bluuebunny/crossref_metadata_2025 huggingface dataset:
Lumbar Scheuermann’s disease found in a patient with osteogenesis imperfecta (OI) caused by a heterozygous mutation in COL1A2 (c.4048G > A): a case report
Authors: Wang Shiwei , Wang Xiaoli , Teng Xiaochun , Li Songbai , Zhang Hanyi , Shan Zhongyan , Li Yushu
Published: June 2021

Background

Osteogenesis imperfecta (OI) is a heterogeneous connective tissue disorder characterized by increased bone fragility and a series of extraskeletal manifestations. Approximately 90 % of OI cases are caused by type I collagen variants encoded by the collagen type I alpha 1 (COL1A1) or type I alpha 2 (COL1A2) gene. Lumbar Scheuermann’s disease is an atypical type of Scheuermann’s disease accompanied by Schmorl’s nodes and irregular endplates but without pronounced kyphosis. Although the etiology of Scheuermann’s disease is unclear, genetic and environmental factors are likely.

Case presentation

Here, we report a 32-year-old male patient who experienced multiple brittle fractures. Gene sequencing revealed a heterozygous mutation, c.4048G > A (p.G1350S), in the COL1A2 gene, and the patient was diagnosed with OI. Magnetic resonance imaging of his thoracolumbar spine revealed multiple Schmorl’s nodes.

Conclusions

This is the first reported case of OI coexisting with the spinal presentation of Scheuermann’s disease. It is speculated that the COL1A2 gene mutation might be an underlying novel genetic cause of Scheuermann’s disease. In conclusion, this case demonstrates the relationship between Scheuermann’s disease and OI for the first time and enriches the genotype-phenotype spectrum of OI.
A qualitative exploration of the unmet information needs of Chinese advanced cancer patients and their informal caregivers
Authors: Wang Tao , Molassiotis Alex , Chung Betty Pui Man , Zheng Si-Lin , Huang Hou-Qiang , Tan Jing-Yu
Published: June 2021

Background

Studies in the West have demonstrated that appropriate informational support is a vital component of cancer care, with positive effects on both patients and their informal caregivers. Since little is known about the information needs of advanced cancer patients and informal caregivers in China, where ‘silence as virtue’ is much more valued and the communication style is less open, this study was therefore conducted to elaborate the information needs of advanced cancer patients and informal caregivers as well as to explore their perceptions and experiences regarding their unmet information needs in the Chinese context.

Methods

This sub-study of a previous cross-sectional survey utilized a qualitative descriptive study design. The approach involved semi-structured interviews that followed an interview guide to collect data. Eligible participants were the advanced cancer patients and informal caregivers who had participated in the previous cross-sectional survey and reported unmet information needs. Each interview was audio-recorded and transcribed verbatim. Descriptive content analysis was used to analyze the data.

Results

Seventeen advanced cancer patients and 15 informal caregivers with unmet information needs participated in the semi-structured interviews, with ages ranging from 32 to 63 years old for patients and from 32 to 70 for informal caregivers. Four categories were extracted from the interviews with the patients and caregivers: (1) types of unmet information needs; (2) reasons for information needs not being met; (3) preferences for the provision of information; and (4) meaning and role of information. Each category had two to four sub-categories for both the patients and the caregivers, which were similar but not completely the same.

Conclusion

The findings indicated that the provision of appropriate information could promote informed decision-making and greater satisfaction with treatment options, reductions in psychological disturbances, and enhanced confidence and ability in self-management and capacity in caregiving. Moreover, information on Traditional Chinese Medicine and food therapy should be increased, particularly for patients at the follow-up stage, while the amount of information on prognosis should be flexible as it could increase patients’ and caregivers’ psychological burden. Healthcare professionals were the most preferred information provider, although their heavy workload resulted in time constraints. In this case, they should provide information to patients and caregivers together as a ‘whole unit.’ At the same time, the value of separate conversations should also be recognized as some caregivers preferred to conceal unpleasant information from the patient.
Feasibility, acceptability and effect of the Mindful Practice curriculum in postgraduate training of general practitioners
Authors: Villarreal Manuel , Hanson Petra , Clarke Amy , Khan Majid , Dale Jeremy
Published: June 2021

Background

Early career general practitioners are known to be at high risk of burnout. There is a need for widely applicable, cost-effective evidence-based interventions to develop trainees’ protective skills and strategies.

Results

Of 120 eligible trainees, 23 (19.2%) expressed interest in participating, 17 subsequently started the course, and 15 completed at least 5 out of its 6 sessions. All psychological measures were stable for the six-week period prior to commencing the course. Following the course, there were statistically significant (p < 0.05) improvements in wellbeing, resilience, mindfulness, emotional exhaustion, disengagement, and stress scores. Participants described numerous benefits, and most stated that they would recommend it to colleagues.

Conclusion

Including mindful practice within general practice vocational training is feasible, and in this study it benefited the psychological wellbeing of participants. Further research is needed to explore ways of increasing uptake and course completion, the sustainability of its effects, and the wider applicability of this approach.
Development of an Implementation Process Model: a Delphi study
Authors: Parker Gillian , Kastner Monika , Born Karen , Berta Whitney
Published: June 2021

Background

There is general scarcity of research on key elements of implementation processes and the factors which impact implementation success. Implementation of healthcare interventions is a complex process. Tools to support implementation can facilitate this process and improve effectiveness of the interventions and clinical outcomes. Understanding the impact of implementation support tools is a critical aspect of this process. The objective of this study was to solicit knowledge and agreement from relevant implementation science and knowledge translation healthcare experts in order to develop a process model of key elements in the implementation process.

