bluuebunny/crossref_metadata_2025 huggingface dataset:
Solvent screening for efficient chemical exfoliation of graphite
Authors: Nu Thanh Ton Nhan , Ha Minh-Quyet , Ikenaga Takuma , Thakur Ashutosh , Dam Hieu-Chi , Taniike Toshiaki
Published: October 2020

Chemical exfoliation of graphite is an effective method to produce graphene of relative high quality, where the choice of solvents plays an important role in the product yield and quality. Here, we performed screening of different solvents and their mixtures for the liquid-phase exfoliation of graphite under ultrasonication. A synergistic effect among aromatic, amine, and halogen groups was identified. The synergy was more effectively exploited when these functional groups were combined through solvent mixtures compared to when they were introduced in the molecular structure of single solvents. The screening results were utilized for a novel machine learning technique based on the Dempster–Shafer theory of evidence to systematically investigate synergistic effects and recommend new solvent combinations. The proposed combination of the experiment and the data-driven approach was demonstrated to be powerful for exploring synergistic solvent combinations.
Metastability triggered reactivity in clusters at realistic conditions: a case study of N-doped (TiO2)
n
for photocatalysis
Authors: Saini Shikha , Basera Pooja , Kumar Manish , Bhumla Preeti , Bhattacharya Saswata
Published: October 2020

We present a strategy, by taking a prototypical model system for photocatalysis (viz. N-doped (TiO2)
n
clusters), to accurately design photocatalyst with enhanced reactivity at a given environmental conditions (i.e. temperature (T), pressure (

p

O

2

) and doping (µ

e
)). Since free energy potential energy surface consists of many competing isomers even in a small energy window, computational design of specific metastable photocatalysts with enhanced activity is extremely challenging. This requires fixing various parameters as follows; (i) favorable formation energy, (ii) low fundamental gap, (iii) low excitation energy, (iv) high vertical electron affinity (VEA) and (v) low vertical ionization potential (VIP) to drive the hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) for water splitting. Here, we show that by integrating several first principles based methodologies that consideration of the global minimum structure alone can severely underestimate the activity. First, we have used a suite of genetic algorithms (namely, searching clusters with conventional minimum total energy ((GA)

E

); searching clusters with specific property i.e. high VEA ((GA)

P

EA

), and low VIP ((GA)

P

IP

)) to model the N-doped (TiO2)
n
( n = 4–10, 15, 20) (meta)stable clusters. Next, we have identified its free energy using ab initio atomistic thermodynamics to confirm that the metastable structures are not too far from the free energy global minima. We find that N-substitution ((N)

O

) prefers to reside at highly coordinated oxygen site, whereas N-interstitial ((NO)

O

) and split-interstitial ((N

2

)

O

) favor the dangling oxygen site. (NO)

O

and (N

2

)

O

doped states are thermodynamically stable at finite temperature (T) and pressure (

p

O

2

). Interestingly, each types of defect (viz. substitution, interstitials) reduce the fundamental gap and excitation energy substantially. However, (N

2

)

O

doped clusters are found to be less probable in the Pourbaix phase diagram, whereas (N)

O

and (NO)

O

doped metastable clusters show significant occupance probability near the phase boundaries. The latter ensures much higher electrocatalytic activity for water splitting than the most stable configurations.
Independent component analysis for pulse compressed frequency modulated thermal wave imaging for inspection of mild steel
Authors: Kaur Kirandeep , Mulaveesala Ravibabu , Rani Anju , Kher Vansha
Published: October 2020

Non-destructive testing & evaluation plays a crucial role in various sectors for testing the reliability of materials. Of the different available non-destructive examination techniques, thermal non-destructive testing provides fast and remote inspection of the materials. Among various widely used thermal non-destructive testing techniques, frequency modulated thermal wave imaging gained its importance due to its higher test sensitivity and resolution. The adopted matched filter approach on the obtained temporal temperature distribution further concentrates supplied excitation energy into a narrow duration high peak power pulse. In this paper, the merits of the reconstructed high peak power pulsed data have been considered and emphasized in the context of independent component analysis. The obtained results clearly indicate that pulse compressed data improves defect detectability, reliability, memory usage, and computational complexity.
A summons to the magistrates’ courts in South Africa and Uganda
Authors: Cooper-Knock S J , Macdonald Anna
Published: October 2020

The expansive literature on law and justice across Africa emphasizes why people do not use lower state courts. Consequently, a striking lack of attention is paid to how and why people do engage with lower state courts. Drawing on a systematic literature review and a multi-sited qualitative study, we make three contributions on this topic. First, we explore how this academic gap emerged. Second, we critique the procedural justice model that currently underlies much ‘access to justice’ programming, which seeks to improve citizens’ engagements with the courts. In place of what we describe as its arithmetic assumptions about institutional engagement, value, and legitimacy, we propose a trifactor framework. Citizen engagement, we argue, occurs as people reconcile how they think the courts should act, how they expect them to act, and how they need them to act in any given instance. Third, drawing on our empirical studies, we highlight that this framework is flexible enough to capture people’s actually existing decision-making in a wide variety of settings and to map how those trade-offs shift throughout the process of their case, providing important insights into ideas of justice and statehood.
Identification of Clock Genes Related to Hypertension in Kidney From Spontaneously Hypertensive Rats
Authors: Murata Yusuke , Ueno Takahiro , Tanaka Sho , Kobayashi Hiroki , Okamura Masahiro , Hemmi Seiichiro , Fuke Yoshinobu , Matsumoto Yoshiaki , Abe Masanori , Fukuda Noboru
Published: October 2020

Background

There is a diurnal variation in the blood pressure fluctuation of hypertension, and blood pressure fluctuation abnormality is considered to be an independent risk factor for organ damage including cardiovascular complications. In the current study, we tried to identify molecules responsible for blood pressure circadian rhythm formation under the control of the kidney biological clock in hypertension.

