bluuebunny/crossref_metadata_2025_split huggingface dataset:
Distant hybrids of Heliocidaris crassispina (♀) and Strongylocentrotus intermedius (♂): identification and mtDNA heteroplasmy analysis
Authors: Zhan Yaoyao , Sun Jingxian , Li Yingying , Cui Dongyao , Zhang Weijie , Yang Limeng , Chang Yaqing 
Published: August 2020

Abstract
Background
Distant hybridization between the sea urchin Heliocidaris crassispina (♀) and the sea urchin Strongylocentrotus intermedius (♂) was successfully performed under laboratory conditions. A new variety of hybrid sea urchin (HS hybrid) was obtained. However, the early-development success rates for the HS hybrids were significantly lower than those of purebred H. crassispina or S. intermedius offspring. In addition, it was difficult to distinguish the HS-hybrid adults from the pure H. crassispina adults, which might lead to confusion in subsequent breeding attempts. In this study, we attempted to develop a method to quickly and effectively identify HS hybrids, and to preliminarily investigate the molecular mechanisms underlying the poor early-development success rates in the HS hybrids.

Results
The hybrid sea urchins (HS hybrids) were identified both morphologically and molecularly. There were no significant differences in the test height to test diameter ratios between the HS hybrids and the parents. The number and arrangement of ambulacral pore pairs in the HS hybrids differed from those of the parental lines, which might serve as a useful morphological character for the identification of the HS hybrids. A primer pair that identified the HS hybrids was screened by comparing the mitochondrial genomes of the parental lines. Moreover, paternal leakage induced mitochondrial DNA heteroplasmy in the HS hybrids, which might explain the low rates of early development success in these hybrids.

Conclusions
The distant-hybrid sea urchins were accurately identified using comparative morphological and molecular genetic methods. The first evidence of mtDNA heteroplasmy after the distant hybridization of an echinoderm was also provided.
Cost-effectiveness of the PDSAFE personalised physiotherapy intervention for fall prevention in Parkinson’s: an economic evaluation alongside a randomised controlled trial
Authors: Xin Yiqiao , Ashburn Ann , Pickering Ruth M. , Seymour Kim Chivers , Hulbert Sophia , Fitton Carolyn , Kunkel Dorit , Marian Ioana , Roberts Helen C. , Lamb Sarah E. , Goodwin Victoria A. , Rochester Lynn , McIntosh Emma ,   on behalf of the PDSAFE Collaborative group, Ashburn A. , Seymour K. , Roberts H. C. , Pickering R. M. , Lamb S. , Ballinger C. , Goodwin V. A. , Rochester L. , Nieuwboer A. , McIntosh E. , Kunkel D. , Hulbert S. , Fitton C. , Marian I. , Xin Y. , Rowsell A. , Summer R. 
Published: August 2020

AbstractBackgroundPDSAFE is an individually-tailored, physiotherapist-delivered, balance, strength and strategy training programme aimed at preventing falls among people with Parkinson’s. We evaluated the cost-effectiveness of PDSAFE compared with usual care for people with Parkinson’s at higher risk of falling, from a UK National Health Service and Personal Social Service perspective.MethodsResource use and quality of life data (EQ-5D-3L) were collected from 238 participants randomised to the PDSAFE intervention and 236 participants randomised to control, at baseline, 3 months, 6 months (primary outcome), and 12 months. Adjusted cost and quality-adjusted life-years (QALYs) were estimated using generalised linear models and uncertainty estimated using a non-parametric bootstrap.ResultsOver 6 months, the PDSAFE intervention was associated with an incremental cost of £925 (95% CI £428 to £1422) and a very small and statistically insignificant QALY gain of 0.008 (95% CI − 0.006 to 0.021). The resulting incremental cost-effectiveness ratio (ICER) was £120,659 per QALY and the probability of the intervention being cost-effective at a UK threshold of £30,000/QALY was less than 1%. The ICER varied substantially across subgroups although no subgroup had an ICER lower than the £30,000 threshold. The result was sensitive to the time horizon with the ICER reducing to £55,176 per QALY when adopting a 12-month time horizon and assuming a sustained treatment effect on QoL, nevertheless, the intervention was still not cost-effective according to the current UK threshold.ConclusionsEvidence from this trial suggests that the PDSAFE intervention is unlikely to be cost-effective at 6 months. The 12-month analysis suggested that the intervention became closer to being cost-effective if quality of life effects were sustained beyond the intervention period, however this would require confirmation. Further research, including qualitative studies, should be conducted to better understand the treatment effect of physiotherapy and its impact on quality of life in people with Parkinson’s given existing mixed evidence on this topic.Trial registrationISRCTN48152791. Registered 17 April 2014.http://www.isrctn.com/ISRCTN48152791
Treatment patterns and comorbid burden of patients newly diagnosed with multiple sclerosis in the United States
Authors: Kern David M. , Cepeda M. Soledad 
Published: August 2020

