bluuebunny/crossref_metadata_2025_split huggingface dataset:
Strategies and Recommendations for Using a Data‐Driven and Risk‐Based Approach in the Selection of First‐in‐Human Starting Dose: An International Consortium for Innovation and Quality in Pharmaceutical Development (IQ) Assessment
Authors: Leach Michael W. , Clarke David O. , Dudal Sherri , Han Chao , Li Chunze , Yang Zheng , Brennan Frank R. , Bailey Wendy J. , Chen Yingxue , Deslandes Antoine , Loberg Lise I. , Mayawala Kapil , Rogge Mark C. , Todd Marque , Chemuturi Nagendra V. 
Published: August 2020

Various approaches to first‐in‐human (FIH) starting dose selection for new molecular entities (NMEs) are designed to minimize risk to trial subjects. One approach uses the minimum anticipated biological effect level (MABEL), which is a conservative method intended to maximize subject safety and designed primarily for NMEs having high perceived safety risks. However, there is concern that the MABEL approach is being inappropriately used for lower risk molecules with negative impacts on drug development and time to patient access. In addition, ambiguity exists in how MABEL is defined and the methods used to determine it. The International Consortium for Innovation and Quality in Pharmaceutical Development convened a working group to understand current use of MABEL and its impact on FIH starting dose selection, and to make recommendations for FIH dose selection going forward. An industry‐wide survey suggested the achieved or estimated maximum tolerated dose, efficacious dose, or recommended phase II dose was > 100‐fold higher than the MABEL‐based starting dose for approximately one third of NMEs, including trials in patients. A decision tree and key risk factor table were developed to provide a consistent, data driven‐based, and risk‐based approach for selecting FIH starting doses.
Refined RGB Strategy for the Synthesis of Polymer‐Based Full Organic Luminescent Nanotubes with Broad Emission Bands
Authors: Petrov Ravil , Loumaigne Matthieu , Barillé Régis , Frère Pierre 
Published: August 2020

AbstractLight‐emitting polymer nanotubes with tailored fluorescence emission bands have been prepared using organic emissive materials based on benzofuran, carbazole, and indolocarbazole scaffolds and investigated with the goal to obtain pure white‐light emission at the nanoscale. The polymer nanostructures were obtained by the anodic aluminium oxide (AAO) template method with PMMA as a transparent polymer matrix and a proficient choice of organic dyes emitting in the blue, green, yellow and red parts of the spectral range. It is demonstrated that combining aqueous dispersions of monochromatic nanotubes is an effective way of generating white light emission due to a simple correlation between the individual color components. Furthermore, it is also possible to target white emission at the nanoscale by adjusting the concentration of the dyes inside single nanotubes in order to obtain optimal color coordinates of ca. 0.3 in the CIE chromaticity diagram.
Hydroxymethylfurfural and its Derivatives: Potential Key Reactants in Adhesives
Authors: Rosenfeld Catherine , Konnerth Johannes , Sailer‐Kronlachner Wilfried , Rosenau Thomas , Potthast Antje , Solt Pia , van Herwijnen Hendrikus W. G. 
Published: August 2020

Abstract5‐Hydroxymethylfurfural (HMF) is a promising bio‐derived platform chemical with a broad scope of application, for example, in the production of solvents, fuels, polymers, or adhesives. The wood and foundry industries are among the largest adhesive users and currently both rely to a large extent on the use of fossil‐based binders, such as by using formaldehyde as a crosslinker in many commercial adhesive systems. The industry is thus looking for suitable alternatives to replace fossil‐based chemicals. HMF and its derivatives are considered to be key renewable reactants in adhesive systems. The core of this Review is the critical evaluation of the potential of HMF and its derivatives in adhesive systems. The technological performance was assessed in the fields of wood‐based materials, sand casting and composites. As an overall conclusion, HMF and its derivatives have a high application potential in alternative adhesives. Clearly, further research is needed to improve the performance and produce economically competitive adhesives.
Nitrogen‐containing flavonoid and their analogs with diverse B‐ring in acetylcholinesterase and butyrylcholinesterase inhibition
Authors: Lu Qiao‐Qiao , Chen Ya‐Ming , Liu Hao‐Ran , Yan Jian‐Ye , Cui Pei‐Wu , Zhang Qian‐Fan , Gao Xiao‐Hui , Feng Xing , Liu Ying‐Zi 
Published: August 2020

