bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel High-Throughput Quantitation of Potent hERG Blocker Dofetilide in Human Plasma by Liquid Chromatography Tandem Mass Spectrometry: Application in a Phase 1 ECG Biomarker Validation Study
Authors: Matta Murali K , Narayanasamy Suresh , Vicente Jose , Zusterzeel Robbert , Patel Vikram , Strauss David G 
Published: June 2019

Abstract
The authors developed a novel, sensitive high-throughput ultra-performance liquid chromatography-tandem mass spectrometric method for the determination of dofetilide in human plasma. To compensate for the matrix effect, a deuterated internal standard was used. The method employed a very low sample volume (50 μL) of plasma for sample processing by using simple protein precipitation extraction in a 96-well plate. The extracted samples were chromatographed on an Acquity BEH C18 column (2.1 × 100 mm, 1.7 μm) and eluted in a gradient manner at a flow rate of 0.5 mL/min for 2 min using 5 mM ammonium formate (0.1% formic acid) and methanol. The calibration curve was linear from 25 to 2,500 pg/mL with a correlation coefficient (r2) ≥ 0.99 (0.9969–0.9980; n = 3). The developed method was validated as per the current United States Food and Drug Administration’s guidance for industry on ‘Bioanalytical Method Validation’. The multiple reaction–monitoring mode was employed for quantitation of dofetilide with m/z 442.2/198.2 and dofetilide d4 with m/z 446.2/198.2. The validated method was used for evaluation of dofetilide concentration in the Comprehensive in vitro Proarrhythmia Assay phase 1 electrocardiogramic biomarker validation study.
Beyond BRCA: Review of Hereditary Syndromes Predisposing to Breast Cancer
Authors: Nguyen Jonathan V , Thomas Martha H 
Published: June 2019

Abstract
The majority of our hereditary breast cancer genes incur not only an increased risk for breast cancer but for other malignancies as well. Knowing whether an individual carries a pathogenic variant in a hereditary breast cancer gene can affect not only screening for the patient but for his or her family members as well. Identifying and appropriately testing individuals via multigene panels allows for risk reduction and early surveillance in at-risk individuals. Radiologists can serve as first-line identifiers of women who are at risk of having an inherited predisposition to breast cancer because they are interacting with all women receiving routine screening mammograms, and collecting family history suggestive of the presence of a mutation. We outline here the 11 genes associated with high breast cancer risk discussed in the National Comprehensive Cancer Network Genetic/Familial High-Risk: Breast and Ovarian (version 3.2019) as having additional breast cancer screening recommendations outside of annual mammography to serve as a guide for breast cancer screening and risk reduction, as well as recommendations for surveillance of nonbreast cancers.
Considerations for Insect Learning in Integrated Pest Management
Authors: Little Catherine M , Chapman Thomas W , Hillier N Kirk 
Published: June 2019

AbstractThe past 100 yr have seen dramatic philosophical shifts in our approach to controlling or managing pest species. The introduction of integrated pest management in the 1970s resulted in the incorporation of biological and behavioral approaches to preserve ecosystems and reduce reliance on synthetic chemical pesticides. Increased understanding of the local ecosystem, including its structure and the biology of its species, can improve efficacy of integrated pest management strategies. Pest management strategies incorporating insect learning paradigms to control insect pests or to use insects to control other pests can mediate risk to nontarget insects, including pollinators. Although our understanding of insect learning is in its early stages, efforts to integrate insect learning into pest management strategies have been promising. Due to considerable differences in cognitive abilities among insect species, a case-by-case assessment is needed for each potential application of insect learning within a pest management strategy.
Loss of hnRNP A1 in murine skeletal muscle exacerbates high-fat diet-induced onset of insulin resistance and hepatic steatosis
Authors: Zhao Mingxia , Shen Lihong , Ouyang Zijun , Li Manru , Deng Guoliang , Yang Chenxi , Zheng Wei , Kong Lingdong , Wu Xuefeng , Wu Xudong , Guo Wenjie , Yin Ye , Xu Qiang , Sun Yang 
Published: June 2019

