bluuebunny/crossref_metadata_2025 huggingface dataset:
Microscopie magnétique à spin unique
Authors: Jacques Vincent , Munsch Mathieu , Chaigneau Marc
Published: June 2021

Les méthodes expérimentales permettant de détecter la résonance de spin électronique de défauts ponctuels du diamant ouvrent de nouvelles perspectives pour le développement de capteurs quantiques à haute sensibilité. De tels capteurs ont notamment démontré des performances exceptionnelles pour l’imagerie magnétique aux échelles nanométriques, conduisant à une transition accélérée vers des solutions commerciales.
Retournement d’aimantation dans un dispositif « Spintronique » par impulsion d’électrons unique ultra-courte
Authors: Hehn Michel , Malinowski Gregory , Mangin Stéphane
Published: June 2021

Portée par l’internet des objets et l’intelligence artificielle, la quantité de données générées et stockées augmente de manière exponentielle. A l’horizon 2030, 20 % de l’électricité mondiale sera utilisée pour le stockage et la gestion des données. Une très large majorité des données est stockée sur des surfaces magnétiques. Nous démontrons que nous pouvons retourner l’aimantation d’une couche ferromagnétique, donc écrire de l’information, grâce à un seul pulse laser femto-seconde.
Une soudeuse pour fibres optiques
Authors: Le Boudec Patrice
Published: June 2021

Les fibres optiques sont de plus en plus utilisées dans des applications autres que les télécommunications. Pour ces différents marchés (scientifiques, industriels, défense, …), les fibres utilisées diffèrent parfois énormément des fibres classiques de type monomode SMF28. Afin d’obtenir des performances à la hauteur des besoins, différentes technologies de soudeuses ont été développées ces dernières années.
Therapie des metastasierten Pankreaskarzinoms in einem integrativen Konzept
Authors: Holzhauer Peter
Published: June 2021

Eine bei Diagnose eines metastasierten Pankreaskopfkarzinoms 70-jährige Patientin befindet sich nach 3-jähriger palliativ ausgerichteter Therapie in einem kontrollierten Erkrankungs- und gutem Allgemeinzustand. Neben Chemotherapie und lokaler Strahlentherapie kommen komplementäre Strategien zum Einsatz. Im Fokus stehen dabei die antiinflammatorische Behandlung mit maritimen ω-3-Fettsäuren, Natriumselenit und Curcumin sowie L-Carnitin zur Kompensation der Sarkopenie.
Non-viral Suicide Gene Therapy: Cytosine Deaminase Gene Directed by
VEGF Promoter and 5-fluorocytosine as a Gene Directed Enzyme/prodrug
System in Breast Cancer Model
Authors: Emamian Manouchehr , Abbaspour Akbar , Shahani Tina , Biglari Alireza , Sharafi Ali
Published: June 2021

The present study investigated the potential of vascular endothelial growth
factor (VEGF) promoter to derive cytosine deaminase (CD) transfected by
polyamidoamine (G4-PAMAM) dendrimers to 4T1 murine breast cancer cell line as
gene-directed enzyme/prodrug therapy. The VEGF promoter and cytosine
deaminase gene were cloned into the pEGFP-N1vector from the genomic DNA of 4T1
and E. coli, respectively. The frequency of transfection for
VEGF-CD-pEGFP-N1 and pEGFP-N1- CD treated groups was 35±3 and
36±4, respectively. MTT assay was perform to evaluate the cytotoxic
effects of converted 5-flurocytosine on 4T1 cells. Also, the optimal
concentration of 5-FC in 4T1 cells transfected by VEGF-CD-pEGFP-N1 plasmid was
evaluated. The GFP expression of transfected 4T1 cells by VEGF-CD-pEGFP-N1were
observed by fluorescent microscopy and flowcytometry. Results demonstrated that
the suicide CD gene was successfully expressed in 4T1 cells determined by RT-PCR
and GFP expression. A concentration of 200 μg/ml 5-FC was
identified as optimal dose of prodrug. Furthermore, the CD/5-FC
enzyme/prodrug system not only demonstrated toxicity on transformed 4T1
cells but also exerted a ‘bystander effect’ determined by MTT
assay. The results showed that by 35% transfection with
VEGF-CD–pEGFP-N1and CD-pEGFP-N1 plasmids, 80% and 90%
inhibition of the cells growth occurred, respectively.
A de novo Synthesis of Oxindoles from Cyclohexanone-Derived γ-Keto-Ester Acceptors Using a Desaturative Amination–Cyclization Approach
Authors: Caldora Henry P. , Govaerts Sebastian , Leonori Daniele , Dighe Shashikant U. , Turner Oliver J.
Published: June 2021

Here we report a desaturative approach for oxindole synthesis. This method uses simple ethyl 2-(2-oxocyclohexyl)acetates and primary amine building blocks as coupling partners. A dual photoredox–cobalt manifold is used to generate a secondary aniline that, upon heating, cyclizes with the pendent ester functionality. The process operates under mild conditions and was applied to the modification of several amino acids, the blockbuster drug mexiletine, as well as the formation of dihydroquinolinones.
Do Body Mass Index Levels Correlate with Tinnitus Among Teachers?
Authors: Marchiori Luciana Lozza de Moraes , Marchiori Glória de Moraes , Carlos Priscila , Benites Samuel Lopes , Mendes Marina Stephany Bobroff , Ciquinato Daiane Soares de Almeida
Published: June 2021

Introduction Working conditions can contribute to the development of lifestyle-related diseases among teachers, including obesity and tinnitus. Describing tinnitus in relation to characteristics and comorbidities can help the treatment and prognosis of teachers affected by this symptom.

