bluuebunny/crossref_metadata_2025_split huggingface dataset:
An immune relevant signature for predicting prognoses and immunotherapeutic responses in patients with muscle‐invasive bladder cancer (MIBC)
Authors: Jiang Wen , Zhu Dandan , Wang Chenghe , Zhu Yu 
Published: February 2020

AbstractImmune checkpoint inhibitors (ICIs) are novel treatments that significantly improve the survival time of MIBC patients, but immunotherapeutic responses are different among MIBC patients. Therefore, it is urgent to find predictive biomarkers that can accurately identify MIBC patients who are sensitive to ICIs. In this study, we computed the relative abundances of 24 immune cells based on the expression profiles of MIBC patients using single‐sample gene set enrichment analysis (ssGSEA). Unsupervised clustering analysis of the 24 immune cells was performed to classify MIBC patients into different immune‐infiltrating groups. Genome (gene mutation and copy number variation), transcriptome (mRNA, lncRNA, and miRNA), and functional enrichment were found to be heterogeneous among different immune‐infiltrating groups. We identified 282 differentially expressed genes (DEGs) associated with immune infiltration by comparing the expression profiles of patients with different immune infiltration profiles, and 20 core prognostic DEGs were identified by univariate Cox regression analysis. An immune‐relevant gene signature (TIM signature) consisting of nine key prognostic DEGs (CCDC80, CD3D, CIITA, FN1, GBP4, GNLY, SPINK1, UBD, and VIM) was constructed using least absolute shrinkage and selection operator (LASSO) Cox regression analysis. Receiver operating characteristic (ROC) curves and subgroup analysis confirmed that the TIM signature was an ideal biomarker for predicting the prognosis of MIBC patients. Its value in predicting immunotherapeutic responses was also validated in The Cancer Genome Atlas (TCGA) cohort (AUC = 0.69, 95% CI = 0.63‐0.74) and the IMvigor210 cohort (AUC = 0.64, 95% = 0.55‐0.74). The TIM signature demonstrates a powerful ability to distinguish MIBC patients with different prognoses and immunotherapeutic responses, but more prospective studies are needed to assess its reliability in the future.
Characterization of Secondary Metabolites in Flowers of Sanguisorba officinalisL. by HPLC‐DAD‐MSn and GC/MS
Authors: Bunse Marek , Lorenz Peter , Stintzing Florian C. , Kammerer Dietmar R. 
Published: February 2020

AbstractThe investigations reported here focus on an in‐depth characterization of the secondary metabolite profile of Sanguisorba officinalis flowers. For this purpose, fresh flowers were extracted with MeOH/H2O and EtOH/H2O and the resulting crude extracts fractionated using CH2Cl2, AcOEt, and BuOH. Individual compounds were characterized by high performance liquid chromatography and gas chromatography coupled with mass spectrometric detection (HPLC‐DAD‐MSn and GC/MS). MeOH/H2O extraction and LC/MSn investigations revealed the occurrence of flavonoid glycosides (quercetin, kaempferol), ellagitannin glycosides and four anthocyanins. Among the latter, two components, i. e., cyanidin‐malonyl‐glucose and cyanidin‐galloyl‐hexose, have not been reported for S. officinalis so far. Furthermore, phenylethylamine was characterized for the first time in Sanguisorba by pH value dependent extraction with CH2Cl2. In addition, AcOEt and BuOH extracts were analyzed by GC/MS both prior to and after acid hydrolysis of secondary metabolites. For this purpose, the extracts were treated with 1 n HCl solution (105 °C, 1 h) and derivatized with BSTFA. Analyses revealed the occurrence of several classes of phenolic compounds, such as gallic acid, hydroxybenzoic acid, hydroxycinnamic acid and ellagic acid derivatives. Additionally, the most prominent ursane‐type triterpenoid (ziyu‐glycoside I) from Sanguisorba and its corresponding aglycone isomers were detected and assigned based on their characteristic fragmentation patterns.
Contemporary balloon aortic valvuloplasty: Changing indications and refined technique
Authors: Dall'Ara Gianni , Tumscitz Carlo , Grotti Simone , Santarelli Andrea , Balducelli Marco , Tarantino Fabio , Saia Francesco 
Published: February 2020

