bluuebunny/crossref_metadata_2025 huggingface dataset:
How achievable are COVID-19 clinical trial recruitment targets? A UK observational cohort study and trials registry analysis
Authors: Cunniffe Nick G , Gunter Simon J , Brown Michael , Burge Sarah W , Coyle Clare , De Soyza Anthony , Dymond Tom , Esmail Hanif , Francis Darrel P , Galloway Jacqui , Galloway James B , Gkrania-Klotsas Effrossyni , Greenaway Jane , Katritsis George , Kanagaratnam Prapa , Knolle Martin D , Leonard Kelly , McIntyre Zoe C , Prudon Ben , Rampling Tommy , Torok Mili Estee , Warne Ben , Yates Mark , Matheson Nicholas J , Su Li , Villar Sofia , Stewart Grant D , Toshner Mark
Published: October 2020

Objectives

To analyse enrolment to interventional trials during the first wave of the COVID-19 pandemic in England and describe the barriers to successful recruitment in the circumstance of a further wave or future pandemics.

Design

We analysed registered interventional COVID-19 trial data and concurrently did a prospective observational study of hospitalised patients with COVID-19 who were being assessed for eligibility to one of the RECOVERY, C19-ACS or SIMPLE trials.

Setting

Interventional COVID-19 trial data were analysed from the clinicaltrials.gov and International Standard Randomized Controlled Trial Number databases on 12 July 2020. The patient cohort was taken from five centres in a respiratory National Institute for Health Research network. Population and modelling data were taken from published reports from the UK government and Medical Research Council Biostatistics Unit.

Participants

2082 consecutive admitted patients with laboratory-confirmed SARS-CoV-2 infection from 27 March 2020 were included.

Main outcome measures

Proportions enrolled, and reasons for exclusion from the aforementioned trials. Comparisons of trial recruitment targets with estimated feasible recruitment numbers.

Results

Analysis of trial registration data for COVID-19 treatment studies enrolling in England showed that by 12 July 2020, 29 142 participants were needed. In the observational study, 430 (20.7%) proceeded to randomisation. 82 (3.9%) declined participation, 699 (33.6%) were excluded on clinical grounds, 363 (17.4%) were medically fit for discharge and 153 (7.3%) were receiving palliative care. With 111 037 people hospitalised with COVID-19 in England by 12 July 2020, we determine that 22 985 people were potentially suitable for trial enrolment. We estimate a UK hospitalisation rate of 2.38%, and that another 1.25 million infections would be required to meet recruitment targets of ongoing trials.

Conclusions

Feasible recruitment rates, study design and proliferation of trials can limit the number, and size, that will successfully complete recruitment. We consider that fewer, more appropriately designed trials, prioritising cooperation between centres would maximise productivity in a further wave.
Intestinal current measurement and nasal potential difference to make a diagnosis of cases with inconclusiveCFTRgenetics and sweat test
Authors: Minso Rebecca , Schulz Angela , Dopfer Christian , Alfeis Nadine , Barneveld Andrea van , Makartian-Gyulumyan Lena , Hansen Gesine , Junge Sibylle , Müller Carsten , Ringshausen Felix C C , Sauer-Heilborn Annette , Stanke Frauke , Stolpe Cornelia , Tamm Stephanie , Welte Tobias , Dittrich Anna-Maria , Tümmler Burkhard
Published: October 2020

Background

Nasal potential difference (NPD) and intestinal current measurements (ICM) are cystic fibrosis transmembrane conductance regulator (CFTR) biomarkers recommended to make a diagnosis in individuals with inconclusive sweat test andCFTRgenetics and a clinical suspicion for cystic fibrosis (CF) or CFTR-related disorder (CFTR-RD).

Methods

NPD and ICM were measured according to standard operating procedures of the European Cystic Fibrosis Society Diagnostic Network Working Group.

Results

We assessed 219 individuals by NPD or ICM who had been referred to our laboratory due to clinical symptoms suggestive of CF, but inconclusive sweat test andCFTRgenetics (median age: 16.3 years, range 0.4 to 76 years). CF or CFTR-related disorder was diagnosed in 22 of 29 patients (76%) with aCFTRgenotype of unknown or variable clinical significance and in 51 of 190 carriers (27%) of one (35/42) or no (16/148) identifiedCFTRmutation. If twoCFTRsequence variants had been identified, the outcome of NPD and ICM was consistent with the classification of the CFTR2 database. Moreover, a suspected false-positive diagnosis of CF was confirmed in seven and withdrawn in eight patients. Of 26 individuals assessed by both NPD and ICM, eleven individuals exhibited discordant tracings of ICM and NPD, with one measurement being in the CF range and the other in the normal range.

Conclusion

The majority of patients whom we diagnosed with CF or CFTR-RD by extended electrophysiology are carriers of the wild-typeCFTRcoding sequence on at least one of their CF alleles. The disease-causing genetic lesions should reside in the non-coding region ofCFTRor elsewhere in the genome, affecting the regulation of CFTR expression in a tissue-depending fashion which may explain the large within-group variability of CFTR activity in the respiratory and intestinal epithelium seen in this group.
Expression of YAP1 and pSTAT3-S727 and their prognostic value in glioma
Authors: Sang Wei , Xue Jing , Su Li-Ping , Gulinar Abulajiang , Wang Qian , Zhai Yang-Yang , Hu Yan-Ran , Gao Hai-Xia , Li Xinxia , Li Qiao-Xing , Zhang Wei
Published: October 2020

Aims

A growing research demonstrated that YAP1 played important roles in gliomagenesis. We explored the expression of YAP1 and STAT3, the relationship between them and the effect of YAP1, STAT3 on prognosis in glioma.

