bluuebunny/crossref_metadata_2025 huggingface dataset:
Adopting and implementing an innovative model to organize diabetes care within First Nations communities: A qualitative assessment
Authors: Wozniak Lisa A. , Soprovich Allison L. , Johnson Jeffrey A. , Eurich Dean T.
Published: May 2021

Background

Diabetes care remains suboptimal in First Nations populations. Innovative and culturally relevant approaches are needed to promote systematic and proactive organization of diabetes care for people living with diabetes on-reserve in Canada. The RADAR model is one strategy to improve care: an integrated disease registry paired with an electronic health record for local community healthcare providers with remote care coordination. We qualitatively assessed adoption and implementation of RADAR in First Nations communities in Alberta to inform its potential spread in the province.

Methods

We used the RE-AIM framework to evaluate adoption and implementation of RADAR in 6 First Nations communities. Using purposeful sampling, we recruited local healthcare providers and remote care coordinators involved in delivering RADAR to participate in telephone or in-person interviews at 6- and 24-months post-implementation. Interviews were digitally recorded, transcribed, and verified for accuracy. Data was analyzed using content analysis and managed using ATLAS.ti 8.

Results

In total, we conducted 21 semi-structured interviews (6 at 6-months; 15 at 24-months) with 11 participants. Participants included 3 care coordinators and 8 local healthcare providers, including registered nurses, licensed practical nurses, and registered dietitians. We found that adoption of RADAR was influenced by leadership as well as appropriateness, acceptability, and perceived value of the model. In addition, we found that implementation of RADAR was variable across communities regardless of implementation supports and appropriate community-specific adaptations.

Conclusions

The variable adoption and implementation of RADAR has implications for how likely it will achieve its anticipated outcomes. RADAR is well positioned for spread through continued appropriate community-based adaptations and by expanding the existing implementation supports, including dedicated human resources to support the delivery of RADAR and the provision of levels of RADAR based on existing or developed capacity among local HCPs.

Trial registration

Not applicable to this qualitative assessment. ISRCTN14359671.
Challenges in valuing and paying for combination regimens in oncology: reporting the perspectives of a multi‐stakeholder, international workshop
Authors: Latimer Nicholas. R , Pollard Daniel , Towse Adrian , Henshall Chris , Sansom Lloyd , Ward Robyn L , Bruce Andrew , Deakin Carla
Published: May 2021

Background

It is increasingly common for two or more treatments for cancer to be combined as a single regimen. Determining value and appropriate payment for such regimens can be challenging. This study discusses these challenges, and possible solutions.

Methods

Stakeholders from around the world attended a 2-day workshop, supported by a background paper. This study captures key outcomes from the discussion, but is not a consensus statement.

Results

Workshop attendees agreed that combining on-patent treatments can result in affordability and value for money challenges that delay or deny patient access to clinically effective treatments in many health systems. Options for addressing these challenges include: (i) Increasing the value of combination therapies through improved clinical development; (ii) Willingness to pay more for combinations than for single drugs offering similar benefit, or; (iii) Aligning the cost of constituent therapies with their value within a regimen. Workshop attendees felt that (i) and (iii) merited further discussion, whereas (ii) was unlikely to be justifiable. Views differed on the feasibility of (i). Key to (iii) would be systems allowing different prices to apply to different uses of a drug.

Conclusions

Common ground was identified on immediate actions to improve access to combination regimens. These include an exploration of the legal challenges associated with price negotiations, and ensuring that pricing systems can support implementation of negotiated prices for specific uses. Improvements to clinical development and trial design should be pursued in the medium and longer term.
Continuity of care experienced by patients in a multi-institutional pancreatic care network: a pilot study
Authors: Hopstaken J. S. , van Dalen D. , van der Kolk B. M. , van Geenen E. J. M. , Hermans J. J. , Gootjes E.C. , Schers H. J. , van Dulmen A. M. , van Laarhoven C. J. H. M. , Stommel M. W. J.
Published: May 2021

Background

Over the past decades, health care services for pancreatic surgery were reorganized. Volume norms were applied with the result that only a limited number of expert centers perform pancreatic surgery. As a result of this centralization of pancreatic surgery, the patient journey of patients with pancreatic tumors has become multi-institutional. To illustrate, patients are referred to a center of expertise for pancreatic surgery whereas other parts of pancreatic care, such as chemotherapy, take place in local hospitals. This fragmentation of health care services could affect continuity of care (COC). The aim of this study was to assess COC perceived by patients in a pancreatic care network and investigate correlations with patient-and care-related characteristics.

