bluuebunny/crossref_metadata_2025 huggingface dataset:
Atroposelective Synthesis of Isoriccardin C through a C−H Activated Heck Type Macrocyclization
Authors: Marx Lisa , Lamberty Daniel , Choppin Sabine , Colobert Françoise , Speicher Andreas
Published: January 2021

Macrocyclization is typically the key step in syntheses of cyclophane‐type natural products. Considering compounds with axially chiral biaryl moieties, the control of atroposelectivity is essential for biological activity and is synthetically challenging. Herein we report on atroposelective macrocyclization involving an oxidative Heck type process and enabling the first atropo‐enantiopure synthesis of isoriccardin C. A chiral sulfinyl auxiliary in the ortho‐position of a biaryl axis (still flexible) was used to induce a C−H activated atropodiastereoselective oxidative Heck coupling (>98 % de). The traceless character of the sulfinyl auxiliary enables the introduction of a hydroxy group to give the target molecule with >98 % ee as well.
Is Europe facing an opioid epidemic: What does European monitoring data tell us?
Authors: Seyler Thomas , Giraudon Isabelle , Noor André , Mounteney Jane , Griffiths Paul
Published: January 2021

This paper addresses the question of whether Europe is facing an opioid epidemic and utilizes data from the European monitoring system on opioid use, harms and availability, to help assess the situation. Data sources covering the last decade on overdose deaths, drug treatment entrants and drug‐related emergencies suggest that the health burden associated with opioid use is mostly related to the consumption of heroin – and to a lesser extent diverted opioid substitution treatment medications – and that it is primarily affecting an ageing cohort of vulnerable users, with little evidence of an increase in initiation. While opioid‐related deaths are currently at much lower levels than in the United States, they still represent a large preventable health burden with differences across EU countries. There is also increasing concern related to the high availability of heroin, illicitly produced synthetic opioids and diverted opioid pain medications on the European drugs market. Trends in the latter categories are poorly monitored and we may miss signs of emerging problems. Moreover, the economic recession following the COVID‐19 pandemic has a potential to lead to resurgence in opioid use and harms.

Significance

This paper looks at data from the European monitoring system to address the question of whether Europe is facing an opioid epidemic. It reviews available health and supply side indicators, considering the limitations of each data source. A summary of the available evidence would suggest that while opioid‐related deaths in Europe represent a large preventable health burden with differences across EU countries, Europe as a whole is not facing an opioid crisis of the size and nature seen in the US.
Application of Precipitation‐based and Nanoparticle‐based Techniques for Fabrication of Potentiometric Sensors for Nano Molar Determination of Chitosan and Polyvinyl Pyrrolidone in Pharmaceutical Formulations and Biological Fluids
Authors: Trabik Yossra A. , Al‐Afify Nourhan KH. , El‐Kosasy Amira M. , Magdy N.
Published: January 2021

Chitosan (CH) is one of the most abundant biopolymers with multiple applications. Polyvinyl pyrrolidone (PVP) has specific binding and detoxification properties that are of great interest in health care. Hence, it arises a crucial urge to develop economic sensors to analyze CH and PVP in pharmaceutical formulations and biological samples. Two portable sensors were fabricated using precipitation‐based technique, and nanoparticles‐based technique, for determination of CH and PVP in sensor 1 and 2; respectively. Linear responses of 10−5 to10−7 M and 10−2 to10−7 M at pH 3.6–4.8 and 7.2–8.4, with ideal Nernstian slopes of 60.00 and 59.83 mV /decade, and nanomolar LODs of 94.90 and 81.20 nM were observed for CH and PVP; respectively. The percentage recoveries were 100.40±1.03 and 100.19±0.64 for sensors 1 and 2; respectively. Both sensors were successfully applied in biological fluids without pre‐treatment. Accurate results were obtained using sensor 1, in pure form, pharmaceutical formulations, human plasma, rat liver and rat brain, as well as sensor 2, in pure form, pharmaceutical formulations and urine samples. The results were statistically compared with the reported methods and no significant difference was observed.
Advances of capillary electrophoresis enantioseparations in pharmaceutical analysis (2017–2020)
Authors: Krait Sulaiman , Konjaria Mari‐Luiza , Scriba Gerhard K. E.
Published: January 2021

Capillary electrophoresis is a powerful technique for the analysis of polar chiral compounds and has been widely accepted for analytical enantioseparations of drug compounds in pharmaceuticals and biological media. In addition, many mechanistic studies have been conducted in an attempt to rationalize enantioseparations in combination with spectroscopic and computational techniques. The present review will focus on recent examples of mechanistic aspects and summarize recent applications of stereoselective pharmaceutical and biomedical analysis published between January 2017 and November 2020. Various separation modes including electrokinetic chromatography in combination with several detection modes including laser‐induced fluorescence, mass spectrometry and contactless conductivity detection will be discussed. A general trend also observed in other analytical techniques is the application of quality by design principles in method development and optimization.
Steel frame with aseismic floor: From the viscoelastic decoupler model to the elastic structural response
Authors: Xiang Yang , Koetaka Yuji , Nishira Kohei
Published: January 2021

