bluuebunny/crossref_metadata_2025_split huggingface dataset:
OCT angiography in optic disc drusen: comparison with structural and functional parameters
Authors: Engelke Hendrik , Shajari Mehdi , Riedel Julian , Mohr Niklas , Priglinger Siegfried G , Mackert Marc J 
Published: November 2019

BackgroundOptic disc drusen (ODD) can cause retinal nerve fibre layer (RNFL) defects with progressive visual field (VF) loss. Microvascular changes are discussed as a cause. We measured the vessel density (VD) of the optic disc in ODD using optical coherence tomography angiography and compared it with a normal population. Another intent was to determine the sensitivity and correlations in comparison with functional (VF) and structural parameters (RNFL, minimum rim width (MRW), ganglion cell complex (GCC)).MethodsWe analysed the VD of 25 patients with ODD and an age-matched control population including 25 healthy participants using AngioVue (Optovue, Fremont, CA, USA). We obtained data about RNFL, GCC, Bruch’s membrane opening MRW (Spectralis HRA & OCT; Heidelberg Engineering, Germany) and VF (standard automated perimetry; SITA 24-2). Low image quality and pathologies interfering with the diagnostics were excluded. Parametric data were analysed using the t-test and non-parametric values using the Mann-Whitney U test. Linear regression analysis was used to determine correlations using the Bravais-Pearson test.ResultsThe VD was significantly reduced in the ODD group especially the peripapillary capillary VD (n=45 vs 50 eyes; mean 43.15% vs 51.70%). Peripapillary RNFL thickness correlated with the VD significantly (r=0.902 (n=44), 0.901 (n=44), 0.866 (n=45)). The RNFL analysis showed a reduction in ODD, especially the superior hemisphere (mean 107 µm, 129 µm; 49 vs 50 eyes). The GCC was significantly lower in the ODD group (n=38 vs 40; mean 87 µm vs 98 µm). Positive correlation between the VD and the GCC was significant (n=37, r=0.532). There is a significant negative correlation (n=19; r=−0.726) between the VD and the pattern standard deviation (PSD).ConclusionThis study reveals significant peripapillary microvascular changes in patients with ODD correlating with the RNFL and GCC reduction. There is a negative correlation between the PSD and the VD.
Development and implementation of electronic medical handovers across psychiatric hospitals: quality improvement initiative
Authors: Skelton Luke , Rogers Jonathan , Kalafatis Chris 
Published: November 2019

A lack of integration between internal processes and failure to use the full potential of information technology (IT) systems is common in psychiatric hospitals. We aimed to reduce the number of out-of-hours medical errors by ensuring that there is consistent and transparent weekend medical handover by creating an electronic handover system that is easy to use, robust and embedded into the existing trust IT systems. We employed quality improvement (QI) methodology to address this issue.After trialling in a single site followed by six cycles of improvement, the weekend medical handover system is now in use across four boroughs and has been integrated into trust policy. It has received qualitative and quantitative evidence of improvement, with 100% of doctors reporting the system improved patient care and a 64% (from 11 to 4 events/year) reduction in moderate, severe and catastrophic adverse incidents occurring out-of-hours within the older adult service (p=0.29, χ21.117).The increasing number of complex patients with comorbid medical illness in psychiatric inpatient services demands robust handover systems similar to that of an acute trust. This QI work offers a template for achieving this across other psychiatric trusts and demonstrates the positive change that can be achieved.
Patterns of sexualised recreational drug use and its association with risk behaviours and sexual health outcomes in men who have sex with men in London, UK: a comparison of cross-sectional studies conducted in 2013 and 2016
Authors: Curtis Tyrone J , Rodger Alison J , Burns Fiona , Nardone Anthony , Copas Andrew , Wayal Sonali 
Published: November 2019

Objective
London has one of the highest identified prevalence of chemsex (sexualised recreational drug use) among men who have sex with men (MSM) in Europe. We examine MSM’s patterns of chemsex and its association with HIV/STI risk behaviours, STI diagnoses and sexual healthcare-seeking behaviours, including if HIV testing behaviour met UK national guidelines (three monthly if engaging in chemsex).

Methods
Cross-sectional survey data from 2013 (n=905) and 2016 (n=739) were collected using anonymous, self-administered questionnaires from MSM recruited in commercial gay venues in London, UK. Descriptive and multivariable analyses, stratified by self-reported HIV status, were conducted. Adjusted prevalence ratios (aPR) with 95% CIs were calculated.