Objective To verify a possible association between tinnitus complaint and body mass index (BMI) in teachers.

Methods Cross-sectional study with a sample of teachers who responded to the Visual Analog Scale (VAS) and to the Tinnitus Handicap Inventory (THI). The BMI (kg/m2) was calculated based on self-reported body weight (in kilograms) divided by height (in meters squared). Nonparametric statistics were applied adopting a significance level < 0.05

Results A total of 83 teachers were assessed, with a mean age 48 ± 9.7 years old; 63.9% (n= 53) were females; 44.6% were eutrophic (n = 37), and 16.9% (n = 14) were obese. Of the total, 19.3% (n = 16) reported tinnitus. No differences were found between the groups and BMI (p > 0.05), although there was a significant difference between the Tinnitus and No Tinnitus groups for age (p < 0.001). The chi-squared test showed an association between age group and tinnitus (p < 0.028); those with tinnitus were in the 49 to 65 years old age group. In addition, there was a moderate correlation between tinnitus parameters (VAS; THI-Functional; THI-Total) and BMI.

Conclusion There was a moderate correlation between tinnitus parameters and BMI indicating that, as the BMI increased, so did the impact of tinnitus in the lives of the teachers. Body mass index should be considered a factor in tinnitus assessment and rehabilitation process.
Newer Stents for Unresectable Malignant Distal Biliary Obstruction: Striving for Perfection!
Authors: Shah Jimil , Rana Surinder Singh
Published: June 2021

Endoscopic biliary stenting is one of the most commonly used palliative procedure in patients with unresectable malignant distal biliary obstruction. Biliary stenting can be performed with either plastic or metallic stents. Stent occlusion and migration are important limitations of currently available stents. Variety of newer stents with varying designs and stent materials like stents with antimigratory properties, antireflux stents, drug-eluting stents, radioactive stents, and bioabsorbable stents are being developed to overcome the limitations of currently available stents. In this article, we are discussing two articles on the newer stent designs (plastic and metal stents) for biliary drainage in patients with unresectable malignant distal biliary obstruction.
The Diagnostic Value of Blood and Urine IP-10 Test in Children Having Active Tuberculosis or Latent Tuberculosis Infection
Authors: Can Salim , Sahin Ayse , Dalgic Nazan , Aygün Deniz
Published: June 2021

Objective This study aimed to investigate interferon-gamma-inducible protein-10 (IP-10) values in serum and urine in pediatric patients in the diagnosis of active tuberculosis (TB) or latent TB infection (LTBI). It also aimed to investigate whether it can be used as a biomarker to distinguish between active TB and LTBI.

Methods Our study comprised active TB (25 patients), LTBI (25 patients), and the “infected” group (50 patients) formed by combining the two groups. As the control group, 37 healthy children were included in the study. TB skin test, plasma IP-10, and urine IP-10 measurements were performed in all patients included in the study. An additional QuantiFERON-TB Gold In-Tube (QFT-GIT) test was performed on patients evaluated as active TB or LTBI.

Results Plasma IP-10 levels of the patients in the active TB, LTBI, and the “infected” groups were significantly higher than the control group (p = 0.022, p = 0.028, and p = 0.007, respectively). Urine IP-10 was successful in distinguishing the active TB and “infected” groups from the control group (p = 0.007 and p = 0.047, respectively). Also, in the combined use of the tests, when QFT-GIT and urine IP-10 were positive together, active TB and LTBI could be distinguished (p = 0.044). Urine IP-10 levels were found to be significantly higher in those with pulmonary TB than those with extrapulmonary TB (p = 0.012).

Conclusion Our findings suggest that IP-10 can be used as a useful biomarker in the diagnosis of active TB in children.
Sigma Metrics: A Valuable Tool for Evaluating the Performance of Internal Quality Control in Laboratory
Authors: Kashyap Akriti , Sampath Sangeetha , Tripathi Preeti , Sen Arijit
Published: June 2021

Background Six Sigma is a widely accepted quality management system that provides an objective assessment of analytical methods and instrumentation. Six Sigma scale typically runs from 0 to 6, with sigma value above 6 being considered adequate and 3 sigma being considered the minimal acceptable performance for a process.

Methodology Sigma metrics of 10 biochemistry parameters, namely glucose, triglycerides, high-density lipoprotein (HDL), albumin, direct bilirubin, alanine transaminase, aspartate transaminase, urea nitrogen, creatinine and uric acid, and hematology parameters such as hemoglobin (Hb), total leucocyte count (TLC), packed cell volume (PCV), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), and platelet were calculated by analyzing internal quality control (IQC) data of 3 months (June–August 2019).

Results Sigma value was found to be > 6 for triglyceride, HDL, Hb, TLC, and MCH, signifying excellent results and no further modification with respect to IQC. Sigma value was between 3 and 6 for glucose, albumin, creatinine, uric acid, PCV, and MCHC, implying the requirement of improvement in quality control (QC) processes. Sigma value of < 3 was seen in AST, ALT, direct bilirubin, urea nitrogen, platelet, and MCV, signifying suboptimal performance.

Discussion Six Sigma provides a more quantitative framework for evaluating process performance with evidence for process improvement and describes how many sigmas fit within the tolerance limits.

Thus, for parameters with sigma value < 3, duplicate testing of the sample along with three QCs three times a day may be used along with stringent Westgard rules for rejecting a run.