AbstractEven if un to improve long‐term prognosis, balloon aortic valvuloplasty (BAV) may be useful in selected patients with symptomatic severe aortic stenosis either as a bridge to surgical or transcatheter valve replacement (aortic valve replacement [AVR] or transcatheter aortic valve implantation [TAVI]) or as a triage strategy for patients with uncertain indications. International guidelines recommend BAV as: a “bridge” to AVR/TAVI, a “trial” in patients with undetermined symptoms, or a “bridge‐to‐decision” in case of comorbidities. However, in clinical practice, BAV is also used as a palliative measure to improve hemodynamics and quality of life in many patients who are excluded from AVR/TAVI. Finally, BAV is often performed during TAVI to facilitate prosthesis delivery, optimize frame expansion, or for bioprosthetic valve fracture in selected valve‐in‐valve procedures. Technical innovations, which allow for a mini‐invasive approach via transradial access and pacing delivered through the wire, have led to a decrease in complications over time. This review focuses on contemporary BAV with a specific emphasis on new indications, innovative techniques, and specific complex patient subgroups.
Kinetics of Photoinduced Reactions at the Single‐Molecule Level: The KACB Method
Authors: Kawai Kiyohiko , Maruyama Atsushi 
Published: February 2020

AbstractThe kinetics of photoinduced reactions can be approached by laser flash photolysis techniques. Although such techniques allow for a detailed understanding of the important photophysics of molecules, they normally require a substantial amount of sample for measurements (>1 nmol), and thus, they are difficult to apply to analytical and diagnostic applications. The photophysics of a fluorescent molecule can be accessed by monitoring the kinetics of the fluctuation of fluorescence, which is called blinking. Blinking is a phenomenon that can be monitored only if molecules are observed at the single‐molecule level. In bulk solution, blinking kinetics can be measured by using fluorescence correlation spectroscopy (FCS), which normally requires more than 105 times less sample than that required for laser flash photolysis. Blinking is controlled to extract fruitful microenvironmental information around a fluorescent molecule, by using a method named kinetic analysis based on the control of fluorescence blinking (KACB). This Concept highlights the adaption of the KACB method to investigate the local conformation of DNA with less than 1 pmol of DNA sample.
A Comprehensive Study on Tetraaryltetrabenzoporphyrins
Authors: Ruppel Michael , Lungerich Dominik , Sturm Sabrina , Lippert Rainer , Hampel Frank , Jux Norbert 
Published: February 2020

AbstractInvited for the cover of this issue are the groups of Lungerich and Jux at the Friedrich‐Alexander University Erlangen‐Nuernberg. The image depicts the synthetic feasibility with a “TATBP tuning shop”, which shows the change of the four meso aryl substituents to modify the performance of the molecule. Read the full text of the article at 10.1002/chem.201904718.
Surface‐Deactivated Core–Shell Metal–Organic Framework by Simple Ligand Exchange for Enhanced Size Discrimination in Aerobic Oxidation of Alcohols
Authors: Kim Seongwoo , Lee Jooyeon , Jeoung Sungeun , Moon Hoi Ri , Kim Min 
Published: February 2020

AbstractMetal–organic frameworks (MOFs) are an attractive catalyst support for stable immobilization of the active sites in their scaffold due to the high tunability of organic ligands. The active site‐functionalized ligands can be easily employed to construct MOFs as porous heterogeneous catalysts. However, the existence of active sites on the external surfaces as well as internal pores of MOFs seriously impedes the selective reaction in the pore. Herein, through a simple post‐synthetic ligand exchange (PSE) method we synthesized surface‐deactivated (only core‐active) core–shell‐type MOF catalysts, which contain 2,2,6,6‐tetramethylpiperidin‐1‐yl)oxyl (TEMPO) groups on the ligand as active sites for aerobic oxidation of alcohols. The porous but catalytically inactive shell ensured the size‐selective permeability by sieving effects and induced all reactions to take place in the pores of the catalytically active core. Because PSE is a facile and universal approach, this can be rapidly applied to a variety of MOF‐based catalysts for enhancing reaction selectivity.
Feasibility, safety, and acute efficacy of the fourth‐generation cryoballoon for ablation of atrial fibrillation: Another step forward?
Authors: Rottner Laura , Mathew Shibu , Reissmann Bruno , Warneke Laura , Martin Isabell , Lemes Christine , Maurer Tilman , Wohlmuth Peter , Ouyang Feifan , Kuck Karl‐Heinz , Metzner Andreas , Rillig Andreas 
Published: February 2020

