bluuebunny/crossref_metadata_2025 huggingface dataset:
Neuronal interleukin-1 receptors mediate pain in chronic inflammatory diseases
Authors: Mailhot Benoit , Christin Marine , Tessandier Nicolas , Sotoudeh Chaudy , Bretheau Floriane , Turmel Roxanne , Pellerin Ève , Wang Feng , Bories Cyril , Joly-Beauparlant Charles , De Koninck Yves , Droit Arnaud , Cicchetti Francesca , Scherrer Grégory , Boilard Eric , Sharif-Naeini Reza , Lacroix Steve
Published: July 2020

Chronic pain is a major comorbidity of chronic inflammatory diseases. Here, we report that the cytokine IL-1β, which is abundantly produced during multiple sclerosis (MS), arthritis (RA), and osteoarthritis (OA) both in humans and in animal models, drives pain associated with these diseases. We found that the type 1 IL-1 receptor (IL-1R1) is highly expressed in the mouse and human by a subpopulation of TRPV1+ dorsal root ganglion neurons specialized in detecting painful stimuli, termed nociceptors. Strikingly, deletion of the Il1r1 gene specifically in TRPV1+ nociceptors prevented the development of mechanical allodynia without affecting clinical signs and disease progression in mice with experimental autoimmune encephalomyelitis and K/BxN serum transfer–induced RA. Conditional restoration of IL-1R1 expression in nociceptors of IL-1R1–knockout mice induced pain behavior but did not affect joint damage in monosodium iodoacetate–induced OA. Collectively, these data reveal that neuronal IL-1R1 signaling mediates pain, uncovering the potential benefit of anti–IL-1 therapies for pain management in patients with chronic inflammatory diseases.
Relative contribution of nonstructural protein 1 in dengue pathogenesis
Authors: Lee Pei Xuan , Ting Donald Heng Rong , Boey Clement Peng Hee , Tan Eunice Tze Xin , Chia Janice Zuo Hui , Idris Fakhriedzwan , Oo Yukei , Ong Li Ching , Chua Yen Leong , Hapuarachchi Chanditha , Ng Lee Ching , Alonso Sylvie
Published: July 2020

Dengue is a major public health concern in the tropical and subtropical world, with no effective treatment. The controversial live attenuated virus vaccine Dengvaxia has boosted the pursuit of subunit vaccine approaches, and nonstructural protein 1 (NS1) has recently emerged as a promising candidate. However, we found that NS1 immunization or passive transfer of NS1 antibodies failed to confer protection in symptomatic dengue mouse models using two non–mouse-adapted DENV2 strains that are highly virulent. Exogenous administration of purified NS1 also failed to worsen in vivo vascular leakage in sublethally infected mice. Neither method of NS1 immune neutralization changed the disease outcome of a chimeric strain expressing a vascular leak-potent NS1. Instead, virus chimerization involving the prME structural region indicated that these proteins play a critical role in driving in vivo fitness and virulence of the virus, through induction of key proinflammatory cytokines. This work highlights that the pathogenic role of NS1 is DENV strain dependent, which warrants reevaluation of NS1 as a universal dengue vaccine candidate.
Targeting CLK3 inhibits the progression of cholangiocarcinoma by reprogramming nucleotide metabolism
Authors: Zhou Qingxin , Lin Meihua , Feng Xing , Ma Fei , Zhu Yuekun , Liu Xing , Qu Chao , Sui Hong , Sun Bei , Zhu Anlong , Zhang Heng , Huang He , Gao Zhi , Zhao Yongxiang , Sun Jiangyun , Bai Yuxian , Jin Junfei , Hong Xuehui , Zou Chang , Zhang Zhiyong
Published: July 2020

CDC-like kinase 3 (CLK3) is a dual specificity kinase that functions on substrates containing serine/threonine and tyrosine. But its role in human cancer remains unknown. Herein, we demonstrated that CLK3 was significantly up-regulated in cholangiocarcinoma (CCA) and identified a recurrent Q607R somatic substitution that represented a gain-of-function mutation in the CLK3 kinase domain. Gene ontology term enrichment suggested that high CLK3 expression in CCA patients mainly was associated with nucleotide metabolism reprogramming, which was further confirmed by comparing metabolic profiling of CCA cells. CLK3 directly phosphorylated USP13 at Y708, which promoted its binding to c-Myc, thereby preventing Fbxl14-mediated c-Myc ubiquitination and activating the transcription of purine metabolic genes. Notably, the CCA-associated CLK3-Q607R mutant induced USP13-Y708 phosphorylation and enhanced the activity of c-Myc. In turn, c-Myc transcriptionally up-regulated CLK3. Finally, we identified tacrine hydrochloride as a potential drug to inhibit aberrant CLK3-induced CCA. These findings demonstrate that CLK3 plays a crucial role in CCA purine metabolism, suggesting a potential therapeutic utility.
Mutations in the exocyst component EXOC2 cause severe defects in human brain development
Authors: Van Bergen Nicole J. , Ahmed Syed Mukhtar , Collins Felicity , Cowley Mark , Vetro Annalisa , Dale Russell C. , Hock Daniella H. , de Caestecker Christian , Menezes Minal , Massey Sean , Ho Gladys , Pisano Tiziana , Glover Seana , Gusman Jovanka , Stroud David A. , Dinger Marcel , Guerrini Renzo , Macara Ian G. , Christodoulou John
Published: July 2020

