bluuebunny/crossref_metadata_2025_split huggingface dataset:
Second opinions in medical oncology
Authors: Olver Ian , Carey Mariko , Bryant Jamie , Boyes Allison , Evans Tiffany , Sanson-Fisher Rob 
Published: July 2020

Abstract
Background
The current study aimed to further our understanding of second opinions among medical oncology patients by examining the proportion of patients who sought a second opinion about their cancer treatment, and why.

Methods
The study was conducted between 2013 and 2015 in three medical oncology clinics located in public hospitals in Australia: in metropolitan New South Wales, metropolitan Queensland, and in Tasmania.
Those patients who provide written informed consent were asked to complete a brief paper and pencil survey in the clinic containing questions on sociodemographic, disease and treatment characteristics. Approximately 1 month later, participants were mailed a second paper and pencil survey which contained questions about whether they had sought a second opinion and their motivation for doing so. Non-responders were followed up by letter at 3 and 6 weeks.

Results
Of 823 patients screened for eligibility, 698 eligible patients, 612 provided consent.
Of those who consented, 355 completed both the initial survey and the second survey and were included in the analyses. Of the 57 patients who sought a second opinion, the most frequent reasons given for doing so were the need for reassurance (49.1%) and the need to consider the range of treatment options (41.8%).
Of the 297 (83.6%) participants who did not seek a second opinion, the main reason was confidence in the first doctor (88.7%). Only 3.1% patients did not know that they could ask for a second opinion. Occasionally the doctor will initiate the referral for a second opinion.

Conclusions
Our study suggests that a minority of cancer patients seek a second opinion at some phase during their care. Most did so for reassurance or to ensure that they had covered all of the treatment options and not because of discomfort or distrust of their treating doctor.
Few patients reported a lack of awareness of second opinions. This suggests that second opinions form part of a patient-centred approach to information provision about care options. Whether the second opinion improves the quality of care or indeed outcomes has been difficult to demonstrate.
Defining rules governing recognition and Fc-mediated effector functions to the HIV-1 co-receptor binding site
Authors: Tolbert William D. , Sherburn Rebekah , Gohain Neelakshi , Ding Shilei , Flinko Robin , Orlandi Chiara , Ray Krishanu , Finzi Andrés , Lewis George K. , Pazgier Marzena 
Published: July 2020

Abstract
Background
The binding of HIV-1 Envelope glycoproteins (Env) to host receptor CD4 exposes vulnerable conserved epitopes within the co-receptor binding site (CoRBS) which are required for the engagement of either CCR5 or CXCR4 co-receptor to allow HIV-1 entry. Antibodies against this region have been implicated in the protection against HIV acquisition in non-human primate (NHP) challenge studies and found to act synergistically with antibodies of other specificities to deliver effective Fc-mediated effector function against HIV-1-infected cells. Here, we describe the structure and function of N12-i2, an antibody isolated from an HIV-1-infected individual, and show how the unique structural features of this antibody allow for its effective Env recognition and Fc-mediated effector function.

Results
N12-i2 binds within the CoRBS utilizing two adjacent sulfo-tyrosines (TYS) for binding, one of which binds to a previously unknown TYS binding pocket formed by gp120 residues of high sequence conservation among HIV-1 strains. Structural alignment with gp120 in complex with the co-receptor CCR5 indicates that the new pocket corresponds to TYS at position 15 of CCR5. In addition, structure-function analysis of N12-i2 and other CoRBS-specific antibodies indicates a link between modes of antibody binding within the CoRBS and Fc-mediated effector activities. The efficiency of antibody-dependent cellular cytotoxicity (ADCC) correlated with both the level of antibody binding and the mode of antibody attachment to the epitope region, specifically with the way the Fc region was oriented relative to the target cell surface. Antibodies with poor Fc access mediated the poorest ADCC whereas those with their Fc region readily accessible for interaction with effector cells mediated the most potent ADCC.