By installing laminated viscoelastic materials (LVEM) between floor slabs and steel beams, the lateral motions of the floor and the frame are decoupled and the structural seismic response is mitigated. This paper presents a study of the elastic seismic performance of the steel frame with this floor system (hereafter termed the aseismic floor). First, the dynamic model of an LVEM under the combined precompression (vertical) and shear (lateral) is checked by experiment. The dynamic shearing behavior of the precompressed LVEM could be well simulated by the pure‐shear model (without precompression) using the modified shear area‐to‐thickness ratio. The storage modulus and the loss factor of the precompressed LVEM could be deemed the same as those without precompression. Second, the time‐varying dynamic properties of LVEM during the seismic response history are processed. In the processing, the transient frequency of LVEM is assumed to be equal to the fundamental frequency of the accordant conventional frame, and the dynamic property of the structure equipped with the aseismic floor is assumed stable throughout the response history. The accuracy of the processing is validated via numerical analyses. Third, based on the processed structural dynamic properties, the effectiveness of a complex Complete‐Quadratic‐Combination (CQC) method for predicting the peak structural seismic response is checked. The CQC method is recalibrated to account for the deviation between the pseudo‐ and relative velocities of the modal oscillators. The recalibrated CQC method could well predict the interstory drift of the frame and the shear deformation of the LVEM.
A method for calculating loss of shale gas during coring based on forward modeling
Authors: He Junbo , Tang Jiren , Lu Zhaohui , Wang Lei , Zhou Jiankun , Tang Bowen
Published: January 2021

The loss of shale gas from conventional wells during coring directly affects the accuracy of measurement of shale gas content and the efficient development and utilization of shale gas. The existing methods to determine shale gas loss are not sufficiently accurate. This study used the forward modeling approach with consideration of the main influencing factors [FM (a, b)] to accurately calculate the volume of shale gas loss. Simulations of shale gas loss were run in an independently developed indoor experimental platform. A comparative analysis with established fitting methods showed that shale gas mainly exists in either a free state or an adsorbed state, and a pressure differential between the interior and exterior of the core is the primary cause of shale gas loss during coring. The FM (a, b) model simulations of shale gas loss showed reductions in average error of 16.77% and 4.6% compared to that of the improved US Bureau of Mines Method (USBM) and the curve fitting method, respectively. This study established a novel, highly accurate and widely applicable method of calculating the volume of lost shale gas.
Experimental investigation of the morphodynamic response of riffles and pools to unsteady flow and increased sediment supply
Authors: Morgan Jacob A. , Nelson Peter A.
Published: January 2021

Gravel‐bed rivers characteristically exhibit shallow riffles in wide sections and deeper pools where the channel becomes constricted and narrow. While rivers can adjust to changing flow and sediment supply through some combination of adjustments of channel slope, bed‐surface sorting, and channel shape, the degree to which riffle‐pools may adopt these changes in response to changing flows and sediment supplies remains unclear. This article presents results from a flume experiment investigating how constant‐ and variable‐width channels adjust their morphology in response to changing flow and increased sediment supply. Two flume geometries were used: (1) constant‐width and (2) variable‐width, characterized by a sinusoidal pattern with a mean width equal to that of the first channel. The variable‐width channel developed bed undulations in phase with the width, representing riffle‐pools. The experiment consisted of three phases for each flume geometry: (1) steady flow, constant sediment supply; (2) unsteady flow, constant sediment supply; and (3) unsteady flow, doubled sediment supply. Unsteady flow was implemented in the form of repeated symmetrical stepped hydrographs, with a mean discharge equal to that in the steady flow phase. In all phases the bed and sediment supply were composed of a sand/gravel mixture ranging from 1 to 8 mm. In both the straight and variable‐width channels, transitioning from steady flow to repeated hydrographs did not result in significant changes in bed morphology. The two channel geometries had different responses to increased sediment supply: the slope of the straight channel increased nearly 40%, while the variable‐width channel reduced the relief between bars and pools and decreased the variability in cross‐sectional elevation with a slight slope increase. Bar‐pool relief varied with repeat discharge hydrographs. Pool elevation changed twice the distance of bar elevations, emphasizing the relevance of pool scour for riffle‐pool self‐maintenance in channels with width variations.
Enhancing physical layer security via a UAV friendly jammer for NOMA‐based IoT systems with imperfect CSI
Authors: Chen Yang , Zhang Zhongpei , Li Binrui
Published: January 2021

In this article, we investigate physical layer security in downlink Internet of Things networks under imperfect channel state information (CSI), in which a controller (Alice) intends to serve two user devices (D1 and D2) simultaneously by using nonorthogonal multiple access (NOMA). Cooperative jamming (CJ) is introduced as a powerful solution for guaranteeing secure transmission. To be specific, we integrate an unmanned aerial vehicle (UAV) jammer that generates artificial noise to confuse multiple noncolluding eavesdroppers (Eves). Considering only D1 requires secure transmission, we develop an adaptive power allocation scheme to maximize the secrecy rate at D1 while meeting the desired quality of service (QoS) threshold at D2. Furthermore, a strategy can be utilized to obtain the optimal location of the UAV jammer is derived for further performance enhancement. Besides, we also examine the impact of the channel uncertainties on system performance. Numerical results are provided to confirm the superiority and applicability of the proposed CJ scheme over benchmark schemes in terms of secrecy performance and effective energy efficiency.
Scenario planning as a strategy process to foster supply chain adaptability: theoretical framework and longitudinal case
Authors: Phadnis Shardul Sharad , Darkow Inga‐Lena
Published: January 2021

