bluuebunny/crossref_metadata_2025 huggingface dataset:
Matter Chern Simons theories in a background magnetic field
Authors: Halder Indranil , Minwalla Shiraz
Published: November 2019

Abstract

We study large N 2+1 dimensional fermions in the fundamental representation of an SU(N)k Chern Simons gauge group in the presence of a uniform background magnetic field for the U (1) global symmetry of this theory. The magnetic field modifies the Schwinger Dyson equation for the propagator in an interesting way; the product between the self energy and the Greens function is replaced by a Moyal star product. Employing a basis of functions previously used in the study of non-commutative solitons, we are able to exactly solve the Schwinger Dyson equation and so determine the fermion propagator. The propagator has a series of poles (and no other singularities) whose locations yield a spectrum of single particle energies at arbitrary t’ Hooft coupling and chemical potential. The usual free fermion Landau levels spectrum is shifted and broadened out; we compute the shifts and widths of these levels at arbitrary t’Hooft coupling. As a check on our results we independently solve for the propagators of the conjecturally dual theory of Chern Simons gauged large N fundamental Wilson Fisher bosons also in a background magnetic field but this time only at zero chemical potential. The spectrum of single particle states of the bosonic theory precisely agrees with those of the fermionic theory under Bose-Fermi duality.
Single-agent ibrutinib in RESONATE-2™ and RESONATE™ versus treatments in the real-world PHEDRA databases for patients with chronic lymphocytic leukemia
Authors: Salles Gilles , Bachy Emmanuel , Smolej Lukas , Simkovic Martin , Baseggio Lucile , Panovska Anna , Besson Hervé , Healy Nollaig , Garside Jamie , Iraqi Wafae , Diels Joris , Pick-Lauer Corinna , Spacek Martin , Urbanova Renata , Lysak Daniel , Hermans Ruben , Lundbom Jessica , Callet-Bauchu Evelyne , Doubek Michael
Published: November 2019

After analyzing treatment patterns in chronic lymphocytic leukemia (CLL) (objective 1), we investigated the relative effectiveness of ibrutinib versus other commonly used treatments (objective 2) in patients with treatment-naïve and relapsed/refractory CLL, comparing patient-level data from two randomized registration trials with two real-world databases. Hazard ratios (HR) and 95% confidence intervals (CIs) were estimated using a multivariate Cox proportional hazards model, adjusted for differences in baseline characteristics. Rituximab-containing regimens were often prescribed in clinical practice. The most frequently prescribed regimens were fludarabine + cyclophosphamide + rituximab (FCR, 29.3%), bendamustine + rituximab (BR, 17.7%), and other rituximab-containing regimens (22.0%) in the treatment-naïve setting (n = 604), other non-FCR/BR rituximab-containing regimens (38.7%) and non-rituximab–containing regimens (28.5%) in the relapsed/refractory setting (n = 945). Adjusted HRs (95% CI) for progression-free survival (PFS) and overall survival (OS), respectively, with ibrutinib versus real-world regimens were 0.23 (0.14–0.37; p < 0.0001) and 0.40 (0.22–0.76; p = 0.0048) in the treatment-naïve setting, and 0.21 (0.16–0.27; p < 0.0001) and 0.29 (0.21–0.41; p < 0.0001) in the relapsed/refractory setting. When comparing real-world use of ibrutinib (n = 53) versus other real-world regimens in relapsed/refractory CLL (objective 3), adjusted HRs (95% CI) were 0.37 (0.22–0.63; p = 0.0003) for PFS and 0.53 (0.27–1.03; p < 0.0624) for OS. This adjusted analysis, based on nonrandomized patient data, suggests ibrutinib to be more effective than other commonly used regimens for CLL.
Influence of a thin amorphous surface layer on de-channeling during aluminum implantation at different temperatures into 4H-SiC
Authors: Linnarsson M. K. , Hallén A. , Vines L.
Published: November 2019

Ion implantation is an important technique in semiconductor processing and has become a key technology for 4H-SiC devices. Today, aluminum (Al) implantations are routinely used for p-type contacts, p+-emitters, terminations and many other applications. However, in all crystalline materials, quite a few ions find a path along a crystal channel, so-called channeling, and these ions travel deep into the crystal. This paper reports on the channeling phenomenon during Al implantation into 4H-SiC, and in particular, the influence of a thin native oxide will be discussed in detail. The effects of thermal lattice vibrations for implantations performed at elevated temperatures will also be elucidated. 100 keV Al ions have been implanted along the [000-1] direction employing samples with 4° miscut. Before implantation, the samples have been aligned using the blocking pattern of backscattered protons. Secondary ion mass spectrometry has been used to record the Al depth distribution. To predict implantation profiles and improve understanding of the role of crystal structure, simulations were performed using the Monte-Carlo binary collision approximation code SIIMPL. Our results show that a thin surface layer of native oxide, less than 1 nm, has a decisive role for de-channeling of aligned implantations. Further, as expected, for implantations at elevated temperatures, a larger degree of de-channeling from major axes is present due to increased thermal vibrations and the penetration depth of channeled aluminum ions is reduced. The values for the mean-square atomic displacements at elevated temperatures have been extracted from experimental depth profiles in combination with simulations.
Transcriptome analysis reveals overlap in fusion genes in a phase I clinical cohort of TNBC and HGSOC patients treated with buparlisib and olaparib
Authors: Eismann Julia , Heng Yujing J. , Waldschmidt Johannes M. , Vlachos Ioannis S. , Gray Kathryn P. , Matulonis Ursula A. , Konstantinopoulos Panagiotis A. , Murphy Charles J. , Nabavi Sheida , Wulf Gerburg M.
Published: November 2019