Methods

This is a pilot study in which patients with (pre) malignant pancreatic tumors discussed in a multidisciplinary tumor board in a Dutch tertiary hospital were asked to participate. Patients were asked to fill out the Nijmegen Continuity of Care-questionnaire (NCQ) (5-point Likert scale). Additionally, their patient-and care-related data were retrieved from medical records. Correlations of NCQ score and patient-and care-related characteristics were calculated with Spearman’s correlation coefficient.

Results

In total, 44 patients were included (92% response rate). Pancreatic cancer was the predominant diagnosis (32%). Forty percent received a repetition of diagnostic investigations in the tertiary hospital. Mean scores for personal continuity were 3.55 ± 0.74 for GP, 3.29 ± 0.91 for the specialist and 3.43 ± 0.65 for collaboration between GPs and specialists. Overall COC was scored with a mean 3.38 ± 0.72. No significant correlations were observed between NCQ score and certain patient-or care-related characteristics.

Conclusion

Continuity of care perceived by patients with pancreatic tumors was scored as moderate. This outcome supports the need to improve continuity of care within multi-institutional pancreatic care networks.
Doctors’ maintenance of professional competence: a qualitative study informed by the theory of planned behaviour
Authors: Wiese Anél , Galvin Emer , O’Farrell Janet , Cotter Jantze , Bennett Deirdre
Published: May 2021

Background

Medical regulators worldwide have implemented programmes of maintenance of professional competence (MPC) to ensure that doctors, throughout their careers, are up to date and fit to practice. The introduction of MPC required doctors to adopt a range of new behaviours. Despite high enrolment rates on these programmes, it remains uncertain whether doctors engage in the process because they perceive benefits like improvements in their practice and professional development or if they solely meet the requirements to retain medical registration. In this study, we aimed to explore the relationship between doctors’ beliefs, intention and behaviour regarding MPC through the lens of the Theory of Planned Behaviour (TPB) to make explicit the factors that drive meaningful engagement with the process.

Methods

We conducted a qualitative study using semi-structured interviews. From a pool of 1258 potential participants, we purposively selected doctors from multiple specialities, age groups, and locations across Ireland. We used thematic analysis, and the TPB informed the analytic coding process.

Results

Forty-one doctors participated in the study. The data analysis revealed doctors’ intention and behaviour and the factors that shape their engagement with MPC. We found that attitudes and beliefs about the benefits and impact of MPC mediated the nature of doctors’ engagement with the process. Some participants perceived positive changes in practice and other gains from participating in MPC, which facilitated committed engagement with the process. Others believed MPC was unfair, unnecessary, and lacking any benefit, which negatively influenced their intention and behaviour, and that was demonstrated by formalistic engagement with the process. Although participants with positive and negative attitudes shared perceptions about barriers to participation, such perceptions did not over-ride strongly positive beliefs about the benefits of MPC. While the requirements of the regulator strongly motivated doctors to participate in MPC, beliefs about patient expectations appear to have had less impact on intention and behaviour.

Conclusions

The findings of this study broaden our understanding of the determinants of doctors’ intention and behaviour regarding MPC, which offers a basis for designing targeted interventions. While the barriers to engagement with MPC resonate with previous research findings, our findings challenge critical assumptions about enhancing doctors’ engagement with the process. Overall, our results suggest that focused policy initiatives aimed at strengthening the factors that underpin the intention and behaviour related to committed engagement with MPC are warranted.
Psychological impact of the COVID-19 pandemic on dental health personnel in Norway
Authors: Uhlen M. M. , Ansteinsson V. E. , Stangvaltaite-Mouhat L. , Korzeniewska L. , Skudutyte-Rysstad R. , Shabestari M. , Mdala I. , Hovden E. A. S.
Published: May 2021

Background

The SARS-CoV-2 pandemic put a pressure on all healthcare professionals and has affected the delivery of health care services globally. There is a need to understand the impact on different health care professionals in different countries. The aim of the present study was to explore the psychological impact of the pandemic among dental staff in Norway in relation to background characteristics, work situation and preparedness of the service.

