bluuebunny/crossref_metadata_2025 huggingface dataset:
Cryo-EM structures reveal distinct mechanisms of inhibition of the human multidrug transporter ABCB1
Authors: Nosol Kamil , Romane Ksenija , Irobalieva Rossitza N. , Alam Amer , Kowal Julia , Fujita Naoya , Locher Kaspar P.
Published: October 2020

Significance

ABCB1 is a membrane transport protein that protects cells from toxic compounds. At the same time, it limits the uptake of orally administered drugs and contributes to multidrug resistance in cancer cells. Small-molecule inhibitors of ABCB1 could alleviate these negative effects, but their development requires detailed insight into how such compounds interfere with ABCB1-catalyzed drug extrusion. Our study shows how ABCB1 inhibitors bind in pairs and can block the function of the transporter by interacting with structural features that are important for its transport function. Our results therefore provide insight into the mechanism of ABCB1 and will be valuable for the development of more effective inhibitors.
The scale dependency of spatial crop species diversity and its relation to temporal diversity
Authors: Aramburu Merlos Fernando , Hijmans Robert J.
Published: October 2020

Significance

There is considerable debate about the effect of changes in and the need to increase biodiversity in agriculture. The spatial scale dependency of crop diversity has not been formally addressed, and this complicates understanding and synthesis. Crop species diversity also has a temporal diversity component of fundamental importance that has been ignored in diversity assessments. To fill this gap, we develop a framework for understanding the scale dependency of spatial crop species diversity and its relation to temporal diversity using 30 m spatial resolution crop species distribution data for the United States. We show that aggregated diversity data can be downscaled to estimate spatial and temporal diversity at the farm scale. We use the results to discuss diversification strategies.
Decoy nanoparticles protect against COVID-19 by concurrently adsorbing viruses and inflammatory cytokines
Authors: Rao Lang , Xia Shuai , Xu Wei , Tian Rui , Yu Guocan , Gu Chenjian , Pan Pan , Meng Qian-Fang , Cai Xia , Qu Di , Lu Lu , Xie Youhua , Jiang Shibo , Chen Xiaoyuan
Published: October 2020

Significance

The COVID-19 pandemic caused by SARS-CoV-2 infection has led to more than 840,000 deaths worldwide as of August 31, 2020. Unfortunately, no licensed vaccine or specific treatment is available right now. Herein, we report a decoy nanoparticle against COVID-19. The decoy nanoparticles were constructed by fusing cell membrane nanovesicles derived from genetically engineered cells, which stably express SARS-CoV-2 receptor ACE2, and human monocytes, which display abundant cytokine receptors. By competing with host cells, these nanodecoys efficiently adsorb viruses and inflammatory cytokines such as IL-6 and GM-CSF. These two functionalities allow effective intervention of viral infection and its associated immune disorder, presenting a promising therapeutic strategy for COVID-19 and other potential epidemics.
Primary and secondary motoneurons use different calcium channel types to control escape and swimming behaviors in zebrafish
Authors: Wen Hua , Eckenstein Kazumi , Weihrauch Vivien , Stigloher Christian , Brehm Paul
Published: October 2020

Significance

Genetic manipulations, functional imaging, and patch-clamp electrophysiology provide new insights into the roles played by the P/Q and N calcium channel types in zebrafish neuromuscular transmission. These two channel types are the mainstay of synaptic transmission among vertebrates and their functional distinctions likely form the basis of their synapse-specific expression. We show that the primary and secondary motoneurons differ in these two calcium channel types, providing independent control over escape and rhythmic swimming behaviors. The control over separate behaviors occurs despite their sharing of the same synapses and postsynaptic receptors. This synapse sharing by presynaptic terminals with functionally distinct calcium channel types calls for investigations into similar processes at other synapses.
Vertical MoS2 on SiO2/Si and graphene: effect of surface morphology on photoelectrochemical properties
Authors: Rosman Nurul Nabila , Mohamad Yunus Rozan , Jeffery Minggu Lorna , Arifin Khuzaimah , Kassim Mohammad B , Mohamed Mohd Ambri
Published: October 2020

Two-dimensional materials have attracted intensive attention recently due to their unique optical and electronic properties and their promising applications in water splitting and solar cells. As a representative layer-structured of transition metal dichalcogenides, MoS2 has attracted considerable devotion owing to its exceptional photo and electro properties. Here, we show that the chemical vapour deposition (CVD) growth of MoS2 on Si photocathode and graphene/Si photocathode can be used to prepare photoelectrocatalysts for water splitting. We explore a bottom‐up method to grow vertical heterostructures of MoS2 and graphene by using the two‐step CVD. Graphene is first grown through ambient-pressure CVD on a Cu substrate and then transferred onto SiO2/Si substrate by using the chemical wet transfer followed by the second CVD method to grow MoS2 over the graphene/SiO2/Si. The effect of the growth temperatures of MoS2 is studied, and the optimum temperature is 800 °C. The MoS2 produced at 800 °C has the highest photocurrent density at −0.23 mA cm−2 in 0.5 M Na2SO4 and −0.51 mA cm−2 in 0.5 M H2SO4 at −0.8 V versus Ag/AgCl. The linear sweep voltammetry shows that MoS2 in 0.5 M H2SO4 has about 55% higher photocurrent density than MoS2 in Na2SO4 due to the higher concentration of protons (H+) in the H2SO4 electrolyte solution. Protons are reduced to H2 at lower overvoltage and hydrogen generation is thus enhanced at higher photocurrent density. MoS2/graphene/SiO2/Si (MGS) has −0.07 mA cm−2 at −0.8 V versus Ag/AgCl of photocurrent density, which is 70% lower than that of bare MoS2 because MGS is thicker compared with MoS2. Thus, MoS2 has potential as a photocatalyst in photoelectrochemical water splitting. The structure and the morphology of MoS2 play an important role in determining the photocurrent performance.
Efficient photon capture on germanium surfaces using industrially feasible nanostructure formation
Authors: Chen Kexun , Isometsä Joonas , Pasanen Toni P , Vähänissi Ville , Savin Hele
Published: October 2020