Methods

DNA microarray analysis was performed in kidneys from 5-week-old spontaneously hypertensive rats (SHRs)/Izm, stroke-prone SHR rats (SHRSP)/Izm, and Wistar Kyoto (WKY)/Izm rats. To detect variation, mouse tubular epithelial cells (TCMK-1) were stimulated with dexamethasone. We performed immunostaining and western blot analysis in the renal medulla of kidney from 5-week-old WKY rats and SHRs.

Results

We extracted 1,032 genes with E-box, a binding sequence for BMAL1 and CLOCK using a Gene Set Enrichment Analysis. In a microarray analysis, we identified 12 genes increased as more than 2-fold in the kidneys of SHRs and SHRSP in comparison to WKY rats. In a periodic regression analysis, phosphoribosyl pyrophosphate amidotransferase (Ppat) and fragile X mental retardation, autosomal homolog 1 (Fxr1) showed circadian rhythm. Immunocytochemistry revealed PPAT-positivity in nuclei and cytoplasm in the tubules, and FXR1-positivity in the cytoplasm of TCMK-1. In 5-week-old WKY rat and SHR kidneys, PPAT was localized in the nucleus and cytoplasm of the proximal and distal tubules, and FXR1 was localized to the cytoplasm of the proximal and distal tubules.

Conclusions

PPAT and FXR1 are pivotal molecules in the control of blood pressure circadian rhythm by the kidney in hypertension.
Changes in the brain directly following alcohol consumption—a study of healthy male individuals, with the use of proton magnetic resonance spectroscopy (1HMRS) and diffusion (DWI)
Authors: Urbanik Andrzej , Kozub Justyna , Karcz Paulina , Ostrogórska Monika
Published: October 2020

Aims

To use proton magnetic resonance spectroscopy (1HMRS) and diffusion weighted imaging (DWI) to identify ethanol in the brain directly after consumption, and examine changes in brain metabolite levels and brain microstructure relative to the duration of time following exposure to alcohol.

Methods

The study involved 44 male volunteers (18–55 years). All brain changes were assessed in the frontal lobes, occipital lobes, basal ganglia and cerebellum, however the detailed analyses focused on the frontal lobes. All participants were examined four times, i.e. before and 0.5-hour, 1 hour and 2 hours after consumption of 150 mL pure vodka (60 g of ethanol).

Results

The highest ethanol levels were identified between 0.5 and 1 hour following alcohol intake. There were significant increases in the concentrations of lipids and lactates approximately one hour after alcohol consumption, and the concentration levels were found to normalise during the following two hours. Some statistically insignificant trends of changes were found for tCr, tCho, mI, GABA, Glc, Glx and tNAA. For the DWI and ADC (Apparent Diffusion Coefficient of water) values, the findings showed statistically insignificant decrease and increase, followed by a tendency towards normalisation. Similar associations in changes of metabolite concentrations and DWI and ADC values were found in the other locations investigated in the study.

Conclusion

A single dose of alcohol as used in this experiment produces increases in lipids and lactates in brain tissues that appear reversible.
The Frequency and Content of Discussions About Alcohol Use in Primary Care and Application of the Chief Medical Officer’s Low-Risk Drinking Guidelines: A Cross-Sectional Survey of General Practitioners and Practice Nurses in the UK
Authors: Birch Jack M , Critchlow Nathan , Calman Lynn , Petty Robert , Rosenberg Gillian , Rumgay Harriet , Vohra Jyotsna
Published: October 2020

Aims

To examine how often general practitioners (GPs) and practice nurses (PNs) working in primary care discuss alcohol with patients, what factors prompt discussions, how they approach patient discussions and whether the Chief Medical Officers’ (CMO) revised low-risk drinking guidelines are appropriately advised.

Methods

Cross-sectional survey with GPs and PNs working in primary care in the UK, conducted January–March 2017 (n = 2020). A vignette exercise examined what factors would prompt a discussion about alcohol, whether they would discuss before or after a patient reported exceeded the revised CMO guidelines (14 units per week) and whether the CMO drinking guidelines were appropriately advised. For all patients, participants were asked how often they discussed alcohol and how they approached the discussion (e.g. used screening tool).

Results

The most common prompts to discuss alcohol in the vignette exercise were physical cues (44.7% of participants) or alcohol-related symptoms (23.8%). Most practitioners (70.1%) said they would wait until a patient was exceeding CMO guidelines before instigating discussion. Two-fifths (38.1%) appropriately advised the CMO guidelines in the vignette exercise, with PNs less likely to do so than GPs (odds ratio [OR] = 0.77, P = 0.03). Less than half (44.7%) reportedly asked about alcohol always/often with all patients, with PNs more likely to ask always/often than GPs (OR = 2.22, P < 0.001). Almost three-quarters said they would enquire by asking about units (70.3%), compared to using screening tools.

