bluuebunny/crossref_metadata_2025_split huggingface dataset:
How do Japanese rate the severity of different diseases and injuries?—an assessment of disability weights for 231 health states by 37,318 Japanese respondents
Authors: Nomura Shuhei , Yamamoto Yoshiko , Yoneoka Daisuke , Haagsma Juanita A. , Salomon Joshua A. , Ueda Peter , Mori Rintaro , Santomauro Damian , Vos Theo , Shibuya Kenji 
Published: April 2021

Abstract
Background
Disability weights (DWs) are weight factors that reflect the severity of health states for estimates of disability-adjusted life years. A new set of global DWs was published for the Global Burden of Diseases and Injuries (GBD) 2013 study, which relied on sampling from various world regions, but included little data for countries in East Asia. This study aimed to measure DWs in Japan using comparable methods, and compare the results with previous estimates from the GBD 2013 DW study.

Methods
We conducted a web-based survey in 2019 to estimate DWs for 231 health states for the Japanese population. The survey included five new health states but otherwise followed the method of the GBD DW measurement study. The survey consisted of 15 paired comparison (PC) questions and 3 population health equivalence questions (PHE) per respondent. We analyzed PC data using probit regression and rescaled results to DW units between 0 (equivalent to full health) and 1 (equivalent to death).

Findings
We considered 37,318 nationally representative respondents. The values of the resulting DWs ranged from 0.707 (95% uncertainty interval (UI) 0.527–0.842) for spinal cord injury at neck level (untreated) to 0.004 (UI 0.001–0.009) for mild anemia. High correlation between Japanese DW and GBD 2013 DW was observed, but there was considerable disagreement. Out of 226 comparable health states, 55 (24.3%) showed more than a factor-of-two difference, of which 41 (74.6%) had a higher value in Japanese DW. Many of the health states with higher DW in the Japan study were injuries, including amputation and fracture, and hearing and vision loss, while mental, behavioral, and substance use disorders generally tended to be lower.

Conclusions
This study has created an empirical basis for assessment of Japanese DWs of health status. The findings from this study based on the Japanese population suggest that there might be contextual differences in rating the severity of health states compared to previous surveys conducted elsewhere.
The exosome journey: from biogenesis to uptake and intracellular signalling
Authors: Gurung Sonam , Perocheau Dany , Touramanidou Loukia , Baruteau Julien 
Published: April 2021

AbstractThe use of exosomes in clinical settings is progressively becoming a reality, as clinical trials testing exosomes for diagnostic and therapeutic applications are generating remarkable interest from the scientific community and investors. Exosomes are small extracellular vesicles secreted by all cell types playing intercellular communication roles in health and disease by transferring cellular cargoes such as functional proteins, metabolites and nucleic acids to recipient cells. An in-depth understanding of exosome biology is therefore essential to ensure clinical development of exosome based investigational therapeutic products. Here we summarise the most up-to-date knowkedge about the complex biological journey of exosomes from biogenesis and secretion, transport and uptake to their intracellular signalling. We delineate the major pathways and molecular players that influence each step of exosome physiology, highlighting the routes of interest, which will be of benefit to exosome manipulation and engineering. We highlight the main controversies in the field of exosome research: their adequate definition, characterisation and biogenesis at plasma membrane. We also delineate the most common identified pitfalls affecting exosome research and development. Unravelling exosome physiology is key to their ultimate progression towards clinical applications.
Combination of subtherapeutic anti-TNF dose with dasatinib restores clinical and molecular arthritogenic profiles better than standard anti-TNF treatment
Authors: Ntari Lydia , Nikolaou Christoforos , Kranidioti Ksanthi , Papadopoulou Dimitra , Christodoulou-Vafeiadou Eleni , Chouvardas Panagiotis , Meier Florian , Geka Christina , Denis Maria C. , Karagianni Niki , Kollias George 
Published: April 2021

Abstract
Background
New medications for Rheumatoid Arthritis (RA) have emerged in the last decades, including Disease Modifying Antirheumatic Drugs (DMARDs) and biologics. However, there is no known cure, since a significant proportion of patients remain or become non-responders to current therapies. The development of new mode-of-action treatment schemes involving combination therapies could prove successful for the treatment of a greater number of RA patients.