Purpose

Fusion genes can be therapeutically relevant if they result in constitutive activation of oncogenes or repression of tumor suppressors. However, the prevalence and role of fusion genes in female cancers remain largely unexplored. Here, we investigate the fusion gene landscape in triple-negative breast cancer (TNBC) and high-grade serous ovarian cancer (HGSOC), two subtypes of female cancers with high molecular similarity but limited treatment options at present.

Methods

RNA-seq was utilized to identify fusion genes in a cohort of 18 TNBC and HGSOC patients treated with the PI3K inhibitor buparlisib and the PARP inhibitor olaparib in a phase I clinical trial (NCT01623349). Differential gene expression analysis was performed to assess the function of fusion genes in silico. Finally, these findings were correlated with the reported clinical outcomes.

Results

A total of 156 fusion genes was detected, whereof 44/156 (28%) events occurred in more than one patient. Low recurrence across samples indicated that the majority of fusion genes were private passenger events. The long non-coding RNA MALAT1 was involved in 97/156 (62%) fusion genes, followed in prevalence by MUC16, FOXP1, WWOX and XIST. Gene expression of FOXP1 was significantly elevated in patients with vs. without FOXP1 fusion (P= 0.02). From a clinical perspective, FOXP1 fusions were associated with a favorable overall survival.

Conclusions

In summary, this study provides the first characterization of fusion genes in a cohort of TNBC and HGSOC patients. An improved mechanistic understanding of fusion genes will support the future identification of innovative therapeutic approaches for these challenging diseases.
Sexual dimorphism in gastric cancer: tumor-associated neutrophils predict patient outcome only for women
Authors: Clausen Franziska , Behrens Hans-Michael , Krüger Sandra , Röcken Christoph
Published: November 2019

Purpose

Tumor-associated neutrophils (TANs) are part of the tumor immune microenvironment (TIME) and may contribute to gastric cancer (GC) biology. We hypothesized that TAN are enriched in the TIME, show sex-specific differences, and correlate with patient outcome.

Methods

We analyzed the distribution and putative tumor biological significance of TANs in a well-characterized, therapy-naïve, European GC cohort using immunohistochemical staining of myeloperoxidase (MPO), and digital image analysis using Definiens Tissue Studio®.

Results

Different tumor compartments were examined, and TAN densities were correlated with various clinicopathological patient characteristics. TAN density showed a large interindividual variability ranging from 0 to 6711.0 TANs/mm2. Intratumoral distribution patterns were inhomogeneous (tumor surface vs. tumor center vs. invasion front) and correlated significantly with Laurén phenotype, tumor grade, and microsatellite status in the tumor center and invasion front. In the multivariate analysis, TAN density in the invasion front was an independent predictor of tumor-specific survival only for women (HR = 2.77, p   < 0.001). In men, no correlation was found between TAN density and survival.

Conclusion

With regard to TANs, our study independently validates sexual dimorphism in GC biology.
Selecting the optimal risk threshold of diabetes risk scores to identify high-risk individuals for diabetes prevention: a cost-effectiveness analysis
Authors: Mühlenbruch Kristin , Zhuo Xiaohui , Bardenheier Barbara , Shao Hui , Laxy Michael , Icks Andrea , Zhang Ping , Gregg Edward W. , Schulze Matthias B.
Published: November 2019

Aims

Although risk scores to predict type 2 diabetes exist, cost-effectiveness of risk thresholds to target prevention interventions are unknown. We applied cost-effectiveness analysis to identify optimal thresholds of predicted risk to target a low-cost community-based intervention in the USA.

Methods

We used a validated Markov-based type 2 diabetes simulation model to evaluate the lifetime cost-effectiveness of alternative thresholds of diabetes risk. Population characteristics for the model were obtained from NHANES 2001–2004 and incidence rates and performance of two noninvasive diabetes risk scores (German diabetes risk score, GDRS, and ARIC 2009 score) were determined in the ARIC and Cardiovascular Health Study (CHS). Incremental cost-effectiveness ratios (ICERs) were calculated for increasing risk score thresholds. Two scenarios were assumed: 1-stage (risk score only) and 2-stage (risk score plus fasting plasma glucose (FPG) test (threshold 100 mg/dl) in the high-risk group).

Results

In ARIC and CHS combined, the area under the receiver operating characteristic curve for the GDRS and the ARIC 2009 score were 0.691 (0.677–0.704) and 0.720 (0.707–0.732), respectively. The optimal threshold of predicted diabetes risk (ICER < $50,000/QALY gained in case of intervention in those above the threshold) was 7% for the GDRS and 9% for the ARIC 2009 score. In the 2-stage scenario, ICERs for all cutoffs ≥ 5% were below $50,000/QALY gained.

