bluuebunny/crossref_metadata_2025 huggingface dataset:
Nanoparticle‐microglial interaction in the ischemic brain is modulated by injury duration and treatment
Authors: Joseph Andrea , Liao Rick , Zhang Mengying , Helmbrecht Hawley , McKenna Michael , Filteau Jeremy R. , Nance Elizabeth
Published: August 2020

Cerebral ischemia is a major cause of death in both neonates and adults, and currently has no cure. Nanotechnology represents one promising area of therapeutic development for cerebral ischemia due to the ability of nanoparticles to overcome biological barriers in the brain. ex vivo injury models have emerged as a high‐throughput alternative that can recapitulate disease processes and enable nanoscale probing of the brain microenvironment. In this study, we used oxygen–glucose deprivation (OGD) to model ischemic injury and studied nanoparticle interaction with microglia, resident immune cells in the brain that are of increasing interest for therapeutic delivery. By measuring cell death and glutathione production, we evaluated the effect of OGD exposure time and treatment with azithromycin (AZ) on slice health. We found a robust injury response with 0.5 hr of OGD exposure and effective treatment after immediate application of AZ. We observed an OGD‐induced shift in microglial morphology toward increased heterogeneity and circularity, and a decrease in microglial number, which was reversed after treatment. OGD enhanced diffusion of polystyrene‐poly(ethylene glycol) (PS‐PEG) nanoparticles, improving transport and ability to reach target cells. While microglial uptake of dendrimers or quantum dots (QDs) was not enhanced after injury, internalization of PS‐PEG was significantly increased. For PS‐PEG, AZ treatment restored microglial uptake to normal control levels. Our results suggest that different nanoparticle platforms should be carefully screened before application and upon doing so; disease‐mediated changes in the brain microenvironment can be leveraged by nanoscale drug delivery devices for enhanced cell interaction.
Chemical Approaches To Analyzing RNA Structure Transcriptome‐Wide
Authors: England Whitney E. , Garfio Chely M. , Spitale Robert C.
Published: August 2020

RNA molecules can fold into complex two‐ and three‐dimensional shapes that are critical for their function. Chemical probes have long been utilized to interrogate RNA structure and are now considered invaluable resources in the goal of relating structure to function. Recently, the power of deep sequencing and careful chemical probe design have merged, permitting researchers to obtain a holistic understanding of how RNA structure can be utilized to control RNA biology transcriptome‐wide. Within this review, we outline the recent advancements in chemical probe design for interrogating RNA structures inside cells and discuss the recent advances in our understanding of RNA biology through the lens of chemical probing.
Severe coronary spasm in a COVID‐19 patient
Authors: Rivero Fernando , Antuña Paula , Cuesta Javier , Alfonso Fernando
Published: August 2020

Myocardial injury is frequently detected in coronavirus disease 2019 (COVID‐19) patients. However, up to one‐third of COVID‐19 patients showing ST‐segment elevation on the electrocardiogram have angiographically normal coronary arteries. We present a case of an acute coronary syndrome due to a coronary spasm in a severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) patient. This pathophysiological mechanism was clearly demonstrated by intracoronary imaging techniques (optical coherence tomography) and invasive vasospasm test.
The evolving role of interventional cardiology in the treatment of pulmonary hypertension
Authors: Gurevich Sergery , Prins Kurt W.
Published: August 2020

Pulmonary hypertension (PH) is a heterogeneous group of diseases defined by a mean pulmonary arterial pressure greater than 20 mmHg. Clinically, PH is classified into five groups and the group of PH generally defines the cause of PH and the therapeutic options. Currently, medical therapies that target the prostacyclin, endothelin, and nitric oxide pathways are used in pulmonary arterial hypertension and chronic thromboembolic PH (CTEPH) patients. Moreover, surgery can improve outcomes in PH as pulmonary thromboendarterectomy can be curative for CTEPH and lung transplantation is used for end‐stage PH. Despite these diverse treatment options, PH patients continue to have high symptom burden and poor long‐term outcomes. However, advances in percutaneous technology are opening new avenues for the management of PH. In this review, we discuss the available data supporting the use of four interventional procedures: balloon atrial septostomy, transcatheter Potts shunt, balloon pulmonary angioplasty, and pulmonary artery denervation for the treatment of PH. These procedures provide hemodynamic and functional improvements in PH patients, but they come with their own unique risk profiles. Hopefully, these procedures will continue to be refined and thereby provide a venue for interventional cardiology to safely and effectively improve outcomes for PH moving forward.
Natural Polyphenol–Vanadium Oxide Nanozymes for Synergistic Chemodynamic/Photothermal Therapy
Authors: Chen Ting , Huang Rongtao , Liang Jiawei , Zhou Bo , Guo Xiao‐Lu , Shen Xing‐Can , Jiang Bang‐Ping
Published: August 2020

