bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative dosimetry of radiography device, MSCT device and two CBCT devices in the elbow region
Authors: Koivisto Juha , van Eijnatten Maureen , Ludlow John , Kiljunen Timo , Shi Xie‐Qi , Wolff Jan
Published: April 2021

The aim of the study was to estimate and to compare effective doses in the elbow region resulting from four different x‐ray imaging modalities. Absorbed organ doses were measured using 11 metal oxide field effect transistor (MOSFET) dosimeters that were placed in a custom‐made anthropomorphic elbow RANDO phantom. Examinations were performed using Shimadzu FH‐21 HR radiography device, Siemens Sensation Open 24‐slice MSCT‐device, NewTom 5G CBCT device, and Planmed Verity CBCT device, and the effective doses were calculated according to ICRP 103 recommendations. The effective dose for the conventional radiographic device was 1.5 µSv. The effective dose for the NewTom 5G CBCT ranged between 2.0 and 6.7 µSv, for the Planmed Verity CBCT device 2.6 µSv and for the Siemens Sensation MSCT device 37.4 µSv. Compared with conventional 2D radiography, this study demonstrated a 1.4–4.6 fold increase in effective dose for CBCT and 25‐fold dose for standard MSCT protocols. When compared with 3D CBCT protocols, the study showed a 6‐19 fold increase in effective dose using a standard MSCT protocol. CBCT devices offer a feasible low‐dose alternative for elbow 3D imaging when compared to MSCT.
Socioeconomic Inequalities in All‐Cause and Cause‐Specific Mortality Among Patients With Osteoarthritis in the Skåne Region of Sweden
Authors: Lindéus Maria , Turkiewicz Aleksandra , Englund Martin , Kiadaliri Ali
Published: April 2021

Objective

To assess the association between education and all‐cause and cause‐specific mortality among patients with osteoarthritis (OA) in comparison to an OA‐free reference cohort.

Methods

Using data from the Skåne Healthcare Register, we identified all residents age ≥45 years in the region of Skåne in southern Sweden with doctor‐diagnosed OA of peripheral joints between 1998 and 2013 (n = 123,993). We created an age‐ and sex‐matched reference cohort without OA diagnosis (n = 121,318). Subjects were followed until death, relocation outside Skåne, or the end of 2014. The relative index of inequality (RII) and the slope index of inequality (SII) were estimated by the Cox model and Aalen's additive hazard model, respectively.

Results

We found an inverse association between education and mortality. The magnitude of relative inequalities in all‐cause mortality were comparable in the OA, with an RII of 1.53 (95% confidence interval [95% CI] 1.46, 1.61), and reference cohorts (RII 1.54 [95% CI 1.47, 1.62]). The absolute inequalities were smaller in the OA cohort (all‐cause deaths per 100,000 person‐years, SII 937 [95% CI 811, 1,063]) compared with the reference cohort (SII 1,265 [95% CI 1,109, 1,421]). Cardiovascular mortality contributed more to the absolute inequalities in the OA cohort than in the reference cohort (60.1% versus 48.1%) while the opposite was observed for cancer mortality (8.5% versus 22.3%).

Conclusion

We found higher all‐cause and cause‐specific mortality in OA patients with lower education. The observed inequalities in the OA cohort reflect the inequalities in the population at large. The greater burden of cardiovascular diseases in OA patients suggests that proper management of cardiovascular risk factors in OA patients is important.
Additive Manufacturing of Aluminum‐Based Metal Matrix Composites—A Review
Authors: Tang Shengyang , Ummethala Raghunandan , Suryanarayana Challapalli , Eckert Jürgen , Prashanth Konda Gokuldoss , Wang Zhi
Published: April 2021

Al‐based metal matrix composites (AMMCs) have found enormous applications in the aerospace, automobile, and other structural applications. Compared with the conventional processes such as casting and powder metallurgy, AMMCs processed by additive manufacturing show a significant difference between microstructure and properties. This work presents the achievements of AMMCs fabricated by additive manufacturing in recent years, which is divided into six sections. Starting with the introduction, this work focuses on different fabrication methods such as composite powders and bulk material production. This is followed by discussing the microstructure in relation to the typical reinforcements and matrices, interface, and defects, and emphasizes the advantages and disadvantages compared with the unreinforced counterparts. The fourth part summarizes the recently obtained mechanical properties and the fifth part discusses the possible strengthening mechanisms and their connection with the mechanical properties. The last part is devoted to concluding the advantages, limitation, and outlook of the additively manufactured AMMCs. This review will provide a comprehensive picture of the processing–microstructure–property‐strengthening mechanisms correlation of these composites.
High‐Performance Large‐Scale Vertical 1T'/2H Homojunction CVD‐Grown Polycrystalline MoTe2 Transistors
Authors: Xie Zijian , Lei Wenyu , Zhang Wenfeng , Liu Yuan , Yang Li , Wen Xiaokun , Chang Haixin
Published: April 2021