AbstractImpairment of glucose (Glu) uptake and storage by skeletal muscle is a prime risk factor for the development of metabolic diseases. Heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) is a highly abundant RNA-binding protein that has been implicated in diverse cellular functions. The aim of this study was to investigate the function of hnRNP A1 on muscle tissue insulin sensitivity and systemic Glu homeostasis. Our results showed that conditional deletion of hnRNP A1 in the muscle gave rise to a severe insulin resistance phenotype in mice fed a high-fat diet (HFD). Conditional knockout mice fed a HFD showed exacerbated obesity, insulin resistance, and hepatic steatosis. In vitro interference of hnRNP A1 in C2C12 myotubes impaired insulin signal transduction and inhibited Glu uptake, whereas hnRNP A1 overexpression in C2C12 myotubes protected against insulin resistance induced by supraphysiological concentrations of insulin. The expression and stability of glycogen synthase (gys1) mRNA were also decreased in the absence of hnRNP A1. Mechanistically, hnRNP A1 interacted with gys1 and stabilized its mRNA, thereby promoting glycogen synthesis and maintaining the insulin sensitivity in muscle tissue. Taken together, our findings are the first to show that reduced expression of hnRNP A1 in skeletal muscle affects the metabolic properties and systemic insulin sensitivity by inhibiting glycogen synthesis.
The Medico-Legal ‘Making’ of ‘The Transgender Child’
Authors: Brunskell-Evans Heather 
Published: June 2019

Abstract
Thirty years ago, the transgender child would have made no sense to the general public, nor to young people. Today, children and adolescents declare themselves transgender, the National Health Service diagnoses ‘gender dysphoria’, and laws and policy are developed which uphold young people’s ‘choice’ to transition and to authorize stages at which medical intervention is permissible and desirable. The figure of the ‘transgender child’ presumed by medicine and law is not a naturally occurring category of person external to medical diagnosis and legal protection. Medicine and law construct the ‘transgender child’ rather than that the ‘transgender child’ exists independently of medico-legal discourse. The ethical issue of whether the child and young person can ‘consent’ to social and medical transition goes beyond legal assessment of whether a person under16 years has the mental capacity to consent, understand to what s/he is consenting, and can express independent wishes. It shifts to examination of the recent making of ‘the transgender child’ through the complex of power/knowledge/ethics of medicine and the law of which the child can have no knowledge but within which its own desires are both constrained and incited.
Magnetic inhibition of convection in O-star envelopes
Authors: MacDonald James , Petit Véronique 
Published: June 2019

ABSTRACT
It has been suggested that the absence of macroturbulence in the atmosphere of NGC 1624−2 is due its strong magnetic field (the strongest known for a massive O star) suppressing convection in its outer layers, removing the mechanism thought responsible for the observed macroturbulence in stars with lower field strengths. Here, we develop and apply a criterion for a uniform magnetic field to suppress convection in stellar envelopes in which radiation pressure is a significant contributor to hydrostatic balance. We find upper mass limits of ∼55 and ∼30 M⊙ for magnetic suppression to be possible in zero-age main-sequence and terminal-age main-sequence stars, respectively. For evolved stars, magnetic suppression of convection can significantly alter the stars’ evolution. For NGC 1624−2, we find that a polar dipole strength of 16.5 ± 5.9 kG is required to suppress convection, in good agreement with the value ∼20 kG measured by spectropolarimetry.
SIRT7 mediates L1 elements transcriptional repression and their association with the nuclear lamina
Authors: Vazquez Berta N , Thackray Joshua K , Simonet Nicolas G , Chahar Sanjay , Kane-Goldsmith Noriko , Newkirk Simon J , Lee Suman , Xing Jinchuan , Verzi Michael P , An Wenfeng , Vaquero Alejandro , Tischfield Jay A , Serrano Lourdes 
Published: June 2019