The selection of suitable nanozymes with easy synthesis, tumor specificity, multifunction, and high therapeutics is meaningful for tumor therapy. Herein, a facile one‐step assembly approach was employed to successfully prepare a novel kind of natural polyphenol tannic acid (TA) hybrid with mixed valence vanadium oxide nanosheets (TA@VOx NSs). In this system, VOx is assembled with TA through metal–phenolic coordination interaction to both introduce superior peroxidase‐like activity and high near infrared (NIR) absorption owing to partial reduction of vanadium from V5+ to V4+. The presence of mixed valence vanadium oxide in TA@VOx NSs is proved to be the key for the catalytic reaction of hydrogen peroxide (H2O2) to .OH, and the corresponding catalytic mechanism of H2O2 by TA@VOx NSs is proposed. Benefitting from such peroxidase‐like activity of TA@VOx NSs, the overproduced H2O2 of the tumor microenvironment allows the realization of tumor‐specific chemodynamic therapy (CDT). As a valid supplement to CDT, the NIR absorption enables TA@VOx NSs to have NIR light‐mediated conversion ability for photothermal therapy (PTT) of cancers. Furthermore, in vitro and in vivo experiments confirmed that TA@VOx NSs can effectively inhibit the growth of tumors by synergistic CDT/PTT. These results offer a promising way to develop novel vanadium oxide‐based nanozymes for enhanced synergistic tumor‐specific treatment.
Electrochemical Synthesis of Carbazoles by Dehydrogenative Coupling Reaction
Authors: Kehl Anton , Schupp Niclas , Breising Valentina M. , Schollmeyer Dieter , Waldvogel Siegfried R.
Published: August 2020

A constant current protocol, employing undivided cells, a remarkably low supporting electrolyte concentration, inexpensive electrode materials, and a straightforward precursor synthesis enabling a novel access to N‐protected carbazoles by anodic N,C bond formation using directly generated amidyl radicals is reported. Scalability of the reaction is demonstrated and an easy deblocking of the benzoyl protecting group is presented.
Ocular dominance plasticity: Molecular mechanisms revisited
Authors: Kasamatsu Takuji , Imamura Kazuyuki
Published: August 2020

Ocular dominance plasticity (ODP) is a type of cortical plasticity operating in visual cortex of mammals that are endowed with binocular vision based on the competition‐driven disparity. Earlier, a molecular mechanism was proposed that catecholamines play an important role in the maintenance of ODP in kittens. Having survived the initial test, the hypothesis was further advanced to identify noradrenaline (NA) as a key factor that regulates ODP in the immature cortex. Later, the ODP‐promoting effect of NA is extended to the adult with age‐related limitations. Following the enhanced NA availability, the chain events downstream lead to the β‐adrenoreceptor‐induced cAMP accumulation, which in turn activates the protein kinase A. Eventually, the protein kinase translocates to the cell nucleus to activate cAMP responsive element binding protein (CREB). CREB is a cellular transcription factor that controls the transcription of various genes, underpinning neuronal plasticity and long‐term memory. In the advent of molecular genetics in that various types of new tools have become available with relative ease, ODP research has lightly adopted in the rodent model the original concepts and methodologies. Here, after briefly tracing the strategic maturation of our quest, the review moves to the later development of the field, with the emphasis placed around the following issues: (a) Are we testing ODP per se? (b) What does monocular deprivation deprive of the immature cortex? (c) The critical importance of binocular competition, (d) What is the adult plasticity? (e) Excitation–Inhibition balance in local circuits, and (f) Species differences in the animal models.
The effect of turbulence on transitional flow in theFDA's benchmark nozzle model using large‐eddy simulation
Authors: Manchester Emily L. , Xu Xiao Yun
Published: August 2020

The Food and Drug Administration's (FDA) benchmark nozzle model has been studied extensively both experimentally and computationally. Although considerable efforts have been made on validations of a variety of numerical models against available experimental data, the transitional flow cases are still not fully resolved, especially with regards to detailed comparison of predicted turbulence quantities with experimental measurements. This study aims to fill this gap by conducting large‐eddy simulations (LES) of flow through the FDA's benchmark model, at a transitional Reynolds number of 2000. Numerical results are compared to previous interlaboratory experimental results, with an emphasis on turbulence characteristics. Our results show that the LES methodology can accurately capture laminar quantities throughout the model. In the pre‐jet breakdown region, predicted turbulence quantities are generally larger than high resolution experimental data acquired with laser Doppler velocimetry. In the jet breakdown regions, where maximum Reynolds stresses occur, Reynolds shear stresses show excellent agreement. Differences of up to 4% and 20% are observed near the jet core in the axial and radial normal Reynolds stresses, respectively. Comparisons between viscous and Reynolds shear stresses show that peak viscous shear stresses occur in the nozzle throat reaching a value of 18 Pa in the boundary layer, whilst peak Reynolds shear stresses occur in the jet breakdown region reaching a maximum value of 87 Pa. Our results highlight the importance in considering both laminar and turbulent contributions towards shear stresses and that neglecting the turbulence effect can significantly underestimate the total shear force exerted on the fluid.
Conjugated Microporous Polymers Doped with Rare Earth Ions: Synthesis, Characterization and Energy Transfer
Authors: Cui Di , Yao Chan , Xu Yanhong , Che Guangbo
Published: August 2020

In order to study the energy transfer between the conjugated polymer and rare‐earth ions, a series of conjugated microporous polymers (CMPs) CMP‐COOH@M (M=Eu3+, Tb3+, La3+, and Sm3+) with different kinds of rare‐earth ions was synthesized, in which the conjugated networks can effectively improve the luminescence of rare‐earth ions due to the effective energy transfer from the CMP network to the rare‐earth ions centers. The absolute quantum yield of CMP‐COOH (ΦFL) is 29.1 %, while the ΦFL value of CMP‐COOH@Eu, CMP‐COOH@Tb, CMP‐COOH@La, and CMP‐COOH@Sm is 9.4, 8.6, 14.3, and 9.1 %, respectively. This result indicates that the quantum efficiency of CMPs network is 1/2‐1/3 of the original one due to the coordination of rare earth ions, that is, rare‐earth ions can be recognized as fine modulators to adjust the emission color of CMPs in a controlled manner through controlling the species of rare‐earth ions.
Propagation properties of dust‐electron‐acoustic waves in weakly magnetized dusty nonthermal plasmas
Authors: Bhowmick Shubhra , Sahu Biswajit
Published: August 2020

