bluuebunny/crossref_metadata_2025_split huggingface dataset:
Opposing Pressures of Speed and Efficiency Guide the Evolution of Molecular Machines
Authors: Wagoner Jason A , Dill Ken A 
Published: August 2019

Abstract
Many biomolecular machines need to be both fast and efficient. How has evolution optimized these machines along the tradeoff between speed and efficiency? We explore this question using optimizable dynamical models along coordinates that are plausible evolutionary degrees of freedom. Data on 11 motors and ion pumps are consistent with the hypothesis that evolution seeks an optimal balance of speed and efficiency, where any further small increase in one of these quantities would come at great expense to the other. For FoF1-ATPases in different species, we also find apparent optimization of the number of subunits in the c-ring, which determines the number of protons pumped per ATP synthesized. Interestingly, these ATPases appear to more optimized for efficiency than for speed, which can be rationalized through their key role as energy transducers in biology. The present modeling shows how the dynamical performance properties of biomolecular motors and pumps may have evolved to suit their corresponding biological actions.
Direct Evidence of an Increasing Mutational Load in Humans
Authors: Aris-Brosou Stéphane 
Published: August 2019

AbstractThe extent to which selection has shaped present-day human populations has attracted intense scrutiny, and examples of local adaptations abound. However, the evolutionary trajectory of alleles that, today, are deleterious has received much less attention. To address this question, the genomes of 2,062 individuals, including 1,179 ancient humans, were reanalyzed to assess how frequencies of risk alleles and their homozygosity changed through space and time in Europe over the past 45,000 years. Although the overall deleterious homozygosity has consistently decreased, risk alleles have steadily increased in frequency over that period of time. Those that increased most are associated with diseases such as asthma, Crohn disease, diabetes, and obesity, which are highly prevalent in present-day populations. These findings may not run against the existence of local adaptations but highlight the limitations imposed by drift and population dynamics on the strength of selection in purging deleterious mutations from human populations.
CFEA: a cell-free epigenome atlas in human diseases
Authors: Yu Fulong , Li Kai , Li Shuangquan , Liu Jiaqi , Zhang Yan , Zhou Meng , Zhao Hengqiang , Chen Hongyan , Wu Nan , Liu Zhihua , Su Jianzhong 
Published: August 2019

AbstractEpigenetic alterations, including 5-methylcytosine (5mC), 5-hydroxymethylcytosine (5hmC) and nucleosome positioning (NP), in cell-free DNA (cfDNA) have been widely observed in human diseases, and many available cfDNA-based epigenome-wide profiles exhibit high sensitivity and specificity in disease detection and classification. However, due to the lack of efficient collection, standardized quality control, and analysis procedures, efficiently integrating and reusing these data remain considerable challenges. Here, we introduce CFEA (http://www.bio-data.cn/CFEA), a cell-free epigenome database dedicated to three types of widely adopted epigenetic modifications (5mC, 5hmC and NP) involved in 27 human diseases. We developed bioinformatic pipelines for quality control and standard data processing and an easy-to-use web interface to facilitate the query, visualization and download of these cell-free epigenome data. We also manually curated related biological and clinical information for each profile, allowing users to better browse and compare cfDNA epigenomes at a specific stage (such as early- or metastasis-stage) of cancer development. CFEA provides a comprehensive and timely resource to the scientific community and supports the development of liquid biopsy-based biomarkers for various human diseases.
A general LC-MS-based RNA sequencing method for direct analysis of multiple-base modifications in RNA mixtures
Authors: Zhang Ning , Shi Shundi , Jia Tony Z , Ziegler Ashley , Yoo Barney , Yuan Xiaohong , Li Wenjia , Zhang Shenglong 
Published: August 2019

Abstract
A complete understanding of the structural and functional potential of RNA requires understanding of chemical modifications and non-canonical bases; this in turn requires advances in current sequencing methods to be able to sequence not only canonical ribonucleotides, but at the same time directly sequence these non-standard moieties. Here, we present the first direct and modification type-independent RNA sequencing method via introduction of a 2-dimensional hydrophobic end-labeling strategy into traditional mass spectrometry-based sequencing (2D HELS MS Seq) to allow de novo sequencing of RNA mixtures and enhance sample usage efficiency. Our method can directly read out the complete sequence, while identifying, locating, and quantifying base modifications accurately in both single and mixed RNA samples containing multiple different modifications at single-base resolution. Our method can also quantify stoichiometry/percentage of modified RNA versus its canonical counterpart RNA, simulating a real biological sample where modifications exist but may not be 100% at a particular site in the RNA. This method is a critical step towards fully sequencing real complex cellular RNA samples of any type and containing any modification type and can also be used in the quality control of modified therapeutic RNAs.
On the association between undocumented immigration and crime in the United States
Authors: Gunadi Christian 
Published: August 2019