Despite the decades long use of scenario planning to formulate corporate strategies, its application for making long‐term decisions in operational settings is limited. We present a theoretical model explaining how scenario planning can help address an important and intractable issue in operations and supply chain management (OSCM): supply chain adaptability. The OSCM literature describes what type of flexibility enables supply chain adaptability, but remains largely silent on how the right flexibility is embedded and enacted in supply chains. Building on the attention‐based view, we outline the antecedents and deterrents of supply chain adaptability. We theorize how “excessive focus on operational exploitation” and “operations‐focused cognition” deter supply chain adaptability, and how scenario planning serves as a strategy process to overcome the deterrents. We illustrate the theoretical model with a longitudinal industry–academia collaborative field study that used scenario planning to formulate, implement, and adapt a chemical company's supply chain strategy over 7 years in Asia's dynamic and unpredictable business environment. We hope that this study at the intersection of foresight studies and OSCM encourages scholarly collaboration between these two largely disparate communities, and provides a foundation for future research amid the growing importance of managing supply chains in unpredictable business environments.
Assessing liquidity‐adjusted risk forecasts
Authors: Berger Theo , Uffmann Christina
Published: January 2021

In this paper, we provide a thorough study on the relevance of liquidity‐adjusted value‐at‐risk (LVaR) and expected shortfall (LES) forecasts. We measure additional liquidity of an asset via the difference between its respective bid and ask prices and we assess the non‐normality of bid–ask spreads, especially in turbulent market times. The empirical assessment comprises German stocks in both calm and turmoil market times, and our results provide evidence that liquidity risk turns out to be crucial for the quality of regulatory risk assessment in turmoil market times. We find that a Cornish–Fisher approximation describes a sensible choice for LVaR forecasts whereas an extreme value approach results in adequate LES forecasts.
Do local and global factors impact the emerging markets' sovereign yield curves? Evidence from a data‐rich environment
Authors: Cepni Oguzhan , Guney Ibrahim Ethem , Kucuksarac Doruk , Hasan Yilmaz M.
Published: January 2021

This paper investigates the relation between yield curve and macroeconomic factors for 10 emerging sovereign bond markets using the sample from January 2006 to April 2019. To this end, the diffusion indices obtained under four categories (global variables, inflation, domestic financial variables, and economic activity) are incorporated by estimating dynamic panel data regressions together with the yield curve factors. Besides, in order to capture dynamic interaction between yield curve and macroeconomic/financial factors, a panel vector autoregressive (VAR) analysis based on the system generalized method of moments (GMM) approach is utilized. Empirical results suggest that the level factor responds to shocks originated from inflation, domestic financial variables, and global variables. Furthermore, the slope factor is affected by shocks in global variables, and the curvature factor appears to be influenced by domestic financial variables. We also show that macroeconomic/financial factors captures significant predictive information over yield curve factors by running individual country factor‐augmented predictive regressions and variable selection algorithms such ridge regression, least absolute shrinkage operator (LASSO), and Elastic Net. Our findings have important implications for policymakers and fund managers by explaining the underlying forces of movements in the yield curve and forecasting accurately dynamics of yield curve factors.
Providing new formulation for white compound chocolate based on mixture of soy flour, sesame paste, and emulsifier: An optimization study using response surface methodology
Authors: Hosseini Abdul Fateh , Mazaheri‐Tehrani Mostafa , Yeganehzad Samira , Razavi Seyed Mohammad Ali
Published: January 2021

This study was aimed at evaluating the suitability of sesame paste as an ingredient in white compound chocolate using response surface methodology. A D‐optimal combined mixture‐process design with three mixture components, sesame paste (15%–30% w/w), soy flour (0%–15% w/w), and milk powder (0%–15% w/w) under variable amount of emulsifier was used to optimize textural (hardness, cohesiveness, and adhesive force) and thermal (Tonset and Tm) properties of white compound chocolate containing sesame paste. The results showed that the linear effect of all the mixture components was significant (p < .05) on the responses. Applying a desirability function method, the optimum proportion of mixture components, and emulsifier level were as follows: sesame paste 15.5% w/w, milk powder 7.5% w/w, soy four 7% w/w, and emulsifier 0% w/w, respectively. At optimum point, hardness, cohesiveness, adhesive force, Tonset, and Tm were 367.07 (N), 0.63, 8.46 (N), 28.1 (°C), and 33.7 (°C), respectively. The predicted values were confirmed through validation experiment.
Comprehensive Genomic Investigation of Coevolution of mcr genes in Escherichia coli Strains via Nanopore Sequencing
Authors: Li Ruichao , Du Pengcheng , Zhang Pei , Li Yan , Yang Xiaorong , Wang Zhiqiang , Wang Juan , Bai Li
Published: January 2021

Horizontal gene transfer facilitates the spread of antibiotic resistance genes, which constitutes a global challenge. However, the evolutionary trajectory of the mobile colistin resistome in bacteria is largely unknown. To investigate the coevolution and fitness cost of the colistin resistance genes in wild strains, different assays to uncover the genomic dynamics of mcr‐1 and mcr‐3 in bacterial populations are utilized. Escherichia coli strains harboring both mcr‐1 and mcr‐3.1/3.5 are isolated and mcr genes are associated with diverse mobile elements. Under exposure to colistin, the mcr‐1‐bearing resistome is stably inherited during bacterial replication, but mcr‐3 is prone to be eliminated in populations of certain strains. In the absence of colistin, the persistence rates of the mcr‐1 and mcr‐3‐bearing subclones varies depending on the genomic background. The decay of the mcr‐bearing bacterial populations can be mediated by the elimination of mcr‐containing segments, large genomic deletions, and plasmid loss. Mobile elements, including plasmids and transposons, are double‐edged swords in the evolution of the resistome. The findings support the idea that antibiotic overuse accounts for global spread of multidrug‐resistant (MDR) bacteria. Therefore, stringent regulation of antibiotic prescription for humans and animals should be performed systematically to alleviate the threat of MDR bacteria.
Relative sea‐level changes along the Fethiye coast (SW Turkey) based on recent archaeological data
Authors: Kızıldağ Nilhan , Özdaş Harun
Published: January 2021