The linear and nonlinear properties of dust‐electron acoustic waves (DEAWs) propagating in magnetized, collisionless, dusty plasma system containing inertial cold electrons, Maxwellian hot electrons, nonthermal ions, and arbitrarily (positively or negatively) charged stationary dust are investigated. The reductive perturbation technique is employed to reduce the basic set of fluid equations to the modified Korteweg‐de Vries equation or Ostrovsky's equation, which governs the dynamics of small amplitude DEAWs in a weakly magnetized dusty nonthermal plasma. The approximate analytical as well as numerical solutions reveal that the basic characteristics of DEA nonlinear structures are found to be significantly modified by the key plasma configuration parameters. It is found that the leading compressive or rarefactive solitary wave structure separates from a trailing wave packet during a considerable time under the influence of magnetic field‐induced Lorentz force.
SCM: Secure and accountable TLS certificate management
Authors: Khan Salabat , Zhang Zijian , Zhu Liehuang , Rahim Mussadiq Abdul , Ahmad Sadique , Chen Ruoyu
Published: August 2020

In classical public‐key infrastructure (PKI), the certificate authorities (CAs) are fully trusted, and the security of the PKI relies on the trustworthiness of the CAs. However, recent failures and compromises of CAs showed that if a CA is corrupted, fake certificates may be issued, and the security of clients will be at risk. As emerging solutions, blockchain‐ and log‐based PKI proposals potentially solved the shortcomings of the PKI, in particular, eliminating the weakest link security and providing a rapid remedy to CAs' problems. Nevertheless, log‐based PKIs are still exposed to split‐world attacks if the attacker is capable of presenting two distinct signed versions of the log to the targeted victim(s), while the blockchain‐based PKIs have scaling and high‐cost issues to be overcome. To address these problems, this paper presents a secure and accountable transport layer security (TLS) certificate management (SCM), which is a next‐generation PKI framework. It combines the two emerging architectures, introducing novel mechanisms, and makes CAs and log servers accountable to domain owners. In SCM, CA‐signed domain certificates are stored in log servers, while the management of CAs and log servers is handed over to a group of domain owners, which is conducted on the blockchain platform. Different from existing blockchain‐based PKI proposals, SCM decreases the storage cost of blockchain from several hundreds of GB to only hundreds of megabytes. Finally, we analyze the security and performance of SCM and compare SCM with previous blockchain‐ and log‐based PKI schemes.
Stevioside protects against rhabdomyolysis‐induced acute kidney injury through PPAR‐γ agonism in rats
Authors: Kaur Tajpreet , Singh Damanpreet , Singh Amrit P. , Pathak Devendra , Arora Saroj , Singh Brahmjot , Kaur Sarabjit , Singh Balbir
Published: August 2020

We explored the potential role of peroxisome proliferator activated receptor‐γ (PPAR‐γ) in stevioside‐mediated renoprotection using rhabdomyolysis‐induced acute kidney injury (AKI) model in rats. Rhabdomyolysis refers to intense skeletal muscle damage, which further causes AKI. Glycerol (50% w/v, 8 ml/kg) was injected intramuscularly in rats to induce rhabdomyolysis. After 24 hr, AKI was demonstrated by quantifying serum creatinine, urea, creatinine clearance, microproteinuria, and electrolytes in rats. Further, oxidative stress was measured by assaying thiobarbituric acid reactive substances, generation of superoxide anion, and reduced glutathione levels. Additionally, serum creatine kinase (CK) level was assayed to determine glycerol‐induced muscle damage in rats. Pathological changes in rat kidneys were studied using hematoxylin–eosin and periodic acid Schiff staining. Moreover, the expression of apoptotic markers (Bcl‐2, Bax) in rat kidneys was demonstrated by immunohistochemistry. Stevioside (10, 25, and 50 mg/kg) was administered to rats, prior to the induction of AKI. In a separate group, bisphenol A diglycidyl ether (BADGE, 30 mg/kg), a PPAR‐γ receptor antagonist was given prior to stevioside administration, which was followed by rhabdomyolysis‐induced AKI in rats. The significant alteration in biochemical and histological parameters in rats indicated AKI, which was attenuated by stevioside treatment. Pretreatment with BADGE abrogated stevioside‐mediated renoprotection, which is suggestive of the involvement of PPAR‐γ in its renoprotective effect. In conclusion, stevioside protects against rhabdomyolysis‐induced AKI, which may be attributed to modulation of PPAR‐γ expression.
Improved detection methods significantly increase the detection window for EPO microdoses
Authors: Martin Laurent , Martin Jean‐Antoine , Collot David , Hoang Olivier , Audran Michel , Ericsson Magnus , Marchand Alexandre
Published: August 2020

To reproduce a potential doping scenario, a 2 week administration of recombinant erythropoietin (rEPO) microdoses alone or in combination with growth hormone (GH) microdoses (three times a week) was performed on healthy and athletic male subjects. The aim of this study was to evaluate the identification capability of rEPO in samples obtained during and post treatment. Detection was tested in urine and blood using the antidoping techniques for rEPO detection (iso‐electric focusing (IEF)‐, sodium‐dodecyl‐sulfate (SDS)‐polyacrylamide gel electrophoresis (PAGE) and for some urine samples the sarcosyl (SAR)‐PAGE method) with some improvements: for blood samples, instead of a simple concentration step, immuno‐extraction of EPO was performed for all urines to limit protein contamination that can affect migration. In addition, elution buffer modifications also improved the quality of migration. The use of a recently validated biotinylated anti‐EPO antibody simplified the protocols, allowing a single transfer step instead of a double‐blot even by IEF with a lowered background. The criteria for suspicious blood and urine samples by IEF were also re‐evaluated. While endogenous EPO was not decreased over the course of the study, EPO microdoses were detectable in blood and urine between 24 h and 72 h after an administration. Detection in urine in combination with SDS‐PAGE was the most sensitive combination for prolonged detection (100% identification after 48 h, 91% after 72 h), slightly better than IEF. Urine samples also tested by SAR‐PAGE indicated a similar sensitivity of detection to SDS‐PAGE. GH co‐administration had no impact on rEPO elimination/detection.
Lessons from joint development for cartilage repair in the clinic
Authors: Thorup Anne‐Sophie , Dell'Accio Francesco , Eldridge Suzanne E.
Published: August 2020