AbstractBackgroundThe second‐generation cryoballoon (CB2) is widely used for pulmonary vein (PV) isolation (PVI) in patients with paroxysmal atrial fibrillation (AF). Recently, the novel fourth‐generation CB (CB‐Advance PRO) was introduced, incorporating a shortened catheter tip.HypothesisThe aim of this study was to evaluate the feasibility and acute efficacy of PVI using the CB‐Advance PRO.MethodsA total of 200 consecutive patients were analyzed. Hundred patients who underwent PVI due to symptomatic, drug‐refractory AF were treated with the CB‐Advance PRO (group I) and were included into this multicenter analysis. A group of 100 patients were treated with the CB2 and acted as controls (group II).ResultsIn total, 739 of 739 PVs (100%) were successfully isolated. There was a nonsignificant trend in the incidence of online registration of PV signals between both groups (group I: 77.9% vs group II: 71.4%, P = .09). Median time to PVI (time to isolation [TTI]) and mean total freezing time were significantly shorter when using the CB‐Advance PRO (group I: 33 [23, 50] vs group II: 40 [26, 60] seconds and group I: 166 ± 29 vs group II: 183 ± 38 seconds, P < .01). In three of 100 (3%) patients of group I and one of 100 (1%) patients of group II, a transient phrenic nerve palsy occurred (P = .62).ConclusionThe use of the novel CB‐Advance PRO is feasible and associated with a significant reduction in mean TTI and mean total freezing time as compared to the CB2.
Base and Covariate Population Pharmacokinetic Analyses of Dupilumab Using Phase 3 Data
Authors: Kovalenko Pavel , Davis John D. , Li Meng , Rippley Ronda , Ardeleanu Marius , Shumel Brad , Graham Neil M.H. , Pirozzi Gianluca , Kamal Mohamed A. , DiCioccio A. Thomas 
Published: February 2020

AbstractPopulation pharmacokinetic base and covariate models were developed to study functional dupilumab for regulatory submissions, using data from healthy volunteers and patients with moderate‐to‐severe atopic dermatitis (AD) receiving intravenous or subcutaneous doses. Sixteen studies were pooled (N = 2115; 202 healthy volunteers, 1913 AD patients). The best model was a 2‐compartment model with linear and Michaelis‐Menten elimination and 3 transit compartments describing absorption. A stepwise approach to model building, with some parameters estimated using mostly rich data and subsequently fixed, was used to avoid adverse effects of sparse data and a steep target‐mediated phase on pharmacokinetic parameters, which require rich sampling for proper estimation. Parameterization of models in terms of rates was a useful alternative to the parameterization in terms of clearances, allowing for a reduced number of covariates while providing accurate predictions. While antidrug antibodies, albumin, race, body mass index, and Eczema Area and Severity Index score were statistically significant covariates, only body weight had a notable effect on central volume, explaining interindividual variability. The model adequately described dupilumab pharmacokinetics in phase 3 trials.
Redesign of enterprise lean production system based on environmental dynamism
Authors: Chen Xiaowu , Jiang Guozhang , Yang Le , Li Gongfa , Xiang Feng 
Published: February 2020

AbstractUnder the background of economic globalization, enterprises face with more severe and uncertain environmental dynamism, and its lean production system redesign strategy is more critical. Firstly, given the dynamic environment that enterprises are facing, the redesign of the lean production system based on the environmental dynamism is proposed. Secondly, environmental dynamism is divided into two dimensions: market dynamics and technology dynamics, which is calculated by the objective method. Thirdly, by establishing the redesigned model of the lean production system based on environmental dynamism, the relationship between environmental dynamism and lean production level is analyzed. Fourth, the data of 251 listed companies from different industries in 2014 to 2017 were analyzed to verify the specific impact of environmental dynamism on the enterprise's lean production level. It was found that the relationship between environmental dynamism and the enterprise lean production level is presented as “U,” “S,” and other more complex relationships. At last, some suggestions are put forward to optimal the redesign of lean production systems under different environmental dynamism.
Charge Transfer and Metastable Ion Dissociation of Multiply Charged Molecular Cations Observed by Using Reflectron Time‐of‐Flight Mass Spectrometry
Authors: Kitashoji Akihiro , Kitagawa Kosei , Fujihara Akimasa , Yatsuhashi Tomoyuki 
Published: February 2020

