bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of Myo-inositol on fertility rates in poor ovarian responder in women undergoing assisted reproductive technique: a randomized clinical trial
Authors: Mohammadi Sahar , Eini Fatemeh , Bazarganipour Fatemeh , Taghavi Seyed Abdolvahab , Kutenaee Maryam Azizi
Published: April 2021

Background

Poor ovarian response to gonadotropin is a significant challenge in assisted reproductive technique (ART) and affect 9–24% of ART cycles. This study aimed to evaluate the effect of Myo-inositol on fertility rates in poor ovarian responder women undergoing assisted reproductive technique.

Methods

This study is a double-blinded randomized controlled study that involved 60 poor ovarian responders included in an ICSI program and divided into two groups; intervention group: 30 patients who have been assuming Inofolic (4 g myo-inositol + 400 μg folic acid) for the before the enrollment day; control group: 30 patients assuming folic acid (400 μg) for the same period. Controlled ovarian stimulation was performed in the same manner in the two groups. The main outcomeswere the assessment of oocytes retrievednumber and quality, ovarian sensitivity index,required dose of Gonadotropinsunits × 1000), fertilization rate, biochemical, and clinical pregnancy rate.

Result

There is no significant difference in clinical characteristics between study groups. The number of oocytes retrieved, number of MII oocytes, number of embryos transferred, chemical, and clinical pregnancy were higher in the intervention group. However, they are not statistically significant in comparison to the control group. The ovarian sensitivity index and fertilization rate were significantly higher in the intervention group than the control group (P > 0.05). The required dose of gonadotropin significantly lower in the intervention group than the control group.

Conclusion

Our results suggest that the supplementation myo-inositol in poor ovarian responders significantly improved the ART outcomes such as fertilization rate gonadotropin, ovarian sensitivity index (OSI) and significantly reduced the required unities of gonadotropin. Additionally, more extensive randomized controlled studies are needed.

Trial registration

Iranian Registry of Clinical Trials, IRCT20180515039668N1, retrospectively registered since 2020-03-16.
Quercetin prevents primordial follicle loss via suppression of PI3K/Akt/Foxo3a pathway activation in cyclophosphamide-treated mice
Authors: Li Jianghui , Long Hui , Cong Yanyan , Gao Hongyuan , Lyu Qifeng , Yu Sha , Kuang Yanping
Published: April 2021

Background

Chemotherapy improves the survival rates of patients with various cancers but often causes some adverse effects, including ovarian damage, characterised by a decrease in primordial follicle stockpiles. Recent studies have revealed that chemotherapy may stimulate the PI3K signalling pathway, thereby resulting in accelerated primordial follicle activation and a decreased ovarian reserve. Quercetin is an inhibitor of the PI3K pathway; however, its protective effects against chemotherapy-induced follicle loss in mice have not been established. In this study, the effects of quercetin in a mouse model of cyclophosphamide-induced ovarian dysfunction were investigated.

Methods

C57BL/6 female mice were used for the study. Paraffin sections of mouse ovaries (n = 30 mice) were stained with haematoxylin and eosin for differential follicle counts. Apoptosis (n = 5 mice per group) was evaluated by TUNEL assay. Immunohistochemical staining for ki67 and Foxo3a (n = 5 mice per group) was performed to evaluate the activation of primordial follicles. The role of the PI3K signalling pathway in the ovaries (n = 45 mice) was assessed by western blotting.

Results

Quercetin attenuated the cyclophosphamide-induced reduction in dormant primordial follicles. Analysis of the PI3K/Akt/Foxo3a pathway showed that quercetin decreased the phosphorylation of proteins that stimulate follicle activation in cyclophosphamide-induced ovaries. Furthermore, quercetin prevented cyclophosphamide-induced apoptosis in early growing follicles and early antral follicles, maintained anti-Müllerian hormone levels secreted by these follicles, and preserved the quiescence of the primordial follicle pool, as determined by intranuclear Foxo3a staining.

Conclusions

Quercetin attenuates cyclophosphamide-induced follicle loss by preventing the phosphorylation of PI3K/Akt/Foxo3a pathway members and maintaining the anti-Müllerian hormone level through reduced apoptosis in growing follicles. Accordingly, quercetin is expected to improve fertility preservation and the prevention of endocrine-related side effects of chemotherapy.
The cost-effectiveness of a culturally tailored parenting program: estimating the value of multiple outcomes
Authors: Nystrand Camilla , Sampaio Filipa , Hoch Jeffrey S. , Osman Fatumo , Feldman Inna
Published: April 2021

Background

Parenting programs can be economically attractive interventions for improving the mental health of both parents and their children. Few attempts have been made to analyse the value of children’s and parent’s outcomes simultaneously, to provide a qualified support for decision making.