Methods

Expression of YAP1, p-YAP1, STAT3, pSTAT3-S727 and pSTAT3-Y705 in 141 cases of low-grade gliomas (LGG) and 74 cases of high-grade gliomas (HGG) of surgical specimens were measured by immunohistochemistry. Pearson’s X2test was used to determine the correlation between immunohistochemical expressions and clinicopathological parameters. Pearson’s or Spearman correlation test was used to determine the association between these proteins expression. Survival analysis was used to investigate the effect of these proteins on prognosis.

Results

High expressions of YAP1, STAT3, pSTAT3-S727 and pSTAT3-Y705 were found in HGG compared with LGG (p=0.000). High expressions of YAP1, STAT3, pSTAT3-S727 and pSTAT3-Y705 were found in 63.5%, 59.5%, 66.2% and 31.1% cases of HGG, respectively. YAP1 expression was associated to tumour location, Ki-67 and P53, STAT3 expression was related with Ki-67 and P53, and the expression of pSTAT3-S727 was associated with Ki-67. There was a significantly positive correlation between YAP1 and pSTAT3-S727 (p<0.0001; r=0.5663). Survival analysis revealed that patients with YAP1 and pSTAT3-S727 coexpression had worse overall survival (OS) and progression-free survival (PFS) (p<0.0001). Tumour grade, age, Ki-67 and YAP1 expression were independent prognostic factors for OS. In LGG group, both YAP1 and pSTAT3-S727 expressions were negative correlation with IDH1 mutation, YAP1 and pSTAT3-S727 coexpression showed worse OS and PFS of glioma patients.

Conclusion

Our research showed that YAP1 and STAT3 were significantly activated in HGG compared with LGG. YAP1 significantly correlated with pSTAT3-S727 in glioma, YAP1 and pSTAT3-S727 coexpression may serve as a reliable prognostic biomarker and therapeutic target for glioma.
Idylla microsatellite instability assay versus mismatch repair immunohistochemistry: a retrospective comparison in gastric adenocarcinoma
Authors: Farmkiss Luke , Hopkins Ilona , Jones Mary
Published: October 2020

Up to 22% of all gastric adenocarcinomas are of the microsatellite instability (MSI) subtype. This subtype may not benefit from conventional adjuvant chemotherapy but does respond to novel immunotherapies. A proportion of MSI gastric adenocarcinomas are associated with inherited disease, inferring an opportunity to screen for further cancers in the patient while also identifying at-risk relatives. Although the importance of MSI subtyping is clear, the methods of detection vary. The main techniques are MSI testing and mismatch repair (MMR) immunohistochemistry (IHC). This study compares a novel Idylla (Biocartis) MSI assay to MMR IHC across 50 biopsies of gastric adenocarcinoma. The methods were concordant across 48 cases. The two discrepant results demonstrated known difficulties in the interpretation of IHC. Idylla MSI testing presents several advantages over MMR IHC but both methods are well established in detecting this subtype of gastric adenocarcinoma. The methods are best regarded as complementary tests, performing most optimally when combined.
Campylobacteriosis following immunosuppression for immune checkpoint inhibitor-related toxicity
Authors: Lee Karla A , Shaw Heather , Bataille Véronique , Nathan Paul
Published: October 2020

Five patients receiving checkpoint inhibitor immunotherapy (CPI) under our care across two cancer centers over a 12-month period have subsequently developed campylobacterosis. All had received immune-suppressive treatment for CPI-related colitis in the weeks or months preceding the detection ofCampylobacterinfection, with negative stool cultures at presentation of CPI-related colitis. The immune-suppression required to treat CPI-related toxicity may lead to an increased risk of enteric infection within the gut. While the underlying immune and biologic mechanisms are not well understood, perturbation of the gut microbiota is an increasingly recognized factor capable of influencing CPI-mediated immune reconstitution and response to therapy. Clinicians should be aware that worsening of colitic symptoms in patients with a history of treatment for CPI-related colitis may be due to enteric infection, and not simply a relapse/deterioration of a previously treated CPI-related colitis. Judicious infectious disease evaluation is necessary for patients receiving CPIs as symptoms can mimic immune-related adverse events (irAEs). Furthermore, the benefits of immune-suppressive therapy for the treatment of presumptive irAEs must be weighed against the possible increased risk for either enteric infection or opportunistic infection. Prospective studies are required to investigate microbiome perturbations, resulting from immune-suppression, and guide future treatment of this patient cohort.
Effect of cyclo-oxygenase inhibitor use during checkpoint blockade immunotherapy in patients with metastatic melanoma and non-small cell lung cancer
Authors: Wang Shang-Jui , Khullar Karishma , Kim Sinae , Yegya-Raman Nikhil , Malhotra Jyoti , Groisberg Roman , Crayton Samuel H , Silk Ann W , Nosher John L , Gentile Michael A , Mehnert Janice M , Jabbour Salma K
Published: October 2020

Background

Immune checkpoint inhibitors (ICIs) improve survival outcomes in metastatic melanoma and non-small cell lung cancer (NSCLC). Preclinical evidence suggests that overexpression of cyclo-oxygenase-2 (COX2) in tumors facilitates immune evasion through prostaglandin E2 production and that COX inhibition synergizes with ICIs to promote antitumor T-cell activation. This study investigates whether concurrent COX inhibitor (COXi) use during ICI treatment compared with ICI alone is associated with improved time-to-progression (TTP), objective response rate (ORR) and overall survival (OS) in patients with metastatic melanoma and NSCLC.