Conclusion

Further research is required to identify mechanisms to increase the frequency of discussions about alcohol and appropriate recommendation of the CMO drinking guidelines to patients.
Classification and review of free PCR primer design software
Authors: Guo Jingwen , Starr David , Guo Huazhang
Published: October 2020

Motivation

Polymerase chain reaction (PCR) has been a revolutionary biomedical advancement. However, for PCR to be appropriately used, one must spend a significant amount of effort on PCR primer design. Carefully designed PCR primers not only increase sensitivity and specificity, but also decrease effort spent on experimental optimization. Computer software removes the human element by performing and automating the complex and rigorous calculations required in PCR primer design. Classification and review of the available software options and their capabilities should be a valuable resource for any PCR application.

Results

This article focuses on currently available free PCR primer design software and their major functions (https://pcrprimerdesign.github.io/). The software are classified according to their PCR applications, such as Sanger sequencing, reverse transcription quantitative PCR, single nucleotide polymorphism detection, splicing variant detection, methylation detection, microsatellite detection, multiplex PCR and targeted next generation sequencing, and conserved/degenerate primers to clone orthologous genes from related species, new gene family members in the same species, or to detect a group of related pathogens. Each software is summarized to provide a technical review of their capabilities and utilities.
Sapling: accelerating suffix array queries with learned data models
Authors: Kirsche Melanie , Das Arun , Schatz Michael C
Published: October 2020

Motivation

As genomic data becomes more abundant, efficient algorithms and data structures for sequence alignment become increasingly important. The suffix array is a widely used data structure to accelerate alignment, but the binary search algorithm used to query, it requires widespread memory accesses, causing a large number of cache misses on large datasets.

Results

Here, we present Sapling, an algorithm for sequence alignment, which uses a learned data model to augment the suffix array and enable faster queries. We investigate different types of data models, providing an analysis of different neural network models as well as providing an open-source aligner with a compact, practical piecewise linear model. We show that Sapling outperforms both an optimized binary search approach and multiple widely used read aligners on a diverse collection of genomes, including human, bacteria and plants, speeding up the algorithm by more than a factor of two while adding <1% to the suffix array’s memory footprint.

Availability and implementation

The source code and tutorial are available open-source at https://github.com/mkirsche/sapling.

Supplementary information

Supplementary data are available at Bioinformatics online.
A representation model for biological entities by fusing structured axioms with unstructured texts
Authors: Lou Peiliang , Dong YuXin , Jimeno Yepes Antonio , Li Chen
Published: October 2020

Motivation

Structured semantic resources, for example, biological knowledge bases and ontologies, formally define biological concepts, entities and their semantic relationships, manifested as structured axioms and unstructured texts (e.g. textual definitions). The resources contain accurate expressions of biological reality and have been used by machine-learning models to assist intelligent applications like knowledge discovery. The current methods use both the axioms and definitions as plain texts in representation learning (RL). However, since the axioms are machine-readable while the natural language is human-understandable, difference in meaning of token and structure impedes the representations to encode desirable biological knowledge.

Results

We propose ERBK, a RL model of bio-entities. Instead of using the axioms and definitions as a textual corpus, our method uses knowledge graph embedding method and deep convolutional neural models to encode the axioms and definitions respectively. The representations could not only encode more underlying biological knowledge but also be further applied to zero-shot circumstance where existing approaches fall short. Experimental evaluations show that ERBK outperforms the existing methods for predicting protein–protein interactions and gene–disease associations. Moreover, it shows that ERBK still maintains promising performance under the zero-shot circumstance. We believe the representations and the method have certain generality and could extend to other types of bio-relation.

Availability and implementation

The source code is available at the gitlab repository https://gitlab.com/BioAI/erbk.

Supplementary information

Supplementary data are available at Bioinformatics online.
Rethinking how Technologies Harm
Authors: Wood Mark A
Published: October 2020

Understanding how technologies contribute to social harms is a perennial issue, animating debate within and well beyond criminology. This article contributes to these debates in two ways. First, it critically examines five of the key approaches criminologists have used to think through how technologies contribute to harms. Second, it proposes a new approach to understanding ‘technology–harm relations’. Bringing the theory of critical realism, Simondon and Floridi into conversation, the proposed approach offers a stratigraphy of harm that enables us to excavate the different layers of human–technology and technology–harm relations. In doing so, it enables us to distinguish between four technology–harm relations that untangle the socio-technicality of harmful events: instrumental utility harms, generative utility harms, instrumental technicity harms and generative technicity harms.
Neuregulin-1 beta 1 is implicated in pathogenesis of multiple sclerosis
Authors: Kataria Hardeep , Hart Christopher G , Alizadeh Arsalan , Cossoy Michael , Kaushik Deepak K , Bernstein Charles N , Marrie Ruth Ann , Yong V Wee , Karimi-Abdolrezaee Soheila
Published: October 2020