Conclusion Sigma metrics help assess analytical methodologies and augment laboratory performance.
Unraveling the association between socioeconomic diversity and consumer price index in a tourism country
Authors: Leng Yan , Babwany Nakash Ali , Pentland Alex
Published: June 2021

Diversity has tremendous value in modern society. Economic theories suggest that cultural and ethnic diversity may contribute to economic development and prosperity. To date, however, the correspondence between diversity measures and the economic indicators, such as the Consumer Price Index, has not been quantified. This is primarily due to the difficulty in obtaining data on the micro behaviors and macroeconomic indicators. In this paper, we explore the relationship between diversity measures extracted from large-scale and high-resolution mobile phone data, and the CPIs in different sectors in a tourism country. Interestingly, we show that diversity measures associate strongly with the general and sectoral CPIs, using phone records in Andorra. Based on these strong predictive relationships, we construct daily, and spatial maps to monitor CPI measures at a high resolution to complement existing CPI measures from the statistical office. The case study on Andorra used in this study contributes to two growing literature: linking diversity with economic outcomes, and macro-economic monitoring with large-scale data. Future study is required to examine the relationship between the two measures in other countries.
Characterizing solar radiation based on frequency amplitude and variability
Authors: McConnon Aili
Published: June 2021

Considering measured solar radiation as a time domain signal to classify the converted frequency series according to amplitude and frequency.
Influence of structural characteristics on cable ampacity and electrical property for cross-linked polyethylene (XLPE) cable
Authors: Xu ZhiHui , Yang Ming , Peng HuaQing , Shi Liang
Published: June 2021

The influence of structural characteristics on the cable ampacity and electrical property of the cross-linked polyethylene (XLPE) cable was presented in this paper. First, four HVAC XLPE cables were selected to detect the structural characteristics by Fourier transform infrared spectroscopy spectrum, gel content, differential scanning calorimetry, and x-ray diffraction measurements. Second, relevant structural parameters were extracted from the measurements. Subsequently, the cable ampacity and electrical property, serving as the macroscopic properties of the cable, were quantified by the measurement of thermal resistivity ρ and breakdown field strength E0. These two parameters reflect the behavior of thermal conduction and electrical conduction, respectively. Finally, the correlation between the structural characteristics and the macroscopic properties was established by linear regression fitting. The results show that the cable ampacity is deeply subjected to the integrity of the XLPE molecular chains and the proportion of secondary crystals within the XLPE. The electrical property is deeply dominated by the crystallinity and lamellar thickness of the primary crystals within the XLPE.
Review on dust deposition and cleaning methods for solar PV modules
Authors: Zhao Weiping , Lv Yukun , Wei Zian , Yan Weiping , Zhou Qingwen
Published: June 2021

Dust accumulation significantly affects the solar PV(Photovoltaic) performance, resulting in a considerable decrease in output power, which can be reduced by 40% with the dust of 4 g/m2. Understanding the dust deposition characteristics of PV modules can provide theoretical support for selecting dust cleaning methods and formulating cleaning strategies. This paper introduced the factors affecting dust accumulation and presented the research status of dust deposition mechanisms. Moreover, the dust cleaning methods were discussed and compared. In future research, a comprehensive particle deposition model including surface energy and other factors could be established to explore the dust accumulation mechanism. Additionally, investigating the particle deposition condition to determine the deposition of particles is beneficial to understanding the dust accumulation characteristics and predicting the dust accumulation amount. Compared with mechanical cleaning methods, the cleaning effect of electrostatic (cleaning efficiency can reach 90%), coating, and acoustic wave methods is superior. If the three methods can be combined, using an electrostatic or coating method to remove small particles and acoustic waves to remove large particles is a promising approach.
Systematics of the Australian golden trapdoor spiders of the
Authors: Wilson Jeremy D. , Rix Michael G.
Published: June 2021

The Australian golden trapdoor spiders of the tribe Euoplini (family Idiopidae) are among the most abundant and diverse of mygalomorph lineages in subtropical eastern Australia. Throughout this highly populated area, species in the monophyletic Euoplos variabilis-group are largely ubiquitous; however, species delimitation has long proven difficult in the group because species are morphologically very similar and have parapatric or even sympatric distributions. We address these challenges in the variabilis-group, and explore the phylogeny and taxonomy of species using an integrative systematic approach. In doing so, we apply a conservative, pragmatic methodology, naming only species for which adequate data are available (namely sequence data and unequivocally linked male specimens), and explicitly stating and mapping material that could not be linked to a species, to aid future research on the group. We describe five new species from south-eastern Queensland –E. booloumba sp. nov., E. jayneae sp. nov., E. raveni sp. nov., E. regalis sp. nov. and E. schmidti sp. nov.; we redescribe two previously named species – E. similaris (Rainbow & Pulleine, 1918) and E. variabilis (Rainbow & Pulleine, 1918); and we reillustrate the recently described E. grandis Wilson & Rix, 2019. The nominate species, E. variabilis, is shown to have a far smaller distribution than previously thought, and E. similaris is given a modern taxonomic description for the first time. A key to adult male specimens is also provided. This study further reveals a case of sympatry between two species within the variabilis-group; both E. raveni sp. nov. and E. schmidti sp. nov. occur in the Brisbane Valley, south of the Brisbane River – a notable result given that closely related mygalomorph species usually occur allopatrically. This work updates what is currently known of the phylogeny and diversity of one of the dominant mygalomorph lineages of subtropical eastern Australia, resolving a complex and highly endemic fauna. http://zoobank.org/urn:lsid:zoobank.org:pub:A4FB92F6-EFFF-4468-B1D8-000D69923996
Museum genomics reveals the rapid decline and extinction of Australian rodents since European settlement
Authors: Roycroft Emily , MacDonald Anna J. , Moritz Craig , Moussalli Adnan , Portela Miguez Roberto , Rowe Kevin C.
Published: June 2021