Methods

A structured questionnaire sent electronically to dentists, dental hygienists and dental assistants inquired information about the lockdown period in Norway (13 March-17 April 2020). Distributions of background characteristics, perceptions of preparedness and psychological impact were calculated. Exploratory factor analysis was performed, and Structural Equation Models (SEMs) were used to compare psychological impact between dental professionals treating patients versus not during lockdown.

Results

Among the 1237 respondents, 58.8% worked clinically with patients. The majority were concerned of becoming infected (71.9%), of infecting others (85.4%) and/or of their family becoming infected (76.9%). Respondents who treated patients felt significantly more insecure about whether having become infected or not. The minority felt discriminated (6.7%), worried about death (11.7%), felt that life was threatening (9.8%) or felt loss of control of their lives (8.9%). More than 80% agreed that their workplace handled the situation well. Four factors were retrieved from the factor analysis. SEMs showed that gender and work experience had a significant effect on the factors Instability, Infection and Concerns. Respondents with work experience ≥10 years were less likely to express fear about Instability and Infection. Personnel reporting that their workplace had adequate equipment were also less concerned, however having adequate equipment did not reduce the factor Loss of control.

Conclusion

The present study showed a considerable psychological impact of the COVID-19 pandemic on dental personnel in Norway regardless of working clinically with patients or not. However, working with patients increased the insecurity about own infection status and of infecting people close to them. A safe working environment and adequate infection control measures are associated with less fear of infection and feeling of instability.
Implementation research approaches to promoting universal health coverage in Africa: a scoping review
Authors: Nnaji Chukwudi A. , Wiysonge Charles S. , Okeibunor Joseph C. , Malinga Thobile , Adamu Abdu A. , Tumusiime Prosper , Karamagi Humphrey
Published: May 2021

Background

Implementation research has emerged as part of evidence-based decision-making efforts to plug current gaps in the translation of research evidence into health policy and practice. While there has been a growing number of initiatives promoting the uptake of implementation research in Africa, its role and effectiveness remain unclear, particularly in the context of universal health coverage (UHC). Hence, this scoping review aimed to identify and characterise the use of implementation research initiatives for assessing UHC-related interventions or programmes in Africa.

Methods

The review protocol was developed based on the methodological framework proposed by Arksey and O’Malley, as enhanced by the Joanna Briggs Institute. The review is reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR). MEDLINE, Scopus and the Cochrane Library were searched. The search also included a hand search of relevant grey literature and reference lists. Literature sources involving the application of implementation research in the context of UHC in Africa were eligible for inclusion.

Results

The database search yielded 2153 records. We identified 12 additional records from hand search of reference lists. After the removal of duplicates, we had 2051 unique records, of which 26 studies were included in the review. Implementation research was used within ten distinct UHC-related contexts, including HIV; maternal and child health; voluntary male medical circumcision; healthcare financing; immunisation; healthcare data quality; malaria diagnosis; primary healthcare quality improvement; surgery and typhoid fever control. The consolidated framework for implementation research (CFIR) was the most frequently used framework. Qualitative and mixed-methods study designs were the commonest methods used. Implementation research was mostly used to guide post-implementation evaluation of health programmes and the contextualisation of findings to improve future implementation outcomes. The most commonly reported contextual facilitators were political support, funding, sustained collaboration and effective programme leadership. Reported barriers included inadequate human and other resources; lack of incentives; perception of implementation as additional work burden; and socio-cultural barriers.