AbstractIn this study, a series of new flavones (2‐phenyl‐chromone), 2‐naphthyl chromone, 2‐anthryl‐chromone, or 2‐biphenyl‐chromone derivatives containing 6 or 7‐substituted tertiary amine side chain were designed, synthesized, and evaluated in acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibition. The results indicated that the alteration of aromatic ring connecting to chromone scaffold brings about a significant impact on biological activity. Compared with flavones, the inhibitory activity of 2‐naphthyl chromone, 2‐anthryl‐chromone derivatives against AChE significantly decreased, while that of 2‐biphenyl chromone derivatives with 7‐substituted tertiary amine side chain is better than relative flavones derivatives. For all new synthesized compounds, the position of tertiary amine side chain obviously influenced the activity of inhibiting AChE. The results above provide great worthy information for the further development of new AChE inhibitors. Among the newly synthesized compounds, compound 5a is potent in AChE inhibition (IC50 = 1.29 ± 0.10 μmol/L) with high selectivity for AChE over BChE (selectivity ratio: 27.96). An enzyme kinetic study of compound 5a suggests that it produces a mixed‐type inhibitory effect against AChE.
A three‐dimensional macroelement for modelling the in‐plane and out‐of‐plane response of masonry walls
Authors: Vanin Francesco , Penna Andrea , Beyer Katrin 
Published: August 2020

SummaryThe seismic performance of unreinforced masonry buildings is commonly assessed using equivalent frame modelling. Its computational efficiency allows for a large number of analyses to be conducted, which are often required to account for epistemic and aleatoric uncertainties. To obtain a full description of the building response, in‐plane and out‐of‐plane failure modes need to be considered, though previous elements for equivalent frame models of unreinforced masonry buildings only account for the in‐plane response. This paper presents the formulation of a three‐dimensional macroelement for modelling the dynamic in‐plane and out‐of‐plane behaviour of masonry panels, which extends the approach of a previously developed macroelement to simulate the in‐plane response. The proposed three‐node, three‐dimensional macroelement is implemented in the software OpenSees and describes the main features of the in‐plane and out‐of‐plane behaviour of a masonry wall, including second‐order geometrical effects and a coupled shear/flexural response. It also allows for the use of complex material models. The proposed element is used to simulate experimental results for in‐plane shear‐compression tests and out‐of‐plane free vibration tests of masonry panels. The implemented element, as well as the example models, is openly shared through the repository https://github.com/eesd-epfl/OpenSees/wiki.
Experimental investigation of the suppression effects of ammonium polyphosphate on explosion characteristics of unsaturated polyester resin dust
Authors: Yang Jie , Yu Yuan , Li Yunhao , Zhang Qingwu , Suo Yifan , Li Changxin , Jiang Juncheng 
Published: August 2020

SummaryThe suppression effects of Ammonium Polyphosphate (APP) with different mass fractions on the maximum explosion pressure (Pmax), the explosibility index (Kst), the minimum ignition energy (MIE) and the minimum ignition temperature (MIT) of unsaturated polyester resin (UPR) dust were studied. Results indicated that the explosion severity and the ignition sensitivity of UPR dust decreased gradually when the mass fractions of APP increased. There existed a minimum inerting concentration (MIC), and the explosion of UPR dust could be suppressed completely by 60 wt% APP. Moreover, APP had a great inhibiting effect on the MIE of UPR dust cloud. The calculated MIE of UPR dust cloud increased from 10 mJ to 998 mJ when the mass fractions of APP increased to 30 wt%. Furthermore, the MIT of UPR dust cloud increased with the increase of the mass fractions of APP. When the mass fraction of APP increased to 80 wt%, the MIT increased by 290°C. The suppression mechanism of APP was studied according to thermogravimetry (TG) and differential scanning calorimetry (DSC) tests. Thermal analysis results showed that the addition of APP could increase the thermal stability of UPR. The suppression mechanism was reflected on the consumption of H and OH radicals.
Transplanting fecal material from wild‐type mice fed black raspberries alters the immune system of recipient mice
Authors: Huang Yi‐Wen , Pan Pan , Echeveste Carla Elena , Wang Hsin‐Tzu , Oshima Kiyoko , Lin Chien‐Wei , Yearsley Martha , Xiao Jianbo , Chen Jiebiao , Sun Chongde , Yu Jianhua , Wang Li‐Shu 
Published: August 2020