Australia has the highest historically recorded rate of mammalian extinction in the world, with 34 terrestrial species declared extinct since European colonization in 1788. Among Australian mammals, rodents have been the most severely affected by these recent extinctions; however, given a sparse historical record, the scale and timing of their decline remain unresolved. Using museum specimens up to 184 y old, we generate genomic-scale data from across the entire assemblage of Australian hydromyine rodents (i.e., eight extinct species and their 42 living relatives). We reconstruct a phylogenomic tree for these species spanning ∼5.2 million years, revealing a cumulative total of 10 million years (>10%) of unique evolutionary history lost to extinction within the past ∼150 y. We find no evidence for reduced genetic diversity in extinct species just prior to or during decline, indicating that their extinction was extremely rapid. This suggests that populations of extinct Australian rodents were large prior to European colonization, and that genetic diversity does not necessarily protect species from catastrophic extinction. In addition, comparative analyses suggest that body size and biome interact to predict extinction and decline, with larger species more likely to go extinct. Finally, we taxonomically resurrect a species from extinction, Gould’s mouse (
Pseudomys gouldii
Waterhouse, 1839), which survives as an island population in Shark Bay, Western Australia (currently classified as
Pseudomys fieldi
Waite, 1896). With unprecedented sampling across a radiation of extinct and living species, we unlock a previously inaccessible historical perspective on extinction in Australia. Our results highlight the capacity of collections-based research to inform conservation and management of persisting species.
Conventional NK cells and tissue-resident ILC1s join forces to control liver metastasis
Authors: Ducimetière Laura , Lucchiari Giulia , Litscher Gioana , Nater Marc , Heeb Laura , Nuñez Nicolás Gonzalo , Wyss Laura , Burri Dominik , Vermeer Marijne , Gschwend Julia , Moor Andreas E. , Becher Burkhard , van den Broek Maries , Tugues Sonia
Published: June 2021

Significance

Innate lymphoid cells hold great promise for the treatment of metastases. Development of effective therapies based on these versatile immune cells, however, is hampered by our limited knowledge of their behavior in the metastatic niche. Here, we describe that defense against liver metastasis requires collaboration between two innate lymphocyte subsets, conventional NK cells (cNKs) and tissue-resident type I innate lymphoid cells (trILC1s). We show that different cancers generate their own particular metastatic niche–inducing specific changes in cNKs and trILC1s. Furthermore, we uncover specific cNK subsets that can be manipulated to improve their antimetastatic potential. Our work contributes to understanding how cancer-specific factors and hepatic innate lymphocytes exert mutual influence and how this can be exploited for therapeutic purposes.
Revisiting the sedimentary record of the rise of diatoms
Authors: Westacott Sophie , Planavsky Noah J. , Zhao Ming-Yu , Hull Pincelli M.
Published: June 2021

Significance

The fossil record has been used to suggest that diatoms rose to become one of the most dominant primary producers in the world over the past 20 million years, thereby transforming the global silicon cycle. Here we provide new evidence that the fossil record of diatoms is strongly influenced by changes in preservation potential. We show that changes in deep-sea sedimentation rate and temperature over the Cenozoic Era (the past 66 million years) would have led to better diatom fossil preservation toward the present, producing an apparent rise that does not necessarily reflect a primary ecological signal. This finding is transformative for our understanding of the Cenozoic silica cycle and diatoms’ role in it.
Bronze Age weight systems as a measure of market integration in Western Eurasia
Authors: Ialongo Nicola , Hermann Raphael , Rahmstorf Lorenz
Published: June 2021

Significance

Increasing evidence shows that Bronze Age civilizations in Western Eurasia were economically interdependent for the procurement of essential raw materials. While this phenomenon hints at the possible formation of the first integrated market in history, recent models do not tackle its macroeconomic implications. Here, we address the customary regulation of weight systems as a measure of market integration. We show that Western Eurasian weight systems are consistent with the origin from a single unit. The information flow was efficient enough to regulate the statistical dispersion of weight systems on a continental scale, without any substantial intervention from political authorities. We argue that this suggests that the market had a concrete potential for an efficient reaction to price fluctuations.
Effect of Ti addition on the microstructure and properties of Cu–Cr alloy
Authors: Fang Hang , Liu Ping , Chen Xiaohong , Zhou Honglei , Fu Shaoli , Liu Kejie , Liu Hang , Guo Weichun
Published: June 2021

The Cu–Cr–Ti alloys with different Ti contents were prepared by vacuum induction melting, solid solution, cold deformation, and ageing treatment. The microstructures, mechanical, and electrical properties of Cu–Cr–Ti alloys were investigated under different Ti contents. The results indicate that the increase of Ti content can improve the mechanical properties of Cu–Cr–Ti alloys, whereas its conductivity decreases significantly. After cold rolling by 80% and ageing at 500°C for 60 min, the Cu-0.3Cr-0.05Ti alloy with the hardness, electrical conductivity, and tensile strength are 162.6 HV, 82.2% IACS, and 510 MPa, respectively. The strengthening mechanism of the studied alloys is mainly attributed to the Orowan precipitation and dislocation strengthening. The addition of Ti in the ageing process can retard the growth and coarsen Cr precipitates.
Fluid dynamics on logarithmic lattices
Authors: Campolina Ciro S , Mailybaev Alexei A
Published: June 2021