Methods
We investigated the effect of the Tyrosine Kinase inhibitors (TKIs) dasatinib and bosutinib, on the human TNF-dependent Tg197 arthritis mouse model. The inhibitors were administered either as a monotherapy or in combination with a subtherapeutic dose of anti-hTNF biologics and their therapeutic effect was assessed clinically, histopathologically as well as via gene expression analysis and was compared to that of an efficient TNF monotherapy.

Results
Dasatinib and, to a lesser extent, bosutinib inhibited the production of TNF and proinflammatory chemokines from arthritogenic synovial fibroblasts. Dasatinib, but not bosutinib, also ameliorated significantly and in a dose-dependent manner both the clinical and histopathological signs of Tg197 arthritis. Combination of dasatinib with a subtherapeutic dose of anti-hTNF biologic agents, resulted in a synergistic inhibitory effect abolishing all arthritis symptoms. Gene expression analysis of whole joint tissue of Tg197 mice revealed that the combination of dasatinib with a low subtherapeutic dose of Infliximab most efficiently restores the pathogenic gene expression profile to that of the healthy state compared to either treatment administered as a monotherapy.

Conclusion
Our findings show that dasatinib exhibits a therapeutic effect in TNF-driven arthritis and can act in synergy with a subtherapeutic anti-hTNF dose to effectively treat the clinical and histopathological signs of the pathology. The combination of dasatinib and anti-hTNF exhibits a distinct mode of action in restoring the arthritogenic gene signature to that of a healthy profile. Potential clinical applications of combination therapies with kinase inhibitors and anti-TNF agents may provide an interesting alternative to high-dose anti-hTNF monotherapy and increase the number of patients responding to treatment.
Non-pharmacological interventions of pain management used during labour; an exploratory descriptive qualitative study of puerperal women in Adidome Government Hospital of the Volta Region, Ghana
Authors: Konlan Kennedy Diema , Afaya Agani , Mensah Eugenia , Suuk Amos Nawunimali , Kombat Dahamata Issahaku 
Published: April 2021

AbstractBackgroundWomen have experienced labour pain over the years as various attempts have been made to effectively manage this pain. There is paucity of literature on the experiences and perceptions about labour pain management with the contemporary Ghanaian health system. This study explored the perspective of puerperal women on the use of non-pharmacological labour pain management at Adidome Government Hospital.MethodsThe study adopted an exploratory descriptive qualitative approach as data was collected through individual interviews. Informed consent was obtained from all participants who were purposely sampled until data saturation was reached on the 17th participant. Interviews were audio recorded and transcribed immediately. Thematic analysis was engaged in three interrelated stages, namely data reduction, data display, and data conclusion to analyse the transcript and field notes. Results were presented with supporting quotes from the transcripts.ResultsThe women described labour pain as very severe, severe and moderate as the pain lasted more than 12 h. The various strategies adopted in managing labour pains included shouting and walking around, crying and screaming and staying calm and snapping the fingers. Other pain management strategies adopted during labour included women engaged in deep breathing exercises, chatting with other people and relatives, diversion therapy, reassurance, taking a shower, assuming side lying positions, and receiving intravenous therapy. The presence of the husband of a labouring woman during labour improved pain bearing ability.ConclusionIt is important that midwives institute pragmatic protocols in the labour ward that ensure a relaxing atmosphere for women in labour, respond to the sensitivity and specificity of labouring women needs and when possible significant others (e.g., husband) of the labouring women could be allowed to visit. Labour wards should be made sound proof to allow women the ability to express themselves satisfactorily during labour without fear of being heard outside.
The expansion of a patient tracer programme to identify and return patients loss to follow up at a large HIV clinic in Trinidad
Authors: Edwards R. Jeffrey , Lyons Nyla , Samaroo-Francis Wendy , Lavia Leon-Omari , John Isshad , Todd Selena , Edwards Jonathan , Boyce Gregory 
Published: April 2021

Abstract
Background
Patients who default from HIV care are usually poorly adherent to antiretroviral treatment which results in suboptimal viral suppression. The study assessed the outcomes of retention in care and viral suppression by expansion of an intervention using two patient tracers to track patients lost to follow up at a large HIV clinic in Trinidad.