Methods

A two round, modified Delphi study involving international experts in knowledge translation and implementation (researchers, scientists, professors, decision-makers) was conducted. Participants rated and commented on all aspects of the process model, including the organization, content, scope, and structure. Delphi questions rated at 75% agreement or lower were reviewed and revised. Qualitative comments supported the restructuring and refinement. A second-round survey followed the same process as Round 1.

Results

Fifty-four experts participated in Round 1, and 32 experts participated in Round 2. Twelve percent (n = 6) of the Round 1 questions did not reach agreement. Key themes for revision and refinement were: stakeholder engagement throughout the process, iterative nature of the implementation process; importance of context; and importance of using guiding theories or frameworks. The process model was revised and refined based on the quantitative and qualitative data and reassessed by the experts in Round 2. Agreement was achieved on all items in Round 2 and the Delphi concluded. Additional feedback was obtained regarding terminology, target users and definition of the implementation process.

Conclusions

High levels of agreement were attained for all sub-domains, elements, and sub-elements of the Implementation Process Model. This model will be used to develop an Implementation Support Tool to be used by healthcare providers to facilitate effective implementation and improved clinical outcomes.
Attributes and generic competencies required of doctors: findings from a participatory concept mapping study
Authors: Ogden Kathryn , Kilpatrick Sue , Elmer Shandell , Rooney Kim
Published: June 2021

Background

Medical education should ensure graduates are equipped for practice in modern health-care systems. Practicing effectively in complex health-care systems requires contemporary attributes and competencies, complementing core clinical competencies. These need to be made overt and opportunities to develop and practice them provided. This study explicates these attributes and generic competencies using Group Concept Mapping, aiming to inform pre-vocational medical education curriculum development.

Methods

Group Concept Mapping is a mixed methods consensus building methodology whereby ideas are generated using qualitative techniques, sorted and grouped using hierarchical cluster analysis, and rated to provide further quantitative confirmation of value. Health service providers from varied disciplines (including medicine, nursing, allied health), health profession educators, health managers, and service users contributed to the conceptual model’s development. They responded to the prompt ‘An attribute or non-clinical competency required of doctors for effective practice in modern health-care systems is...’ and grouped the synthesized responses according to similarity. Data were subjected to hierarchical cluster analysis. Junior doctors rated competencies according to importance to their practice and preparedness at graduation.

Results

Sixty-seven contributors generated 338 responses which were synthesised into 60 statements. Hierarchical cluster analysis resulted in a conceptual map of seven clusters representing: value-led professionalism; attributes for self-awareness and reflective practice; cognitive capability; active engagement; communication to build and manage relationships; patient-centredness and advocacy; and systems awareness, thinking and contribution. Logic model transformation identified three overarching meta-competencies: leadership and systems thinking; learning and cognitive processes; and interpersonal capability. Ratings indicated that junior doctors believe system-related competencies are less important than other competencies, and they feel less prepared to carry them out.

Conclusion

The domains that have been identified highlight the competencies necessary for effective practice for those who work within and use health-care systems. Three overarching domains relate to leadership in systems, learning, and interpersonal competencies. The model is a useful adjunct to broader competencies frameworks because of the focus on generic competencies that are crucial in modern complex adaptive health-care systems. Explicating these will allow future investigation into those that are currently well achieved, and those which are lacking, in differing contexts.
Network governance theory as basic pattern for promoting financial support system of the poor in Iranian health system
Authors: Etemadi Manal , Kenis Patrick , Ashtarian Kioomars , Abolghasem Gorji Hasan , Mohammadi Kangarani Hannaneh
Published: June 2021

Background

The share of out-of-pocket payments in Iranian families has the greatest burden on the poor and lead to an impoverishment caused by catastrophic health expenditures. In order to improve access of the poor to public resources, it is necessary to create a better governance system and effective policy-making. The purpose of this study is to improve network effectiveness of the Iranian health system and to design a financial protection network for the poor, based on the network governance theory.

Methods

We are using a quantitative method framework in conjunction with a Social network analysis (SNA) strategy. To draw an optimal network, we conducted interviews with experts by focusing on the arrangement and relationship among different institutions. The research sample was purposefully selected. We used UCINET software for data analysis and NetDraw software to draw networks.

Results

In this article, an optimal network was proposed with the following characteristics: First, the problem of the density of relationships among several central institutions and the isolation of the other institutions have been solved. Second, in our model, the relationships have been distributed in a balanced manner among all institutions in the network. Third, the number of participants has been reduced and consensus on poor people support policies has been achieved in this optimal network. Forth, executive organizations keep their central positions and upper institutions are not at the central position, so that the power is distributed in favor of more balanced governance. However, in order to increase efficiency and to have coherent decision-making, it is necessary to establish a “core” for this optimal network. The “core” has to include the organizations with the most relationship with others.