2D transition metal dichalcogenides (TMDs) have emerged as an ideal alternative to silicon in advanced electronics. Especially, MoTe2 attracts peculiar attention since it offers a unique opportunity of resolving critical electrical contacts. Currently, although MoTe2‐based coplanar semiconductor‐metal circuitry realized by epitaxial growth and chemical assembly has been demonstrated, while still suffers from the requirement of extremely accurate synthesis process control. Here, a facile strategy is demonstrated to fabricate large scale and high performance MoTe2 transistors with a 1T'/2H vertical homojunction structure by combining a spatial and phase controlled MoTe2 scalable synthesis and a scalable universal transfer method with water‐soluble poly‐vinylpyrrolidone and poly‐(vinyl alcohol) bilayer mediator. Both high quality 1T'‐ and 2H‐ MoTe2 with controlled dimensions can be scalable synthesized via a shadow mask assisted chemical vapor deposition method. These as‐synthesized MoTe2 patterns can be successfully transferred to a wide range of substrates at a high yield >80% with well‐retained properties to construct transistors with a complex vertical 1T'/2H‐MoTe2/HfAlO2 structure. The devices exhibit an on/off current ratio surpassing 104 and a typical mobility of ≈29 cm2 V−1 s−1. The developed scaled strategy of combining both scalable MoTe2 synthesis and transfer offers a feasible way for potential MoTe2‐based large‐scale electronics.
Functionalization of Low‐k Polyimide Gate Dielectrics with Self‐Assembly Monolayer Toward High‐Performance Organic Field‐Effect Transistors and Circuits
Authors: Zheng Yingshuang , Yu Li , Wang Zhongwu , Chen Xiaosong , Li Jie , Zou Ye , Ji Deyang , Li Liqiang , Hu Wenping
Published: April 2021

The functionalization of polymer dielectrics with self‐assembly monolayer is still a big issue to be resolved due to the lack of particular anchoring sites on their surface for specific binding. To this end, hydroxyl groups are a kind of commonly used anchoring sites, which can be effectively produced on polymer surface by oxygen plasma treatment. In this work, the modification methods are investigated and the assembly conditions of self‐assembly monolayer are characterized on the surface of low‐k polyimide (PI) gate dielectric layers. As a result, the device performance can be enhanced by an order of magnitude under the optimal modified state compared with the initial state. In addition, the charge transport mechanism of organic semiconductor on PI surface is studied through temperature‐variable experiments. Furthermore, organic logic circuits (NAND gate, NOR gate, inverter, and oscillator) are manufactured using modified PI as insulating layers. The functionalization of polymer dielectrics with self‐assembly monolayer offers an effective strategy to improve the device performance in organic electronics.
Technical Challenges and Perspectives for the Commercialization of Solution‐Processable Solar Cells
Authors: Liu Hongtao , Yu Ming‐Hsuan , Lee Chia‐Chen , Yu Xinyu , Li Yibin , Zhu Zonglong , Chueh Chu‐Chen , Li Zhong'an , Jen Alex K.‐Y.
Published: April 2021

As the new‐generation photovoltaic technologies, organic solar cells (OSCs) and perovskite solar cells (PVSCs) offer significant advantages over Si‐ and CdTe‐based solar cells, that is, facile low‐temperature solution processability and excellent cost‐performance ratios. At present, OSCs and PVSCs have achieved very high certified power conversion efficiencies of 17.5% and 25.5%, respectively, which have already approached the efficiencies needed for commercial applications. However, there are still several obstacles that need to be overcome before they can be deployed as new‐generation of printable photovoltaic technologies. More efforts also need to be devoted to finding applicable methods for manufacturing highly efficient, large‐area devices and improving their long‐term operational stability. Thus, this article provides a comprehensive review on the current status and technical challenges for commercializing these two solution‐processable solar cells.
Plasmonic Saturable Absorbers
Authors: Zhao Di , Liu Yi , Qiu Jianrong , Liu Xiaofeng
Published: April 2021

Plasmonic materials are able to spatially confine light to a nanometer scale far smaller than the diffraction limit, resulting in drastically enhanced electrical field strength and stimulating applications in nonlinear optics, energy, and biomedicine. Resonant excitation of plasmonic nanostructures by ultrafast pulses results in a subpicosecond‐scale transient photobleaching that originates from the thermalization and cooling of hot carriers, which manifests strong optical nonlinearity that is leveraged for optical modulation and switching. Herein, recent advances in the use of noble and non‐noble metal‐based plasmonic materials as saturable absorbers (SAs) in both solid‐state and fiber lasers for the generation of Q‐switched and mode‐locked pulses are discussed. Starting with a brief introduction on the operation mechanisms of pulsed lasers and photophysics of plasmonics, a discussion on the nonlinear optical (NLO) properties as well as the recent developments of pulsed lasers driven by these plasmonic SAs is focused upon. The pros and cons of using different plasmonic materials for SAs in terms of their material properties and linear/NLO responses are further analyzed. Along with a short summary of the current progress of plasmonic SAs, highlight future challenges in the development of plasmonic SAs for practical laser systems are finally highlighted.
The Recent Progress in Cellulose Paper‐Based Triboelectric Nanogenerators
Authors: Liang Shuaibo , Wang Yanyun , Liu Qian , Yuan Tao , Yao Chunli
Published: April 2021

Developing new energy technology is a significant challenge in the context of the energy crisis. As a novel energy conversion device to convert mechanical energy into electricity, the triboelectric nanogenerator (TENG) has attracted significant attention in the past few years. The choice of component materials directly affects the cost, environmental performance, output performance, and preparation process of a TENG. In recent years, cellulose paper has become an ideal material for fabricating a TENG due to its lightweight, biodegradability, low‐cost, high flexibility, environmental friendliness, porosity, and easy modification. Cellulose paper‐based TENG has become a hot topic in the field of green energy. This paper systematically summarizes the research progress of the cellulose paper‐based TENG. The advantages of cellulose paper as raw material to fabricate a TENG, followed by introducing the different roles of cellulose paper in paper‐based TENGs, are first discussed. Then the recent progress in energy storage, performance optimization methods, hybridization, and applications of cellulose paper‐based TENGs is successively elaborated. Finally, some perspectives and challenges for the future development of cellulose paper‐based TENG are discussed to provide guidance.
Nanotechnologies for Intracellular Protein Delivery: Recent Progress in Inorganic and Organic Nanocarriers
Authors: Le Saux Sarah , Aubert‐Pouëssel Anne , Ouchait Lyria , Mohamed Khaled Elhady , Martineau Pierre , Guglielmi Laurence , Devoisselle Jean‐Marie , Legrand Philippe , Chopineau Joël , Morille Marie
Published: April 2021