Abstract
Background
The treatment landscape for multiple sclerosis (MS) is quickly evolving. Understanding real-world treatment patterns of patients is necessary to identifying potential gaps in care.

Methods
Patients with incident MS were identified from a large national claims database during 1/1/2014–6/30/2019. Patients had ≥2 diagnoses for MS or an inpatient hospitalization with a primary diagnosis of MS. Patients were required to have enrollment in the database ≥1 year prior to and ≥ 1 year following their first MS diagnosis. Treatment sequences were captured for all available disease modifying therapies (DMTs) during all available follow-up. Presence of comorbid conditions were captured during the one year prior to and following (and including) the index date; absolute change in prevalence from the pre- to post-index periods was calculated.

Results
We identified 5691 patients with incident MS. Common comorbidities included physical symptoms (e.g., pain, weakness, fatigue), mental health conditions (anxiety, depression), and cardiovascular/metabolic conditions (hypertension, hyperlipidemia, diabetes, obesity). Just 1994 (35.0%) of patients received a DMT at any time during follow-up. Of those receiving a DMT, 28.2% went on to receive a second line of therapy, 5.8% received a third, and just 0.9% went on to a fourth line. Use of more than one DMT concomitantly occurred in just 1.8% of all treated patients. Glatiramer and dimethyl fumarate were by far the most common first-line treatments received accounting for nearly 62% of patients receiving a DMT.

Conclusion
Approximately two-thirds of patients newly diagnosed with MS did not receive a DMT and the disease is accompanied by a significant comorbid burden.
A short course of oral ranitidine as a novel treatment for toddler’s diarrhea: a parallel-group randomized controlled trial
Authors: Uwaezuoke Samuel N. , Ndu Ikenna K. , Eneh Chizoma I. , Anusiem Chikere A. , Ayuk Adaeze C. 
Published: August 2020

AbstractBackgroundThe current paradigm for treating toddler’s diarrhea comprises dietary modification and fluid restriction. Previous studies show that probiotics and proton-pump inhibitors (PPIs) or H2blockers could control diarrhea associated with functional gastrointestinal disorders (FGIDs). This study aims to determine and compare the efficacy of a short course of oral ranitidine and a probiotic in the treatment of toddler’s diarrhea.MethodsThis study was a parallel-group randomized controlled trial (RCT). We sequentially enrolled 40 patients who met the eligibility criteria. We randomly assigned 20 patients to the oral ranitidine group, ten patients to the probiotic group, and ten patients to the placebo group. In the oral ranitidine group, patients received oral ranitidine (3 mg/kg/day) once daily for 10 days; in the probiotic and placebo groups, they were administered 5 to 10 billion colony-forming units (CFUs) per day of lyophilizedLactobacillus rhamnosusand 50 mg of once-daily oral vitamin C tablet respectively for 10 days. Stool frequency and consistency on the 10th day of the interventions were recorded as the primary outcomes. We used the Student’s t-test to determine if there were significant differences in the mean daily stool frequencies in the three intervention groups. Ap-value < 0.05 was adopted as the level of statistical significance.ResultsIn the ranitidine group, stool frequency decreased significantly from an average of five per day on the first day to an average of approximately one per day on the 10th day of intervention (t = 10.462,p <  0.001). Additionally, stool consistency normalized on the 10th day of intervention. In the probiotic group, there was a significant reduction in stool frequency from an average of five per day on the first day to four per day on the 10th day (t = 2.586,p = 0.041), although stool consistency remained loose. However, stool consistency and frequency were not significantly affected in the placebo group (t = 1.964,p = 0.072).ConclusionOral ranitidine is more effective than probiotics in reducing stool frequency and normalizing stool consistency in toddler’s diarrhea. We recommend multi-center trials with appropriate study designs to confirm and validate this finding.Trial registrationISRCTN,ISRCTN10783996. Registered 8 April 2016-Registered retrospectively.
International time trends in sudden unexpected infant death, 1969–2012
Authors: Müller-Nordhorn Jacqueline , Schneider Alice , Grittner Ulrike , Neumann Konrad , Keil Thomas , Willich Stefan N. , Binting Sylvia 
Published: August 2020

