bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacokinetics, safety, and activity of trabectedin as first‐line treatment in elderly patients who are affected by advanced sarcoma and are unfit to receive standard chemotherapy: A phase 2 study (TR1US study) from the Italian Sarcoma Group
Authors: Grosso Federica , D’Ambrosio Lorenzo , Zucchetti Massimo , Ibrahim Toni , Tamberi Stefano , Matteo Cristina , Rulli Eliana , Comandini Danila , Palmerini Emanuela , Baldi Giacomo Giulio , DeCensi Andrea , Bergaglio Marina , Marra Domenico , Marchesi Emanuela , Siri Giacomo , D’Incalci Maurizio , Grignani Giovanni 
Published: August 2020

BackgroundAlthough elderly patients (≥70 years) represent 30% of new diagnoses of soft tissue sarcoma (STS), they are underrepresented in clinical trials and are often unfit to receive standard anthracycline‐based chemotherapy. Trabectedin is registered as a second‐line treatment for advanced STS and is characterized by a favorable safety profile.MethodsThe aim of this single‐arm, phase 2 study was to investigate trabectedin (scheduled dose, 1.3‐1.5 mg/m2) as a first‐line treatment in elderly patients with advanced stage STS who are inoperable and are unfit to receive standard anthracycline‐based chemotherapy. The coprimary endpoints were progression‐free survival at 3 months (PFS3) and the rate of clinically limiting toxicities (CLTs). We also conducted an ancillary study on pharmacokinetics.ResultsTwenty‐four patients (12 men and 12 women) with a median age of 79 years (interquartile range [IQR], 74‐83 years) were enrolled. The histological subtype was leiomyosarcoma in 46%, liposarcoma in 33%, and other histotypes in 21%. The median number of trabectedin courses was 4 (IQR, 3‐6), with 7 patients (29%) receiving ≥6 cycles. Eight patients (33%) required dose reductions. The most frequent grade 3/4 adverse events were neutropenia in 9 patients (38%), fatigue in 5 patients (21%), and aminotransferase elevation in 5 patients (21%). PFS3, median PFS, and overall survival were 71% (80% CI, 57%‐81%), 4 months, and 12 months, respectively. Ten patients (42% [80% CI, 28%‐57%]) experienced CLTs. Trabectedin Cmax, half‐life, clearance, and distribution volume were 1.28 ng/mL (standard deviation [SD], 0.58 ng/mL), 26.70 hours (SD, 9.09 hours), 39.98 L/h/m2 (SD, 14.08 L/h/m2), and 1460 L/m2 (SD, 561 L/m2), respectively.ConclusionTrabectedin can be administered safely to elderly patients with STS who are unfit to receive anthracyclines. Pharmacokinetics in the elderly population was superimposable to historical data.
Trustworthy blockchain‐based medical Internet of thing for minimal invasive surgery training simulator
Authors: Tai Yonghang , Wang Yinjia , Wang Zhifeng , Li Feiyan , Wei Lei , Pan Lei , Zhang Jun , Shi Junsheng 
Published: August 2020

SummaryRealistic modeling of mechanical behavior of soft tissue has been recognized as an essential part for medical Internet of thing for minimal invasive surgery (MIS) training simulator. Therefore, the blockchain‐based constitutive model is crucial for mechanical response of soft tissue modeling. In this article, based on the Ogden second order model, a novel hyperplastic model was presented to describe the stress‐stretch relationship in the MIS training system. To validate this theoretical model, two experimental techniques (uniaxial compression and uniaxial tensile) were conducted to obtain data related to stress‐strain in the blockchain system, which plays an important role in investigating the mechanical behavior of soft tissue. Our results show that the new model has a satisfied coincidence of the experimental data than other existing models. Furthermore, the viscoelastic properties of soft tissue were investigated and a viscoelastic model based on three‐parameter was utilized to interpret the viscoelastic behavior of the soft tissue. The contributions of this article include several biomechanical tests that were performed to investigate the soft tissue hyperelastic and viscoelastic properties in the MIS system, and theoretical guidance for simulating soft tissue mechanical behavior in the blockchain‐based simulation system.
Centerband‐Only Detection of Exchange NMR with Natural‐Abundance Correction Reveals an Expanded Unit Cell in Phenylalanine Crystals
Authors: Xue Kai , Dervisoglu Riza , Sowa Heidrun , Andreas Loren B. 
Published: August 2020