Conclusion

The result revealed that the usefulness of network analysis as a tool for proposing the effectiveness of governance. By strengthening the relationship among the main actors, an organized system of network management can be achieved. The network has to include all actors from different levels, from policy-making to implementation. The network also has to clarify the tasks from identifying the poor to covering costs. From an academic perspective, this study showed the adequacy of network analysis as a tool for policy sciences. Governance in our optimal health financial protection model follows the shared-governance pattern due to its high density, low centralization and low distance. The model of network governance can be the source of changes in the health governance system. It is a necessary structural condition to provide access to universal health coverage.
Verifying the placement and length of feeding tubes in canine and feline neonates
Authors: Furthner Etienne , Kowalewski Mariusz Paweł , Torgerson Paul , Reichler Iris Margaret
Published: June 2021

Background

Tube feeding is a common procedure in neonatology. In humans, tube misplacement reportedly occurs in up to 59% of all cases and may lead to perforation in 1.1% of preterm intubated neonates. While numerous studies on optimal tube placement have been performed in human neonates, current recommendations on tube feeding in canine and feline neonatology are based, at best, on studies performed in adult animals. Herein, we aimed to test ultrasonography as a tool to verify tube placement in puppies and kittens and to compare different anatomical predictive markers used in human, canine and feline neonates.

Results

The predictive tube length when held bent between the last rib and the mouth may induce trauma compared to when held straight. A strong positive linear correlation was observed between birthweight and gastric cardia localization. Ultrasonography findings were similar to coeliotomy findings. Stomach volume was less than 2 mL per 100 g in the less-than-one-day-old studied puppies (n = 25) and kittens (n = 28).

Conclusions

A weight-based equation was calculated to help predict appropriate tube placement. Ultrasonography can be used to control gastric tube placement, and neonates less than one-day-old have a smaller stomach capacity. Further studies are required to evaluate whether more-than-one-day-old puppies follow the same linear correlation with their weight. Further in vivo studies are warranted to determine the gold standard procedure for tube feeding in neonatal puppies and kittens.
A survey on the prevalence of diarrhea in a Portuguese population of police working dogs
Authors: Alves J. C. , Jorge P. , Santos A.
Published: June 2021

Background

Diarrhea is considered the most common clinical sign of chronic gastrointestinal disease in dogs and affects a considerable portion of working and sporting dogs. We aimed to determine the prevalence of diarrhea in police working dogs and evaluate the relationship between feeding, activity level, and animal characteristics with clinical signs. In an observational, prospective study, information on 188 dogs was collected. For each patient, age, sex, breed, specific mission, number of animals at the same housing location, and activity level was recorded. A body condition (BCS) and canine inflammatory bowel disease activity index (CIBDAI) scores were determined, and feces classified according to the Bristol Stool Form Scale. The Kruskal-Wallis test was used to compare recorded data between breeds, mission, age, and sex. Multiple regression was run to predict BCS score, increased defecation frequency, diarrhea, CIBDAI scores, Bristol stool scores, diarrhea from activity level, number of animals at the same housing location, breed, and mission. A p < 0.05 was set.

Results

Animals in the sample (male n = 96, female n = 92) had a mean age of 5.2 ± 3.2 years and a bodyweight of 24.1 ± 7.2 kg. Four main dog breeds were represented, 80 Belgian Malinois Shepherd Dogs, 52 German Shepherd Dogs, 25 Labrador Retrievers, and 19 Dutch Shepherd Dog. A prevalence of diarrhea of 10.6% was determined, with 4% of dogs having liquid diarrhea. Dogs classified as “extremely active” were more likely to have a low BCS, and the level of activity contributed to diarrhea and BCS prediction.

Conclusion

Police working dogs frequently experience diarrhea episodes, which lead to clinical disease and performance loss. Investigation of aetiologies is required.
Identification of COVID-19 B-cell epitopes with phage-displayed peptide library
Authors: Guo Jing-You , Liu I-Ju , Lin Hsiu-Ting , Wang Mei-Jung , Chang Yu-Ling , Lin Shin-Chang , Liao Mei-Ying , Hsu Wei-Chia , Lin Yi-Ling , Liao James C. , Wu Han-Chung
Published: June 2021

Background

Coronavirus disease 19 (COVID-19) first appeared in the city of Wuhan, in the Hubei province of China. Since its emergence, the COVID-19-causing virus, SARS-CoV-2, has been rapidly transmitted around the globe, overwhelming the medical care systems in many countries and leading to more than 3.3 million deaths. Identification of immunological epitopes on the virus would be highly useful for the development of diagnostic tools and vaccines that will be critical to limiting further spread of COVID-19.

Methods

To find disease-specific B-cell epitopes that correspond to or mimic natural epitopes, we used phage display technology to determine the targets of specific antibodies present in the sera of immune-responsive COVID-19 patients. Enzyme-linked immunosorbent assays were further applied to assess competitive antibody binding and serological detection. VaxiJen, BepiPred-2.0 and DiscoTope 2.0 were utilized for B-cell epitope prediction. PyMOL was used for protein structural analysis.

Results

36 enriched peptides were identified by biopanning with antibodies from two COVID-19 patients; the peptides 4 motifs with consensus residues corresponding to two potential B-cell epitopes on SARS-CoV-2 viral proteins. The putative epitopes and hit peptides were then synthesized for validation by competitive antibody binding and serological detection.