Methods
Two Social Workers were trained as patient tracers and hired for 15 months (April 2017–June 2018) to call patients who were lost to follow up for 30 days or more during the period July 2016–May 2018 at the HIV clinic Medical Research Foundation of Trinidad and Tobago.

Results
Over the 15-month period, of the of 2473 patients who missed their scheduled visits for 1 month or more, 261 (10.6%) patients were no longer in active care—89 patients dead, 65 migrated, 55 hospitalized, 33 transferred to another treatment clinic and 19 incarcerated. Of the remaining 2212 patients eligible for tracing, 1869 (84.5%) patients were returned to care, 1278 (68.6%) were virally unsuppressed (viral load > 200 copies/ml) and 1727 (92.4%) were re-initiated on ART. Twelve months after their return, 1341 (71.7%) of 1869 patients were retained in care and 1154 (86.1%) of these were virally suppressed. Multivariate analysis using logistic regression showed that persons were more likely to be virally suppressed if they were employed (OR, 1.39; 95% CI 1.07–1.80), if they had baseline CD4 counts < 200 cells/mm3 (OR, 1.71; 95% CI 1.26–2.32) and if they were retained in care at 12 months (OR, 2.48; 95% CI 1.90–3.24). Persons initiated on ART for 4–6 years (OR, 3.09; 95% CI 1.13–8.48,), 7–9 years (OR, 3.97; 95% CI 1.39–11.31), > 10 years (OR, 5.99; 95% CI 1.74–20.64 were more likely to be retained in care.

Conclusions
Patient Tracing is a feasible intervention to identify and resolve the status of patients who are loss to follow up and targeted interventions such as differentiated care models may be important to improve retention in care.
Task-specific training for improving propulsion symmetry and gait speed in people in the chronic phase after stroke: a proof-of-concept study
Authors: Alingh J. F. , Groen B. E. , Kamphuis J. F. , Geurts A. C. H. , Weerdesteyn V. 
Published: April 2021

AbstractBackgroundAfter stroke, some individuals have latent, propulsive capacity of the paretic leg, that can be elicited during task-specific gait training. The aim of this proof-of-concept study was to investigate the effect of five-week robotic gait training for improving propulsion symmetry by increasing paretic propulsion in chronic stroke survivors.MethodsTwenty-nine individuals with chronic stroke and impaired paretic propulsion (≥ 8% difference in paretic vs. non-paretic propulsive impulse) were enrolled. Participants received ten 60-min sessions of individual robotic gait training targeting paretic propulsion (five weeks, twice a week), complemented with home exercises (15 min/day) focusing on increasing strength and practicing learned strategies in daily life. Propulsion measures, gait kinematics and kinetics, self-selected gait speed, performance of functional gait tasks, and daily-life mobility and physical activity were assessed five weeks (T0) and one week (T1) before the start of intervention, and one week (T2) and five weeks (T3) after the intervention period.ResultsBetween T0 and T1, no significant differences in outcomes were observed, except for a marginal increase in gait speed (+ 2.9%). Following the intervention, propulsion symmetry (+ 7.9%) and paretic propulsive impulse had significantly improved (+ 8.1%), whereas non-paretic propulsive impulse remained unchanged. Larger gains in propulsion symmetry were associated with more asymmetrical propulsion at T0. In addition, following the intervention significantly greater paretic trailing limb angles (+ 6.6%) and ankle plantarflexion moments (+ 7.1%) were observed. Furthermore, gait speed (+ 7.2%), 6-Minute Walk Test (+ 6.4%), Functional Gait Assessment (+ 6.5%), and daily-life walking intensity (+ 6.9%) had increased following the intervention. At five-week follow-up (T3), gains in all outcomes were retained, and gait speed had further increased (+ 3.6%).ConclusionsThe post-intervention gain in paretic propulsion did not only translate into improved propulsion symmetry and gait speed, but also pertained to performance of functional gait tasks and daily-life walking activity levels. These findings suggest that well-selected chronic stroke survivors may benefit from task-specific targeted training to utilize the residual propulsive capacity of the paretic leg. Future research is recommended to establish simple baseline measures for identification of individuals who may benefit from such training and confirm benefits of the used training concepts in a randomized controlled trial.Trial registration:Registry number ClinicalTrials.gov (www.clinicaltrials.gov): NCT04650802, retrospectively registered 3 December 2020.
Validity, reliability, and sensitivity to motor impairment severity of a multi-touch app designed to assess hand mobility, coordination, and function after stroke
Authors: Mollà-Casanova Sara , Llorens Roberto , Borrego Adrián , Salinas-Martínez Bárbara , Serra-Añó Pilar 
Published: April 2021