The exocyst, an octameric protein complex, is an essential component of the membrane transport machinery required for tethering and fusion of vesicles at the plasma membrane. We report pathogenic variants in an exocyst subunit, EXOC2 (Sec5). Affected individuals have severe developmental delay, dysmorphism, and brain abnormalities; variability associated with epilepsy; and poor motor skills. Family 1 had two offspring with a homozygous truncating variant in EXOC2 that leads to nonsense-mediated decay of EXOC2 transcript, a severe reduction in exocytosis and vesicle fusion, and undetectable levels of EXOC2 protein. The patient from Family 2 had a milder clinical phenotype and reduced exocytosis. Cells from both patients showed defective Arl13b localization to the primary cilium. The discovery of mutations that partially disable exocyst function provides valuable insight into this essential protein complex in neural development. Since EXOC2 and other exocyst complex subunits are critical to neuronal function, our findings suggest that EXOC2 variants are the cause of the patients’ neurological disorders.
Japanese encephalitis virus–primed CD8+ T cells prevent antibody-dependent enhancement of Zika virus pathogenesis
Authors: Chen Dong , Duan Zhiliang , Zhou Wenhua , Zou Weiwei , Jin Shengwei , Li Dezhou , Chen Xinyu , Zhou Yongchao , Yang Lan , Zhang Yanjun , Shresta Sujan , Wen Jinsheng
Published: July 2020

Cross-reactive anti-flaviviral immunity can influence the outcome of infections with heterologous flaviviruses. However, it is unclear how the interplay between cross-reactive antibodies and T cells tilts the balance toward pathogenesis versus protection during secondary Zika virus (ZIKV) and Japanese encephalitis virus (JEV) infections. We show that sera and IgG from JEV-vaccinated humans and JEV-inoculated mice cross-reacted with ZIKV, exacerbated lethal ZIKV infection upon transfer to mice, and promoted viral replication and mortality upon ZIKV infection of the neonates born to immune mothers. In contrast, transfer of CD8+ T cells from JEV-exposed mice was protective, reducing the viral burden and mortality of ZIKV-infected mice and abrogating the lethal effects of antibody-mediated enhancement of ZIKV infection in mice. Conversely, cross-reactive anti-ZIKV antibodies or CD8+ T cells displayed the same pathogenic or protective effects upon JEV infection, with the exception that maternally acquired anti-ZIKV antibodies had no effect on JEV infection of the neonates. These results provide clues for developing safe anti-JEV/ZIKV vaccines.
Potent human broadly neutralizing antibodies to hepatitis B virus from natural controllers
Authors: Hehle Verena , Beretta Maxime , Bourgine Maryline , Ait-Goughoulte Malika , Planchais Cyril , Morisse Solen , Vesin Benjamin , Lorin Valérie , Hieu Thierry , Stauffer Andrea , Fiquet Oriane , Dimitrov Jordan D. , Michel Marie-Louise , Ungeheuer Marie-Noëlle , Sureau Camille , Pol Stanislas , Di Santo James P. , Strick-Marchand Hélène , Pelletier Nadège , Mouquet Hugo
Published: July 2020

Rare individuals can naturally clear chronic hepatitis B virus (HBV) infection and acquire protection from reinfection as conferred by vaccination. To examine the protective humoral response against HBV, we cloned and characterized human antibodies specific to the viral surface glycoproteins (HBsAg) from memory B cells of HBV vaccinees and controllers. We found that human HBV antibodies are encoded by a diverse set of immunoglobulin genes and recognize various conformational HBsAg epitopes. Strikingly, HBsAg-specific memory B cells from natural controllers mainly produced neutralizing antibodies able to cross-react with several viral genotypes. Furthermore, monotherapy with the potent broadly neutralizing antibody Bc1.187 suppressed viremia in vivo in HBV mouse models and led to post-therapy control of the infection in a fraction of animals. Thus, human neutralizing HBsAg antibodies appear to play a key role in the spontaneous control of HBV and represent promising immunotherapeutic tools for achieving HBV functional cure in chronically infected humans.
Prostaglandin E2 stimulates the epithelial sodium channel (ENaC) in cultured mouse cortical collecting duct cells in an autocrine manner
Authors: Mansley Morag K. , Niklas Christian , Nacken Regina , Mandery Kathrin , Glaeser Hartmut , Fromm Martin F. , Korbmacher Christoph , Bertog Marko
Published: July 2020

Prostaglandin E2 (PGE2) is the most abundant prostanoid in the kidney, affecting a wide range of renal functions. Conflicting data have been reported regarding the effects of PGE2 on tubular water and ion transport. The amiloride-sensitive epithelial sodium channel (ENaC) is rate limiting for transepithelial sodium transport in the aldosterone-sensitive distal nephron. The aim of the present study was to explore a potential role of PGE2 in regulating ENaC in cortical collecting duct (CCD) cells. Short-circuit current (ISC) measurements were performed using the murine mCCDcl1 cell line known to express characteristic properties of CCD principal cells and to be responsive to physiological concentrations of aldosterone and vasopressin. PGE2 stimulated amiloride-sensitive ISC via basolateral prostaglandin E receptors type 4 (EP4) with an EC50 of ∼7.1 nM. The rapid stimulatory effect of PGE2 on ISC resembled that of vasopressin. A maximum response was reached within minutes, coinciding with an increased abundance of β-ENaC at the apical plasma membrane and elevated cytosolic cAMP levels. The effects of PGE2 and vasopressin were nonadditive, indicating similar signaling cascades. Exposing mCCDcl1 cells to aldosterone caused a much slower (∼2 h) increase of the amiloride-sensitive ISC. Interestingly, the rapid effect of PGE2 was preserved even after aldosterone stimulation. Furthermore, application of arachidonic acid also increased the amiloride-sensitive ISC involving basolateral EP4 receptors. Exposure to arachidonic acid resulted in elevated PGE2 in the basolateral medium in a cyclooxygenase 1 (COX-1)–dependent manner. These data suggest that in the cortical collecting duct, locally produced and secreted PGE2 can stimulate ENaC-mediated transepithelial sodium transport.
Flow and shortcuts along the Shaker Kv channel slow inactivation gating cycle
Authors: Nirenberg Valerie Abigail , Yifrach Ofer
Published: July 2020