Conclusions

Intervening in those with ≥ 7% diabetes risk based on the GDRS or ≥ 9% on the ARIC 2009 score would be cost-effective. A risk score threshold ≥ 5% together with elevated FPG would also allow targeting interventions cost-effectively.
Dynamic response of RNA editing to temperature in grape by RNA deep sequencing
Authors: Zhang Aidi , Jiang Xiaohan , Zhang Fuping , Wang Tengfei , Zhang Xiujun
Published: November 2019

RNA editing is a post-transcriptional process of modifying genetic information on RNA molecules, which provides cells an additional level of gene expression regulation. Unlike mammals, in land plants, RNA editing converts C-to-U residues in organelles. However, its potential roles in response to different stressors (heat, salt, and so on) remains unclear. Grape is one of the most popular and economically important fruits in the world, and its production, like other crops, must deal with abiotic and biotic stresses, which cause reductions in yield and fruit quality. In our study, we tested the influence of the environmental factor temperature on RNA editing process in the whole mRNA from grape organelle. In total, we identified 122 and 627 RNA editing sites in chloroplast and mitochondria respectively with the average editing efficiency nearly ~ 60%. The analyses revealed that number of non-synonymous editing sites were higher than that of synonymous editing sites, and the amino acid substitution type tends to be hydrophobic. Additionally, the overall editing level decreased with the temperature rises, especially for several gene transcripts in chloroplast and mitochondria (matK, ndhB, etc.). We also found that the expression level of most PPR genes decreased with the temperature rises, which may contribute to the decline of RNA editing efficiency at high temperature. Our findings suggested that the RNA editing events were very sensitive to heat stress; the changes of amino acid in RNA editing genes may contribute to the stress adaption for grape.
End-of-life vehicle management: a comprehensive review
Authors: Karagoz Selman , Aydin Nezir , Simic Vladimir
Published: November 2019

Waste management is gaining very high importance in recent years. As automotive is one of the most critical sectors worldwide, which is rapidly increasing, the management of end-of-life vehicles (ELVs) gains importance day by day. Due to legislation and new regulations, actors like users, producers, and treatment facilities are being conferred new responsibilities in the ELV management process. Besides, the ELV management is of vital importance for environment conservation, circular economy and sustainable development. All of these reasons are making the ELV management such a crucial issue to study. Today, the ELV management is a well-positioned and emergent research area. However, the available review papers are focused only on a small area of the ELV management, such as reverse logistics, recovery infrastructure, disassemblability, etc. Besides, a review of state-of-the-art mathematical models for the ELV management is still missing. This paper aims to provide an extensive content analysis overview of studies on the ELV management. A total of 232 studies published in the period 2000–2019 are collected, categorized, reviewed and analyzed. A critical review of the published literature is provided. Gaps in the literature are identified to clarify and suggest future research directions. This review can provide a source of references, valuable insights, and opportunities for researchers interested in the ELV management and inspire their additional attention.
Remote monitoring of chronic heart failure patients: invasive versus non-invasive tools for optimising patient management
Authors: Veenis J. F. , Brugts J. J.
Published: November 2019

Exacerbations of chronic heart failure (HF) with the necessity for hospitalisation impact hospital resources significantly. Despite all of the achievements in medical management and non-pharmacological therapy that improve the outcome in HF, new strategies are needed to prevent HF-related hospitalisations by keeping stable HF patients out of the hospital and focusing resources on unstable HF patients. Remote monitoring of these patients could provide the physicians with an additional tool to intervene adequately and promptly. Results of telemonitoring to date are inconsistent, especially those of telemonitoring with traditional non-haemodynamic parameters. Recently, the CardioMEMS device (Abbott Inc., Atlanta, GA, USA), an implantable haemodynamic remote monitoring sensor, has shown promising results in preventing HF-related hospitalisations in chronic HF patients hospitalised in the previous year and in New York Heart Association functional class III in the United States. This review provides an overview of the available evidence on remote monitoring in chronic HF patients and future perspectives for the efficacy and cost-effectiveness of these strategies.
Situated transformations of women and gender relations in small-scale fisheries and communities in a globalized world
Authors: Frangoudes Katia , Gerrard Siri , Kleiber Danika
Published: November 2019

The need to uncover, interrogate, and integrate women’s contributions to fisheries in research and development has never been clearer. As coastal and fisheries management continues to look to the Sustainable Development Goals and the Voluntary Guidelines for Securing Sustainable Small-Scale Fisheries in the context of Food Security and Poverty Eradication, as frameworks and mandates, gender equity and equality have become a central concern. To fill the still existing gap of documentation and theoretical engagement, in this thematic collection, we gather together voices from researchers and practitioners from around the world, with one overarching common approach of using a gender lens to examine the relationship between humans and aquatic resources. Drawing on Donna Haraway’s classic feminist concept of situated knowledges, we examine the many and varied approaches researchers are using to engage with the intersection of gender and fisheries. Beginning and ending with two reviews that examine where gender and fisheries has come from, and where it is going, this thematic issue includes case studies from 10 countries, engaging in the topic at various scales (individual, household, national, institutional etc.), and using multiple methodological approaches. Taken together, these pieces explore the mechanism by which women’s contribution to fisheries are overlooked and provide direct evidence to contest the persistent invisibility of women in fishing, fisheries labor, and fisheries decision-making. Going beyond the evidence of women’s contributions, the authors go further to examine different coastal contexts, intersectional identities such as age, and explore gender transformative approaches to fisheries development.
Prevalence of anemia and iron profile among children and adolescent with low socio-economic status
Authors: Andriastuti Murti , Ilmana Ganda , Nawangwulan Serra Avilia , Kosasih Kartika Anastasia
Published: November 2019