Open problems in fluid dynamics, such as the existence of finite-time singularities (blowup), explanation of intermittency in developed turbulence, etc, are related to multi-scale structure and symmetries of underlying equations of motion. Significantly simplified equations of motion, called toy-models, are traditionally employed in the analysis of such complex systems. In these models, equations are modified preserving just a part of the structure believed to be important. Here we propose a different approach for constructing simplified models, in which instead of simplifying equations one introduces a simplified configuration space: velocity fields are defined on multi-dimensional logarithmic lattices with proper algebraic operations and calculus. Then, the equations of motion retain their exact original form and, therefore, naturally maintain most scaling properties, symmetries and invariants of the original systems. Classification of such models reveals a fascinating relation with renowned mathematical constants such as the golden mean and the plastic number. Using both rigorous and numerical analysis, we describe various properties of solutions in these models, from the basic concepts of existence and uniqueness to the blowup development and turbulent dynamics. In particular, we observe strong robustness of the chaotic blowup scenario in the three-dimensional incompressible Euler equations, as well as the Fourier mode statistics of developed turbulence resembling the full three-dimensional Navier–Stokes system.
Lax connections in

-deformed integrable field theories *
Authors: Chen Bin , Hou Jue , Tian Jia
Published: June 2021

In this work, we attempt to construct the Lax connections of

-deformed integrable field theories in two different ways. With reasonable assumptions, we make an ansatz and find the Lax pairs in the

-deformed affine Toda theories and the principal chiral model by solving the Lax equations directly. This method is straightforward, but it may be difficult to apply for general models. We then make use of a dynamic coordinate transformation to read the Lax connection in the deformed theory from the undeformed one. We find that once the inverse of the transformation is available, the Lax connection can be read easily. We show the construction explicitly for a few classes of scalar models and find consistency with those determined using the first method.
TiO2/PFO inorganic-organic hybrid heterojunction for self-powered blue light photodetector
Authors: Xie Yanru , Yao Yicun , Zhang Dong , Li Hefu , Wang Qingru , Zhang Liqiang
Published: June 2021

Organic-inorganic hybrid heterojunction is very promising for low cost and high performance photodetection device application. We have fabricated a heterojunction composed of n-type inorganic TiO2 nanorod arrays and p-type organic semiconductor polymer [9,9-bis-(2-ethylhexyl)-9H-fluorene-2,7-diyl] (PFO). A peak of 0.32 mA W−1 was observed locating at 410 nm in spectral responsivity curve. The photocurrent response was rapid, repeatable as well as consistent. Under weak blue light (410 nm, 75 μW cm−2) irradiance, the rise time and decay time were observed to be 0.16 and 0.12 s, respectively. These results demonstrated that TiO2/PFO heterojuncton could bring prospect for the development of self-powered blue light photodetectors with high spectral selectivity.
The association of glucagon with disease severity and progression in patients with autosomal dominant polycystic kidney disease: an observational cohort study
Authors: Knol Martine G E , Kramers Bart J , Gansevoort Ron T , van Gastel Maatje D A
Published: June 2021

Background

Mammalian target of rapamycin (mTOR) inhibitors and ketogenesis have been shown to ameliorate disease progression in experimental autosomal dominant polycystic kidney disease (ADPKD). Glucagon is known to lower mTOR activity and stimulate ketogenesis. We hypothesized that in ADPKD patients, higher endogenous glucagon is associated with less disease severity and progression.

Methods

Data were analysed from 664 Dutch ADPKD patients participating in the Developing Intervention Strategies to Halt Progression of ADPKD observational cohort, including patients >18 years of age with an estimated glomerular filtration rate (eGFR) ≥15 mL/min/1.73 m2 and excluding patients with concomitant diseases or medication use that may impact the natural course of ADPKD. The association between glucagon and disease severity and progression was tested using multivariate linear regression and mixed modelling, respectively.

Results

The median glucagon concentration was 5.0 pmol/L [interquartile range (IQR) 3.4–7.2) and differed significantly between females and males [4.3 pmol/L (IQR 2.9–6.0) and 6.6 (4.5–9.5), P < 0.001, respectively]. Intrasubject stability of glucagon in 30 patients showed a strong correlation (Pearson’s correlation coefficient 0.893; P < 0.001). Moreover, glucagon showed significant associations with known determinants (sex, body mass index and copeptin; all P < 0.01) and known downstream effects (glucose, haemoglobin A1c and cholesterol; all P < 0.05), suggesting that glucagon was measured reliably. Cross-sectionally, glucagon was associated with eGFR and height-adjusted total kidney volume, but in the opposite direction of our hypothesis, and these lost significance after adjustment for confounders. Glucagon was not associated with an annual decline in kidney function or growth in kidney volume.

Conclusions

These data do not provide evidence for a role of endogenous glucagon as a protective hormone in ADPKD. Intervention studies are needed to determine the relation between glucagon and ADPKD.
Polypharmacy and medication use in patients with chronic kidney disease with and without kidney replacement therapy compared to matched controls
Authors: van Oosten Manon J M , Logtenberg Susan J J , Hemmelder Marc H , Leegte Martijn J H , Bilo Henk J G , Jager Kitty J , Stel Vianda S
Published: June 2021

Background

This study aims to examine polypharmacy (PP) prevalence in patients with chronic kidney disease (CKD) Stage G4/G5 and patients with kidney replacement therapy (KRT) compared with matched controls from the general population. Furthermore, we examine risk factors for PP and describe the most commonly dispensed medications.

Methods

Dutch health claims data were used to identify three patient groups: CKD Stage G4/G5, dialysis and kidney transplant patients. Each patient was matched to two controls based on age, sex and socio-economic status (SES) score. We differentiated between ‘all medication use’ and ‘chronic medication use’. PP was defined at three levels: use of ≥5 medications (PP), ≥10 medications [excessive PP (EPP)] and ≥15 medications [hyper PP (HPP)].