Conclusions

The identified B-cell epitopes on SARS-CoV-2 may aid investigations into COVID-19 pathogenesis and facilitate the development of epitope-based serological diagnostics and vaccines.
Mepolizumab improves clinical outcomes in patients with severe asthma and comorbid conditions
Authors: Gibson Peter G. , Prazma Charlene M. , Chupp Geoffrey L. , Bradford Eric S. , Forshag Mark , Mallett Stephen A. , Yancey Steve W. , Smith Steven G. , Bel Elisabeth H.
Published: June 2021

Background

Comorbidities can complicate the management of severe asthma; therefore, the presence of comorbid conditions or traits often need to be considered when considering treatment options for patients with severe asthma. The aim of this analysis is to investigate the efficacy of mepolizumab in patients with severe eosinophilic asthma and comorbidities.

Methods

This was a post hoc analysis (GSK ID:209140) of data from the Phase IIb/III studies DREAM, MENSA, SIRIUS, and MUSCA. Patients aged ≥ 12 years with severe eosinophilic asthma were randomized to: mepolizumab 750, 250, or 75 mg intravenously or placebo (DREAM); mepolizumab 75 mg intravenously or 100 mg subcutaneously or placebo (MENSA); or mepolizumab 100 mg subcutaneously or placebo (SIRIUS and MUSCA) every 4 weeks for 24 weeks in SIRIUS and MUSCA, 32 weeks in MENSA or 52 weeks in DREAM. In this analysis the primary endpoint was the annual rate of clinically significant exacerbations; secondary endpoints were Asthma Control Questionnaire-5 score, St George’s Respiratory Questionnaire total score, and pre-bronchodilator forced expiratory volume in 1 s at study end. Subgroups were based on comorbidities at baseline.

Results

Overall, 1878 patients received placebo (n = 689) or mepolizumab (n = 1189). Across all comorbidity subgroups mepolizumab reduced the rate of clinically significant exacerbations by 44–68% versus placebo, improved Asthma Control Questionnaire-5 score by 0.27–0.59 points, and improved St George’s Respiratory Questionnaire total score by 5.0–11.6 points. Pre-bronchodilator forced expiratory volume in 1 s was improved by 27.1–286.9 mL in all but one comorbidity subgroup, the diabetes mellitus subgroup.

Conclusions

Mepolizumab reduces exacerbations, and improves asthma control, health-related quality of life, and lung function in patients with severe eosinophilic asthma despite comorbid conditions, including upper respiratory conditions, psychopathologies, cardiovascular conditions, gastroesophageal reflux disease, diabetes mellitus, and obesity.

Trial registration: https://clinicaltrials.gov/ DREAM, MEA112997/NCT01000506; MENSA, MEA115588/NCT01691521; SIRIUS, MEA115575/NCT01842607; MUSCA, 200862/NCT02281318.
Patients’ treatment limitations as predictive factor for mortality in COVID-19: results from hospitalized patients of a hotspot region for SARS-CoV-2 infections
Authors: Budweiser Stephan , Baş Şevki , Jörres Rudolf A. , Engelhardt Sebastian , von Delius Stefan , Lenherr Katharina , Deerberg-Wittram Jens , Bauer Andreas
Published: June 2021

Background

In hospitalized patients with SARS-CoV-2 infection, outcomes markedly differ between locations, regions and countries. One possible cause for these variations in outcomes could be differences in patient treatment limitations (PTL) in different locations. We thus studied their role as predictor for mortality in a population of hospitalized patients with COVID-19.

Methods

In a region with high incidence of SARS-CoV-2 infection, adult hospitalized patients with PCR-confirmed SARS-CoV-2 infection were prospectively registered and characterized regarding sex, age, vital signs, symptoms, comorbidities (including Charlson comorbidity index (CCI)), transcutaneous pulse oximetry (SpO2) and laboratory values upon admission, as well as ICU-stay including respiratory support, discharge, transfer to another hospital and death. PTL assessed by routine clinical procedures comprised the acceptance of ICU-therapy, orotracheal intubation and/or cardiopulmonary resuscitation.

Results

Among 526 patients included (median [quartiles] age 73 [57; 82] years, 47% female), 226 (43%) had at least one treatment limitation. Each limitation was associated with age, dementia and eGFR (p < 0.05 each), that regarding resuscitation additionally with Charlson comorbidity index (CCI) and cardiac disease. Overall mortality was 27% and lower (p < 0.001) in patients without treatment limitation (12%) compared to those with any limitation (47%). In univariate analyses, age and comorbidities (diabetes, cardiac, cerebrovascular, renal, hepatic, malignant disease, dementia), SpO2, hemoglobin, leucocyte numbers, estimated glomerular filtration rate (eGFR), C-reactive protein (CRP), Interleukin-6 and LDH were predictive for death (p < 0.05 each). In multivariate analyses, the presence of any treatment limitation was an independent predictor of death (OR 4.34, 95%-CI 2.10–12.30; p = 0.001), in addition to CCI, eGFR < 55 ml/min, neutrophil number > 5 G/l, CRP > 7 mg/l and SpO2 < 93% (p < 0.05 each).

Conclusion

In hospitalized patients with SARS-CoV-2, the percentage of patients with treatment limitations was high. PTL were linked to age, comorbidities and eGFR assessed upon admission and strong, independent risk factors for mortality. These findings might be useful for further understanding of COVID-19 mortality and its regional variations.