Results
Comparing the 2013 and 2016 surveys, chemsex prevalence in the past year remained stable, in both HIV-negative/unknown-status MSM (20.9% in 2013 vs 18.7% in 2016, p=0.301) and HIV-positive MSM (41.6% in 2013 vs 41.7% in 2016, p=0.992). Combined 2013–2016 data showed that compared with other MSM, those reporting chemsex were more likely to report HIV/STI risk behaviours, including condomless anal intercourse with serodifferent HIV-status partners (HIV-negative/unknown-status men: aPR 2.36, 95% CI 1.68 to 3.30; HIV-positive men: aPR 4.19, 95% CI 1.85 to 9.50), and STI diagnoses in the past year (HIV-negative/unknown-status men: aPR 2.10, 95% CI 1.64 to 2.69; HIV-positive men: aPR 2.56, 95% CI 1.57 to 4.20). 68.6% of HIV-negative/unknown-status men reporting chemsex attended sexual health clinics and 47.6% had tested for HIV more than once in the past year.

Conclusions
Chemsex in London MSM remained stable but high, particularly among HIV-positive men. Irrespective of HIV status, chemsex was associated with engagement in HIV/STI risk behaviours. Frequency of HIV testing in the past year among HIV-negative/unknown-status men was below national recommendations. Promoting combination prevention strategies, including three monthly HIV/STI testing, access to pre-exposure prophylaxis/antiretroviral treatment and behavioural interventions among MSM reporting chemsex, remains vital to address sexual health inequalities in MSM.
Constraining the parameters of high-dimensional models with active learning
Authors: Caron Sascha , Heskes Tom , Otten Sydney , Stienen Bob 
Published: November 2019

AbstractConstraining the parameters of physical models with $$>5-10$$>5-10 parameters is a widespread problem in fields like particle physics and astronomy. The generation of data to explore this parameter space often requires large amounts of computational resources. The commonly used solution of reducing the number of relevant physical parameters hampers the generality of the results. In this paper we show that this problem can be alleviated by the use of active learning. We illustrate this with examples from high energy physics, a field where simulations are often expensive and parameter spaces are high-dimensional. We show that the active learning techniques query-by-committee and query-by-dropout-committee allow for the identification of model points in interesting regions of high-dimensional parameter spaces (e.g. around decision boundaries). This makes it possible to constrain model parameters more efficiently than is currently done with the most common sampling algorithms and to train better performing machine learning models on the same amount of data. Code implementing the experiments in this paper can be found on GitHub "Image missing"
Conformal GUT inflation, proton lifetime and non-thermal leptogenesis
Authors: Kumar K. Sravan , Moniz Paulo Vargas 
Published: November 2019

AbstractIn this paper, we generalize Coleman–Weinberg (CW) inflation in grand unified theories (GUTs) such as $$\text {SU}(5)$$SU(5) and $$\text {SO}(10)$$SO(10) by means of considering two complex singlet fields with conformal invariance. In this framework, inflation emerges from a spontaneously broken conformal symmetry. The GUT symmetry implies a potential with a CW form, as a consequence of radiative corrections. The conformal symmetry flattens the above VEV branch of the CW potential to a Starobinsky plateau. As a result, we obtain $$n_{s}\sim 1-\frac{2}{N}$$ns∼1-2N and $$r\sim \frac{12}{N^2}$$r∼12N2 for $$N\sim $$N∼ 50–60 e-foldings. Furthermore, this framework allow us to estimate the proton lifetime as $$\tau _{p}\lesssim 10^{40}$$τp≲1040 years, whose decay is mediated by the superheavy gauge bosons. Moreover, we implement a type I seesaw mechanism by weakly coupling the complex singlet, which carries two units of lepton number, to the three generations of singlet right handed neutrinos (RHNs). The spontaneous symmetry breaking of global lepton number amounts to the generation of neutrino masses. We also consider non-thermal leptogenesis in which the inflaton dominantly decays into heavy RHNs that sources the observed baryon asymmetry. We constrain the couplings of the inflaton field to the RHNs, which gives the reheating temperature as $$10^{6}\text { GeV}\lesssim T_{R}<10^{9}$$106GeV≲TR<109 GeV.
A Personalized Music Recommender System Using User Contents, Music Contents and Preference Ratings
Authors: Su Ja-Hwung , Chin Chu-Yu , Liao Yi-Wen , Yang Hsiao-Chuan , Tseng Vincent S. , Hsieh Sun-Yuan 
Published: November 2019