Methods

We retrospectively reviewed 90 metastatic melanoma and 37 metastatic NSCLC patients, treated with ICI between 2011 and 2019. Differences in TTP and OS by ICI+COXi versus ICI alone were compared using Kaplan-Meier and Cox regression. Interaction between ICI+COXi versus ICI alone and pretreatment neutrophil–lymphocyte ratio (NLR) was examined. Independent radiology review per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 was performed.

Results

For patients with melanoma, median TTP was significantly prolonged in ICI+COXi versus ICI alone (245 vs 100.5 days, p=0.002). On multivariate analysis, ICI+COXi associated with increased TTP (HR 0.36, 95% CI 0.2 to 0.66, p=0.001), adjusted for age, pretreatment NLR, and gender. For NSCLC patients, ICI+COXi also associated with increased TTP compared with ICI alone on multivariate analysis (HR 0.45; 95% CI 0.21 to 0.97; p=0.042) adjusted for age. ORR at 6 months was significantly higher in patients who received ICI+COXi compared with ICI alone in both melanoma (58.6% vs 19.2%, p=0.0005) and NSCLC (73.7% vs 33.3%, p=0.036) cohorts. In the melanoma cohort, high pretreatment NLR (>5) associated with decreased TTP (HR 3.21, 95% CI 1.64 to 6.3; p=0.0007); however, ICI+COXi significantly associated with increased TTP in high NLR (>5) patients (HR 0.08, 95% CI 0.03 to 0.25), but not in low NLR (≤5) patients (HR 0.65, 95% CI 0.32 to 1.32). Similar outcomes were found in an adjusted melanoma cohort after RECIST review.

Conclusions

Our study suggests that COXi use concurrently with ICI significantly associated with longer TTP and improved ORR at 6 months in patients with metastatic melanoma and NSCLC compared with ICI alone. Furthermore, COXi use appears to reverse the negative prognostic effect of a high NLR by prolonging TTP in patients with melanoma.
89Zr-pembrolizumab biodistribution is influenced by PD-1-mediated uptake in lymphoid organs
Authors: van der Veen Elly L , Giesen Danique , Pot-de Jong Linda , Jorritsma-Smit Annelies , De Vries Elisabeth G E , Lub-de Hooge Marjolijn N
Published: October 2020

Background

To better predict response to immune checkpoint therapy and toxicity in healthy tissues, insight in the in vivo behavior of immune checkpoint targeting monoclonal antibodies is essential. Therefore, we aimed to study in vivo pharmacokinetics and whole-body distribution of zirconium-89 (89Zr) labeled programmed cell death protein-1 (PD-1) targeting pembrolizumab with positron-emission tomography (PET) in humanized mice.

Methods

Humanized (huNOG) and non-humanized NOG mice were xenografted with human A375M melanoma cells. PET imaging was performed on day 7 post 89Zr-pembrolizumab (10 µg, 2.5 MBq) administration, followed by ex vivo biodistribution studies. Other huNOG mice bearing A375M tumors received a co-injection of excess (90 µg) unlabeled pembrolizumab or 89Zr-IgG4 control (10 µg, 2.5 MBq). Tumor and spleen tissue were studied with autoradiography and immunohistochemically including PD-1.

Results

PET imaging and biodistribution studies showed high 89Zr-pembrolizumab uptake in tissues containing human immune cells, including spleen, lymph nodes and bone marrow. Tumor uptake of 89Zr-pembrolizumab was lower than uptake in lymphoid tissues, but higher than uptake in other organs. High uptake in lymphoid tissues could be reduced by excess unlabeled pembrolizumab. Tracer activity in blood pool was increased by addition of unlabeled pembrolizumab, but tumor uptake was not affected. Autoradiography supported PET findings and immunohistochemical staining on spleen and lymph node tissue showed PD-1 positive cells, whereas tumor tissue was PD-1 negative.

Conclusion

89Zr-pembrolizumab whole-body biodistribution showed high PD-1-mediated uptake in lymphoid tissues, such as spleen, lymph nodes and bone marrow, and modest tumor uptake. Our data may enable evaluation of 89Zr-pembrolizumab whole-body distribution in patients.
Real-world treatment switching to sacubitril/valsartan in patients with heart failure with reduced ejection fraction: A cohort study
Authors: Ganesananthan Sashiananthan , Shah Nisar , Shah Parin , Elsayed Hossam , Phillips Julie , Parkes Ann , Morgan Angharad , Yousef Zaheer
Published: October 2020

Background

Sacubitril/valsartan is an effective treatment for heart failure with reduced ejection fraction (HFrEF) based on clinical trial data. However, little is known about its use or impact in real-world practice. The aim of this study was to describe our routine clinical experience of switching otherwise optimally treated patients with HFrEF to sacubitril/valsartan with respect to patient outcomes such as quality of life (QoL) and echocardiographic variables.

Methods and results

From June 2017 to May 2019, 80 consecutive stable patients with HFrEF on established and maximally tolerated guideline-directed HF therapies were initiated on sacubitril/valsartan with bimonthly uptitration. Clinical assessment, biochemistry, echocardiography and QoL were compared pretreatment and post-treatment switching. We were able to successfully switch 89% of patients from renin–angiotensin axis inhibitors to sacubitril/valsartan (71 of 80 patients). After 3 months of switch therapy, we observed clinically significant and incremental improvements in blood pressure (systolic blood pressure 123 vs 112 mm Hg, p<0.001; diastolic blood pressure 72 vs 68 mm Hg, p=0.004), New York Heart Association functional classification score (2.3 vs 1.9, p<0.001), Minnesota Living with Heart Failure Questionnaire score (46 vs 38, p=0.016), left ventricular ejection fraction (26% vs 33%, p<0.001) and left ventricular end systolic diameter (5.2 vs 4.9 cm, p=0.013) compared with baseline. There were no significant changes in renal function or serum potassium.