Closing the cycle of Kv channel slow inactivation gating.
Enhancing Phase Sensitivity in Mach–Zehnder Interferometers for Arbitrary Input States
Authors: Liang Hongbin , Pei Jiancheng , Wang Xiaoguang
Published: July 2020

To enhance the phase sensitivity of Mach–Zehnder interferometers, we use a tunable phase shift before the light beams are injected into the interferometer. The analytical result of the optimal phase shift is obtained, which only depends on the initial input states. For a non-zero optimal phase shift, the phase sensitivity of the interferometers in the output ports is always enhanced. We can achieve this enhancement for most states, including entangled and mixed states. The optimal phase shift is exhibited in three examples. Compared to previous methods, this scheme provides a general way to improve phase sensitivity and could find wide applications in optical phase estimations.
Dimensional analysis and the correspondence between classical and quantum uncertainty
Authors: Gattus V , Karamitsos S
Published: July 2020

Heisenberg’s uncertainty principle is often cited as an example of a ‘purely quantum’ relation with no analogue in the classical limit where ℏ → 0. However, this formulation of the classical limit is problematic for many reasons, one of which is dimensional analysis. Since ℏ is a dimensionful constant, we may always work in natural units in which ℏ = 1. Dimensional analysis teaches us that all physical laws can be expressed purely in terms of dimensionless quantities. This indicates that the existence of a dimensionally consistent constraint on ΔxΔp requires the existence of a dimensionful parameter with units of action, and that any definition of the classical limit must be formulated in terms of dimensionless quantities (such as quantum numbers). Therefore, bounds on classical uncertainty (formulated in terms of statistical ensembles) can only be written in terms of dimensionful scales of the system under consideration, and can be readily compared to their quantum counterparts after being non-dimensionalized. We compare the uncertainty of certain coupled classical systems and their quantum counterparts (such as harmonic oscillators and particles in a box), and show that they converge in the classical limit. We find that since these systems feature additional dimensionful scales, the uncertainty bounds are dependent on multiple dimensionless parameters, in accordance with dimensional considerations.
Development of NVW-SAEs with nonlinear correlation metrics for quality-relevant feature learning in process data modeling
Authors: Yuan Xiaofeng , Ou Chen , Wang Yalin
Published: July 2020

Soft sensors have become reliable tools for predicting difficult-to-measure quality variables in modern industrial process modeling. Feature representation is a key step to construct accurate soft sensor models. In the past decade, deep learning has shown great capacity of feature extractor for soft sensor modeling. However, most existing deep networks cannot capture quality-related features for output prediction. To deal with this problem, a variable-wise weighted stacked autoencoder (VW-SAE) was previously proposed to learn deep quality-related features, in which a variable weighted objective function is designed to learn quality-related features layer by layer. However, only linear correlation is considered for variable weighting, which is insufficient to extract quality-related features fully. In this paper, nonlinear VW-SAEs (NVW-SAEs) are constructed to enhance the learning capability for deep quality-related features, in which three correlation metrics are utilized to measure the nonlinear variable relationships and learn deep quality-related features. The prediction results show that NVW-SAEs can effectively extract quality-related features from process data. Two public data sets and an industrial debutanizer are used to validate the effectiveness of the NVW-SAEs.
Conductive filament evolution dynamics revealed by cryogenic (1.5 K) multilevel switching of CMOS-compatible Al2O3/TiO2 resistive memories
Authors: Beilliard Yann , Paquette François , Brousseau Frédéric , Ecoffey Serge , Alibart Fabien , Drouin Dominique
Published: July 2020

Non-volatile resistive switching devices are considered as prime candidates for next-generation memory applications operating at room temperature and above, such as resistive random-access memories or brain-inspired in-memory computing. However, their operability in cryogenic conditions remains to be mastered to adopt these devices as building blocks enabling large-scale quantum technologies via quantum–classical electronics co-integration. This study demonstrates multilevel switching at 1.5 K of Al2O3/TiO2-x
resistive memory devices fabricated with complementary metal-oxide-semiconducto-compatible processes and materials. The I–V characteristics exhibit a negative differential resistance (NDR) effect due to a Joule-heating-induced metal-insulator transition of the Ti4O7 conductive filament. Carrier transport analysis of all multilevel switching I–V curves show that while the insulating regime follows the space charge limited current (SCLC) model for all resistance states, the conduction in the metallic regime is dominated by SCLC and trap-assisted tunneling for low- and high-resistance states respectively. A non-monotonic conductance evolution is observed in the insulating regime, as opposed to the continuous and gradual conductance increase and decrease obtained in the metallic regime during the multilevel SET and RESET operations. Cryogenic transport analysis coupled to an analytical model accounting for the metal-insulator-transition-induced NDR effects and the resistance states of the device provide new insights on the conductive filament evolution dynamics and resistive switching mechanisms. Our findings suggest that the non-monotonic conductance evolution in the insulating regime is due to the combined effects of longitudinal and radial variations of the Ti4O7 conductive filament during the switching. This behavior results from the interplay between temperature- and field-dependent geometrical and physical characteristics of the filament.
Boundary element modelling of ultrasonic Lamb waves for structural health monitoring
Authors: Li Jun , Sharif Khodaei Zahra , Aliabadi M H
Published: July 2020