AbstractLong interspersed elements-1 (LINE-1, L1) are retrotransposons that hold the capacity of self-propagation in the genome with potential mutagenic outcomes. How somatic cells restrict L1 activity and how this process becomes dysfunctional during aging and in cancer cells is poorly understood. L1s are enriched at lamin-associated domains, heterochromatic regions of the nuclear periphery. Whether this association is necessary for their repression has been elusive. Here we show that the sirtuin family member SIRT7 participates in the epigenetic transcriptional repression of L1 genome-wide in both mouse and human cells. SIRT7 depletion leads to increased L1 expression and retrotransposition. Mechanistically, we identify a novel interplay between SIRT7 and Lamin A/C in L1 repression. Our results demonstrate that SIRT7-mediated H3K18 deacetylation regulates L1 expression and promotes L1 association with elements of the nuclear lamina. The failure of such activity might contribute to the observed genome instability and compromised viability in SIRT7 knockout mice. Overall, our results reveal a novel function of SIRT7 on chromatin organization by mediating the anchoring of L1 to the nuclear envelope, and a new functional link of the nuclear lamina with transcriptional repression.
HMMRATAC: a Hidden Markov ModeleR for ATAC-seq
Authors: Tarbell Evan D , Liu Tao 
Published: June 2019

Abstract
ATAC-seq has been widely adopted to identify accessible chromatin regions across the genome. However, current data analysis still utilizes approaches initially designed for ChIP-seq or DNase-seq, without considering the transposase digested DNA fragments that contain additional nucleosome positioning information. We present the first dedicated ATAC-seq analysis tool, a semi-supervised machine learning approach named HMMRATAC. HMMRATAC splits a single ATAC-seq dataset into nucleosome-free and nucleosome-enriched signals, learns the unique chromatin structure around accessible regions, and then predicts accessible regions across the entire genome. We show that HMMRATAC outperforms the popular peak-calling algorithms on published human ATAC-seq datasets. We find that single-end sequenced or size-selected ATAC-seq datasets result in a loss of sensitivity compared to paired-end datasets without size-selection.
SMARTer single cell total RNA sequencing
Authors: Verboom Karen , Everaert Celine , Bolduc Nathalie , Livak Kenneth J , Yigit Nurten , Rombaut Dries , Anckaert Jasper , Lee Simon , Venø Morten T , Kjems Jørgen , Speleman Frank , Mestdagh Pieter , Vandesompele Jo 
Published: June 2019

Abstract
Single cell RNA sequencing methods have been increasingly used to understand cellular heterogeneity. Nevertheless, most of these methods suffer from one or more limitations, such as focusing only on polyadenylated RNA, sequencing of only the 3′ end of the transcript, an exuberant fraction of reads mapping to ribosomal RNA, and the unstranded nature of the sequencing data. Here, we developed a novel single cell strand-specific total RNA library preparation method addressing all the aforementioned shortcomings. Our method was validated on a microfluidics system using three different cancer cell lines undergoing a chemical or genetic perturbation and on two other cancer cell lines sorted in microplates. We demonstrate that our total RNA-seq method detects an equal or higher number of genes compared to classic polyA[+] RNA-seq, including novel and non-polyadenylated genes. The obtained RNA expression patterns also recapitulate the expected biological signal. Inherent to total RNA-seq, our method is also able to detect circular RNAs. Taken together, SMARTer single cell total RNA sequencing is very well suited for any single cell sequencing experiment in which transcript level information is needed beyond polyadenylated genes.
Banks’ Balance Sheets and Liquidation Values: Evidence from Real Estate Collateral
Authors: Ramcharan Rodney 
Published: June 2019