Conclusions

This review demonstrates that implementation research can be used to achieve UHC-related outcomes in Africa. It has identified important facilitators and barriers to the use of implementation research for promoting UHC in the region.
Cell culture-based production and in vivo characterization of purely clonal defective interfering influenza virus particles
Authors: Hein Marc D. , Arora Prerna , Marichal-Gallardo Pavel , Winkler Michael , Genzel Yvonne , Pöhlmann Stefan , Schughart Klaus , Kupke Sascha Y. , Reichl Udo
Published: May 2021

Background

Infections with influenza A virus (IAV) cause high morbidity and mortality in humans. Additional to vaccination, antiviral drugs are a treatment option. Besides FDA-approved drugs such as oseltamivir or zanamivir, virus-derived defective interfering (DI) particles (DIPs) are considered promising new agents. IAV DIPs typically contain a large internal deletion in one of their eight genomic viral RNA (vRNA) segments. Consequently, DIPs miss the genetic information necessary for replication and can usually only propagate by co-infection with infectious standard virus (STV), compensating for their defect. In such a co-infection scenario, DIPs interfere with and suppress STV replication, which constitutes their antiviral potential.

Results

In the present study, we generated a genetically engineered MDCK suspension cell line for production of a purely clonal DIP preparation that has a large deletion in its segment 1 (DI244) and is not contaminated with infectious STV as egg-derived material. First, the impact of the multiplicity of DIP (MODIP) per cell on DI244 yield was investigated in batch cultivations in shake flasks. Here, the highest interfering efficacy was observed for material produced at a MODIP of 1E−2 using an in vitro interference assay. Results of RT-PCR suggested that DI244 material produced was hardly contaminated with other defective particles. Next, the process was successfully transferred to a stirred tank bioreactor (500 mL working volume) with a yield of 6.0E+8 PFU/mL determined in genetically modified adherent MDCK cells. The produced material was purified and concentrated about 40-fold by membrane-based steric exclusion chromatography (SXC). The DI244 yield was 92.3% with a host cell DNA clearance of 97.1% (99.95% with nuclease digestion prior to SXC) and a total protein reduction of 97.2%. Finally, the DIP material was tested in animal experiments in D2(B6).A2G-Mx1r/rmice. Mice infected with a lethal dose of IAV and treated with DIP material showed a reduced body weight loss and all animals survived.

Conclusion

In summary, experiments not only demonstrated that purely clonal influenza virus DIP preparations can be obtained with high titers from animal cell cultures but confirmed the potential of cell culture-derived DIPs as an antiviral agent.
The effects of melatonin treatment on oxidative stress induced by ovariohysterectomy in dogs
Authors: Salavati Sina , Mogheiseh Asghar , Nazifi Saeed , Amiri Atefeh , Nikahval Behrooz
Published: May 2021

Background

As one of the most common surgeries performed in veterinary medicine, ovariohysterectomy (OHE) can induce oxidative stress in dogs. The antioxidant properties of melatonin have been confirmed in various studies. This study aimed to investigate the effects of melatonin administration on oxidative stress in dogs before and after OHE. In this study, 25 mature female intact dogs were selected and randomly divided into five equal groups: Melatonin (melatonin, no surgery), OHE (no melatonin, surgery), OHE + melatonin (melatonin, surgery), anesthesia+melatonin (melatonin, sham surgery), and control (no melatonin, no surgery) groups. Melatonin (0.3 mg/Kg/day, p.o.) was administrated to the dogs in the melatonin, OHE + melatonin, and anesthesia+melatonin groups on days − 1, 0, 1, 2, and 3 (day 0 = OHE). Blood sampling was performed on days − 1, 1, 3, and 5 of the study. Blood samples were immediately transferred to the laboratory and sera were separated and stored at − 20 °C. Superoxide dismutase (SOD), glutathione peroxidase (GPX), catalase (CAT) and malondialdehyde (MDA) concentrations were measured with commercial kits.

Results

The levels of SOD, GPX and CAT were significantly higher in the melatonin and anesthesia+melatonin groups compared to those of the control group at days 3 and 5. The level of antioxidant enzymes significantly decreased in the OHE group compared to that of other groups at days 3 and 5. The administration of melatonin increased the level of antioxidant enzymes in ovariohysterectomized dogs. Ovariohysterectomy significantly increased the concentration of MDA in comparison to that of other groups at day 3. Melatonin administration significantly decreased the level of MDA in melatonin, anesthetized, and ovariohysterectomized dogs at day 3.