Abstract
Approximately 11 million undocumented individuals live in the United States. At the same time, there are concerns that the presence of undocumented immigrants may contribute to an increase in crime rates. In this article, I examine the institutionalization rate of undocumented immigrants and quantify the change in crime rates attributable to undocumented immigration. The analysis yields a few main results. First, despite possessing characteristics usually associated with crime, undocumented immigrants are 33% less likely to be institutionalized compared to US natives. Second, there is no evidence that undocumented immigrants who have spent more time in the USA are more likely to be institutionalized compared to those who have been in the USA for a shorter time. There is evidence, however, that arriving at a younger age is associated with higher institutionalization rate. Finally, overall property and violent crime rates across US states are not statistically significantly increased by undocumented immigration.
Acceptability and Feasibility of a Pharmacist-Led Human Immunodeficiency Virus Pre-Exposure Prophylaxis Program in the Midwestern United States
Authors: Havens Joshua P , Scarsi Kimberly K , Sayles Harlan , Klepser Donald G , Swindells Susan , Bares Sara H 
Published: August 2019

Abstract

Background
Human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP) substantially reduces the risk of HIV acquisition, yet significant barriers exist to its prescription and use. Incorporating pharmacists in the PrEP care process may help increase access to PrEP services.

Methods
Our pharmacist-led PrEP program (P-PrEP) included pharmacists from a university-based HIV clinic, a community pharmacy, and 2 community-based clinics. Through a collaborative practice agreement, pharmacists conducted PrEP visits with potential candidates for PrEP, according to the recommended Centers for Disease Control and Prevention guidelines, and authorized emtricitabine-tenofovir disoproxil fumarate prescriptions. Demographics and retention in care over 12 months were summarized, and participant satisfaction and pharmacist acceptability with the P-PrEP program were assessed by Likert-scale questionnaires.

Results
Sixty patients enrolled in the P-PrEP program between January and June 2017 completing 139 visits. The mean age was 34 years (range, 20–61 years), and 88% identified as men who have sex with men, 91.7% were men, 83.3% were white, 80% were commercially insured, and 89.8% had completed some college education or higher. Participant retention at 3, 6, 9, and 12 months was 73%, 58%, 43%, and 28%, respectively. To date, no participant has seroconverted. One hundred percent of the participants who completed the patient satisfaction questionnaire would recommend the P-PrEP program. Pharmacists reported feeling comfortable performing point-of-care testing and rarely reported feeling uncomfortable during PrEP visits (3 occasions, 2.2%) or experiencing workflow disruption (1 occasion, 0.7%).

Conclusions
Implementation of a pharmacist-led PrEP program is feasible and associated with high rates of patient satisfaction and pharmacist acceptability.
Crime and networks: ten policy lessons
Authors: Lindquist Matthew J , Zenou Yves 
Published: August 2019

AbstractSocial network analysis can help us understand the root causes of delinquent behaviour and crime and provide practical guidance for the design of crime prevention policies. To illustrate these points, we first present a selective review of several key network studies and findings from the criminology and police studies literature. We then turn to a presentation of recent contributions made by network economists. We highlight ten policy lessons and provide a discussion of recent developments in the use of big data and computer technology.
Lotus japonicus Triterpenoid Profile and Characterization of the CYP716A51 and LjCYP93E1 Genes Involved in Their Biosynthesis In Planta
Authors: Suzuki Hayato , Fukushima Ery Odette , Shimizu Yuko , Seki Hikaru , Fujisawa Yukiko , Ishimoto Masao , Osakabe Keishi , Osakabe Yuriko , Muranaka Toshiya 
Published: August 2019