In this paper, a novel boundary element plate formulation is proposed to model ultrasonic Lamb waves in both pristine and cracked plates for structural health monitoring (SHM) applications. Lamb waves are generated and sensed by piezoelectric discs. An equivalent pin-force model is newly proposed to represent the actuation effect of piezoelectric discs, which is more accurate than the classical pin-force model. The boundary element formulation is presented in the Laplace-transform domain based on plate theories, which allows three-dimensional analysis of Lamb wave behaviours, such as propagation and interaction with cracks, in thin-walled structures. A damage detection algorithm is used for crack localization alongside the BEM-simulated data. The BEM solutions show excellent agreement with both 3D finite element simulation and experimental results.
Determination of Fluorescence Quantum Yields in Scattering Media
Authors: Lagorio María Gabriela
Published: July 2020

The fluorescence quantum yield is a measure of the efficiency of photon emission and quantifies the luminescent performance of a given sample. The determination of fluorescence quantum yields, particularly in scattering media, is relevant in the areas of materials science, technology and photonics. It is equally crucial when studying fluorescent bioanalytical probes and biological systems either for medical applications, physiological analyses or the interpretation of optical signals in nature. This type of determination represents a challenge since light scattering introduces an appreciable complexity in the measurements. Hence, the use of experimentally accurate methods and the understanding of their basis and principles is indispensable for obtaining reliable results. In addition, light re-absorption processes are usually very significant in these systems and the experimental quantum yields normally differ from the true quantum yields of the fluorophore. The first purpose of this work is to provide a clear and comprehensive compilation of the various optical methods that can be used for the determination of quantum yields in scattering media. A second purpose is to present the correction models to account for light re-absorption processes, applicable in each case. The advantages and disadvantages of each methodology are comparatively discussed, the difference between experimental and true quantum yield is clarified and it is explained which should be used depending on the case. Several examples previously published in literature are illustrated. The methods presented here are adequate for the study of very diverse samples such as suspensions, solid powders, films, animal tissues and even plant material.
Investigation of dielectric properties and methylene intactness under multiple environmental stresses for high voltage epoxy composites
Authors: Khattak Abraiz , Imran Kashif , Faiza  , Ali Asghar , Ulasyar Abasin , Haq Azhar Ul , Amin Muhammad , Khan Adam
Published: July 2020

Epoxy decays its dielectric characteristics and exhibits degradation of main hydrocarbon on exposure to multiple environmental stresses. Inorganic oxides-based epoxy composites have been performingwell in many applications and short-term testing; therefore, evaluation of their dielectric and structural characteristics under extreme weathering conditions may also unleash enhancement in these characteristics. To explore dielectric properties and degradation of main hydrocarbon group, neat epoxy and silica-based epoxy microcomposite (15% micro-silica loading) and nanocomposites (5% nano-silica loading)have been prepared and subjected to acid rain, heat, ultra-violet radiation, salt fog, and humidity in a chamber that was specially fabricated in view ofservice conditions. Interesting results were obtained before and after aging. Enhanced intactness of methylene group was observed in nanocomposite followed by micro composite. Similarly, for epoxy nanocomposites not only higher dielectric constant, lower energy dissipation and conductivity was recorded before application of stresses, but also nanocomposite showed superior sustainability in these properties after aging. In all analyses, microcomposites performed better than neat epoxy but in conductivity the results of both samples were found comparable.
Circulating Pregenomic Hepatitis B Virus RNA Is Primarily Full-length in Chronic Hepatitis B Patients Undergoing Nucleos(t)ide Analogue Therapy
Authors: Anderson Mark , Gersch Jeffery , Luk Ka-Cheung , Dawson George , Carey Ivana , Agarwal Kosh , Shah Pir , Dusheiko Geoffrey , Lau Daryl , Cloherty Gavin
Published: July 2020

Hepatitis B virus RNA is detectable in the serum of infected patients; however, the RNA species has been questioned. We tested 1827 specimens using a quantitative dual-target quantitative polymerase chain reaction assay and determined that full-length pregenomic RNA is the primary source. These results clarify the major identity of circulating HBV RNA species.
Implantation technique and optimal subcutaneous defibrillator chest position: a PRAETORIAN score-based study
Authors: Francia Pietro , Biffi Mauro , Adduci Carmen , Ottaviano Luca , Migliore Federico , De Bonis Silvana , Dello Russo Antonio , De Filippo Paolo , Viani Stefano , Bongiorni Maria Grazia , Caravati Fabrizio , Lavalle Carlo , Landolina Maurizio Eugenio , Pisanò Ennio , Giorgi Davide , Lovecchio Mariolina , Valsecchi Sergio , Diemberger Igor
Published: July 2020

Aims

The traditional technique for subcutaneous implantable cardioverter-defibrillator (S-ICD) implantation involves three incisions and a subcutaneous pocket. Recently, a two-incision and intermuscular (IM) technique has been adopted. The PRAETORIAN score is a chest radiograph-based tool that predicts S-ICD conversion testing. We assessed whether the S-ICD implantation technique affects optimal position of the defibrillation system according to the PRAETORIAN score.