AbstractBy constantly stimulating intestinal immunity, gut microbes play important regulatory roles, and their possible involvement in human physical and mental disorders beyond intestinal diseases suggests the importance of maintaining homeostasis in the gut microbiota. Both transplantation of fecal microbiota and dietary interventions have been shown to restore microbial homeostasis in recipients. In the current study with wild‐type mice, we combined these two approaches to determine if transplanting fecal material from mice fed black raspberries (BRB, 5%) altered recipients’ immune system. The donors received a control or 5% BRB diet, and fecal transplantation was performed every other day 15 times into recipients fed control diet. Afterward, we used flow cytometry to analyze populations of CD3+ T, CD4+ T, CD8+ T cells, and NK cells among bone marrow cells, splenocytes, and peripheral blood mononuclear cells (PBMCs) collected from the recipients. We found that BRB‐fecal material that contained both fecal microbiota and their metabolites increased NK cell populations among bone marrow cells, splenocytes, and PBMCs, and raised levels of CD8+ T cells in splenocytes. Our findings suggest that fecal transplantation can modulate the immune system and might therefore be valuable for managing a range of physical and mental disorders.
When will China fulfill its carbon‐related intended nationally determined contributions? An in‐depth environmental Kuznets curve analysis
Authors: Meng Ming , Shang Wei , Wang Xinfang , Pang Tingting 
Published: August 2020

AbstractConsidering the enormous amounts of carbon dioxide (CO2) emissions generated in China, the country's fulfillment of its Intended Nationally Determined Contributions (INDCs) is essential in achieving the goal of mitigating global climate change delineated in the Paris Agreement. In order to forecast the future development of China's carbon‐related INDC indicators, this research uses a segmented quadratic equation to fit the relationship between economic level and CO2 emissions and a hybrid trend extrapolation model to forecast the emission‐related indicators. The empirical analysis shows that China's CO2 emission peak appeared in 2018 with an emission amount of 9.36 billion tons. The future CO2 emissions after 2018 will present a fluctuating and slowly decreasing trend. As to the carbon intensity, China will meet the INDC target (lower by 60–65% from the 2005 level) in 2022–2023. At that time, China's CO2 emissions will be 8.43–7.96 billion tons and GDP will reach 109.71–125.39 trillion yuan. Furthermore, the empirical analysis also shows that even if China's carbon intensity target is successfully realized, it will still have considerable potential for further reduction. © 2020 Society of Chemical Industry and John Wiley & Sons, Ltd.
Treatment flows after outsourcing public insurance provision: Evidence from Florida Medicaid
Authors: Munnich Elizabeth L. , Richards Michael R. 
Published: August 2020

AbstractWhile politics can determine what public goods are available, elected officials must decide on the method of allocation. Commonly, governments provide public health insurance directly or pay private parties to administer it on their behalf. Such contracting can leverage private sector expertise but also raises agency concerns. In particular, little is known about how private provision of public health insurance impacts medical decision‐making and treatment flows for low‐income populations. An example comes from the Medicaid program, which has increasingly relied on outside insurers to deliver health services to enrollees. We exploit a large legislative intervention in Florida to show that Medicaid managed care (MMC) organizations generally do not skimp on short‐run treatment delivery in the inpatient setting. In fact, patients with severe and chronic illnesses receive more inpatient services under these contracts, especially in relation to managing care transitions. We also document increased competition in the MMC market following the state's policy intervention.
Dynamic volatility linkages and hedging between commodities and sectoral stock returns in Turkey: Evidence from SVAR‐cDCC‐GARCH model
Authors: Civcir İrfan , Akkoç Uğur 
Published: August 2020