Abstract
Lotus japonicus is an important model legume plant in several fields of research, such as secondary (specialized) metabolism and symbiotic nodulation. This plant accumulates triterpenoids; however, less information regarding its composition, content and biosynthesis is available compared with Medicago truncatula and Glycine max. In this study, we analyzed the triterpenoid content and composition of L. japonicus. Lotus japonicus accumulated C-28-oxidized triterpenoids (ursolic, betulinic and oleanolic acids) and soyasapogenols (soyasapogenol B, A and E) in a tissue-dependent manner. We identified an oxidosqualene cyclase (OSC) and two cytochrome P450 enzymes (P450s) involved in triterpenoid biosynthesis using a yeast heterologous expression system. OSC9 was the first enzyme derived from L. japonicus that showed α-amyrin (a precursor of ursolic acid)-producing activity. CYP716A51 showed triterpenoid C-28 oxidation activity. LjCYP93E1 converted β-amyrin into 24-hydroxy-β-amyrin, a metabolic intermediate of soyasapogenols. The involvement of the identified genes in triterpenoid biosynthesis in L. japonicus plants was evaluated by quantitative real-time PCR analysis. Furthermore, gene loss-of-function analysis of CYP716A51 and LjCYP93E1 was conducted. The cyp716a51-mutant L. japonicus hairy roots generated by the genome-editing technique produced no C-28 oxidized triterpenoids. Likewise, the complete abolition of soyasapogenols and soyasaponin I was observed in mutant plants harboring Lotus retrotransposon 1 (LORE1) in LjCYP93E1. These results indicate that the activities of these P450 enzymes are essential for triterpenoid biosynthesis in L. japonicus. This study increases our understanding of triterpenoid biosynthesis in leguminous plants and provides information that will facilitate further studies of the physiological functions of triterpenoids using L. japonicus.
Arabidopsis SCO Proteins Oppositely Influence Cytochrome c Oxidase Levels and Gene Expression during Salinity Stress
Authors: Mansilla Natanael , Welchen Elina , Gonzalez Daniel H 
Published: August 2019

Abstract
SCO (synthesis of cytochrome c oxidase) proteins are involved in the insertion of copper during the assembly of cytochrome c oxidase (COX), the final enzyme of the mitochondrial respiratory chain. Two SCO proteins, namely, homolog of copper chaperone 1 and 2 (HCC1 and HCC2) are present in seed plants, but HCC2 lacks the residues involved in copper binding, leading to uncertainties about its function. In this study, we performed a transcriptomic and phenotypic analysis of Arabidopsis thaliana plants with reduced expression of HCC1 or HCC2. We observed that a deficiency in HCC1 causes a decrease in the expression of several stress-responsive genes, both under basal growth conditions and after applying a short-term high salinity treatment. In addition, HCC1 deficient plants show a faster decrease in chlorophyll content, photosystem II quantum efficiency and COX levels after salinity stress, as well as a faster increase in alternative oxidase capacity. Notably, HCC2 deficiency causes opposite changes in most of these parameters. Bimolecular fluorescence complementation analysis indicated that both proteins are able to interact. We postulate that HCC1 is a limiting factor for COX assembly during high salinity conditions and that HCC2 probably acts as a negative modulator of HCC1 activity through protein–protein interactions. In addition, a direct or indirect role of HCC1 and HCC2 in the gene expression response to stress is proposed.
Association of health-risk behaviors and depressive symptoms and anxiety symptoms: a school-based sample of Chinese adolescents
Authors: Luo Xiaomin , Zhou Yu , Zheng Ruimin , Li Xin , Dai Yue , Narayan Anuradha , Huang Xiaona , Tian Xiaobo , Jin Xi , Mei Lili , Xie Xinyan , Gu Huaiting , Hou Fang , Liu Lingfei , Luo Xiu , Meng Heng , Zhang Jiajia , Song Ranran 
Published: August 2019