AbstractA multiply charged molecule expands the range of a mass window and is utilized as a precursor to provide rich sequence coverage; however, reflectron time‐of‐flight mass spectrometer has not been well applied to the product ion analysis of multiply charged precursor ions. Here, we demonstrate that the range of the mass‐to‐charge ratio of measurable product ions is limited in the cases of multiply charged precursor ions. We choose C6F6 as a model molecule to investigate the reactions of multiply charged molecular cations formed in intense femtosecond laser fields. Measurements of the time‐of‐flight spectrum of C6F6 by changing the potential applied to the reflectron, combined with simulation of the ion trajectory, can identify the species detected behind the reflectron as the neutral species and/or ions formed by the collisional charge transfer. Moreover, the metastable ion dissociations of doubly and triply charged C6F6 are identified. The detection of product ions in this manner can diminish interference by the precursor ion. Moreover, it does not need precursor ion separation before product ion analysis. These advantages would expand the capability of mass spectrometry to obtain information about metastable ion dissociation of multiply charged species.
Soft winter wheat outyields hard winter wheat in a subhumid environment: Weather drivers, yield plasticity, and rates of yield gain
Authors: Lollato Romulo P. , Roozeboom Kraig , Lingenfelser Jane F. , da Silva Cristiano Lemes , Sassenrath Gretchen 
Published: February 2020

AbstractDespite the proximity in zones of adaptation for soft and hard winter wheat (SWW and HWW; Triticum aestivum L.), agronomic evaluations have been confined to market class. Our objectives were to compare SWW and HWW regarding yield and agronomic attributes; genotype, environment, and their interaction; and rates of yield gain. Yield, grain volume weight, heading date, and plant height were collected from 40 adjacent studies evaluating HWW and SWW cultivars in 20 Kansas environments (n = 2,885). Growing season weather partially explained the variability in yield (47–51%), heading date (58–92%), and plant height (67–80%). Yield was greater in SWW than in HWW (3.73 vs. 3.48 Mg ha−1), and a quadratic relationship between the 10th, mean, and 90th percentile yields suggested that SWW has a greater yield potential than HWW, although grain volume weight was greater in HWW (743 vs. 733 kg m−3). An asymmetric yield response for both classes was associated with greater phenotypic plasticity, which portrayed a more positive response for SWW. We performed a literature review that suggested a greater genetic gain for SWW than for HWW (33 vs. 17 kg ha−1 yr−1). This gain, however, represented a smaller portion of the regional yield gain (considering both genetic gain and adoption of agronomic practices) of each class (72 vs. 81%). We concluded that SWW outyields HWW due to greater rates of genetic gain, partially due to breeding in higher yield environments, and more positive phenotypic plasticity of yield in high‐yielding environments coupled to yield stability in excessively moist environments.
Cultural dimensions, Global Reporting Initiatives commitment, and corporate social responsibility issues: New evidence from Organisation for Economic Co‐operation and Development banks
Authors: Sannino Giuseppe , Lucchese Manuela , Zampone Giovanni , Lombardi Rosa 
Published: February 2020

AbstractThis paper aims to examine the effect of cultural dimensions such as the power distance, individualism, masculinity, uncertainty avoidance, long‐term orientation, and indulgence on the Global Reporting Initiatives (GRI) commitment effect of corporate social responsibility reports by the Organisation for Economic Co‐operation and Development (OECD) banks. Adopting the stakeholder theory and the Hofstede's cultural dimension, we investigated the GRI commitment level and its determinants, using a sample of 819 firm‐year observations from 2012 to 2018 belonging to 27 countries. Thus, we collected data from BvD BankFocus database, selecting 180 OECD banks. Applying a statistical regression analysis, our findings show a significant influence of masculinity, uncertainty avoidance, long‐term orientation, and indulgence on the GRI commitment level in the context of corporate social responsibility. Additionally, our results highlight the effect of cultural dimensions of countries in the application of the GRI guidelines and investigate the reasons for this different commitment effect. Results of this paper are directed to academic community, practitioners, and policymakers as theoretical and practical advances.
Ecosystem responses to channel restoration decline with stream size in urban river networks
Authors: Levi Peter S. , McIntyre Peter B. 
Published: February 2020