AbstractHigh volatility in international prices of strategic commodities like oil and gold can have negative effects on the macroeconomics of the emerging economies and their stock markets. This study deals with the analysis of the dynamic relationship between oil, gold and sectoral stock returns in Turkey after the global financial crises. Movements of the sectoral stock returns with the international oil and gold returns have been examined by the Structural Vector Autoregression ‐ corrected Generalized Autoregressive Conditional Heteroskedasticity (SVAR‐cDCC‐GARCH) framework. Our results support the presence of time‐varying co‐movement and volatility spillover from gold and oil to Turkish sectoral stock market. The investigation of volatility has shown that shocks are highly persistent in the long run for all sectoral indices. Furthermore, our results indicate that volatility spillover from international commodity to sectoral indices vary significantly. Results imply that Turkey needs dynamic macroeconomic policies to manage the spillover effects of volatility. The results are also valuable to investors in reducing the risk of their portfolios by diversifying and hedging their investment across different sectors.
Why do some merger and acquisitions deals fail? A global perspective
Authors: Attah‐Boakye Rexford , Guney Yilmaz , Hernandez‐Perdomo Elvis , Mun Johnathan 
Published: August 2020

AbstractWe analyse why some merger and acquisitions (M&A) deals are withdrawn paying particular attention to the economic freedom and legal environment of countries. We use a large dataset based on deals worldwide from over 140 countries during the period 1977–2014. Our core finding is that the likelihood of a deal's withdrawal tends to increase if the economic freedom/quality of legal environment of the acquiring (target) firm's country is higher (lower). These core findings matter more for the non‐financial sector, during non‐crisis years, and in developed financial markets. We also report that the deals have higher tendency to be withdrawn if the target firm's size is larger or its profitability is lower; and the acquiring firm's size is smaller. Furthermore, our analyses reveal that deal characteristics (i.e., deal attitude, means of payment, deal size, ownership sought) also matter in affecting the outcome of announced M&A deals.
Contemporaneous linkages: Funding liquidity and stock market spirals
Authors: Mishra Ajay Kumar , Parikh Bhavik , Spahr Ronald W. 
Published: August 2020

AbstractWe observe, especially during financial crisis periods, that central bank policies may trigger credit rationing and borrowing cost increases, resulting in contemporaneous institutional lender and market maker funding illiquidity. In turn, funding illiquidity is transmitted through banks and broker/dealers to market illiquidity of individual stocks. Thus, funding illiquidity, often originating with central bank monetary policy, is contemporaneously conveyed through institutional lenders, transferred to broker/dealers and spawns interconnected stock market illiquidity spirals and loss spirals. Our results are consistent and robust across different models that control for endogenous and exogenous factors.
On the persistence of UK inflation: A long‐range dependence approach
Authors: Caporale Guglielmo Maria , Gil‐Alana Luis Alberiko , Trani Tommaso 
Published: August 2020

AbstractThis paper examines the degree of persistence in UK inflation by applying long‐memory methods to historical data that span the period from 1660 to 2016. Specifically, we use both parametric and non‐parametric fractional integration techniques, that are more general than those based on the classical I(0) vs. I(1) dichotomy. Further, we carry out break tests to detect any shifts in the degree of persistence, and also run rolling‐window and recursive regressions to investigate its evolution over time. On the whole, the evidence suggests that the degree of persistence of UK inflation has been relatively stable following the Bretton Woods period, despite the adoption of different monetary regimes. The estimation of an unobserved‐components stochastic volatility model sheds further light on the issues of interest by showing that post‐Bretton Woods changes in UK inflation are attributable to a fall in the volatility of permanent shocks. The same type of analysis carried out for US inflation, for comparison purposes, leads to broadly similar conclusions.
A latent‐factor‐driven endogenousregime‐switching non‐Gaussianmodel: Evidence from simulation and application
Authors: Bu Ruijun , Cheng Jie , Jawadi Fredj 
Published: August 2020

AbstractRegime‐switching models are widely used in empirical economics and finance research for their ability to identify and account for the impact of latent regimes or states on the behaviour of the interested variables. Meanwhile, empirical evidence often reveals complex non‐Gaussian characteristics in the state‐dependent dynamics. We generalize the latent‐factor‐driven endogenous regime‐switching Gaussian model of Chang, et al.,Journal of Econometrics, 2017,196, 127–143 by allowing the state‐dependent conditional distributions to be non‐Gaussian. Our setup is more general and promises substantially broader relevance and applicability to empirical studies. We provide evidence to justify our generalization by a simulation study and a real data application. Our simulation results confirm that when the state‐dependent dynamics are misspecified, the bias of model parameter estimates, the power of the likelihood ratio test against endogenous regime changes, and the quality of the extracted latent factor all deteriorate quite considerably. In addition, our application to the S&P 500 index return data reveals strong evidence in favour of our non‐Gaussian assumption, and the superiority of our model specification delivers an important risk management implication.
Successful treatment of recurrent small cell carcinoma of urinary bladder with pembrolizumab
Authors: Hatayama Tomoya , Hayashi Tetsutaro , Matsuzaki Shinji , Masumoto Hiroshi , Yanai Hiroyuki , Abdi Hamidreza , Teishima Jun , Hasegawa Yasuhisa 
Published: August 2020