Methods and results

We analysed consecutive patients undergoing S-ICD implantation. The χ2 test and regression analysis were used to determine the association between the PRAETORIAN score and implantation technique. Two hundred and thirteen patients were enrolled. The S-ICD generator was positioned in an IM pocket in 174 patients (81.7%) and the two-incision approach was adopted in 199 (93.4%). According to the PRAETORIAN score, the risk of conversion failure was classified as low in 198 patients (93.0%), intermediate in 13 (6.1%), and high in 2 (0.9%). Patients undergoing the two-incision and IM technique were more likely to have a low (<90) PRAETORIAN score than those undergoing the three-incision and subcutaneous technique (two-incision: 94.0% vs. three-incision: 78.6%; P = 0.004 and IM: 96.0% vs. subcutaneous: 79.5%; P = 0.001). Intermuscular plus two-incision technique was associated with a low-risk PRAETORIAN score (hazard ratio 3.76; 95% confidence interval 1.01–14.02; P = 0.04). Shock impedance was lower in PRAETORIAN low-risk patients than in intermediate-/high-risk categories (66 vs. 96 Ohm; P = 0.001). The PRAETORIAN score did not predict shock failure at 65 J.

Conclusion

In this cohort of S-ICD recipients, combining the two-incision technique and IM generator implantation yielded the lowest PRAETORIAN score values, indicating optimal defibrillation system position.

Clinical trial registration

http://clinicaltrials.gov/ Identifier: NCT02275637.
Hyperglycemia suppresses the regulatory effect of hypoxia-inducible factor-1α in pulmonary Aspergillus fumigatus infection
Authors: Ye Yao , Chen Yu , Sun Jianjun , Zhang Hanyin , Meng Yanling , Li Wenyang , Wang Wei
Published: July 2020

Aspergillus fumigatus is one of the most common fungal infections involved in the pulmonary diseases. Hypoxia-inducible factor-1α (HIF-1α) is important for antifungal immunity. Diabetes is a risk factor of pulmonary A. fumigatus infection and could affect the expression of HIF-1α. The aim of this investigation was to evaluate the role of HIF-1α in pulmonary A. fumigatus infection in diabetes. In murine model, we found diabetic mice had aggravated pulmonary A. fumigatus infection and declined expression of HIF-1α following pulmonary A. fumigatus infection. And these changes could be corrected by dimethyloxalylglycine (DMOG), the agonist of HIF-1α. In cell experiment, after A. fumigatus stimulation, hyperglycemic state was with a decreased HIF-1α expression and increased NLRP3/IL-1β signal pathway. The percentages of Th1 and Treg cells decreased, while percentages of Th2 and Th17 increased in hyperglycemic group. DMOG suppressed A. fumigatus-stimulated NLRP3 and IL-1β expressions in hyperglycemic group and corrected Th and Treg cells differentiation. These regulatory effects of DMOG could be dampened by activating of NLRP3. These data indicated that hyperglycemia suppressed the regulatory effect of HIF-1α in pulmonary A. fumigatus infection, which can affect Th and Treg cells differentiation by regulating the NLRP3/IL-1β signal pathway.
Variation between hospitals and reviewers in detection of adverse events identified through medical record review in Korea
Authors: Kim Sukyeong , Shin Ho Gyun , Jo A E Jeong , Min Ari , Ock Minsu , Hwang Jee-In , Jeong Youngjin , Park Moon Sung , Lee Jong Bouk , Chang Tae I K , Song Eunhyang , Kim Heungseon , Lee Sang-Il
Published: July 2020

Objectives

This study utilized the method of medical record review to determine characteristics of adverse events that occurred in the inpatient units of hospitals in Korea as well as the variations in adverse events between institutions.

Design

A two-stage retrospective medical record review was conducted. The first stage was a nurse review, where two nurses reviewed medical records of discharged patients to determine if screening criteria had been met. In the second stage, two physicians independently reviewed medical records of patients identified in the first stage, to determine whether an adverse event had occurred.

Setting

Inpatient units of six hospitals.

Participants

Medical records of 2 596 patients randomly selected were reviewed in the first stage review.

Intervention(s)

N/A.

Main Outcome Measure(s)

Adverse events.

Results

A total of 277 patients (10.7%) were confirmed to have had one or more adverse event(s), and a total of 336 adverse events were identified. Physician reviewers agreed about whether an adverse event had occurred for 141 patients (5.4%). The incidence rate of adverse events was at least 1.3% and a maximum of 19.4% for each hospital. Most preventability scores were less than four points (non-preventable), and there were large variations between reviewers and institutions.