Abstract
Background Depressive symptoms and anxiety symptoms of adolescents not only affect youth but also have wide-ranging impacts on the health of adults. The study was carried out to determine the epidemiological characteristics of depressive symptoms and anxiety symptoms and the associations between the two and health-risk behaviors in Chinese adolescents.
Methods Participants were recruited from the junior and senior high schools in China. Data were collected by self-designed questionnaires. The questionnaires included questions about demographic characteristics, depressive symptom scales, anxiety symptom scales and nine categories of health-risk behaviors. Descriptive analysis and binary logistic regression were performed by SPSS 21.0 software.
Results There were 4.4% of the participants with depressive symptoms. Approximately 32.0% of the participants had anxiety symptoms. Girls and general senior school students were risk factors for depressive symptoms and anxiety symptoms. Multiple health-risk behaviors were associated with depressive symptoms and anxiety symptoms in Chinese adolescents.
Conclusion Depressive symptoms and anxiety symptoms were prevalent in Chinese adolescents. Their distribution was affected by certain health-risk behaviors. Multiple health-risk behaviors were associated with depressive symptoms and anxiety symptoms in Chinese adolescents.
Analysis and forecast of the HIV/AIDS epidemic in Mainland China, 1985–2016
Authors: Guo Zuiyuan , Xiao Dan , Xu Shuang , He Kevin 
Published: August 2019

Abstract

Background
We aimed to forecast the number of unidentified and newly acquired HIV-infected individuals each year and to estimate the effectiveness of government prevention and control programs in China.

Methods
Dynamic and stochastic models were established based on officially published data regarding the four main modes of transmission: male homosexual sexual behavior, heterosexual sexual behavior, injection drug use (IDU) and plasma donation. Finally, we performed sensitivity analyses on model parameters.

Results
Nationally, by December 2016, approximately 280 790 individuals were estimated to have an unidentified HIV infection, with transmission via male homosexual sexual behavior (n = 100 710), heterosexual sexual behavior (n = 174 310), IDU (n = 5 620) and plasma donation (n = 150). Moreover, 196 970 newly acquired HIV-infected individuals were expected in 2016, via male homosexual sexual behavior (n = 78 610), heterosexual sexual behavior (n = 116,540), IDU (n = 1820), and plasma donation (n &lt; 2).

Conclusions
Our results show that HIV transmission via IDU and plasma donation has been effectively controlled; transmission via heterosexual sexual contact is being somewhat controlled; however, transmission via male homosexual sexual contact is not controlled. Hence, China should strengthen efforts aimed at control of unsafe sexual behaviors.
Non-medical use of loperamide in the UK and the USA
Authors: Webb N E , Wood D M , Black J C , Amioka E , Dart R C , Dargan P I 
Published: August 2019

Summary

Background
Loperamide is a mu-opioid receptor agonist that is available as an over-the-counter anti-motility agent in the US and UK; recommended maximum doses of 12-16 mg/day. Anecdotal reports of non-medical use (NMU) have increased over the past decade with supra-therapeutic doses (70-800 mg/day) associated with cardiotoxicity. Little data exists on the prevalence of loperamide NMU.

Aim
The aim of this study was to determine the prevalence of loperamide NMU in the UK and US and to describe characteristics of non-medical loperamide users.

Design
The Researched, Abuse, Diversion and Addiction Related Surveillance (RADARS® ) Survey of Nonmedical Use of Prescription Drugs (NMURx) was utilized to study NMU of loperamide among the adult population in the UK and US in 2017. The RADARS® NMURx is anonymous and self-administered online.

Methods
A total of 40,029 completed surveys were included (10,019 from the UK and 30,010 from the US). Respondents were asked questions about medical and NMU of loperamide, frequency of and reasons for NMU, route of use problematic drug use markers, and demographics.

Results
Prevalence of lifetime loperamide use (95% CI) and lifetime NMU of loperamide were: UK 28.5% (27.67-29.4), and 0.66% (0.5-0.8), respectively; US 33.7% (33.1-34.2), and 5.19% (4.9-5.5), respectively. Problematic drug use markers were elevated in those who reported NMU of loperamide in both the UK and US, however high-risk use was more prevalent in the UK than in the US.