Recently, the advances in communication technologies have made music retrieval easier. Without downloading the music, the users can listen to music through online music websites. This incurs a challenging issue of how to provide the users with an effective online listening service. Although a number of past studies paid attention to this issue, the problems of new user, new item and rating sparsity are not easy to solve. To deal with these problems, in this paper, we propose a novel music recommender system that fuses user contents, music contents and preference ratings to enhance the music recommendation. For dealing with problem of new user, the user similarities are calculated by user profiles instead of traditional ratings. By the user similarities, the unknown ratings can be predicted using user-based Collaborative Filtering (CF). For dealing with problems of rating sparsity and new items, the unknown ratings are initialized by acoustic features and music genre ratings. Because the unknown ratings are initially imputed, the rating data will be enriched. Thereupon, the user preference can be predicted effectively by item-based CF. The evaluation results show that our proposed music recommender system performs better than the state-of-the-arts methods in terms of Root Mean Squared Error.
In Vitro Susceptibility and Florfenicol Resistance inCitrobacterIsolates and Whole-Genome Analysis of Multidrug-ResistantCitrobacter freundii
Authors: Zhou Wangxiao , Chen Qianqian , Qian Changrui , Shen Kai , Zhu Xinyi , Zhou Danying , Lu Wei , Sun Zhewei , Liu Hongmao , Li Kewei , Xu Teng , Bao Qiyu , Lu Junwan 
Published: November 2019

The genusCitrobacteris an opportunistic pathogen causing infections in animals, and the published data for its resistance to florfenicol are scarce. In this study, we investigated the antimicrobial susceptibility and molecular characteristics of florfenicol resistance genes amongCitrobacterisolates from animal and relevant environmental samples and conducted a comparative analysis of a multidrug-resistantCitrobacter freundiistrain isolated from a rabbit. Among 20Citrobacterstrains isolated from animal samples, resistance was most commonly observed to ampicillin (100%), tetracycline (75%), streptomycin (65%), florfenicol (60%), chloramphenicol (60%), and aztreonam (50%), while all the strains found in environmental samples were resistant to few antibiotics. The florfenicol resistance genefloRwas detected in 12 isolates (48%, 12/25) from animal samples, and all of thefloR-positive isolates were resistant to florfenicol with minimum inhibitory concentration (MIC) values ≥256 μg/mL. Sequencing and comparative analysis of the plasmids from a multidrug-resistantC. freundiiisolate named R47 showed that thefloR-containing region in the plasmid pR47-54 was a truncated transposon-like structure and could be found on both plasmids and chromosomes of bacteria of either animal or human origin. Furthermore, a range of antimicrobial and metal resistance genes associated with mobile genetic elements could be identified in pR47-54 and the other plasmid pR47-309 ofC. freundiiR47. These results provide in-depth views into the phenotypic and molecular characteristics ofCitrobacterisolates recovered from animal and relevant environmental samples, as well as highlight the role horizontal gene transfer plays in the dissemination of plasmid-encoded resistance genes.
Mevalonate Pathway Provides Ubiquinone to Maintain Pyrimidine Synthesis and Survival in p53-Deficient Cancer Cells Exposed to Metabolic Stress
Authors: Kaymak Irem , Maier Carina R. , Schmitz Werner , Campbell Andrew D. , Dankworth Beatrice , Ade Carsten P. , Walz Susanne , Paauwe Madelon , Kalogirou Charis , Marouf Hecham , Rosenfeldt Mathias T. , Gay David M. , McGregor Grace H. , Sansom Owen J. , Schulze Almut 
Published: November 2019