Conclusions

Administration of melatonin on day − 1, 0, 1, 2 and 3 modulate the oxidative stress induced by OHE in dogs by increasing antioxidant enzymes concentration and decreasing MDA levels.
Comprehensive analysis of prognostic value and immune infiltration of kindlin family members in non-small cell lung cancer
Authors: Su Xiaoshan , Liu Ning , Wu Weijing , Zhu Zhixing , Xu Yuan , He Feng , Chen Xinfu , Zeng Yiming
Published: May 2021

Background

Kindlin Family Members have been reported to be aberrantly expressed in various human cancer types and involved in tumorigenesis, tumor progression, and chemoresistance. However, their roles in non-small cell lung cancer (NSCLC) remain poorly elucidated.

Methods

We analyzed the prognostic value and immune infiltration of Kindlins in NSCLC through Oncomine, GEPIA, UALCAN, CCLE, Kaplan‑Meier plotter, cBioPortal, TIMER, GeneMANIA, STRING, and DAVID database. Additionally, the mRNA expression levels of Kindlins were verified in 30 paired NSCLC tissues and NSCLC cell lines by real-time PCR.

Results

The expression level of FERMT1 was remarkably increased in NSCLC tissues and NSCLC cell lines, while FERMT2 and FERMT3 were reduced. Kindlins expressions were associated with individual cancer stages and nodal metastasis. We also found that higher expression level of FERMT1 was obviously correlated with worse overall survival (OS) in patients with NSCLC, while higher FERMT2 was strongly associated with better overall survival (OS) and first progression (FP). Additionally, the expression of FERMT2 and FERMT3 were obviously correlated with the immune infiltration of diverse immune cells. Functional enrichment analysis has shown that Kindlins may be significantly correlated with intracellular signal transduction, ATP binding and the PI3K-Akt signaling pathway in NSCLC.

Conclusions

The research provides a new perspective on the distinct roles of Kindlins in NSCLC and likely has important implications for future novel biomarkers and therapeutic targets in NSCLC.
Bioinformatic identification of hub genes and related transcription factors in low shear stress treated endothelial cells
Authors: Yang Yang , Xu Xiangshan
Published: May 2021

Background

Recent evidences indicated that shear stress is critical in orchestrating gene expression in cardiovascular disease. It is necessary to identify the mechanism of shear stress influencing gene expression in physiology and pathophysiology conditions. This paper aimed to identify candidate hub genes and its transcription factors with bioinformatics.

Methods

We analyzed microarray expression profile of GSE16706 to identify differentially expressed genes (DEGs) in low shear stress (1 dyne/cm2) treated human umbilical vein endothelial cells (HUVECs) compared with static condition for 24 h.

Results

652 DEGs, including 333 up-regulated and 319 down-regulated DEGs, were screen out. Functional enrichment analysis indicated enrichment items mainly included cytokine-cytokine receptor interaction and cell cycle. Five hub genes (CDC20, CCNA2, KIF11, KIF2C and PLK1) and one significant module (score = 17.39) were identified through protein–protein interaction (PPI) analysis. Key transcriptional factor FOXC1 displayed close interaction with all the hub genes via gene-transcriptional factor network. Single-gene GSEA analysis indicated that CDC20 was linked to the G2M_CHECKPOINT pathway and cell cycle pathway.

Conclusions

By using integrated bioinformatic analysis, a new transcriptional factor and hub-genes network related to HUVECs treated with low shear stress were identified. The new regulation mechanism we discovered may be a promising potential therapeutic target for cardiovascular disease.
The impact of weight loss related to risk of new-onset atrial fibrillation in patients with type 2 diabetes mellitus treated with sodium–glucose cotransporter 2 inhibitor
Authors: Chan Yi-Hsin , Chen Shao-Wei , Chao Tze-Fan , Kao Yi-Wei , Huang Chien-Ying , Chu Pao-Hsien
Published: May 2021

Background

Sodium–glucose cotransporter 2 inhibitor (SGLT2i) use reduces body weight (BW) in patients with type 2 diabetes mellitus (T2DM). Obesity and T2DM are strong risk factors of new-onset atrial fibrillation (AF). However, whether BW loss following SGLT2i treatment reduces AF risk in patients with T2DM remains unclear.