IntroductionSmall cell carcinoma of urinary bladder is rare and has an aggressive malignant behavior and poor prognosis. Advanced bladder cancers are treated with immune checkpoint inhibitors, however, its efficacy for small cell carcinoma of urinary bladder is unclear.Case presentationA 54‐year‐old female, diagnosed with clinical stage T2N0M0 small cell carcinoma of urinary bladder, underwent radical cystectomy after three cycles of etoposide‐cisplatin neoadjuvant chemotherapy. Despite the fact that pathological examination revealed no residual carcinoma in bladder in her cystectomy specimen, local recurrence of a 60‐mm mass detected in the follow‐up investigation 7.5 months later. This was completely treated by pembrolizumab without any adverse effects. Immunohistochemical staining revealed that the tumor had no programmed death ligand 1 expression but it showed CD8‐positive T‐lymphocyte infiltration into the tumor.ConclusionImmune checkpoint inhibitors might have curative potentials for treatment of small cell carcinoma of urinary bladder.
Lung-Specific Risk Factors Associated With Incident Hip Fracture in Current and Former Smokers
Authors: Bon Jessica , Nouraie Seyed Mehdi , Smith Kenneth J , Dransfield Mark T , McDonald Merry-Lynn , Hoffman Eric A , Newell John D , Comellas Alejandro P , Saha Punam K , Bowler Russell P , Regan Elizabeth A 
Published: August 2020

ABSTRACT
Hip fractures are associated with significant morbidity and mortality in smokers with lung disease, but whether lung-specific factors are associated with fracture risk is unknown. Our goal was to determine whether lung-specific factors associate with incident hip fracture and improve risk discrimination of traditional fracture risk models in smokers. The analysis consisted of a convenience sample of 9187 current and former smokers (58,477 participant follow-up years) participating in the Genetic Epidemiology of chronic obstructive pulmonary disease (COPD) longitudinal observational cohort study. Participants were enrolled between 2008 and 2011 with follow-up data collection through July 2018. Traditional risk factors associated with incident hip fracture (n = 361) included age, female sex, osteoporosis, prevalent spine and hip fracture, rheumatoid arthritis, and diabetes. Lung-specific risk factors included post-bronchodilator percent forced expiratory volume in 1 s (FEV1%) predicted (OR, 0.95; 95% CI, 0.92–0.99 for each 10% increase), Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification (OR, 1.09; 95% CI, 1.002–1.19 for each higher stage), presence of CT-determined emphysema (OR, 1.34; 95% CI, 1.06–1.69), symptom scores (OR, 1.10; 95% CI, 1.03–1.19 for each higher unit score), 6-min walk distance (OR, 0.92; 95% CI, 0.90–0.95 for each 30-m increase), body mass index, airflow obstruction, dyspnea, and exercise (BODE) index (OR, 1.07; 95% CI, 1.01–1.13 for each higher unit score), total exacerbations (OR, 1.13; 95% CI, 1.10–1.16 per exacerbation), and annual exacerbations (OR, 1.37; 95% CI, 1.21–1.55 per exacerbation). In multivariable modeling, age, black race, osteoporosis, prevalent hip and spine fracture, rheumatoid arthritis, and diabetes were associated with incident hip fracture. The presence of emphysema, 6-min walk distance, and total number of exacerbations added to traditional models improved risk discrimination (integrated discrimination improvement [IDI] values 0.001 [95% CI, 0.0003–0.002], 0.001 [95% CI, 0.0001–0.002], and 0.008 [95% CI, 0.003–0.013], corresponding to relative IDIs of 12.8%, 6.3%, and 34.6%, respectively). These findings suggest that the incorporation of lung-specific risk factors into fracture risk assessment tools may more accurately predict fracture risk in smokers. © 2020 American Society for Bone and Mineral Research.