From recombinant insulin to monoclonal antibodies, proteins have become essential drugs in the therapeutic arsenal and respond to a broad spectrum of diseases. While commercially available proteins have an extracellular activity, intracellular targets can be a powerful alternative to treat many pathologies such as cancers and immune disorders, but also infectious diseases. Nevertheless, to enter the cell and reach the target organelle or molecule, therapeutic proteins have to face numerous barriers (internalization, endosomal escape, and cytoplasm trafficking). In view of the fragile nature and high heterogeneity of proteins in terms of size, charge, and hydrophilic/lipophilic profile, the development of an efficient cytoplasm delivery system remains a long‐standing challenge. The discovery of several gene editing tools (Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR), involving caspase 9 (Cas9) protein (CRISPRCas9), transcription activator‐like effectors (TALEs) or other zinc‐finger proteins (ZFPs)) has particularly boosted this research field in the last decade. Among delivery systems that can be used in vivo, some synthetic nanovectors offer interesting opportunities. In this review, the authors describe the most recent progress in the development of inorganic (silica, gold, phosphate, metal–organic framework, carbon nanoparticles) as well as organic (polymer, lipid) nanoparticles, both applied to intracellular protein delivery.
Progress and Prospects of Regulatory Functions Mediated by Nitric Oxide on Immunity and Immunotherapy
Authors: Hu Qian , Shi Jingyu , Zhang Jiao , Wang Yi , Guo Yuanyuan , Zhang Zhiping
Published: April 2021

Nitric oxide (NO), as a crucial signaling biomolecule, is closely involved in the cardiovascular, immune, and central nervous system. NO not only participates in the proliferation, differentiation, and activation of immune cells but also regulates the secretion and function of immune‐related cytokines. Meanwhile, NO plays an important role in regulating diversified pathological processes, such as cancer, autoimmune disease, pathogenic infection, and so on. Therefore, the intensive immunological study of NO has been expected to provide valuable approaches to the clinical prevention and treatment of these related diseases. Since NO has a wide range of chemical activities and biological functions, the pleiotropic effects of NO are affected by its production, concentration and duration, target cell types and subtypes, species, and pathogenesis of the immune‐related diseases. It is thus necessary to create and develop certain platforms of drugs and related preparations that can precisely regulate NO for immunotherapy. This review summarizes the regulatory functions exerted by NO in immune response, and the pathological mechanisms of tumor, autoimmune disease, and pathogenic infection in which NO is involved. The application and trend of therapeutic strategies based on the direct regulation of NO in immunotherapy are further discussed.
Layer‐Controlled Low‐Power Tunneling Transistors Based on SnS Homojunction
Authors: Liang Jiakun , Li Hong , Liu Fengbin , Lu Jing
Published: April 2021

Utilizing the layer‐controlled bandgap of a 2D material is an effective way of improving a tunneling field‐effect transistor (TFET) device's performance because of the narrowing tunneling barrier. An ab initio quantum transport method is used to study the SnS homojunction TFETs at a sub‐10 nm scale through layer controlling. The optimal SnS homojunction TFET has a bilayer SnS as the source electrode, which possesses a low leakage current like the ML SnS TFET and a high on‐state current like the BL SnS TFET. The low SSave_4dec (subthreshold swing over four decades of the drain currents) of ≈47–48 mV dec−1 and I60 (drain current at 60 mV dec−1) of ≈1.1–1.2 µA µm−1 implies the BL source SnS TFET, a fast low‐power (LP) device. The optimal BL source SnS TFET with a gate length of Lg = 10 nm exceeds the LP device requirement of the International Technology Roadmap for Semiconductors (ITRS) (2013 version), and its negative capacitance counterparts can exceed the ITRS 2028 target for LP device at Lg = 5 nm.
On the Molecular Mechanism of a Photo‐Responsive Phase Change Memory
Authors: Amirjalayer Saeed
Published: April 2021

Inducing well‐defined transitions by external stimuli between different states of matter is at the core of responsive functional materials. Using light to interconvert between states with distinct and externally readable features such as optical properties, these photo‐responsive phase change materials (PCMs) are ideal candidates for photonic applications. In this context, correlating macroscopic phenomena with properties at the atomistic level is crucial to systematically tailor the performance of PCMs. In particular, to establish a bottom‐up strategy to engineer PCMs based on molecular building units, a detailed understanding of the dynamic properties is needed. Therefore, an atomistic study is reported capturing the structural evolution during the light‐induced phase transition of a tetra‐(azobenzene)‐methane based PCM. This out‐of‐equilibrium dynamics is accurately represented by an atomistic potential, developed using a population swapping genetic algorithm. The molecular mechanism of the phase transition is deciphered and the refractive index of the periodic matrix is investigated. Due to an interplay of structural rigidity and flexibility, already small structural rearrangements lead to alteration of the optical properties, which is fundamental to ensure high data‐transfer rates. By correlating molecular properties with the resulting functionality, the reported work provides an important step towards in silico engineering of photo‐responsive PCMs.
Terahertz Driven Reversible Topological Phase Transition of Monolayer Transition Metal Dichalcogenides
Authors: Zhou Jian , Xu Haowei , Shi Yongliang , Li Ju
Published: April 2021