Nanostructured surfaces are known to provide excellent optical properties for various photonics devices. Fabrication of such nanoscale structures to germanium (Ge) surfaces by metal assisted chemical etching (MACE) is, however, challenging as Ge surface is highly reactive resulting often in micron-level rather than nanoscale structures. Here we show that by properly controlling the process, it is possible to confine the chemical reaction only to the vicinity of the metal nanoparticles and obtain nanostructures also in Ge. Furthermore, it is shown that controlling the density of the nanoparticles, concentration of oxidizing and dissolving agents as well as the etching time plays a crucial role in successful nanostructure formation. We also discuss the impact of high mobility of charge carriers on the chemical reactions taking place on Ge surfaces. As a result we propose a simple one-step MACE process that results in nanoscale structures with less than 10% surface reflectance in the wavelength region between 400 and 1600 nm. The method consumes only a small amount of Ge and is thus industrially viable and also applicable to thin Ge layers.
A 12-pole VHF band high selective high temperature superconducting filter
Authors: Yu Xiao , Xi Weibin , Wu Songtao , Yan Peiguang
Published: October 2020

A 12-pole VHF band high temperature superconducting (HTS) filter with a spiral quarter-wavelength resonator is introduced. The coupling characteristics of the proposed resonator, cross structure and external quality factor is analyzed in detail. The HTS filter is fabricated on a 3-inch-diameter double-sided DyBa2Cu3O7 HTS thin film with a LAO substrate and measured with a low-temperature test system at 77 K. The measured filter has a center frequency of 119.93 MHz and a 1-dB passband of 10.04 dB. Due to the introduction of transmission zeros, the rectangular coefficient (BW60dB/BW1dB) of the measured filter is about 1.20, which shows excellent selectivity. The measured results are in good agreement with the simulated ones.
Effect of impeller geometry on bubble breakage and the contributions of different breakage mechanisms in a stirred tank
Authors: Alabdly Hussein A , Majdi Hasan Sh , Hamad Muayad F , Hathal Mustafa M , Hasan Basim O
Published: October 2020

The effect of impeller geometry on bubble breakage in a stirred tank was investigated for a range of impeller Reynolds number (Re) using a high speed imaging method. The bubble dynamic behavior and breakage mechanism were investigated for four different impeller geometries namely, two-flat blades impeller, four-flat blades impeller, four-twisted blades impeller, and two-pinned blades impeller. The performance of each geometry was investigated by determining the breakage probability and number of fragments (daughter bubbles) produced. The contributions of dominant breakage mechanisms for each geometry were specified and discussed by identifying the breakage locations relative to the impeller. Three main breakage mechanisms were observed, namely: bubble collision with the blade, bubble breakage by blade shear, and breakage by turbulent fluctuation away from the blade. The number of fragments by each breakage mechanism was specified for the entire range of Re. The four-flat blades impeller exhibited the highest breakage probability and produced the highest number of fragments. The Pinned blades gave a high performance compared to the smooth blades, especially at higher Re. This is considered to be due to the high turbulence level provided by this type of impeller. The twisted blades impeller showed low bubble breakage probability compared with the other geometries. Breakages by collision with the blades and by shearing effect resulted in a higher number of fragments compared to the breakages caused by turbulent fluctuations. The number of fragments produced by ‘collision with blade’ exhibited a higher dependence on Re than by ‘blade shear’ or by ‘turbulent fluctuations’.
Two-phase modeling of flow control of laminar Fe3O4-water nanofluid flow around the cylinder by Kelvin force of wire magnetic field using ferro hydrodynamics principles
Authors: Motlagh Saber Yekani , Tolouei Ehsan , Tolouei Iman
Published: October 2020

Controlling the destructive behavior of the wake region and consequently drag reduction are great challenges in fluid mechanics and ocean engineering. In this paper, the effect of the non-uniform magnetic field on controlling the flow and consequently drag reduction has been studied in laminar flow of magnetic nanofluid around a circular cylinder. The source of the magnetic field is a single current-carrying wire located in the center of the cylinder. The nanofluid consists of Fe3O4 as nanoparticles and water as the base flow. The ranges of Reynolds number (Re), volume fraction (ϕ), and the diameters of nanoparticles are 1.6 < Re < 180, 0 < ϕ < 0.04 and 15 < dp < 25, respectively.