Methods

A within trial cost-effectiveness evaluation was conducted, comparing Ladnaan, a culturally tailored parenting program for Somali-born parents, with a waitlist control. Quality-adjusted life years (QALY) for parents were estimated by mapping the General Health Questionnaire-12 to Euroqol’s EQ-5D-3L to retrieve utilities. Behavioural problems in children were measured using the Child Behaviour Checklist (CBCL). Intervention costs were estimated for the trial. A net benefit regression framework was employed to study the cost-effectiveness of the intervention, dealing with multiple effects in the same analysis to estimate different combinations of willingness-to pay (WTP) thresholds.

Results

For a WTP of roughly €300 for a one point improvement in total problems on the CBCL scale (children), Ladnaan is cost-effective. In contrast, the WTP would have to be roughly €580,000 per QALY (parents) for it to be cost-effective. Various combinations of WTP values for the two outcomes (i.e., CBCL and QALY) may be used to describe other scenarios where Ladnaan is cost-effective.

Conclusions

Decision-makers interested in multiple effects must take into account combinations of effects in relation to budget, in order to obtain cost-effective results. A culturally adapted parenting program may be cost-effective, depending on the primary outcome, or multiple outcomes of interest.

Trial registration clinicaltrials.gov, NCT02114593. Registered 15 April 2014—prospectively registered, https://www.clinicaltrials.gov/ct2/results?recrs=&cond=&term=NCT02114593&cntry=&state=&city=&dist=
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

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

The 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

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

Background

Women 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.

Methods

The 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.

Results

The 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.

Conclusion

It 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

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

Background

After 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.

Methods

Twenty-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.

Results

Between 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%).

Conclusions

The 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

Background

The 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.

Methods

The 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.

Results

Significant 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.

Conclusions

The 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

Gene 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

Background

Achieving 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.

Methods

We 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.

Results

Twelve 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.

Conclusion

The 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

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
Finding associations in a heterogeneous setting: statistical test for aberration enrichment
Authors: Mezlini Aziz M. , Das Sudeshna , Goldenberg Anna
Published: April 2021

Most two-group statistical tests find broad patterns such as overall shifts in mean, median, or variance. These tests may not have enough power to detect effects in a small subset of samples, e.g., a drug that works well only on a few patients. We developed a novel statistical test targeting such effects relevant for clinical trials, biomarker discovery, feature selection, etc. We focused on finding meaningful associations in complex genetic diseases in gene expression, miRNA expression, and DNA methylation. Our test outperforms traditional statistical tests in simulated and experimental data and detects potentially disease-relevant genes with heterogeneous effects.
Application of systems biology-based in silico tools to optimize treatment strategy identification in Still’s disease
Authors: Segú-Vergés Cristina , Coma Mireia , Kessel Christoph , Smeets Serge , Foell Dirk , Aldea Anna
Published: April 2021

Background

Systemic juvenile idiopathic arthritis (sJIA) and adult-onset Still’s disease (AOSD) are manifestations of an autoinflammatory disorder with complex pathophysiology and significant morbidity, together also termed Still’s disease. The objective of the current study is to set in silico models based on systems biology and investigate the optimal treat-to-target strategy for Still’s disease as a proof-of-concept of the modeling approach.

Methods

Molecular characteristics of Still’s disease and data on biological inhibitors of interleukin (IL)-1 (anakinra, canakinumab), IL-6 (tocilizumab, sarilumab), and glucocorticoids as well as conventional disease-modifying anti-rheumatic drugs (DMARDs, methotrexate) were used to construct in silico mechanisms of action (MoA) models by means of Therapeutic Performance Mapping System (TPMS) technology. TPMS combines artificial neuronal networks, sampling-based methods, and artificial intelligence. Model outcomes were validated with published expression data from sJIA patients.

Results

Biologicals demonstrated more pathophysiology-directed efficiency than non-biological drugs. IL-1 blockade mainly acts on proteins implicated in the innate immune system, while IL-6 signaling blockade has a weaker effect on innate immunity and rather affects adaptive immune mechanisms. The MoA models showed that in the autoinflammatory/systemic phases of Still’s disease, in which the innate immunity plays a pivotal role, the IL-1β-neutralizing antibody canakinumab is more efficient than the IL-6 receptor-inhibiting antibody tocilizumab. MoA models reproduced 67% of the information obtained from expression data.