Multiple sclerosis is characterized by immune mediated neurodegeneration that results in progressive, life-long neurological and cognitive impairments. Yet, the endogenous mechanisms underlying multiple sclerosis pathophysiology are not fully understood. Here, we provide compelling evidence that associates dysregulation of neuregulin-1 beta 1 (Nrg-1β1) with multiple sclerosis pathogenesis and progression. In the experimental autoimmune encephalomyelitis model of multiple sclerosis, we demonstrate that Nrg-1β1 levels are abated within spinal cord lesions and peripherally in the plasma and spleen during presymptomatic, onset and progressive course of the disease. We demonstrate that plasma levels of Nrg-1β1 are also significantly reduced in individuals with early multiple sclerosis and is positively associated with progression to relapsing-remitting multiple sclerosis. The functional impact of Nrg-1β1 downregulation preceded disease onset and progression, and its systemic restoration was sufficient to delay experimental autoimmune encephalomyelitis symptoms and alleviate disease burden. Intriguingly, Nrg-1β1 therapy exhibited a desirable and extended therapeutic time window of efficacy when administered prophylactically, symptomatically, acutely or chronically. Using in vivo and in vitro assessments, we identified that Nrg-1β1 treatment mediates its beneficial effects in EAE by providing a more balanced immune response. Mechanistically, Nrg-1β1 moderated monocyte infiltration at the blood-CNS interface by attenuating chondroitin sulphate proteoglycans and MMP9. Moreover, Nrg-1β1 fostered a regulatory and reparative phenotype in macrophages, T helper type 1 (Th1) cells and microglia in the spinal cord lesions of EAE mice. Taken together, our new findings in multiple sclerosis and experimental autoimmune encephalomyelitis have uncovered a novel regulatory role for Nrg-1β1 early in the disease course and suggest its potential as a specific therapeutic target to ameliorate disease progression and severity.
Bufalin inhibits human diffuse large B-cell lymphoma tumorigenesis by inducing cell death through the Ca2+/NFATC1/cMYC pathway
Authors: Song Jincheng , Zou Dan , Zhao Xiaoxuan , Chen Yang , Lv Fei , Wang Song , Sui Dan , Han Qiuyue , Yang Chunjiao , Wang Ximing , Liu Bofang , Deng Mingming , Zhang Ye
Published: October 2020

The 5-year survival rate of diffuse large B-cell lymphoma (DLBCL) can reach 60%. However, nearly half of patients undergo relapse/refractory issues with a survival period of less than 2 years. New therapeutic approaches are therefore needed to improve chemotherapy efficacy and patient survival. Bufalin (BF), isolated from the traditional Chinese medicine Chansu, has been reported to play an anticancer role in multiple cancer cell types. However, there are few reports of the effects of BF on the growth of DLBCL. In the present study, we demonstrated that BF exerts antitumor activity in DLBCL cells, both in vitro and in vivo. Treatment of DLBCL cells with BF resulted in increased proliferation and apoptosis in a dose- and time-dependent manner. Daily intraperitoneal injection of 1.5 mg/kg BF significantly delayed DLBCL xenograft growth in NOD/SCID mice without affecting body weight. Bioinformatics analysis showed that BF may regulate NFATC1 protein and affect expression of its downstream gene, cMYC. Our results suggest that BF can attenuate NFATC1 translocation by reducing the intracellular calcium concentration; BF may also have a low synergistic effect with cyclosporin A. In conclusion, we demonstrated that BF exerts antitumor activity that is mediated at least in part by the Ca2+/NFATC1/cMYC pathway. Our findings suggest that BF can be effectively applied as a novel potential therapeutic agent for DLBCL.
Elimination of NF-κB signaling in Vimentin+ stromal cells attenuates tumorigenesis in a mouse model of Barrett’s Esophagus
Authors: Anand Akanksha , Fang Hsin-Yu , Mohammad-Shahi Donja , Ingermann Jonas , Baumeister Theresa , Strangmann Julia , Schmid Roland M , Wang Timothy C , Quante Michael
Published: October 2020

Chronic inflammation induces Barrett’s Esophagus (BE) which can advance to esophageal adenocarcinoma. Elevated levels of interleukin (IL)-1b, IL-6 and IL-8 together with activated nuclear factor-kappaB (NF-κB), have been identified as important mediators of tumorigenesis. The inflammatory milieu apart from cancer cells and infiltrating immune cells contains myofibroblasts (MFs) that express aSMA and Vimentin. As we observed that increased NF-κB activation and inflammation correlates with increased MF recruitment and an accelerated phenotype we here analyze the role of NF-κB in MF during esophageal carcinogenesis in our L2-IL-1B mouse model. To analyze the effect of NF-κB signaling in MFs, we crossed L2-IL-1B mice to tamoxifen inducible Vim-Cre (Vim-CreTm) mice and floxed RelA (p65fl/fl) mice to specifically eliminate NF-κB signaling in MF (IL-1b.Vim-CreTm.p65fl/fl). The interaction of epithelial cells and stromal cells was further analyzed in mouse BE organoids and patient-derived human organoids. Histological scoring of IL-1b.Vim-CreTm.p65fl/fl mice showed a significantly attenuated phenotype compared with L2-IL-1B mice, with mild inflammation, decreased metaplasia and no dysplasia. This correlated with decreased proliferation and increased differentiation in cardia tissue of IL-1b.Vim-CreTm.p65fl/fl compared with L2-IL-1B mice. Distinct changes of cytokines and chemokines within the local microenvironment in IL-1b.Vim-CreTm.p65fl/fl mice reflected the histopathological abrogated phenotype. Co-cultured NF-κB inhibitor treated MF with mouse BE organoids demonstrated NF-κB-dependent growth and migration. MFs are essential to form an inflammatory and procarcinogenic microenvironment and NF-κB signaling in stromal cells emerges as an important driver of esophageal carcinogenesis. Our data suggest anti-inflammatory approaches as preventive strategies during surveillance of BE patients.
Reconsidering the Border between the Visual and Posterior Parietal Cortex of Mice
Authors: Gilissen Sara R J , Farrow Karl , Bonin Vincent , Arckens Lutgarde
Published: October 2020