Results

The PP prevalence for all medication use was 87, 93 and 95% in CKD Stage G4/G5, dialysis and kidney transplant patients, respectively. For chronic medication use, this was 66, 70 and 75%, respectively. PP and comorbidity prevalence were higher in patients than in controls. EPP was 42 times more common in young CKD Stage G4/G5 patients (ages 20–44 years) than in controls, while this ratio was 3.8 in patients ≥75 years. Older age (64–75 and ≥75 years) was a risk factor for PP in CKD Stage G4/G5 and kidney transplant patients. Dialysis patients ≥75 years of age had a lower risk of PP compared with their younger counterparts. Additional risk factors in all patients were low SES, diabetes mellitus, vascular disease, hospitalization and an emergency room visit. The most commonly dispensed medications were proton pump inhibitors (PPIs) and statins.

Conclusions

CKD Stage G4/G5 patients and patients on KRT have a high medication burden, far beyond that of individuals from the general population, as a result of their kidney disease and a large burden of comorbidities. A critical approach to medication prescription in general, and of specific medications like PPIs and statins (in the dialysis population), could be a first step towards more appropriate medication use.
Ultra-Early Differential Diagnosis of Acute Cerebral Ischemia and Hemorrhagic Stroke by Measuring the Prehospital Release Rate of GFAP
Authors: Mattila Olli S , Ashton Nicholas J , Blennow Kaj , Zetterberg Henrik , Harve-Rytsälä Heini , Pihlasviita Saana , Ritvonen Juhani , Sibolt Gerli , Nukarinen Tiina , Curtze Sami , Strbian Daniel , Pystynen Mikko , Tatlisumak Turgut , Kuisma Markku , Lindsberg Perttu J
Published: June 2021

Background

Plasma glial fibrillary acidic protein (GFAP) and tau are promising markers for differentiating acute cerebral ischemia (ACI) and hemorrhagic stroke (HS), but their prehospital dynamics and usefulness are unknown.

Methods

We performed ultra-sensitivite single-molecule array (Simoa®) measurements of plasma GFAP and total tau in a stroke code patient cohort with cardinal stroke symptoms [National Institutes of Health Stroke Scale (NIHSS) ≥3]. Sequential sampling included 2 ultra-early samples, and a follow-up sample on the next morning.

Results

We included 272 cases (203 ACI, 60 HS, and 9 stroke mimics). Median (IQR) last-known-well to sampling time was 53 (35–90) minutes for initial prehospital samples, 90 (67–130) minutes for secondary acute samples, and 21 (16–24) hours for next morning samples. Plasma GFAP was significantly higher in patients with HS than ACI (P < 0.001 for <1 hour and <3 hour prehospital samples, and <3 hour secondary samples), while total tau showed no intergroup difference. The prehospital GFAP release rate (pg/mL/minute) occurring between the 2 very early samples was significantly higher in patients with HS than ACI [2.4 (0.6–14.1)] versus 0.3 (−0.3–0.9) pg/mL/minute, P < 0.001. For cases with <3 hour prehospital sampling (ACI n = 178, HS n = 59), a combined rule (prehospital GFAP >410 pg/mL, or prehospital GFAP 90–410 pg/mL together with GFAP release >0.6 pg/mL/minute) enabled ruling out HS with high certainty (NPV 98.4%) in 68% of patients with ACI (sensitivity for HS 96.6%, specificity 68%, PPV 50%).

Conclusions

In comparison to single-point measurement, monitoring the prehospital GFAP release rate improves ultra-early differentiation of stroke subtypes. With serial measurement GFAP has potential to improve future prehospital stroke diagnostics.
Programmed Cell Death Ligand 1-Expressing Circulating Tumor Cells: A New Prognostic Biomarker in Non-Small Cell Lung Cancer
Authors: Sinoquet Léa , Jacot William , Gauthier Ludovic , Pouderoux Stéphane , Viala Marie , Cayrefourcq Laure , Quantin Xavier , Alix-Panabières Catherine
Published: June 2021

Background

In non-small cell lung cancer (NSCLC), analysis of programmed cell death ligand 1 (PD-L1) expression in circulating tumor cells (CTCs) is a potential alternative to overcome the problems linked to the tumor biopsy spatiotemporal heterogeneity. However, the prognostic significance of PD-L1-positive [PD-L1(+)] CTCs remains controversial.

Methods

We prospectively evaluated the correlation with clinicopathological variables and prognostic value of PD-L1(+) CTCs, detected with the FDA-cleared CellSearch® system, in 54 patients with advanced NSCLC.

Results

We detected CTCs and PD-L1(+) CTCs in 43.4% and 9.4% of patients with NSCLC. PD-L1 expression concordance between tumor tissue and CTCs was low (54%). The presence of PD-L1(+) CTC correlated with the absence of gene alterations in tumor tissue and with poor prognosis-related biological variables (anemia, hyponatremia, increased lactate dehydrogenase). In univariate analysis, absence of gene alterations, number of metastatic sites, prior systemic therapies, and presence of CTCs and PD-L1(+) CTCs were associated with worse overall survival, whereas PD-L1 expression in tumor tissue was not. In multivariate analysis, squamous cell carcinoma histology, number of prior systemic treatments, and the presence of CTC were significantly associated with overall survival. Survival was worse in patients with PD-L1(+) CTCs than in patients with PD-L1-negative CTC or without any CTC.