Conclusions

Systems biology-based modeling supported the preferred use of biologics as an immunomodulatory treatment strategy for Still’s disease. Our results reinforce the role for IL-1 blockade on innate immunity regulation, which is critical in systemic autoinflammatory diseases. This further encourages early use on Still’s disease IL-1 blockade to prevent the development of disease or drug-related complications. Further analysis at the clinical level will validate the findings and help determining the timeframe of the window of opportunity for canakinumab treatment.
Helicobacter cinaedi bacteraemia secondary to enterocolitis in an immunocompetent patient
Authors: Rasmussen Sofie Larsen , Ørsted Iben , Tarpgaard Irene Harder , Nielsen Hans Linde
Published: April 2021

Background

Helicobacter cinaediare motile, gram-negative spiral rods with a natural reservoir in the intestinal tract of hamsters and rhesus monkeys. In humans,H. cinaedihas been reported in different human infections like fever, abdominal pain, gastroenteritis, proctitis, diarrhoea, erysipelas, cellulitis, arthritis, and neonatal meningitis typically diagnosed by positive blood cultures. Even thoughH. cinaedihas been detected from human blood and stool the entry ofH. cinaediinto the blood stream was undocumented until quite recently. The use of pulse-field gel electrophoresis (PFGE) demonstrated that stool- and blood-derivedH. cinaedistrains were consistent.

Case presentation

Here, we describe a rare Danish case ofH. cinaedibacteraemia in an immunocompetent 44-year-old male with diarrhoea. We isolatedH. cinaedifrom a blood culture taken at admission, and from a FecalSwab taken at day six despite ongoing antibiotic therapy. Next, we made a genetic comparison of both isolates by use of Multi-locus sequence typing (MLST)- and Single nucleotide polymorphism (SNP)-analysis. The two isolates were identical with zero SNPs and by use of MLST the isolate was identified as a novel ST20, confirming previous data of the intestinal tract as a route ofH. cinaedibacteraemia. The results of our AST showed a resistance pattern with higher MICs for ciprofloxacin and clarithromycin than for ampicillin, amoxicillin, gentamicin, and imipenem. The patient was cured with targeted therapy with pivampicillin; however, the primary source of transmission was unknown.

Conclusions

In conclusion, this case ofH. cinaedibacteraemia secondary to enterocolitis in an immunocompetent patient provide clear evidence that one route of infection occurs through translocation from the intestinal tract to the bloodstream.Helicobacter cinaedifrom blood and faeces were identical with a novel ST20, resistant to ciprofloxacin and clarithromycin however, the patient was cured with oral pivampicillin.
Network slicing: a next generation 5G perspective
Authors: Subedi Prashant , Alsadoon Abeer , Prasad P. W. C. , Rehman Sabih , Giweli Nabil , Imran Muhammad , Arif Samrah
Published: April 2021

Fifth-generation (5G) wireless networks are projected to bring a major transformation to the current fourth-generation network to support the billions of devices that will be connected to the Internet. 5G networks will enable new and powerful capabilities to support high-speed data rates, better connectivity and system capacity that are critical in designing applications in virtual reality, augmented reality and mobile online gaming. The infrastructure of a network that can support stringent application requirements needs to be highly dynamic and flexible. Network slicing can provide these dynamic and flexible characteristics to a network architecture. Implementing network slicing in 5G requires domain modification of the preexisting network architecture. A network slicing architecture is proposed for an existing 5G network with the aim of enhancing network dynamics and flexibility to support modern network applications. To enable network slicing in a 5G network, we established the virtualisation of the underlying physical 5G infrastructure by utilising technological advancements, such as software-defined networking and network function virtualisation. These virtual networks can fulfil the requirement of multiple use cases as required by creating slices of these virtual networks. Thus, abstracting from the physical resources to create virtual networks and then applying network slicing on these virtual networks enable the 5G network to address the increased demands for high-speed communication.
An integrated scheduling algorithm for multi-device-processes with the strategy of exchanging adjacent parallel processes of the same device
Authors: Wang Zhen , Zhang Xiaohuan , Cao Yuxiao , Lai Guoming
Published: April 2021