Conclusion
Our data identify a previously unknown binding site for TYS within the assembled CoRBS of the HIV-1 virus. In addition, our combined structural-modeling-functional analyses provide new insights into mechanisms of Fc-effector function of antibodies against HIV-1, in particular, how antibody binding to Env antigen affects the efficiency of ADCC response.
Blood transcriptomic discrimination of bacterial and viral infections in the emergency department: a multi-cohort observational validation study
Authors: Sampson Dayle , Yager Thomas D. , Fox Brian , Shallcross Laura , McHugh Leo , Seldon Therese , Rapisarda Antony , Hendriks Roslyn A. , Brandon Richard B. , Navalkar Krupa , Simpson Nandi , Stafford Sian , Gil Eliza , Venturini Cristina , Tsaliki Evi , Roe Jennifer , Chain Benjamin , Noursadeghi Mahdad 
Published: July 2020

Abstract
Background
There is an urgent need to develop biomarkers that stratify risk of bacterial infection in order to support antimicrobial stewardship in emergency hospital admissions.

Methods
We used computational machine learning to derive a rule-out blood transcriptomic signature of bacterial infection (SeptiCyte™ TRIAGE) from eight published case-control studies. We then validated this signature by itself in independent case-control data from more than 1500 samples in total, and in combination with our previously published signature for viral infections (SeptiCyte™ VIRUS) using pooled data from a further 1088 samples. Finally, we tested the performance of these signatures in a prospective observational cohort of emergency department (ED) patients with fever, and we used the combined SeptiCyte™ signature in a mixture modelling approach to estimate the prevalence of bacterial and viral infections in febrile ED patients without microbiological diagnoses.

Results
The combination of SeptiCyte™ TRIAGE with our published signature for viral infections (SeptiCyte™ VIRUS) discriminated bacterial and viral infections in febrile ED patients, with a receiver operating characteristic area under the curve of 0.95 (95% confidence interval 0.90–1), compared to 0.79 (0.68–0.91) for WCC and 0.73 (0.61–0.86) for CRP. At pre-test probabilities 0.35 and 0.72, the combined SeptiCyte™ score achieved a negative predictive value for bacterial infection of 0.97 (0.90–0.99) and 0.86 (0.64–0.96), compared to 0.90 (0.80–0.94) and 0.66 (0.48–0.79) for WCC and 0.88 (0.69–0.95) and 0.60 (0.31–0.72) for CRP. In a mixture modelling approach, the combined SeptiCyte™ score estimated that 24% of febrile ED cases receiving antibacterials without a microbiological diagnosis were due to viral infections. Our analysis also suggested that a proportion of patients with bacterial infection recovered without antibacterials.

Conclusions
Blood transcriptional biomarkers offer exciting opportunities to support precision antibacterial prescribing in ED and improve diagnostic classification of patients without microbiologically confirmed infections.
Optimized homomorphic encryption solution for secure genome-wide association studies
Authors: Blatt Marcelo , Gusev Alexander , Polyakov Yuriy , Rohloff Kurt , Vaikuntanathan Vinod 
Published: July 2020

Abstract
Background
Genome-Wide Association Studies (GWAS) refer to observational studies of a genome-wide set of genetic variants across many individuals to see if any genetic variants are associated with a certain trait. A typical GWAS analysis of a disease phenotype involves iterative logistic regression of a case/control phenotype on a single-neuclotide polymorphism (SNP) with quantitative covariates. GWAS have been a highly successful approach for identifying genetic-variant associations with many poorly-understood diseases. However, a major limitation of GWAS is the dependence on individual-level genotype/phenotype data and the corresponding privacy concerns.

Methods
We present a solution for secure GWAS using homomorphic encryption (HE) that keeps all individual data encrypted throughout the association study. Our solution is based on an optimized semi-parallel GWAS compute model, a new Residue-Number-System (RNS) variant of the Cheon-Kim-Kim-Song (CKKS) HE scheme, novel techniques to switch between data encodings, and more than a dozen crypto-engineering optimizations.

Results
Our prototype can perform the full GWAS computation for 1,000 individuals, 131,071 SNPs, and 3 covariates in about 10 minutes on a modern server computing node (with 28 cores). Our solution for a smaller dataset was awarded co-first place in iDASH’18 Track 2: “Secure Parallel Genome Wide Association Studies using HE”.