More than 250 years ago, William Hunter stated that when cartilage is destroyed it never recovers. In the last 20 years, the understanding of the mechanisms that lead to joint formation and the knowledge that some of these mechanisms are reactivated in the homeostatic responses of cartilage to injury has offered an unprecedented therapeutic opportunity to achieve cartilage regeneration. Very large investments in ambitious clinical trials are finally revealing that, although we do not have perfect medicines yet, disease modification is a feasible possibility for human osteoarthritis.
Muscle dysmorphia: A systematic and meta‐analytic review of the literature to assess diagnostic validity
Authors: Cooper Marita , Eddy Kamryn T. , Thomas Jennifer J. , Franko Debra L. , Carron‐Arthur Bradley , Keshishian Ani C. , Griffiths Kathleen M.
Published: August 2020

Objective

Although muscle dysmorphia (MD) is a new addition to DSM‐5 as a specifier of body dysmorphic disorder (BDD), previous studies have treated MD as a stand‐alone diagnosis. We aimed to assess the validity of MD as a stand‐alone diagnosis via systematic and meta‐analytic review of MD literature using both Robins and Guze criteria and additional criteria from Kendler.

Method

We performed a systematic search of ProQuest, PsycInfo, and PubMed databases for the period of January 1993 to October 2019 resulting in 40 papers to examine Robins and Guze's criteria (clinical picture) as well as those added by Kendler (antecedent validators; concurrent validators; predictive validators).

Results

We identified two distinct symptomatic presentations of MD using cluster analysis, a behavioral type and cognitive/behavioral type. For examining the concurrent validators, quantitative meta‐analyses differentiated MD populations from controls; however, results were inconclusive in delineating MD from existing disorders. For assessing antecedent and predictive validators, the symptomatic profiles, treatment response, and familial links for MD were similar to those for BDD and for eating disorders.

Discussion

We found preliminary support for MD as a clinically valid presentation, but insufficient evidence to determine whether it is best categorized as a specifier of BDD or unique psychiatric condition.
Synthesis of Fluorinated Chlorophylls‐a and Their Bio/Physico‐Chemical Properties
Authors: Ogasawara Shin , Nakano Kohei , Tamiaki Hitoshi
Published: August 2020

Pheophytin(Pheo)‐a as the free base of chlorophyll(Chl)‐a, was fluorinated at the 20‐position using N‐fluorobenzenesulfonimide, followed by insertion of a magnesium cation at the central position to afford 20‐fluoro‐Chl‐a. On the other hand, 32,32‐difluoro‐Chl‐a was obtained from Pheo‐d possessing the 3‐formyl group by the Wittig reaction using (triphenylphosphonio)difluoroacetate and the successive magnesium insertion. The synthetic 20‐fluoro‐ and 32,32‐difluoro‐Chls‐a showed similar optical properties and enzymatic hydrolysis of the phytyl ester to original (intact) Chl‐a. By contrast, their 132‐stereochemical inversion (epimerization) occurred more rapidly, and the removal of their central magnesium (pheophytinization) was more tolerant than Chl‐a due to the electronic effect of the fluorine atom(s) through the chlorin π‐system in a molecule. Since a fluorine atom is comparable in the size to a hydrogen atom, these chemically stable fluorinated Chls‐a are promising as the synthetic alternatives to naturally occurring Chl‐a, and are useful for the structural and functional investigation in oxygenic phototrophs.
n‐ZnO/p‐NiO Core/Shell‐Structured Nanorods for Piezoelectric Nanogenerators
Authors: A Han Sang , Hwang Soo Min , Seung Wanchul , Kim Tae Yun , Park Min-Sik , Lee Ju-Hyuck , Kim Sang-Woo , Kim Jung Ho
Published: August 2020

Energy‐harvesting technologies, which can generate electrical energy from various energy sources, such as solar, thermal, and mechanical movement that are commonly found in the local environment, supply permanent and environmentally friendly energy. In addition, related research has been in the spotlight because it provides power by harvesting and converting a naturally occurring energy source without a charging process through external power. Piezoelectric nanogenerators (PENGs) based on piezoelectric materials have attracted much attention due to their high energy‐conversion efficiency, capability for miniaturization, and light weight. Zinc oxide (ZnO), which has a wurtzite crystal structure, is a representative piezoelectric material. The defects that are inevitably present in ZnO nanorods (NRs), however, generate excessive free electrons, which reduce the piezoelectric potential and thus reduce the output characteristics. Herein, ZnO–NiO core–shell structure–based PENGs are designed to enhance their piezoelectric output performance by reducing excess electrons in the ZnO NRs using a p‐type semiconducting NiO layer. The thickness and structure of the NiO coated on the ZnO NRs are observed and analyzed by adjusting the molar concentration of solution for the NiO layer coating, and the effects of these on the piezoelectric output are discussed.
Estimating economic losses of midrise reinforced concrete shear wall buildings in sedimentary basins by combining empirical and simulated seismic hazard characterizations
Authors: Kourehpaz Pouria , Molina Hutt Carlos , Marafi Nasser A. , Berman Jeffrey W. , Eberhard Marc O.
Published: August 2020