Background:

A national health survey in Indonesia conducted in 2013 showed that the prevalence of anemia in school-aged children and adolescents tripled from a survey conducted in 2007. Children and adolescents are particularly susceptible to iron deficiency anemia (IDA) and iron deficiency (ID) because of their rapid growth and puberty. Teenage girls are at risk because of their menstrual bleeding. Low socioeconomic status in children and adolescents is also a strong risk factor for experiencing iron defi­ciency. Studies regarding the prevalence of ID and IDA in Indonesia still vary and are lacking. This study aims to describe the prevalence of anemia in children and adolescents with low socioeconomic conditions.

Methods:

This is a cross-sectional study conducted at two schools in the suburbs of Jakarta on children and adolescents aged 6–18 years old. Personal data and laboratory identities (complete peripheral blood count, reticulocyte hemoglobin content, ferritin, transferrin saturation, and C-reactive protein) were collected to determine iron status. Analysis was performed using SPSS program version 22.0.

Results:

The overall prevalence of anemia was 14.0%. The prevalence of IDA, ID without anemia, and iron depletion was 5.8%, 18.4%, and 4.3%, respectively. The prevalence of IDA, ID, and iron depletion was higher in females than in males.

Conclusion:

The overall prevalence of anemia in children and adolescents is lower than the national data. Special consideration needs to be taken for the female population, who are more at risk of developing ID and IDA.
Employability Assessment in Australian Total and Permanent Disability Insurance Claims: A Survey of Claims Professionals’ Views
Authors: Black Margaret , Matthews Lynda R. , Millington Michael J.
Published: November 2019

Employability assessment was developed to help claims professionals decide total and permanent disability insurance claims, yet it has not been empirically evaluated. This descriptive study sought formative knowledge about employability assessment from claims professionals working in the multibillion-dollar Australian life insurance total and permanent disability market. Claims assessors (n = 53) and technical advisors (n = 51) responded to a nationwide online survey. Participants found employability assessment was cost effective and very useful in deciding claims. Having an objective, realistic, and clear picture of a claimant’s employment prospects was important. Highly rated components of employability assessment included transferable skills analysis; summary of education, training and experience; job match rationale; and labour market analysis with employer contact. Face-to-face claimant interviews were favoured by 56% of participants, particularly when there was legal involvement. Standardised provider training and certification were recommended to improve report quality and withstand scrutiny of the courts. Billing time estimates are higher than extant costs for assessment tasks. More than half (56%) the participants considered rehabilitation counsellors were best qualified to conduct employability assessments. The study findings contribute new knowledge to this emergent field and point to further research into quality and cost of employability assessment, and provider accreditation.
KMS states on theC*-algebras of Fell bundles over groupoids
Authors: AFSAR ZAHRA , SIMS AIDAN
Published: November 2019

We consider fibrewise singly generated Fell bundles over étale groupoids. Given a continuous real-valued 1-cocycle on the groupoid, there is a natural dynamics on the cross-sectional algebra of the Fell bundle. We study the Kubo–Martin–Schwinger equilibrium states for this dynamics. Following work of Neshveyev on equilibrium states on groupoidC*-algebras, we describe the equilibrium states of the cross-sectional algebra in terms of measurable fields of states on theC*-algebras of the restrictions of the Fell bundle to the isotropy subgroups of the groupoid. As a special case, we obtain a description of the trace space of the cross-sectional algebra. We apply our result to generalise Neshveyev’s main theorem to twisted groupoidC*-algebras, and then apply this to twistedC*-algebras of strongly connected finitek-graphs.
Causes of Oceanic Crustal Thickness Oscillations Along a 74‐M Mid‐Atlantic Ridge Flow Line
Authors: Shinevar William J. , Mark Hannah F. , Clerc Fiona , Codillo Emmanuel A. , Gong Jianhua , Olive Jean‐Arthur , Brown Stephanie M. , Smalls Paris T. , Liao Yang , Le Roux Véronique , Behn Mark D.
Published: November 2019