Abstract
Background
Sudden unexpected infant death (SUID) - including sudden infant death syndrome (SIDS) - continues to be a major contributor to infant mortality worldwide. Our objective was to analyse time trends and to identify country-clusters.

Methods
The National Statistical Offices of 52 countries provided the number of deaths and live births (1969–2012). We calculated infant mortality rates per 1000 live births for SUID, SIDS, and all-cause mortality. Overall, 29 countries provided sufficient data for time course analyses of SUID. To sensitively model change over time, we smoothed the curves of mortality rates (1980–2010). We performed a hierarchical cluster analysis to identify clusters of time trends for SUID and SIDS, including all-cause infant mortality.

Results
All-cause infant mortality declined from 28.5 to 4.8 per 1000 live births (mean 12.4; 95% confidence interval 12.0–12.9) between 1969 and 2012. The cluster analysis revealed four country-clusters. Clusters 1 and 2 mostly contained countries showing the typical peak of SUID mortality during the 1980s. Cluster 1 had higher SUID mortality compared to cluster 2. All-cause infant mortality was low in both clusters but higher in cluster 1 compared to cluster 2. Clusters 3 and 4 had low rates of SUID without a peak during the 1980s. Cluster 3 had the highest all-cause infant mortality of all clusters. Cluster 4 had an intermediate all-cause infant mortality. The time trends of SUID and SIDS mortality were similar.

Conclusions
The country-specific time trends in SUID varied considerably. The identification of country-clusters may promote research into how changes in sleep position, smoking, immunisation, or other factors are related to our findings.
Observed trends in the magnitude of socioeconomic and area-based inequalities in use of caesarean section in Ethiopia: a cross-sectional study
Authors: Shibre Gebretsadik , Idriss-Wheeler Dina , Bishwajit Ghose , Yaya Sanni 
Published: August 2020

AbstractBackgroundIn Ethiopia, there is a paucity of studies on inequality in caesarean section using methodologically rigorous and well-established approaches. In this study, we showed extent and the overtime dynamics of inequality in caesarean section in Ethiopia following rigorous methodologies.MethodsThe data for analysis came from Ethiopia Demographic and Health Surveys (EDHS) conducted between 2000 and 2016. We used the World Health Organization’s (WHO) Health Equity Assessment Toolkit (HEAT) to analyze the data. Caesarean delivery was disaggregated by four equity stratifiers, namely education, wealth, residence and regions. Relative and absolute summary measures were calculated for each equity stratifier to capture inequality from different perspectives. 95% Uncertainty Interval was calculated around a point estimate to measure statistical significance.ResultsWe found large socioeconomic and area-based inequalities in use of caesarean section in all study surveys. The inequalities have occurred in favour of socioeconomically advantaged women and those living in urban areas and certain regions such as Addis Ababa. While area-related inequality had generally increased with time, socioeconomic inequality showed fluctuation. Adoption of different measures in the study for the inequality analysis has caused the emergence of mix of patterns in caesarean section inequality over time.ConclusionsIn all the surveys, wealthy and more educated women, and those residing in urban areas had higher chance of obtaining caesarean delivery. Policy makers should work to ensure caesarean section that is in the accepted normal range. More emphasis should be drawn to subpopulation with under use of caesarean section while at the same time, discouraging unjustified use of it.
The impact of injury definitions on measures of injury occurrence in classical music students: a prospective cohort study
Authors: Steemers Suze , van Middelkoop Marienke , de Boks Gideon G. , van Rijn Rogier M. , Bierma-Zeinstra Sita M. A. , Stubbe Janine H. 
Published: August 2020