Conclusion

This study provides real-world clinical practice data demonstrating incremental improvements in functional and echocardiographic outcomes in optimally treated patients with HFrEF switched to sacubitril/valsartan. The data provide evidence beyond that observed in clinical trial settings of the potential benefits of sacubitril/valsartan when used as part of a multidisciplinary heart failure programme.
Antidiabetic Effects and Mechanisms of Rosemary (Rosmarinus officinalisL.) and its Phenolic Components
Authors: Bao Tian-Qi , Li Yi , Qu Cheng , Zheng Zu-Guo , Yang Hua , Li Ping
Published: October 2020

Diabetes mellitus is a chronic endocrine disease result from absolute or relative insulin secretion deficiency, insulin resistance, or both, and has become a major and growing public healthy menace worldwide. Currently, clinical antidiabetic drugs still have some limitations in efficacy and safety such as gastrointestinal side effects, hypoglycemia, or weight gain. Rosmarinus officinalis is an aromatic evergreen shrub used as a food additive and medicine, which has been extensively used to treat hyperglycemia, atherosclerosis, hypertension, and diabetic wounds. A great deal of pharmacological research showed that rosemary extract and its phenolic constituents, especially carnosic acid, rosmarinic acid, and carnosol, could significantly improve diabetes mellitus by regulating glucose metabolism, lipid metabolism, anti-inflammation, and anti-oxidation, exhibiting extremely high research value. Therefore, this review summarizes the pharmacological effects and underlying mechanisms of rosemary extract and its primary phenolic constituents on diabetes and relative complications both in vitro and in vivo studies from 2000 to 2020, to provide some scientific evidence and research ideas for its clinical application.
Pattern Dynamics in a Diffusive Gierer–Meinhardt Model
Authors: Chen Mengxin , Wu Ranchao , Chen Liping
Published: October 2020

The purpose of the present paper is to investigate the pattern formation and secondary instabilities, including Eckhaus instability and zigzag instability, of an activator–inhibitor system, known as the Gierer–Meinhardt model. Conditions on the Hopf bifurcation and the Turing instability are obtained through linear stability analysis at the unique positive equilibrium. Then, the method of weakly nonlinear analysis is used to derive the amplitude equations. Especially, by adding a small disturbance to the Turing instability critical wave number, the spatiotemporal Newell–Whitehead–Segel equation of the stripe pattern is established. It is found that Eckhaus instability and zigzag instability may occur under certain conditions. Finally, Turing and non-Turing patterns are obtained via numerical simulations, including spotted patterns, mixed patterns, Eckhaus patterns, spatiotemporal chaos, nonconstant steady state solutions, spatially homogeneous periodic solutions and spatially inhomogeneous solutions in two-dimensional or one-dimensional space. Theoretical analysis and numerical results are in good agreement for this diffusive Gierer–Meinhardt model.
Higher Codimension Bifurcation Analysis of Predator–Prey Systems with Nonmonotonic Functional Responses
Authors: Yao Jinhui , Li Guihua , Guo Gang
Published: October 2020

In this paper, we study the dynamic behaviors of a predator–prey system with a general form of nonmonotonic functional response. Through analysis, it is found that the system exists in extinction equilibrium, boundary equilibrium and two positive equilibria, one or no positive equilibrium. Furthermore, the conditions are given such that the boundary equilibrium is a saddle, node or a saddle-node point of codimension 1, 2 or 3. Then, some conditions are obtained so that the unique positive equilibrium of the system is a cusp point of codimension 2, 3 and higher or a saddle-node one of codimension 1 or 3, or a nilpotent saddle-node of codimension 4. When there are two positive equilibria in the system, the equilibrium with a large number of preys is a saddle point. For the other one, the system may undergo Hopf bifurcation. To verify our conclusion, we consider the functional response function in the literature [ Zhu et al., 2002 ; Xiao & Ruan, 2001 ]. Finally, we give a brief discussion and numerical simulation.
Spatiotemporal Dynamics of a Modified Leslie–Gower Model with Weak Allee Effect
Authors: Liu Yuying , Wei Junjie
Published: October 2020

In this paper, we consider a diffusive Leslie–Gower model with weak Allee effect in prey. We first study the global existence and non-negativity of the solutions by using the upper-lower solution method. We analyze the local stability of the positive constant steady state and prove the global attractivity by means of the LaSalle’s invariance principle. Additionally, we derive the parameter region that makes the positive constant steady state stable, and conclude that the boundary of this region contains a Hopf bifurcation curve and countable Turing curves. Thus, we get the existence of Turing–Hopf bifurcation and Turing–Turing bifurcation. Moreover, we calculate the normal form of the Turing–Hopf singularity on the center manifold. Our theoretical analysis shows that the system may produce a pair of spatially inhomogeneous steady states, spatially homogeneous periodic solutions, transient spatially inhomogeneous periodic solutions or even other solutions near the Turing–Hopf singularity. Finally, we carry out some numerical simulations for illustrating the analytical results.
On the Correlation Dimension of Discrete Fractional Chaotic Systems
Authors: Ma Li , Liu Xianggang , Liu Xiaotong , Zhang Ying , Qiu Yu , Li Kaiyan
Published: October 2020