We investigated three coastal archaeological sites along the coast of Fethiye (south‐western Turkey, eastern Mediterranean) to reveal relative sea‐level changes that have occurred since early Byzantine times. Focusing on this little known period, the most recent archaeological data are presented here, providing new data for the history of sea‐level changes. Current elevations of submerged archaeological remains relative to present sea level were measured, and relative sea‐level change was determined, based on an approximation of the original elevation. The contemporary archaeological structures revealed three different sea levels in adjacent areas. Taking into account the time of the last use of the structures, instead of their time of construction, we suggest a relative sea‐level rise at a minimum rate of 1.6 ± 0.3 mm/year for Şövalye Island, 2.1 ± 0.3 mm/year for Gemiler Island, and 2.2 ± 0.6 mm/year for Ölüdeniz Lagoon for the last 1400 years. A comparison of the study results and geoarchaeological data from nearby sites on the western coasts of Fethiye Gulf revealed the degree of sea‐level change impact upon coastal archaeological sites. Results demonstrate that the seismically active Fethiye coast has been strongly influenced by the vertical tectonic movement since early Byzantine times.
Hydrothermal evolution and ore genesis of the Jiamante Au deposit in Western Tianshan, Xinjiang, China: Evidence from the geology, fluid inclusions, and C–H–O–S–Pb isotopes
Authors: Zheng Shao‐Hua , Gu Xue‐Xiang , Peng Yi‐Wei , Zhang Yong‐Mei , Wang Xin‐Li , Wang Guan‐Nan
Published: January 2021

The Jiamante Au deposit is one of the important deposits in the Axi ore cluster of the Western Tianshan, Xinjiang. The orebodies occurring mainly as quartz‐sulphide veins are hosted in Late Devonian volcanoclastic rocks and granitic porphyries, and structurally controlled by a group of NNW‐ and NNE‐ trending extensional faults and volcanic breccias. Primary metallic minerals are chalcopyrite, galena, pyrite, sphalerite, and native gold, with minor amounts of bismuthinite and bismuth. Nonmetallic minerals are dominated by quartz, sericite, chlorite, and calcite. Medium to low temperature hydrothermal alterations are well developed and characterized by silicification, beresitization, phyllic alteration, and chloritization. Two hydrothermal stages were identified: (a) the main‐ore quartz‐sulphide stage; and (b) the post‐ore quartz‐calcite stage. Microthermometric measurements indicate that the primary biphase liquid‐rich aqueous fluid inclusions within quartz of the main‐ore stage homogenize at temperatures (Th) of 176 to 251°C and have salinities of 2.1 to 7.4 wt% NaCleqv. A lower range of homogenization temperatures (169 to 212°C) and salinities (1.6 to 5.2 wt% NaCleqv) were obtained in calcite of the post‐ore stage. The fluid characteristics of moderate to low temperatures and salinities imply that the ore‐forming process occurred in an epithermal environment. In addition, there is a positive relationship between Th and salinities consistent with the fluid mixing trend. Together with H–O isotopic data (δDH2O = −118 to −97‰ and δ18OH2O = −5.5 to −1.6‰) and fluid characteristics, it is suggested that the ore‐forming fluids were a mixture of magmatic and meteoric waters. The δ13C values for CO2 in the hydrothermal fluids range from −3.2 to −2.7‰, and the sulphides have δ34S values of −5.2 to 2.9‰ with relatively uniform Pb isotopic compositions (206Pb/204Pb = 18.228 to 18.287, 207Pb/204Pb = 15.574 to 15.617, and 208Pb/204Pb = 38.151 to 38.251), indicating that the ore‐forming materials were magmatic sources that were derived directly from magmatic fluids and/or leached from volcanic‐subvolcanic rocks by hydrothermal fluids. Combined with the evidence from the mineralization and alteration, fluid inclusions, and C–H–O–S–Pb isotopes suggest that the Jiamante deposit is an intermediate‐sulphidation epithermal Au deposit. A combination of fluid mixing and fluid–rock interactions is inferred as the important factors causing ore deposition. According to the close spatial and temporal relationship between intermediate‐epithermal deposits and porphyry deposits, it is further suggested that porphyry‐type mineralization should have a good potential at the deep sites of the Jiamante deposit and its vicinity.
The effect of conscientiousness on procrastination: The interaction between the self‐control and motivation neural pathways
Authors: Gao Kanxin , Zhang Rong , Xu Ting , Zhou Fan , Feng Tingyong
Published: January 2021