AbstractBackgroundMultiple definitions are used to investigate injuries in musicians, resulting in a wide range of prevalence rates. The aim of this study is to establish the impact of different injury definitions on the prevalence of injuries and disability in classical music students. Moreover, the practical implications of using different injury definitions are considered.MethodsA prospective cohort study among first-year classical music students was performed using bi-monthly questionnaires focusing on injuries. Three injury definitions were used: 1) all MSK complaints injury (any MSK complaint resulting in a VAS pain score > 0 in the past eight weeks), 2) medical attention injury (any MSK complaint that resulted in a student consulting a health provider in the past eight weeks), 3) time-loss injury (any MSK complaint that resulted in partly/completely missing music classes or activities in the past eight weeks). For all injury definitions prevalences were calculated and compared. Furthermore, the Disabilities of the Arm, Shoulder and Hand performing arts module (DASH-pa) was used to calculate disability scores for all three injury definitions.ResultsTwenty-nine classical music students participated in the current study. The total response rate over one academic year was 85.3%. One year prevalences of all MSK complaints, medical attention and time-loss were 96.6, 17.2 and 13.8% respectively. The bi-monthly prevalences ranged from 74.1 to 96.0% for all MSK complaints, from 5.6 to 11.5% for medical attention injuries and from 0 to 11.5% for time loss injuries. Scores on the DASH-pa ranged from 15.6 to 26.9 for MSK complaints, 33.3 to 50 for medical attention and 47.9 to 62.5 for time-loss injuries.ConclusionThe choice of injury definition is a critical factor affecting the outcome of music injury surveillance studies. To reach a consensus, it is therefore important to consider the different injury definitions depending on the goal of the injury surveillance and the practical implications.
Concurrent validity and reliability of measuring range of motion during the cervical flexion rotation test with a novel digital goniometer
Authors: Luedtke Kerstin , Schoettker-Königer Thomas , Hall Toby , Reimer Christine , Grassold Maike , Hasselhoff-Styhler Petra , Neulinger Christian , Obrocki Max , Przyhoda Philipp , Schäfer Axel 
Published: August 2020

Abstract
Background
Headache is a common and costly health problem. Although the pathogenesis of headache is heterogeneous, reported contributing factors are dysfunctions of the upper cervical spine. The flexion rotation test (FRT) is a commonly used diagnostic test to detect upper cervical movement impairment. A digital goniometer may support precise measurement of movement impairment in the upper cervical spine. However, its reliability and validity is not assessed, yet. The aim of this study was to investigate the reliability and validity of the digital goniometer compared to an ultrasound-based movement analysis system.

Methods
Two separate cross-sectional studies were conducted using the digital goniometer EasyAngle (Meloq AB, Stockholm, Sweden) for a) investigating the concurrent validity of upper cervical range of motion (ROM) during the FRT and b) determining the inter- and intra-rater reliability in the target population of patients with head and neck pain. Sixty-two participants, 39 with and 23 without head and neck pain, were recruited for the concurrent validity study. For the reliability study, a total of 50 participants were recruited. Intraclass correlation coefficients (ICC) and Bland Altmann plots were used to assess validity and ICC values, Bland Altmann plots as well as Kappa coefficients were used for estimating intra-rater and inter-rater reliability.

Results
Concurrent validity was strong with an ICC (2,1) of 0.97 for ROM to either side (95%CI = 0.95–0.98). Bland Altman Plots revealed a mean difference between measurement systems of 0.5° for the left and 0.11° for the right side.
The inter-rater ICC (2,1) was 0.66 (95%CI 0.47–0.79, p <  0.001, SEM 6.6°), indicating good reliability. The limits of agreement were between 10.25° and − 11.89°, the mean difference between both raters was − 0.82°. Intra-rater reliability for the measurement of ROM during the FRT was between 0.96 (ICC 3,1) for rater 1 and 0.94 (ICC 3,1) for rater 2.

Conclusions
The digital goniometer demonstrated strong concurrent validity and good to strong reliability and can be used in clinical practice to accurately determine movement impairment in the upper cervical spine.

