bluuebunny/crossref_metadata_2025_split huggingface dataset:
Solubility-Weighted Index: fast and accurate prediction of protein solubility
Authors: Bhandari Bikash K , Gardner Paul P , Lim Chun Shen 
Published: June 2020

Abstract

Motivation
Recombinant protein production is a widely used technique in the biotechnology and biomedical industries, yet only a quarter of target proteins are soluble and can therefore be purified.

Results
We have discovered that global structural flexibility, which can be modeled by normalized B-factors, accurately predicts the solubility of 12 216 recombinant proteins expressed in Escherichia coli. We have optimized these B-factors, and derived a new set of values for solubility scoring that further improves prediction accuracy. We call this new predictor the ‘Solubility-Weighted Index’ (SWI). Importantly, SWI outperforms many existing protein solubility prediction tools. Furthermore, we have developed ‘SoDoPE’ (Soluble Domain for Protein Expression), a web interface that allows users to choose a protein region of interest for predicting and maximizing both protein expression and solubility.

Availability and implementation
The SoDoPE web server and source code are freely available at https://tisigner.com/sodope and https://github.com/Gardner-BinfLab/TISIGNER-ReactJS, respectively. The code and data for reproducing our analysis can be found at https://github.com/Gardner-BinfLab/SoDoPE_paper_2020.

Supplementary information
Supplementary data are available at Bioinformatics online.
Development of WEE2 kinase inhibitors as novel non-hormonal female contraceptives that target meiosis†
Authors: Hanna Carol B , Mudaliar Deepti , John Kristen , Allen C Leigh , Sun Luxin , Hawkinson Jon E , Schönbrunn Ernst , Georg Gunda I , Jensen Jeffrey T 
Published: June 2020

Abstract
WEE2 oocyte meiosis inhibiting kinase is a well-conserved oocyte specific kinase with a dual regulatory role during meiosis. Active WEE2 maintains immature, germinal vesicle stage oocytes in prophase I arrest prior to the luteinizing hormone surge and facilitates exit from metaphase II arrest at fertilization. Spontaneous mutations at the WEE2 gene locus in women have been linked to total fertilization failure indicating that selective inhibitors to this kinase could function as non-hormonal contraceptives. Employing co-crystallization with WEE1 G2 checkpoint kinase inhibitors, we revealed the structural basis of action across WEE kinases and determined type I inhibitors were not selective to WEE2 over WEE1. In response, we performed in silico screening by FTMap/FTSite and Schrodinger SiteMap analysis to identify potential allosteric sites, then used an allosterically biased activity assay to conduct high-throughput screening of a 26 000 compound library containing scaffolds of known allosteric inhibitors. Resulting hits were validated and a selective inhibitor that binds full-length WEE2 was identified, designated GPHR-00336382, along with a fragment-like inhibitor that binds the kinase domain, GPHR-00355672. Additionally, we present an in vitro testing workflow to evaluate biological activity of candidate WEE2 inhibitors including; (1) enzyme-linked immunosorbent assays measuring WEE2 phosphorylation activity of cyclin dependent kinase 1 (CDK1; also known as cell division cycle 2 kinase, CDC2), (2) in vitro fertilization of bovine ova to determine inhibition of metaphase II exit, and (3) cell-proliferation assays to look for off-target effects against WEE1 in somatic (mitotic) cells.
Adipokines expression and epithelial cell polarity in normal and cancerous breast tissue
Authors: Coradini Danila , Gambazza Simone , Oriana Saro , Ambrogi Federico 
Published: June 2020