The modified Buongiorno model that contains the magnetophoresis term is utilized to perform two-phase modeling of magnetic nanofluid flow. Finite volume method and PISO (Pressure-implicit With Splitting Of Operators) algorithm are utilized for the discretization of the governing unsteady equations including conservation laws of mass, volume fraction transport, and momentum equations by considering the ferrohydrodynamics (FHD) force as the source term. The results showed a significant effect of magnetic field intensity and volume fraction on the flow parameters such as drag coefficient, strouhal number, wake length, etc. In general, increasing the magnetic field in various volume fractions and various nanoparticle diameters reduces the amount of drag coefficient. The effective parameters for flow controlling are ordered as follows regarding their effectiveness: magnetic field intensity, volume fraction and diameter of the nanoparticles, respectively.
Hybrid real- and reciprocal-space full-field imaging with coherent illumination
Authors: Li Po-Nan , Wakatsuki Soichi , Pianetta Piero A , Liu Yijin
Published: October 2020

We present a novel diffractive imaging method that harnesses a low-resolution real-space image to guide the phase retrieval. A computational algorithm is developed to utilise such prior knowledge as a real-space constraint in the iterative phase retrieval procedure. Numerical simulations and proof-of-concept experiments are carried out, demonstrating our method’s capability of reconstructing high-resolution details that are otherwise inaccessible with traditional phasing algorithms. With the present method, we formulate a conceptual design for the coherent imaging experiments at a next-generation x-ray light source.
Influence of temperature on the creep behaviour by macroindentation of Cocos nucifera shells and Canarium schweinfurthii cores (bio-shellnut wastes in Cameroon)
Authors: Ganou Koungang Bernard Morino , Ndapeu Dieunedort , Tchuindjang Jerôme Tchoufang , Ntcheping Bernard Wenga , Tchemou Gilbert , Bistac Sophie , Njeugna Ebénézer , Courard Luc
Published: October 2020

The aim of this study was to show how temperature modifies the mechanical characteristics of the Cocos nucifera (CN) shells and the Canarium schweinfurthii (CS) cores. The test consisted in performing an instrumented macroindentation on prismatic specimens in an adiabatic chamber; the indentation carried out according to four temperature ranges (30 °C, 50 °C, 70 °C, 90 °C). The Oliver and Pharr method is used for the analysis of mechanical parameters in indentation: reduced Young’s modulus, hardness, creep coefficient. These parameters have enabled to estimate indirect characteristics such as toughness and ultimate mechanical stress to be obtained. The creep data are simulated to have the rheological model to these materials by considering the statistical criteria. As a global observation, when the temperature increases, the mechanical parameters decrease; although CN is more sensitive to the temperature gradient than CS, these 2 materials show performances that allow them to be classified as engineering polymer materials according to the Ashby diagram.
Development and optical characterization of an atmospheric pressure non-thermal plasma jet for superhydrophobic surface fabrication
Authors: Khanikar Rakesh Ruchel , Boruah Palash Jyoti , Bailung H
Published: October 2020

Atmospheric pressure non-thermal plasma jets are becoming subject of great attention in various fields such as plasma processing and biomedical applications due to their ability to produce highly reactive species and good reaction chemistry at low gas temperatures. In the present study, a non-thermal plasma jet operating on argon gas at atmospheric pressure aimed mainly towards surface modification and thin film deposition applications has been developed. Optical emission spectroscopy is used to evaluate the plasma parameters. The gas temperature (800 ± 50 K) is estimated from OH(A-X) rotational band. The excitation temperature is measured using intensity ratio of two argon lines and is found to be 0.241–0.273 eV and the corresponding electron temperatures have been measured. Electron density of the order of 1014 cm−3 has been obtained from the Stark broadening of Balmer H
β
line. The plasma jet has been successfully employed to deposit a superhydrophobic thin film of SiwCxHyOz using hexamethyldisiloxane (HMDSO) precursor monomer. The deposited film has been analyzed using XRD, FTIR, SEM, AFM, and contact angle analyzer. All the treated surfaces have shown superhydrophobic property with a contact angle greater than 150° showing numerous potential in various applications. This method is a relatively easy and environmental friendly way of fabricating superhydrophobic surfaces.
Stability of strong detonation waves for Majda’s model with general ignition functions
Authors: Jung Soyeun , Yang Zhao , Zumbrun Kevin
Published: October 2020

For strong detonation waves of the inviscid Majda model, spectral stability was established by Jung and Yao for waves with step-type ignition functions, by a proof based largely on explicit knowledge of wave profiles. In the present work, we extend their stability results to strong detonation waves with more general ignition functions where explicit profiles are unknown. Our proof is based on reduction to a generalized Sturm-Liouville problem, similar to that used by Sukhtayev, Yang, and Zumbrun to study spectral stability of hydraulic shock profiles of the Saint-Venant equations.
Minimal prezygotic isolation between ecologically divergent sibling species
Authors: Talavera Janelle B , Collosi Emma , Clark Meaghan I , Robertson Jeanne M , Gray David A
Published: October 2020