Conclusions
Many of the HE optimizations presented in our paper are general-purpose, and can be used in solving challenging problems with large datasets in other application domains.
Decentralized genomics audit logging via permissioned blockchain ledgering
Authors: Pattengale Nicholas D. , Hudson Corey M. 
Published: July 2020

Abstract
Background
One of the tasks in the iDASH Secure Genome Analysis Competition in 2018 was to develop blockchain-based immutable logging and querying for a cross-site genomic dataset access audit trail. The specific challenge was to design a time/space efficient structure and mechanism of storing/retrieving genomic data access logs, based on MultiChain version 1.0.4 (https://www.multichain.com/).

Methods
Our technique uses the MultiChain stream application programming interface (which affords treating MultiChain as a key value store) and employs a two-level index, which naturally supports efficient queries of the data for single clause constraints. The scheme also supports heuristic and binary search techniques for queries containing conjunctions of clause constraints, and timestamp range queries. Of note, all of our techniques have complexity independent of inserted data set size, other than the timestamp ranges, which logarithmically scale with input size.

Results
We implemented our insertion and querying techniques in Python, using the MultiChain library Savoir (https://github.com/dxmarkets/savoir), and comprehensively tested our implementation across a benchmark of datasets of varying sizes. We also tested a port of our challenge submission to a newer version of MultiChain (2.0 beta), which natively supports multiple indices.

Conclusions
We presented creative and efficient techniques for storing and querying log file data in MultiChain 1.0.4 and 2.0 beta. We demonstrated that it is feasible to use a permissioned blockchain ledger for genomic query log data when data volume is on the order of hundreds of megabytes and query times of dozens of minutes is acceptable. We demonstrated that evolution in the ledger platform (MultiChain 1 to 2) yielded a 30%-40% increase in insertion efficiency. All source code for this challenge has been made available under a BSD-3 license from https://github.com/sandialabs/idash2018task1/.
LPS aggravates lung inflammation induced by RSV by promoting the ERK-MMP-12 signaling pathway in mice
Authors: Chen Shenglin , Xie Jun , Zhao Keting , Ren Luo , Deng Yu , Xie Xiaohong , Chen Shiyi , Xu Hongmei , Long Xiaoru , Liu Enmei 
Published: July 2020

Abstract
Background
RSV can lead to persistent airway inflammation and airway hyperresponsiveness (AHR), and is intimately associated with childhood recurrent wheezing and asthma, but the underlying mechanisms remain unclear. Lipopolysaccharide (LPS) is also implicated in the onset and exacerbation of asthma. However, whether inhalation of LPS can boost airway inflammation induced by RSV is not clear. In this study, we utilized an LPS- and RSV-superinfected mouse model to explore underlying pathogenesis.

Methods
Mice were infected with RSV on day 0 and inoculated with LPS from day 35 to day 41, samples were collected on day 42. Inflammatory cells, lung histopathology and AHR were measured. Cytokines were detected by ELISA and ERK, JNK, p38 was determined by western blot. MMP408, PD98059, SP600125 and SB203580 were used to inhibit MMP-12, ERK, JNK and p38 respectively.

Results
LPS exposure superimposed on RSV-infected lungs could lead to more vigorous cellular influx, lung structures damage, augmented AHR and higher MMP-12 levels. Inhibition of MMP-12 or ERK signaling pathway in vivo both diminished LPS-driven airway inflammation and AHR.

Conclusions
Exposure to LPS in RSV-infected mice is associated with enhanced increases in ERK-MMP-12 expression that translates into increased lung inflammation and AHR. These findings contribute novel information to the field investigating the onset of post-RSV bronchiolitis recurrent wheezing as a result of LPS exposure.
A cultural and gender-based approach to understanding patient adjustment to chronic heart failure
Authors: Surikova Jelena , Payne Ada , Miller Karen-Lee , Ravaei Arian , Nolan Robert P. 
Published: July 2020

Abstract
Background
Persons identifying as Black, Chinese, or South Asian make up the largest minority groups in Canada. Individuals with chronic heart failure (CHF) from these groups experience a greater rate of re-hospitalization and poorer quality of life. Although experts agree that culture can shape the experience of CHF, little is known about how patients from these minority populations define a good quality of life with CHF and what barriers they experience when carrying out self-care behaviours. The aim of this qualitative study was to examine cultural and gender-based influences on quality of life in patients with CHF.

