bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of a mobile phone-based interactive voice response software on tuberculosis treatment outcomes in Uganda (CFL-TB): a protocol for a randomized controlled trial
Authors: Byonanebye Dathan Mirembe , Mackline Hope , Sekaggya-Wiltshire Christine , Kiragga Agnes N. , Lamorde Mohammed , Oseku Elizabeth , King Rachel , Parkes-Ratanshi Rosalind 
Published: June 2021

Abstract
Background
Throughout the last decade, tuberculosis (TB) treatment success has not surpassed 90%, the global target. The impact of mobile health interventions (MHIs) on TB treatment outcomes is unknown, especially in low- and middle-income countries (LMICs). MHIs, including interactive voice response technology (IVRT), may enhance adherence and retention in the care of patients with tuberculosis and improve TB treatment outcomes. This study seeks to determine the impact of IVRT-based MHI on TB treatment success (treatment completion and cure rates) in patients with TB receiving care at five public health facilities in Uganda.

Methods
We used a theory-based and human-centered design (HCD) to adapt an already piloted software to design “Call for life-TB” (CFL-TB), an MHI that utilizes IVRT to deliver adherence and appointment reminders and allows remote symptom reporting. This open-label, multicenter, randomized controlled trial (RCT), with nested qualitative and economic evaluation studies, will determine the impact of CFL-TB on TB treatment success in patients with drug-susceptible TB in Uganda. Participants (n = 274) at the five study sites will be randomized (1:1 ratio) to either control (standard of care) or intervention (adherence and appointment reminders, and health tips) arms. Multivariable regression models will be used to compare treatment success, adherence to treatment and clinic appointments, and treatment completion at 6 months post-enrolment. Additionally, we will determine the cost-effectiveness, acceptability, and perceptions of stakeholders. The study received national ethical approval and was conducted in accordance with the international ethical guidelines.

Discussion
This randomized controlled trial aims to evaluate interactive voice response technology in the context of resource-limited settings with a high burden of TB and high illiteracy rates. The software to be evaluated was developed using HCD and the intervention was based on the IMB model. The software is tailored to the local context and is interoperable with the MHI ecosystem. The HCD approach ensures higher usability of the MHI by integrating human factors in the prototype development. This research will contribute towards the understanding of the implementation and impact of the MHI on TB treatment outcomes and the health system, especially in LMICs.

Trial registration
ClinicalTrials.govNCT04709159. Registered on January 14, 2021.
Excretion of Histomonas meleagridis following experimental co-infection of distinct chicken lines with Heterakis gallinarum and Ascaridia galli
Authors: Daş Gürbüz , Wachter Lukas , Stehr Manuel , Bilic Ivana , Grafl Beatrice , Wernsdorf Patricia , Metges Cornelia C. , Hess Michael , Liebhart Dieter 
Published: June 2021

Abstract
Background
Histomonosis is a severe re-emerging disease of poultry caused by Histomonas meleagridis, a protozoan parasite which survives in the environment via the cecal worm Heterakis gallinarum. Following infection, the parasites reside in the ceca and are excreted via host feces. In the present work, male birds of conventional broiler (Ross 308, R), layer (Lohmann Brown Plus, LB) and a dual-purpose (Lohmann Dual, LD) chicken line were infected with 250 embryonated eggs of Ascaridia galli and Heterakis gallinarum, respectively, with the latter nematode harboring Histomonas meleagridis, to investigate a co-infection of nematodes with the protozoan parasite in different host lines.

Methods
In weekly intervals, from 2 to 9 weeks post infection (wpi), individual fecal samples (n = 234) from the chickens were collected to quantify the excretion of H. meleagridis by real-time PCR and to determine the number of nematode eggs per gram (EPG) in order to elucidate excretion dynamics of the flagellate and the nematodes. This was further investigated by indirect detection using plasma samples of the birds to detect antibodies specific for H. meleagridis and worms by ELISA. The infection with H. meleagridis was confirmed by histopathology and immunohistochemistry to detect the flagellate in the cecum of representing birds.