This paper shows how terahertz light can drive ultrafast topological phase transitions in monolayer transition metal dichalcogenides (TMDs). The phase transition is induced by the light interaction with both electron and phonon subsystems in the material. The mechanism of such a phase transition is formulated by thermodynamics theory: the Gibbs free energy landscape can be effectively modulated under light, and the relative stability between different (meta‐)stable phases can be switched. This mechanism is applied to TMDs and reversible phase transitions between the topologically trivial 2H and nontrivial 1T′ phases are predicted, providing appropriate light frequency, polarization, and intensity are applied. The large energy barrier on the martensitic transformation path can be significantly reduced, yielding a small energy barrier phase transition with fast kinetics. Compared with other phase transition schemes, light illumination has great advantages, such as its non‐contact nature and easy tunability. The reversible topological phase transition can be applicable in high‐resolution fast data storage and in‐memory computing devices.
Myocardial Viability Imaging using Manganese‐Enhanced MRI in the First Hours after Myocardial Infarction
Authors: Jasmin Nur Hayati , Thin May Zaw , Johnson Robert D. , Jackson Laurence H. , Roberts Thomas A. , David Anna L. , Lythgoe Mark F. , Yang Philip C. , Davidson Sean M. , Camelliti Patrizia , Stuckey Daniel J.
Published: April 2021

Early measurements of tissue viability after myocardial infarction (MI) are essential for accurate diagnosis and treatment planning but are challenging to obtain. Here, manganese, a calcium analogue and clinically approved magnetic resonance imaging (MRI) contrast agent, is used as an imaging biomarker of myocardial viability in the first hours after experimental MI. Safe Mn2+ dosing is confirmed by measuring in vitro beating rates, calcium transients, and action potentials in cardiomyocytes, and in vivo heart rates and cardiac contractility in mice. Quantitative T1 mapping‐manganese‐enhanced MRI (MEMRI) reveals elevated and increasing Mn2+ uptake in viable myocardium remote from the infarct, suggesting MEMRI offers a quantitative biomarker of cardiac inotropy. MEMRI evaluation of infarct size at 1 h, 1 and 14 days after MI quantifies myocardial viability earlier than the current gold‐standard technique, late‐gadolinium‐enhanced MRI. These data, coupled with the re‐emergence of clinical Mn2+‐based contrast agents open the possibility of using MEMRI for direct evaluation of myocardial viability early after ischemic onset in patients.
A Poly‐Crystalline Silicon Nanowire Transistor with Independently Controlled Double‐Gate for Physically Unclonable Function by Multi‐States and Self‐Destruction
Authors: Yu Ji‐Man , Yun Gyeong‐Jun , Kim Moon‐Seok , Han Joon‐Kyu , Kim Da‐Jin , Choi Yang‐Kyu
Published: April 2021

With the advance of internet of things, numerous electronic devices are being connected to each other through the internet. As the number of connections has increased, security has become increasingly important. Physically unclonable function (PUF) is one of the essential approaches that can be used to secure data in device. In this work, an independently controlled double‐gate (ICDG) transistor composed of a poly‐crystalline silicon (poly‐Si) nanowire channel for PUF is first demonstrated. Simply fabricated using CMOS processes, the so‐called PUF transistor harnesses multi‐states and self‐destruction for advanced security. The randomness in the poly‐Si nanowire channel is established by the randomly distributed poly‐Si grains. This random distribution means each transistor has a different threshold voltage (Vth). Moreover, multi‐states composed of a primary bit and a secondary bit, can be distinguished by gate‐biasing. The primary bit is identified by applying the same gate voltage to an electrically tied double‐gate. The secondary bit is discerned by applying a different gate voltage to the ICDG. Security key capacity is doubled using the multi‐states, without increasing footprint. Based on reinforced randomness, the PUF transistor exhibits enhanced uniqueness and unpredictability. In addition, this PUF transistor is untraceable by electrical self‐destructibility when external hacking is attempted.
Rapid enthalpy prediction of transition states using molecular graph convolutional network
Authors: Gong Siyuan , Wang Yutong , Tian Yajie , Wang Li , Liu Guozhu
Published: April 2021

The rapid development of machine learning has provided low‐cost and high‐throughput molecular energy prediction methods; however, the direct energy prediction of transition states (TSs) in radical reactions has received little attention, which can facilitate the rapid construction of potential energy surface (PES) and chemical reactivity inference. Here, we present a generic descriptor of TSs, molecules and radicals to realize the simultaneous prediction of their enthalpy of formation through the augmented molecular graph convolutional network (MGCN). It is proved that the network can rapidly (within milliseconds per prediction) and accurately predict the enthalpy of various types of samples, of which the mean absolute error (MAE) of the held‐out test set is 1.44 kcal/mol (>50% samples less than 1.0 kcal/mol) with high R2 (0.925–0.998) among all categories. The PES constructed from predictions is close to the calculated results by density functional theory (DFT) and conforms to the trend of chemical reactivity.
Participatory Research Approaches with Youth: Ethics, Engagement, and Meaningful Action
Authors: Teixeira Samantha , Augsberger Astraea , Richards‐Schuster Katie , Sprague Martinez Linda
Published: April 2021

