bluuebunny/crossref_metadata_2025 huggingface dataset:
Heat‐ and Light‐Responsive Materials Through Pairing Dynamic Thiol–Michael and Coumarin Chemistry
Authors: Chakma Progyateg , Wanasinghe Shiwanka V. , Morley Colleen N. , Francesconi Sebastian C. , Saito Kei , Sparks Jessica L. , Konkolewicz Dominik
Published: May 2021

Covalent adaptable networks (CANs) based on the thiol–Michael (TM) linkages can be thermal and pH responsive. Here, a new vinyl‐sulfone‐based thiol–Michael crosslinker is synthesized and incorporated into acrylate‐based CANs to achieve stable materials with dynamic properties. Because of the reversible TM linkages, excellent temperature‐responsive re‐healing and malleability properties are achieved. In addition, for the first time, a photoresponsive coumarin moiety is incorporated with TM‐based CANs to introduce light‐mediated reconfigureability and postpolymerization crosslinking. Overall, these materials can be on demand dynamic in response to heat and light but can retain mechanical stability at ambient condition.
Copyright's impact on data mining in academic research
Authors: Handke Christian , Guibault Lucie , Vallbé Joan‐Josep
Published: May 2021

With the proliferation of digital data, data mining (DM)—in the sense of the discovery of valuable structures in large sets of data—is expected to increase the productivity of many types of research. This paper discusses how copyright affects DM by academic researchers. In some territories, academic DM is lawful if researchers have lawful access to input works. In other territories such as the European Union, lawful DM additionally requires specific consent by rights holders. Based on bibliometric data and quasi‐experimental research designs, we show that where academic DM requires specific rights holder consent: (1) DM publications make up a significantly lower share of total research output, and (2) stronger rule of law is associated with less DM research. To our knowledge, this study is the first to empirically document an adverse effect of intellectual property (IP) on innovation under particular circumstances. There is strong evidence that copyright exceptions or limitations promote the adoption of DM research.
Impact of assimilating Mode‐S EHS winds in the Met Office's high‐resolution NWP model
Authors: Li Zhihong
Published: May 2021

Aircraft play an important role in providing in‐situ upper air observations for use in numerical weather prediction (NWP) models. Aircraft observations of wind, temperature and humidity have been routinely assimilated into NWP models for decades. More recently, the Met Office has installed a network of six receivers to collect Mode‐Select Enhanced Surveillance (Mode‐S EHS) broadcasts and derive wind and temperature information. The paper focuses on the assimilation of high‐frequency (sub‐hourly) Mode‐S winds into the Met Office's hourly cycling high‐resolution NWP model, which employs four‐dimensional‐variational data assimilation (4D‐Var). An observing system experiment (OSE) experiment was carried out to assess the impact of additionally assimilating Mode‐S wind data on the model forecasts in both summer and winter. It is shown that assimilating Mode‐S winds has a positive benefit on the forecast skill in the first 6 hr wind profiles, with an improvement of the mean bias and root mean square (RMS) errors of up to 0.5 m·s−1 in the first hour and 0.3 m·s−1 in the sixth hour. The assimilation of Mode‐S winds is also seen to be beneficial to the near‐surface‐focused UK NWP composite index, and to the hourly precipitation accumulations in fractions skill score (FSS) for forecasts up to 9 hr ahead.
Shape sensitivity analysis for electromagnetic cavities
Authors: Lamberti Pier Domenico , Zaccaron Michele
Published: May 2021

We study the dependence of the eigenvalues of time‐harmonic Maxwell's equations in a cavity upon variation of its shape. The analysis concerns all eigenvalues both simple and multiple. We provide analyticity results for the dependence of the elementary symmetric functions of the eigenvalues splitting a multiple eigenvalue, as well as a Rellich‐Nagy‐type result describing the corresponding bifurcation phenomenon. We also address an isoperimetric problem and characterize the critical cavities for the symmetric functions of the eigenvalues subject to isovolumetric or isoperimetric domain perturbations and prove that balls are critical. We include known formulas for the eigenpairs in a ball and calculate the first one.
A note on the structure of prescribed gradient–like domains of non–integrable vector fields
Authors: Tudoran Răzvan M.
Published: May 2021

Given a geometric structure on
with
(e.g., Euclidean, symplectic, Minkowski, and pseudo‐Euclidean), we analyze the set of points inside the domain of definition of an arbitrary given
vector field, where the value of the vector field equals the value of the left/right gradient–like vector field of some fixed
potential function, although a natural non‐integrability condition holds at each such a point. More precisely, we prove that if not empty, this is a Borel set which admits a cover consisting of at most
regularly embedded
m−dimensional submanifolds of
, and consequently, its Hausdorff dimension is less or equal to m. Particular examples of gradient–like vector fields include the class of gradient vector fields with respect to Euclidean or pseudo‐Euclidean inner products, and the class of Hamiltonian vector fields associated to symplectic structures on
. The main result of this article provides a geometric version of the similar result for the classical gradient vector field.
Deep learning‐based multi‐modal computing with feature disentanglement for MRI image synthesis
Authors: Fei Yuchen , Zhan Bo , Hong Mei , Wu Xi , Zhou Jiliu , Wang Yan
Published: May 2021

Purpose

Different Magnetic resonance imaging (MRI) modalities of the same anatomical structure are required to present different pathological information from the physical level for diagnostic needs. However, it is often difficult to obtain full‐sequence MRI images of patients owing to limitations such as time consumption and high cost. The purpose of this work is to develop an algorithm for target MRI sequences prediction with high accuracy, and provide more information for clinical diagnosis.