Divergence in mating signals typically accompanies speciation. We examine two ecologically divergent sibling species of crickets to assess the degree and timing of the evolution of prezygotic reproductive isolation. Gryllus saxatilis occurs in rocky habitats throughout western North America with long-winged individuals capable of long-distance dispersal; Gryllus navajo is endemic to red-rock sandstone areas of south-eastern Utah and north-eastern Arizona and has short-winged individuals only capable of limited dispersal. Previous genetic work suggested some degree of introgression and/or incomplete lineage sorting is likely. Here we: (1) use restriction site associated DNA sequencing (RAD-seq) genetic data to describe the degree of genetic divergence among species and populations; (2) examine the strength of prezygotic isolation by (i) quantifying differences among male mating songs, and (ii) testing whether females prefer G. saxatilis or G. navajo calling songs. Our results show that genetically distinct “pure” species populations and genetically intermediate populations exist. Male mating songs are statistically distinguishable, but the absolute differences are small. In playback experiments, females from pure populations had no preference based on song; however, females from a genetically intermediate population preferred G. navajo song. Together these results suggest that prezygotic isolation is minimal, and mediated by female behaviour in admixed populations.
Developmental and epileptic encephalopathies: what we do and do not know
Authors: Specchio Nicola , Curatolo Paolo
Published: October 2020

Developmental encephalopathies, including intellectual disability and autistic spectrum disorder, are frequently associated with infant epilepsy. Epileptic encephalopathy is used to describe an assumed causal relationship between epilepsy and developmental delay. Developmental encephalopathies pathogenesis more independent from epilepsy is supported by the identification of several gene variants associated with both developmental encephalopathies and epilepsy, the possibility for gene-associated developmental encephalopathies without epilepsy, and the continued development of developmental encephalopathies even when seizures are controlled. Hence, ‘developmental and epileptic encephalopathy’ may be a more appropriate term than epileptic encephalopathy. This update considers the best studied ‘developmental and epileptic encephalopathy’ gene variants for illustrative support for ‘developmental and epileptic encephalopathy’ over epileptic encephalopathy. Moreover, the interaction between epilepsy and developmental encephalopathies is considered with respect to influence on treatment decisions. Continued research in genetic testing will increase access to clinical tests, earlier diagnosis, better application of current treatments, and potentially provide new molecular-investigated treatments.
Intricacies of aetiology in intrafamilial degenerative disease
Authors: Lowry Jessica L , Ryan Éanna B , Esengul Y Taylan , Siddique Nailah , Siddique Teepu
Published: October 2020

The genetic underpinnings of late-onset degenerative disease have typically been determined by screening families for the segregation of genetic variants with the disease trait in affected, but not unaffected, individuals. However, instances of intrafamilial etiological heterogeneity, where pathogenic variants in a culprit gene are not shared among all affected family members, continue to emerge and confound gene-discovery and genetic counselling efforts. Discordant intrafamilial cases lacking a mutation shared by other affected family members are described as disease phenocopies. This description often results in an over-simplified acceptance of an environmental cause of disease in the phenocopy cases, while the role of intrafamilial genetic heterogeneity, shared de novo mutations or epigenetic aberrations in such families is often ignored. On a related note, it is now evident that the same disease-associated variant can be present in individuals exhibiting clinically distinct phenotypes, thereby genetically uniting seemingly unrelated syndromes to form a spectrum of disease. Herein, we discuss the intricacies of determining complex degenerative disease aetiology and suggest alternative mechanisms of disease transmission that may account for the apparent missing heritability of disease.
Ultra-trace Extraction of Two Bactericides Via Ultrasound-Assisted Dispersive Liquid-Liquid Microextraction
Authors: Gao Xun , Si Xinxin , Yuan Yunxia , Chen Kexin , Qin Kunming
Published: October 2020

Background

A simple, rapid and sensitive method coupling ultrasound-assisted dispersive liquid-liquid microextraction (DLLME) with ultra-high performance liquid chromatography-tandem mass spectrometry was developed for the simultaneous determination of malachite green (MG) and crystal violet (CV) in different water samples.

Objective

In ultrasound-assisted DLLME procedure, several parameters affecting the extraction efficiency, including pH, type and volume of the extraction and dispersive solvents, extraction time, ionic strength, were optimized to improve the accuracy and precision of this method.

Methods

MG and CV were extracted and preconcentrated using dichloromethane and acetonitrile as the extraction and dispersive solvents, respectively.

Results

Under the optimum conditions, the proposed method affords good linearity in the range of 0.40–20.0 ng/L, and the limit of detections were 0.21 and 0.32 ng/L for MG and CV, respectively. The recoveries of the method at three spiked levels were in the range of 83.4–94.2% with relative standard deviations lower than 4.7% (n = 3).

Conclusions

Satisfactorily, no significant matrix effect has been found as the data ranged between 68% and 102%.
The cardiac impact of cisplatin-based chemotherapy in survivors of testicular cancer: a 30-year follow-up
Authors: Bjerring Anders W , Fosså Sophie D , Haugnes Hege S , Nome Ragnhild , Stokke Thomas M , Haugaa Kristina H , Kiserud Cecilie E , Edvardsen Thor , Sarvari Sebastian I
Published: October 2020

Aims

Cisplatin-based chemotherapy (CBCT) is essential in the treatment of metastatic testicular cancer (TC) but has been associated with long-term risk of cardiovascular morbidity and mortality. Furthermore, cisplatin can be detected in the body decades after treatment. We aimed to evaluate the long-term impact of CBCT on cardiac function and morphology in TC survivors 30 years after treatment.