Conclusions

Given the level of variation in the identified adverse events, further studies that include more medical institutions in their investigations are needed, and a third-party committee should be involved to address the reliability issues regarding the occurrence and characteristics of the adverse events.
Constraining the dense matter equation-of-state with radio pulsars
Authors: Hu Huanchen , Kramer Michael , Wex Norbert , Champion David J , Kehl Marcel S
Published: July 2020

Radio pulsars provide some of the most important constraints for our understanding of matter at supranuclear densities. So far, these constraints are mostly given by precision mass measurements of neutron stars (NS). By combining single measurements of the two most massive pulsars, J0348+0432 and J0740+6620, the resulting lower limit of 1.98 M⊙ (99 per cent confidence) of the maximum NS mass, excludes a large number of equations of state (EOSs). Further EOS constraints, complementary to other methods, are likely to come from the measurement of the moment of inertia (MOI) of binary pulsars in relativistic orbits. The Double Pulsar, PSR J0737−3039A/B, is the most promising system for the first measurement of the MOI via pulsar timing. Reviewing this method, based in particular on the first MeerKAT observations of the Double Pulsar, we provide well-founded projections into the future by simulating timing observations with MeerKAT and the SKA. For the first time, we account for the spin-down mass-loss in the analysis. Our results suggest that an MOI measurement with 11 per cent accuracy (68 per cent confidence) is possible by 2030. If by 2030 the EOS is sufficiently well known, however, we find that the Double Pulsar will allow for a 7 per cent test of Lense–Thirring precession, or alternatively provide a ∼3σ-measurement of the next-to-leading order gravitational wave damping in GR. Finally, we demonstrate that potential new discoveries of double NS systems with orbital periods shorter than that of the Double Pulsar promise significant improvements in these measurements and the constraints on NS matter.
The tensile strength of compressed dust samples and the catastrophic disruption threshold of pre-planetary matter
Authors: San Sebastián I L , Dolff A , Blum J , Parisi M G , Kothe S
Published: July 2020

During the planetary formation process, mutual collisions among planetesimals take place, impacting on their porosities. The outcome of these collisions depends, among other parameters, on the tensile strength of the colliding objects. In the first stage of this work, we performed impact experiments into dust samples, assembled with material analogous to that of the primitive Solar System, to obtain highly compressed samples that represent the porosities measured in chondritic meteorites. In the second stage, we obtained the tensile strengths of the compressed dust samples by the Brazilian Disc Test. We found a correlation between the tensile strength and the volume filling factor of the compressed dust samples and obtained the corresponding critical fragmentation strength in mutual collisions and its dependence on the volume filling factor. Finally, we give prescriptions for the catastrophic disruption threshold as a function of the object size, for different values of the volume filling factor.
Price, Income, and Affordability as the Determinants of Tobacco Consumption: A Practitioner’s Guide to Tobacco Taxation
Authors: Nargis Nigar , Stoklosa Michal , Shang Ce , Drope Jeffrey
Published: July 2020

Introduction

Tobacco product prices and consumers’ income are the two major economic determinants of tobacco demand. The affordability of tobacco products is dependent on the price of tobacco products relative to consumer income. Increase in tobacco tax is expected to lead to higher price, lower affordability, and reduced consumption. Price elasticity and affordability elasticity are used in analyzing the effect of tobacco tax increases on tobacco consumption and public health. The availability of both parameters raises the question of which one to apply in policy discussions.

Aims and Methods

Using global data on cigarette consumption, price, income, and tobacco control measures for 169 countries over 2007–2016, this study estimated the price elasticity and affordability elasticity of cigarette consumption by country income classification using country-specific fixed effects model for panel data.

Results

The estimates show that the restriction of equal strength of the effects of price and income changes on tobacco consumption maintained in affordability elasticity estimation is valid for low- and middle-income countries, while it is rejected for high-income countries.

Conclusions

Affordability elasticity may prove to be a useful parameter to explain and predict the sensitivity of consumers to tobacco tax and price policy changes under conditions of robust economic growth, which are more likely to be observed in countries with initial low- or middle-income setting. It can provide a reasonable benchmark for tobacco tax and price increase necessary to effectively reduce affordability and consumption of tobacco, which can form a basis for building systematic tax and price increases into the tobacco tax policy mechanism.

Implications

Price elasticity measures the sensitivity of consumers to changes in real prices, holding real income constant. Affordability elasticity measures the sensitivity of consumers to price changes adjusted for inflation and income changes. Existing scientific literature on tobacco demand abounds in both price and affordability elasticity estimates, without providing a clear explanation of the theoretical and policy implications of using one parameter over the other. By estimating and comparing price and affordability elasticities for high-income and low-and-middle-income countries separately, this article offers a guide to the practitioners in tobacco taxation for evaluating the effectiveness of tax-induced price increases on tobacco consumption.
The association between psychological factors and pain exacerbations in hip osteoarthritis
Authors: Fu Kai , Metcalf Ben , Bennell Kim L , Zhang Yuqing , Deveza Leticia A , Robbins Sarah R , Hunter David J
Published: July 2020

Objectives

To evaluate the association between psychological factors and pain exacerbations in people with hip OA.

Methods

Eligible participants with symptomatic hip OA were instructed to complete online questionnaires every 10 days over a 90-day follow-up period. In addition, they were required to complete the questionnaire whenever they perceived they were experiencing a hip pain exacerbation. Hip pain exacerbation was defined as an increase of 2 points in pain intensity compared with baseline on an 11-point numeric rating scale (0–10). The Depression, Anxiety and Stress Scale–21 Items, Positive and Negative Affect Schedule, Pain Catastrophizing Scale and Pain Self-Efficacy Questionnaire were used to evaluate psychological factors. The associations of these with risk of hip pain exacerbation were examined by conditional logistic regression.