Methods

We propose a deep learning‐based multi‐modal computing model for MRI synthesis with feature disentanglement strategy. To take full advantage of the complementary information provided by different modalities, multi‐modal MRI sequences are utilized as input. Notably, the proposed approach decomposes each input modality into modality‐invariant space with shared information and modality‐specific space with specific information, so that features are extracted separately to effectively process the input data. Subsequently, both of them are fused through the adaptive instance normalization (AdaIN) layer in the decoder. In addition, to address the lack of specific information of the target modality in the test phase, a local adaptive fusion (LAF) module is adopted to generate a modality‐like pseudo‐target with specific information similar to the ground truth.

Results

To evaluate the synthesis performance, we verify our method on the BRATS2015 dataset of 164 subjects. The experimental results demonstrate our approach significantly outperforms the benchmark method and other state‐of‐the‐art medical image synthesis methods in both quantitative and qualitative measures. Compared with the pix2pixGANs method, the PSNR improves from 23.68 to 24.8. Moreover the ablation studies have also verified the effectiveness of important components of the proposed method.

Conclusion

The proposed method could be effective in prediction of target MRI sequences, and useful for clinical diagnosis and treatment.
Validating pore size estimates in a complex microfiber environment on a human MRI system
Authors: Huang Chu‐Chung , Hsu Chih‐Chin Heather , Zhou Feng‐Lei , Kusmia Slawomir , Drakesmith Mark , Parker Geoff J. M. , Lin Ching‐Po , Jones Derek K.
Published: May 2021

Purpose

Recent advances in diffusion‐weighted MRI provide “restricted diffusion signal fraction” and restricting pore size estimates. Materials based on co‐electrospun oriented hollow cylinders have been introduced to provide validation for such methods. This study extends this work, exploring accuracy and repeatability using an extended acquisition on a 300 mT/m gradient human MRI scanner, in substrates closely mimicking tissue, that is, non‐circular cross‐sections, intra‐voxel fiber crossing, intra‐voxel distributions of pore‐sizes, and smaller pore‐sizes overall.

Methods

In a single‐blind experiment, diffusion‐weighted data were collected from a biomimetic phantom on a 3T Connectom system using multiple gradient directions/diffusion times. Repeated scans established short‐term and long‐term repeatability. The total scan time (54 min) matched similar protocols used in human studies. The number of distinct fiber populations was estimated using spherical deconvolution, and median pore size estimated through the combination of CHARMED and AxCaliber3D framework. Diffusion‐based estimates were compared with measurements derived from scanning electron microscopy.

Results

The phantom contained substrates with different orientations, fiber configurations, and pore size distributions. Irrespective of one or two populations within the voxel, the pore‐size estimates (~5 μm) and orientation‐estimates showed excellent agreement with the median values of pore‐size derived from scanning electron microscope and phantom configuration. Measurement repeatability depended on substrate complexity, with lower values seen in samples containing crossing‐fibers. Sample‐level repeatability was found to be good.

Conclusion

While no phantom mimics tissue completely, this study takes a step closer to validating diffusion microstructure measurements for use in vivo by demonstrating the ability to quantify microgeometry in relatively complex configurations.
Topological synthesis of crystalline Ag/T‐Nb2O5 nanobelts with enhanced solar photoelectrochemical properties for splitting water
Authors: Wen Puhong , Jiang Xiaowen , He Qian , Hu Dengwei , Ren Lijun , Zhao Weixing
Published: May 2021

The tetragonal phase Nb2O5 (T‐Nb2O5) nanobelts with preferentially exposed the (010) facet have been successfully prepared for the first time by insitu topological reaction using the KNb3O8 nanobelts as the precursor. Meanwhile, the transformation mechanism of the crystal structure and morphology from the layered KNb3O8 nanobelt to the T‐Nb2O5 nanobelt was revealed in detail by using XRD, FE‐SEM, TEM, HRTEM, SAED, UV‐vis DRS, EDX, XPS, and Raman spectra. In addition, Ag deposited T‐Nb2O5 (Ag/T‐Nb2O5) nanobelts were prepared by photo‐reduction reaction. The photoelectrochemical properties of the T‐Nb2O5 nanobelts and Ag/T‐Nb2O5 nanobelts as a photocatalyst were evaluated by splitting water under simulated sunlight. The results show that the photocurrent density generated by the prepared Ag/T‐Nb2O5 sample is 48.1 µA∙cm−2, which is 2.3 times that of the T‐Nb2O5 sample, and the prepared tetragonal phase T‐Nb2O5 nanobelts produce a photocurrent value 1.5 times that of the contrast orthogonal phase O‐Nb2O5 nanosheets. It indicates that the (010) facet of the tetragonal phase Nb2O5 is one of the highest photocatalytic active surfaces, and the visible light utilization efficiency of the T‐Nb2O5 nanobelt with Ag deposited on the surface has been significantly improved, which implies that it has potential applications in the field of photocatalysis.
One‐dimensional nanomaterial supported metal single‐atom electrocatalysts: Synthesis, characterization, and applications
Authors: Zhao Haoyue , Zhang Chuanxiong , Li Han , Fang Jian
Published: May 2021