In this manuscript, we explore the promise and challenges of youth participatory action research (YPAR), paying particular attention to ethical issues and power dynamics that emerge in the context of research partnerships between youth and adults. We begin by reviewing the key tenets of YPAR and then go on to discuss how these tenets are often at odds with dominant approaches to research. We describe the tension between the values of YPAR and the systems and structures embedded in the academy. Further, we elucidate how adultism and the capitalist nature of the academy intersect with white supremacy culture, posing significant barriers to meaningful youth participation in community research partnerships. We then describe ways in which participatory scholars can disrupt these systems as well as larger paradigm shifts in the culture of academia that will be required to elevate youth voices and to amplify their efforts for equity.
Systematic Review of Cultural Aspects of Stigma and Mental Illness among Racial and Ethnic Minority Groups in the United States: Implications for Interventions
Authors: Misra Supriya , Jackson Valerie W. , Chong Jeanette , Choe Karen , Tay Charisse , Wong Jazmine , Yang Lawrence H.
Published: April 2021

Stigma is integral to understanding mental health disparities among racial and ethnic minority groups in the United States. We conducted a systematic review to identify empirical studies on cultural aspects of mental illness stigma (public, structural, affiliative, self) among three racial and ethnic minority groups (Asian Americans, Black Americans, Latinx Americans) from 1990 to 2019, yielding 97 articles. In comparison studies (N = 25), racial and ethnic minority groups often expressed greater public and/or self‐stigma than White American groups. In within‐group studies (N = 65; Asian American, n = 21; Black American, n = 18; Latinx American; n = 26), which were primarily qualitative (73%), four major cultural themes emerged: 1) service barriers including access and quality (structural stigma); 2) family experiences including concealment for family’s sake, fear of being a burden, and stigma extending to family (affiliative stigma); 3) lack of knowledge about mental illness and specific cultural beliefs (public stigma); and 4) negative emotional responses and coping (self‐stigma). These findings confirmed stigma has both similar and unique cultural aspects across groups. Despite this, few studies tested stigma reduction interventions (N = 7). These cultural insights can inform contextual change at the health systems and community levels to reduce stigma, and empowerment at the interpersonal and individual levels to resist stigma.
Smith–Magenis syndrome: Report of morphological and new functional cardiac findings with review of the literature
Authors: Onesimo Roberta , Versacci Paolo , Delogu Angelica Bibiana , De Rosa Gabriella , Pugnaloni Flaminia , Blandino Rita , Leoni Chiara , Calcagni Giulio , Digilio Maria C. , Zollino Marcella , Marino Bruno , Zampino Giuseppe
Published: April 2021

Smith–Magenis syndrome (SMS) is a genetic disorder characterized by multiple congenital anomalies, sleep disturbance, behavioral impairment, and intellectual disability. Its genetic cause has been defined as an alteration in the Retinoic Acid‐Induced 1 gene. Cardiac anomalies have been reported since the first description of this condition in patients with 17p11.2 deletion. Variable cardiac defects, including ventricular septal defects, atrial septal defects, tricuspid stenosis, mitral stenosis, tricuspid and mitral regurgitation, aortic stenosis, pulmonary stenosis, mitral valve prolapse, tetralogy of Fallot, and total anomalous pulmonary venous connection, have been anecdotally reported and systematic case series are still lacking. Herein, we define the spectrum of the cardiac phenotype and describe for the first time the cardiac function in a large cohort of pediatric patients with SMS. Revision of the literature and correlations between genotype and cardiac phenotype was performed.
Novel strategies for the characterization of cancellous bone morphology: Virtual isolation and analysis
Authors: Veneziano Alessio , Cazenave Marine , Alfieri Fabio , Panetta Daniele , Marchi Damiano
Published: April 2021

Objectives

The advent of micro‐computed tomography (μCT) made cancellous bone more accessible than ever before. Nevertheless, the characterization of cancellous bone is made difficult by its inherent complexity and the difficulties in defining homology across datasets. Here we propose novel virtual methodological approaches to overcome those issues and complement existing methods.

Materials and methods

We present a protocol for the isolation of the whole cancellous region within a μCT scanned bone. This method overcomes the subsampling issues and allows studying cancellous bone as a single unit. We test the protocol on a set of primate bones. In addition, we describe a set of morphological indices calculated on the topological skeleton of the cancellous bone: node density, node connectivity, trabecular angle, trabecular tortuosity, and fractal dimension. The usage of the indices is shown on a small comparative sample of primate femoral heads.

Results

The isolation protocol proves reliable in isolating cancellous structures from several different bones, regardless of their shape. The indices seem to detect some functional differences, although further testing on comparative samples is needed to clarify their potential for the study of cancellous architecture.

Conclusions

The approaches presented overcome some of the difficulties of trabecular bone studies. The methods presented here represent an alternative or supporting method to the existing tools available to address the biomechanics of cancellous bone.
Unravelling the Neural Basis of Spatial Delusions After Stroke
Authors: Alves Pedro N. , Fonseca Ana C. , Silva Daniela P. , Andrade Matilde R. , Pinho‐e‐Melo Teresa , Thiebaut de Schotten Michel , Martins Isabel P.
Published: April 2021

Objective

Knowing explicitly where we are is an interpretation of our spatial representations. Reduplicative paramnesia is a disrupting syndrome in which patients present a firm belief of spatial mislocation. Here, we studied the largest sample of patients with delusional misidentifications of space (ie, reduplicative paramnesia) after stroke to shed light on their neurobiology.

Methods

In a prospective, cumulative, case‐control study, we screened 400 patients with acute right‐hemispheric stroke. We included 64 cases and 233 controls. First, lesions were delimited and normalized. Then, we computed structural and functional disconnection maps using methods of lesion‐track and network‐mapping. The maps were compared, controlling for confounders. Second, we built a multivariate logistic model, including clinical, behavioral, and neuroimaging data. Finally, we performed a nested cross‐validation of the model with a support‐vector machine analysis.