Clinical trial registration ClinicalTrials.gov Identifier: NCT04344171
Reintroduction of immunosuppressive medications in pediatric rheumatology patients with histoplasmosis: a case series
Authors: Brown Rachel A. , Barbar-Smiley Fatima , Yildirim-Toruner Cagri , Ardura Monica I. , Ardoin Stacy P. , Akoghlanian Shoghik
Published: June 2021

Background

Children with rheumatic diseases (cRD) receiving immunosuppressive medications (IM) are at a higher risk for acquiring potentially lethal pathogens, includingHistoplasma capsulatum(histoplasmosis), a fungal infection that can lead to prolonged hospitalization, organ damage, and death. Withholding IM during serious infections is recommended yet poses risk of rheumatic disease flares. Conversely, reinitiating IM increases risk for infection recurrence. Tumor necrosis factor alpha inhibitor (TNFai) biologic therapy carries the highest risk for histoplasmosis infection after epidemiological exposure, so other IM are preferred during active histoplasmosis infection. There is limited guidance as to when and how IM can be reinitiated in cRD with histoplasmosis. This case series chronicles resumption of IM, including non-TNFai biologics, disease-modifying anti-rheumatic drugs (DMARDs), and corticosteroids, following histoplasmosis among cRD.

Case presentation

We examine clinical characteristics and outcomes of 9 patients with disseminated or pulmonary histoplasmosis and underlying rheumatic disease [juvenile idiopathic arthritis (JIA), childhood-onset systemic lupus erythematosus (cSLE), and mixed connective tissue disease (MCTD)] after reintroduction of IM. All DMARDs and biologics were halted at histoplasmosis diagnosis, except hydroxychloroquine (HCQ), and patients began antifungals. Following IM discontinuation, all patients required systemic or intra-articular steroids during histoplasmosis treatment, with 4/9 showing Cushingoid features. Four patients began new IM regimens [2 abatacept (ABA), 1 HCQ, and 1 methotrexate (MTX)] while still positive for histoplasmosis, with 3/4 (ABA, MTX, HCQ) later clearing their histoplasmosis and 1 (ABA) showing decreasing antigenemia. Collectively, 8/9 patients initiated or continued DMARDs and/or non-TNFai biologic use (5 ABA, 1 tocilizumab, 1 ustekinumab, 3 MTX, 4 HCQ, 1 leflunomide). No fatalities, exacerbations, or recurrences of histoplasmosis occurred during follow-up (median 33 months).

Conclusions

In our cohort of cRD, histoplasmosis course following reintroduction of non-TNFai IM was favorable, but additional studies are needed to evaluate optimal IM management during acute histoplasmosis and recovery. In this case series, non-TNFai biologic, DMARD, and steroid treatments did not appear to cause histoplasmosis recurrence. Adverse events from corticosteroid use were common. Further research is needed to implement guidelines for optimal use of non-TNFai (like ABA), DMARDs, and corticosteroids in cRD following histoplasmosis presentation.
A novel lncRNA ARST represses glioma progression by inhibiting ALDOA-mediated actin cytoskeleton integrity
Authors: Sun Jun , He Dong , Fu Yibing , Zhang Rui , Guo Hua , Wang Zhaojuan , Wang Yanan , Gao Taihong , Wei Yanbang , Guo Yuji , Pang Qi , Liu Qian
Published: June 2021

Background

Glioma is one of the most aggressive malignant brain tumors that is characterized with inevitably infiltrative growth and poor prognosis. ARST is a novel lncRNA whose expression level is significantly decreased in the patients with glioblastoma multiforme. However, the exact mechanisms of ARST in gliomagenesis are largely unknown.

Methods

The expressions of ARST in the glioma samples and cell lines were analyzed by qRT-PCR. FISH was utilized to detect the distribution of ARST in the glioma cells. CCK-8, EdU and flow cytometry were used to examine cellular viability, proliferation and apoptosis. Transwell and wound-healing assays were performed to determine the migratory and invasive abilities of the cells. Intracranial tumorigenesis models were established to explore the roles of ARST in vivo. RNA pulldown assay was used to examine proteins that bound to ARST. The activities of key enzymes in the glycolysis and production of lactate acid were measured by colorimetry. In addition, RIP, Co-IP, western blot and immunofluorescence were used to investigate the interaction and regulation between ARST, F-actin, ALDOA and cofilin.

Results

In this study, we reported that ARST was downregulated in the gliomas. Overexpression of ARST in the glioma cells significantly suppressed various cellular vital abilities such as cell growth, proliferation, migration and invasion. The tumorigenic capacity of these cells in vivo was reduced as well. We further demonstrated that the tumor suppressive effects of ARST could be mediated by a direct binding to a glycolytic enzyme aldolase A (ALDOA), which together with cofilin, keeping the polymerization and depolymerization of actin filaments in an orderly dynamic equilibrium. Upregulation of ARST interrupted the interaction between ALDOA and actin cytoskeleton, which led to a rapid cofilin-dependent loss of F-actin stress fibers.