Gravity, magnetic, and bathymetry data collected along a continuous 1,400‐km‐long spreading‐parallel flow line across the Mid‐Atlantic Ridge indicate significant tectonic and magmatic fluctuations in the formation of oceanic crust over a range of time scales. The transect spans from 28 Ma on the African Plate to 74 Ma on the North American plate, crossing the Mid‐Atlantic Ridge at 35.8°N. Gravity‐derived crustal thicknesses vary from 3–9 km with a standard deviation of 1.0 km. Spectral analysis of bathymetry and residual mantle Bouguer anomaly show a diffuse power at >1 Myr and concurrent peaks at 390, 550, and 950 kyr. Large‐scale (>10 km) mantle thermal and compositional heterogeneities, variations in upper mantle flow, and detachment faulting likely generate the >1 Myr diffuse power. The 550‐ and 950‐kyr peaks may reflect the presence of magma solitons and/or regularly spaced ~7.7 and 13.3 km short‐wavelength mantle compositional heterogeneities. The 390‐kyr spectral peak corresponds to the characteristic spacing of faults along the flow line. Fault spacing also varies over longer periods (>10 Myr), which we interpret as reflecting long‐lived changes in the fraction of tectonically versus magmatically accommodated extensional strain. A newly discovered off‐axis oceanic core complex (Kafka Dome) found at 8 Ma on the African plate further suggests extended time periods of tectonically‐dominated plate separation. Fault spacing negatively correlates with gravity‐derived crustal thickness, supporting a strong link between magma input and fault style at mid‐ocean ridges.
Embryonic progenitor pools generate diversity in fine-scale excitatory cortical subnetworks
Authors: Ellender Tommas J. , Avery Sophie V. , Mahfooz Kashif , Scaber Jakub , von Klemperer Alexander , Nixon Sophie L. , Buchan Matthew J. , van Rheede Joram J. , Gatti Aleksandra , Waites Cameron , Pavlou Hania J. , Sims David , Newey Sarah E. , Akerman Colin J.
Published: November 2019

The mammalian neocortex is characterized by a variety of neuronal cell types and precise arrangements of synaptic connections, but the processes that generate this diversity are poorly understood. Here we examine how a pool of embryonic progenitor cells consisting of apical intermediate progenitors (aIPs) contribute to diversity within the upper layers of mouse cortex. In utero labeling combined with single-cell RNA-sequencing reveals that aIPs can generate transcriptionally defined glutamatergic cell types, when compared to neighboring neurons born from other embryonic progenitor pools. Whilst sharing layer-associated morphological and functional properties, simultaneous patch clamp recordings and optogenetic studies reveal that aIP-derived neurons exhibit systematic biases in both their intralaminar monosynaptic connectivity and the post-synaptic partners that they target within deeper layers of cortex. Multiple cortical progenitor pools therefore represent an important factor in establishing diversity amongst local and long-range fine-scale glutamatergic connectivity, which generates subnetworks for routing excitatory synaptic information.
Application of convolutional neural networks to breast biopsies to delineate tissue correlates of mammographic breast density
Authors: Mullooly Maeve , Ehteshami Bejnordi Babak , Pfeiffer Ruth M. , Fan Shaoqi , Palakal Maya , Hada Manila , Vacek Pamela M. , Weaver Donald L. , Shepherd John A. , Fan Bo , Mahmoudzadeh Amir Pasha , Wang Jeff , Malkov Serghei , Johnson Jason M. , Herschorn Sally D. , Sprague Brian L. , Hewitt Stephen , Brinton Louise A. , Karssemeijer Nico , van der Laak Jeroen , Beck Andrew , Sherman Mark E. , Gierach Gretchen L.
Published: November 2019

Breast density, a breast cancer risk factor, is a radiologic feature that reflects fibroglandular tissue content relative to breast area or volume. Its histology is incompletely characterized. Here we use deep learning approaches to identify histologic correlates in radiologically-guided biopsies that may underlie breast density and distinguish cancer among women with elevated and low density. We evaluated hematoxylin and eosin (H&E)-stained digitized images from image-guided breast biopsies (n = 852 patients). Breast density was assessed as global and localized fibroglandular volume (%). A convolutional neural network characterized H&E composition. In total 37 features were extracted from the network output, describing tissue quantities and morphological structure. A random forest regression model was trained to identify correlates most predictive of fibroglandular volume (n = 588). Correlations between predicted and radiologically quantified fibroglandular volume were assessed in 264 independent patients. A second random forest classifier was trained to predict diagnosis (invasive vs. benign); performance was assessed using area under receiver-operating characteristics curves (AUC). Using extracted features, regression models predicted global (r = 0.94) and localized (r = 0.93) fibroglandular volume, with fat and non-fatty stromal content representing the strongest correlates, followed by epithelial organization rather than quantity. For predicting cancer among high and low fibroglandular volume, the classifier achieved AUCs of 0.92 and 0.84, respectively, with epithelial organizational features ranking most important. These results suggest non-fatty stroma, fat tissue quantities and epithelial region organization predict fibroglandular volume. The model holds promise for identifying histological correlates of cancer risk in patients with high and low density and warrants further evaluation.
Food authentication from shotgun sequencing reads with an application on high protein powders
Authors: Haiminen Niina , Edlund Stefan , Chambliss David , Kunitomi Mark , Weimer Bart C. , Ganesan Balasubramanian , Baker Robert , Markwell Peter , Davis Matthew , Huang B. Carol , Kong Nguyet , Prill Robert J. , Marlowe Carl H. , Quintanar André , Pierre Sophie , Dubois Geraud , Kaufman James H. , Parida Laxmi , Beck Kristen L.
Published: November 2019