AbstractThe front cover artwork is provided by Dr. Loren Andreas's solid state NMR group. The image shows phenylalanine crystals and NMR data performed at low temperature that reveals the expanded unit cell. Read the full text of the Communication at 10.1002/cphc.202000517.
A Deep‐Red to Near Infrared (NIR) Fluorescent Probe Based on a Sulfur‐Modified Rhodamine Derivative with Two Spirolactone Rings
Authors: Tian Xinyu , Liu Huawei , Wei Fangfang , Wang Xiangchuan , Zhao Shunan , Liu Chuangjun , Tse Yu Chung , Wong Keith Man‐Chung 
Published: August 2020

AbstractWe report the synthesis, characterization, and photophysical and ion‐binding properties of deep‐red to near‐infrared (NIR) fluorescent rhodamine derivatives, bearing two spirolactone rings and substitution of the oxygen atoms in the xanthene ring with sulfur atoms (1‐S). The diastereoisomeric cis‐ and trans‐forms of the rhodamine derivative were separated and the cis‐form (cis‐1‐S) was structurally characterized by X‐ray crystallography. Upon treatment with Hg2+ ion, cis‐1‐S was converted into the dual spirolactone ring‐opened species, resulting in significant color change and fluorescence enhancement. Substitution of the oxygen atoms with sulfur and extended π‐conjugation across the fused six‐membered rings upon the two rings‐opening processes in the presence of Hg2+ ion led to a significant red‐shift of absorption (623 nm) and fluorescence (706 nm) peaks, compared to the ordinary rhodamine. Furthermore, the intracellular Hg2+‐sensing properties of the cis‐1‐S have been studied by confocal microscopy.
Détente: A Practical Understanding of P values and Bayesian Posterior Probabilities
Authors: Ruberg Stephen J. 
Published: August 2020

Null hypothesis significance testing (NHST) with its benchmark P value < 0.05 has long been a stalwart of scientific reporting and such statistically significant findings have been used to imply scientifically or clinically significant findings. Challenges to this approach have arisen over the past 6 decades, but they have largely been unheeded. There is a growing movement for using Bayesian statistical inference to quantify the probability that a scientific finding is credible. There have been differences of opinion between the frequentist (i.e., NHST) and Bayesian schools of inference, and warnings about the use or misuse of P values have come from both schools of thought spanning many decades. Controversies in this arena have been heightened by the American Statistical Association statement on P values and the further denouncement of the term “statistical significance” by others. My experience has been that many scientists, including many statisticians, do not have a sound conceptual grasp of the fundamental differences in these approaches, thereby creating even greater confusion and acrimony. If we let A represent the observed data, and B represent the hypothesis of interest, then the fundamental distinction between these two approaches can be described as the frequentist approach using the conditional probability pr(A | B) (i.e., the P value), and the Bayesian approach using pr(B | A) (the posterior probability). This paper will further explain the fundamental differences in NHST and Bayesian approaches and demonstrate how they can co‐exist harmoniously to guide clinical trial design and inference.
Complications of hyaluronic fillers
Authors: Hall Mehreen , Glick Brad P. 
Published: August 2020

AbstractBackgroundNonsurgical facial rejuvenation has become increasingly popular between dermatologic and plastic surgery offices. Hyaluronic acid (HA), a naturally produced polysaccharide in the human body is used in the esthetic field to restore facial volume loss. Injectors must have a keen understanding of facial anatomy and the properties behind HA soft‐tissue filler injections to minimize the likelihood of an adverse event. The objective of this article is to outline the complications that arise with HA soft‐tissue filler injectables and provide information on potential agents that can aid in reducing both short and long‐term adverse events.Materials and MethodsPubMed search terms were utilized for this article.ResultsHA adverse events can be classified under early onset versus delayed onset depending when patients and providers first notice signs and symptoms. The early onset complications can be identified as erythema, pain, ecchymosis, nodules, the tyndall effect, and vascular occlusion. Late onset complications can be seen as biofilm and granulomas.ConclusionsThough a plethora of complications can arise from HA filler, many are self‐resolving and do not leave the patient with any long‐term complications. As the arsenal of soft‐tissue injectables continues to expand, it is acutely important to understand the various properties of each soft‐tissue filler, its use, and where anatomically it is best suited. Moreover, injectors and providers must have a thorough understanding and ability to conceptualize facial anatomy and understand proper injection technique as well as correct planes of injection. This is the foundation to successful HA injection and patients must be aware of the risks associated with HA facial rejuvenation. Employing an aseptic cleansing technique, proper injection protocol, and early recognition and intervention should an adverse event occur, can decrease the risk of long‐term complications in this patient population.
Bone mineral density spectrum in individuals with type 1 diabetes, latent autoimmune diabetes in adults, and type 2 diabetes
Authors: Hu Yuhang , Li Xia , Yan Xiang , Huang Gan , Dai Ruchun , Zhou Zhiguang 
Published: August 2020