Methods and results

TC survivors treated with CBCT (1980–94) were recruited from the longitudinal Norwegian Cancer Study in Testicular Cancer Survivors and compared with a control group matched for sex, age, smoking status, and heredity for coronary artery disease. All participants underwent laboratory tests, blood pressure measurement, and 2D and 3D echocardiography including 2D speckle-tracking strain analyses. Ninety-four TC survivors, on average 60 ± 9 years old, received a median cumulative cisplatin dose of 780 mg (IQR 600–800). Compared with controls, TC survivors more frequently used anti-hypertensive (55% vs. 24%, P < 0.001) and lipid-lowering medication (44% vs. 18%, P < 0.001). TC survivors had worse diastolic function parameters with higher E/e′-ratio (9.8 ± 3.2 vs. 7.7 ± 2.5, P < 0.001), longer mitral deceleration time (221 ± 69 vs. 196 ± 57ms, P < 0.01), and higher maximal tricuspid regurgitation velocity (25 ± 7 vs. 21 ± 4 m/s, P = 0.001). The groups did not differ in left or right ventricular systolic function, prevalence of arrhythmias, or valvular heart disease. Cumulative cisplatin dose did not correlate with cardiac parameters.

Conclusion

No signs of overt or subclinical reduction in systolic function were identified. Long-term cardiovascular adverse effects three decades after CBCT may be limited to metabolic dysfunction and worse diastolic function in TC survivors.
Aortic valve replacement due to granulomatosis with polyangiitis: a case series
Authors: Uijtterhaegen Gilles , De Donder Laura , Ameloot Eline , Lefebvre Kristof , Van Dorpe Jo , De Pauw Michel , François Katrien
Published: October 2020

Background

Granulomatosis with polyangiitis (GPA), formerly known as Wegener’s granulomatosis, is a systemic inflammatory process predominantly affecting upper and lower respiratory tract and kidneys. Valvular heart disease is a rare manifestation of GPA.

Case summary

We report two cases of acute valvular heart disease mimicking acute endocarditis caused by GPA. Both patients were middle-aged females with acute aortic valve regurgitation suggestive of possible infective endocarditis. In their recent medical history, atypical otitis and sinusitis were noted. The first patient was admitted with heart failure and the second patient because of persisting fever. Echocardiogram revealed severe aortic regurgitation with an additional structure on two cusps, suggestive of infective endocarditis in both patients. Urgent surgical replacement was performed; however, intraoperative findings did not show infective endocarditis, but severe inflammatory changes of the valve and surrounding tissue. In both patients, the valve was replaced by a prosthetic valve. Microscopic examination of the valve/myocardial biopsy showed diffuse acute and chronic inflammation with necrosis and necrotizing granulomas, compatible with GPA after infectious causes were excluded. Disease remission was obtained in both patients, in one patient with Rituximab and in the other with Glucocorticoids and Cyclophosphamide. Both had an uneventful follow-up.

Discussion

Granulomatosis with polyangiitis can be a rare cause of acute aortic valve regurgitation mimicking infective endocarditis with the need for surgical valve replacement. Atypical ear, nose, and throat symptoms can be a first sign of GPA. Symptom recognition is important for early diagnosis and appropriate treatment to prevent further progression of the disease.
Variation in general practitioners’ depression care following certification of sickness absence: a registry-based cohort study
Authors: Riiser Sharline , Haukenes Inger , Baste Valborg , Smith-Sivertsen Tone , Hetlevik Øystein , Ruths Sabine
Published: October 2020

Background

Depression is more prevalent among women and people with low socio-economic status. Uncertainties exist about how general practitioner (GP) depression care varies with patients’ social position.

Objective

To investigate associations between patients’ gender and educational status combined and GP depression care following certification of sickness absence.

Methods

Nationwide registry-based cohort study, Norway, 2012–14. Reimbursement claims data from all consultations in general practice for depression were linked with information on socio-demographic data, social security benefits and depression medication. The study population comprised all individuals aged 25–66 years with taxable income, sick-listed with a new depression diagnosis in general practice in 2013 (n = 8857). We defined six intersectional groups by combining educational level and gender. The outcome was type of GP depression care during sick leave: follow-up consultation(s), talking therapy, medication and referral to secondary care. Associations between intersectional groups and outcome were estimated using generalized linear models.

Results

Among long-term absentees (17 days or more), highly educated women were less likely to receive medication compared to all other patient groups [relative risk (RR) ranging from 1.17 (95% confidence interval 1.03–1.33) to 1.49 (1.29–1.72)] and more likely to receive talking therapy than women with medium [RR = 0.90 (0.84–0.98)] or low [RR = 0.91 (0.85–0.98)] education.