Conclusions

Our study suggests that the presence of PD-L1(+) CTCs is associated with poor prognosis in patients with advanced NSCLC. Studies with larger samples are needed to confirm our results and to determine how PD-L1(+) CTC detection could help to predict the response or resistance to anti-PD-1/PD-L1 therapies.

 

Clinical trial registration NCT02866149
Normalization of left ventricular filling pressure after cardiac surgery for the Loeffler’s endocarditis: a case report
Authors: Carcaterra Andrea , Mock Stéphane , Müller Hajo , Testuz Ariane
Published: June 2021

Background

Loeffler endocarditis is a rare restrictive cardiomyopathy, characterized by hypereosinophilia and fibrous thickening of the endocardium causing progressive onset of heart failure and appearance of thrombi on the walls of the heart chambers.

Case summary

A 72-year-old man known for hypertension and dyslipidaemia consults for progressive dyspnoea up to New York Heart Association (NYHA) Classes 2–3 over 3 weeks. The biological balance sheet shows a high eosinophil level and an echocardiography shows a mild echodensity fixed to the left apex. After exclusion of a secondary cause of hypereosinophilia, diagnosis of endomyocardial fibrosis in the context of a hypereosinophilic syndrome (HES) is therefore retained. The patient’s clinical presentation with cardiac involvement leads us to start a treatment with corticosteroids. The patient is then regularly followed every 6 months with an initially stable course without complications. Two years later, he develops progressive signs of heart failure. Transthoracic echocardiography shows a left ventricular (LV) dilatation with a normal ejection fraction, but decreased volume due to a large echodense mass in the apex, and moderate aortic regurgitation caused by myocardial infiltration. In view of this rapid evolution, resection of the LV mass with concomitant aortic valve replacement is performed. Pathology confirms eosinophilic infiltration. The clinical course is very good with a patient who remains stable with dyspnoea NYHA Classes 1–2, and echocardiography at 1 year shows a normalization of LV filling pressure.

Discussion

HES represents a heterogeneous group of disorders characterized by overproduction of eosinophils. One of the major causes of mortality is associated cardiac involvement. Endocardial fibrosis and mural thrombosis are frequent cardiac findings. Echocardiography plays a crucial role in initial diagnosis of endomyocardial fibrosis, and for regular follow-up in order to adapt medical treatment and monitor haemodynamic evolution of the restrictive physiology and of valvular damage caused by the disease’s evolution. This case also shows that surgery can normalize filling pressure and allow a clear improvement on the clinical condition even at the terminal fibrotic state.
Run-off Elections in the Laboratory
Authors: Bouton Laurent , Gallego Jorge , Llorente-Saguer Aniol , Morton Rebecca
Published: June 2021

We study experimentally the properties of the majority run-off system and compare them to those of plurality rule. Our focus is on Duverger’s famous prediction that the plurality rule leads to higher co-ordination of votes on a limited number of candidates than the majority run-off rule. We find strong co-ordination forces under both systems. However, as predicted by the theory, in some cases these forces are stronger under plurality. Despite these differences in voting behaviour, we find small and mostly not significant differences in electoral outcomes and, hence, voters’ welfare.
Fecal Microbiota Transplantation for Severe or Fulminant Clostridioides difficile Infection: Systematic Review and Meta-analysis
Authors: Song Yi Nong , Yang David Yi , Veldhuyzen van Zanten Sander , Wong Karen , McArthur Eric , Song Claire Zhao , Ianiro Gianluca , Cammarota Giovanni , Kelly Colleen , Fischer Monika , Russell Lindsey , Kao Dina
Published: June 2021

Background

Severe or fulminant Clostridioides difficile infection (SFCDI) is associated with significant morbidity and mortality. Emerging evidence suggests fecal microbiota transplant (FMT) may be a promising therapy for SFCDI.

Aim

This systematic review determines the safety and efficacy of FMT in medically refractory SFCDI.

Methods

A systematic search of the literature was conducted using PubMed (1965 to 2020), Web of Science (1900 to 20), EMBASE (1974 to 2020), and Cochrane Review (1945 to 2020). Quality appraisal by NIH Study Quality Assessment tools, and data extraction were performed by two teams of independent researchers. The primary outcome was resolution of SFCDI 4 weeks after the final FMT. Pooled resolution rates were calculated using generalized linear mixed models estimates.

Results

Two hundred and forty patients from 10 studies (8 case series, 1 case–control and 1 randomized study) were included with 209 individual patient-level data. FMT resulted in resolution of SFCDI within 4 weeks in 211/240 individuals for a pooled estimate of 88% (95% confidence interval [CI]: 0.83 to 0.91). The mean number of FMT required was 1.6 for severe and 2.0 for fulminant CDI resolution. The pooled proportional estimates for patients requiring CDI-directed antimicrobials after FMT was 50% (95% CI: 0.06 to 0.94) for severe CDI and 67.0% (95% CI: 0.30 to 0.91) for fulminant CDI. Serious adverse event rates were low.