This paper is mainly devoted to the investigation of discrete-time fractional systems in three aspects. Firstly, the fractional Bogdanov map with memory effect in Riemann–Liouville sense is obtained. Then, via constructing suitable controllers, the fractional Bogdanov map is shown to undergo a transition from regular state to chaotic one. Meanwhile, the positive largest Lyapunov exponent is calculated by the Jacobian matrix algorithm to distinguish the chaotic areas. Finally, the Grassberger–Procaccia algorithm is employed to evaluate the correlation dimension of the controlled fractional Bogdanov system under different parameters. The main results show that the correlation dimension converges to a fixed value as the embedding dimension increases for the controlled fractional Bogdanov map in chaotic state, which also coincides with the conclusion driven by the largest Lyapunov exponent. Moreover, three-dimensional fractional Stefanski map is considered to further verify the effectiveness and generality of the obtained results.
The Proto-Lorenz System in Its Chaotic Fractional and Fractal Structure
Authors: Doungmo Goufo Emile Franc
Published: October 2020

It is not common in applied sciences to realize simulations which depict fractal representation in attractors’ dynamics, the reason being a combination of many factors including the nature of the phenomenon that is described and the type of differential operator used in the system. In this work, we use the fractal-fractional derivative with a fractional order to analyze the modified proto-Lorenz system that is usually characterized by chaotic attractors with many scrolls. The fractal-fractional operator used in this paper is a combination of fractal process and fractional differentiation, which is a relatively new concept with most of the properties and features still to be known. We start by summarizing the basic notions related to the fractal-fractional operator. After that, we enumerate the main points related to the establishment of proto-Lorenz system’s equations, leading to the [Formula: see text]th cover of the proto-Lorenz system that contains [Formula: see text] scrolls ([Formula: see text]). The triple and quadric cover of the resulting fractal and fractional proto-Lorenz system are solved using the Haar wavelet methods and numerical simulations are performed. Due to the impact of the fractal-fractional operator, the system is able to maintain its chaotic state of attractor with many scrolls. Additionally, such attractor can self-replicate in a fractal process as the derivative order changes. This result reveals another great feature of the fractal-fractional derivative with fractional order.
Dynamic Analysis of a Population Competition Model with Disease in One Species and Group Defense in Another Species
Authors: Cheng Xue , Luo Jianfeng , Zhao Yi
Published: October 2020

In this paper, we study the dynamics of an ecoepidemic competition system where the individuals of one population gather together in herds with a defensive strategy, showing social behavior, while another predator population is subject to a transmissible disease and behaves individually. By analyzing the existence and stability of the equilibria of the system, we find that the relatively isolated population can be eradicated, or the population with group defense can live alone eventually under some constraints. Infected individuals end up in two possible situations. In the first case, the disease is eventually eliminated, meaning that only healthy and group-defense individuals in the system can survive. In the other case, the spread of the disease is controlled and eventually all three individuals can coexist. We also conduct a correlation analysis using competition parameter and recovery rate of disease as birfurcation parameters in order to study the transcritical bifurcation, saddle-node bifurcation and Hopf bifurcation. The long-term dynamics of the boundary and interior equilibria are demonstrated by numerical simulations.
Nonlinear Dynamic Response of FG Graphene Platelets Reinforced Composite Beam with Edge Cracks in Thermal Environment
Authors: Yang Zhicheng , Tam Meifung , Zhang Yingyan , Kitipornchai Sritawat , Lv Jiangen , Yang Jie
Published: October 2020

This paper presents a numerical investigation on the nonlinear dynamic response of multilayer functionally graded graphene platelets reinforced composite (FG-GPLRC) beam with open edge cracks in thermal environment. It is assumed that graphene platelets (GPLs) in each GPLRC layer are uniformly distributed and randomly oriented with its concentration varying layer-wise along the thickness direction. The effective material properties of each GPLRC layer are predicted by Halpin-Tsai micromechanics-based model. Finite element method is employed to calculate the dynamic response of the cracked FG-GPLRC beam. It is found that the maximum dynamic deformation of the cracked FG-GPLRC beam under dynamic loading is quite sensitive to the crack location and grows with an increase in the crack depth ratio (CDR) and temperature rise. The influences of GPL distribution, concentration, geometry as well as the boundary conditions on the dynamic response characteristics of cracked FG-X-GPLRC beams are also investigated comprehensively.
Quantum simulation dynamics and circuit synthesis of FMO complex on an NMR quantum computer
Authors: Mahdian M. , Yeganeh H. Davoodi , Dehghani A.
Published: October 2020

Recently, the dynamics simulation of light-harvesting complexes as an open quantum system, in the weak and strong coupling regimes, has received much attention. In this paper, we investigate a digital quantum simulation approach of the Fenna–Matthews–Olson (FMO) photosynthetic pigment-protein complex surrounded with a Markovian bath, i.e. memoryless, based on a nuclear magnetic resonance (NMR) quantum computer. For this purpose, we apply the decoupling (recoupling) method, which is turn off (on) the couplings, and also Solovay–Kitaev techniques to decompose Hamiltonian and Lindbladians into efficient elementary gates on an NMR simulator. Finally, we design the quantum circuits for the unitary and nonunitary part due to the system-environment interactions of the open system dynamics.
A LITERATURE REVIEW ON THE DEFINITION OF SHARING ECONOMY
Authors: WEILI LIU , KHAN HAYAT
Published: October 2020