Results

The most frequent misidentification subtype was confabulatory mislocation (56%), followed by place reduplication (19%), and chimeric assimilation (13%). Our results indicate that structural disconnection is the strongest predictor of the syndrome and included 2 distinct streams, connecting right fronto‐thalamic and right occipitotemporal structures. In the multivariate model, the independent predictors of reduplicative paramnesia were the structural disconnection map, lesion sparing of right dorsal fronto‐parietal regions, age, and anosognosia. Good discrimination accuracy was demonstrated (area under the curve = 0.80 [0.75–0.85]).

Interpretation

Our results localize the anatomic circuits that may have a role in the abnormal spatial‐emotional binding and in the defective updating of spatial representations underlying reduplicative paramnesia. This novel data may contribute to better understand the pathophysiology of delusional syndromes after stroke. ANN NEUROL 2021;89:1181–1194
Sampling and Analysis in Flow: The Keys to Smarter, More Controllable, and Sustainable Fine‐Chemical Manufacturing
Authors: Morin Mathieu A. , Zhang Wenyao (Peter) , Mallik Debasis , Organ Michael G.
Published: April 2021

Process analytical technology (PAT) is a system designed to help chemists better understand and control manufacturing processes. PAT systems operate through the combination of analytical devices, reactor control elements, and mathematical models to ensure the quality of the final product through a quality by design (QbD) approach. The expansion of continuous manufacturing in the pharmaceutical and fine‐chemical industry requires the development of PAT tools suitable for continuous operation in the environment of flow reactors. This requires innovative approaches to sampling and analysis from flowing media to maintain the integrity of the reactor content and the analyte of interest. The following Review discusses examples of PAT tools implemented in flow chemistry for the preparation of small organic molecules, and applications of self‐optimization tools.
Excellent electromagnetic interference shielding and mechanical properties accomplished in a manganese dioxide decorated graphene/polymer composite
Authors: Pradhan Sudip , Goswami Debottam , Ghorai Sanjoy Kumar , Ratna Debdatta , Chattopadhyay Santanu
Published: April 2021

In this work, we have incorporated pristine graphene and graphene sheets decorated with α and δ forms of manganese dioxide in a hydrogenated nitrile butadiene rubber matrix to obtain high‐performance composites. The dual mixing technique was adopted to fabricate the composites having enhanced tensile, dielectric, and electromagnetic interference (EMI) shielding properties. The pristine graphene was introduced at various loadings, however, the α and δ manganese dioxide doped graphene was integrated at a single 8 phr concentration onto the rubber matrix. At an optimized concentration of 8 phr graphene in the matrix, a 101% increase in the tensile strength was observed compared to the unfilled rubber. An excellent improvement in the dielectric properties and a high EMI shielding value of 24.5 dB was observed for the15 phr loaded composite having a thickness of 2 mm. The composites should principally find applications as a robust and lightweight EMI shielding material.
Cloning, expression, purification, and biochemical characterization of CpxR protein from pectobacterium carotovorum
Authors: He Xiaoliang , Zhang Jing , Wang Shuai , Yang Zi , Zhang Huan , Zhou Xiaohui
Published: April 2021

The cpxR gene, encoding a new cytoplasmic response regulator, which effects virulence, biofilm formation, chemotaxis, resistance to antimicrobials, and controls soft rot, was amplified by the polymerase chain reaction, cloned into the prokaryotic expression vector pET‐15b, and expressed through the induction of isopropyl‐β‐d‐thiogalactoside in Escherichia coli BL21 (DE3). Then, highly purified and stable CpxR protein was produced by nickel affinity chromatography and fast protein liquid chromatography, digested by thrombin and identified by Western blotting. Furthermore, the structure of the CpxR protein was estimated by circular dichroism spectroscopy and SWISS‐MODEL. The CpxR protein was a functional part in signal transduction and bacterial resistance for Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. The resear ch of the protein stability indicated the CpxR protein had excellent thermal stability and was suitable for crystallization. Then the small crystals of CpxR protein were found in the crystallizing tank. The latest 34 cpxR sequences from the public database were selected and analyzed by molecular clustering and multisequence alignment. These cpxR sequences were roughly divided into four categories. These results laid an important foundation for the further structural study of the CpxR protein.
A novel approach to residence time distribution characterization in a mAb continuous process
Authors: Brantley Tim , Bogue Jon , Denny Kurtis , Elouafiq Sanaa , Madren Seth , Nakhle Bassam , Khattak Sarwat
Published: April 2021

Residence time distribution modeling of integrated perfusion to capture process can elucidate the impact of product quality excursions and filter fouling on monoclonal antibody production. In this case study, a glycosylation inhibitor and fluorescently labeled antibody are applied to the continuous process to study protein quality modulation, perfusion filter fouling, and unit operation hold times. The unit operations were modeled as continuous‐stirred tank reactors and the residence time distribution of a small molecule glycan inhibitor and impact on glycosylation were characterized. A fluorescently labeled antibody was applied as a tracer molecule and confirmed the impact of packed cell volume and filter fouling. This study demonstrates how a biologics continuous process can be modeled and characterized through residence time distribution to ensure a robust, well‐understood process.
The effects of flux on the clearance of minute virus of mice during constant flux virus filtration
Authors: Fan Rong , Namila Fnu , Sansongko Davar , Wickramasinghe S. Ranil , Jin Mi , Kanani Dharmesh , Qian Xianghong
Published: April 2021