Results

Of 252 participants recruited, 131 (52.0%) contributed both case and control period data and were included in the analysis. A significant association was found between Pain Catastrophizing Scale overall score (1 point increase) with hip pain exacerbations (odds ratio: 1.07, 95% CI: 1.04, 1.11). An increase of a minimal important change (5.5 points) of Pain Self-Efficacy Questionnaire score was associated with a lower odds of pain exacerbations (odds ratio: 0.74, 95% CI: 0.65, 0.85). No significant associations were found between Depression, Anxiety and Stress Scale–21 Items or Positive and Negative Affect Schedule scores with hip pain exacerbations.

Conclusion

Both pain catastrophizing and pain self-efficacy beliefs were associated with pain exacerbations in people with hip OA, but other psychological factors including depression, anxiety and stress or positive and negative affects, were not associated with pain exacerbations.
The trust and the waqf (comparative analysis)
Authors: Gvelesiani Irina
Published: July 2020

The trust is an outstanding creature of common law of the Middle Ages. It has gained international recognition essentially for its tripartite structure and unique character. Bifurcation of rights became a label of the trust and made it flexible and adaptable to various transfers. There are numerous debates regarding the origin of the trust. This article deals with the issue of Islamic origin. The methodology of the research is oriented to comparative analysis, which considers the comparison of the traditional models of the trust and the waqf. The parallel is drawn between the juridical and linguistic peculiarities.
Update on Pressure Injuries: A Review of the Literature
Authors: Saindon Kelly , Berlowitz Dan R.
Published: July 2020

The literature on pressure injuries continues to expand at a rapid rate, and keeping up to date with the current knowledge base is challenging. This summary describes six important new articles published in 2018 or 2019 about pressure injury pathophysiology, prevention, treatment, and epidemiology. For each article, a description of the results is provided, and then a comment about the significance of the results is offered. The new knowledge contained in this review should impact how clinicians incorporate the latest evidence-based practice for pressure injuries.

GENERAL PURPOSE

To provide information about the latest evidence-based practice related to pressure injuries (PIs).

TARGET AUDIENCE

This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and nurses with an interest in skin and wound care.

LEARNING OBJECTIVES/OUTCOMES

After participating in this educational activity, the participant should be better able to:

1. Identify risk factors and prevention strategies for PI.

2. Explain issues related to the treatment of PI.
Extracorporeal Membrane Oxygenation for Amniotic Fluid Embolism-Induced Cardiac Arrest in the First Trimester of Pregnancy: A Case Report
Authors: Creel-Bulos Christina , Hassani Brian , Stentz Michael J. , Budhrani Gaurav , Daneshmand Mani A. , Jabaley Craig S. , Groff Robert F.
Published: July 2020

Objectives:

Amniotic fluid embolism is a rare obstetric emergency that can be accompanied by profound hypoxemia, coagulopathy, hemorrhage, and cardiogenic shock. Extracorporeal membrane oxygenation may provide a rescue strategy in amniotic fluid embolism with cardiopulmonary collapse. Approaches to anticoagulation must be balanced against the risk of hemorrhage with concomitant coagulopathy. Although extracorporeal membrane oxygenation has been described for cardiopulmonary collapse in the setting of amniotic fluid embolism, its initiation as a bridge to hemostasis and cardiopulmonary recovery in amniotic fluid embolism–induced hemorrhagic and cardiogenic shock remains a novel resuscitation strategy.

Design, Subject, and Intervention:

We present a case detailing the initiation of extracorporeal life support with veno-arterio-venous extracorporeal membrane oxygenation in a patient with hemorrhagic shock and cardiopulmonary failure due to amniotic fluid embolism. The patient was ultimately discharged home 19 days after presentation free from neurologic or other significant disability.

Main Results and Conclusion:

Through this case, we describe a tailored approach to extracorporeal life support initiation and advanced extracorporeal membrane oxygenation management as a bridge to recovery in patients with mixed shock. Additionally, we discuss how the culmination of prehospital, outpatient and inpatient provider teamwork, easily portable extracorporeal membrane oxygenation equipment, and multispecialty collaboration can afford promising therapeutic options for patients who were previously deemed ineligible for extracorporeal life support.
Fundamentals of liquid biopsies in metastatic prostate cancer: from characterization to stratification
Authors: van Dessel Lisanne F. , Martens John W.M. , Lolkema Martijn P.
Published: July 2020

Purpose of review

In this review, we provide an overview of the recent developments and prospects on the applications of blood-based liquid biopsies, including circulating tumor DNA and circulating tumor cells, in metastatic prostate cancer.

Recent findings

Guidelines and consensus statements have been formulated to standardize preanalytical conditions that affect liquid biopsy analysis. Currently, there are four FDA approved assays for the analysis of liquid biopsies and many quantitative and qualitative assays are being developed. Comprehensive analyses of cell-free tumor DNA (ctDNA) and circulating tumor cells (CTCs) demonstrate that they adequately reflect the genomic makeup of the tumor and may thus complement or even replace tumor biopsies. The assessment of genomic aberrations in ctDNA can potentially predict therapy response and detect mechanisms of resistance. CTC count is not only a strong prognosticator in metastatic prostate cancer but can also measure therapy response.