AbstractCell polarity is crucial for the correct structural and functional organization of epithelial tissue. Its disruption can lead to loss of the apicobasal polarity, alteration in the intracellular components, misregulation of the pathways involved in cell proliferation and cancer promotion. Very recent in vitro/in vivo findings demonstrated that obesity-associated alterations in tissue adipokines protein level negatively affect epithelial polarity. We performed an in silico study to investigate whether such alterations also occur in surgical samples. We aimed to explore the relationship among the expression of the genes coding for leptin (LEP), adiponectin (ADIPOQ), adipokine receptors (LEPR, ADIPOR1 and ADIPOR2), and a panel of polarity-associated genes in normal tissue from breast reduction mammoplasty, and a series of paired samples of histologically normal (HN) tissue and invasive cancer. Results indicated that, in normal tissue, the expression of adipokines and their receptors negatively correlated with that of the polarity-associated genes and GGT1, which codes for γ-glutamyl transferase (GGT) enzyme, a marker of cell distress and membrane disruption. This negative correlation progressively decreased in HN and cancerous tissue, and loss of correlation between ADIPOR2 and polarity-associated genes appeared the most noticeable alteration. Given the growing role of obesity in breast cancer etiology and the opposite action of leptin and adiponectin in epithelial tissue remodeling, ADIPOR2 loss could be addressed as a key mechanism leading to an unbalanced leptin stimulatory activity, subsequent cell polarity disruption and eventually tumor initiation, a finding that requires to be confirmed also at the protein level and with in vivo models.
Implementation of a Mandatory Influenza Vaccine Policy: A 10-Year Experience
Authors: Kitt Eimear , Burt Sharon , Price Susan M , Satchell Lauren , Offit Paul A , Sammons Julia S , Coffin Susan E 
Published: June 2020

Abstract

Background
Influenza vaccination of healthcare workers (HCWs) has been recommended for more than 30 years. In 2009, HCWs were designated as a priority group by the Centers for Disease Control and Prevention. Current HCW vaccination rates are 78% across all settings and reach approximately 92% among those employed in hospital settings. Over the last decade, it has become clear that mandatory vaccine policies result in maximal rates of HCW immunization.

Methods
In this observational 10-year study, we describe the implementation of a mandatory influenza vaccination policy in a dedicated quaternary pediatric hospital setting by a multidisciplinary team. We analyzed 10 years of available data from deidentified occupational health records from 2009–2010 through the 2018–2019 influenza seasons. Descriptive statistics were performed using Stata v15 and Excel.

Results
Sustained increases in HCW immunization rates above 99% were observed in the 10 years postimplementation, in addition to a reduction in exemption requests and healthcare-associated influenza. In the year of implementation, 145 (1.6%) HCWs were placed on temporary suspension for failure to receive the vaccine without documentation of an exemption, with 9 (0.06%) subsequently being terminated. Since then, between 0 and 3 HCWs are terminated yearly for failure to receive the vaccine.

Conclusions
Implementation of our mandatory influenza vaccination program succeeded in successfully increasing the proportion of immunized HCWs at a quaternary care children’s hospital, reducing annual exemption requests with a small number of terminations secondary to vaccine refusal. Temporal trends suggest a positive impact on the safety of our patients.
Intact Human Immunodeficiency Virus (HIV) Reservoir Estimated by the Intact Proviral DNA Assay Correlates With Levels of Total and Integrated DNA in the Blood During Suppressive Antiretroviral Therapy
Authors: Papasavvas Emmanouil , Azzoni Livio , Ross Brian N , Fair Matthew , Yuan Zhe , Gyampoh Kwasi , Mackiewicz Agnieszka , Sciorillo Amanda C , Pagliuzza Amelie , Lada Steven M , Wu Guoxin , Goh Shih Lin , Bahnck-Teets Carolyn , Holder Daniel J , Zuck Paul D , Damra Mohammad , Lynn Kenneth M , Tebas Pablo , Mounzer Karam , Kostman Jay R , Abdel-Mohsen Mohamed , Richman Douglas , Chomont Nicolas , Howell Bonnie J , Montaner Luis J 
Published: June 2020

Abstract
Accurate characterization of the human immunodeficiency virus (HIV) reservoir is imperative to develop an effective cure. HIV was measured in antiretroviral therapy-suppressed individuals using the intact proviral DNA assay (IPDA), along with assays for total or integrated HIV DNA, and inducible HIV RNA or p24. Intact provirus correlated with total and integrated HIV.
Trends in the Nontuberculous Mycobacterial Disease Mortality Rate in Japan: A Nationwide Observational Study, 1997–2016
Authors: Harada Ko , Hagiya Hideharu , Funahashi Tomoko , Koyama Toshihiro , Kano Mitsunobu R , Otsuka Fumio 
Published: June 2020

Abstract

Background
The incidence of nontuberculous mycobacterial (NTM) infections has been increasing worldwide, becoming a significant healthcare burden especially among elderly people. This study aimed to evaluate the trends in NTM-associated mortality in Japan.