Conclusions

Our findings suggest that GPs provide equitable depression care regarding consultations and referrals for all intersectional groups but differential drug treatment and talking therapy for highly educated women. GPs need to be aware of these variations to provide personalized care and to prevent reproducing inequity.
Activation of cellular immune response in insect model host Galleria mellonella by fungal α-1,3-glucan
Authors: Stączek Sylwia , Zdybicka-Barabas Agnieszka , Wiater Adrian , Pleszczyńska Małgorzata , Cytryńska Małgorzata
Published: October 2020

Alpha-1,3-glucan, in addition to β-1,3-glucan, is an important polysaccharide component of fungal cell walls. It is reported for many fungal species, including human pathogenic genera: Aspergillus, Blastomyces, Coccidioides, Cryptococcus, Histoplasma and Pneumocystis, plant pathogens, e.g. Magnaporthe oryzae and entomopathogens, e.g. Metarhizium acridum. In human and plant pathogenic fungi, α-1,3-glucan is considered as a shield for the β-1,3-glucan layer preventing recognition of the pathogen by the host. However, its role in induction of immune response is not clear. In the present study, the cellular immune response of the greater wax moth Galleria mellonella to Aspergillus niger α-1,3-glucan was investigated for the first time. The changes detected in the total hemocyte count (THC) and differential hemocyte count (DHC), formation of hemocyte aggregates and changes in apolipophorin III localization indicated activation of G. mellonella cellular mechanisms in response to immunization with A. niger α-1,3-glucan. Our results, which have clearly demonstrated the response of the insect immune system to this fungal cell wall component, will help in understanding the α-1,3-glucan role in immune response against fungal pathogens not only in insects but also in mammals, including humans.
A Pathophysiological Model for COVID-19: Critical Importance of Transepithelial Sodium Transport upon Airway Infection
Authors: Gentzsch Martina , Rossier Bernard C
Published: October 2020

The Coronavirus Disease 2019 (COVID-19) pandemic remains a serious public health problem and will continue to be until effective drugs and/or vaccines are available. The rational development of drugs critically depends on our understanding of disease mechanisms, that is, the physiology and pathophysiology underlying the function of the organ targeted by the virus. Since the beginning of the pandemic, tireless efforts around the globe have led to numerous publications on the virus, its receptor, its entry into the cell, its cytopathic effects, and how it triggers innate and native immunity but the role of apical sodium transport mediated by the epithelial sodium channel (ENaC) during the early phases of the infection in the airways has received little attention. We propose a pathophysiological model that defines the possible role of ENaC in this process.
Increasing Life-Space Mobility in Community-Dwelling Older Persons With Cognitive Impairment Following Rehabilitation: A Randomized Controlled Trial
Authors: Ullrich Phoebe , Werner Christian , Bongartz Martin , Eckert Tobias , Abel Bastian , Schönstein Anton , Kiss Rainer , Hauer Klaus
Published: October 2020

Background

Community-dwelling older persons with cognitive impairment (CI) following discharge from geriatric rehabilitation are at high risk of losing life-space mobility (LSM). Interventions to improve their LSM are, however, still lacking. The aim of this study was to evaluate the effects of a CI-specific, home-based physical training and activity promotion program on LSM.

Methods

Older persons with mild-to-moderate CI (Mini-Mental State Examination: 17–26 points) discharged home from rehabilitation were included in this double-blinded, randomized, placebo-controlled trial with a 12-week intervention period and 12-week follow-up period. The intervention group received a CI-specific, home-based strength, balance, and walking training supported by tailored motivational strategies. The control group received a placebo activity. LSM was evaluated by the Life-Space Assessment in Persons with Cognitive Impairment, including a composite score for LSM and 3 subscores for maximal, equipment-assisted, and independent life space. Mixed-model repeated-measures analyses were used.

Results

One hundred eighteen participants (82.3 ± 6.0 years) with CI (Mini-Mental State Examination: 23.3 ± 2.4) were randomized. After the intervention, the home-based training program resulted in a significant benefit in the Life-Space Assessment in Persons with Cognitive Impairment composite scores (b = 8.15; 95% confidence interval: 2.89–13.41; p = .003) and independent life-space subscores (b = 0.39; 95% confidence interval: 0.00–0.78; p = .048) in the intervention group (n = 63) compared to control group (n = 55). Other subscores and follow-up results were not significantly different.

Conclusions

The home-based training program improved LSM and independent life space significantly in this vulnerable population. Effects were not sustained over the follow-up. The program may represent a model for improved transition from rehabilitation to the community to prevent high risk of LSM restriction.
Risk Factors for Hospital Admission After a Fall: A Prospective Cohort Study of Community-Dwelling Older People
Authors: Abell Jessica G , Lassale Camille , Batty G David , Zaninotto Paola
Published: October 2020

Background

Falls in later life that require admission to hospital have well-established consequences for future disability and health. The likelihood and severity of a fall will result from the presence of one or more risk factors. The aim of this study is to examine risk factors identified for their ability to prevent falls and to assess whether they are associated with hospital admission after a fall.

Methods

Analyses of data from the English Longitudinal Study of Aging (ELSA), a prospective cohort study. In a sample of 3783 men and women older than 60 years old, a range of potential risk factors measured at Wave 4 (demographic, social environment, physical, and mental functioning) were examined as predictors of fall-related hospitalizations, identified using International Classification of Diseases, 10th Revision (ICD-10) code from linked hospital records in the United Kingdom. Subdistribution hazard models were used to account for competing risk of death.

Results

Several risk factors identified by previous work were confirmed. Suffering from urinary incontinence (subdistribution hazard ratio = 1.49; 95% CI: 1.14, 1.95) and osteoporosis (subdistribution hazard ratio = 1.48; 95% CI: 1.05, 2.07), which are not commonly considered at an early stage of screening, were found to be associated with hospital admission after a fall. Both low and moderate levels of physical activity were also found to somewhat increase the risk of hospital admission after a fall.