The posterior parietal cortex (PPC) contributes to multisensory and sensory-motor integration, as well as spatial navigation. Based on primate studies, the PPC is composed of several subdivisions with differing connection patterns, including areas that exhibit retinotopy. In mice the composition of the PPC is still under debate. We propose a revised anatomical delineation in which we classify the higher order visual areas rostrolateral area (RL), anteromedial area (AM), and Medio-Medial-Anterior cortex (MMA) as subregions of the mouse PPC. Retrograde and anterograde tracing revealed connectivity, characteristic for primate PPC, with sensory, retrosplenial, orbitofrontal, cingulate and motor cortex, as well as with several thalamic nuclei and the superior colliculus in the mouse. Regarding cortical input, RL receives major input from the somatosensory barrel field, while AM receives more input from the trunk, whereas MMA receives strong inputs from retrosplenial, cingulate, and orbitofrontal cortices. These input differences suggest that each posterior PPC subregion may have a distinct function. Summarized, we put forward a refined cortical map, including a mouse PPC that contains at least 6 subregions, RL, AM, MMA and PtP, MPta, LPta/A. These anatomical results set the stage for a more detailed understanding about the role that the PPC and its subdivisions play in multisensory integration-based behavior in mice.
NECAB1 and NECAB2 are Prevalent Calcium-Binding Proteins of CB1/CCK-Positive GABAergic Interneurons
Authors: Miczán Vivien , Kelemen Krisztina , Glavinics Judit R , László Zsófia I , Barti Benjámin , Kenesei Kata , Kisfali Máté , Katona István
Published: October 2020

The molecular repertoire of the “Ca2+-signaling toolkit” supports the specific kinetic requirements of Ca2+-dependent processes in different neuronal types. A well-known example is the unique expression pattern of calcium-binding proteins, such as parvalbumin, calbindin, and calretinin. These cytosolic Ca2+-buffers control presynaptic and somatodendritic processes in a cell-type-specific manner and have been used as neurochemical markers of GABAergic interneuron types for decades. Surprisingly, to date no typifying calcium-binding proteins have been found in CB1 cannabinoid receptor/cholecystokinin (CB1/CCK)-positive interneurons that represent a large population of GABAergic cells in cortical circuits. Because CB1/CCK-positive interneurons display disparate presynaptic and somatodendritic Ca2+-transients compared with other interneurons, we tested the hypothesis that they express alternative calcium-binding proteins. By in silico data mining in mouse single-cell RNA-seq databases, we identified high expression of Necab1 and Necab2 genes encoding N-terminal EF-hand calcium-binding proteins 1 and 2, respectively, in CB1/CCK-positive interneurons. Fluorescent in situ hybridization and immunostaining revealed cell-type-specific distribution of NECAB1 and NECAB2 throughout the isocortex, hippocampal formation, and basolateral amygdala complex. Combination of patch-clamp electrophysiology, confocal, and STORM super-resolution microscopy uncovered subcellular nanoscale differences indicating functional division of labor between the two calcium-binding proteins. These findings highlight NECAB1 and NECAB2 as predominant calcium-binding proteins in CB1/CCK-positive interneurons.
Impact of Screening and Treatment ofUreaplasmaspecies on Hyperammonemia Syndrome in Lung Transplant Recipients: A Single Center Experience
Authors: Roberts Scott C , Bharat Ankit , Kurihara Chitaru , Tomic Rade , Ison Michael G
Published: October 2020

Background

Infection with Ureaplasma species (spp) has been linked to fatal hyperammonemia syndrome (HS) in lung transplant recipients. We sought to characterize the epidemiology of Ureaplasma spp in candidates and donors and describe outcomes of antimicrobial therapy in preventing and treating HS.

Methods

Candidate testing for Ureaplasma spp was performed with urine culture and polymerase chain reaction (PCR) pretransplant. Positive candidates were treated with levofloxacin. Donor testing was performed with bronchoalveolar lavage (BAL) culture and PCR intraoperatively. From 7/2014 to 2/2017 patients were treated according to results; from 2/2017 to 10/2018 recipients received empiric levofloxacin and azithromycin at transplant until testing returned negative. HS was defined as new onset altered mental status after transplant with ammonia > 200 µmol/L.

Results

In total, 60 patients who underwent lung transplant were included. And 80% (n = 48) of patients had negative screening tests in donor and candidate pre-lung transplant, 8.3% (n = 5) of recipients had positive Ureaplasma spp testing in urine pre-transplant, and 13.3% (n = 8) had positive donor BAL testing at the time of lung transplant. Three patients developed HS a median of 7 days posttransplant; 2 died of HS. Recipients of organs with Ureaplasma spp who received empiric therapy did not develop HS. Donors with Ureaplasma spp were younger and more sexually active.

Conclusions

Donor-derived Ureaplasma spp in lung transplant was associated with HS. Screening lung donors for Ureaplasma spp might allow for targeted therapy to reduce risk for development of HS, but future confirmatory studies are needed.
The Vitamin D Metabolite Ratio Is Independent of Vitamin D Binding Protein Concentration
Authors: Ginsberg Charles , Hoofnagle Andrew N , Katz Ronit , Becker Jessica O , Kritchevsky Stephen B , Shlipak Michael G , Sarnak Mark J , Ix Joachim H
Published: October 2020

Background

25-Hydroxyvitamin D [25(OH)D] may be a poor marker of vitamin D status as it reflects differences in vitamin D binding protein (VDBP) between individuals. The vitamin D metabolite ratio [VMR, ratio of 24,25(OH)2D3 to 25(OH)D3] is a marker of vitamin D status that has been hypothesized to be independent of variability in VDBP. This hypothesis has not been directly evaluated.