Methods
This study used vital statistics data and data on all NTM-associated deaths (N = 18 814) among individuals aged ≥40 years in Japan from 1997 to 2016. We calculated the crude and age-adjusted mortality rates by age and sex and used joinpoint regression to analyze trends and estimate the average annual percentage change (AAPC). We compared crude NTM- and tuberculosis-associated mortality rates by sex.

Results
The overall crude annual mortality rate increased from 0.63/100 000/year in 1997 to 1.93/100 000/year in 2016 and was the highest among individuals aged 80–84 years. The AAPC of the crude mortality rates among men of all ages and women aged 40–59 years were stable but increased among women aged 60–79 years (3.5%; 95% confidence interval [CI], 2.8–4.3) and ≥80 years (4.3%; 95% CI, 3.7–4.9). Among men, the age-adjusted mortality rates did not show a significant trend, while among women, the rates increased over the study period (AAPC, 4.6%; 95% CI, 2.7–6.6). In women, the crude NTM-associated mortality rate exceeded the tuberculosis mortality rate in 2014, 2015, and 2016.

Conclusions
NTM mortality increased in Japan between 1997 and 2016, especially among the elderly female population. Given the increasing NTM-associated mortality and the susceptible aging population, public health authorities in Japan should pay greater attention to NTM infections.
Tricuspid valve geometry and right heart remodelling: insights into the mechanism of atrial functional tricuspid regurgitation
Authors: Utsunomiya Hiroto , Harada Yu , Susawa Hitoshi , Ueda Yusuke , Izumi Kanako , Itakura Kiho , Hidaka Takayuki , Shiota Takahiro , Nakano Yukiko , Kihara Yasuki 
Published: June 2020

Abstract

Aims
We sought to investigate tricuspid valve (TV) geometry and right heart remodelling in atrial functional tricuspid regurgitation (AF-TR) as compared with ventricular functional TR with sinus rhythm (VF-TR).

Methods and results
Transoesophageal 3D echocardiography datasets of the TV and right ventricle were acquired in 51 symptomatic patients with severe TR (AF-TR, n = 23; VF-TR, n = 28). Three-dimensional right ventricular (RV) endocardial surfaces were reconstructed throughout the cardiac cycle and then postprocessed using semiautomated integration and segmentation software to calculate position of papillary muscle (PM) tips. Compared with VF-TR, AF-TR had more dilated and posteriorly displaced annulus and less leaflet tethering angles with more prominent right atrium and smaller RV end-systolic volume. On the XY (annular) plane, the centre of annulus was getting closer towards the anterior and posterior PM tips and was going away from the medial PM tip caused by prominent annular dilatation in AF-TR. On the Z-axis, the position of each PM tip in AF-TR was not so much displaced apically as that in VF-TR. Multiple linear regression analyses revealed that right atrial volume and right atrial/RV end-systolic volume ratio were determinants of annular area and orientation in AF-TR, respectively (both P &lt; 0.001). Additionally, the posteromedial-directed component of posterior PM tip position and the apically directed component of the position of all three PM tips were independently associated with TV tethering angles of each leaflet in AF-TR (all P &lt; 0.02).

Conclusion
Right heart remodelling and its association with 3D TV geometry differ entirely between AF-TR and VF-TR, which may offer distinctive therapeutic implication.
Relationship Between Frailty and Depression Among Community-Dwelling Older Adults: The Mediating and Moderating Role of Social Support
Authors: Jin Yaru , Si Huaxin , Qiao Xiaoxia , Tian Xiaoyu , Liu Xinyi , Xue Qian-Li , Wang Cuili 
Published: June 2020

Abstract

Background and Objectives
Frailty is associated with depression in older adults and reduces their social support. However, the mechanism underlying such relationship remains unclear. We aim to examine whether social support acts as a mediator or moderator in the relationship between frailty and depression.

Research Design and Methods
This cross-sectional study was conducted among 1,779 community-dwelling older adults aged 60 and older. Frailty, social support, and depressive symptoms were measured by the Physical Frailty Phenotype, Social Support Rating Scale, and five-item Geriatric Depression Scale, respectively. Data were also collected on age, gender, years of schooling, monthly income, cognitive function, number of chronic diseases, physical function, and pain.

Results
Linear regression models showed that subjective support and support utilization, but not objective support, mediated and moderated the relationship between frailty and depressive symptoms. The Johnson–Neyman technique determined a threshold of 30 for subjective support, but not for support utilization, beyond which the detrimental effect of frailty on depressive symptoms was offset.