AbstractUrban streams are often severely impaired due to channelization, high loads of nutrients and contaminants, and altered land cover in the watershed. Physical restoration of stream channels is widely used to offset the effects of urbanization on streams, with the goal of improving ecosystem structure and function. However, these efforts are rarely guided by strategic analysis of the factors that mediate the responsiveness of stream ecosystems to restoration. Given that ecological gradients from headwater streams to mainstem rivers are ubiquitous, we posited that location within a river network could mediate the benefits of channel restoration. We studied existing stream restorations in Milwaukee, Wisconsin, to determine (1) whether restorations improve ecosystem function (e.g., nutrient uptake, whole‐stream metabolism) and (2) how ecosystem responses vary by position in the urban river network. We quantified a suite of physicochemical and biological metrics in six pairs of contiguous restored and concrete channel reaches, spanning gradients in baseflow discharge (19–196 L/s) and river network position (i.e., headwater to mainstem). Hydrology differed dramatically between the restored and concrete reaches; water velocity was reduced 2‐ to 13‐fold while water residence time was 50–5,000% greater in adjacent restored reaches. Restored reaches had shorter nutrient uptake lengths for ammonium, nitrate, and phosphate, as well as higher whole‐stream metabolism. Furthermore, the majority of reaches were autotrophic (i.e., gross primary production > ecosystem respiration), which is not common in stream ecosystems. The difference in ecosystem functioning between restored and unrestored reaches was generally largest in headwaters and declined to equivalence in mainstem restorations. Our results suggest that headwater sites offer higher return on investment compared to larger downstream channels, where ecosystem responsiveness is low. If this pattern proves to be general, the scaling of ecosystem responses with river size could be integrated into planning guidelines for urban stream restorations to enhance the societal and ecological benefits of these expensive interventions.
Wildflower plantings promote blue orchard bee, Osmia lignaria (Hymenoptera: Megachilidae), reproduction in California almond orchards
Authors: Boyle Natalie K. , Artz Derek R. , Lundin Ola , Ward Kimiora , Picklum Devon , Wardell Gordon I. , Williams Neal M. , Pitts‐Singer Theresa L. 
Published: February 2020

AbstractConcerns over the availability of honeybees (Apis mellifera L.) to meet pollination demands have elicited interest in alternative pollinators to mitigate pressures on the commercial beekeeping industry. The blue orchard bee, Osmia lignaria (Say), is a commercially available native bee that can be employed as a copollinator with, or alternative pollinator to, honeybees in orchards. To date, their successful implementation in agriculture has been limited by poor recovery of bee progeny for use during the next spring. This lack of reproductive success may be tied to an inadequate diversity and abundance of alternative floral resources during the foraging period. Managed, supplementary wildflower plantings may promote O. lignaria reproduction in California almond orchards. Three wildflower plantings were installed and maintained along orchard edges to supplement bee forage. Plantings were seeded with native wildflower species that overlapped with and extended beyond almond bloom. We measured bee visitation to planted wildflowers, bee reproduction, and progeny outcomes across orchard blocks at variable distances from wildflower plantings during 2015 and 2016. Pollen provision composition was also determined to confirm O. lignaria wildflower pollen use. Osmia lignaria were frequently observed visiting wildflower plantings during, and after, almond bloom. Most O. lignaria nesting occurred at orchard edges. The greatest recovery of progeny occurred along the orchard edges having the closest proximity (80 m) to managed wildflower plantings versus edges farther away. After almond bloom, O. lignaria nesting closest to the wildflower plantings collected 72% of their pollen from Phacelia spp., which supplied 96% of the managed floral area. Phacelia spp. pollen collection declined with distance from the plantings, but still reached 17% 800 m into the orchard. This study highlights the importance of landscape context and proximity to supplementary floral resources in promoting the propagation of solitary bees as alternative managed pollinators in commercial agriculture.