Metal single‐atom catalysts (MSACs) have attracted considerable attention in the field of electrocatalysis due to their maximized atomic utilization, high activity, and superior selectivity. As a class of supported catalyst, the type of support material plays a key role in stabilizing metal single atoms (MSAs) and improving the overall catalytic performance. One‐dimensional (1D) nanomaterials are regarded as ideal supports for MSACs owing to many of their unique advantages, such as controllable surface physicochemical properties, large specific surface area, efficient electron transfer pathway, and great flexibility in element selection. Therefore, recently developed MSACs supported by various types of 1D nanostructured substrates have shown fascinating electrocatalytic performance towards a wide range of electrochemical reactions and demonstrated great potential in practical applications. In this review, we summarize recent progress of 1D nanomaterial supported MSACs, from material synthesis, characterization, and theoretical calculation to their performance in five different kinds of electrochemical applications. In particular, the major synthetic strategies of these advanced MSACs and their catalytic performance and mechanisms in various electrocatalytic reactions are extensively discussed. Finally, the remaining challenges and future prospects of 1D nanomaterial supported MSACs are provided.
The Sherman–Morrison–Woodbury formula for generalized linear matrix equations and applications
Authors: Hao Yue , Simoncini Valeria
Published: May 2021

We discuss the use of a matrix‐oriented approach for numerically solving the dense matrix equation AX + XAT + M1XN1 + … + MℓXNℓ = F, with ℓ ≥ 1, and Mi, Ni, i = 1, … , ℓ of low rank. The approach relies on the Sherman–Morrison–Woodbury formula formally defined in the vectorized form of the problem, but applied in the matrix setting. This allows one to solve medium size dense problems with computational costs and memory requirements dramatically lower than with a Kronecker formulation. Application problems leading to medium size equations of this form are illustrated and the performance of the matrix‐oriented method is reported. The application of the procedure as the core step in the solution of the large‐scale problem is also shown. In addition, a new explicit method for linear tensor equations is proposed, that uses the discussed matrix equation procedure as a key building block.
Validating the Implementation Leadership Scale in Chinese nursing context: A cross‐sectional study
Authors: Hu Jiale , Gifford Wendy , Ruan Hong , Harrison Denise , Li Qingge , Ehrhart Mark G. , Harrison Mary‐Ann , Barrowman Nick , Aarons Gregory A.
Published: May 2021

Aim

This study aimed to evaluate the validity, reliability and acceptability of the Implementation Leadership Scale in the Chinese nursing context.

Design

This study utilized a cross‐sectional design.

Methods

This study was conducted in one general tertiary hospital with 234 nurses (85.3% response rate) from 35 clinical units in China. Content validity, structural validity, convergent validity, reliability (internal consistency), agreement indices and acceptability were evaluated. The data collection was from December 1st, 2017 to June 30th, 2018.

Results

Confirmatory factor analysis demonstrated a good model fit to the four‐factor implementation leadership model. The psychometric testing also indicated good convergent validity, high internal consistency and acceptable aggregation. Most participants completed the scale in two minutes or less and agreed or strongly agreed that the questions were relevant to implementation leadership, clear and easy to answer.

Conclusions

This study demonstrated that the Chinese Implementation Leadership Scale is a valid, reliable and pragmatic tool for measuring strategic leadership for implementing evidence‐based practices.
Death metal: Evidence for the impact of lead poisoning on childhood health within the Roman Empire
Authors: Moore Joanna , Filipek Kori , Kalenderian Vana , Gowland Rebecca , Hamilton Elliott , Evans Jane , Montgomery Janet
Published: May 2021

The use of lead was ubiquitous throughout the Roman Empire, including material for water pipes, eating vessels, medicine, and even as a sweetener for wine. The toxicity of lead is well established today, resulting in long‐term psychological and neurological deficits as well as metabolic diseases. Children are particularly susceptible to the effects of lead, and it is likely that the widespread use of this deadly metal among Roman populations led to a range of adverse health effects. Indeed, lead poisoning has even been implicated in the downfall of the Roman Empire. This research examines, for the first time, the direct effect of lead poisoning on the inhabitants of the Empire. It explores whether the dramatic increase in lead during this period contributed to the failure to thrive evident within the skeletal remains of Roman children. Lead concentration and paleopathological analyses were used to explore the association between lead burdens and health during the Roman period. This study includes 173 individuals (66 adults and 107 non‐adults) from five sites, AD 1st–4th centuries, located throughout the Roman Empire. Results show a negative correlation between age‐at‐death and core tooth enamel lead concentrations. Furthermore, higher lead concentrations were observed in children with skeletal evidence of metabolic disease than those without. This study provides the first bioarcheological evidence that lead poisoning was a contributing factor to the high infant mortality and childhood morbidity rates seen within the Roman world.
PI3K signalling in chronic obstructive pulmonary disease and opportunities for therapy
Authors: Moradi Sharif , Jarrahi Esmaeil , Ahmadi Ali , Salimian Jafar , Karimi Mehrdad , Zarei Azadeh , Azimzadeh Jamalkandi Sadegh , Ghanei Mostafa
Published: May 2021