Methods

We measured 25(OH)D3, 24,25(OH)2D3, 1,25(OH)2D3, and VDBP in 377 community-dwelling older adults that participated in the Health Aging and Body Composition Study. 24,25(OH)2D3 and 25(OH)D3 were used to calculate the VMR. We used linear regression to assess the relationship between VDBP with the VMR, 24,25(OH)2D3, 25(OH)D3, and 1,25(OH)2D3.

Results

Participants had mean age 75 ± 3 years, 52% were female, 40% were black, and 24% had chronic kidney disease. VDBP concentrations were associated with sex, serum albumin, and VDBP phenotype in multivariable models. In fully adjusted models, each 1% higher VDBP was associated with a 0.92%[95% CI(0.37,1.49%)], 0.76% (0.39, 1.13%), and 0.57% (0.29, 0.85%), higher 24,25(OH)2D3, 25(OH)D3, and 1,25(OH)2D3. The VMR was independent of VDBP concentration, [0.16%(-0.11, 0.44) higher VMR per 1% higher VDBP, P = .25].

Conclusions

The VMR was independent of VDBP concentration, whereas VDBP was strongly directly associated with the individual vitamin D metabolite concentrations. Prior studies evaluating only 25(OH)D3 may have been confounded by absence of data on VDBP status. The VMR may serve as an important biomarker of vitamin D status and clinical outcomes that can be utilized in populations with a large spectrum of VDBP concentrations.
SDVoIP—A Software-Defined VoIP Framework For SIP And Dynamic QoS
Authors: Gandotra Rahil , Perigo Levi
Published: October 2020

Software-defined networking (SDN) allows for the decoupling of the control and data planes, enabling more programmability and a global view of the network. Previous research indicates that traditional applications recreated using SDN principles allow for more granularity and customization. In this research, we extend the insights behind SDN to develop a Voice over Internet Protocol (VoIP) framework with the objective to enhance traditional Session Initiation Protocol (SIP) operation and quality of service (QoS) approaches. The contributions of this research are 2-fold: first, an SIP control application is implemented, which communicates with an SDN controller to provide VoIP call registration and call routing capabilities, thereby eliminating the need for specialized SIP proxy hardware devices; second, a dynamic QoS application is developed that provides the ability to make network-wide QoS decisions based on real-time network measurements of latency, bandwidth and packet loss. Functional validation of the framework is performed to verify its operation. The experiment results indicate that the proposed framework allows for enhancements to traditional QoS implementations.
CCA-Almost-Full Anonymous Group Signature with Verifier Local Revocation in the Standard Model
Authors: Ma Sha , Huang Qiong
Published: October 2020

Group signature (GS) allows each member in a group to do signatures anonymously on behalf of the group under management of a group authority. Membership revocation has been a central issue in GS and widely studied so far. The mechanism of verifier local revocation for GS, first formalized by Boneh and Shacham, has an advantage of making the signers free from fetching the up-to-date information of the revoked users and practicality in the scenario of periodically update in the large population of group users. Most of work related to group signature with verifier-local revocation either can only achieve selfless anonymity or have inefficient constructions due to complicate primitives. Aiming to a recent chosen ciphertext attack-almost-full anonymous notion for GS, this paper presents an efficient GS with verifier local revocation in the standard model by adding a new primitive plaintext searchable encryption into Groth’s GS under Canard et al.’s framework. We prove that it has backward unlinkability to ensure that all signatures generated by the user before the revocation remain anonymous, even if it is revoked later.
Spatio-Temporal Model for Predicting Spring Hatch of the Spotted Lanternfly (Hemiptera: Fulgoridae)
Authors: Smyers Erica C , Urban Julie M , Dechaine Andrew C , Pfeiffer Douglas G , Crawford Stephen R , Calvin Dennis D
Published: October 2020

The effect of temperature on the rate of spotted lanternfly, Lycorma delicatula (White) (Hemiptera: Fulgoridae), egg development was investigated for a population in Pennsylvania. Mean developmental duration (days ± SE) for egg hatch was evaluated at five constant temperatures of 19.9, 24.2, 25.1, 26.7, and 30°C using egg masses laid during the fall of 2018 and collected in 2019 from Berks Co., Pennsylvania. Base temperature thresholds for egg development were estimated using intercept and slope parameters by fitting a linear relationship between average temperature and developmental rate for the Pennsylvania study, two Korean studies, and the combined data sets. The base threshold estimates were then used to calculate seasonal accumulated degree-days (ADD) and construct logistic equations for predicting cumulative proportion of hatch in the spring. The fitted logistic prediction equations were then graphed against the egg hatch observations from field sites in Pennsylvania (2017) and Virginia (2019). When base temperature estimates from the three studies and combined studies were used to calculate ADD, the logistic models predicted similar timing for seasonal egg hatch. Because the slopes and intercepts for these four data sets were not statistically different, a base temperature threshold of 10.4°C derived from the combined model is a good estimate for computing ADD to predict spotted lanternfly spring emergence across a spatio-temporal scale. The combined model was linked with open source weather database and mapping programs to provide spatiotemporal prediction maps to aid pest surveillance and management efforts for spotted lanternfly.
Left ventricular segmental strain and the prediction of cancer therapy-related cardiac dysfunction
Authors: Demissei Biniyam G , Fan Yong , Qian Yiwen , Cheng Henry G , Smith Amanda M , Shimamoto Kelsey , Vedage Natasha , Narayan Hari K , Scherrer-Crosbie Marielle , Davatzikos Christos , Ky Bonnie
Published: October 2020

Aims

We aimed to determine the early changes and predictive value of left ventricular (LV) segmental strain measures in women with breast cancer receiving doxorubicin.