Abstract
This paper finds that declining bank equity or liquidity reduces liquidation values of bank-owned real estate and accelerates the pace of asset sales. Buyers of these assets earn significant returns for providing liquidity to banks, as prices tend to rebound sharply after sales by illiquid banks. Lower liquidation values also depress the prices of nearby real estate transactions. Policy interventions, such as equity injections and central bank asset purchases, increase liquidation values by providing institutions with the balance sheet capacity to slow asset sales. This evidence suggests that balance sheet adjustments at financial institutions can explain real asset price dynamics.
Authors have furnished an Internet Appendix, which is available on the Oxford University Press Web site next to the link to the final published paper online.
Subcellular Targets of Zinc Oxide Nanoparticles During the Aging Process: Role of Cross-talk Between Mitochondrial Dysfunction and Endoplasmic Reticulum Stress in the Genotoxic Response
Authors: Wang Meimei , Wang Juan , Liu Yun , Wang Jingjing , Nie Yaguang , Si Bo , Liu Ying , Wang Xue , Chen Shaopeng , Hei Tom K , Wu Lijun , Zhao Guoping , Xu An 
Published: June 2019

Abstract
Zinc oxide nanoparticles (ZnO NPs) are being produced abundantly and applied increasingly in various fields. The special physicochemical characteristics of ZnO NPs make them incline to undergo physicochemical transformation over time (aging), which modify their bioavailability and toxicity. However, the subcellular targets and the underlying molecular mechanisms involved in the genotoxicity induced by ZnO NPs during aging process are still unknown. This study found that the acute cytotoxic effects of fresh ZnO NPs was largely regulated by mitochondria-dependent apoptosis, which the level of cleaved Caspase-3 and mitochondria damage were significantly higher than that of 60-day-aged ZnO NPs. In contrast, aged ZnO NPs induced more reactive oxygen species (ROS) production and endoplasmic reticulum (ER) stress marker protein (BIP/GRP78) expression and their genotoxicity could be dramatically suppressed by either ROS scavengers (dimethyl sulfoxide, catalase, and sodium azide) or ER stress inhibitor (4-phenylbutyrate). Using mitochondrial-DNA deficient (ρ0) AL cells, we further found that ER stress induced by aged ZnO NPs was triggered by ROS generated from mitochondria, which eventually mediated the genotoxicity of aged NPs. Our data provided novel information on better understanding the contribution of subcellular targets to the genotoxic response of ZnO NPs during the aging process.
Functional outcome and muscle wasting in adults with tetanus
Authors: Trung Truong N , Duoc Nguyen V T , Nhat Le T H , Yen Lam M , Hao Nguyen V , Truong Nguyen T , Duong Ha T H , Thuy Duong B , Phong Nguyen T , Tan Le V , Puthucheary Zudin A , Thwaites C Louise 
Published: June 2019

Abstract

Background
In many countries, in-hospital survival from tetanus is increasing, but long-term outcome is unknown. In high-income settings, critical illness is associated with muscle wasting and poor functional outcome, but there are few data from resource-limited settings. In this study we aimed to assess muscle wasting and long-term functional outcome in adults with tetanus.

Methods
In a prospective observational study involving 80 adults with tetanus, sequential rectus femoris ultrasound measurements were made at admission, 7 days, 14 days and hospital discharge. Functional outcome was assessed at hospital discharge using the Timed Up and Go test, Clinical Frailty Score, Barthel Index and RAND 36-item Short Form Health Survey (SF-36) and 3 and 6 months after discharge using the SF-36 and Barthel Index.

Results
Significant muscle wasting occurred between hospital admission and discharge (p&lt;0.01), particularly in severe disease, where a median 23.49% (interquartile range 10.01–26.07) reduction in rectus femoris cross-sectional area occurred in those with severe (Ablett grades 3 and 4) disease. Muscle mass at discharge was related to objective and subjective measures of physical and emotional function at discharge and 3 and 6 months after discharge. In patients &gt;70 y of age, functional recovery at 6 months was reduced compared with younger patients. Hospital-acquired infection and age were risk factors for muscle wasting.