Chronic obstructive pulmonary disease (COPD) is a chronic lung disease characterised by airway inflammation and progressive obstruction of the lung airflow. Current pharmacological treatments include bronchodilators, alone or in combination with steroids, or other anti‐inflammatory agents, which have only partially contributed to the inhibition of disease progression and mortality. Therefore, further research unravelling the underlying mechanisms is necessary to develop new anti‐COPD drugs with both lower toxicity and higher efficacy. Extrinsic signalling pathways play crucial roles in COPD development and exacerbations. In particular, phosphoinositide 3‐kinase (PI3K) signalling has recently been shown to be a major driver of the COPD phenotype. Therefore, several small‐molecule inhibitors have been identified to block the hyperactivation of this signalling pathway in COPD patients, many of them showing promising outcomes in both preclinical animal models of COPD and human clinical trials. In this review, we discuss the critically important roles played by hyperactivated PI3K signalling in the pathogenesis of COPD. We also critically review current therapeutics based on PI3K inhibition, and provide suggestions focusing on PI3K signalling for the further improvement of the COPD phenotype. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Hydrochlorothiazide and risk of melanoma subtypes
Authors: Habel Laurel A. , Achacoso Ninah , Fireman Bruce , Pedersen Sidsel Arnspang , Pottegård Anton
Published: May 2021

Background

Hydrochlorothiazide (HCTZ), a common diuretic known to be photosensitizing and previously associated with non‐melanoma skin cancer, was recently reported to be associated with two melanoma subtypes, nodular and lentigo, among residents of Denmark. Our goal was to examine whether Danish findings could be replicated in a US cohort, using a similar study design and analysis.

Methods

Among non‐Hispanic White enrollees of Kaiser Permanente Northern California, we conducted an analysis of 9176 melanoma cases and 264 781 controls, matched on age, sex and time in health plan. We examined use of HCTZ prior to cancer diagnosis (cases) or comparable date for controls, categorized as never use, ever use and high use (≥50 000 mg). Electronic health records provided data on prescriptions, cancer diagnoses, and covariates. Conditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for education, income and number of dermatology, internal medicine and urgent care visits.

Results

We observed a small increase in risk of melanoma, all types combined, associated with high use (≥50 000 mg) of HCTZ (OR = 1.11, 95% CI 1.00–1.23) and no evidence of a dose–response. Risk was more elevated for lentigo subtype (OR = 1.57, 95% CI 1.01–2.42). The somewhat elevated risk for nodular subtype was not statistically significant (OR = 1.22, 95% CI 0.78–1.90). There was very little association of high use with the superficial spreading subtype (OR = 1.05, 95% CI 0.80–1.37).

Conclusions

Our findings support a recent report of an association between high use of HCTZ and increased risk of the lentigo subtype of melanoma.
Synthesis and characterization of porous polydimethylsiloxane structures with adjustable porosity and pore morphology using emulsion templating technique
Authors: Abshirini Mohammad , Saha Mrinal C. , Cummings Laura , Robison Thomas
Published: May 2021

Porous polydimethylsiloxane (PDMS) framework with adjustable pore structures has been fabricated by polymerization of the continuous phase in the emulsion templates. Different types of surfactants, including nonionic (Triton X‐100), cationic (Benzalkonium chloride), anionic (sodium dodecyl sulfate), and silicone‐based block copolymer were used to stabilize the water‐in‐oil emulsion system. Deionized water with a wide range of internal phases varying from 10% to 60% by weight was employed to make the low internal phase emulsion and medium internal phase emulsion. The effect of surfactant type, surfactant concentration, and the internal phase volume on the stability of the emulsion, pore morphology, and pore size distribution was explored. The stability of the emulsion was investigated by comparing the pore morphology of the cured sample at different set times, such as 0, 6, and 72 h. Scanning electron microscopy was employed for the characterization of the porous structures. The image analysis was conducted, and the pore size distribution, porosity, and open‐cell ratio of each sample were calculated. Interconnected pores have been seen in the porous PDMS made from emulsions with an internal phase larger than 30%. The results demonstrated that the frequency of open‐cell pores and the pore size is dependent on the surfactant types.
Miniaturization of InGaP/InGaAs/Ge solar cells for micro‐concentrator photovoltaics
Authors: Albert Pierre , Jaouad Abdelatif , Hamon Gwenaëlle , Volatier Maïté , Valdivia Christopher E. , Deshayes Yannick , Hinzer Karin , Béchou Laurent , Aimez Vincent , Darnon Maxime
Published: May 2021

Micro‐concentrator photovoltaic (CPV), incorporating micro‐scale solar cells within concentrator photovoltaic modules, promises an inexpensive and highly efficient technology that can mitigate the drawbacks that impede standard CPV, such as resistive power losses. In this paper, we fabricate micro‐scale multijunction solar cells designed for micro‐CPV applications. A generic process flow, including plasma etching steps, was developed for the fabrication of complete InGaP/InGaAs/Ge microcells with rectangular, circular, and hexagonal active areas down to 0.089 mm2 (0.068‐mm2 mesa). Large cells (>1 mm2) demonstrate good electrical performance under one sun AM1.5D illumination, but a degradation in the open‐circuit voltage (VOC) is observed on the smallest cells. This effect is attributed to perimeter recombination for which a passivation effect by the antireflective coating partially recovers the VOC. The VOC penalty for small cells is also reduced under high‐intensity illumination, from 3.8% under sun to 1.0% at 974 suns. High intensity illumination yields an efficiency of 33.8% under 584 suns for a 0.25‐mm2 and microcells are expected to show higher efficiency than standard cells under very high concentration.
Unzipping and scrambling reaction‐induced sequence control of copolymer chains via temperature changes during cationic ring‐opening copolymerization of cyclic acetals and cyclic esters
Authors: Higuchi Motoki , Kanazawa Arihiro , Aoshima Sadahito
Published: May 2021