Methods

We used a medical database from a multicenter health care provider in Taiwan, which included 10,237 patients with T2DM, from June 1, 2016 to December 31, 2018, whose BW data at baseline and at 12 weeks of SGLT2i treatment were available. Patients were followed up from the drug index date until the occurrence of new-onset AF, discontinuation of the SGLT2i, or the end of the study period, whichever occurred first.

Results

The patients’ baseline body mass index (BMI) was 28.08$$\pm$$±4.88 kg/m2. SGLT2i treatment was associated with a BW loss of 1.35$$\pm$$±3.28 kg (1.78%$$\pm$$±4.47%). There were 37.4%, 47.0%, and 15.6% of patients experienced no-BW loss (n = 3832), BW loss 0.0–4.9% (n = 4814), and$$\ge$$≥5.0% (n = 1591) following SGLT2i treatment, respectively. Compared with patients with baseline BMI < 23 kg/m2, AF risk significantly increased in patients with baseline BMI$$\ge$$≥27.5 kg/m2(Pfor trend = 0.015). Compared with those without BW loss after SGLT2i treatment, AF risk significantly decreased with a BW loss of$$\ge$$≥5.0% (adjusted hazard ratios [95% confidence intervals]: 0.39[0.22–0.68]). Use of diuretics, old age, high-dose SGLT2i, higher estimated glomerular filtration rate, and baseline BMI were independent factors associated with a BW loss of$$\ge$$≥5.0% following SGLT2i initiation. By contrast, neither baseline BMI nor BW loss after SGLT2i treatment predicted major cardiovascular adverse events or heart failure hospitalization risk (Pfor trend > 0.05).

Conclusion

BW loss of ≥ 5.0% following SGLT2i treatment was associated with a lower risk of new-onset AF in patients with T2DM in real-world practice.
MSCs loaded with oncolytic reovirus: migration and in vivo virus delivery potential for evaluating anti-cancer effect in tumor-bearing C57BL/6 mice
Authors: Seyed-Khorrami Seyed-Mahmood , Soleimanjahi Hoorieh , Soudi Sara , Habibian Ala
Published: May 2021

Background and aims

Several oncolytic viruses applications have been approved in the clinic or in different phases of clinical trials. However, these methods have some rudimentary problems. Therefore, to enhance the delivery and quality of treatment, considering the advantage of cell carrier-based methods such as Mesenchymal Stem Cells (MSC) have been proposed. This study was designed to evaluate the performance and quality of cancer treatment based on MSCs loaded by oncolytic reovirus in the cancerous C57BL/6 mouse model. Also, we evaluated MSCs migration potency in vitro and in vivo following the oncolytic reovirus infection.

Methods

C57BL/6 mice were inoculated with TC-1 cell lines and tumors were established in the right flank. Mice were systemically treated with reovirus, MSCs-loaded with reovirus, MSCs, and PBS as a control in separated groups. Effects of infected AD-MSCs with reovirus on tumor growth and penetration in the tumor site were monitored. All groups of mice were monitored for two months in order to therapeutic and anticancer potential. After treatments, tumor size alteration and apoptosis rate, as well as cytokine release pattern was assessed.

Results

The results of the current study indicated that the effect of reovirus infection on AD-MSCs is not devastating the migration capacity especially in MOI 1 and 5 while intact cells remain. On the other hand, MSCs play an efficient role as a carrier to deliver oncolytic virus into the tumor site in comparison with systemic administration of reovirus alone. Apoptosis intensity relies on viral titration and passing time. Followed by systemic administration, treatment with oncolytic reovirus-infected AD-MSCs and MSCs alone had shown significant inhibition in tumor growth. Also, treatment by reovirus causes an increase in IFN-γ secretion.