Methods and results

In a cohort of 237 women with breast cancer receiving doxorubicin with or without trastuzumab, 1151 echocardiograms were prospectively acquired over a median (Q1–Q3) of 7 (2–24) months. LV ejection fraction (LVEF) and 36 segmental strain measures were core lab quantified. A supervised machine learning (ML) model was then developed using random forest regression to identify segmental strain measures predictive of nadir LVEF post-doxorubicin completion. Cancer therapy-related cardiac dysfunction (CTRCD) was defined as a ≥10% absolute LVEF decline pre-treatment to a value <50%. Median (Q1–Q3) baseline age was 48 (41–57) years. Thirty-five women developed CTRCD, and eight of these developed symptomatic heart failure. From pre-treatment to doxorubicin completion, longitudinal strain worsened across the basal and mid-LV segments but not in the apical segments; circumferential strain worsened primarily in the septum; radial strain worsened uniformly and transverse strain remained unchanged across all LV segments. In the ML model, anterolateral and inferoseptal circumferential strain were the most predictive features; longitudinal and transverse strain in the basal inferoseptal, anterior, basal anterolateral, and apical lateral segments were also top predictive features. The addition of predictive segmental strain measures to a model including age, cancer therapy regimen, hypertension, and LVEF increased the area under the curve (AUC) from 0.70 (95% confidence interval (CI) 0.60–0.80) to 0.87 (95% CI 0.81–0.92), ΔAUC = 0.18 (95% CI 0.08–0.27) for the prediction of CTRCD.

Conclusion

Our findings suggest that segmental strain measures can enhance cardiotoxicity risk prediction in women with breast cancer receiving doxorubicin.
Myocardial perfusion scintigraphy for risk stratification of patients with coronary artery disease: the AMICO registry
Authors: Gimelli Alessia , Pugliese Nicola Riccardo , Buechel Ronny R , Coceani Michele , Clemente Alberto , Kaufmann Philipp A , Marzullo Paolo
Published: October 2020

Aims

We assessed the prognostic value of myocardial perfusion scintigraphy (MPS) with cadmium–zinc–telluride in addition to clinical and coronary anatomy analysis.

Methods and results

We prospectively enrolled 1464 patients (26% females, 69.5 ± 10.4 years) referred for stress-rest MPS. All the patients underwent invasive coronary angiography (1171, 80%) or coronary computed tomography angiography (293, 20%). We defined a composite endpoint of cardiovascular death and non-fatal MI. After an 8-year follow-up, summed stress score (SSS) had the highest accuracy in predicting primary endpoint with a ROC-derived cut-off of SSS >8 (>10% myocardium). SSS >8 portended the lowest survival probability at Kaplan–Meier analysis (P < 0.0001 for the composite endpoint and individual components). The Cox-regression analysis indicated SSS as an independent predictor of the composite endpoint, along with fasting blood glucose and total cholesterol and contrary to coronary anatomy parameters. Patients with SSS >8 treated with optimal medical therapy (OMT) had the largest area of necrosis, the lower ischaemic burden, the most compromised LV systo-diastolic function and the highest LV mass, but received a less aggressive treatment in comparison to early revascularized patients. Survival analysis revealed patients with SSS ≤8 had the greater freedom from events, irrespective of the treatment strategy, while the group with SSS >8 and OMT had the worst outcome, followed by patients with SSS >8 and early revascularization (log-rank test: all P < 0.0001).

Conclusion

MPS-SSS constitutes a strong independent predictor of future adverse events after adjustment for multiple clinical parameters and coronary angiography. In particular, MPS could help risk stratification of patients who did not undergo early revascularization.
Effect of alcohol consumption on the risk of adverse events in atrial fibrillation: from the COmparison study of Drugs for symptom control and complication prEvention of Atrial Fibrillation (CODE-AF) registry
Authors: Lim Chewan , Kim Tae-Hoon , Yu Hee Tae , Lee So-Ryoung , Cha Myung-Jin , Lee Jung-Myung , Park Junbeom , Park Jin-Kyu , Kang Ki-Woon , Shim Jaemin , Uhm Jae-Sun , Kim Jun , Park Hyung Wook , Choi Eue-Keun , Kim Jin-Bae , Lee Young Soo , Joung Boyoung
Published: October 2020

Aims

The aim of this study is to determine the relationship between alcohol consumption and atrial fibrillation (AF)-related adverse events in the AF population.

Methods and results

A total of 9411 patients with nonvalvular AF in a prospective observational registry were categorized into four groups according to the amount of alcohol consumption—abstainer-rare, light (<100 g/week), moderate (100–200 g/week), and heavy (≥200 g/week). Data on adverse events (ischaemic stroke, transient ischaemic attack, systemic embolic event, or AF hospitalization including for AF rate or rhythm control and heart failure management) were collected for 17.4 ± 7.3 months. A Cox proportional hazard models was performed to calculate hazard ratios (HRs), and propensity score matching was conducted to validate the results. The heavy alcohol consumption group showed an increased risk of composite adverse outcomes [adjusted hazard ratio (aHR) 1.32, 95% confidence interval (CI) 1.06–1.66] compared with the reference group (abstainer-rare group). However, no significant increased risk for adverse outcomes was observed in the light (aHR 0.88, 95% CI 0.68–1.13) and moderate (aHR 0.91, 95% CI 0.63–1.33) groups. In subgroup analyses, adverse effect of heavy alcohol consumption was significant, especially among patients with low CHA2DS2-VASc score, without hypertension, and in whom β-blocker were not prescribed.