A temperature change‐dependent sequence transformation of copolymer chains was demonstrated by a method based on tandem depolymerization and transacetalization reactions during the cationic ring‐opening copolymerization of cyclic acetals and cyclic esters. In this study, the position of polymerization‐depolymerization equilibrium was controlled by the reaction temperature rather than by the decrease in monomer concentration under vacuum conditions, as in our previous study. First, the conditions for efficient copolymerization were optimized, with a particular focus on the structures of cyclic acetals and cyclic esters. Subsequently, sequence transformation induced by temperature change was examined during the copolymerization of 2‐methyl‐1,3‐dioxepane (generated in situ from 4‐hydroxybutyl vinyl ether) and δ‐valerolactone using EtSO3H. The homosequence length of cyclic acetals decreased during depolymerization (unzipping) at the oxonium chain ends upon increasing the temperature from 30 to 90 °C, while transacetalization (scrambling) of the main chain transferred midchain cyclic acetal homosequences to the oxonium chain ends. As a result of the cycle of unzipping and scrambling reactions, an alternating‐like copolymer was obtained. Interestingly, the possibility of reversible sequence transformation upon heating and cooling was also demonstrated.
Effects of peripherally inserted central catheter on dosimetry of the blood vessel region in volumetric modulated arc therapy planning for lung cancer
Authors: Bi Suyan , Zhao Mang , Ma Jun , Chen Zhijian , Liang Jun
Published: May 2021

Objective

A peripherally inserted central catheter (PICC) is a safe and effective drug delivery method of chemoradiotherapy for lung cancer. However, the risk of vascular damage to patients who require PICC implantation during radiotherapy may be increased. This study compared dosimetry differences in the blood vessel region, as well as the planning target volume and other organs at risk between two volumetric modulated arc therapy plans with and without a PICC for lung cancer. The aim of which was to provide guidance for clinicians to select the proper PICC implantation time.

Methods

A total of 10 male patients with PICCs who received chemoradiotherapy for lung cancer in Cancer Hospital Chinese Academy of Medical Sciences, Shenzhen Center between 1 January 2019 and 30 November 2019 were included. The prescription dose was 50 Gy in 25 fractions. Two volumetric modulated arc therapy plans, with and without a PICC, were designed for each selected patient on a Varian Eclipse 13.6™ planning system. Statistical analysis of the blood vessel dose distribution of the PICC region and the target dose distribution, including the homogeneity index and conformity index, as well as irradiation doses to the lungs, heart, esophagus, and spinal cord, was carried out for the two groups and the differences were compared.

Results

When comparing the two plans, the mean dose (Dmean) of the PICC region for the plan with PICC was lower than that for the plan without(P = 0.01). The conformity index of the target, the maximum dose (Dmax) and minimum dose (Dmin) of the blood vessel of the PICC region, ranged from 2 to 20% in both groups, with no significant difference (conformity index: P = 0.87, Dmax: P = 0.81, Dmin: P = 0.83). There was no statistically significant difference in the D2% (P = 0.34) and D98% (P = 0.30) of the target, V20% (P = 0.34) and V30% (P = 0.34) of the heart, Dmax (P > 0.05) and Dmin (P > 0.05) of the esophagus, V5% (P = 0.34), V20% (P = 0.33), V30% (P = 0.17), and Dmean (P = 0.33) of the lungs, and Dmax (P = 0.34) of the spinal cord between the two groups of plans.

Conclusion

Despite the lack of significance in the dose distribution of the target and organs at risk, the effect of dosimetry in the blood vessel region of the PICC is obvious. As a result, the PICC will affect the dose distribution of the blood vessel region of the PICC and the target close to the PICC region. It is inadvisable to implant a PICC during radiation therapy.
Inverse agonism at the Na/K‐ATPase receptor reverses EMT in prostate cancer cells
Authors: Banerjee Moumita , Li Zhichuan , Gao Yingnyu , Lai Fangfang , Huang Minqi , Zhang Zhongbing , Cai Liquan , Sanabria Juan , Gao Tianyan , Xie Zijian , Pierre Sandrine V.
Published: May 2021

The surface expression of Na/K‐ATPase α1 (NKA) is significantly reduced in primary prostate tumors and further decreased in bone metastatic lesions. Here, we show that the loss of cell surface expression of NKA induces epithelial–mesenchymal transition (EMT) and promotes metastatic potential and tumor growth of prostate cancer (PCa) by decreasing the expression of E‐cadherin and increasing c‐Myc expression via the activation of Src/FAK pathways. Mechanistically, reduced surface expression of NKA in PCa is due to increased endocytosis through the activation of NKA/Src receptor complex. Using a high‐throughput NKA ligand‐screening platform, we have discovered MB5 as an inverse agonist of the NKA/Src receptor complex, capable of blocking the endocytosis of NKA. MB5 treatment increased NKA expression and E‐cadherin in PCa cells, which reversed EMT and consequently decreased the invasion and growth of spheroid models and tumor xenografts. Thus, we have identified a hitherto unrecognized mechanism that regulates EMT and invasiveness of PCa and demonstrated for the first time the feasibility of identifying inverse agonists of receptor NKA/Src complex and their potential utility as anticancer drugs. We, therefore, conclude that cell surface expression of α1 NKA can be targeted for the development of new therapeutics against aggressive PCa and that MB5 may serve as a prototype for drug development against EMT in metastatic PCa.
A polymorphism in the promoter of FRAS1 is a candidate SNP associated with metastatic prostate cancer
Authors: Wang Victoria , Geybels Milan S. , Jordahl Kristina M. , Gerke Travis , Hamid Anis , Penney Kathryn L. , Markt Sarah C. , Freedman Matthew , Pomerantz Mark , Lee Gwo‐Shu M. , Rana Huma , Börnigen Daniela , Rebbeck Timothy R. , Huttenhower Curtis , Eeles Ros A. , Stanford Janet L. , Consortium Practical , Berndt Sonja I. , Claessens Frank , Sørensen Karina D. , Park Jong Y. , Vega Ana , Usmani Nawaid , Mucci Lorelei , Sweeney Christopher J.
Published: May 2021