Studies of recorded ground motions and simulations have shown that deep sedimentary basins can greatly increase the intensity of earthquake ground motions within a period range of approximately 1–4 s, but the economic impacts of basin effects are uncertain. This paper estimates key economic indicators of seismic performance, expressed in terms of earthquake‐induced repair costs, using empirical and simulated seismic hazard characterizations that account for the effects of basins. The methodology used is general, but the estimates are made for a series of eight‐ to 24‐story residential reinforced concrete shear wall archetype buildings in Seattle, WA, whose design neglects basin effects. All buildings are designed to comply with code‐minimum requirements (i.e., reference archetypes), as well as a series of design enhancements, which include (a) increasing design forces, (b) decreasing drift limits, and (c) a combination of these strategies. As an additional reference point, a performance‐based design is also assessed. The performance of the archetype buildings is evaluated for the seismic hazard level in Seattle according to the 2018 National Seismic Hazard Model (2018 NSHM), which explicitly considers basin effects. Inclusion of basin effects results in an average threefold increase in annualized losses for all archetypes. Incorporating physics‐based ground motion simulations to represent the large‐magnitude Cascadia subduction interface earthquake contribution to the hazard results in a further increase of 22% relative to the 2018 NSHM. The most effective of the design strategies considered combines a 25% increase in strength with a reduction in drift limits to 1.5%.
Anomaly traffic detection and correlation in Smart Home automation IoT systems
Authors: Gajewski Mariusz , Mongay Batalla Jordi , Mastorakis George , Mavromoustakis Constandinos X.
Published: August 2020

Smart building automation systems are increasingly the target of hacking attacks. Moreover, they may be used as a tool for attacks against targets located out of the native Home Area Network (HAN). These attacks are often resulted in changes in traffic volume, damaged packets, increased message traffic, and so on. Symptoms of attacks can be detected as anomalies in traffic model and recognized by a software agent run on Home Gateway. Although these anomalies are detected locally, it may help network provider to protect his resources as well as other resources of his clients. For that purpose, network operator should be able to recognize anomalies and correlate them on the network level. In this way, the network operator has the ability to protect both its own network and HANs of its clients. This article shows that Smart Home security might be coupled with the providers' network security policy. For that reason, security tasks should be performed both in HAN and providers' data center. This article describes a novel strategy for anomaly detection that provides shared responsibility between a service client and the network provider. It uses a machine learning approach for classifying the monitoring data and correlation in searching suspicious behavior across the network resources at the service provider's data center.
Volcanism‐induced sedimentation and model: A case study of the Upper Jurassic‐Lower Cretaceous sediments in the Liuhe‐Tonghua Basin, NE China
Authors: Zhou Yang , Cheng Rihui , Shen Yanjie , Xu Zhongjie , Song Libin , Liu Guodong
Published: August 2020

Understanding how the lacustrine environment adapts to volcanism and the relevant products is one of the key goals of volcaniclastic sedimentology. Mixed sediments can be deposited in lacustrine basins during the interaction between volcano and environment. This article is focus on the lithology, lithofacies, association, and sedimentary sequence of the Late Jurassic‐Early Cretaceous mixed sediments from the Liuhe‐Tonghua Basin, revealing the transportation‐accumulation processes of volcanic materials from subaerial eruption into water or subaqueous eruption mingling with terrigenous clasts. Four kinds of mixed‐sediment rocks are identified including tuffaceous sandstone, tuff‐lapilli tuff, breccia‐agglomerate/lava and tuff lava/lava, and six lithofacies associations are identified: (a) base surge and pyroclastic flow, interpreted as the middle‐distal end of a mixed‐fan delta; (b) base surge‐pyroclastic flow and turbidite flow, interpreted as the distal end of a mixed‐fan delta; (c) base surge‐pyroclastic flow‐turbidite flow and mud deposits, interpreted as a mixed subaqueous fan; (d) sand sheet of the base surge and mud deposits, interpreted as a deepwater region; (e) subaerial volcanic edifice, interpreted as a volcanic vent‐proximal slope; (f) subaqueous volcanic edifice, interpreted as a volcanic slope. These associations may exhibit different spatial occurrences and palaeogeographic distributions, representing the transition from a volcanic to a sedimentary environment in the source to sink system, and an ideal mixed sedimentation model is established based on these associations and relevant mud deposits. These associations also exhibit a typical volcanic‐sedimentary sequence including terrigenous lowstand sediments in extensional settings and mixed volcanic and terrigenous transgressive‐highstand sediments in trans‐extensional settings. This article presents a case of volcaniclastic sedimentation (mixed sedimentation) of Cretaceous volcano‐fault basin in Northeast China, which can provide a reference for the lacustrine volcaniclastic deposition in other similar genetic basins around the world.
Programmed cell death ligand‐1 and cytotoxic T cell infiltrates in metastatic cutaneous squamous cell carcinoma of the head and neck
Authors: Kraft Stefan , Gadkaree Shekhar K. , Deschler Daniel G. , Lin Derrick T. , Hoang Mai P. , Emerick Kevin S.
Published: August 2020

Background

Metastatic cutaneous squamous cell carcinoma (cSCC) carries a poor prognosis. Increased numbers of CD8+ cytotoxic T cells are associated with a favorable prognosis and programmed cell death receptor‐1 is a suppressor of the CD8+ cytotoxic T cell response. We aim to define their expression in metastatic cutaneous squamous cell carcinoma.