AbstractBackgroundThe assessment of upper-limb motor impairments after stroke is usually performed using clinical scales and tests, which may lack accuracy and specificity and be biased. Although some instruments exist that are capable of evaluating hand functions and grasping during functional tasks, hand mobility and dexterity are generally either not specifically considered during clinical assessments or these examinations lack accuracy. This study aimed to determine the convergent validity, reliability, and sensitivity to impairment severity after a stroke of a dedicated, multi-touch app, named theHand Assessment Test.MethodsThe hand mobility, coordination, and function of 88 individuals with stroke were assessed using the app, and their upper-limb functions were assessed using theFugl-Meyer Assessment for Upper Extremity, theJebsen-Taylor Hand Function Test, theBox and Block Test,and theNine Hole Peg Test. Twenty-three participants were further considered to investigate inter- and intra-rater reliability, standard error of measurement, and the minimal detectable change threshold of the app. Finally, participants were categorized according to motor impairment severity and the sensitivity of the app relative to these classifications was investigated.ResultsSignificant correlations, of variable strengths, were found between the measurements performed by the app and the clinical scales and tests. Variable reliability, ranging from moderate to excellent, was found for all app measurements. Exercises that involved tapping and maximum finger-pincer grasp were sensitive to motor impairment severity.ConclusionsThe convergent validity, reliability, and sensitivity to motor impairment severity of the app, especially of those exercises that involved tapping and the maximum extension of the fingers, together with the widespread availability of the app, could support the use of this and similar apps to complement conventional clinical assessments of hand function after stroke.
Optimization of AAV vectors to target persistent viral reservoirs
Authors: Colón-Thillet Rossana , Jerome Keith R. , Stone Daniel 
Published: April 2021

AbstractGene delivery of antiviral therapeutics to anatomical sites where viruses accumulate and persist is a promising approach for the next generation of antiviral therapies. Recombinant adeno-associated viruses (AAV) are one of the leading vectors for gene therapy applications that deliver gene-editing enzymes, antibodies, and RNA interference molecules to eliminate viral reservoirs that fuel persistent infections. As long-lived viral DNA within specific cellular reservoirs is responsible for persistent hepatitis B virus, Herpes simplex virus, and human immunodeficiency virus infections, the discovery of AAV vectors with strong tropism for hepatocytes, sensory neurons and T cells, respectively, is of particular interest. Identification of natural isolates from various tissues in humans and non-human primates has generated an extensive catalog of AAV vectors with diverse tropisms and transduction efficiencies, which has been further expanded through molecular genetic approaches. The AAV capsid protein, which forms the virions' outer shell, is the primary determinant of tissue tropism, transduction efficiency, and immunogenicity. Thus, over the past few decades, extensive efforts to optimize AAV vectors for gene therapy applications have focused on capsid engineering with approaches such as directed evolution and rational design. These approaches are being used to identify variants with improved transduction efficiencies, alternate tropisms, reduced sequestration in non-target organs, and reduced immunogenicity, and have produced AAV capsids that are currently under evaluation in pre-clinical and clinical trials. This review will summarize the most recent strategies to identify AAV vectors with enhanced tropism and transduction in cell types that harbor viral reservoirs.
How has sustainable development goals declaration influenced health financing reforms for universal health coverage at the country level? A scoping review of literature
Authors: Odoch Walter Denis , Senkubuge Flavia , Hongoro Charles 
Published: April 2021