Background

Inflammation and one of its mediators, NF‐kappa B (NFκB), have been implicated in prostate cancer carcinogenesis. We assessed whether germline polymorphisms associated with NFκB are associated with the risk of developing lethal disease (metastases or death from prostate cancer).

Methods

Using a Bayesian approach leveraging NFκB biology with integration of publicly available datasets we used a previously defined genome‐wide functional association network specific to NFκB and lethal prostate cancer. A dense‐module‐searching method identified modules enriched with significant genes from a genome‐wide association study (GWAS) study in a discovery data set, Physicians' Health Study and Health Professionals Follow‐up Study (PHS/HPFS). The top 48 candidate single nucleotide polymorphisms (SNPs) from the dense‐module‐searching method were then assessed in an independent prostate cancer cohort and the one SNP reproducibly associated with lethality was tested in a third cohort. Logistic regression models evaluated the association between each SNP and lethal prostate cancer. The candidate SNP was assessed for association with lethal prostate cancer in 6 of 28 studies in the prostate cancer association group to investigate cancer associated alterations in the genome (PRACTICAL) Consortium where there was some medical record review for death ascertainment which also had SNP data from the ONCOARRAY platform. All men self‐identified as Caucasian.

Results

The rs1910301 SNP which was reproducibly associated with lethal disease was nominally associated with lethal disease (odds ratio [OR] = 1.40; p = .02) in the discovery cohort and the minor allele was also associated with lethal disease in two independent cohorts (OR = 1.35; p = .04 and OR = 1.35; p = .07). Fixed effects meta‐analysis of all three cohorts found an association: OR = 1.37 (95% confidence interval [CI]: 1.15–1.62, p = .0003). This SNP is in the promoter region of FRAS1, a gene involved in epidermal‐basement membrane adhesion and is present at a higher frequency in men with African ancestry. No association was found in the subset of studies from the PRACTICAL consortium studies which had a total of 106 deaths out total of 3263 patients and a median follow‐up of 4.4 years.

Conclusions

Through its connection with the NFκB pathway, a candidate SNP with a higher frequency in men of African ancestry without cancer was found to be associated with lethal prostate cancer across three well‐annotated independent cohorts of Caucasian men.
Amino acid sequence identification of goji berry cyclic peptides and anticervical carcinoma activity detection
Authors: Ji Hongxia , Ma Junxia , Guo Lianjun , Huang Yongmei , Wang Weihong , Sun Xiuyan , Sun Rongchun
Published: May 2021

The goji berry is widely used as tonics; however, the antihuman cervical carcinoma effect and underlying mechanism of goji berry peptide remain to be elucidated. The cyclic peptides are appealing targets in antitumor agent development, and in current study, three novel goji berry cyclic peptides (GCPs) were isolated and amino acid sequence identified. Among them, GCP‐1 (Cycle‐(Trp‐Glu‐His‐Thr)) inhibited proliferation and induced human cervical cancer (HeLa) cells apoptosis and blocked the HeLa cells in G0/G1 phase significantly. Furthermore, the GCP‐1 also inhibited the cervical carcinoma growth in vivo. Moreover, GCP‐1 suppressed the cyclin expression and activated the caspase cascade and poly(ADP‐ribose) polymerase. Of note, GCP‐1 may be a promising novel inhibitor of human cervical cancer.
An artificial neural network−pharmacokinetic model and its interpretation using Shapley additive explanations
Authors: Ogami Chika , Tsuji Yasuhiro , Seki Hiroto , Kawano Hideaki , To Hideto , Matsumoto Yoshiaki , Hosono Hiroyuki
Published: May 2021

We developed a method to apply artificial neural networks (ANNs) for predicting time‐series pharmacokinetics (PKs), and an interpretable the ANN‐PK model, which can explain the evidence of prediction by applying Shapley additive explanations (SHAP). A previous population PK (PopPK) model of cyclosporin A was used as the comparison model. The patients’ data were used for the ANN‐PK model input, and the output by ANN was the clearance (CL). The estimated CL value from the ANN were substituted into the one‐compartment with one‐order absorption model, the concentrations were calculated, and the parameters of ANN were updated by the back‐propagation method. Kernel SHAP was applied to the trained model and the SHAP value of each input was calculated. The root mean squared error for the PopPK model and the ANN‐PK model were 41.1 and 31.0 ng/ml, respectively. The goodness of fit plots for the ANN‐PK model represented more convergence to y = x compared with that for the PopPK model, with good model performance for the ANN‐PK model. The most influential factors on CL output were age and body weight from the evaluation using Kernel SHAP, and these factors were incorporated into the PopPK model as the significant covariates of CL. The ANN‐PK model could handle time‐series data and showed higher prediction accuracy then the conventional PopPK model, and the scientific validity for the model could be evaluated by applying SHAP.