Discussion and Implications
Social support underlies the association of frailty with depression, and its protective role varies by type. Interventions on depression should address improving perceptions and utilization of social support among frail older adults rather than simply providing them with objective support.
Galactic Circos: User-friendly Circos plots within the Galaxy platform
Authors: Rasche Helena , Hiltemann Saskia 
Published: June 2020

Abstract

Background
Circos is a popular, highly flexible software package for the circular visualization of complex datasets. While especially popular in the field of genomic analysis, Circos enables interactive graphing of any analytical data, including alternative scientific domain data and non-scientific data. This high degree of flexibility also comes with a high degree of complexity, which may present an obstacle for researchers not trained in programming or the UNIX command line. The Galaxy platform provides a user-friendly browser-based graphical interface incorporating a broad range of “wrapped” command line tools to facilitate accessibility.

Findings
We have developed a Galaxy wrapper for Circos, thus combining the power of Circos with the accessibility and ease of use of the Galaxy platform. The combination substantially simplifies the specification and configuration of Circos plots for end users while retaining the power to produce publication-quality visualizations of complex multidimensional datasets.

Conclusions
Galactic Circos enables the creation of publication-ready Circos plots using only a web browser, via the Galaxy platform. Users may download the full set of Circos configuration files of their plots for further manual customization. This version of Circos is available as an open-source installable application from the Galaxy ToolShed, with its use clarified in a training manual hosted by the Galaxy Training Network.
An Autonomous EU Functionality Doctrine for Shape Exclusions
Authors: Suthersanen Uma , Mimler Marc D 
Published: June 2020

Abstract
Exclusionary subject matter are often underpinned by public interest considerations. In the case of shapes of products, the Court of Justice of the European Union has aligned the interpretation of the relevant exclusionary provisions within design and trade mark laws. More recently, European jurisprudence within copyright law in relation to conditions of protection has imported the same considerations so as to regulate the protection of shapes of products. This article explores the multitude of doctrinal and policy reasons underpinning shape exclusions and argues that the Court is consciously creating an EU autonomous functionality doctrine within intellectual property law. We also argue that the Court is building a European macro-rationale within these laws namely to ensure that protection does not unduly restrict market freedom and competition.
Delivering a primary-level non-communicable disease programme for Syrian refugees and the host population in Jordan: a descriptive costing study
Authors: Ansbro Éimhín , Garry Sylvia , Karir Veena , Reddy Amulya , Jobanputra Kiran , Fardous Taissir , Sadique Zia 
Published: June 2020

Abstract
The Syrian conflict has caused enormous displacement of a population with a high non-communicable disease (NCD) burden into surrounding countries, overwhelming health systems’ NCD care capacity. Médecins sans Frontières (MSF) developed a primary-level NCD programme, serving Syrian refugees and the host population in Irbid, Jordan, to assist the response. Cost data, which are currently lacking, may support programme adaptation and system scale up of such NCD services. This descriptive costing study from the provider perspective explored financial costs of the MSF NCD programme. We estimated annual total, per patient and per consultation costs for 2015–17 using a combined ingredients-based and step-down allocation approach. Data were collected via programme budgets, facility records, direct observation and informal interviews. Scenario analyses explored the impact of varying procurement processes, consultation frequency and task sharing. Total annual programme cost ranged from 4 to 6 million International Dollars (INT$), increasing annually from INT$4 206 481 (2015) to INT$6 739 438 (2017), with costs driven mainly by human resources and drugs. Per patient per year cost increased 23% from INT$1424 (2015) to 1751 (2016), and by 9% to 1904 (2017), while cost per consultation increased from INT$209 to 253 (2015–17). Annual cost increases reflected growing patient load and increasing service complexity throughout 2015–17. A scenario importing all medications cut total costs by 31%, while negotiating importation of high-cost items offered 13% savings. Leveraging pooled procurement for local purchasing could save 20%. Staff costs were more sensitive to reducing clinical review frequency than to task sharing review to nurses. Over 1000 extra patients could be enrolled without additional staffing cost if care delivery was restructured. Total costs significantly exceeded costs reported for NCD care in low-income humanitarian contexts. Efficiencies gained by revising procurement and/or restructuring consultation models could confer cost savings or facilitate cohort expansion. Cost effectiveness studies of adapted models are recommended.
Break Down the Silos: A Conceptual Framework on Multisectoral Approaches to the Prevention and Control of Vector-Borne Diseases
Authors: Zhong Qingxia , Fouque Florence 
Published: June 2020