Trial registration
German Registry of Clinical Trials DRKS00013051.
Modelling the suppression of a malaria vector using a CRISPR-Cas9 gene drive to reduce female fertility
Authors: North Ace R. , Burt Austin , Godfray H. Charles J. 
Published: August 2020

AbstractBackgroundGene drives based on CRISPR-Cas9 technology are increasingly being considered as tools for reducing the capacity of mosquito populations to transmit malaria, and one of the most promising options is driving endonuclease genes that reduce the fertility of female mosquitoes. In particular, there is much interest in constructs that target the conserved mosquito doublesex (dsx) gene such that the emergence of functional drive-resistant alleles is unlikely. Proof of principle that these constructs can lead to substantial population suppression has been obtained in population cages, and they are being evaluated for use in sub-Saharan Africa. Here, we use simulation modelling to understand the factors affecting the spread of this type of gene drive over a one million-square kilometre area of West Africa containing substantial environmental and social heterogeneity.ResultsWe found that a driving endonuclease gene targeting female fertility could lead to substantial reductions in malaria vector populations on a regional scale. The exact level of suppression is influenced by additional fitness costs of the transgene such as the somatic expression of Cas9, and its deposition in sperm or eggs leading to damage to the zygote. In the absence of these costs, or of emergent drive-resistant alleles that restore female fertility, population suppression across the study area is predicted to stabilise at ~ 95% 4 years after releases commence. Small additional fitness costs do not greatly affect levels of suppression, though if the fertility of females whose offspring transmit the construct drops by more than ~ 40%, then population suppression is much less efficient. We show the suppression potential of a drive allele with high fitness costs can be enhanced by engineering it also to express male bias in the progeny of transgenic males. Irrespective of the strength of the drive allele, the spatial model predicts somewhat less suppression than equivalent non-spatial models, in particular in highly seasonal regions where dry season stochasticity reduces drive efficiency. We explored the robustness of these results to uncertainties in mosquito ecology, in particular their method of surviving the dry season and their dispersal rates.ConclusionsThe modelling presented here indicates that considerable suppression of vector populations can be achieved within a few years of using a female sterility gene drive, though the impact is likely to be heterogeneous in space and time.
The role of vegetative cell fusions in the development and asexual reproduction of the wheat fungal pathogen Zymoseptoria tritici
Authors: Francisco Carolina Sardinha , Zwyssig Maria Manuela , Palma-Guerrero Javier 
Published: August 2020

Abstract
Background
The ability of fungal cells to undergo cell-to-cell communication and anastomosis, the process of vegetative hyphal fusion, allows them to maximize their overall fitness. Previous studies in a number of fungal species have identified the requirement of several signaling pathways for anastomosis, including the so far best characterized soft (So) gene, and the MAPK pathway components MAK-1 and MAK-2 of Neurospora crassa. Despite the observations of hyphal fusions’ involvement in pathogenicity and host adhesion, the connection between cell fusion and fungal lifestyles is still unclear. Here, we address the role of anastomosis in fungal development and asexual reproduction in Zymoseptoria tritici, the most important fungal pathogen of wheat in Europe.

Results
We show that Z. tritici undergoes self-fusion between distinct cellular structures, and its mechanism is dependent on the initial cell density. Contrary to other fungi, cell fusion in Z. tritici only resulted in cytoplasmic mixing but not in multinucleated cell formation. The deletion of the So orthologous ZtSof1 disrupted cell-to-cell communication affecting both hyphal and germling fusion. We show that Z. tritici mutants for MAPK-encoding ZtSlt2 (orthologous to MAK-1) and ZtFus3 (orthologous to MAK-2) genes also failed to undergo anastomosis, demonstrating the functional conservation of this signaling mechanism across species. Additionally, the ΔZtSof1 mutant was severely impaired in melanization, suggesting that the So gene function is related to melanization. Finally, we demonstrated that anastomosis is dispensable for pathogenicity, but essential for the pycnidium development, and its absence abolishes the asexual reproduction of Z. tritici.

Conclusions
We demonstrate the role for ZtSof1, ZtSlt2, and ZtFus3 in cell fusions of Z. tritici. Cell fusions are essential for different aspects of the Z. tritici biology, and the ZtSof1 gene is a potential target to control septoria tritici blotch (STB) disease.