At present, Multi-Devices-Process Integrated Scheduling Algorithm with Time-Selective Strategy for Process Sequence (MISATPS) is an advanced algorithm in the field of integrated scheduling with multi-devices-process problems. This algorithm ignores the influence of the pre-process on the post-process when solving the multi-devices-process integrated scheduling problem, which leads to the problem of poor closeness between serial processes and poor parallelism between parallel processes. This paper points out that there is no restriction of scheduling sequence between parallel processes on the same processing device. It can be scheduled flexibly of the sequence between parallel processes of the same device. Therefore, based on the scheduling scheme of MISATPS, the algorithm is improved by applying the interchange strategy and the interchange adjustment strategy of multi-device adjacent parallel process. In this way, the influence of the pre-process on the post-process is avoided, the compactness of the serial process and the parallelism of the parallel process are improved, and the scheduling result is optimized.
Intraoperative and postoperative outcomes of robot-assisted cholecystectomy: a systematic review
Authors: Shenoy Rivfka , Mederos Michael A. , Ye Linda , Mak Selene S. , Begashaw Meron M. , Booth Marika S. , Shekelle Paul G. , Wilson Mark , Gunnar William , Maggard-Gibbons Melinda , Girgis Mark D.
Published: April 2021

Background

Rapid adoption of robotic-assisted general surgery procedures, particularly for cholecystectomy, continues while questions remain about its benefits and utility. The objective of this study was to compare the clinical effectiveness of robot-assisted cholecystectomy for benign gallbladder disease as compared with the laparoscopic approach.

Methods

A literature search was performed from January 2010 to March 2020, and a narrative analysis was performed as studies were heterogeneous.

Results

Of 887 articles screened, 44 met the inclusion criteria (range 20–735,537 patients). Four were randomized controlled trials, and four used propensity-matching. There were variable comparisons between operative techniques with only 19 out of 44 studies comparing techniques using the same number of ports. Operating room time was longer for the robot-assisted technique in the majority of studies (range 11–55 min for 22 studies, p < 0.05; 15 studies showed no difference; two studies showed shorter laparoscopic times), while conversion rates and intraoperative complications were not different. No differences were detected for the length of stay, surgical site infection, or readmissions. Across studies comparing single-port robot-assisted to multi-port laparoscopic cholecystectomy, there was a higher rate of incisional hernia; however, no differences were noted when comparing single-port robot-assisted to single-port laparoscopic cholecystectomy.

Conclusions

Clinical outcomes were similar for benign, elective gallbladder disease for robot-assisted compared with laparoscopic cholecystectomy. Overall, the rates of complications were low. More high-quality studies are needed as the robot-assisted technique expands to more complex gallbladder disease, where its utility may prove increasingly beneficial.

Systematic review registration

PROSPERO CRD42020156945
New characterizations of weights on dynamic inequalities involving a Hardy operator
Authors: Saker S. H. , Alzabut J. , Saied A. I. , O’Regan D.
Published: April 2021

In this paper, we establish some new characterizations of weighted functions of dynamic inequalities containing a Hardy operator on time scales. These inequalities contain the characterization of Ariňo and Muckenhoupt when $\mathbb{T}=\mathbb{R}$
T
=
R
, whereas they contain the characterizations of Bennett–Erdmann and Gao when $\mathbb{T}=\mathbb{N}$
T
=
N
.
On superstability of exponential functional equations
Authors: Noori Batool , Moghimi M. B. , Najati Abbas , Park Choonkil , Lee Jung Rye
Published: April 2021

The aim of this paper is to prove the superstability of the following functional equations:
$$\begin{aligned}& f \bigl(P(x,y) \bigr)= g(x)h(y), \\& f(x+y)=g(x)h(y). \end{aligned}$$

f

(
P
(
x
,
y
)
)

=
g
(
x
)
h
(
y
)
,

f
(
x
+
y
)
=
g
(
x
)
h
(
y
)
.
Stability analysis of swarming model with time delays
Authors: Himakalasa Adsadang , Wongkaew Suttida
Published: April 2021

A swarming model is a model that describes the behavior of the social aggregation of a large group of animals or the community of humans. In this work, the swarming model that includes the short-range repulsion and long-range attraction with the presence of time delay is investigated. Moreover, the convergence to a consensus representing dispersion and cohesion properties is proved by using the Lyapunov functional approach. Finally, numerical results are provided to demonstrate the effect of time delay on the motion of the group of agents.
Validation of the Arabic version of the “12-item short-form health survey” (SF-12) in a sample of Lebanese adults
Authors: Haddad Chadia , Sacre Hala , Obeid Sahar , Salameh Pascale , Hallit Souheil
Published: April 2021

Background

In clinical practice, quality of life measures can be used alongside some types of assessment to give valuable information that can identify areas that influence an individual and help the clinician make the best healthcare choices. This study aimed to investigate the psychometric properties of the Arabic version of the 12-item short-form health survey (SF-12) in a sample of Lebanese adults.