Study Highlights

WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?

A black‐box property of an artificial neural network (ANN) decreases the scientific confidence of the model, and making it difficult to utilize the ANN in the medical field. Moreover, difficulty in handling the time‐series data is a significant problem for applying the ANN for pharmacometrics study.

WHAT QUESTION DID THIS STUDY ADDRESS?

How can we apply the ANN for predicting the time‐series pharmacokinetics (PKs) , and confirm the scientific validity of the ANN model?

WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?

Using the ANN in combination with a conventional compartment (ANN‐PK) model enabled to handle the time‐series PK data, and the predicting performance of the model was higher than that of the population PK model. Furthermore, we could evaluate the scientific validity of the ANN model by applying the Shapley additive explanations.

HOW MIGHT THIS CHANGE DRUG DISCOVERY, DEVELOPMENT, AND/OR THERAPEUTICS?

We expect that our study will contribute to develop the interpretable ANN model, which can predict the time‐series PKs, drug efficacies, and side effects with high prediction performance.
Poly(3,4‐ethylenedioxythiophene)‐poly(styrenesulfonate) Modified by Water for Efficient Inverted Perovskite Solar Cells
Authors: Xiong Jian , Zhao Qian , Liu Weizhi , Dai Zhongjun , Fan Baojin , Xue Xiaogang , Huang Yu , Zhang Xiuyun , Zhang Zheling , Cai Ping , Dai Qilin , Zhang Jian
Published: May 2021

Poly(3,4‐ethylenedioxythiophene)/poly(styrenesulfonate) (PEDOT:PSS) is a popular hole transport material in inverted perovskite solar cells (PSCs). However, it is required to modify the PEDOT:PSS to achieve high‐performance PSCs. Herein, a facile method to modify PEDOT:PSS using water to improve the performance of inverted PSCs is developed. The modification impact on the physical properties of the PEDOT:PSS films is systemically studied. The results show that the transmittance and resistance of the PEDOT:PSS layer are greatly improved by modification using water without changing its work function. The growth of perovskite films on PEDOT:PSS is also influenced by the modification of PEDOT:PSS using water. Better crystallinity and larger grain sizes of the perovskite film are also achieved, leading to recombination loss being greatly reduced and the performance of the devices significantly improved. The PSCs based on modified PEDOT:PSS exhibit a higher power conversion efficiency (PCE) of 17.28 % and higher open‐circuit voltage (V
oc) of 1.06 V compared to control devices prepared with unmodified PEDOT:PSS (PCE = 12.49%, V
oc  = 0.99 V). This work provides a facile method to modify PEDOT:PSS to prepare high‐performance inverted PSCs.
MnNBr Monolayer: A High‐Temperature Ferromagnetic Half‐Metal with Type‐II Weyl Fermions
Authors: Shi Yongting , Li Lingjun , Cui Xin , Song Tielei , Liu Zhifeng
Published: May 2021

For spintronics, it is highly desirable to obtain stable low‐dimensional materials with ferromagnetic ground state, 100% spin polarization, and high Curie temperature. Moreover, type‐II Weyl fermions are also desired for realizing high‐speed anisotropic transport. Herein, based on first‐principles calculations, the orthorhombic MnNBr monolayer is identified as a needed ferromagnetic half‐metal, which not only has a high Curie temperature (910 K), but also holds type‐II Weyl state with Lorentz symmetry broken. Analysis of the stability reveals that the MnNBr monolayer is energetically, mechanically, dynamically, and thermally stable. Remarkably, in the vicinity of the Fermi level there exist both type‐I and titled type‐II Weyl states, whose nodes form continuously distributed Weyl loops. Under intrinsic out‐of‐plane magnetization, they are robust against spin–orbital coupling due to the protection of glide mirror symmetry. Moreover, near the type‐II Weyl point, there is direction‐dependent band dispersion: the largest fermion velocities can be found in the
k
path of G–X (up to 6.86 × 105 m s−1), while quasi‐flat bands with negligible band dispersion can be found along the direction being parallel to G–Y. This indicates that MnNBr monolayer should be a promising candidate for further applications of high‐speed anisotropic transport and studies of strongly correlated electronic states.
Conditional assurance: the answer to the questions that should be asked within drug development
Authors: Temple Jane R. , Robertson Jon R.
Published: May 2021

In this paper, we extend the use of assurance for a single study to explore how meeting a study's pre‐defined success criteria could update our beliefs about the true treatment effect and impact the assurance of subsequent studies. This concept of conditional assurance, the assurance of a subsequent study conditional on success in an initial study, can be used assess the de‐risking potential of the study requiring immediate investment, to ensure it provides value within the overall development plan. If the planned study does not discharge sufficient later phase risk, alternative designs and/or success criteria should be explored. By transparently laying out the different design options and the risks associated, this allows for decision makers to make quantitative investment choices based on their risk tolerance levels and potential return on investment.