Constant flux virus filtration experiments were conducted to evaluate minute virus of mice retention behavior of four commercial virus filters for continuous bioprocessing applications. Fluxes chosen were guided by the Peclet number and the processing logistics as well as based on the filter characteristics. At the low flux condition of 5 (LMH) when diffusive force dominates, a significant breakthrough was observed for all the filtrate fractions for the filtration of a low fouling monoclonal antibody for three of the four filters. When both diffusive and convective forces are equally important at 40 LMH, virus breakthrough in buffer chase was observed only in one of the four filters investigated. When convective force dominates at 60 LMH or above, a high degree of virus clearance was observed for all three parvovirus filters investigated. Our work shed light on virus clearance during constant flux virus filtration for future continuous biomanufacturing.
Comparison of chemical constituents of Bupleurum marginatum var. stenophyllum and Bupleurum chinense DC. using UHPLC–Q‐TOF–MS based on a metabonomics approach
Authors: Xia Zhaodi , Liu Xia , Tong Liguo , Wang Han , Feng Mali , Xi Xiaohu , He Pan , Qin Xuemei
Published: April 2021

The overall chemical composition of Bupleurum marginatum var. stenophyllum and Bupleurum chinense DC. was compared in this study. Metabolites were identified using ultra‐high‐performance liquid chromatography–quadrupole time‐of‐flight mass spectrometry. Multivariate statistical analysis techniques such as principal component analysis were used to conduct metabonomics analysis and study the correlation between different components. Principal component analysis results showed a clear distinction among medicinal materials of different origins and divided them into different categories, consistent with the results of hierarchical cluster analysis. Both partial least squares discriminant analysis (PLS‐DA) and orthogonal partial least squares discriminant analysis (OPLS‐DA) showed that the two materials could be distinguished clearly. Using PLS‐DA and OPLS‐DA combined with the S‐plot and a variable importance in the projection (VIP) score >1, 24 differential metabolites were screened and identified; all of the metabolites were triterpenoid saponins. In addition, SPSS 25.0 and Metabo Analyst 4.0 were used to analyze significant differences in the relative contents of different compounds in the two materials. This study has successfully provided not only a new direction for research based on the chemical substances identified and the quality evaluation of Bupleuri Radix but also a better theoretical basis for the expansion of medicinal sources and their clinical application.
Human liver‐expressed antimicrobial peptide 2 elevation in the cerebrospinal fluid in bacterial meningitis
Authors: Sakai Katsuya , Shiomi Kazutaka , Mochizuki Hitoshi , Islam Md Nurul , Nabekura Hiroki , Tanida Ryota , Sakoda Hideyuki , Nakazato Masamitsu
Published: April 2021

Objective

To study the presence of liver‐expressed antimicrobial peptide 2 (LEAP2) in human cerebrospinal fluid (CSF) and to measure its concentrations in neurological disorders.

Materials & Methods

We identified the presence of LEAP2 in human CSF by chromatographic analysis and a LEAP2‐specific enzyme immunoassay. We measured LEAP2 concentrations in the CSF of 35 patients with neurological disorders.

Results

CSF LEAP2 concentrations in the bacterial meningitis group (mean ± SD, 9.32 ± 3.76 ng/ml) were significantly higher (p < .05) than those in the other four groups (psychosomatic disorder, 0.56 ± 0.15 ng/ml; peripheral autoimmune disease, 1.00 ± 0.60 ng/ml; multiple sclerosis, 0.62 ± 0.30 ng/ml; aseptic meningitis, 1.59 ± 0.69 ng/ml).

Conclusions

This is the first study to identify the presence of human LEAP2 in the CSF. Levels of LEAP2 were increased in the CSF of patients with bacterial meningitis. LEAP2 may have potential as a biomarker for bacterial meningitis.
Tumor genomic, transcriptomic, and immune profiling characterizes differential response to first‐line platinum chemotherapy in high grade serous ovarian cancer
Authors: Weberpals Johanne I. , Pugh Trevor J. , Marco‐Casanova Paola , Goss Glenwood D. , Andrews Wright Natalie , Rath Prisni , Torchia Jonathon , Fortuna Alexander , Jones Gemma N. , Roudier Martine P. , Bernard Laurence , Lo Bryan , Torti Dax , Leon Alberto , Marsh Kayla , Hodgson Darren , Duciaume Marc , Howat William J. , Lukashchuk Natalia , Lazic Stanley E. , Whelan Doreen , Sekhon Harmanjatinder S.
Published: April 2021

Background

In high grade serous ovarian cancer (HGSOC), there is a spectrum of sensitivity to first line platinum‐based chemotherapy. This study molecularly characterizes HGSOC patients from two distinct groups of chemotherapy responders (good vs. poor).

Methods

Following primary debulking surgery and intravenous carboplatin/paclitaxel, women with stage III–IV HGSOC were grouped by response. Patients in the good response (GR) and poor response (PR) groups respectively had a progression‐free intervals (PFI) of ≥12 and ≤6 months. Analysis of surgical specimens interrogated genomic and immunologic features using whole exome sequencing. RNA‐sequencing detected gene expression outliers and inference of immune infiltrate, with validation by targeted NanoString arrays. PD‐L1 expression was scored by immunohistochemistry (IHC).

Results

A total of 39 patient samples were analyzed (GR = 20; PR = 19). Median PFI for GR and PR patient cohorts was 32 and 3 months, respectively. GR tumors were enriched for loss‐of‐function BRCA2 mutations and had a significantly higher nonsynonymous mutation rate compared to PR tumors (p = 0.001). Samples from the PR cohort were characterized by mutations in MGA and RAD51B and trended towards a greater rate of amplification of PIK3CA, MECOM, and ATR in comparison to GR tumors. Gene expression analysis by NanoString correlated increased PARP4 with PR and increased PD‐L1 and EMSY with GR. There was greater tumor immune cell infiltration and higher immune cell PD‐L1 protein expression in the GR group.

