bluuebunny/crossref_metadata_2025_split huggingface dataset:
Time-Sampled Population Sequencing Reveals the Interplay of Selection and Genetic Drift in Experimental Evolution of
Potato Virus Y
Authors: Kutnjak Denis , Elena Santiago F. , Ravnikar Maja 
Published: June 2017

ABSTRACT

RNA viruses are one of the fastest-evolving biological entities. Within their hosts, they exist as genetically diverse populations (i.e., viral mutant swarms), which are sculpted by different evolutionary mechanisms, such as mutation, natural selection, and genetic drift, and also the interactions between genetic variants within the mutant swarms. To elucidate the mechanisms that modulate the population diversity of an important plant-pathogenic virus, we performed evolution experiments with
Potato virus Y
(PVY) in potato genotypes that differ in their defense response against the virus. Using deep sequencing of small RNAs, we followed the temporal dynamics of standing and newly generated variations in the evolving viral lineages. A time-sampled approach allowed us to (i) reconstruct theoretical haplotypes in the starting population by using clustering of single nucleotide polymorphisms' trajectories and (ii) use quantitative population genetics approaches to estimate the contribution of selection and genetic drift, and their interplay, to the evolution of the virus. We detected imprints of strong selective sweeps and narrow genetic bottlenecks, followed by the shift in frequency of selected haplotypes. Comparison of patterns of viral evolution in differently susceptible host genotypes indicated possible diversifying evolution of PVY in the less-susceptible host (efficient in the accumulation of salicylic acid).

IMPORTANCE
High diversity of within-host populations of RNA viruses is an important aspect of their biology, since they represent a reservoir of genetic variants, which can enable quick adaptation of viruses to a changing environment. This study focuses on an important plant virus,
Potato virus Y
, and describes, at high resolution, temporal changes in the structure of viral populations within different potato genotypes. A novel and easy-to-implement computational approach was established to cluster single nucleotide polymorphisms into viral haplotypes from very short sequencing reads. During the experiment, a shift in the frequency of selected viral haplotypes was observed after a narrow genetic bottleneck, indicating an important role of the genetic drift in the evolution of the virus. On the other hand, a possible case of diversifying selection of the virus was observed in less susceptible host genotypes.
Electrophysiological findings show generalised post-photoreceptoral deficiency in macular telangiectasia type 2
Authors: Ledolter Anna A , Holder Graham E , Ristl Robin , Schmidt-Erfurth Ursula , Ritter Markus 
Published: June 2017

BackgroundPhotoreceptor damage, reported in single observations, has been suggested to contribute to the disease pathogenesis in macular telangiectasia type 2 (MacTel2). The purpose of this study was to ascertain whether the photoreceptor or post-photoreceptoral function is affected in MacTel2 and could be detected using electrophysiological examination.MethodsThirty-five eyes from 18 patients (15 men, aged 60.1±9.6 years, range 38–77 years) with MacTel2 were included in the study. All patients underwent standard ophthalmic examination followed by pattern electroretinography (PERG) and full-field ERG. The data were compared against 22 normal control subjects (10 men, age 59.83±6.28 years, range 48–76).ResultsMean PERG P50 amplitude and peak time in patients with MacTel2 did not differ significantly from control values (p>0.2) but P50 amplitude was subnormal in three patients. The mean scotopic rod b-wave amplitude was significantly lower in patients than in healthy controls (p=0.027). A lower dark-adapted 10.0 b-wave (p=0.06) but not a-wave amplitude (p=0.58) was present in patients with MacTel2. Photopic single-flash a-wave and b-wave amplitudes did not differ between patient and control groups (p=0.2 and 0.3), but 30 Hz flicker peak time was significantly later in patients with MacTel2 with no effect on amplitude (p=0.04 and 0.7).ConclusionBoth scotopic (rod system dominated) and photopic ERGs (cone system) are consistent with post-photoreceptoral dysfunction. There was no electrophysiological evidence of dysfunction at the level of the photoreceptor.
Evaluating the short-term and long-term effects of an internet-based aural rehabilitation programme for hearing aid users in general clinical practice: a randomised controlled trial
Authors: Malmberg Milijana , Lunner Thomas , Kähäri Kim , Andersson Gerhard 
Published: June 2017