Results
The excretion of H. meleagridis could already be observed from the 2nd wpi in some birds and increased to 100% in the last week of the experiment in all groups independent of the genetic line. This increase could be confirmed by ELISA, even though the number of excreted H. meleagridis per bird was generally low. Overall, histomonads were detected in 60% to 78% of birds with temporary differences between the different genetic lines, which also showed variations in the EPG and worm burden of both nematodes.

Conclusions
The infection with H. gallinarum eggs contaminated with H. meleagridis led to a permanent excretion of the flagellate in host feces. Differences in the excretion of H. meleagridis in the feces of genetically different host lines occurred intermittently. The excretion of the protozoan or its vector H. gallinarum was mostly exclusive, showing a negative interaction between the two parasites in the same host.

Graphic abstract
Peak week recommendations for bodybuilders: an evidence based approach
Authors: Escalante Guillermo , Stevenson Scott W. , Barakat Christopher , Aragon Alan A. , Schoenfeld Brad J. 
Published: June 2021

AbstractBodybuilding is a competitive endeavor where a combination of muscle size, symmetry, “conditioning” (low body fat levels), and stage presentation are judged. Success in bodybuilding requires that competitors achieve their peak physique during the day of competition. To this end, competitors have been reported to employ various peaking interventions during the final days leading to competition. Commonly reported peaking strategies include altering exercise and nutritional regimens, including manipulation of macronutrient, water, and electrolyte intake, as well as consumption of various dietary supplements. The primary goals for these interventions are to maximize muscle glycogen content, minimize subcutaneous water, and reduce the risk abdominal bloating to bring about a more aesthetically pleasing physique. Unfortunately, there is a dearth of evidence to support the commonly reported practices employed by bodybuilders during peak week. Hence, the purpose of this article is to critically review the current literature as to the scientific support for pre-contest peaking protocols most commonly employed by bodybuilders and provide evidence-based recommendations as safe and effective strategies on the topic.
Does the epigenetic clock GrimAge predict mortality independent of genetic influences: an 18 year follow-up study in older female twin pairs
Authors: Föhr Tiina , Waller Katja , Viljanen Anne , Sanchez Riikka , Ollikainen Miina , Rantanen Taina , Kaprio Jaakko , Sillanpää Elina 
Published: June 2021

AbstractBackgroundEpigenetic clocks are based on DNA methylation (DNAm). It has been suggested that these clocks are useable markers of biological aging and premature mortality. Because genetic factors explain variations in both epigenetic aging and mortality, this association could also be explained by shared genetic factors. We investigated the influence of genetic and lifestyle factors (smoking, alcohol consumption, physical activity, chronic diseases, body mass index) and education on the association of accelerated epigenetic aging with mortality using a longitudinal twin design. Utilizing a publicly available online tool, we calculated the epigenetic age using two epigenetic clocks, Horvath DNAmAge and DNAm GrimAge, in 413 Finnish twin sisters, aged 63–76 years, at the beginning of the 18-year mortality follow-up. Epigenetic age acceleration was calculated as the residuals from a linear regression model of epigenetic age estimated on chronological age (AAHorvath, AAGrimAge, respectively). Cox proportional hazard models were conducted for individuals and twin pairs.ResultsThe results of the individual-based analyses showed an increased mortality hazard ratio (HR) of 1.31 (CI95: 1.13–1.53) per one standard deviation (SD) increase in AAGrimAge. The results indicated no significant associations of AAHorvathwith mortality. Pairwise mortality analyses showed an HR of 1.50 (CI95: 1.02–2.20) per 1 SD increase in AAGrimAge. However, after adjusting for smoking, the HR attenuated substantially and was statistically non-significant (1.29; CI95: 0.84–1.99). Similarly, in multivariable adjusted models the HR (1.42–1.49) was non-significant. In AAHorvath, the non-significant HRs were lower among monozygotic pairs in comparison to dizygotic pairs, while in AAGrimAgethere were no systematic differences by zygosity. Further, the pairwise analysis in quartiles showed that the increased within pair difference in AAGrimAgewas associated with a higher all-cause mortality risk.ConclusionsIn conclusion, the findings suggest that DNAm GrimAge is a strong predictor of mortality independent of genetic influences. Smoking, which is known to alter DNAm levels and is built into the DNAm GrimAge algorithm, attenuated the association between epigenetic aging and mortality risk.
ScrumOntoBDD: Agile software development based on scrum, ontologies and behaviour-driven development
Authors: Lopes de Souza Pedro , Lopes de Souza Wanderley , Ferreira Pires Luís 
Published: June 2021