Conclusions

Several predictors of having a fall, severe enough to require hospital admission, have been confirmed. In particular, urinary incontinence should be considered at an earlier point in the assessment of risk.
Association of maternal diabetes with neurodevelopmental disorders: autism spectrum disorders, attention-deficit/hyperactivity disorder and intellectual disability
Authors: Chen Shuyun , Zhao Sixian , Dalman Christina , Karlsson Håkan , Gardner Renee
Published: October 2020

Background

Maternal diabetes has been associated with a risk of neurodevelopmental disorders (NDDs) in offspring, though the common co-occurrence of autism spectrum disorders (ASD), attention-deficit/hyperactivity disorder (ADHD) and intellectual disability (ID) is rarely considered, nor is the potential for confounding by shared familial factors (e.g. genetics).

Methods

This population-based cohort study used data from Psychiatry Sweden, a linkage of Swedish national registers, to follow 2 369 680 individuals born from 1987 to 2010. We used population-averaged logit models to examine the association between exposure to maternal type 1 diabetes mellitus (T1DM), pre-gestational type 2 diabetes mellitus (T2DM) or gestational diabetes mellitus (GDM), and odds of NDDs in offspring. Subgroup analysis was then performed to investigate the timings of GDM diagnosis during pregnancy and its effect on the odds of NDDs in offspring. We compared these results to models considering paternal lifetime T1DM and T2DM as exposures.

Results

Overall, 45 678 individuals (1.93%) were diagnosed with ASD, 20 823 (0.88%) with ID and 102 018 (4.31%) with ADHD. All types of maternal diabetes were associated with odds of NDDs, with T2DM most strongly associated with any diagnosis of ASD (odds ratioadjusted 1.37, 95% confidence interval 1.03–1.84), ID (2.09, 1.53–2.87) and ADHD (1.43, 1.16–1.77). Considering common co-morbid groups, the associations were strongest between maternal diabetes and diagnostic combinations that included ID. Paternal T1DM and T2DM diagnoses were also associated with offspring NDDs, but these associations were weaker than those with maternal diabetes. Diagnosis of GDM between 27 and 30 weeks of gestation was generally associated with the greatest risk of NDDs in offspring, with the strongest associations for outcomes that included ID.

Conclusion

The association of maternal diabetes with NDDs in offspring varies depending on the co-morbid presentation of the NDDs, with the greatest odds associated with outcomes that included ID. Results of paternal-comparison studies suggest that the above associations are likely to be partly confounded by shared familial factors, such as genetic liability.
A Bijective Proof of the ASM Theorem Part II: ASM Enumeration and ASM–DPP Relation
Authors: Fischer Ilse , Konvalinka Matjaž
Published: October 2020

This paper is the 2nd in a series of planned papers that provide 1st bijective proofs of alternating sign matrix (ASM) results. Based on the main result from the 1st paper, we construct a bijective proof of the enumeration formula for ASMs and of the fact that ASMs are equinumerous with descending plane partitions. We are also able to refine these bijections by including the position of the unique $1$ in the top row of the matrix. Our constructions rely on signed sets and related notions. The starting point for these constructions were known “computational” proofs, but the combinatorial point of view led to several drastic modifications. We also provide computer code where all of our constructions have been implemented.
Human Immunodeficiency Virus Type 1 Vpu Inhibitor, BIT225, in Combination with 3-Drug Antiretroviral Therapy: Inflammation and Immune Cell Modulation
Authors: Luscombe Carolyn A , Avihingsanon Anchalee , Supparatpinyo Khuanchai , Gatechompol Sivaporn , Han Win Min , Ewart Gary D , Thomson Audrey S , Miller Michelle , Becker Stephen , Murphy Robert L
Published: October 2020

BIT225 is a first-in-class inhibitor of human immunodeficiency virus (HIV) type 1 Vpu. A phase II trial enrolled 36 HIV-1–infected, treatment-naive participants in Thailand to receive standard-of-care antiretroviral therapy (ART), tenofovir disoproxil fumarate/emtricitabine/efavirenz (Atripla), with 100 or 200 mg of BIT225 or placebo (daily) for 12 weeks. Combined treatment with BIT225 and ART was found to be generally safe and well tolerated, with antiviral efficacy comparable to that of ART alone. The secondary end point—soluble CD163, a marker of monocyte/macrophage inflammation—was noted to be significantly decreased in the BIT225 arm. Plasma-derived activated CD4+ and CD8+ T cells, natural killer cells, and interleukin 21 were increased in those treated with BIT225. These findings are consistent with inhibition of the known effects of HIV Vpu and may reflect clinically important modulation of inflammatory and immune function. Further clinical study is planned to both confirm and extend these important findings in treatment-naive, and treatment-experienced individuals.