Here we propose that using shotgun sequencing to examine food leads to accurate authentication of ingredients and detection of contaminants. To demonstrate this, we developed a bioinformatic pipeline, FASER (Food Authentication from SEquencing Reads), designed to resolve the relative composition of mixtures of eukaryotic species using RNA or DNA sequencing. Our comprehensive database includes >6000 plants and animals that may be present in food. FASER accurately identified eukaryotic species with 0.4% median absolute difference between observed and expected proportions on sequence data from various sources including sausage meat, plants, and fish. FASER was applied to 31 high protein powder raw factory ingredient total RNA samples. The samples mostly contained the expected source ingredient, chicken, while three samples unexpectedly contained pork and beef. Our results demonstrate that DNA/RNA sequencing of food ingredients, combined with a robust analysis, can be used to find contaminants and authenticate food ingredients in a single assay.
A quantitative description of the transition between intuitive altruism and rational deliberation in iterated Prisoner’s Dilemma experiments
Authors: Gallotti Riccardo , Grujić Jelena
Published: November 2019

What is intuitive: pro-social or anti-social behaviour? To answer this fundamental question, recent studies analyse decision times in game theory experiments under the assumption that intuitive decisions are fast and that deliberation is slow. These analyses keep track of the average time taken to make decisions under different conditions. Lacking any knowledge of the underlying dynamics, such simplistic approach might however lead to erroneous interpretations. Here we model the cognitive basis of strategic cooperative decision making using the Drift Diffusion Model to discern between deliberation and intuition and describe the evolution of the decision making in iterated Prisoner’s Dilemma experiments. We find that, although initially people’s intuitive decision is to cooperate, rational deliberation quickly becomes dominant over an initial intuitive bias towards cooperation, which is fostered by positive interactions as much as frustrated by a negative one. However, this initial pro-social tendency is resilient, as after a pause it resets to the same initial value. These results illustrate the new insight that can be achieved thanks to a quantitative modelling of human behavior.
Associations of parental age with offspring all-cause and cause-specific adult mortality
Authors: Carslake David , Tynelius Per , van den Berg Gerard J. , Davey Smith George
Published: November 2019

People are having children later in life. The consequences for offspring adult survival have been little studied due to the need for long follow-up linked to parental data and most research has considered offspring survival only in early life. We used Swedish registry data to examine all-cause and cause-specific adult mortality (293,470 deaths among 5,204,433 people, followed up to a maximum of 80 years old) in relation to parental age. For most common causes of death adult survival was improved in the offspring of older parents (HR for all-cause survival was 0.96 (95% CI: 0.96, 0.97) and 0.98 (0.97, 0.98) per five years of maternal and paternal age, respectively). The childhood environment provided by older parents may more than compensate for any physiological disadvantages. Within-family analyses suggested stronger benefits of advanced parental age. This emphasises the importance of secular trends; a parent’s later children were born into a wealthier, healthier world. Sibling-comparison analyses can best assess individual family planning choices, but our results suggested a vulnerability to selection bias when there is extensive censoring. We consider the numerous causal and non-causal mechanisms which can link parental age and offspring survival, and the difficulty of separating them with currently available data.
A dose response model for quantifying the infection risk of antibiotic-resistant bacteria
Authors: Chandrasekaran Srikiran , Jiang Sunny C.
Published: November 2019

Quantifying the human health risk of microbial infection helps inform regulatory policies concerning pathogens, and the associated public health measures. Estimating the infection risk requires knowledge of the probability of a person being infected by a given quantity of pathogens, and this relationship is modeled using pathogen specific dose response models (DRMs). However, risk quantification for antibiotic-resistant bacteria (ARB) has been hindered by the absence of suitable DRMs for ARB. A new approach to DRMs is introduced to capture ARB and antibiotic-susceptible bacteria (ASB) dynamics as a stochastic simple death (SD) process. By bridging SD with data from bench experiments, we demonstrate methods to (1) account for the effect of antibiotic concentrations and horizontal gene transfer on risk; (2) compute total risk for samples containing multiple bacterial types (e.g., ASB, ARB); and (3) predict if illness is treatable with antibiotics. We present a case study of exposure to a mixed population of Gentamicin-susceptible and resistant Escherichia coli and predict the health outcomes for varying Gentamicin concentrations. Thus, this research establishes a new framework to quantify the risk posed by ARB and antibiotics.
Impact of Direct Acting Antivirals on Survival in Patients with Chronic Hepatitis C and Hepatocellular Carcinoma
Authors: Kamp William M. , Sellers Cortlandt M. , Stein Stacey , Lim Joseph K. , Kim Hyun S.
Published: November 2019

With the increasing use of direct-acting antivirals (DAA) for treatment of chronic hepatitis C virus (HCV) infection, we looked at the impact of DAA use and 12-week sustained viral response (SVR12) in patients with hepatocellular carcinoma (HCC) and HCV. This is a retrospective analysis of 969 HCC patients diagnosed from 2005 to 2016 at an urban tertiary-care hospital. Kaplan-Meier curves and multivariable Cox proportional hazards models were used to assess survival. Median overall survival of the cohort was 24.2 months. 470 patients had HCV (56%). 123 patients received DAA therapies for HCV (26.2%), 83 of whom achieved SVR12 (67.4%). HCV-positive and HCV-negative patients had similar survival, 20.7 months vs 17.4 months (p = 0.22). Patients receiving DAA therapy had an overall survival of 71.8 months vs 11.6 months for patients without (p < 0.0001). DAA patients who achieved SVR12 had an overall survival of 75.6 months vs. 26.7 months in the non SVR12 group (p < 0.0001). Multivariable analysis revealed AJCC, Child-Pugh Score, MELD, tumor size, tumor location, cancer treatment type, receiving DAA treatment and achieving SVR12 had independent influence on survival (p < 0.05). This suggests DAA therapy and achieving SVR12 is associated with increased overall survival in HCV patients with HCC.
Correlative light and scanning electron microscopy (CLSEM) for analysis of bacterial infection of polarized epithelial cells
Authors: Kommnick Carina , Lepper Andrea , Hensel Michael
Published: November 2019