Conclusion
NMU of loperamide is common. In the current international environment of opioid addiction involving both therapeutic and illicit opioids, awareness of the NMU of loperamide is important.
Comparing Cross-Section and Time-Series Factor Models
Authors: Fama Eugene F , French Kenneth R 
Published: August 2019

Abstract
We use the cross-section regression approach of Fama and MacBeth (1973) to construct cross-section factors corresponding to the time-series factors of Fama and French (2015). Time-series models that use only cross-section factors provide better descriptions of average returns than time-series models that use time-series factors. This is true when we impose constant factor loadings and when we use time-varying loadings that are natural for time-series factors and time-varying loadings that are natural for cross-section factors.
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.
Bubbles and Financial Professionals
Authors: Weitzel Utz , Huber Christoph , Huber Jürgen , Kirchler Michael , Lindner Florian , Rose Julia 
Published: August 2019

AbstractThe efficiency of financial markets and their potential to produce bubbles are central topics in academic and professional debates. Yet, little is known about the contribution of financial professionals to price efficiency. We run 116 experimental markets with 412 professionals and 502 students. We find that professional markets with bubble drivers – capital inflows or high initial capital supply – are susceptible to bubbles, although they are more efficient than student markets. In mixed markets with students, bubbles also occur, but professionals act as price stabilizers. We show that heterogeneous price beliefs drive overpricing, especially in bubble-prone market environments.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.
Risk of progression of interstitial pneumonia with autoimmune features to a systemic autoimmune rheumatic disease
Authors: Alevizos Michail K , Giles Jon T , Patel Nina M , Bernstein Elana J 
Published: August 2019

Abstract

Objective
The aim of this study was to determine the risk of developing a systemic autoimmune rheumatic disease (ARD) after an initial diagnosis of interstitial pneumonia with autoimmune features (IPAF).

Methods
We performed a retrospective cohort study of patients with interstitial lung disease (ILD) who were evaluated at Columbia University Irving Medical Center from 2009 to 2017. We divided patients with idiopathic ILD into two groups: those who met IPAF criteria and those who did not meet IPAF criteria at initial ILD diagnosis. We examined the association between IPAF and diagnosis of ARD during the follow-up period using a multivariable-adjusted logistic regression model.

Results
Of the 697 patients with ILD who were screened, 174 met inclusion criteria (50 met IPAF criteria and 124 did not). During a median follow-up period of 5.2 years, 16% (8/50) of subjects with IPAF were diagnosed with an ARD compared with 1.6% (2/124) of subjects without IPAF (P = 0.001). Adjusting for age, sex, smoking status and use of immunosuppressive therapy, the odds of progressing to an ARD were 14 times higher in subjects with IPAF than in those without IPAF (odds ratio 14.18, 95% CI 1.44–138.95, P = 0.02).

Conclusion
The presence of IPAF confers an increased risk of developing an ARD. Patients with IPAF should therefore be followed closely for the development of an ARD.
Comorbidities in familial Mediterranean fever: analysis of 2000 genetically confirmed patients
Authors: Balcı-Peynircioğlu Banu , Kaya-Akça Ümmüşen , Arıcı Zehra Serap , Avcı Edibe , Akkaya-Ulum Z Yeliz , Karadağ Ömer , Kalyoncu Umut , Bilginer Yelda , Yılmaz Engin , Özen Seza 
Published: August 2019

Abstract

Objectives
FMF is the most common periodic fever syndrome, characterized by recurrent episodes of fever and serosal inflammation accompanied with high acute phase reactants. The analysis of possible comorbidities is important to understand the impact of these conditions on clinical care and whether they share a common aetiological pathway. In this study, we aimed to evaluate the comorbidities associated with FMF patients in a large genetically diagnosed cohort.

Methods
We retrospectively evaluated the medical and genetic records of FMF patients who were followed up by rheumatologists in Hacettepe University for 15 years. The FMF patients who had homozygous or compound heterozygous mutations were included in the study. Comorbidities associated with FMF were divided into three groups: (i) comorbidities directly related to FMF, (ii) comorbidities due to increased innate inflammation, and (iii) comorbidities that were regarded as being incidental.

Results
A total of 2000 patients with a diagnosis of FMF were enrolled in the study. Among them 636 were children (31.8%) and M694V was the most common mutation in patients with associated inflammatory conditions. The frequency of AS, Iga Vasculitis (Henoch–Schönlein purpura), juvenile idiopathic arthritis, polyarteritis nodosa, multiple sclerosis and Behçet’s disease were increased in patients with FMF when compared with those in the literature.

Conclusion
This study represents the largest genetically confirmed cohort and compares the frequencies with existing national and international figures for each disease. The increased innate immune system inflammation seen in FMF may be considered as a susceptibility factor since it predisposes to certain inflammatory conditions.