Conclusions

Taken together, it is concluded that ARST performs its function via a non-metabolic pathway associated with ALDOA, which otherwise modifies the morphology and invasive properties of the glioma cells. This has added new perspective to its role in tumorigenesis, thus providing potential target for glioma diagnosis, therapy, and prognosis.
SWE and SMI ultrasound techniques for monitoring needling treatment of ankylosing spondylitis: study protocol for a single-blinded randomized controlled trial
Authors: Wang Mengyu , Fu Wen , Meng Lingcui , Liu Jia , Wu Lihua , Peng Yingjun , Li Ziping
Published: June 2021

Background

Ankylosing spondylitis (AS) is a high-incidence disease in young men that interferes with patients’ physical and mental wellbeing and overall quality of life (QoL). It is often accompanied by arthralgia, stiffness, and limited lumbar flexibility. Acupuncture is safe and effective for reducing the symptoms of AS, but the underlying mechanisms by which it does so are not fully understood. Therefore, to objectively assess acupuncture efficacy, which is critical for patients making informed decisions about appropriate treatments, we will use shear-wave elastography (SWE) and superb microvascular imaging (SMI) ultrasound techniques to evaluate elasticity of lumbar paraspinal muscles and blood flow to the sacroiliac joint (SIJ) in AS.

Methods

We will recruit a total of 60 participants diagnosed with AS and 30 healthy subjects. Participants will be randomly allocated 1:1 to either an acupuncture group or a sham control acupuncture group. Primary-outcome measures will be musculoskeletal ultrasound, Ankylosing Spondylitis Quality of Life Scale (ASQoL), Bath Ankylosing Spondylitis Metrology Index (BASMI), and the Visual Analogue Scale (VAS) for pain. Secondary outcome measures will be the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Function Index (BASFI), and Fatigue Scale-14 (FS-14). We will monitor the effect of acupuncture or sham acupuncture on blood flow and SIJ inflammation using SMI, lumbar-muscle stiffness using SWE and the lumbar paraspinal-muscle cross-sectional area (CSA) using a two-dimensional (2D) grayscale imaging. QoL, physical function, and fatigue will be assessed using an evaluation scale or questionnaire developed for this study, with outcomes measured by the ASQoL, BASMI, BASDAI, BASFI, and FS-14. Healthy subjects will not receive acupuncture but undergo only musculoskeletal ultrasound at baseline. Acupuncture and sham control acupuncture interventions will be conducted for 30 min, 2–3 times/week for 12 weeks. Musculoskeletal ultrasound will be conducted at baseline and post-intervention, while other outcomes will be measured at baseline, 6 weeks, and post-intervention. The statistician, outcome assessor, and participants will be blinded to treatment allocation.

Discussion

The results of this single-blinded, randomized trial with sham controls could help demonstrate the efficacy of acupuncture and clarify whether musculoskeletal ultrasound could be used to evaluate AS.

Trial registration

ClinicalTrials.gov ChiCTR2000031476. Registered 3 April 2020.
Techno-economic evaluation of microalgae high-density liquid fuel production at 12 international locations
Authors: Roles John , Yarnold Jennifer , Hussey Karen , Hankamer Ben
Published: June 2021

Background

Microalgae-based high-density fuels offer an efficient and environmental pathway towards decarbonization of the transport sector and could be produced as part of a globally distributed network without competing with food systems for arable land. Variations in climatic and economic conditions significantly impact the economic feasibility and productivity of such fuel systems, requiring harmonized technoeconomic assessments to identify important conditions required for commercial scale up.

Methods

Here, our previously validatedTechno-economic and Lifecycle Analysis(TELCA) platform was extended to provide a direct performance comparison of microalgae diesel production at 12 international locations with variable climatic and economic settings. For each location, historical weather data, and jurisdiction-specific policy and economic inputs were used to simulate algal productivity, evaporation rates, harvest regime, CapEx and OpEx, interest and tax under location-specific operational parameters optimized for Minimum Diesel Selling Price (MDSP, US$ L−1). The economic feasibility, production capacity and CO2-eqemissions of a defined 500 ha algae-based diesel production facility is reported for each.

Results

Under a for-profit business model, 10 of the 12 locations achieved a minimum diesel selling price (MDSP) under US$ 1.85 L−1/ US$ 6.99 gal−1. At a fixed theoretical MDSP of US$ 2 L−1(US$ 7.57 gal−1) these locations could achieve a profitable Internal Rate of Return (IRR) of 9.5–22.1%. Under a public utility model (0% profit, 0% tax) eight locations delivered cost-competitive renewable diesel at an MDSP of < US$ 1.24 L−1(US$ 4.69 gal−1). The CO2-eqemissions of microalgae diesel were about one-third of fossil-based diesel.

Conclusions

The public utility approach could reduce the fuel price toward cost-competitiveness, providing a key step on the path to a profitable fully commercial renewable fuel industry by attracting the investment needed to advance technology and commercial biorefinery co-production options. Governments’ adoption of such an approach could accelerate decarbonization, improve fuel security, and help support a local COVID-19 economic recovery. This study highlights the benefits and limitations of different factors at each location (e.g., climate, labour costs, policy, C-credits) in terms of the development of the technology—providing insights on how governments, investors and industry can drive the technology forward.