Clinical Trials Registration. Australian New Zealand Clinical Trials Registry (Universal Trial Number U1111-1191-2194).
How has ASEAN+3 financial cooperation affected global financial governance?
Authors: Kring William N. , Grimes William W.
Published: October 2020

In the wake of the Asian Financial Crisis, East Asia’s efforts to enhance regional financial cooperation raised the possibility of East Asia playing a more assertive role in global financial governance. However, despite the region’s increased voice in governance and economic weight, East Asian financial systems and markets have mostly adapted to global norms developed in New York, London, and Washington, DC. We argue that the failure of East Asia to push an alternative vision of financial governance reflects both the lack of regional political unity and, more crucially, the divisions of interests both between and within key East Asian economies. Despite nearly universal regional dissatisfaction with global standards and institutions in the wake of the Asian Financial Crisis, these two factors have combined to prevent the development of a distinctive regional model that could be promoted at the global level.
Species Diversity in the Braconid Wasp Genus Allorhogas (Doryctinae) Associated With Cynipid Galls on Live Oaks (Quercus: Fagaceae) Using Natural History, Phylogenetics, and Morphology
Authors: Samacá-Sáenz Ernesto , Egan Scott P , Zaldívar-Riverón Alejandro
Published: October 2020

The discovery of new biodiversity, during an age of unprecedented extinction, is vital for all the life sciences and the quality of human life. One ecologically and economically important group that requires attention is the hymenopteran family Braconidae, which is estimated to include thousands of undescribed species. Here we assessed the genetic structure and species diversification in the braconid wasp genus Allorhogas Gahan (Doryctinae) that were reared from galls of five cynipid wasp species associated with three live oak species (Fagaceae: Quercus: subsection Virentes) in the southeastern United States. We explored genetic variation in the single-locus barcoding COI region of the mitochondrial DNA (mtDNA), and conducted analyses with different DNA sequence-based species delimitation approaches both for the above marker and genome-wide nuclear data using ultraconserved elements (UCEs). We found high variation in the mtDNA barcoding region among specimens of Allorhogas reared from galls made by different cynipid species in distinct plant organs and among specimens reared from the same type of gall from two separate geographic regions. In addition, our analyses of mtDNA and multilocus nuclear data were concordant in consistently delimiting at least five genetic lineages. We combined this molecular evidence with morphological data to describe four new species and redescribe the type species of the genus, Allorhogas gallicola Gahan, which exhibited similar morphological, ecological, and biogeographic characteristics to the four new species. This study highlights the importance of carrying detailed rearing surveys to uncover the intricate species interactions and species diversity that is present in gall-former systems.
First international quality control programme for laboratories measuring antimicrobial drugs to support dose individualization in critically ill patients
Authors: Wallenburg E , Brüggemann R J , Asouit K , Teulen M , de Haan A F J , Franssen E J F , Aarnoutse R E
Published: October 2020

Objectives

International quality control (proficiency testing) programmes are instituted to safeguard the analytical performance of laboratories and to aid these laboratories in identifying sources of error in their analytical methods. We describe the first international quality control programme for antimicrobial agents that are frequently used in critically ill patients.

Methods

Spiked plasma samples with ceftazidime, ciprofloxacin, flucloxacillin, piperacillin, sulfamethoxazole, N-acetyl sulfamethoxazole and trimethoprim were shipped to 22 laboratories from eight different countries. Acceptable accuracy by the performing laboratory was defined if measurements were within 80%–120% limits of the true weighed-in concentrations.

Results

A total of 81% of the measurements (ranging between 56% and 100%, dependent on drug) were within the 80%–120% limits of the true weighed-in concentrations.

Conclusions

We found a relatively good performance of the participating laboratories in measuring eight different antimicrobial drugs. Nevertheless, some of the antimicrobial drugs were not measured properly as up to 44% of the measurements was inaccurate depending on the drug. Our results emphasize the need for and utility of an ongoing quality control programme.
Oral and parenteral antibiotic use in Norwegian nursing homes: are primary care institutions becoming our new local hospitals?
Authors: Harbin Nicolay Jonassen , Haug Jon Birger , Romøren Maria , Lindbæk Morten
Published: October 2020

Background

Norwegian nursing homes (NHs) have over the last 10 years increasingly applied the use of parenteral treatment, which in turn allows more broad-spectrum use of antibiotics. Previous studies from Norwegian NHs have for the most part not described parenteral formulations.

Objectives

To describe systemic antibiotic use in Norwegian NHs.

Methods

Thirty-seven NHs in the county of Østfold, Norway, were invited to participate in this retrospective cross-sectional study. Associated pharmacies provided sales data for systemic antibiotic use for the participating NHs for 1 year (October 2015 to October 2016). General institutional characteristics were collected through a questionnaire.

Results

Thirty-four NHs participated in the study. Mean use of antibiotics was 9.5 DDD/100 bed days (range 0.6–30.9 DDD/100 bed days). Oral antibiotics accounted for 83% and parenteral antibiotics for 17% of the total antibiotic use. Of parenteral antibiotics, ampicillin was most used (31.1%) followed by cefotaxime (17.7%) and penicillin G (16.6%). The proportion of antibiotics compliant with guideline recommendations was 60%. Being a short-term NH was associated with increased antibiotic use, with an unstandardized coefficient of 13.1 (95% CI 4.2–21.9; P = 0.005).

Conclusions

We found a high level of total and parenteral antibiotic use compared with previous studies from Norwegian NHs. Data showed wide variations in total antibiotic use and that only a moderate proportion of the antibiotic use was considered guideline compliant. This highlights the necessity of further implementation strategies regarding the national guidelines for antibiotic use in NHs.