Procrastination is a prevalent and universal problematic behavior, largely impairing individual's health, wealth and well‐being. Substantial studies have confirmed that conscientiousness, one of the big five personality, showed markedly inverse relation with procrastination. However, it is hitherto unknown about the neural basis underlying the impact of conscientiousness on procrastination. To address this issue, we employed the voxel‐based morphometry (VBM) and resting‐state functional connectivity (RSFC) methods to explore the neural substrates of conscientiousness responsible for procrastination (N = 330). In line with previous findings, the behavioral results showed a strong negative correlation between conscientiousness and procrastination (r = −.75). The VBM analysis found that conscientiousness was positively correlated with gray matter (GM) volumes in the left dorsal‐lateral prefrontal cortex (dlPFC), right orbital frontal cortex (OFC) and right putamen, but negatively correlated with that in the left insula. Moreover, the RSFC results revealed that both dlPFC‐IPL (inferior parietal lobule) and dlPFC‐PCC (posterior cingulate gyrus) functional connectivity were positively associated with conscientiousness, while the functional connectivity of parahippocampal gyrus (PHC)‐putamen and insula‐IPL were negatively associated with conscientiousness. More importantly, the structural equation modeling (SEM) integrating RSFC results were well fitted for the influence process of conscientiousness on procrastination by both self‐control (i.e., dlPFC‐IPL, dlPFC‐PCC) and motivation pathways (i.e., PHC‐putamen, insula‐IPL). The current findings suggest that self‐control and motivation could be the two neural pathways underlying the impact of conscientiousness on procrastination, which provides a new perspective to understand the relationship between conscientiousness and procrastination.
What is the best method for prevention of postparotidectomy Frey syndrome? Network meta‐analysis
Authors: Mashrah Mubarak Ahmed , Aldhohrah Taghrid , Abdelrehem Ahmed , Koraitim Mohamed , Wang Liping
Published: January 2021

Background

Prevention of Frey syndrome (FS) after parotidectomy using an interposition barrier has long been gaining a wide popularity; however, there is no clear evidence regarding which preventive technique is more effective. The aim of this network meta‐analysis (NMA) is to answer the question: What is the best method for prevention of FS after parotidectomy?

Methods

A comprehensive search of the PubMed, Embase, SCOPUS, and Cochrane library was conducted to identify the eligible studies. The outcome was the incidence of subjective Frey syndrome (SFS) and objective Frey syndrome (OFS). The Bayesian NMA accompanied with a random effects model and 95% credible intervals (CrIs) were calculated using GeMTC R package.

Results

Thirty‐four studies (n = 2987 patients) with five interventions, namely Alloderm (ADM), temporoparietal fascia (TPF), sternocleidomastoid muscle (SCM), superficial musculoaponeurotic system (SMAS), and free fat graft (FFG), were compared together and with no interposition barrier (NB). The results of NMA showed a statistically significant reduction in both SFS and OFS when ADM, TPF, SMAS, FFG, and SCM were compared with NB. No statistical differences were observed when comparing ADM, SCM, SMAS, FFG, and TPF. TPF ranked the best of all treatments (59.4%) and was associated with the least incidence of SFS; whereas ADM ranked the best of all treatments (61.1%) and was associated with the least incidence of OFS.

Conclusions

All interventions (TPF flap, ADM, FFG, SMAS, and SCM) were associated with a significant reduction in the incidence of FS when compared with NB. TPF and ADM showed the best outcome with the least incidence of SFS and OFS, respectively.
Laryngeal soft tissue sarcoma: Systematic review and individual patient data analysis of 300 cases
Authors: Ramdulari Anjali V. , Izzuddeen Yousra , Benson Rony , Mallick Supriya , Venkatesulu Bhanuprasad , Giridhar Prashanth
Published: January 2021

Background

Laryngeal sarcoma is rare. We performed a systematic review and individual patient analysis to evaluate the patterns of care, prognostic factors, and role of radiotherapy in laryngeal soft tissue sarcoma.

Methods

A systematic search on PubMed and Google scholar was done. An individual patient data analysis was done.

Results

Of the 300 cases of laryngeal sarcoma, 80% underwent surgery. 44% underwent larynx preservation surgery and 25% received radiotherapy with surgery. Median progression free survival (PFS) was 48 months and overall survival (OS) of 224 months for the entire cohort. Patients with large primary, cartilage invasion, and positive margins had numerically worse PFS. Cartilage invasion and primary tumor size >3 cm were the most common risk factors for adjuvant radiation therapy. Patients receiving radiotherapy were not associated with better survival.

Conclusion

Laryngeal sarcoma associated with a good survival. Larynx preservation surgery is feasible in nearly half patients. Adjuvant radiotherapy may be warranted in patients poor prognostic factors.
Dynamic Transcriptional and Epigenetic Changes Drive Cellular Plasticity in the Liver
Authors: Merrell Allyson J. , Peng Tao , Li Jinyang , Sun Kathryn , Li Bin , Katsuda Takeshi , Grompe Markus , Tan Kai , Stanger Ben Z.
Published: January 2021

Background and Aims

Following liver injury, a fraction of hepatocytes adopt features of biliary epithelial cells (BECs) in a process known as biliary reprogramming. The aim of this study was to elucidate the molecular events accompanying this dramatic shift in cellular identity.