Abstract
The need for multisectoral approaches (MSAs) in prevention and control of vector-borne diseases (VBDs) has been identified. VBD programs often involve collaborations between health and nonhealth sectors; however, a systematic framework describing the process, requirements, challenges, and benefits of MSAs has been missing. A recent guidance document from UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases provides a framework to implement MSAs for prevention and control of VBDs. This article gives an introduction to the guidance document and describes the conceptual framework and coordination process. The next steps will be to test the framework through implementation research in specific VBD cases studies. The guidance document will thus be refined based on iterative and comprehensive monitoring and evaluation systems to assess the performance and impact of MSAs. The advocacy for MSA and necessary capacity building will be integrated into the testing of the framework.
Methylated derivatives of l-tyrosine in reaction catalyzed by l-amino acid oxidase: isotope and inhibitory effects
Authors: Pająk Małgorzata 
Published: June 2020

Abstractl-Amino acid oxidase (LAAO) is widely distributed in nature and shows important biological activity. It induces cell apoptosis and has antibacterial properties. This study was designed to investigate the effect of methyl substituent on its activity as methylated derivatives of l-tyrosine, labelled with short-lived B+ emitters, have been used in oncological diagnostics. To study isotope effects in the oxidative deamination of O-methyl-l-tyrosine, the deuterated isotopomer, i.e. O-methyl-[2-2H]-l-tyrosine, was synthesized by isotope exchange, catalyzed enzymatically by tryptophanase. Isotope effects were determined using the spectrophotometric non-competitive method. The values of isotope effects indicate that the α-C–H bond cleavage occurs in the rate determining step of the investigated reaction and α-hydrogen plays a role in the substrate binding process at the enzyme active site. The inhibitory effect on LAAO activity was studied with α-methyl-l-tyrosine and N-methyl-l-tyrosine. The mode of inhibition was determined based on Lineweavear–Burk plots intersections. α-Methyl-l-tyrosine has been found a mixed type inhibitor of the investigated enzyme, whereas N-methyl-l-tyrosine is a non-competitive inhibitor of LAAO.
Do Preschoolers’ Neuropsychological Functioning and Hyperactivity/Inattention Predict Social Functioning Trajectories Through Childhood?
Authors: Karlsberg Bennett Jenna , O’Neill Sarah , Rajendran Khushmand , Halperin, Jeffrey M 
Published: June 2020

Abstract

Objective
This longitudinal study examined whether preschool attention deficit hyperactivity disorder (ADHD) symptoms and neuropsychological functioning predicted trajectories of children’s social functioning from age 3 to 4 through 12 years.

Methods
Three- and four-year-old children (N = 208; 72.6% boys) were evaluated annually through age 12. Parent and teacher Attention Deficit/Hyperactivity Disorder Rating Scale, Fourth Edition responses during the initial evaluation were used to categorize preschoolers as “High” or “Low” risk for ADHD. Children’s neuropsychological functioning was assessed using the NEPSY. Teachers’ reports of children’s social functioning were obtained annually from preschool through age 12 years using the Adaptability, Functional Communication, and Social Skills subscales of the Behavioral Assessment System for Children, Second Edition. Hierarchical linear modeling was used to assess the trajectories of social functioning and determine whether preschoolers’ neuropsychological functioning and ADHD risk status predicted social functioning at age 12 years, and/or change in social functioning throughout childhood. All models controlled for baseline socioeconomic status.

Results
High Risk children had significantly lower teacher-rated Adaptability and Social Skills at age 12 years. High Risk children and those with lower Verbal neuropsychological functioning in preschool had lower teacher-rated Functional Communication at 12 years old. Lower preschool Verbal neuropsychological functioning predicted greater positive change in teacher-rated Functional Communication across childhood.

Conclusions
Early identification of and intervention for children exhibiting ADHD behaviors is critical given the enduring negative impact of these behaviors on social functioning. Screening preschoolers for verbal difficulties is encouraged given their long-term impact on children’s ability to clearly express thoughts and feelings and obtain and provide information.