AbstractWhen developing a Learning Management System (LMS) using Scrum, we noticed that it was quite often necessary to redefine some system behaviour scenarios, due to ambiguities in the requirement specifications, or due to misinterpretations of stories reported by the Product Owners (POs). The definition of test suites was also cumbersome, resulting in test suites that were incomplete or did not at all comply with the system requirements. Based on this experience and to deal with these problems, in this paper, we propose the ScrumOntoBDD approach to agile software development, which combines Scrum, ontologies and Behaviour-Driven Development (BDD). This approach is centred on the concepts and techniques of Scrum and BDD and focuses on the planning and analysis phases of the software life cycle, since the BDD tools currently provide little support to these phases, while most of the problems during the LMS development were found exactly there. We claim that our approach improves the software development practices in this respect. Furthermore, ScrumOntoBDD employs ontologies in order to reduce ambiguities intrinsic to the use of a natural language as a BDD ubiquitous language. In this paper, we illustrate and systematically evaluate our approach, showing that it is beneficial since it improves the communication between members of an agile development team.
Network meta-analysis of short-term effects of different strategies in the conservative treatment of AIS
Authors: Li Kepeng , Miao Jun , Zhang Jingan 
Published: June 2021

Abstract
Purpose
To evaluate the short-term effects of different conservative treatments on in adolescent idiopathic scoliosis.

Methods
By searching the relevant literature of adolescent idiopathic scoliosis, the curative effects of the three regimens of bracing therapy combined with scoliosis-specific exercises, simple treatment with brace and simple scoliosis-specific exercises were compared. Review manager 5.3, Stata MP16 and Network software packages were used for Reticular Meta-analysis of Cobb’s angles before and after treatment.

Results
A total of 364 patients were included in four clinical studies. Reticular meta-analysis showed that the short-term effect of bracing treatment combined with scoliosis-specific exercises was better than that of treatment with brace and scoliosis-specific exercises, with effects of 2.71(95% CI 0.83–4.58) and 3.67(95% CI 1.21–6.14), respectively. There was no statistical difference between simple bracing therapy and scoliosis-specific exercises.

Conclusion
Among the three common conservative treatments of adolescent idiopathic scoliosis, the short-term effect of bracing treatment combined with scoliosis-specific exercises is better than that of bracing treatment or scoliosis-specific exercises.
Organizational forms and technical efficiency of the dairy processing industry in Southern Brazil
Authors: Beber Caetano Luiz , Lakner Sebastian , Skevas Ioannis 
Published: June 2021

AbstractThe objective of this article is to assess the determinants of the technical efficiency of dairy processing firms in Southern Brazil while accounting for their different organizational forms, namely cooperatives and investor-owned firms. The data from 243 milk processors in southern Brazil, including firm structure, management capacity, and organizational choice of dairies, were analyzed. A production frontier is specified to estimate technical efficiency and identify its potential driving sources. Bayesian techniques are used to estimate the model. An average efficiency of 77% indicates that the actual output is 23% below its potential, which implies that output could, on average, be increased by approximately 31.6%, under ceteris paribus conditions. Economies of scale were also detected. The analysis reveals that the management capacity within companies is the main determinant of efficiency. Idle capacities of processing plants are an important source of inefficiencies and cooperatives are more efficient than investor-owned firms, despite their transaction costs potentially being higher and the five vaguely defined property rights inherent to the traditional cooperatives which they must overcome. Knowledge about the cooperatives’ objectives other than profit maximization would provide a more realistic comparison against investor-owned firms. This study assessed the determinants of the efficiency levels of dairy processing companies in an emerging economy using a unique own dataset with data collected at a plant level. Based on the results, manifold managerial and political implications have been derived that can benefit the dairy industry of developing and emerging economies.
Whole exome sequencing reveals a novel LRBA mutation and clonal hematopoiesis in a common variable immunodeficiency patient presented with hemophagocytic lymphohistiocytosis
Authors: Ren Yanling , Xiao Feng , Cheng Fei , Huang Xin , Li Jianhu , Wang Xiaogang , Lang Wei , Zhou Xinping , Lan Jianping , Tong Hongyan 
Published: June 2021