Approach and Results

We applied the techniques of bulk RNA‐sequencing (RNA‐seq), single‐cell RNA‐seq, and assay for transposase‐accessible chromatin with high‐throughput sequencing to define the epigenetic and transcriptional changes associated with biliary reprogramming. In addition, we examined the role of TGF‐β signaling by profiling cells undergoing reprogramming in mice with hepatocyte‐specific deletion in the downstream TGF‐β signaling component mothers against decapentaplegic homolog 4 (Smad4). Biliary reprogramming followed a stereotyped pattern of altered gene expression consisting of robust induction of biliary genes and weaker repression of hepatocyte genes. These changes in gene expression were accompanied by corresponding modifications at the chromatin level. Although some reprogrammed cells had molecular features of “fully differentiated” BECs, most lacked some biliary characteristics and retained some hepatocyte characteristics. Surprisingly, single‐cell analysis of Smad4 mutant mice revealed a dramatic increase in reprogramming.

Conclusion

Hepatocytes undergo widespread chromatin and transcriptional changes during biliary reprogramming, resulting in epigenetic and gene expression profiles that are similar to, but distinct from, native BECs. Reprogramming involves a progressive accumulation of biliary molecular features without discrete intermediates. Paradoxically, canonical TGF‐β signaling through Smad4 appears to constrain biliary reprogramming, indicating that TGF‐β can either promote or inhibit biliary differentiation depending on which downstream components of the pathway are engaged. This work has implications for the formation of BECs and bile ducts in the adult liver.
Impact of COVID‐19 on health and safety in the construction sector
Authors: Stiles Shelly , Golightly David , Ryan Brendan
Published: January 2021

Construction has been significantly affected by COVID‐19 yet is critical to the post‐COVID economic recovery. Specifically, construction needs to be constantly aware of safety and risk balanced with timely project delivery. Guidance for COVID‐19 must therefore be implemented in a way that reflects working practice and pressures. There is, however, a potential knowledge gap regarding the practical feasibility and impact of applying COVID‐19 measures within construction, made more difficult by factors such as the temporary nature of projects and complex working arrangements. This article presents a commentary on safe construction during, and beyond, COVID‐19, covering the human factors challenges and practicalities of implementing COVID‐19 measures. We observe that while guidance is strong on risk management, understanding of how best to implement this guidance is not yet stable. Also, care must be taken that implementing guidance does not detract from general safety, which is also challenged by increased pressures on delivery arising from COVID‐19. There may, however, be opportunities for safer working practice arising from new awareness of health, hygiene, and safety risk. The role of safety leadership is overlooked in guidance yet is vital to ensure safe application of COVID‐19 working practices. The key message is that COVID‐19 needs to be integrated and promoted within a general risk management approach, in part because this takes account of differing priorities regarding safety risks, rather than overly focussing on COVID‐19, and also because the effectiveness of COVID‐19 mitigations can be amplified by integration with pre‐existing safety processes.
Multiple characteristics of three‐dimensional radiative Cross fluid with velocity slip and inclined magnetic field over a stretching sheet
Authors: Wahab Hafiz Abdul , Hussain Shah Syed Zahir , Ayub Assad , Sabir Zulqurnain , Bilal Muhammad , Altamirano Gilder Cieza
Published: January 2021

This article focuses on the three‐dimensional Cross fluid flow of a radiative nanofluid over an expanding sheet with aligned magnetic field, chemical reaction, and heat generation phenomenon. The stretching sheet has convective heat and slip boundary conditions. The similarity variables are properly used for the conversion of a dimensional mathematical model into a nondimensional one. The transformed ordinary differential equations are handled for the numerical outcomes of the suggested fluidic model by incorporating the shooting scheme. Furthermore, the numeric investigations are also compared by bvp4c MATLAB built‐in package. In a limited case, both the techniques are checked with already published articles, thereby revealing good agreement. Furthermore, the effects of few parameters like Prandtl number, Weissenberg number, heat generation, stretching rate parameter, magnetic parameter, thermal radiation, Brownian and thermophoresis parameters, and Lewis number on concentration, temperature, and velocity profiles have been presented using figures and numerical tables. The strong intensity of the magnetic field across the fluid and increment in the inclination angle (ϑ) result in a lower velocity profile. Temperature is more prominent for the higher slip mechanism. Furthermore, there in an increase in thermophoretic force, which pushes the nanoparticles, and this mixing of nanoparticles helps to increase the concentration profile. A higher Cross fluid index responds to a larger velocity.
Multislip and Soret–Dufour influence on nonlinear convection flow of MHD dissipative Casson fluid over a slendering stretching sheet with generalized heat flux phenomenon
Authors: Akolade Mojeed T. , Idowu Amos. S. , Adeosun Adeshina T.
Published: January 2021

In the present investigation, Soret–Dufour and multislip's impact on magnetohydrodynamics (MHD) Casson fluid flow encompassing variable thermophysical features in the nonlinear convection process is analyzed. It is believed that to any effective heat and mass transfer enhancement, the relaxation of such fluid and material time along with the thermo‐physical features, are well estimated. In this model, a magnetic field of nonuniform strength is applied perpendicular to the slendering sheet with variable thickness, and nonlinear convection flow is considered in this generalized heat flux examination. An appropriate similarity variable is implemented on the governing equations embedding the variable viscosity, thermal conductivity, and generalized Fourier's law to drive ordinary differential equations. Galerkin weighted residual approach is utilized to calculate the flow field among other flow characteristics. The novel flow features are discussed therein. Modified Fourier and multislip's parameters are seen to have downsized the velocity and temperature field greatly. Thermal and solutal buoyancy effects are more pronounced in nonlinear form compared to the linear model. Dufour number influences both velocity and energy fields positively but negates the concentration field, while the Soret number gives an opposing characterization.
Phosphorus retention in constructed wetlands enhanced by zeolite‐ and clinopyroxene‐dominated lava sand
Authors: Alewell Christine , Huang Jen‐How , McLaren Timothy I. , Huber Lea , Bünemann Else K.
Published: January 2021