Methods

Cytotoxic T cell infiltrates and tumoral PD‐L1 expression in lymph node metastases from patients with cSCC of the head and neck were analyzed.

Results

High tumoral PD‐L1 expression, intratumoral and peritumoral CD8+ cell density in metastases were significantly associated with poor primary tumor differentiation. Low PD‐L1 expression, intratumoral and peritumoral CD8+ density were associated with lower grade primary tumor differentiation. Low PD‐L1 expression correlated with disease progression.

Conclusions

Increased expression of PD‐L1 correlates with increased CD8+ cell density. Increased expression of PD‐L1 in poorly differentiated tumors may be more likely to benefit from anti PD‐1/PD‐L1 therapy.
Prediction of distant metastases in patients with squamous cell carcinoma of head and neck using DWI and DCE‐MRI
Authors: Chawla Sanjeev , Kim Sungheon G , Loevner Laurie A , Wang Sumei , Mohan Suyash , Lin Alexander , Poptani Harish
Published: August 2020

Background

The primary purpose was to evaluate the prognostic potential of diffusion imaging (DWI) and dynamic contrast enhanced magnetic resonance imaging (DCE‐MRI) in predicting distant metastases in squamous cell carcinoma of head and neck (HNSCC) patients. The secondary aim was to examine differences in DWI and DCE‐MRI‐derived parameters on the basis of human papilloma virus (HPV) status, differentiation grade, and nodal stage of HNSCC.

Methods

Fifty‐six patients underwent pretreatment DWI and DCE‐MRI. Patients were divided into groups who subsequently did (n = 12) or did not develop distant metastases (n = 44). Median values of apparent diffusion coefficient (ADC), volume transfer constant (Ktrans), and mean intracellular water‐lifetime (τi) and volume were computed from metastatic lymph nodes and were compared between two groups. Prognostic utility of HPV status, differentiation grading, and nodal staging was also evaluated both in isolation or in combination with MRI parameters in distinguishing patients with and without distant metastases. Additionally, MRI parameters were compared between two groups based on dichotomous HPV status, differentiation grade, and nodal stage.

Results

Lower but not significantly different Ktrans (0.51 ± 0.15 minute−1 vs 0.60 ± 0.05 minute−1) and not significantly different τi (0.13 ± 0.03 second vs 0.19 ± 0.02 second) were observed in patients who developed distant metastases than those who did not. Additionally, no significant differences in ADC or volume were found. τi, was the best parameter in discriminating two groups with moderate sensitivity (67%) and specificity (61.4%). Multivariate logistic regression analyses did not improve the overall prognostic performance for combination of all variables. A trend toward higher τi was observed in HPV‐positive patients than those with HPV‐negative patients. Also, a trend toward higher Ktrans was observed in poorly differentiated HNSCCs than those with moderately differentiated HNSCCs.

Conclusion

Pretreatment DCE‐MRI may be useful in predicting distant metastases in HNSCC.
Clinical evaluation of an automated virtual surgical planning platform for mandibular reconstruction
Authors: Wang Edward , Durham J. Scott , Anderson Donald W. , Prisman Eitan
Published: August 2020

Background

Virtual surgical planning (VSP), via commercial services or developed in‐house, has been applied to facilitate head and neck reconstruction. We evaluate a custom, automated planning software.

Methods

Prospectively, VSP of 25 consecutive patients undergoing segmental mandibular reconstruction was performed. Postoperative CT was used to assess structural accuracy of VSP. Operative time, length of stay, and complication rate of the prospective cohort were compared with those of 25 consecutive retrospective historical cases.

Results

The deviations between the plan and execution in mandibular width, projection, and volumetric overlap were 2.32 ± 3.91, 2.39 ± 1.72, and 0.59 ± 0.51 mm respectively. Compared with historical data, there was a significant reduction in operative time and length of stay, and no significant difference in complication rates.

Conclusion

This is the largest prospective series evaluating an in‐house VSP workflow for mandibular reconstruction and the first clinical evaluation of an automated planning platform.
A Systematic Review of Patient‐Reported Outcomes in Primary Biliary Cholangitis and Primary Sclerosing Cholangitis
Authors: Kim Hannah P. , Lieber Sarah R. , Rogers Michael E. , Moon Andrew M. , Loiselle Marci , Walker Jennifer , Assis David N. , Safer Ricky , Gomel Rachel , Evon Donna M.
Published: August 2020

Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are associated with decreased health‐related quality of life and debilitating symptoms. These experiences can be defined as patient‐reported outcome (PRO) concepts and measured using PRO instruments. We identified all PRO concepts and instruments used in the PBC and PSC literature. This systematic review identified PBC and/or PSC studies from January 1, 1990, to May 6, 2019, that measured at least one PRO concept. Study population, design, PRO concept, PRO instrument, and validation data for PRO instruments were investigated. We provided descriptive statistics of PRO concepts and instruments used, stratified by population type. Use of PRO concepts and instruments were assessed over time. The search yielded 318 articles (69% in PBC, 18% in PSC, 13% in both, and 24% in drug trials). Forty‐nine unique PRO concepts were identified. The five most common PRO concepts included pruritus (25%), fatigue (19%), broad health‐related quality of life (16%), gastrointestinal adverse events (6%), and physical adverse events (6%). Only 60% of PRO concepts were measured with a PRO instrument, most of which were nonvalidated visual analogue or numeric rating scales. Only three of 83 PRO instruments were developed with feedback from the target populations (one for PBC, one for PSC, and one for both), and only six documented any psychometric testing in the target populations. Use of PRO instruments increased over time from 30% in the 1990s to 67% by 2019. Conclusion: The overwhelming majority of PRO instruments used in PBC/PSC were nonspecific and lacked patient validation or empirical justification. Significant opportunities exist to use qualitative methods to better understand patient experiences, and translate this knowledge into meaningful, patient‐driven study outcomes.
Biopsy Validated Study of Biomarkers for Liver Fibrosis and Transplant Prediction in Inherited Cholestasis
Authors: Shiau Henry , Guffey Danielle , Loomes Kathleen M. , Seidman Christa , Ragozzino Emily , Molleston Jean P. , Schady Deborah , Leung Daniel H.
Published: August 2020