AbstractCommon variable immunodeficiency (CVID) was a kind of primary immunodeficiency disorders with heterogeneous phenotype and genotype. Lipopolysaccharide-responsive and beige-like anchor (LRBA) mutation was identified as disease associated in CVID, advanced genetic method will help to detect atypical cases. We report a case of adult patient manifested as hemophagocytic lymphohistiocytosis (HLH), bone marrow examination suggested prosperity to MDS, manifested as increased immature myeloid cells and dysplastic hematopoiesis. Whole exome sequencing (WES) identified a novel heterogeneous c.1876T > C (p.W626R) mutation in LRBA and four somatic mutations: ASXL1 (c.1967dupA); PTPN11 (c.226G > A), U2AF1 (c.101C > T and c.470A > G), among which ASXL1 was a high-risk marker of clonal hematopoiesis. Combined with her recurrent severe infections and immune abnormalities such as hypoimmunoglobulinemia, the patient was diagnosed with CVID. Subsequent hematopoietic stem cell transplantation saved her from severe cytopenia and immune deficiency. This case report highlights the great promise of utilization of WES for diagnosing rare disease with atypical manifestations and guiding further treatment.
Assessment of safety and tolerability of remogliflozin etabonate (GSK189075) when administered with total daily dose of 2000 mg of metformin
Authors: Dobbins Robert , Hussey Elizabeth K. , O’Connor-Semmes Robin , Andrews Susan , Tao Wenli , Wilkison William O. , Cheatham Bentley , Sagar Katare , Hanmant Barkate 
Published: June 2021

Abstract
Background
Patients with type 2 diabetes mellitus (T2DM) are characterized by an elevated glycemic index and are at a higher risk for complications such as cardiovascular disease, nephropathy, retinopathy and peripheral neuropathy. Normalization of glycemic index can be achieved by dosing combinations of metformin with other anti-diabetic drugs. The present study (Clintrials number NCT00519480) was conducted to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of remogliflozinetabonate, an SGLT2 inhibitor, withdoses (500 mg and 750 mg BID) greater than the commercial dose (100 mg BID)in combination with metformin with minimum daily dose of 2000 mg given in two divided doses.

Methods
This was a randomized, double-blinded, repeat dose study in 50 subjects with T2DM. The study was conducted in three phases; run-in, randomization, and treatment. All subjects were on a stable metformin dosing regimen. Cohort 1 subjects were randomly allocated to receive either remogliflozin etabonate 500 mg BID or placebo BID (2:1) in addition to metformin. Cohort 2 subjects were administered with either remogliflozin etabonate 750 mg BID or placebo BID (2:1) in addition to metformin for 13 days. All the subjects were assessed for safety (adverse events, lactic acid levels, vital signs, electrocardiogram [ECG]), pharmacokinetic evaluation, and pharmacodynamics (Oral Glucose Tolerance Testing) parameters.

Results
Co-administration of remogliflozin etabonate and metformin was well tolerated in all subjects during the observation period. There were no severe or serious adverse events (SAEs) and no increase in lactic acid concentration was reported during the study. The statistical results showed that concomitant administration of remogliflozin etabonate, either 500 mg or 750 mg BID, with metformin had no effect on the pharmacokinetics of metformin. The accumulation ratios, Day 13 vs. Day 1, for AUC values of remogliflozin etabonate and its metabolites were all very close to 1, indicating no accumulation in plasma concentrations of remogliflozin etabonate and its metabolites. Mean glucose values from baseline and glucose and insulin values following oral glucose tolerance test (OGTT) were decreased in all treatment groups.

Conclusion
Co-administration of doses of remogliflozin etabonate (500 mg BID or 750 mg BID) greater than the commercial dose (100 mg BID) with metformin (2000 mg BID) was shown to be safe and effective during the observation period.