Constructed wetlands (CWs) are engineered systems for treating wastewater by sequestering nutrients and contaminants. Our aim was to assess the main phosphorus (P) binding states in operating CWs to assess P saturation and indications on P recycling potential of filter materials, which might be necessary under future peak P scenarios. The investigated vertical flow CWs (operation time up to 16 years) are based on either fluviatile (Fluv) sand or zeolite‐ (Ze‐LS) and clinopyroxene (Cl‐LS)‐dominated lava sand. Organic and inorganic P accumulated in all CWs independent of filter materials and showed a considerable increase with operation time. Concentrations of P decreased sharply with depth in the Fluv‐CWs compared to only a slight decrease in the lava sand CWs, with P concentrations of deeper horizons approximating the relatively P enriched original lava sand substrates. Orthophosphate was the dominant pool in all CWs, while the sum of organic fractions ranged between 11% and 33%. Sequential extraction indicated that P was mainly associated with Fe and Al (hydr)oxides for Fluv‐CWs and Ze‐LS‐CWs, while Ca and Mg bound mineral phosphates dominated in Cl‐LS‐CWs. Oxalate extractions pointed to a clear dominance of P fractions associated with poorly crystalline Fe‐ and Al‐(oxy)hydroxides. Solution 31P NMR analyses revealed that inositol hexakisphosphates were a major pool of organic P in surface layers of CWs, which increased with operation time. With a maximum of 0.5% P content, filter sands do not appear to be a suitable fertilizer for direct application to agricultural fields. The dominance of inorganic, poorly crystalline P species point to potentially high desorption capacity which might be investigated further, to assess recycling potential of P or usage of filter materials as soil amendments with relatively high plant available P. The latter might become feasible and economically attractive under future P scarcity. Simultaneously, P saturation indexes (DPS) did not indicate an imminent P saturation of filters, since P accumulation was not restricted by binding to Al and Fe minerals.
Nitrate removal processes in the riverbed during a single‐peak flood event
Authors: Jiang Qihao , Jin Guangqiu , Tang Hongwu , Xu Junzeng , Wei Qi , Li Ling
Published: January 2021

The effect of the interplay between unsteady flow and bedform in a flood event on nitrogen cycling in the hyporheic zone (HZ) remains poorly understood. In this study, a reactive transport groundwater model with different flood hydrographs was proposed to investigate the effect of modified hyporheic flow on nitrate dynamics in the HZ, including nitrate source‐sink function, response to the single‐peak flood event and removal efficiency. The results demonstrate that there exists an optimal range of river channel gradients that could enhance the biogeochemical reactions (respiration, nitrification and denitrification) in a flood event. The HZ acts as a nitrate sink especially after the flood event, and its source‐sink function is independent of the unsteady discharge/stage conditions. The nitrate in the HZ has a hysteretic response to peak stage/discharge, and its removal efficiency is decreased by up to 70% compared to steady flow conditions. These findings not only provide a better understanding of nitrogen dynamics under the effect of unsteady channel flow, but also can be applied for river restoration to efficiently remove nitrate in the HZ by modifying river channel gradients.
The impact of a 1‐hour time interval between pazopanib and subsequent intake of gastric acid suppressants on pazopanib exposure
Authors: Krens Stefanie D. , Lubberman Floor J. E. , van Egmond Marthe , Jansman Frank G. A. , Burger David M. , Hamberg Paul , Vervenne Walter L. , Gelderblom Hans , van der Graaf Winette T. A. , Desar Ingrid M. E. , van Herpen Carla M. L. , van Erp Nielka P.
Published: January 2021

Co‐treatment with gastric acid suppressants (GAS) in patients taking anticancer drugs that exhibit pH‐dependant absorption may lead to decreased drug exposure and may hamper drug efficacy. In our study, we investigated whether a 1‐hour time interval between subsequent intake of pazopanib and GAS could mitigate this negative effect on drug exposure. We performed an observational study in which we collected the first steady‐state pazopanib trough concentration (Cmin) levels from patients treated with pazopanib 800 mg once daily (OD) taken fasted or pazopanib 600 mg OD taken with food. All patients were advised to take GAS 1 hour after pazopanib. Patients were grouped based on the use of GAS and the geometric (GM) Cmin levels were compared between groups for each dose regimen. Additionally, the percentage of patients with exposure below the target threshold of 20.5 mg/L and the effect of the type of PPI was explored. The GM Cmin levels were lower in GAS users vs non‐GAS users for both the 800 and 600 mg cohorts (23.7 mg/L [95% confidence interval [CI]: 21.1‐26.7] vs 28.2 mg/L [95% CI: 25.9‐30.5], P = .015 and 26.0 mg/L [95% CI: 22.4‐30.3] vs 33.5 mg/L [95% CI: 30.3‐37.1], P = .006). Subtherapeutic exposure was more prevalent in GAS users vs non‐GAS users (33.3% vs 19.5% and 29.6% vs 14%). Sub‐analysis showed lower GM pazopanib Cmin in patients who received omeprazole, while minimal difference was observed in those receiving pantoprazole compared to non‐users. Our research showed that a 1‐hour time interval between intake of pazopanib and GAS did not mitigate the negative effect of GAS on pazopanib exposure and may hamper pazopanib efficacy.
Bank lending margins in a negative interest rate environment
Authors: Boungou Whelsy , Mawusi Charles
Published: January 2021