Methods
Purposive sampling included 30 patients (67% male), 18 to 75 years of age, who self-identified as Black (n = 8), Chinese (n = 9), or South Asian (n = 6). Caucasians (n = 7) were included as a comparison group. Semi-structured interviews (see the online appendix), lasting approximately 60 min, were conducted, which focused on personal understanding of CHF and living with the disease, including impact on lifestyle and quality of life. An inductive qualitative approach with thematic content analysis was used to develop key insights into individual experience of CHF, as well as cultural and gender-based influences on self-care and quality of life. Descriptive statistics were generated from questionnaire responses.

Results
Five key themes emerged from the narrative analysis of participant interviews: (i) CHF as an emergent reality, (ii) quality of life and disruption of lifecourse milestones, (iii) the challenge to accept CHF and re-evaluation of quality of life; (iv) impact on social activities essential to quality of life, and (v) life with CHF as a commitment to culturally tailored self-care. Participants described the unique impact of CHF on their quality of life, including life trajectory milestones such as dating, parenting, and retirement planning, as well as the importance of accepting their diagnosis, and the reframing goals for living well with heart failure. Positive and negative impacts on social relationships were noted, including sexual intimacy and interactions with spouses, other family members, and co-workers.

Conclusions
Study findings highlight important lifespan, cultural, and gender considerations that can inform the improvement of patient care and quality of life for patients and their families.
Patients’ confidence in treatment decisions for early stage non-small cell lung cancer (NSCLC)
Authors: Pompili Cecilia , Holch Patricia , Rogers Zoe , Absolom Kate , Clayton Beverly , Franks Kevin , Bekker Hilary , Velikova Galina 
Published: July 2020

Abstract
Background
In early-stage Non-Small Cell Lung Cancer (NSCLC) patients, little is known about how to measure patient participation in Shared-Decision Making (SDM). We examined the psychometric properties and clinical acceptability of the Decision Self-Efficacy scale (DSE) in a cohort of patients undergoing to Stereotactic Ablative Radiotherapy (SABR) or Video-assisted Thoracoscopic Surgery (VATS) to capture patient involvement in treatment decisions.

Methods
In the context of a prospective longitudinal study (Life after Lung Cancer-LiLAC) involving 244 patients with early-stage NSCLC, 158 (64.7%) patients completed the DSE either on paper or electronically online prior to treatment with SABR or VATS pulmonary resection. DSE psychometric properties were examined using: principal components analysis of item properties and internal structure, and internal construct validity; we also performed a sensitivity analysis according to Eastern Cooperative Oncology Group Performance Status (ECOG PS), gender, age and treatment received (VATS or SABR) difference.

Results
Exploratory factor analysis using polychoric correlations substantiated that the 11 item DSE is one scale accounting for 81% of the variance. We calculated a value of 0.96 for Cronbach’s alpha for the total DSE score.
DSE scores did not differ by gender (p = 0.37), between the two treatment groups (p = 0.09) and between younger and older patients (p = 0.4). However, patients with an ECOG PS > 1 have a DSE mean of 73.8 (SD 26) compared to patients with a PS 0–1 who have a DSE mean of 85.8 (SD 20.3 p = 0.002).

Conclusion
Findings provide preliminary evidence for the reliability and validity of the DSE questionnaire in this population. However, future studies are warranted to identify the most appropriate SDM tool for clinical practice in the lung cancer treatment field.
Stakeholders’ experiences of the public health research process: time to change the system?
Authors: Laird Yvonne , Manner Jillian , Baldwin Louise , Hunter Ruth , McAteer John , Rodgers Sarah , Williamson Chloë , Jepson Ruth 
Published: July 2020

Abstract
Background
The importance of engaging stakeholders in the research process is well recognised. Whilst engagement is important, guidelines and practices vary for how stakeholders should be involved in research and how to facilitate effective collaborative relationships.