AbstractObjectiveTo assess bone mineral density (BMD) and associated clinical factors in patients with type 1 diabetes (T1D), latent autoimmune diabetes in adults (LADA), and type 2 diabetes (T2D) and in non‐diabetic subjects.MethodsTotal 108 age‐, sex‐, disease duration‐, and postmenopausal ratio‐matched patients with T1D, LADA, and T2D each and 216 age‐, sex‐, and postmenopausal ratio‐matched non‐diabetic controls. Anthropometric, biochemical, and BMD data were collected and analysed.ResultsBMD of total hip and lumbar spine of individuals in the LADA group was lower than those in the T2D and control groups but higher than those in the T1D group. After adjusting for body mass index (BMI), a significant difference in BMD in the lumbar spine was seen between groups. After adjustment for smoking, BMI, 25‐(OH) vitamin D, calcium, haemoglobin A1c, and diabetic complication scores, BMD values of patients in LADA group were not significantly different from those of patients in T1D and T2D groups. Multiple stepwise regression analysis showed that BMD was (a) positively associated with weight and C‐peptide, and negatively associated with age in patients with diabetes, (b) positively associated with C‐peptide in the T1D and LADA groups. The proportion of patients with osteoporosis in the T1D, LADA, T2D, and control groups was 55.6%, 45.4%, 34.3%, and 26.9%, respectively.ConclusionsBMD values in T1D, LADA, and T2D were in an increasing order of mention. Patients with autoimmune diabetes were more susceptible to osteoporosis. A lower C‐peptide level may be responsible for decreased BMD in individuals with autoimmune diabetes.
Forest density intensifies the importance of snowpack to growth in water‐limited pine forests
Authors: Gleason Kelly E. , Bradford John B. , D’Amato Anthony W. , Fraver Shawn , Palik Brian J. , Battaglia Michael A. 
Published: August 2020

AbstractWarming climate and resulting declines in seasonal snowpack have been associated with drought stress and tree mortality in seasonally snow‐covered watersheds worldwide. Meanwhile, increasing forest density has further exacerbated drought stress due to intensified tree–tree competition. Using a uniquely detailed data set of population‐level forest growth (n = 2,495 sampled trees), we examined how inter‐annual variability in growth relates to snow volume across a range of forest densities (e.g., competitive environments) in sites spanning a broad aridity gradient across the United States. Forest growth was positively related to snowpack in water‐limited forests located at low latitude, and this relationship was intensified by forest density. However, forest growth was negatively related to snowpack in a higher latitude more energy‐limited forest, and this relationship did not interact with forest density. Future reductions in snowpack may have contrasting consequences, as growth may respond positively in energy‐limited forests and negatively in water‐limited forests; however, these declines may be mitigated by reducing stand density through forest thinning.
Genetic hitchhiking, mitonuclear coadaptation, and the origins of mt DNA barcode gaps
Authors: Hill Geoffrey E. 
Published: August 2020