Conclusion

FMT appears effective in treating SFCDI patients with low adverse events, but requires multiple treatments with a significant proportion of patients requiring additional anti-CDI antibiotics to achieve resolution. The optimal route of FMT delivery remains unknown. The presence of pseudomembranous colitis may guide additional FMT or anti-CDI antibiotic treatment.
Variation in Genetic Mechanisms for Plumage Polymorphism in Skuas (Stercorarius)
Authors: Janssen Kirstin , Bustnes Jan Ove , Mundy Nicholas I
Published: June 2021

Coloration is evolutionarily labile and so provides an excellent trait for examining the repeatability of evolution. Here, we investigate the repeatability of the evolution of polymorphic variation in ventral plumage coloration in skuas (Stercorarius: Stercorariidae). In 2 species, arctic (S. parasiticus) and pomarine skuas (S. pomarinus), plumage polymorphism was previously shown to be associated with coding changes at the melanocortin-1 receptor (MC1R) locus. Here, we show that polymorphism in a third species, the south polar skua (S. maccormicki), is not associated with coding variation at MC1R or with variation at a Z-linked second candidate locus, tyrosinase-related protein 1 (TYRP1). Hence, convergent evolution of plumage polymorphisms in skuas is only partly repeatable at the level of the genetic locus involved. Interestingly, the pattern of repeatability in skuas is aligned not with phylogeny but with the nature of the phenotypic variation. In particular, south polar skuas show a strong sex bias to coloration that is absent in the other species, and it may be that this has a unique genetic architecture.
#10: Tropism, Susceptibility, and Infectivity of Differentiated Human Tonsillar Epithelial Cells by Different Influenza Viruses
Authors: Okda* Faten A , Webby Richard
Published: June 2021

Introduction

Influenza viruses cause significant socioeconomic impact due to annual outbreaks and pandemic risks. Human tonsil epithelium cells (HTEC) are a heterogeneous group of actively differentiating epithelia comprising stratified squamous epithelium and reticulated crypt cells with abundant keratin expression.

Hypothesis

We hypothesized that the tonsils are a primary site for influenza infection and sustained viral replication.

Methods and Results

Primary HTEC (ScienCell Research Laboratories) were grown using an air-liquid interface and infected apically with different influenza viruses at various MOIs to measure viral growth kinetics. These cells were highly differentiated, with subpopulations of cells including ciliated, non-ciliated cells and specialized cells with secretory functions. There was a heterogenous distribution of both human-like (α2,6-linked) and avian-like (α2,3-linked) sialic acid receptors. The HTEC surface and crypts were lined with pseudostratified columnar ciliated cells possessing both α2,6-linked and α2,3-linked sialic acid receptors that were interrupted by patches of reticular epithelial cells. The HTEC epithelial cells were permissive for growth of influenza A and B viruses. A subset of cells, mostly ciliated cells, underwent apoptosis while others including non-ciliated cells remained intact despite being positive for influenza virus nucleoprotein. Interestingly, differences were seen between subtypes with colocalization of H3N2 virus and non-ciliated cells while H1N1 virus mostly associated with ciliated cells.

Conclusion

Our results implicated human tonsillar crypt epithelium as a site for influenza virus replication. The tonsil epithelium cell culture differentiated system provides a valuable in vitro model for studying cellular tropism, infectivity, cytokines immune response and the pathogenesis of influenza viruses for better development of effective universal vaccine and therapies against different strains of influenza viruses.
#12: The Safety and antibody kinetics of COVID-19 Convalescent Plasma for the Treatment of Moderate to Severe Cases of SARS-CoV-2 Infection in Pediatric Patients
Authors: Galvis Alvaro E , Morphew Tricia , Ehwerhemuepha Louis , Osborne Stephanie , Enriquez Claudia , Imfeld Karen , Hoag Janet , Nieves Delma , Ashouri Negar , Singh Jajist , Nugent Diane , Arrieta Antonio
Published: June 2021

Introduction

A novel Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified as the pathogen responsible for a serious, life threatening respiratory infection (COVID-19) initially reported in Wuhan, China which rapidly spread worldwide resulting in global pandemic. Multiple immunological and pharmacological therapies have been evaluated with variable results. Convalescent plasma has been used in previous outbreaks such as Influenza 1918 and 2009, Ebola, MERS and SARS with good efficacy and safety reported. There have been multiple large reports on the safety of COVID-19 convalescent plasma (CCP) for the treatment of this serious infection in the adults; controversy has ensued regarding its efficacy. Pediatric data on CCP use are limited.

Methods

We conducted a prospective, open label treatment trial using CCP (10 ml/kg up to 1 unit) for the treatment of COVID-19 in pediatric patients with moderate to severe disease or high risk for serious illness. Safety and antibody kinetics and outcome data were collected.

Results

Eighteen moderate to severe COVID19 pediatric patients were enrolled and received CCP early in their illness (median days of symptoms XX). We observed no infusion related adverse events, no hematological or metabolic adverse events were noted during the hospitalization and at 3 weeks after infusion follow up. Sixteen patients demonstrated significant clinical improvement by day seven post infusion, as measured by the WHO eight-category ordinal severity scale for COVID-19. Presence of SARS-COV-2 anti-nucleocapsid IgG was demonstrated in all CCP specimens, a significant increase in antibodies was demonstrated in CCP recipients 24 hours after receiving CCP. Sustained high levels of anti- SARS-COV-2 anti-nucleocapsid IgG was demonstrated at 7- and 21-days post-transfusion. A transient IgM response not associated with CCP was noted. Eleven (61.1%) patients were discharge to home by day 7 post CCP infusion. One patient remained on invasive ventilatory support 21 days after CCP infusion and was eventually discharged to an intermediate care facility, one patient died retrospectively confirmed to have been brain death before receiving CCP.

Conclusion

We conclude that CCP was well tolerated in pediatric patients. CCP resulted in rapid increase of antibodies and sustained levels 21 days after infusion suggesting that CCP did not interfere with patients own immune response. More data are necessary to establish efficacy of this intervention in children, but our patients clinical course suggests benefit of CCP. Pediatric patients with moderate to severe COVID-19 may benefit of CCP when used early in the course of illness in conjunction with other immunological or antiviral interventions as needed.