This paper aims to review the literature on the definitions of sharing economy. For this study, a total of 280 papers have been collected and then limited to 75 published papers which have given the sharing economy definitions in their studies. This study shows different definitions related to the sharing economy where differences in definitions and their similarities are shown. This study gives deep detail about the definitions of the term sharing economy which gives complete information about definitions till the date of publication of this study on sharing economy definition.
An integrated organic–inorganic geochemical characterization of Paleogene sediments in No.1 Structural Belt of the Nanpu Sag, Bohai Bay Basin, eastern China: implications for the origin of organic matter
Authors: Guo Yu , Gang Wenzhe , Gao Gang , Yang Shangru , Jiang Chong , Chen Guo , Zhu Chuanzhen , Li Xiaofeng , Wang Yifan , Dong Yuexia , Goldberg Karin
Published: October 2020

Paleogene sediments, especially the third member of the Dongying Formation (Ed
3
) and the first and third members of the Shahejie Formation (Es
1
and Es
3
), have been regarded as the most important source rocks in the Nanpu Sag. Organic and inorganic analyses, including Rock-Eval pyrolysis, gas chromatography-mass spectrometry, and element geochemistry, in 91 mudstone samples, were used to reconstruct the palaeoenvironmental conditions, such as palaeoclimate, palaeo-salinity and palaeo-redox conditions, and to recognize the origin of organic matter. The results show that Es
3
has a higher TOC content than Es
1
and Ed
3
. Hydrocarbon genetic potential (S
1
 + S
2
) of the samples indicate fair to good hydrocarbon potential. The kerogen type of Ed
3
and Es
1
source rocks are Type II
1
–II
2
, while Es
3
source rocks are dominated by Type II
2
–III kerogens. Biomarkers and inorganic geochemical indicatives of source rocks, such as Pr/Ph, V/(V + Ni) and Cu/Zn, indicate a lacustrine environment with fresh to brackish water under suboxic to anoxic conditions during deposition. Ed
3
source rocks are characterized by low G/C
30
H (gamacerane/C
30
hopane) (<0.1), TT/C
30
H (tricyclic terpane/C
30
hopane) and S/H (serane/hopane), high Pr/Ph (pristane/phytane) and C
24
TeT/C
23
TT (C
24
tetracyclic terpane/C
23
tricyclic terpane), indicating mixed input of both algae and terrestrial higher plants, dominated by terrestrial higher plants. Es
1
source rocks display medium G/C
30
H, TT/C
30
H, S/H, Pr/Ph and C
24
TeT/C
23
TT, indicative of a mixed input of both algae and terrestrial higher plants. Es
3
source rocks are characterized by high G/C
30
H (>0.1), TT/C
30
H and S/H, low Pr/Ph and C
24
TeT/C
23
TT, typical of a mixed input of algae and terrestrial higher plants, with algal dominance. Ed
3
, Es
1
and Es
3
source rocks were mostly deposited in semi-arid to humid-warm climate conditions, with an average temperature higher than 15°C. This study suggests that suitable temperatures, a fresh to brackish lacustrine environment and suboxic to anoxic conditions could result in a high organic matter concentration and preservation, thus providing prerequisites for the formation of high-quality source rocks.

Supplementary material
: Tables S1–S3 are available at
https://doi.org/10.6084/m9.figshare.c.5227684
Key controls on the hydraulic properties of fault rocks in carbonates
Authors: Michie E. A. H. , Cooke A. P. , Kaminskaite I. , Stead J. C. , Plenderleith G. E. , Tobiss S. D. , Fisher Q. J. , Yielding G. , Freeman B.
Published: October 2020

A significant knowledge gap exists when analysing and predicting the hydraulic behaviour of faults within carbonate reservoirs. To improve this, a large database of carbonate fault rock properties has been collected from 42 exposed faults, from seven countries. Faults analysed cut a range of lithofacies, tectonic histories, burial depths and displacements. Porosity and permeability measurements from
c.
400 samples have been made, with the goal of identifying key controls on the flow properties of fault rocks in carbonates. Intrinsic and extrinsic factors have been examined, such as host lithofacies, juxtaposition, host porosity and permeability, tectonic regime, displacement, and maximum burial depth, as well as the depth at the time of faulting. The results indicate which factors may have had the most significant influence on fault rock permeability, improving our ability to predict the sealing or baffle behaviour of faults in carbonate reservoirs. Intrinsic factors, such as host porosity, permeability and texture, appear to play the most important role in fault rock development. Extrinsic factors, such as displacement and kinematics, have shown lesser or, in some instances, a negligible control on fault rock development. This conclusion is, however, subject to two research limitations: lack of sufficient data from similar lithofacies at different displacements, and a low number of samples from thrust regimes.

Thematic collection:
This article is part of the Fault and top seals collection available at:
https://www.lyellcollection.org/cc/fault-and-top-seals-2019
Recent Advances in the Analyses of Demand for Agricultural Insurance in Developing and Emerging Countries
Authors: Ali Williams , Abdulai Awudu , Mishra Ashok K.
Published: October 2020

Despite the significant risks and uncertainties that farmers in developing and emerging countries face in their production process, efforts at encouraging them to adopt agricultural insurance to mitigate their production risks have mainly yielded little success. This article reviews the recent literature on the demand for agricultural insurance in developing and emerging countries, by presenting the state of uptake, drivers of the demand for it, and the potential welfare gains from it. Our review reveals that while risk aversion is necessary for the demand for agricultural insurance, liquidity constraints, rates of time preference, basis risk, and trust are equally relevant in explaining the demand for insurance in poor countries. An interesting observation is the increasing number of studies that employ randomized control trials to analyze farmers’ uptake of agricultural insurance in developing and emerging countries. Our comprehensive review finds some information gaps in the literature, and we propose some avenues for further research.
Using a Combination of Electrochemical and Photoelectron Transfer Reactions to Gain New Insights into Oxidative Cyclization Reactions
Authors: Graaf Matthew D. , Gonzalez Luisalberto , Medcalf Zach , Moeller Kevin D.
Published: October 2020