Methods
This study aimed to explore the perspectives and experiences of stakeholders involved in the policy and practice area of outdoor space and non-communicable disease prevention. Stakeholders interviewed included academics, practitioners, policy-makers, knowledge brokers and a funder.

Results
The findings suggest that stakeholders had positive experiences when engaged meaningfully in the research process, where research projects were carefully planned and managed with attention to context and culture, and where the research team was effective, respectful and communicative. These factors help to facilitate the translation of research into policy and practice. However, multiple challenges of collaborative research were identified which related to structural and systemic challenges, building and maintaining relationships, use and collection of data and information, cultural perceptions of research and research generation, and getting evidence into action. Participants felt that changing the funding system, exploring more collaborative research methodologies, improved research translation, and more effective collaborative relationships at all stages of the research process could address some of these challenges.

Conclusions
The findings highlight that, whilst stakeholder engagement in research was considered important, structural, cultural and individual practices impacted how this worked in practice. Identifying and testing solutions to address these challenges could improve synergies between research, policy, and practice and lead to the production of impactful research that reduces wastage of public funding, improves implementation of findings and ultimately improves public health outcomes.
Comparison of different optomotor response readouts for visual testing in experimental autoimmune encephalomyelitis-optic neuritis
Authors: Hecker Christina , Dietrich Michael , Issberner Andrea , Hartung Hans-Peter , Albrecht Philipp 
Published: July 2020

AbstractOptomotor response is increasingly used in preclinical research for evaluating the visual function in rodents. However, the most suitable measuring protocol for specific scientific questions is not always established. We aimed to determine the optimal parameters for visual function analysis in experimental autoimmune encephalomyelitis optic neuritis (EAEON), an animal model for multiple sclerosis. Contrast sensitivity as well as spatial frequency both had a low variance and a good test-retest reliability. Also, both parameters were able to differentiate between the EAEON and the control group. Correlations with the retinal degeneration, assessed by optical coherence tomography, the infiltration of immune cells, and the clinical disability score revealed that spatial frequency was superior to contrast sensitivity analysis. We therefore conclude that spatial frequency testing is better suited as visual acuity assessment in C57Bl/6 J EAEON mice. Furthermore, contrast sensitivity measurements are more time consuming, possibly leading to more stress for the animals.
Comparison of tobacco import and tobacco control in five countries: lessons learned for Indonesia
Authors: Ahsan Abdillah , Wiyono Nur Hadi , Veruswati Meita , Adani Nadhila , Kusuma Dian , Amalia Nadira 
Published: July 2020

Abstract
Background
With a 264 million population and the second highest male smoking prevalence in the world, Indonesia hosted over 60 million smokers in 2018. However, the government still has not ratified the Framework Convention on Tobacco Control. In the meantime, tobacco import increases rapidly in Indonesia. These create a double, public health and economic burden for Indonesia’s welfare.

Objective
Our study analyzed the trend of tobacco import in five countries: Indonesia, Pakistan, Bangladesh, Zimbabwe, and Mozambique. Also, we analyze the tobacco control policies implemented in these countries and determine some lessons learn for Indonesia.

Methods
We conducted quantitative analyses on tobacco production, consumption, export, and import during 1990–2016 in the five countries. Data were analyzed using simple ordinary least square regressions, correcting for time series autocorrelation. We also conducted a desk review on the tobacco control policies implemented in the five countries.

Results
While local production decreased by almost 20% during 1990–2016, the proportion of tobacco imports out of domestic production quadrupled from 17 to 65%. Similarly, the ratio of tobacco imports to exports reversed from 0.7 (i.e., exports were higher) to 2.9 (i.e., import were 2.9 times higher than export) in 1990 and 2016, respectively. This condition is quite different from the other four respective countries in the observation where their tobacco export is higher than the import. From the tobacco control point of view, the four other countries have ratified the Framework Convention on Tobacco Control (FCTC).

Conclusion
The situation is unlikely for Indonesia to either reduce tobacco consumption or improve the local tobacco farmer’s welfare, considering that the number of imports continued to increase. Emulating from the four countries, Indonesia must ratify the FCTC and implement stricter tobacco control policies to decrease tobacco consumption and import.