ObjectiveGuided internet-based intervention beyond hearing aid (HA) fitting has been shown to be efficacious in randomised controlled trials (RCTs). However, internet interventions have rarely been applied clinically as a part of regular aural rehabilitation (AR). Our aim was to evaluate the effectiveness of internet-based AR for HA users from a clinical population.Outcome measuresThe Hearing Handicap Inventory for the Elderly (HHIE) was used as the primary outcome measure, and the Communication Strategies Scale (CSS) and the Hospital Anxiety and Depression Scale were used as secondary outcome measures. All questionnaires were administered before and directly after the intervention and at 6 months postintervention.MethodsWe used a parallel group design (RCT). The data were collected in 2013–2014 at three different clinics. Seventy-four HA users were randomly assigned to receive either full internet-based AR (intervention group, n=37) or one element of the internet-based AR (control group, n=37).ResultsData were analysed following the intention-to-treat principle. Each group showed improved HHIE scores over time and did not differ significantly from each other. The intervention group showed significantly greater improvement compared with the control group for the CSS total and thenon-verbalsubscale scores. The intervention group and control group were also subdivided into two age groups: 20–59 years and 60–80 years. Significantly better improvement on the CSS total andnon-verbalsubscale scores was found in the older group compared with the younger participants.ConclusionsThis study indicates that participants in an internet-based intervention applied in general clinical practice showed improved self-reported communication skills compared with a control group. Receiving a full intervention was not more effective in improving self-reported hearing problems than receiving just one element of the internet-based intervention.Trial registration numberThis trial is registered at ClinicalTrals.gov,NCT01837550; results.
Impact of iron fortification on the geospatial patterns of malaria and non-malaria infection risk among young children: a secondary spatial analysis of clinical trial data from Ghana
Authors: Aimone Ashley M , Brown Patrick , Owusu-Agyei Seth , Zlotkin Stanley H , Cole Donald C 
Published: June 2017

ObjectivesPatterns of infection among children with varying levels of iron status in a malaria endemic area may vary spatially in ways requiring integrated infection and iron deficiency control programmes. The objective of this secondary analysis was to determine the geospatial factors associated with malaria and non-malaria infection status among young Ghanaian children at the end of a 5-month iron intervention trial.DesignCluster-randomised controlled trial.SettingRural GhanaParticipants1943 children (6–35 months of age) with geocoded compounds.InterventionsPoint-of-use fortification with micronutrient powders containing vitamins and minerals with or without iron.Primary and secondary outcome measuresGeneralised linear geostatistical models with a Matern spatial correlation function were used to analyse four infection response variables, defined using different combinations of inflammation (C-reactive protein, CRP >5 mg/L) and malaria parasitaemia. Analyses were also stratified by treatment group to assess the independent effects of the iron intervention.ResultsThe by-group and combined-group analyses both showed that baseline infection status was the most consistent predictor of endline infection risk, particularly when infection was defined using parasitaemia. In the No-iron group, age above 24 months and weight-for-length z-score at baseline were associated with high CRP at endline. Higher asset score was associated with a 12% decreased odds of endline infection, defined as CRP >5 mg/L and/or parasitaemia (OR 0.88, 95% credible interval 0.78 to 0.98), regardless of group. Maps of the predicted risk and spatial random effects showed a defined low-risk area around the District centre, regardless of how infection was defined.ConclusionIn a clinical trial setting of iron fortification, where all children receive treated bed nets and access to malaria treatment, there may be geographical variation in the risk of infection with distinct high-risk and low-risk areas, particularly around municipal centres.Trial registration numberclinicaltrials.gov,NCT01001871.
Protocol for a randomised controlled trial of the effect of dapagliflozin, metformin and exercise on glycaemic variability, body composition and cardiovascular risk in prediabetes (the PRE-D Trial)
Authors: Færch Kristine , Amadid Hanan , Nielsen Lea Bruhn , Ried-Larsen Mathias , Karstoft Kristian , Persson Frederik , Jørgensen Marit Eika 
Published: June 2017