Conclusions

Our research demonstrates that tumors from HGSOC patients responding poorly to first line chemotherapy have a distinct molecular profile characterized by actionable drug targets including PARP4.
Monalbidins A–E, Decalins with Potential Cytotoxic Activities from Marine Derived Fungus Monascus albidus BB3
Authors: Guo Qi , Lan Wen‐Jian , Chen Liu‐Ping , Lam Chi‐Keung , Feng Gong‐Kan , Deng Rong , Zhu Xiao‐Feng , Li Hou‐Jin
Published: April 2021

Five new decalins, monalbidins A–E (1, 2 and 7–9), together with 16 known compounds (3–6 and 10–21), were isolated from the AcOEt extract of marine derived fungus Monascus albidus BB3 cultured in GPY medium. Among the known compounds, 1‐hydroxymonacolin L (11), dehydromonacolin J (15), 8‐O‐acetylmonacolin J (19) and O‐acetylmonacolin K (21) were separated from natural sources for the first time. Their structures were determined by comprehensive analysis on the 1D and 2D NMR, HR‐ESI‐MS, UV and IR data, and their absolute configurations were assigned by experimental and calculated ECD data, and X‐ray single‐crystal diffraction analysis. Monalbidins C and D (7 and 8), monacolin K methyl ester (13), dehydromonacolin L (14), dehydromonacolin K (16), monacolin K (20) and O‐acetylmonacolin K (21) showed moderate cytotoxicity against human cancer cell lines SUNE1, HepG2, QGY7701, HCT116 and MDA‐MB‐231.
Clinical outcomes after permanent polymer or polymer‐free stent implantation in patients with diabetes mellitus: The ReCre8 diabetes substudy
Authors: van Hemert Nicole D. , Rozemeijer Rik , Voskuil Michiel , Stein Mèra , Frambach Peter , Rittersma Saskia Z. , Kraaijeveld Adriaan O. , Leenders Geert E. H. , van der Harst Pim , Agostoni Pierfrancesco , Stella Pieter R. ,   The ReCre8 Study Investigators
Published: April 2021

Objectives

The purpose of this analysis was to compare target‐lesion failure (TLF) of a permanent polymer zotarolimus‐eluting stent (PP‐ZES) versus a polymer‐free amphilimus‐eluting stent (PF‐AES) in diabetics.

Background

The improvement of outcomes with new‐generation drug‐eluting stent as seen in the general population is less pronounced among diabetics. The PF‐AES introduces an elution‐technology with potential enhanced performance in diabetics.

Methods

In this subanalysis of the ReCre8 trial, patients were randomized to either a PP‐ZES or PF‐AES after stratification for diabetes and troponin status. The primary device‐oriented endpoint was TLF, a composite of cardiac death, target‐vessel myocardial infarction and target‐lesion revascularization.

Results

In the ReCre8 trial, 304 (20%) patients were diabetic and 96 (6%) had insulin‐dependent diabetes mellitus. There was no statistically significant difference between the two study arms regarding the primary endpoint (PP‐ZES 7.2% vs. PF‐AES 4.0%; p = .21), although the composite of net adverse clinical events was higher in the PP‐ZES arm (15.7 vs. 8.0%; p = .035). Stent thrombosis was low in both groups with no cases in the PP‐ZES arm and 1 case in the PF‐AES arm (p = .32). Regarding insulin‐treated diabetics, TLF was higher in the PP‐ZES arm (14.9 vs. 2.1%; p = .022).

Conclusions

Diabetics could potentially benefit from a dedicated stent, releasing sirolimus with a lipophilic carrier (amphilimus‐formulation). Future trials should confirm the potential benefit of a PF‐AES in this population.
Design and Synthesis of New Withaferin A Inspired Hedgehog Pathway Inhibitors
Authors: Bonandi Elisa , Mori Mattia , Infante Paola , Basili Irene , Di Marcotullio Lucia , Calcaterra Andrea , Catti Federica , Botta Bruno , Passarella Daniele
Published: April 2021

Withanolides constitute a well‐known family of plant‐based alkaloids characterised by widespread biological properties, including the ability of interfering with Hedgehog (Hh) signalling pathway. Following our interest in natural products and in anticancer compounds, we report here the synthesis of a new class of Hh signalling pathway inhibitors, inspired by withaferin A, the first isolated member of withanolides. The decoration of our scaffolds was rationally supported by in silico studies, while functional evaluation revealed promising candidates, confirming once again the importance of natural products as inspiration source for the discovery of novel bioactive compounds. A stereoselective approach, based on Brown chemistry, allowed the obtainment and the functional evaluation of the enantiopure hit compounds.
Schneller und schlauer
Authors: Schäfer Petra
Published: April 2021

Covestro treibt den Einsatz von Künstlicher Intelligenz (KI) im Unternehmen als auch in der gesamten chemischen Industrie noch stärker voran. Dazu untersucht der Leverkusener Werkstoffhersteller im Rahmen mehrerer Pilotprojekte über verschiedene Unterneh
Potenzial der Altanlagen nutzen
Authors: Dietrich Peter
Published: April 2021

Beim Neubau von Prozessanlagen lassen sich Industrie 4.0‐Konzepte vergleichsweise leicht verwirklichen. Bei Bestands‐ oder Brownfield‐Anlagen, die bisher über den 4…20 mA Standard kommunizieren, war dies bisher nicht mit vertretbarem Aufwand möglich. Nun