This paper lays out the derivation of conditional assurance, discusses how changing the design of a planned study will impact the conditional assurance of a future study, as well as presenting a simple illustrative example of how this methodology could be used to transparently compare development plans to aid decision making within an organisation.
Tank‐Circuit Assisted Coupling Method for Sympathetic Laser Cooling
Authors: Tu Bingsheng , Hahne Felix , Arapoglou Ioanna , Egl Alexander , Heiße Fabian , Höcker Martin , König Charlotte , Morgner Jonathan , Sailer Tim , Weigel Andreas , Wolf Robert , Sturm Sven
Published: May 2021

The coupling of the motion of two ion species in separate Penning traps via a common tank circuit is discussed. The enhancement of the coupling assisted by the tank circuit is demonstrated by an avoided crossing behavior measurement of the motional modes of two coupled ions. An intermittent laser cooling method for sympathetic cooling is proposed and a theoretical description is provided. The technique enables tuning of the coupling strength between two ion species in separate traps and thus allows for efficient sympathetic cooling of an arbitrary type of single ion for high‐precision Penning‐trap experiments.
Deterministic Integration of hBN Emitter in Silicon Nitride Photonic Waveguide
Authors: Elshaari Ali W. , Skalli Anas , Gyger Samuel , Nurizzo Martin , Schweickert Lucas , Esmaeil Zadeh Iman , Svedendahl Mikael , Steinhauer Stephan , Zwiller Val
Published: May 2021

Hybrid integration provides an important avenue for incorporating atom‐like solid‐state single‐photon emitters into photonic platforms that possess no optically‐active transitions. Hexagonal boron nitride (hBN) is particularly interesting quantum emitter for hybrid integration, as it provides a route for room‐temperature quantum photonic technologies, coupled with its robustness and straightforward activation. Despite the recent progress of integrating hBN emitters in photonic waveguides, a deterministic, site‐controlled process remains elusive. Here, the integration of selected hBN emitter in silicon nitride waveguide is demonstrated. A small misalignment angle of 4° is shown between the emission‐dipole orientation and the waveguide propagation direction. The integrated emitter maintains high single‐photon purity despite subsequent encapsulation and nanofabrication steps, delivering quantum light with zero delay second order correlation function . The results provide an important step toward deterministic, large scale, quantum photonic circuits at room temperature using atom‐like single‐photon emitters.
Catamenial haemoptysis in females with cystic fibrosis: a case series with review of management strategies
Authors: Bozkanat Kubra M. , West Natalie E. , Ladores Sigrid , Montemayor Kristina , Tupayachi Ortiz Maria Gabriela , Christianson Mindy , Jain Raksha
Published: May 2021

Catamenial haemoptysis, the expectoration of blood during menses, has not been extensively reported in the cystic fibrosis (CF) literature. We describe four cases (age range: 25–34 years) of catamenial haemoptysis across four CF centres in the United States. These cases may represent thoracic endometriosis versus hormonal fluctuations in airway inflammation or infection resulting in bronchial artery bleeding. We identify common and nuanced management strategies including use of pro‐coagulants, hormone contraceptives, anti‐inflammatories, bronchial artery embolization, and use of the newer cystic fibrosis transmembrane conductance regulator (CFTR) modulators.
Intrapleural fibrinolysis in acute non‐traumatic retained haemothorax
Authors: Foo Chuan T. , Herre Jurgen
Published: May 2021

Haemothorax is an accumulation of blood in the pleural space. Retained haemothorax refers to blood that cannot be drained from the pleural cavity and is associated with an increased risk of empyema and fibrothorax often necessitating surgical evacuation. We describe our experience of using intrapleural fibrinolytic therapy in three patients with different bleeding risk and acute non‐traumatic retained haemothorax. The first was a 41‐year‐old female with disseminated Candida guilliermondii sepsis and an iatrogenic haemothorax, second was a 48‐year‐old female with transfusion‐dependent acute myeloid leukaemia and spontaneous haemothorax, and the third was a 72‐year‐old female with spontaneous haemothorax from newly diagnosed lung cancer. All patients received one to two doses of intrapleural alteplase without any bleeding complications and resolution of retained haemothorax. This case series demonstrates the successful application and safety of this approach as an alternative to surgery in a well‐resourced environment with close monitoring and ready access to blood transfusion.
Visual‐electromagnetic system: A novel fusion‐based monocular localization, reconstruction, and measurement for flexible ureteroscopy
Authors: Fu Zuoming , Jin Ziyi , Zhang Chongan , Dai Yu , Gao Xiaofeng , Wang Zeyu , Li Ling , Ding Guoqing , Hu Haiyi , Wang Peng , Ye Xuesong
Published: May 2021

Background

During flexible ureteroscopy (FURS), surgeons may lose orientation due to intrarenal structural similarities and complex shape of the pyelocaliceal cavity. Decision‐making required after initially misjudging stone size will also increase the operative time and risk of severe complications.

Methods

A intraoperative navigation system based on electromagnetic tracking (EMT) and simultaneous localization and mapping (SLAM) was proposed to track the tip of the ureteroscope and reconstruct a dense intrarenal three‐dimensional (3D) map. Furthermore, the contour lines of stones were segmented to measure the size.

Results

Our system was evaluated on a kidney phantom, achieving an absolute trajectory accuracy root mean square error (RMSE) of 0.6 mm. The median error of the longitudinal and transversal measurements was 0.061 and 0.074 mm, respectively. The in vivo experiment also demonstrated the effectiveness.

Conclusion

The proposed system worked effectively in tracking and measurement. Further, this system can be extended to other surgical applications involving cavities, branches and intelligent robotic surgery.