Abstract

Oncogene activation and loss of tumor suppressor function changes the metabolic activity of cancer cells to drive unrestricted proliferation. Moreover, cancer cells adapt their metabolism to sustain growth and survival when access to oxygen and nutrients is restricted, such as in poorly vascularized tumor areas. We show here that p53-deficient colon cancer cells exposed to tumor-like metabolic stress in spheroid culture activated the mevalonate pathway to promote the synthesis of ubiquinone. This was essential to maintain mitochondrial electron transport for respiration and pyrimidine synthesis in metabolically compromised environments. Induction of mevalonate pathway enzyme expression in the absence of p53 was mediated by accumulation and stabilization of mature SREBP2. Mevalonate pathway inhibition by statins blocked pyrimidine nucleotide biosynthesis and induced oxidative stress and apoptosis in p53-deficient cancer cells in spheroid culture. Moreover, ubiquinone produced by the mevalonate pathway was essential for the growth of p53-deficient tumor organoids. In contrast, inhibition of intestinal hyperproliferation by statins in an Apc/KrasG12D-mutant mouse model was independent of de novo pyrimidine synthesis. Our results highlight the importance of the mevalonate pathway for maintaining mitochondrial electron transfer and biosynthetic activity in cancer cells exposed to metabolic stress. They also demonstrate that the metabolic output of this pathway depends on both genetic and environmental context.

Significance:
These findings suggest that p53-deficient cancer cells activate the mevalonate pathway via SREBP2 and promote the synthesis of ubiquinone that plays an essential role in reducing oxidative stress and supports the synthesis of pyrimidine nucleotide.
Dual mTORC1/2 Inhibition Sensitizes Testicular Cancer Models to Cisplatin Treatment
Authors: Rosas-Plaza Ximena , de Vries Gerda , Meersma Gert Jan , Suurmeijer Albert J.H. , Gietema Jourik A. , van Vugt Marcel A.T.M. , de Jong Steven 
Published: November 2019

Abstract
Testicular cancer is the most common cancer type among young men. Despite highly effective cisplatin-based chemotherapy, around 20% of patients with metastatic disease will still die from the disease. The aim of this study was to explore the use of kinase inhibitors to sensitize testicular cancer cells to cisplatin treatment. Activation of kinases, including receptor tyrosine kinases and downstream substrates, was studied in five cisplatin-sensitive or -resistant testicular cancer cell lines using phospho-kinase arrays and Western blotting. The phospho-kinase array showed AKT and S6 to be among the top phosphorylated proteins in testicular cancer cells, which are part of the PI3K/AKT/mTORC pathway. Inhibitors of most active kinases in the PI3K/AKT/mTORC pathway were tested using apoptosis assays and survival assays. Two mTORC1/2 inhibitors, AZD8055 and MLN0128, strongly enhanced cisplatin-induced apoptosis in all tested testicular cancer cell lines. Inhibition of mTORC1/2 blocked phosphorylation of the mTORC downstream proteins S6 and 4E-BP1. Combined treatment with AZD8055 and cisplatin led to reduced clonogenic survival of testicular cancer cells. Two testicular cancer patient-derived xenografts (PDX), either from a chemosensitive or -resistant patient, were treated with cisplatin in the absence or presence of kinase inhibitor. Combined AZD8055 and cisplatin treatment resulted in effective mTORC1/2 inhibition, increased caspase-3 activity, and enhanced tumor growth inhibition. In conclusion, we identified mTORC1/2 inhibition as an effective strategy to sensitize testicular cancer cell lines and PDX models to cisplatin treatment. Our results warrant further investigation of this combination therapy in the treatment of patients with testicular cancer with high-risk relapsed or refractory disease.
In Vivo Epigenetic CRISPR Screen Identifies Asf1a as an Immunotherapeutic Target in Kras-Mutant Lung Adenocarcinoma
Authors: Li Fei , Huang Qingyuan , Luster Troy A. , Hu Hai , Zhang Hua , Ng Wai-Lung , Khodadadi-Jamayran Alireza , Wang Wei , Chen Ting , Deng Jiehui , Ranieri Michela , Fang Zhaoyuan , Pyon Val , Dowling Catríona M. , Bagdatlioglu Ece , Almonte Christina , Labbe Kristen , Silver Heather , Rabin Alexandra R. , Jani Kandarp , Tsirigos Aristotelis , Papagiannakopoulos Thales , Hammerman Peter S. , Velcheti Vamsidhar , Freeman Gordon J. , Qi Jun , Miller George , Wong Kwok-Kin 
Published: November 2019

Abstract

Despite substantial progress in lung cancer immunotherapy, the overall response rate in patients with KRAS-mutant lung adenocarcinoma (LUAD) remains low. Combining standard immunotherapy with adjuvant approaches that enhance adaptive immune responses—such as epigenetic modulation of antitumor immunity—is therefore an attractive strategy. To identify epigenetic regulators of tumor immunity, we constructed an epigenetic-focused single guide RNA library and performed an in vivo CRISPR screen in a KrasG12D/Trp53−/− LUAD model. Our data showed that loss of the histone chaperone Asf1a in tumor cells sensitizes tumors to anti–PD-1 treatment. Mechanistic studies revealed that tumor cell–intrinsic Asf1a deficiency induced immunogenic macrophage differentiation in the tumor microenvironment by upregulating GM-CSF expression and potentiated T-cell activation in combination with anti–PD-1. Our results provide a rationale for a novel combination therapy consisting of ASF1A inhibition and anti–PD-1 immunotherapy.