Conclusions
Significant muscle wasting during hospitalization occurred in patients with tetanus, the extent of which correlates with functional outcome.
Within-host infectious disease models accommodating cellular coinfection, with an application to influenza†
Authors: Koelle Katia , Farrell Alex P , Brooke Christopher B , Ke Ruian 
Published: June 2019

Abstract
Within-host models are useful tools for understanding the processes regulating viral load dynamics. While existing models have considered a wide range of within-host processes, at their core these models have shown remarkable structural similarity. Specifically, the structure of these models generally consider target cells to be either uninfected or infected, with the possibility of accommodating further resolution (e.g. cells that are in an eclipse phase). Recent findings, however, indicate that cellular coinfection is the norm rather than the exception for many viral infectious diseases, and that cells with high multiplicity of infection are present over at least some duration of an infection. The reality of these cellular coinfection dynamics is not accommodated in current within-host models although it may be critical for understanding within-host dynamics. This is particularly the case if multiplicity of infection impacts infected cell phenotypes such as their death rate and their viral production rates. Here, we present a new class of within-host disease models that allow for cellular coinfection in a scalable manner by retaining the low-dimensionality that is a desirable feature of many current within-host models. The models we propose adopt the general structure of epidemiological ‘macroparasite’ models that allow hosts to be variably infected by parasites such as nematodes and host phenotypes to flexibly depend on parasite burden. Specifically, our within-host models consider target cells as ‘hosts’ and viral particles as ‘macroparasites’, and allow viral output and infected cell lifespans, among other phenotypes, to depend on a cell’s multiplicity of infection. We show with an application to influenza that these models can be statistically fit to viral load and other within-host data, and demonstrate using model selection approaches that they have the ability to outperform traditional within-host viral dynamic models. Important in vivo quantities such as the mean multiplicity of cellular infection and time-evolving reassortant frequencies can also be quantified in a straightforward manner once these macroparasite models have been parameterized. The within-host model structure we develop here provides a mathematical way forward to address questions related to the roles of cellular coinfection, collective viral interactions, and viral complementation in within-host viral dynamics and evolution.
Efferocytosis perpetuates substance accumulation inside macrophage populations
Authors: Ford Hugh Z. , Zeboudj Lynda , Purvis Gareth S. D. , ten Bokum Annemieke , Zarebski Alexander E. , Bull Joshua A. , Byrne Helen M. , Myerscough Mary R. , Greaves David R. 
Published: June 2019

In both cells and animals, cannibalism can transfer harmful substances from the consumed to the consumer. Macrophages are immune cells that consume their own dead via a process called cannibalistic efferocytosis. Macrophages that contain harmful substances are found at sites of chronic inflammation, yet the role of cannibalism in this context remains unexplored. Here we take mathematical and experimental approaches to study the relationship between cannibalistic efferocytosis and substance accumulation in macrophages. Through mathematical modelling, we deduce that substances which transfer between individuals through cannibalism will concentrate inside the population via a coalescence process. This prediction was confirmed for macrophage populations inside a closed system. We used image analysis of whole slide photomicrographs to measure both latex microbead and neutral lipid accumulation inside murine bone marrow-derived macrophages (10
4
–

10

5

cells

) following their stimulation into an inflammatory state
ex vivo
. While the total number of phagocytosed beads remained constant, cell death reduced cell numbers and efferocytosis concentrated the beads among the surviving macrophages. As lipids are also conserved during efferocytosis, these cells accumulated lipid derived from the membranes of dead and consumed macrophages (becoming macrophage foam cells). Consequently, enhanced macrophage cell death increased the rate and extent of foam cell formation. Our results demonstrate that cannibalistic efferocytosis perpetuates exogenous (e.g. beads) and endogenous (e.g. lipids) substance accumulation inside macrophage populations. As such, cannibalism has similar detrimental consequences in both cells and animals.