Conclusion

Our findings suggest that heavy alcohol consumption increases the risk of adverse events in patients with AF, whereas light or moderate alcohol consumption does not.
Prevalence and prognostic association of ventricular arrhythmia in non-ischaemic heart failure patients: results from the DANISH trial
Authors: Boas Rune , Thune Jens Jakob , Pehrson Steen , Køber Lars , Nielsen Jens C , Videbæk Lars , Haarbo Jens , Korup Eva , Bruun Niels Eske , Brandes Axel , Eiskjær Hans , Thøgersen Anna M , Philbert Berit T , Svendsen Jesper Hastrup , Dixen Ulrik
Published: October 2020

Aims

Improved risk stratification to identify non-ischaemic heart failure patients who will benefit from primary prophylactic implantable cardioverter-defibrillator (ICD) is needed. We examined the potential of ventricular arrhythmia to identify patients who could benefit from an ICD.

Methods and results

A total of 850 non-ischaemic systolic heart failure patients with left ventricle ≤35% and elevated N-terminal pro-brain natriuretic peptides had a 24-h Holter monitor recording performed. We examined present non-sustained ventricular tachycardia (NSVT), defined as ≥3 consecutive premature ventricular contractions (PVCs) with a rate of ≥100/min, and number of PVCs per hour stratified into low (<30) and high burden (≥30) groups. Outcome measures were overall mortality, sudden cardiac death (SCD), and cardiovascular death (CVD). In total, 193 patients died, 49 from SCD and 125 from CVD. Non-sustained ventricular tachycardia (365 patients) was significantly associated with increased all-cause mortality [hazard ratio (HR) 1.47; 95% confidence interval (CI) 1.07–2.03; P = 0.02] and to CVD (HR 1.89; CI 1.25–2.87; P = 0.003). High burden PVC (352 patients) was associated with increased all-cause mortality (HR1.38; CI 1.00–1.90; P = 0.046) and with CVD (HR 1.78; CI 1.19–2.66; P = 0.005). There was no statistically significant association with SCD for neither NSVT nor PVC. In interaction analyses, neither NSVT (P = 0.56) nor high burden of PVC (P = 0.97) was associated with survival benefit from ICD implantation.

Conclusion

Ventricular arrhythmia in non-ischaemic heart failure patients was associated with a worse prognosis but could not be used to stratify patients to ICD implantation.
Matrix inhibition by Salmonella excludes uropathogenic E. coli from biofilm
Authors: Miryala Sandeep , Nair Veena G , Chandramohan S , Srinandan C S
Published: October 2020

Biofilm is a predominant lifestyle of bacteria that comprises of cells as collectives enmeshed in a polymeric matrix. Biofilm formation is vital for bacterial species as it provides access to nutrients and protects the cells from environmental stresses. Here we show that interference in biofilm matrix production is a strategy by the competing bacterial species to reduce the ability of the other species to colonize a surface. Escherichia coli colonies that differ in matrix production display different morphologies on Congo red agar media, which we exploited for screening bacterial isolates capable of inhibiting the matrix. The cell-free supernatants from growth culture of the screened isolates impaired uropathogenic E. coli (UPEC) UTI89 strain's biofilm. A physicochemical analysis suggested that the compound could be a glycopeptide or a polysaccharide. Isolates that inhibited matrix production belonged to species of the family Enterobacteriaceae such as Shigella, Escherichia, Enterobacter and Salmonella. Competition experiments between the isolates and the UPEC strain resulted in mutual inhibition, particularly during biofilm formation causing significant reduction in productivity and fitness. Furthermore, we show that Salmonella strains competitively excluded the UPEC strain in the biofilm by inhibiting its matrix production, highlighting the role of interference competition.
Calcium Signaling in Pancreatic Immune CellsIn situ
Authors: Gryshchenko Oleksiy , Gerasimenko Julia V , Petersen Ole H , Gerasimenko Oleg V
Published: October 2020

Immune cells were identified in intact live mouse pancreatic lobules and their Ca2+ signals, evoked by various agents, characterized and compared with the simultaneously recorded Ca2+ signals in neighboring acinar and stellate cells. Immunochemistry in the live lobules indicated that the pancreatic immune cells most likely are macrophages. In the normal pancreas the density of these cells is very low, but induction of acute pancreatitis (AP), by a combination of ethanol and fatty acids, markedly increased the number of the immune cells. The principal agent eliciting Ca2+ signals in the pancreatic immune cells was ATP, but these cells also frequently produced Ca2+ signals in response to acetylcholine and to high concentrations of bradykinin. Pharmacological studies, using specific purinergic agonists and antagonists, indicated that the ATP-elicited Ca2+ signals were mediated by both P2Y1 and P2Y13 receptors. The pancreatic immune cells were not electrically excitable and the Ca2+ signals generated by ATP were primarily due to release of Ca2+ from internal stores followed by store-operated Ca2+ entry through Ca2+ release-activated Ca2+ channels. The ATP-induced intracellular Ca2+ liberation was dependent on both IP3 generation and IP3 receptors. We propose that the ATP-elicited Ca2+ signal generation in the pancreatic immune cells is likely to play an important role in the severe inflammatory response to the primary injury of the acinar cells that occurs in AP.