Varun Kumar R. S. , Madhukesh J. K. , Prasannakumara B. C. , Ramesh G. K. 
Published: June 2021

AbstractThe investigations on the flow of non‐Newtonian fluids are becoming one of the major topics in the research field. These liquids have substantial applications in industrial and engineering fields such as drilling rigs, food processing, paint and adhesives, nuclear reactors and cooling systems. On the other hand, hybrid nanofluids play a major role in the heat transfer process. Keeping this in mind, the motion of Casson hybrid nanofluid squeezing flow between two parallel plates with the effect of heat source and thermophoretic particle deposition is examined here. The partial differential equations that govern fluid flow are converted into ordinary differential equations using appropriate similarity variables and those equations are numerically solved using the Runge–Kutta–Fehlberg fourth–fifth‐order method by implementing the shooting scheme. The graphs depict the effects of a number of key parameters on fluid profiles in the absence and presence of the Casson parameter. These graphs show that fluid velocity enhances with the augmentation of the local porosity parameter. Thermal dispersal upsurges for enhancement of heat source/sink parameter and the concentration profile escalates for an upsurge of the thermophoretic parameter. Skin friction enhances with enhancement in the local porosity parameter.
Maternal Socs3 knockdown attenuates postnatal obesity caused by an early life environment of maternal obesity and intrauterine overnutrition in progeny mice
Authors: Zhu Feng , Zhang Dawei , Shen Fangfang , Xu Ke , Huang Xin , Liu Jue , Zhang Jin , Teng Yiqun 
Published: June 2021

AbstractPathological states in the early life environment of mammalian offspring, including maternal obesity and intrauterine overnutrition, can induce obesity and metabolic disorder later in life. Leptin resistance caused by upregulation of Socs3 in the hypothalamus of offspring was believed to be the main mechanism of this effect. In this study, obese mother (OM) and lean mother (LM) models were generated by feeding C57BL/6N female mice a high‐fat diet or standard lean diet, respectively. Additionally, an obese mother with intervention (OMI) model was generated by injecting the high‐fat diet group with Socs3‐shRNA lentivirus during early pregnancy. The offspring of the groups was correspondingly named OM‐F1, LM‐F1, and OMI‐F1, representing progeny mouse models of different early life environments. The offspring were fed a high‐fat diet to test their propensity for obesity. The body weight, food intake and fat accumulation were higher, while glucose intolerance and insulin resistance were worse in the OM‐F1 group than LM‐F1 group. By contrast, the obesity phenotype, hyperphagia and metabolic disorder were alleviated in the OMI‐F1 group compared with the OM‐F1 group. The mechanism was identified that downregulation of hypothalamic SOCS3 resulted in an increased level of p‐STAT3 and p‐JAK2, which ameliorated the leptin resistance and restored the lean expression of appetite regulatory genes (Pomc and Agrp) in hypothalamus of OMI‐F1 group. Taken together, these results indicate that reducing maternal Socs3 expression during pregnancy can attenuate obesity caused by the early life environment in mice, which may inspire therapies that enable obese mothers to bear metabolically healthy children.