Liquid biopsies may provide a temporal snapshot of the biologic variables that affect tumor growth and progression in metastatic prostate cancer. Liquid biopsies could inform on prognostic, predictive, and response measures. However, prospective clinical trials need to be performed to provide definitive validation of the clinical value of the most advanced assays.
HIPEC in advanced epithelial ovarian cancer: why is there controversy?
Authors: Vermorken Jan B. , van Dam Peter , Brand Alison
Published: July 2020

Purpose of review

The randomized OVHIPEC study provided further evidence that adding heated intraperitoneal chemotherapy (HIPEC) to interval cytoreductive surgery significantly improved recurrence-free and overall survival in stage III epithelial ovarian cancer (EOC) patients, who were ineligible for primary cytoreductive surgery due to extensive intraperitoneal disease. Because opinions have been divided as to whether HIPEC is now a new standard of care for advanced EOC, the pros and cons of this approach are examined. A comparison with the ongoing discussion about the role of intraperitoneal chemotherapy is made.

Recent findings

For both techniques, experience is crucial and a learning curve essential. Compared with intraperitoneal chemotherapy, intraoperative application of HIPEC provides superior distribution through the peritoneal cavity. HIPEC, as given in OVHIPEC, did not significantly increase adverse events, had no negative effect on quality of life and was cost-effective.

Despite the ongoing debate about HIPEC, an important first step in attempting to demonstrate the efficacy of HIPEC in the first-line setting has been made with OVHIPEC. Critics have been of value to optimize future trials with HIPEC in patients with EOC.
Concordance Analysis of the 23-Gene Expression Signature (myPath Melanoma) With Fluorescence In Situ Hybridization Assay and Single Nucleotide Polymorphism Array in the Analysis of Challenging Melanocytic Lesions: Results From an Academic Medical Center
Authors: Castillo Stephanie A. , Pham Anh K. , Dagrosa Alicia T. , Yan Shaofeng , Barton Dorothea T. , Lefferts Joel A. , Linos Konstantinos
Published: July 2020

Background:

Fluorescence in situ hybridization (FISH) and single nucleotide polymorphism (SNP) arrays are well-established molecular tests for the analysis of challenging melanocytic lesions. A 23-gene expression signature (GES), marketed as myPath Melanoma, is a recently introduced molecular test that categorizes melanocytic lesions as “benign,” “malignant,” and “indeterminate.” There are few studies on the concordance between FISH, SNP, and GES in the analysis of melanocytic lesions.

Methods:

A single-institution retrospective analysis of 61 contiguous cases of challenging melanocytic lesions with molecular analysis by 2 or more techniques. The primary objective was to determine the intertest agreement, which was calculated as percent agreement. A secondary objective was to determine the combined-test performance, that is, the frequency of obtaining a successful test (a test with an abnormal or normal, benign or malignant result) when 2 or more molecular tests were performed.

Results:

Of the 61 cases, 58 cases were submitted for analysis using the GES assay, 44 cases were submitted for FISH analysis, and 21 cases were submitted for SNP array analysis. Percent agreement between GES and FISH array was 50.9% (18/34), which improved to 69.7% (18/23) when indeterminate/equivocal results were excluded. Similarly, percent agreement between GES and SNP array was 57.1% (8/14); this improved to 77.8% (7/9) when indeterminate/equivocal results were excluded. In 44% of cases submitted for GES and FISH and in 39% of cases submitted for GES and SNP, one test was successful and the other was not.

Conclusion:

For challenging melanocytic lesions, the choice of a molecular test is consequential as the GES assay correlated with FISH and SNP arrays approximately only half of the time. This improved when cases with indeterminate/equivocal results were excluded from the calculations. The combined-test analysis supports the utility of conducting more than one molecular test, as this increased the odds of obtaining a successful test.
Low medication adherence is associated with decline in health-related quality of life: results of a longitudinal analysis among older women and men with hypertension
Authors: Peacock Erin , Joyce Cara , Craig Leslie S. , Lenane Zachary , Holt Elizabeth W. , Muntner Paul , Krousel-Wood Marie
Published: July 2020

Objective:

The aim of this study was to determine the association of low antihypertensive medication adherence with decline in health-related quality of life (HRQOL) over 1 year.

Methods:

We used data from older men and women with hypertension (n = 1525) enrolled in the Cohort Study of Medication Adherence among Older Adults. Adherence was measured using the validated self-report four-item Krousel-Wood Medication Adherence Scale (K-Wood-MAS-4) (low adherence = score ≥1) and prescription refill-based proportion of days covered (PDC) (low adherence = PDC < 0.80). We defined decline in HRQOL as a decrease in Mental Component Summary (MCS) or Physical Component Summary (PCS) score (from the RAND 36-Item Health Survey 1.0 administered at two time points – at the time of adherence assessment and 1 year later) equivalent to the minimal important difference (MID) for each respective summary score, calculated as the average of MID estimates derived from distribution and anchor-based approaches.

Results:

The prevalence of low adherence was 38.6% using the K-Wood-MAS-4 and 23.9% using PDC. On the basis of mean MID estimates of 4.40 for MCS and 5.16 for PCS, 21.8 and 25.2% of participants experienced a decline in MCS and PCS, respectively, over 1 year. Low adherence was associated with a decline in MCS for K-Wood-MAS-4 [prevalence ratio = 1.32, 95% confidence interval (95% CI) 1.08–1.62, P = 0.008], but not PDC (prevalence ratio  = 1.17, 95% CI 0.94–1.47, P = 0.168). Low adherence was not associated with decline in PCS (K-Wood-MAS-4: prevalence ratio  = 0.95, 95% CI 0.79–1.16; PDC: prevalence ratio  = 1.10, 95% CI 0.90–1.35).

Conclusion:

Low self-report medication adherence is associated with decline in mental HRQOL over 1 year in older adults with hypertension.