Following the 2008 Global Financial Crisis, the central banks of many advanced economies resorted to unconventional monetary policies including, the adoption of a negative interest rate policy, aimed at spurring economic recovery and growth. The effectiveness of this policy remains an ongoing debate and largely limited to theoretical assertions. Using a dataset of 9,638 banks from 41 countries over the period 2009–2018, and a Difference‐in‐Differences estimator, this paper examines whether the adoption of a negative interest rate policy has any effect on bank lending margins. We find that bank margins have contracted in countries where negative rates have been implemented. Our results suggest that, in a negative interest rate environment, the rate on loans declines faster than the rate on retail deposits. Moreover, we show that the effects of negative interest rate policy (NIRP) on bank lending margins were stronger for smaller, less capitalized, deposit‐dependent banks. Finally, our findings indicate that banks reliant on retail deposits increased lending in response to NIRP.
Prediction of adverse neonatal outcome among newborns born through meconium‐stained amniotic fluid
Authors: Levin Gabriel , Tsur Abraham , Shai Daniel , Cahan Tal , Shapira Moran , Meyer Raanan
Published: January 2021

Objective

To study maternal and intrapartum factors associated with adverse neonatal outcome in deliveries complicated by meconium‐stained amniotic fluid (MSAF).

Methods

A retrospective cohort study of all women with singleton gestations undergoing trial of labor with MSAF during 2011–2020. Deliveries with adverse neonatal outcome were compared with deliveries without.

Results

Overall, 11 329 were included; 376 (3.3%) neonates were diagnosed with adverse neonatal outcomes. Multivariable regression analysis underlined the following factors as independently associated with composite adverse neonatal outcome: pregestational diabetes (odds ratio [OR] 3.21, 95% confidence interval [CI] 1.09–9.43, P = 0.031), polyhydramnios (OR 2.14, 95% CI 1.33–3.44, P = 0.002), fever (OR 2.52, 95% CI 1.67–3.80, P < 0.001), and amnioinfusion (OR 1.73, 95% CI 1.24–2.2438, P = 0.003). When 0, 1, 2, and 3 of the independent risk factors identified were present, the rates of adverse neonatal outcome were 2.9%, 5.5%, 10.0%, and 100%, respectively.

Conclusion

The current study's results suggest that special attention should be payed to deliveries complicated by MSAF and with any of the following factors—polyhydramnios, intrapartum fever, amnioinfusion, and pregestational diabetes.
Pregnancy‐related venous thromboembolism and HIV infection
Authors: Schapkaitz Elise , Libhaber Elena , Rhemtula Haroun , Gerber Annika , Jacobson Barry F. , Chauke Lawrence , Büller Harry R.
Published: January 2021

Objective

To assess risk factors for venous thromboembolism (VTE) in African women in order to guide thromboprophylaxis.

Methods

A case‐control study was performed at a specialist obstetric unit in South Africa from July 1, 2017 to June 30, 2020. We identified 128 cases with VTE and 640 controls, matched for gestation.

Results

Prepartum risk factors associated with VTE included; medical comorbidities (odds ratios [OR] 5.32, 95% confidence intervals [CI] 1.82–15.56), human immunodeficiency virus (HIV) (OR 2.84, 95% CI 1.50–5.41), and hospital admission or immobility (OR 5.33, 95% CI 1.17–24.22). Postpartum, the following were identified as significant risk factors; medical comorbidities (OR 23.72, 95% CI 8.75–64.27), hospital admission or immobility (OR 13.18, 95% CI 5.04–34.49), systemic infection (OR 4.48, 95% CI 1.28–15.68), HIV (OR 3.20, 95% CI 1.49–6.87), pre‐eclampsia and fetal growth restriction (OR 2.74, 95% CI 1.18–6.36), and postpartum hemorrhage (OR 4.38, 95% CI 1.75–10.97). Antiretroviral therapy, opportunistic infections, and viral load >50 copies/ml, however, were not associated with VTE risk among HIV‐infected participants.

Conclusion

HIV was a significant risk factor for pregnancy‐related thrombosis. This was independent of traditional HIV risk factors. As such, future studies are recommended to explore the mechanisms of thrombosis associated with HIV infection.
Identifying the relation between feedback preferences and performance
Authors: Bacotti Janelle K. , Grauerholz‐Fisher Emma , Morris Samuel L. , Vollmer Timothy R.
Published: January 2021

Performance feedback is a common organizational behavior management intervention (Gravina et al., 2018) that typically yields consistent effects when combined with other procedures (Alvero et al., 2001). A noteworthy characteristic that might affect feedback effectiveness is timing (Lechermeier & Fassnacht, 2018). Given the frequent use and practical utility of feedback, we assessed feedback preference across three feedback timing options: after step, after trial, and after session. We used a direct‐choice paradigm to assess feedback timing preferences with undergraduate students completing two multistep computerized tasks. The data obtained suggest that most participants shifted their preference from relatively proximal (e.g., after step) to distal feedback (e.g., after session) as they acquired the tasks. A few participants' preferences varied despite increases in performance. We discuss implications based on the current findings and future directions for research.