Radical cation initiated cyclization reactions can be triggered by the one electron oxidation of an electron-rich olefin using either electrochemistry or visible light and a photoredox catalyst. In principle, the two methods can be used to give complimentary products with the electrolysis leading to products derived from a net two electron oxidation and the photoelectron transfer method being compatible with the formation of products from a redox neutral process. However, we are finding an increasing number of oxidative cyclization reactions that require the rapid removal of a second electron in order to form high yields of the desired product. In those cases, the electrochemical method can provide a superior approach to accessing the necessary two electron oxidation pathway. With that said, it is a combination of the two methods that provides the mechanistic insight needed to understand when a reaction has this requirement, and we are finding that the use of photoredox catalysis in combination with electrochemical methods is changing our understanding of even the most successful anodic cyclization reactions run to date.
Enhancement of Tunneling CNTFET Performance Using a High-k Dielectric Pocket
Authors: Ossaimee M. , Salem N. , Abouelatta M. , Shaker A.
Published: October 2020

The Tunneling Carbon Nanotube FET (T-CNTFET) is one of the most promising alternatives to the conventional MOSFET. However, T-CNTFET suffers mainly from low ON-current. In this paper, we propose a modified hetero-dielectric T-CNTFET in which a dielectric pocket is inserted near the source-channel interface. The impact of the length of the dielectric pocket and its shift from source/channel barrier on DC and high-frequency performance is investigated. The performance parameters are studied by examining ON-current (I
ON) and cutoff frequency (f

T
) as measures for the DC and high frequency behavior, respectively. It is demonstrated that the condition of an optimum design for the pocket position concerning I
ON is different from that regarding f

T
and a compromise should be met in order to obtain the best performance. Based on our developed 2D quantum simulations, it is shown that a high-k pocket having a length of 12.5% of the channel length may result in an increase of 65% in I

ON
with no deterioration in f

T
. Moreover, a little shift of 20% of the pocket length towards the source region doesn’t degrade I

ON
and enhances f

T
.
Afferent renal innervation in anti-Thy1.1 nephritis in rats
Authors: Rodionova Kristina , Veelken Roland , Hilgers Karl F. , Paulus Eva-Maria , Linz Peter , Fischer Michael J. M. , Schenker Martina , Reeh Peter , Tiegs Gisa , Ott Christian , Schmieder Roland , Schiffer Mario , Amann Kerstin , Ditting Tilmann
Published: October 2020

Afferent renal nerves exhibit a dual function controlling central sympathetic outflow via afferent electrical activity and influencing intrarenal immunological processes by releasing peptides such as calcitonin gene-related peptide (CGRP). We tested the hypothesis that increased afferent and efferent renal nerve activity occur with augmented release of CGRP in anti-Thy1.1 nephritis, in which enhanced CGRP release exacerbates inflammation. Nephritis was induced in Sprague-Dawley rats by intravenous injection of OX-7 antibody (1.75 mg/kg), and animals were investigated neurophysiologically, electrophysiologically, and pathomorphologically 6 days later. Nephritic rats exhibited proteinuria (169.3 ± 10.2 mg/24 h) with increased efferent renal nerve activity (14.7 ± 0.9 bursts/s vs. control 11.5 ± 0.9 bursts/s, n = 11, P < 0.05). However, afferent renal nerve activity (in spikes/s) decreased in nephritis (8.0 ± 1.8 Hz vs. control 27.4 ± 4.1 Hz, n = 11, P < 0.05). In patch-clamp recordings, neurons with renal afferents from nephritic rats showed a lower frequency of high activity following electrical stimulation (43.4% vs. 66.4% in controls, P < 0.05). In vitro assays showed that renal tissue from nephritic rats exhibited increased CGRP release via spontaneous (14 ± 3 pg/mL vs. 6.8 ± 2.8 pg/ml in controls, n = 7, P < 0.05) and stimulated mechanisms. In nephritic animals, marked infiltration of macrophages in the interstitium (26 ± 4 cells/mm2) and glomeruli (3.7 ± 0.6 cells/glomerular cross-section) occurred. Pretreatment with the CGRP receptor antagonist CGRP8–37reduced proteinuria, infiltration, and proliferation. In nephritic rats, it can be speculated that afferent renal nerves lose their ability to properly control efferent sympathetic nerve activity while influencing renal inflammation through increased CGRP release.
Retromer is involved in epithelial Na+ channel trafficking
Authors: Cheung Tanya T. , Geda Anna C. , Ware Adam W. , Rasulov Sahib R. , Tenci Polly , Hamilton Kirk L. , McDonald Fiona J.
Published: October 2020