IntroductionThe primary aim of this study is to compare the efficacy of three short-term glucose-lowering interventions (exercise, metformin and dapagliflozin) on glycaemic variability in overweight or obese men and women with elevated diabetes risk (ie, prediabetes, defined as haemoglobin A1c(HbA1c)39–47 mmol/mol / 5.7%–6.4%). The secondary aims are to investigate the effects of the interventions on body composition and cardiometabolic risk factors.Methods and analysisThe Pre-D Trial is an investigator-initiated, randomised, controlled, parallel, open-label, superiority trial. The study aims to assign 120 participants in a 1:1:1:1 ratio to receive one of four interventions for 13 weeks: (1) dapagliflozin (10 mg once daily); (2) metformin (850 mg twice daily); (3) exercise (interval training, 5 days a week, 30 min per session); or (4) control (lifestyle advice). After the 13 weeks of intervention, a follow-up period of 13 weeks will follow to study the long-term effects of the interventions. The primary endpoint is reduction from baseline to end-of treatment (13 weeks) in mean amplitude of glycaemic excursions measured by continuous glucose monitoring. The secondary endpoints include concomitant changes in various measures of glucose metabolism, body weight, cardiorespiratory fitness, blood pressure, plasma lipids, objectively measured physical activity and dietary intake.Ethics and disseminationThe study protocol has been approved by the Ethics Committee of the Capital Region and the Danish Medicines Agency. Approval of data and biobank storage has been obtained from the Danish Data Protection Board. The study will be carried out according to the Declaration of Helsinki and to the regulations for good clinical practice. The results from this trial will allow a number of research questions concerning the effect of exercise versus dapagliflozin or metformin in HbA1c-defined prediabetes to be addressed.Trial registrationNCT02695810
Dyspnoea-12: a translation and linguistic validation study in a Swedish setting
Authors: Sundh Josefin , Ekström Magnus 
Published: June 2017

BackgroundDyspnoea consists of multiple dimensions including the intensity, unpleasantness, sensory qualities and emotional responses which may differ between patient groups, settings and in relation to treatment. The Dyspnoea-12 is a validated and convenient instrument for multidimensional measurement in English. We aimed to take forward a Swedish version of the Dyspnoea-12.MethodsThe linguistic validation of the Dyspnoea-12 was performed (Mapi Language Services, Lyon, France). The standardised procedure involved forward and backward translations by three independent certified translators and revisions after feedback from an in-country linguistic consultant, the developerand three native physicians. The understanding and convenience of the translated version was evaluated using qualitative in-depth interviews with five patients with dyspnoea.ResultsA Swedish version of the Dyspnoea-12 was elaborated and evaluated carefully according to international guidelines. The Swedish version, ‘Dyspné−12’, has the same layout as the original version, including 12 items distributed on seven physical and five affective items. The Dyspnoea-12 is copyrighted by the developer but can be used free of charge after permission for not industry-funded research.ConclusionA Swedish version of the Dyspnoea-12 is now available for clinical validation and multidimensional measurement across diseases and settings with the aim of improved evaluation and management of dyspnoea.
A cross-sectional study measuring vanadium and chromium levels in paediatric patients with CKD
Authors: Filler Guido , Kobrzynski Marta , Sidhu Hargun Kaur , Belostotsky Vladimir , Huang Shih-Han S , McIntyre Chris , Yang Liju 
Published: June 2017