AbstractDNA barcoding based on mitochondrial (mt) nucleotide sequences is an enigma. Neutral models of mt evolution predict DNA barcoding cannot work for recently diverged taxa, and yet, mt DNA barcoding accurately delimits species for many bilaterian animals. Meanwhile, mt DNA barcoding often fails for plants and fungi. I propose that because mt gene products must cofunction with nuclear gene products, the evolution of mt genomes is best understood with full consideration of the two environments that impose selective pressure on mt genes: the external environment and the internal genomic environment. Moreover, it is critical to fully consider the potential for adaptive evolution of not just protein products of mt genes but also of mt transfer RNAs and mt ribosomal RNAs. The tight linkage of genes on mt genomes that do not engage in recombination could facilitate selective sweeps whenever there is positive selection on any element in the mt genome, leading to the purging of mt genetic diversity within a population and to the rapid fixation of novel mt DNA sequences. Accordingly, the most important factor determining whether or not mt DNA sequences diagnose species boundaries may be the extent to which the mt chromosomes engage in recombination.
Hydrological and productive impacts of recent land‐use and land‐cover changes in the semiarid Chaco: Understanding novel water excess in water scarce farmlands
Authors: Giménez Raul , Mercau Jorge L. , Bert Federico E. , Kuppel Sylvain , Baldi German , Houspanossian Javier , Magliano Patricio N. , Jobbágy Esteban G. 
Published: August 2020

AbstractOver the last decades, the rapid replacement of native forests by crops and pastures in the Argentinean semiarid Chaco plains has triggered unprecedented groundwater level raises resulting from deep drainage increases, leading to the first massive waterlogging event on records (~25,000 Ha flooded in 2015 near Bandera, one of the most cultivated clusters of the Chaco). In this paper, we link this episode to the ongoing deforestation and cropping scheme shifts through the combined analysis of remote sensing data, agricultural surveys, local farmer information and hydrologic modelling. From 2000 to 2015, the agricultural area of Bandera increased from 21% to 50%, mostly at the expense of dry forests. In this period, agriculture migrated from more intensive (i.e., double‐cropping) to more water‐conservative (i.e., late‐summer single crops) schemes as a general strategy to reduce drought risks. These changes reduced regional evapotranspiration and increased the intensity of deep drainage in wet years. Contrasting cropping schemes displayed significant evapotranspiration differences, but all of them experienced substantial drainage losses (~100–200 mm) during the wettest year (2014/2015), suggesting that cropping adjustments have a limited capacity to halt the generation of water excesses. Nearly 50% of the cropped area in Bandera could not be sown or harvested following the groundwater recharge event of 2014/2015. In the ongoing context of shallow and rising water tables, the introduction of novel cropping schemes that include deep‐rooted perennials, to promote transpirative groundwater discharge, seems crucial to avoid the recurrence of water excesses and their associated dryland salinity risk in the region.
Why administrative leaders take pro‐environmental leadership actions: Evidence from an eco‐compensation programme in China
Authors: Wang Xiaohu , Xiao Hanyu , Chen Kai , Niu Xuejiao 
Published: August 2020

AbstractPro‐environmental leadership behaviours have been examined as the result of institutional forces, though anecdotes suggest the significant role of individual leaders. Little is known about this role in environmental policy implementation, and few empirical studies explore pro‐environmental leadership behaviours in the public sector. In this study, we empirically test a typology of pro‐environmental leadership behaviours and examine administrative leaders' motives for engaging in pro‐environmental behaviours. We then establish the relevance of our findings in environmental policy implementation. We empirically confirm the construct validity of pro‐environmental leadership behaviours that require leaders should articulate a policy vision, change followers' perception, and take symbolic actions. Our findings show that leaders' environmental efforts are largely prompted by legal compliance and motivated by instrumental self‐interest (e.g. increased economic opportunities), and normative values of engaging with broad sustainability issues may also have limited but potentially long‐lasting effects. Moreover, the evidence also suggests the importance of a workplace environment conducive to pro‐environmental leadership behaviours. These findings can be used to develop local strategies that stress policy implementation capacity building to induce pro‐environmental leadership behaviours in China.
Cost‐effectiveness of dapagliflozin as a treatment for heart failure with reduced ejection fraction: a multinational health‐economic analysis of DAPA‐HF
Authors: McEwan Phil , Darlington Oliver , McMurray John J.V. , Jhund Pardeep S. , Docherty Kieran F. , Böhm Michael , Petrie Mark C. , Bergenheim Klas , Qin Lei 
Published: August 2020