The epithelial Na+ channel (ENaC) located at the apical membrane in many epithelia is the rate-limiting step for Na+ reabsorption. Tight regulation of the plasma membrane population of ENaC is required, as hypertension or hypotension may result if too many or too few ENaCs are present. Endocytosed ENaC travels to the early endosome and is then either trafficked to the lysosome for degradation or recycled back to the plasma membrane. Recently, the retromer recycling complex, located at the early endosome, has been implicated in plasma membrane protein recycling pathways. We hypothesized that the retromer is required for recycling of ENaC. Stabilization of retromer function with the retromer stabilizing chaperone R55 increased ENaC current, whereas knockdown or overexpression of individual retromer and associated proteins altered ENaC current and cell surface population of ENaC. KIBRA was identified as an ENaC-binding protein allowing ENaC to link to sorting nexin 4 to alter ENaC trafficking. Knockdown of the retromer-associated cargo-binding sorting nexin 27 protein did not alter ENaC current, whereas CCDC22, a CCC-complex protein, coimmunoprecipitated with ENaC, and CCDC22 knockdown decreased ENaC current and population at the cell surface. Together, our results confirm that retromer and the CCC complex play a role in recycling of ENaC to the plasma membrane.
Class IIa HDAC inhibitor TMP195 alleviates lipopolysaccharide-induced acute kidney injury
Authors: Zhang Wei , Guan Yinjie , Bayliss George , Zhuang Shougang
Published: October 2020

Sepsis-associated acute kidney injury (SA-AKI) is associated with high mortality rates, but clinicians lack effective treatments except supportive care or renal replacement therapies. Recently, histone deacetylase (HDAC) inhibitors have been recognized as potential treatments for acute kidney injury and sepsis in animal models; however, the adverse effect generated by the use of pan inhibitors of HDACs may limit their application in people. In the present study, we explored the possible renoprotective effect of a selective class IIa HDAC inhibitor, TMP195, in a murine model of SA-AKI induced by lipopolysaccharide (LPS). Administration of TMP195 significantly reduced increased serum creatinine and blood urea nitrogen levels and renal damage induced by LPS; this was coincident with reduced expression of HDAC4, a major isoform of class IIa HDACs, and elevated histone H3 acetylation. TMP195 treatment following LPS exposure also reduced renal tubular cell apoptosis and attenuated renal expression of neutrophil gelatinase-associated lipocalin and kidney injury molecule-1, two biomarkers of tubular injury. Moreover, LPS exposure resulted in increased expression of BAX and cleaved caspase-3 and decreased expression of Bcl-2 and bone morphogenetic protein-7 in vivo and in vitro; TMP195 treatment reversed these responses. Finally, TMP195 inhibited LPS-induced upregulation of multiple proinflammatory cytokines/chemokines, including intercellular adhesion molecule-1, monocyte chemoattractant protein-1, tumor necrosis factor-α, and interleukin-1β, and accumulation of inflammatory cells in the injured kidney. Collectively, these data indicate that TMP195 has a powerful renoprotective effect in SA-AKI by mitigating renal tubular cell apoptosis and inflammation and suggest that targeting class IIa HDACs might be a novel therapeutic strategy for the treatment of SA-AKI that avoids the unintended adverse effects of a pan-HDAC inhibitor.
T cell-derived extracellular vesicles are elevated in essential HTN
Authors: La Salvia Sabrina , Musante Luca , Lannigan Joanne , Gigliotti Joseph Christopher , Le Thu H. , Erdbrügger Uta
Published: October 2020

Extracellular vesicles (EVs) are novel mediators of cell-to-cell communication and appear to mediate the pathogenesis of hypertension (HTN). However, the mechanisms underlying the involvement of EVs in HTN remain unclear. The adaptive and innate immune systems play an important role affecting the kidney and vasculature in animal models of HTN. Evolving evidence shows that immune cell-derived EVs can modulate the immune system in a paracrine fashion and therefore may mediate the effects of inflammation in the pathogenesis of HTN. Therefore, we aimed to understand if specific subtypes of leukocyte/immune cell-derived EVs are altered in essential HTN using an in vivo model of angiotensin II (ANG II)-induced HTN. After 4 wk of ANG II treatment, EVs were isolated from the blood and kidney. EV origin and counts were characterized with Imaging Flow Cytometry, antibody panels targeting platelets, endothelial cells, and leukocytes including B and T cells, monocytes, and neutrophils. Leukocyte-derived EVs (CD45+) were elevated in the circulation and kidney tissue in ANG II-induced HTN. Subgroup analysis depicted T cell-derived EVs (CD3+) to be significantly elevated in ANG II-induced HTN (3.50 e+5 particles/mL) compared with control groups (9.16 e+4 particles/mL, P = 0.0106). T cell-derived EVs also significantly correlated with systolic blood pressure levels ( r2 = 0.898, P = 0.0012). In summary, leukocyte-derived EVs, and more specifically T cell-derived EVs (CD3+), are elevated in ANG II-induced HTN in the circulation and kidney tissue and correlate well with blood pressure severity. EVs from the circulation and kidney may be sensitive biomarkers for HTN and end-organ damage and may lead to new mechanistic insights in this silent disease.
An Analytical Optimisation Framework for Airport Terminal Capacity Expansion
Authors: Alodhaibi Sultan , Burdett Robert L. , Yarlagadda Prasad K. D. V.
Published: October 2020

This article considers how to allocate additional physical resources within airport terminals. An optimization model was developed to determine where additional resources should be placed to minimise passenger waiting times. The objective function is stochastic and can only be evaluated using discrete event simulation. As this model is stochastic and nonlinear, a Simulated Annealing (SA) metaheuristic was implemented and tested. The SA algorithm repeatedly perturbs a resource allocation solution using one of two methods. The first method is creating new solution randomly in each iteration, and the second method is local search that is mimicked by any move of the current solution of x solution chosen randomly in its neighborhood. Numerical testing shows that the random approach is best, and solutions that are 12.11% better can be obtained.