Significance:
Using an in vivo epigenetic CRISPR screen, we identified Asf1a as a critical regulator of LUAD sensitivity to anti–PD-1 therapy. Asf1a deficiency synergized with anti–PD-1 immunotherapy by promoting M1-like macrophage polarization and T-cell activation. Thus, we provide a new immunotherapeutic strategy for this subtype of patients with LUAD.
See related commentary by Menzel and Black, p. 179.
This article is highlighted in the In This Issue feature, p. 161
To Sleep or Not to Sleep—Is it a Question?
Authors: Faust Joan 
Published: November 2019

Amidst the many trials Donne experienced during his 1623 illness recounted in his Devotions upon Emergent Occasions are bouts of insomnia introduced in Devotion 15 and implied in Devotions 16–18 with the unceasing tolls of bells in the nearby church commemorating the dying and dead. Donne’s agonized longing for the comfort of sleep as he lay day after day and night after night for fourteen days to the disease’s crisis, then over three months of slow recuperation, hits readers where they live: in all probability, all of us have tossed and turned on long sleepless nights. But is Donne preoccupation with sleep an anomaly among seventeenth-century writers, peculiar to his 1623 illness, and another example of Donne’s excessive focus on his own body, or did other Early Modern writers and theorists demonstrate an obsession with sleep? And more importantly, was insomnia a hindrance to his creativity before, during, and after his illness? A look at Donne’s Devotions in light of Early Modern theories of sleep and “not to sleep” indicates that Donne’s work not only documents his own personal sufferings and anxiety about liminal states but also illustrates Early Modern beliefs about insomnia, its causes, and even its benefits. Insomnia was not a temporary and isolated stage of Donne’s 1623 illness but a burden throughout his life, possibly serving as a source of his creativity and linking him to other sleepless writers of his time and beyond.
The genus Anaphothrips (Thysanoptera, Thripidae) in China, with three new species
Authors: CUI YANZE , WANG JUN 
Published: November 2019

A key to, and distributional information about, is given concerning the 11 Anaphothrips species known from China, including the descriptions of three new species: A. nonporous sp. n., A. oroqeni sp. n. and A. qinghaiensis sp. n. The male and micropterous female of A. beijing Mirab-balou, Chen & Tong and the male of A. populi Zhang & Tong are described for the first time. The European species A. atroapterus Priesner is newly recorded from China.
Targeting the Fetal Body and/or Mother–Child Connection: Vital Conflicts and Abortion
Authors: Watt Helen , McCarthy Anthony 
Published: November 2019

Is the “act itself” of separating a pregnant woman and her previable child neither good nor bad morally, considered in the abstract? Recently, Maureen Condic and Donna Harrison have argued that such separation is justified to protect the mother’s life and that it does not constitute an abortion as the aim is not to kill the child. In our article on maternal–fetal conflicts, we agree there need be no such aim to kill (supplementing aims such as to remove). However, we argue that to understand “abortion” as performed only where the death of the child is intended is to define the term too narrowly. Respect for the mother, the fetus, and the bond between them goes well beyond avoiding any such aim. We distinguish between legitimate maternal treatments simply aimed at treating or removing a damaged part of the woman and illegitimate treatments that focus harmfully on the fetal body and its presence within the mother’s body. In obstetrics as elsewhere, not all side effects for one subject of intervention can be outweighed by intended benefits for another. Certain side effects of certain intended interventions are morally conclusive. Summary: How should one respond to “vital conflicts” in pregnancy where the mother’s life or health is at risk? We argue that, in addition to avoiding any aim of ending life, one must avoid the similarly unacceptable aims of evicting the baby pre-viability and invading its body, including its placenta, in a lethally harmful way. Even at the cost of real and important benefits for the mother such as increased safety and protection of fertility, we must manage cases always in a way that respects the inviolable bodily rights of both mother and child and crucially, the unique bond between them.