Alagille syndrome (ALGS) and progressive familial intrahepatic cholestasis (PFIC) are inherited cholestatic disorders with risk of developing end‐stage liver disease requiring liver transplantation (LT). We investigated aspartate aminotransferase‐to‐platelet ratio index (APRI), Fibrosis‐4 score (FIB‐4), and conjugated bilirubin as biomarkers to assess fibrosis severity and risk for LT among children with ALGS and PFIC. This multicenter, cross‐sectional study included 64 children with ALGS or PFIC (per genetics or strict clinical criteria) with APRI, FIB‐4, and conjugated bilirubin levels collected within ±90 days of their most recent liver biopsy. A single, blinded pathologist staged all biopsies (metavir; F0‐F2: nonsevere, F3‐F4: severe). Logistic regression and area under the receiver operating characteristic curve analysis (AUC) were used to assess biomarker associations with fibrosis severity and risk for LT. In ALGS, only APRI distinguished F3‐F4 (AUC 0.72, P = 0.012), with a cutoff greater than 2.97 demonstrating a sensitivity of 61.5% (95% confidence interval 0.32, 0.86) and specificity of 81.5% (0.62, 0.94). In ALGS, a 50% increase of APRI increased the odds of F3‐F4 by 1.31‐fold (1.04, 1.65; P = 0.023). In ALGS, APRI (AUC 0.87; P < 0.001) and FIB‐4 (AUC 0.84; P < 0.001) were able to predict risk for LT. In PFIC, only APRI distinguished F3‐4 (AUC 0.74, P = 0.039), with a cutoff greater than 0.99 demonstrating a sensitivity of 80% (0.44, 0.98) and specificity of 64.3% (0.35, 0.87). In PFIC, only FIB‐4 was able predict risk for LT (AUC 0.80; P = 0.002). In ALGS or PFIC, conjugated bilirubin could not distinguish F3‐F4 or predict risk for LT. Conclusion: This liver biopsy–validated study suggests that APRI is able to distinguish F3‐F4 from F0‐F2 in ALGS and PFIC. APRI and FIB‐4 may also serve as predictors of risk for LT in ALGS (APRI and FIB‐4) and PFIC (FIB‐4).
Numerical and experimental study of a thermosyphon closed‐loop system for domestic applications
Authors: Jasim Ayoob Khalid , Freegah Basim , Alhamdo Mohammed Hamed
Published: August 2020

A numerical and experimental study has been conducted to enhance the thermal performance of the thermosyphon system. The enhancement response focused on the temperature of both the working fluid within the system loop and water inside the tank. To achieve this, three models were investigated to increase the surface area of the riser pipe without changing the amount of the working fluid. The first one (model A) involved increasing the diameter of the riser pipe and inserting a closed tube inside it to maintain the same amount of working fluid. The second method (model B) involved adding toroidal fins around the riser pipe. However, the third model (model C) combined both models (A and B). The thermal performance of the thermosyphon system for the conventional model has been compared experimentally. Furthermore, numerical simulations for all cases have been done using commercial computational fluid dynamics, ANSYS R 19.3 software. The results show that there is good agreement between the experimental and numerical results. Furthermore, it is found that the thermal responses of models A and B are approximately equal and both are higher than that of the traditional model. Moreover, the thermal performance of model C is found to be higher than those of all the other models under study.
Cu‐Al2O3/H2O hybrid nanofluid flow past a porous stretching sheet due to temperatue‐dependent viscosity and viscous dissipation
Authors: Venkateswarlu Bhumavarapu , Satya Narayana Panyam Venkata
Published: August 2020

The resent development of research in the field of nano technology introduced hybrid nanofluids which are advanced classes of fluids with augmented thermal properties and it gives better results comparing to regular nanofluid. The aim of the present work is to study the significant effects of variable viscosity and viscous dissipation on a porous stretching sheet in the presence of hybrid nanofluid and radiative heating. In this model, two types of nanoparticles, namely copper (Cu) and alumina oxide (Al2O3), are suspended in the base fluid H2O to form a hybrid nanoliquid. The novelty of this study is to introduce variable viscosity along with natural convection in the momentum equation and viscous dissipation in the energy equation. Mathematical modeling is employed in this study, whereby partial differential equations for the fluid flow are constructed and transformed to a set of ordinary differential equations, and hence resolved computationally by Runge‐Kutta‐Fehlberg method along with shooting scheme. The most important results for relevant parameters concerning the flow heat measure, surface drag, and heat transfer coefficients are thoroughly examined and presented graphically for both Cu‐Al2O3/water hybrid nanofluids. There is an increase in hybrid nanofluid velocity profile with mounting values of , and the Cu‐water nanofluid converges to the boundary more quickly than the hybrid nanofluid due to the occurrence of variable viscosity. The results concluded that the Nusselt number of the viscous fluid is lower than that of the nanofluid and hence the hybrid nanofluid (ie, heat transfer rate: normal fluid < nanofluid < hybrid nanofluid). The outcomes of present investigations are in close agreement with the viscous fluid as a particular case.
Experimental study of closed‐loop thermosyphon with a different evaporator geometry
Authors: Aljuboori Adeeb A. A. , Ahmed Saba Y. , Jabbar Mohammed Y.
Published: August 2020