Infection of mammalian host cells by bacterial pathogens is a highly dynamic process and microscopy is instrumental to reveal the cellular and molecular details of host-pathogen interactions. Correlative light and electron microscopy (CLEM) combines the advantages of three-dimensional live cell imaging with ultrastructural analysis. The analyses of adhesion to, and invasion of polarized epithelial cells by pathogens often deploys scanning electron microscopy (SEM), since surface structures of the apical brush border can be analyzed in detail. Most available CLEM approaches focus on relocalization of separated single cells in different imaging modalities, but are not readily applicable to polarized epithelial cell monolayers, since orientation marks on substrate are overgrown during differentiation. To address this problem, we developed a simple and convenient workflow for correlative light and scanning electron microscopy (CLSEM), using gold mesh grids as carrier for growth of epithelial cell monolayers, and for imaging infection. The approach allows fast live cell imaging of bacterial infection of polarized cells with subsequent analyses by SEM. As examples for CLSEM applications, we investigated trigger invasion by Salmonella enterica, zipper invasion by Listeria monocytogenes, and the enterocyte attachment and effacement phenotype of enteropathogenic Escherichia coli. Our study demonstrates the versatile use of gold mesh grids for CLSEM of the interaction of bacterial pathogens with the apical side of polarized epithelial cells.
Tadalafil Treatment Improves Inflammation, Cognitive Function, And Mismatch Negativity Of Patients With Low Urinary Tract Symptoms And Erectile Dysfunction
Authors: Urios Amparo , Ordoño Felipe , García-García Raquel , Mangas-Losada Alba , Leone Paola , José Gallego Juan , Cabrera-Pastor Andrea , Megías Javier , Fermin Ordoño Juan , Felipo Vicente , Montoliu Carmina
Published: November 2019

Patients with Benign prostatic hyperplasia, low urinary tract symptoms, and erectile dysfunction (BPH/LUTS-ED) present chronic inflammation. We studied in patients with BPH/LUTS-ED the effect of tadalafil treatment (5 mg/day) on changes in peripheral inflammation, cognitive function, and the auditory evoked potential, “mismatch negativity” (MMN). Nine patients with BPH/LUTS-ED and 12 controls performed psychometric tests, MMN. IL-6, IL-17, IL-18, cGMP and CD4+CD28− autoreactive T-cells were measured in blood. Patients with BPH/LUTS-ED performed psychometric tests, MMN, and blood extraction at baseline and after tadalafil treatment. Patients with BPH/LUTS-ED showed increased CD4+CD28− autoreactive T-cells (p < 0.05), and higher levels of pro-inflammatory interleukins IL-6 (p < 0.001), IL-17 and IL-18 (p < 0.05), compared to controls. Patients got lower scores than controls in psychometric tests assessing mental processing speed and attention (p < 0.05), and showed lower amplitude (p < 0.01) and area (p < 0.05) of MMN wave than controls. Inflammatory, psychometric and electrophysiological parameters were normalized after tadalafil treatment. In conclusion, there is a pro-inflammatory environment in blood in patients with BPH/LUTS-ED which would induce cognitive impairment and alter MMN. Phosphodiesterase-5 inhibition with tadalafil exerts anti-inflammatory effects and ameliorates cognitive function and MMN parameters. Tadalafil could be a promising candidate for chronic treatment in other inflammatory pathologies associated with mild cognitive impairment.
Cooling history and emplacement of a pyroxenitic lava as proxy for understanding Martian lava flows
Authors: Murri Mara , Domeneghetti Maria C. , Fioretti Anna M. , Nestola Fabrizio , Vetere Francesco , Perugini Diego , Pisello Alessandro , Faccenda Manuele , Alvaro Matteo
Published: November 2019

Terrestrial analogues are often investigated to get insights into the geological processes occurring on other planetary bodies. Due to its thickness and petrological similarities, the pyroxenitic layer of the 120m-thick magmatic pile Theo’s Flow (Archean Abitibi greenstone belt Ontario, Canada), has always been regarded as the terrestrial analogue for Martian nakhlites. However, its origin and cooling history and, as a consequence those of nakhlites, have always been a matter of vigorous debate. Did this lava flow originate from a single magmatic event similar to those supposed to occur on Mars or do the different units derive from multiple eruptions? We demonstrate, by a combination of geothermometric constraints on augite single crystals and numerical simulations, that Theo’s Flow has been formed by multiple magma emplacements that occurred at different times. This discovery supports the idea that the enormous lava flows with similar compositions observed on Mars could be the result of a process where low viscosity lavas are emplaced during multiple eruptions. This has profound implications for understanding the multiscale mechanisms of lava flow emplacement on Earth and other planetary bodies.
Exploring anticancer activity of structurally modified benzylphenoxyacetamide (BPA); I: Synthesis strategies and computational analyses of substituted BPA variants with high anti-glioblastoma potential
Authors: Stalinska Joanna , Houser Lisa , Rak Monika , Colley Susan B. , Reiss Krzysztof , Jursic Branko S.
Published: November 2019