ObjectivesAlthough many secondary effects of high levels of vanadium (V) and chromium (Cr) overlap with symptoms seen in paediatric patients with chronic kidney disease (CKD), their plasma V and Cr levels are understudied.DesignAncillary cross-sectional study to a prospective, longitudinal, randomised controlled trial.SettingChildren’s Hospital of Western Ontario, London Health Sciences Centre, London, Ontario, Canada.Participants36 children and adolescents 4–18 years of age with CKD.Interventions1–6 trace element measurements per patient. Cystatin C (CysC) estimated glomerular filtration rate (eGFR) was calculated using the Filler formula. Plasma V and Cr levels were measured using high-resolution sector field inductively coupled mass spectrometry. Anthropomorphic data and blood parameters were collected from our electronic chart programme. Water Cr and V data were obtained from the Ontario Water (Stream) Quality Monitoring Network.Primary and secondary outcome measuresPrimary outcomes: plasma Cr and V. Secondary outcomes: age, season, CysC, CysC eGFR, and Cr and V levels in environmental water.ResultsThe median (IQR) eGFR was 51 mL/min/1.73 m2(35, 75). The median V level was 0.12 µg/L (0.09, 0.18), which was significantly greater than the 97.5th percentile of the reference interval of 0.088 µg/L; 32 patients had at least one set of V levels above the published reference interval. The median Cr level was 0.43 µg/L (0.36, 0.54), which was also significantly greater than the established reference interval; 34 had at least one set of Cr levels above the published reference interval. V and Cr levels were moderately correlated. Only some patients had high environmental exposure.ConclusionsOur study suggests that paediatric patients with CKD have elevated plasma levels of V and Cr. This may be the result of both environmental exposure and a low eGFR. It may be necessary to monitor V and Cr levels in patients with an eGFR <30 mL/min/1.73 m2.Trial registration numberNCT02126293; HC#172241.
Patient-reported outcome measures (PROMs) for assessing perceived listening effort in hearing loss: protocol for a systematic review
Authors: Hughes Sarah E , Rapport Frances L , Boisvert Isabelle , McMahon Catherine M , Hutchings Hayley A 
Published: June 2017

IntroductionIn the UK, it is estimated that a disabling hearing loss (HL) affects 1 in 6 people. HL has functional, economic and social-emotional consequences for affected individuals. Intervention for HL focuses on improving access to the auditory signal using hearing aids or cochlear implants. However, even if sounds are audible and speech is understood, individuals with HL often report increased effort when listening.Listening effort (LE) may be measured using self-reported measures such as patient-reported outcome measures (PROMs). PROMs are validated questionnaires completed by patients to measure their perceptions of their own functional status and well-being. When selecting a PROM for use in research or clinical practice, it is necessary to appraise the evidence of a PROM’s acceptability to patients, validity, responsiveness and reliability.Methods and analysisA systematic review of studies evaluating the measurement properties of PROMs available to measure LE in HL will be undertaken. MEDLINE, EMBASE, CINAHL, PsychINFO and Web of Science will be searched electronically. Reference lists of included studies, key journals and the grey literature will be hand-searched to identify further studies for inclusion. Two reviewers will independently complete title, abstract and full-text screening to determine study eligibility. Data on the characteristics of each study and each PROM will be extracted. Methodological quality of the included studies will be appraised using the COnsensus-based Standards for the selection of health Measurement INstruments, the quality of included PROMs appraised and the credibility of the evidence assessed. A narrative synthesis will summarise extracted data.Ethics and disseminationEthical permission is not required, as this study uses data from published research. Dissemination will be through publication in peer-reviewed journals, conference presentations and the lead author’s doctoral dissertation. Findings may inform the selection of PROMs used to measure LE in HL.
The eSMART study protocol: a randomised controlled trial to evaluate electronic symptom management using the advanced symptom management system (ASyMS) remote technology for patients with cancer
Authors: Maguire Roma , Fox Patricia A , McCann Lisa , Miaskowski Christine , Kotronoulas Grigorios , Miller Morven , Furlong Eileen , Ream Emma , Armes Jo , Patiraki Elisabeth , Gaiger Alexander , Berg Geir V , Flowerday Adrian , Donnan Peter , McCrone Paul , Apostolidis Kathi , Harris Jenny , Katsaragakis Stylianos , Buick Alison R , Kearney Nora 
Published: June 2017