In this study, the effect of evaporator geometry on the loop thermosyphon's heat transfer coefficient is experimentally verified by using water as a working fluid with three filling ratios (50%, 70%, 90%), constant heat input (185 W), and condenser cooling water flow rate remaining constant at 2 Lpm. Three evaporator pipes are used (I: straight; II: helical coil evaporator with a diameter of 100‐mm coil and two turns; III: helical coil evaporator with a diameter of 50‐mm coil and four turns). From the experimental results, it can be observed that the performance of evaporator III is higher than the two other forms. A greater heat transfer coefficient value is found in case of type III evaporator and is equivalent to 2456 W/m2·°C. The maximum thermal resistance reduction occurs in the type III evaporator (37.32%), and the highest effective thermal conductivity for the same type is 6.123e + 05 W/m·°C. The experimental results demonstrate good agreement with the empirical equations.
Coprescription of mood stabilizers in schizophrenia, dosing, and clinical correlates: An international study
Authors: Lim Wai Kwong , Chew Qian Hui , He Yan‐Ling , Si Tian‐Mei , Chiu Fung‐Kum Helen , Xiang Yu‐Tao , Kato Takahiro A. , Kanba Shigenobu , Shinfuku Naotaka , Lee Min‐Soo , Park Seon‐Cheol , Park Yong‐Chon , Chong Mian‐Yoon , Lin Shih‐Ku , Yang Shu‐Yu , Tripathi Adarsh , Avasthi Ajit , Grover Sandeep , Kallivayalil Roy Abraham , Udomratn Pichet , Chee Kok Yoon , Tanra Andi J. , Rabbani Md Golam , Javed Afzal , Kathiarachchi Samudra , Waas Dulshika , Myint Wing Aung , Sartorius Norman , Tran Van Cuong , Nguyen Kim Viet , Tan Chay‐Hoon , Baldessarini Ross J. , Sim Kang
Published: August 2020

Objective

Studies examining coprescription and dosages of mood stabilizers (MSs) with antipsychotics for psychotic disorders are infrequent. Based on sparse extant data and clinical experience, we hypothesized that adjunctive MS use would be associated with certain demographic (e.g., younger age), clinical factors (e.g., longer illness duration), and characteristics of antipsychotic treatment (e.g., multiple or high antipsychotic doses).

Methods

Within an Asian research consortium focusing on pharmaco‐epidemiological factors in schizophrenia, we evaluated rates of MS coprescription, including high doses (>1000 mg/day lithium‐equivalents) and clinical correlates.

Results

Among 3557 subjects diagnosed with schizophrenia in 14 Asian countries, MSs were coprescribed with antipsychotics in 13.6% (n= 485) of the sample, with 10.9% (n= 53) on a high dose. Adjunctive MS treatment was associated (allp< 0.005) with demographic (female sex and younger age), setting (country and hospitalization), illness (longer duration, more hospitalizations, non‐remission of illness, behavioral disorganization, aggression, affective symptoms, and social–occupational dysfunction), and treatment‐related factors (higher antipsychotic dose, multiple antipsychotics, higher body mass index, and greater sedation). Patients given high doses of MSs had a less favorable illness course, more behavioral disorganization, poorer functioning, and higher antipsychotic doses.

Conclusions

Schizophrenia patients receiving adjunctive MS treatment in Asian psychiatric centers are more severely ill and less responsive to simpler treatment regimens.
Differential expression patterns of glycosphingolipids and C‐type lectin receptors on immune cells in absence of functional regulatory T cells
Authors: Jirmo Adan C. , Rossdam Charlotte , Grychtol Ruth , Happle Christine , Gerardy‐Schahn Rita , Buettner Falk F. R. , Hansen Gesine
Published: August 2020

Background

Glycosylation is a common and complex type of protein posttranslational modification. Altered glycosylation of immunoglobulins in autoimmune diseases has led to the “altered glycan hypothesis” postulating existence of a unique glycan signature on immune cells and extracellular proteins characterized by site‐specific relative abundances of individual glycan structures and glycosylation patterns. However, it is not clear how glycosylation on leukocyte subpopulations differ between states of health or inflammation.

Hypothesis

Glycosphingolipid patterns on immune cells of forkhead‐box‐P3‐deficient scurfy mice differs from those on wild‐type immune cells.

Methods

T cells and dendritic cells were isolated from spleens of either wild‐type or age‐matched scurfy mice. Glycosphingolipids of CD4+ T cells and splenic dendritic cells from wild‐type and scurfy mice were then analyzed by multiplexed capillary gel electrophoresis coupled to laser‐induced fluorescence detection (xCGE‐LIF). In addition, flow cytometry and ChipCytometry were used to access expression patterns of various C‐type lectin receptors on antigen‐presenting cells from various organs of both wild‐type and scurfy mice.

Results

We, hereby report differential expression of glycosphingolipids in health and under inflammatory conditions as reflected in wild‐type and scurfy mice. Furthermore, we observed that the absence of functional regulatory T cells correlated with elevated expression of CLEC‐7A and CD205 but a reduction in levels of CLEC12A and CD206 on antigen‐presenting cells.

Conclusion

We hereby show that the absence of functional regulatory T cells affects expression pattern and quantities of glycosphingolipids on immune cells. Thus, glycosphingolipids could serve as biomarkers for mapping genetical and homeostatic perturbances such as those resulting from a diseased condition.