Graphic abstract
Effects of short-term dietary restriction on plasma metabolites and the subcutaneous fat area according to metabolic status in obese individuals: a case–control study
Authors: Jang Hye Yoon , Han Youngmin , Yoo Hye Jin , Lee Jong Ho , Kim Minjoo
Published: June 2021

Background

Research elucidating the metabolic mechanisms that differentiate subtypes of obesity has been increasing. We aimed to investigate the effects of a 12-week dietary intervention on the metabolomic profiles of obese subjects.

Methods

Subjects followed a 12-week dietary restriction protocol consisting of a 300 kcal/day reduction in their usual caloric intake. Twenty-nine obese subjects were included and divided into two groups: the metabolic status maintenance group (n = 17, controls) and the metabolic status improvement group (n = 12, tests). We analyzed the somatometric and biochemical parameters and performed ultra-performance liquid chromatography-mass spectrometry analysis of the plasma metabolites.

Results

At 12 weeks, the fat percentage, whole fat area (WFA), subcutaneous fat area (SFA) at the L1 vertebra, and the levels of triglycerides, gamma-glutamyltransferase (gamma-GT), and leptin were markedly decreased in the metabolic status improvement group, while the level of high-density lipoprotein cholesterol increased compared with that in the metabolic status maintenance group. Metabolomic profiling at 12 weeks showed substantial differences in 4-aminobutyraldehyde (p = 0.005) and 4’-apo-β-carotenal (p = 0.024) between the two groups. Furthermore, an AUC value of 0.89 was obtained for the following seven featured biomarkers: triglycerides, gamma-GT, leptin, fat percentage, WFA, and SFA at the L1 vertebra, and 4-aminobutyraldehyde.

Conclusions

We demonstrated that 4-aminobutyraldehyde and related regional fat distribution parameters were strongly associated with obesity according to metabolic status. Thus, these biomarkers are potentially valuable in confirming the efficacy of short-term interventions and predicting metabolic status in obese individuals.

Trials registration:This study was registered at ClinicalTrials.gov under NCT03135132 (registered 1 May 2017—retrospectively registered).
Mixtures of natural antimicrobials can reduce Campylobacter jejuni, Salmonella enterica and Clostridium perfringens infections and cellular inflammatory response in MDCK cells
Authors: Balta Igori , Marcu Adela , Linton Mark , Kelly Carmel , Gundogdu Ozan , Stef Lavinia , Pet Ioan , Ward Patrick , Deshaies Myriam , Callaway Todd , Sopharat Phittawat , Gradisteanu-Pircalabioru Gratiela , Corcionivoschi Nicolae
Published: June 2021

Background

The classification of natural antimicrobials as potential antibiotic replacements is still hampered by the absence of clear biological mechanisms behind their mode of action. This study investigated the mechanisms underlying the anti-bacterial effect of a mixture of natural antimicrobials (maltodextrin, citric acid, sodium citrate, malic acid, citrus extract and olive extract) against Campylobacter jejuni RC039, Salmonella enterica SE 10/72 and Clostridium perfringens ATCC® 13124 invasion of Madin–Darby Canine Kidney cells (MDCK).

Results

Minimum sub-inhibitory concentrations were determined for Campylobacter jejuni (0.25%), Salmonella enterica (0.50%) and Clostridium perfringens (0.50%) required for the in vitro infection assays with MDCK cells. The antimicrobial mixture significantly reduced the virulence of all three pathogens towards MDCK cells and restored the integrity of cellular tight junctions through increased transepithelial resistance (TEER) and higher expression levels of ZO-1 (zonula occludens 1) and occludin. This study also identified the ERK (external regulated kinase) signalling pathway as a key mechanism in blocking the pro-inflammatory cytokine production (IL-1β, IL-6, IL-8, TNF-α) in infected cells. The reduction in hydrogen peroxide (H2O2) production and release by infected MDCK cells, in the presence of the antimicrobial mixture, was also associated with less tetrathionate formed by oxidation of thiosulphate (p < 0.0001).

Conclusion

The present study describes for the first time that mixtures of natural antimicrobials can prevent the formation of substrates used by bacterial pathogens to grow and survive in anaerobic environments (e.g. tetrathionate). Moreover, we provide further insights into pathogen invasion mechanisms through restoration of cellular structures and describe their ability to block the ERK–MAPK kinase pathway responsible for inflammatory cytokine release
Dietary nitrate and population health: a narrative review of the translational potential of existing laboratory studies
Authors: Shannon Oliver M. , Easton Chris , Shepherd Anthony I. , Siervo Mario , Bailey Stephen J. , Clifford Tom
Published: June 2021

Background

Dietary inorganic nitrate (NO3−) is a polyatomic ion, which is present in large quantities in green leafy vegetables and beetroot, and has attracted considerable attention in recent years as a potential health-promoting dietary compound. Numerous small, well-controlled laboratory studies have reported beneficial health effects of inorganic NO3− consumption on blood pressure, endothelial function, cerebrovascular blood flow, cognitive function, and exercise performance. Translating the findings from small laboratory studies into ‘real-world’ applications requires careful consideration.