Structural variations of the benzylphenoxyacetamide (BPA) molecular skeleton were explored as a viable starting point for designing new anti-glioblastoma drug candidates. Hand-to-hand computational evaluation, chemical modifications, and cell viability testing were performed to explore the importance of some of the structural properties in order to generate, retain, and improve desired anti-glioblastoma characteristics. It was demonstrated that several structural features are required to retain the anti-glioblastoma activity, including a carbonyl group of the benzophenone moiety, as well as 4′-chloro and 2,2-dimethy substituents. In addition, the structure of the amide moiety can be modified in such a way that desirable anti-glioblastoma and physical properties can be improved. Via these structural modifications, more than 50 compounds were prepared and tested for anti-glioblastoma activity. Four compounds were identified (HR28, HR32, HR37, and HR46) that in addition to HR40 (PP1) from our previous study, have been determined to have desirable physical and biological properties. These include high glioblastoma cytotoxicity at low μM concentrations, improved water solubility, and the ability to penetrate the blood brain barrier (BBB), which indicate a potential for becoming a new class of anti-glioblastoma drugs.
Rotational Three-dimensional OCTA: a Notable New Imaging Tool to Characterize Type 3 Macular Neovascularization
Authors: Borrelli Enrico , Sacconi Riccardo , Klose Gerd , de Sisternes Luis , Bandello Francesco , Querques Giuseppe
Published: November 2019

This study explored whether rotational three-dimensional (3D) visualization of optical coherence tomography angiography (OCTA) volume data may yield valuable information regarding type 3 macular neovascularization (MNV). In this retrospective, cross-sectional study, we collected data from 15 eyes (13 patients) with treatment-naïve type 3 MNV in their post-nascent stage and age-related macular degeneration (AMD). Subjects were imaged with the SS-OCT system (PLEX Elite 9000, Carl Zeiss Meditec Inc., Dublin, CA, USA). The OCTA volume data were processed with a prototype volume projection removal algorithm and then analyzed using volumetric visualization techniques in order to obtain a 3D visualization of the region occupied by type 3 MNV. The two-dimensional and three-dimensional OCTA images were investigated. Mean ± SD age was 75.1 ± 7.4 years. BCVA was 0.42 ± 0.21 LogMAR in the study eyes. Considering the cohort of analyzed eyes, on rotational 3D OCTA images, a total of 35 neovascular lesions (vs 22 lesions detected on 2D OCTA images) rising from the deep vascular complex and variably spanning the outer retinal layers and eventually reaching the RPE/sub-RPE space were detected. Nine of 35 lesions had a saccular shape, while the remaining cases had a filiform shape. On rotational 3D OCTA images, these lesions were inclined on the three planes, instead of perpendicular to the RPE/Bruch’s membrane. In conclusion, this study used an algorithm to obtain rotational three-dimensional visualization of type 3 MNV. This approach seems to increase the detection rate for these lesions and to be useful to offer new insight into type 3 MNV.
Immune cell type, cell activation, and single cell heterogeneity revealed by label-free optical methods
Authors: Pavillon Nicolas , Smith Nicholas I.
Published: November 2019

Measurement techniques that allow the global analysis of cellular responses while retaining single-cell sensitivity are increasingly needed in order to understand complex and dynamic biological processes. In this context, compromises between sensitivity, degree of multiplexing, throughput, and invasiveness are often unavoidable. We present here a noninvasive optical approach that can retrieve quantitative biomarkers of both morphological and molecular phenotypes of individual cells, based on a combination of quantitative phase imaging and Raman spectroscopy measurements. We then develop generalized statistical tools to assess the influence of both controlled (cell sub-populations, immune stimulation) and uncontrolled (culturing conditions, animal variations, etc.) experimental parameters on the label-free biomarkers. These indicators can detect different macrophage cell sub-populations originating from different progenitors as well as their activation state, and how these changes are related to specific differences in morphology and molecular content. The molecular indicators also display further sensitivity that allow identification of other experimental conditions, such as differences between cells originating from different animals, allowing the detection of outlier behaviour from given cell sub-populations.
The origin of the exceptionally low activation energy of oxygen vacancy in tantalum pentoxide based resistive memory
Authors: Hur Ji-Hyun
Published: November 2019

It is well known that collective migrations of oxygen vacancies in oxide is the key principle of resistance change in oxide-based resistive memory (OxRAM). The practical usefulness of OxRAM mainly arises from the fact that these oxygen vacancy migrations take place at relatively low operating voltages. The activation energy of oxygen vacancy migration, which can be inferred from the operational voltage of an OxRAM, is much smaller compared to the experimentally measured activation energy of oxygen, and the underlying mechanism of the discrepancy has not been highlighted yet. We ask this fundamental question in this paper for tantalum oxide which is one of the most commonly employed oxides in OxRAMs and try the theoretical answer based on the first-principles calculations. From the results, it is proven that the exceptionally large mobility of oxygen vacancy expected by the switching model can be well explained by the exceptionally low activation barrier of positively charged oxygen vacancy within the two-dimensional substructure.