Methods

This cross-sectional study performed between July and November 2019 recruited 269 participants. Cronbach’s alpha was used to assess the reliability of the SF-12 questionnaire, and a factor analysis using the principal component analysis was performed to confirm its construct validity.

Results

The mean score for the “physical component summary (PCS-12)” was 50.27 ± 8.94 (95 % CI: 49.18–51.36) and for the “Mental component summary (MCS-12)” was 44.95 ± 12.17 (95 % CI: 43.47–46.43). A satisfactory Cronbach’s alpha was found for the two components: MCS (α = 0.707) and PCS (α = 0.743). The principal component analysis converged over a two-factor solution (physical and mental), explaining a total variance of 55.75 %. Correlations between the SF-12 scales and single items were significant, showing a good construct validity. The “physical functioning”, “role physical”, “bodily pain”, and “general health” subscales were highly associated with “PCS-12”, while the “vitality”, “social functioning”, “role emotional”, and “mental health” subscales were more associated with MCS-12.

Conclusions

The Arabic version of the SF-12 is a reliable, easy-to-use, and valid tool to measure health-related quality of life in the general population. Future studies using a larger sample size and focusing on questionnaire psychometric properties are necessary to confirm our findings.
Effect of low salicylate diet on clinical and inflammatory markers in patients with aspirin exacerbated respiratory disease – a randomized crossover trial
Authors: Sowerby Leigh J. , Patel Krupal B. , Schmerk Crystal , Rotenberg Brian W. , Rocha Taciano , Sommer Doron D.
Published: April 2021

Background

Aspirin-exacerbated respiratory disease (AERD) is characterized by eosinophilic rhinosinusitis, nasal polyposis, and bronchial asthma, along with the onset of respiratory reactions after the ingestion of nonsteroidal anti-inflammatory drugs (NSAIDs) or acetylsalicylic acid (ASA). In addition to the therapeutic routines and surgical options available, a low dietary intake of food salicylate has been suggested as adjunctive therapy for this condition. This study aimed to assess the influence of a short-term low salicylate diet on inflammatory markers in patients with AERD and whether that would result in symptomatic improvement.

Methods

Prospective study with randomization to either a high or low salicylate diet for 1 week, followed by cross-over to the other study arm. Participants were asked to record their dietary salicylate for each week of the study. Urinary creatinine, salicylate and leukotriene levels were measured at the time of recruitment, end of week one and end of week two and the SNOT-22 questionnaire was filled out at the same time points.

Results

A total of seven participants completed the study. There was no statistical difference in the urinary salicylate and leukotriene levels between the two diets; nevertheless, participants on low salicylate diet reported improved SNOT-22 symptoms scores ( p = 0.04), mainly in the rhinologic, ear/facial, and sleep dysfunction symptom domains. In addition, these last two domains outcomes were more significant than the minimal clinically important difference.

Conclusions

A short-term low salicylate diet may not result in biochemical outcomes changes but seems to provide significant symptomatic relief for patients with AERD.

Trial registration

NCT01778465 ( www.clinicaltrials.gov )

Graphical abstract
Application of modified green algae Nannochloropsis sp. as adsorbent in the simultaneous adsorption of Methylene Blue and Cu(II) cations in solution
Authors: Buhani  , Wijayanti Tri Agus , Suharso  , Sumadi  , Ansori Muslim
Published: April 2021

Biomass of algae is a very potent adsorbent for absorbing aqueous waste containing heavy metals and organic dyes. This study purposes to confirm the ability of adsorbents from green algae Nannochloropsis sp. modified with silica (ASN) and followed by coating magnetite particles (ASN-MPs) to absorb simultaneously the mixture of Methylene Blue (ME) and Cu(II) cations in aqueous solution. Simultaneous sorption of ME and Cu(II) cations to ASN and ASN-MPs was carried out by the batch method with the interaction pH condition 7, contact time 90 min, and initial concentrations of ME and Cu(II) cations (0.1–1.0 mM). Based on adsorption data, Cu(II) cations have a greater adsorption rate and capacity (qm) compared to ME at the same contact time and initial concentration. The adsorption capacity (qm) values of the bi-component ME and Cu(II) cation mixture in ASN and ASN-MPs were 1.39 × 10− 1 and 5.32 × 10− 1 mmol g− 1, respectively, with the binary Langmuir adsorption isotherm constant for Cu(II) cations greater than ME. Modified adsorbent from algae Nannochloropsis sp. with silica matrix and magnetite particle coating is an adsorbent that has a high effectiveness in the collective sorption of ME and Cu(II) cations. Therefore, these adsorbents can be used for the adsorption of cation mixtures of heavy metals and organic dyes that are cationic in solution.