Main body

This article provides a brief overview of the existing empirical evidence basis for the purported health-promoting effects of dietary NO3− consumption. Key areas for future research are then proposed to evaluate whether promising findings observed in small animal and human laboratory studies can effectively translate into clinically relevant improvements in population health. These proposals include: 1) conducting large-scale, longer duration trials with hard clinical endpoints (e.g. cardiovascular disease incidence); 2) exploring the feasibility and acceptability of different strategies to facilitate a prolonged increase in dietary NO3− intake; 3) exploitation of existing cohort studies to explore associations between NO3− intake and health outcomes, a research approach allowing larger samples sizes and longer duration follow up than is feasible in randomised controlled trials; 4) identifying factors which might account for individual differences in the response to inorganic NO3− (e.g. sex, genetics, habitual diet) and could assist with targeted/personalised nutritional interventions; 5) exploring the influence of oral health and medication on the therapeutic potential of NO3− supplementation; and 6) examining potential risk of adverse events with long term high- NO3− diets.

Conclusion

The salutary effects of dietary NO3− are well established in small, well-controlled laboratory studies. Much less is known about the feasibility and efficacy of long-term dietary NO3− enrichment for promoting health, and the factors which might explain the variable responsiveness to dietary NO3− supplementation between individuals. Future research focussing on the translation of laboratory data will provide valuable insight into the potential applications of dietary NO3− supplementation to improve population health.
HealthSWEDE: costs with sublingual immunotherapy—a Swedish questionnaire study
Authors: Olsson Petter , Skröder Carl , Ahlbeck Lars , Hjalte Frida , Welin Karl-Olof , Westin Ulla , Andersson Morgan , Ahlström-Emanuelsson Cecilia , Cardell Lars-Olaf
Published: June 2021

Background

The aim of this cross-sectional survey was to compare the health-economic consequences for allergic rhinitis (AR) patients treated with sublingual Immunotherapy (SLIT) in terms of direct and indirect costs with a reference population of patients receiving standard of care pharmacological therapy.

Methods

Primary objective was to analyse the health-economic consequences of SLIT for grass pollen allergy in Sweden vs reference group waiting for subcutaneous immunotherapy (SCIT). A questionnaire was mailed to two groups of AR patients.

Results

The questionnaire was distributed to 548 patients, 307 with SLIT and 241 in reference group (waiting for SCIT). Response rate was 53.8%. Mean annual costs were higher for reference patients than SLIT group; € 3907 (SD 4268) vs € 2084 (SD 1623) p < 0.001. Mean annual direct cost was higher for SLIT-patients, € 1191 (SD 465) than for reference, € 751 (SD 589) p < 0.001. Mean annual indirect costs for combined absenteeism and presenteeism were lower for patients treated with SLIT, € 912 (SD 1530), than for reference, € 3346 (SD 4120) p < 0.001, with presenteeism as main driver.

Conclusions

SLIT seems to be a cost-beneficial way to treat seasonal AR. This information might be used to guide future recommendations.
Left ventricular noncompaction—a rare cause of triad: heart failure, ventricular arrhythmias, and systemic embolic events: a case report
Authors: Toader Despina , Paraschiv Alina , Tudorașcu Petrișor , Tudorașcu Diana , Bataiosu Constantin , Balșeanu Adrian
Published: June 2021

Background

Left ventricular noncompaction is a rare cardiomyopathy characterized by a thin, compacted epicardial layer and a noncompacted endocardial layer, with trabeculations and recesses that communicate with the left ventricular cavity. In the advanced stage of the disease, the classical triad of heart failure, ventricular arrhythmia, and systemic embolization is common. Segments involved are the apex and mid inferior and lateral walls. The right ventricular apex may be affected as well.

Case presentation

A 29-year-old Caucasian male was hospitalized with dyspnea and fatigue at minimal exertion during the last months before admission. He also described a history of edema of the legs and abdominal pain in the last weeks. Physical examination revealed dyspnea, pulmonary rales, cardiomegaly, hepatomegaly, and splenomegaly. Electrocardiography showed sinus rhythm with nonspecific repolarization changes. Twenty-four-hour Holter monitoring identified ventricular tachycardia episodes with right bundle branch block morphology. Transthoracic echocardiography at admission revealed dilated left ventricle with trabeculations located predominantly at the apex but also in the apical and mid portion of lateral and inferior wall; end-systolic ratio of noncompacted to compacted layers > 2; moderate mitral regurgitation; and reduced left ventricular ejection fraction. Between apical trabeculations, multiple thrombi were found. The right ventricle had normal morphology and function. Speckle-tracking echocardiography also revealed systolic left ventricle dysfunction and solid body rotation. Abdominal echocardiography showed hepatomegaly and splenomegaly. Abdominal computed tomography was suggestive for hepatic and renal infarctions. Laboratory tests revealed high levels of N-terminal pro-brain natriuretic peptide and liver enzymes. Cardiac magnetic resonance evaluation at 1 month after discharge confirmed the diagnosis. The patient received anticoagulants, antiarrhythmics, and heart failure treatment. After 2 months, before device implantation, he presented clinical improvement, and echocardiographic evaluation did not detect thrombi in the left ventricle. Coronary angiography was within normal range. A cardioverter defibrillator was implanted for prevention of sudden cardiac death.

Conclusions

Left ventricular noncompaction is rare cardiomyopathy, but it should always be considered as a possible diagnosis in a patient hospitalized with heart failure, ventricular arrhythmias, and systemic embolic events. Echocardiography and cardiac magnetic resonance are essential imaging tools for diagnosis and follow-up.