Trial registration
ClinicalTrials.gov, NCT00519480. Registered:22 August 2007.
Far eastern curlew and whimbrel prefer flying low - wind support and good visibility appear only secondary factors in determining migratory flight altitude
Authors: Galtbalt Batbayar , Lilleyman Amanda , Coleman Jonathan T. , Cheng Chuyu , Ma Zhijun , Rogers Danny I. , Woodworth Bradley K. , Fuller Richard A. , Garnett Stephen T. , Klaassen Marcel 
Published: June 2021

AbstractBackgroundIn-flight conditions are hypothesized to influence the timing and success of long-distance migration. Wind assistance and thermal uplift are thought to reduce the energetic costs of flight, humidity, air pressure and temperature may affect the migrants’ water balance, and clouds may impede navigation. Recent advances in animal-borne long-distance tracking enable evaluating the importance of these factors in determining animals’ flight altitude.MethodsHere we determine the effects of wind, humidity, temperature, cloud cover, and altitude (as proxy for climbing costs and air pressure) on flight altitude selection of two long-distance migratory shorebirds, far eastern curlew (Numenius madagascariensis) and whimbrel (Numenius phaeopus). To reveal the predominant drivers of flight altitude selection during migration we compared the atmospheric conditions at the altitude the birds were found flying with conditions elsewhere in the air column using conditional logistic mixed effect models.ResultsOur results demonstrate that despite occasional high-altitude migrations (up to 5550 m above ground level), our study species typically forego flying at high altitudes, limiting climbing costs and potentially alleviating water loss and facilitating navigation. While mainly preferring migrating at low altitude, notably in combination with low air temperature, the birds also preferred flying with wind support to likely reduce flight costs. They avoided clouds, perhaps to help navigation or to reduce the risks from adverse weather.ConclusionsWe conclude that the primary determinant of avian migrant’s flight altitude selection is a preference for low altitude, with wind support as an important secondary factor. Our approach and findings can assist in predicting climate change effects on migration and in mitigating bird strikes with air traffic, wind farms, power lines, and other human-made structures.
The time is now: why we must identify and address health disparities in sport and recreation injury
Authors: Baker Charlotte , Chinaka Oziomachukwu , Stewart Elizabeth C. 
Published: June 2021

Abstract
Background
Social and structural determinants of health (SDOH) are the conditions in which individuals are born, live, learn, work, play, worship, and age. These drivers of health are integral in contextualizing the understanding and prevention of sport and recreation injury (SRI), and recognizing their impact is necessary to provide a complete and accurate picture of health and health outcomes related to injury.

Main
Reducing disparities and achieving equity in sports and recreation is possible in part by improving data collection methodologies and utilization. Often, many SDOH have considerable effect on SRI. Although SRI epidemiology frequently examines differences by sex, there is limited inclusion of factors such as socioeconomic status, housing, gender, and food security, in sport specific data sources or in analysis of sport recreation and injury using other sources (e.g. administrative data). The ongoing dual epidemics in the United States – racism and COVID-19 – have emphasized the importance of having and utilizing SDOH data to reduce the burden of injury and disproportionate effects on our diverse population.

Conclusion
Moving forward, to address disparities in SRI, SDOH must be included as a part of research priorities, health related goals, and policies. This difference can be made in developing consistency in data collection and utilization. This will provide an accurate picture of the intersections and interdisciplinary changes required to design the best approach to problems to develop solutions. Future data collection and utilization should prioritize SDOH.
Recognition and management of rapid-onset gluten ataxias: case series
Authors: Newrick Laurence , Hoggard Nigel , Hadjivassiliou Marios 
Published: June 2021

Abstract
Background
Most immune-mediated cerebellar ataxias, including those associated with gluten sensitivity (Gluten Ataxia), tend to present subacutely and usually progress gradually. Acute presentations with rapid progression outside the context of paraneoplastic cerebellar degeneration require prompt diagnosis and early access to disease-modifying immunotherapy in order to avert severe and permanent neurological disability.

Case presentations
We describe three cases of rapid-onset Gluten Ataxia, an immune-mediated cerebellar ataxia due to gluten sensitivity. We detail their presentation, clinical and neuroimaging findings, and our treatment strategy with immunotherapy.

Conclusions
Our cases highlight the potential for immune-mediated cerebellar ataxias to present acutely, with rapid-onset symptoms and devastating neurological consequences. We caution against the diagnosis of ‘post-infective cerebellitis’ in adults, and advocate early consideration of an immune-mediated cerebellar ataxia and initiation of immunotherapy to prevent irreversible cerebellar damage.