IntroductionWhile some evidence exists that real-time remote symptom monitoring devices can decrease morbidity and prevent unplanned admissions in oncology patients, overall, these studies have significant methodological weaknesses. The electronic Symptom Management using the Advanced Symptom Management System (ASyMS) Remote Technology (eSMART) study is designed to specifically address these weaknesses with an appropriately powered, repeated-measures, parallel-group stratified randomised controlled trial of oncology patients.Methods and analysisA total of 1108 patients scheduled to commence first-line chemotherapy (CTX) for breast, colorectal or haematological cancer will be recruited from multiple sites across five European countries.Patients will be randomised (1:1) to the ASyMS intervention (intervention group) or to standard care currently available at each site (control group). Patients in the control and intervention groups will complete a demographic and clinical questionnaire, as well as a set of valid and reliable electronic patient-reported outcome measures at enrolment, after each of their CTX cycles (up to a maximum of six cycles) and at 3, 6, 9 and 12 months after completion of their sixth cycle of CTX. Outcomes that will be assessed include symptom burden (primary outcome), quality of life, supportive care needs, anxiety, self-care self-efficacy, work limitations and cost effectiveness and, from a health professional perspective, changes in clinical practice (secondary outcomes).Ethics and disseminationEthical approval will be obtained prior to the implementation of all major study amendments. Applications will be submitted to all of the ethics committees that granted initial approval.eSMART received approval from the relevant ethics committees at all of the clinical sites across the five participating countries. In collaboration with the European Cancer Patient Coalition (ECPC), the trial results will be disseminated through publications in scientific journals, presentations at international conferences, and postings on the eSMART website and other relevant clinician and consumer websites; establishment of an eSMART website (www.esmartproject.eu) with publicly accessible general information; creation of an eSMART Twitter Handle, and production of a toolkit for implementing/utilising the ASyMS technology in a variety of clinical practices and other transferable health care contexts.Trial registration numberNCT02356081.
Attitudes and behaviours of adolescents towards antibiotics and self-care for respiratory tract infections: a qualitative study
Authors: Hawking Meredith KD , Lecky Donna M , Touboul Lundgren Pia , Aldigs Eman , Abdulmajed Hind , Ioannidou Eleni , Paraskeva-Hadjichambi Demetra , Khouri Pauline , Gal Micaela , Hadjichambis Andreas Ch. , Mappouras Demetrios , McNulty Cliodna AM 
Published: June 2017

BackgroundTo understand attitudes and behaviours of adolescents towards antibiotics, antimicrobial resistance and respiratory tract infections.DesignQualitative approach informed by the Theory of Planned Behaviour. Semi-structured interviews and focus groups were undertaken. We aimed to inform the development of an intervention in an international setting to improve antibiotic use among adolescents; therefore on completion of thematic analysis, findings were triangulated with qualitative data from similar studies in France, Saudi Arabia and Cyprus to elucidate differences in the behaviour change model and adaptation to diverse contexts.Setting7 educational establishments from the south of England.Participants53 adolescents (16–18 years) participated in seven focus groups and 21 participated in interviews.ResultsMost participants had taken antibiotics and likened them to other common medications such as painkillers; they reported that their peers treat antibiotics like a ‘cure-all’ and that they themselves were not interested in antibiotics as a discussion topic. They demonstrated low knowledge of the difference between viral and bacterial infections.Participants self-cared for colds and flu but believed antibiotics are required to treat other RTIs such as tonsillitis, which they perceived as more ‘serious’. Past history of taking antibiotics for RTIs instilled the belief that antibiotics were required for future RTIs. Those who characterised themselves as ‘non-science students’ were less informed about antibiotics and AMR. Most participants felt that AMR was irrelevant to them and their peers. Some ‘non-science’ students thought resistance was a property of the body, rather than bacteria.ConclusionAddressing adolescents’ misperceptions about antibiotics and the treatment of RTIs using a behaviour change intervention should help improve antibiotic awareness and may break the cycle of patient demand for antibiotics to treat RTIs amongst this group. Schools should consider educating all students in further education about antibiotic usage and AMR, not only those taking science.