AbstractBackgroundAchieving universal health coverage (UHC) requires health financing reforms (HFR) in many of the countries. HFR are inherently political. The sustainable development goals (SDG) declaration provides a global political commitment context that can influence HFR for UHC at national level. However, how the declaration has influenced HFR discourse at the national level and how ministries of health and other stakeholders are using the declaration to influence reforms towards UHC have not been explored. This review was conducted to provide information and lessons on how SDG declaration can influence health financing reforms for UHC based on countries experiences.MethodsWe conducted a rapid review of literature and followed the preferred reporting items for systematic review and meta-analysis (PRISMA) guideline. We conducted a comprehensive electronic search on Ovid Medline, PubMed, EBSCO, Scopus, Web of Science. In searching the electronic databases, we combined various conceptual terms for “sustainable development goals” and “health financing” using Boolean operators. In addition, we conducted manual searched using google scholar.ResultsTwelve articles satisfied our eligibility criteria. The included articles were analyzed thematically, and the results presented narratively. The SDG declaration has provided an enabling environment for putting in place necessary legislations, reforming health financing organization, and revisions of national health polices to align to the country’s commitment on UHC. However, there is limited information on the process; how health ministries and other stakeholders have used SDG declaration to advocate, lobby, and engage various constituencies to support HFR for UHC.ConclusionThe SDG declaration can be a catalyst for health financing reform, providing reference for necessary legislations and policies for financing UHC. However, to facilitate better cross-country learning on how SDG declaration catalyzes HFR for UHC there, is need to examine the processes of how stakeholders have used the declaration as window of opportunity to accelerate reforms.
Statistical analysis plan for the COMPARE trial: a 3-arm randomised controlled trial comparing the effectiveness of Constraint-induced Aphasia Therapy Plus and Multi-modality Aphasia Therapy to usual care in chronic post-stroke aphasia (COMPARE)
Authors: Rose Miranda L. , Rai Tapan , Copland David , Nickels Lyndsey , Togher Leanne , Meinzer Marcus , Godecke Erin , Kim Joosup , Cadilhac Dominique A. , Hurley Melanie , Wilcox Cassie , Carragher Marcella 
Published: April 2021

Abstract
Background
While high-quality meta-analyses have confirmed the effectiveness of aphasia therapy after stroke, there is limited evidence for the comparative effectiveness of different aphasia interventions. Two commonly used interventions, Constraint-induced Aphasia Therapy Plus (CIAT Plus) and Multi-modality Aphasia Therapy (M-MAT), are hypothesised to rely on diverse underlying neural mechanisms for recovery and may be differentially responsive to aphasia severity. COMPARE is a prospective randomised open-blinded end-point trial designed to determine whether, in people with chronic post-stroke aphasia living in the community, CIAT Plus and M-MAT provide greater therapeutic benefit compared to usual care, are differentially effective according to aphasia severity, and are cost-effective. This paper details the statistical analysis plan for the COMPARE trial developed prior to data analysis.

Methods
Participants (n = 216) are randomised to one of three arms, CIAT Plus, M-MAT or usual care, and undertake therapy with a study trained speech pathologist in groups of three participants stratified by aphasia severity. Therapy occurs for 3 h blocks per day for 10 days across 2 weeks. The primary clinical outcome is aphasia severity as measured by the Western Aphasia Battery-Revised Aphasia Quotient (WAB-R-AQ) immediately post intervention. Secondary outcomes include WAB-R-AQ at 12-week follow-up, and functional communication, discourse efficiency, multimodal communication, and health-related quality of life immediately post intervention and at 12-week follow-up.

Results
Linear mixed models (LMMs) will be used to analyse differences between M-MAT and UC, and CIAT-Plus and UC on each outcome measure immediately and at 12 weeks post-intervention. The LMM for WAB-R-AQ will assess the differences in efficacy between M-MAT and CIAT-Plus. All analyses will control for baseline aphasia severity (fixed effect) and for the clustering effect of treatment groups (random effect).

Discussion
This trial will provide relative effectiveness data for two common interventions for people with chronic post-stroke aphasia, and highlight possible differential effects based on aphasia severity. Together with the health economic analysis data, the results will enable more informed personalised prescription for aphasia therapy after stroke.

Trial registration
Australian New Zealand Clinical Trials Registry: ACTRN 12615000618550. Registered on 15 June 2016