AbstractAimTo estimate the cost‐effectiveness of dapagliflozin added to standard therapy, vs. standard therapy only, in patients with heart failure (HF) with reduced ejection fraction (HFrEF), from the perspective of UK, German, and Spanish payers.Methods and resultsA lifetime Markov model was built to estimate outcomes in patients with HFrEF. Health states were defined by Kansas City Cardiomyopathy Questionnaire total symptom score, type 2 diabetes and worsening HF events. The incidence of worsening HF and all‐cause mortality was estimated using negative binomial regression models and parametric survival analysis, respectively. Direct healthcare costs (2019 British pounds/Euro) and patient‐reported outcomes (EQ‐5D) were sourced from the existing literature and the Dapagliflozin And Prevention of Adverse‐outcomes in Heart Failure trial (DAPA‐HF), respectively; the median duration of follow‐up in DAPA‐HF was 18.2 months (range: 0–27.8). Future costs and effects were discounted at 3.0% for the Spanish and German analyses and 3.5% for the UK analysis. In the UK setting, treatment with dapagliflozin was estimated to increase life‐years and quality‐adjusted life‐years (QALYs) from 5.62 to 6.20 (+0.58) and 4.13 to 4.61 (+0.48), respectively, and reduce lifetime hospitalizations for HF (925 and 820 events per 1000 patients for placebo and dapagliflozin, respectively). Similar results were obtained for Germany and Spain. The incremental cost‐effectiveness ratios were £5822, €5379 and €9406/QALY in the UK, Germany and Spain, respectively. In probabilistic sensitivity analyses, more than 90% of simulations were cost‐effective at a willingness‐to‐pay threshold of £20 000/QALY in UK and €20 000/QALY in Germany and Spain.ConclusionDapagliflozin is likely to be a cost‐effective treatment for HFrEF in the UK, German and Spanish healthcare systems.
Electrocatalysis of Methanol on the Platinum‐Gold Bimetallic Microstructures Codeposited with Silicate Sol‐gel on Indium Tin Oxide Electrode
Authors: Praveen Raju , Ramaraj Ramasamy 
Published: August 2020

AbstractA facile one‐step electrochemical codeposition of platinum‐gold (PtAu) alloy materials embedded in N‐[3‐(trimethoxysilyl)propyl] ethylenediamine (EDAS) silicate sol‐gel on indium‐tin‐oxide electrode (ITO/EDAS‐PtAu) is reported. The x‐ray diffraction patterns, X‐ray photoelectron spectroscopy analysis, scanning electron microscopy, energy dispersive X‐ray analysis, elemental mapping, line scan spectra and cyclic voltammetric studies showed the formation of PtAu bimetallic microstructures at the ITO/EDAS‐PtAu electrodes. The electrochemically codeposited PtAu alloy microstructures materials showed profound enhancement for methanol oxidation reaction in alkaline medium. The observed results revealed that the present facile synthetic methodology for the preparation of PtAu alloy microstructures materials embedded in silicate sol‐gel (ITO/EDAS‐PtAu) modified electrode is a promising approach and the modified electrode showed enhanced mass activity and stability towards methanol oxidation reaction.
Study on self‐assembly of colloidal particles at high ionic strength with stimulated emission depletion microscopy
Authors: Neupane Bhanu B. , Zhong Yaning , Wang Gufeng 
Published: August 2020

AbstractUnderstanding the spatial organization of nano‐ and micro‐sized particle is very important in the fabrication of complex structures having unprecedented properties. Study on self‐assembly of submicroscopic colloidal particles at high ionic strength solution at single particle resolution can provide new insight into the nanoscale interactions. In this study, we studied the self assembly behavior of negatively charged 0.2 and 1 μm colloidal particles at high ionic strength on glass‐solution interface that is, in situ environment. The self‐assembled 0.2 μm particles could not be resolved with conventional confocal and epi‐fluorescent microscopy, so a home‐built continuous wave stimulated emission depletion (STED) microscope was used for the study. We found that particles self‐assemble into ordered and disordered structures at higher and lower ionic strength solution, respectively. The optical imaging methods allowed us to measure inter‐particle gap at second energy minimum directly. Interestingly, we found that the inter‐particle gap in the wet self‐assembly higher than the classical Derjaguin, Landau, Verwey, and Overbeek (DLVO) theory predicted. The in situ investigation of particle self‐assembly at high ionic strength will provide more insight for the understanding nanoscale interactions.