Conclusion

The results of in vitro and in vivo study confirmed the tumor-homing properties of infected AD-MSCs and the significant antitumor activity of this platform. Hence, our results showed that the cell carrier strategy using oncolytic reovirus-loaded AD-MSCs enhanced virus delivery, infiltration, and antitumor activity can be effectively applied in most cancers.
iRFP (near-infrared fluorescent protein) imaging of subcutaneous and deep tissue tumours in mice highlights differences between imaging platforms
Authors: Hall C. , von Grabowiecki Y. , Pearce S. P. , Dive C. , Bagley S. , Muller P. A. J.
Published: May 2021

Background

In vivo imaging using fluorescence is used in cancer biology for the detection, measurement and monitoring of tumours. This can be achieved with the expression of fluorescent proteins such as iRFP, which emits light at a wavelength less attenuated in biological tissues compared to light emitted by other fluorescent proteins such as GFP or RFP. Imaging platforms capable of detecting fluorescent tumours in small animals have been developed but studies comparing the performance of these platforms are scarce.

Results

Through access to three platforms from Xenogen, Bruker and Li-Cor, we compared their ability to detect iRFP-expressing subcutaneous tumours as well as tumours localised deeper within the body of female NSG mice. Each platform was paired with proprietary software for image analyse, but the output depends on subjective decisions from the user. To more objectively compare platforms, we developed an ‘in house’ software-based approach which results in lower measured variability between mice.

Conclusions

Our comparisons showed that all three platforms allowed for reliable detection and monitoring of subcutaneous iRFP tumour growth. The biggest differences between platforms became apparent when imaging deeper tumours with the Li-Cor platform detecting most tumours and showing the highest dynamic range.
Health system responsiveness: a systematic evidence mapping review of the global literature
Authors: Khan Gadija , Kagwanja Nancy , Whyle Eleanor , Gilson Lucy , Molyneux Sassy , Schaay Nikki , Tsofa Benjamin , Barasa Edwine , Olivier Jill
Published: May 2021

Background

The World Health Organisation framed responsiveness, fair financing and equity as intrinsic goals of health systems. However, of the three, responsiveness received significantly less attention. Responsiveness is essential to strengthen systems’ functioning; provide equitable and accountable services; and to protect the rights of citizens. There is an urgency to make systems more responsive, but our understanding of responsiveness is limited. We therefore sought to map existing evidence on health system responsiveness.

Methods

A mixed method systemized evidence mapping review was conducted. We searched PubMed, EbscoHost, and Google Scholar. Published and grey literature; conceptual and empirical publications; published between 2000 and 2020 and English language texts were included. We screened titles and abstracts of 1119 publications and 870 full texts.

Results

Six hundred twenty-one publications were included in the review. Evidence mapping shows substantially more publications between 2011 and 2020 (n = 462/621) than earlier periods. Most of the publications were from Europe (n = 139), with more publications relating to High Income Countries (n = 241) than Low-to-Middle Income Countries (n = 217). Most were empirical studies (n = 424/621) utilized quantitative methodologies (n = 232), while qualitative (n = 127) and mixed methods (n = 63) were more rare. Thematic analysis revealed eight primary conceptualizations of ‘health system responsiveness’, which can be fitted into three dominant categorizations: 1) unidirectional user-service interface; 2) responsiveness as feedback loops between users and the health system; and 3) responsiveness as accountability between public and the system.

Conclusions

This evidence map shows a substantial body of available literature on health system responsiveness, but also reveals evidential gaps requiring further development, including: a clear definition and body of theory of responsiveness; the implementation and effectiveness of feedback loops; the systems responses to this feedback; context-specific mechanism-implementation experiences, particularly, of LMIC and fragile-and conflict affected states; and responsiveness as it relates to health equity, minority and vulnerable populations. Theoretical development is required, we suggest separating ideas of services and systems responsiveness, applying a stronger systems lens in future work. Further agenda-setting and resourcing of bridging work on health system responsiveness is suggested.
Sphingolipid lysosomal storage diseases: from bench to bedside
Authors: Abed Rabbo Muna , Khodour Yara , Kaguni Laurie S. , Stiban Johnny
Published: May 2021

Johann Ludwig Wilhelm Thudicum described sphingolipids (SLs) in the late nineteenth century, but it was only in the past fifty years that SL research surged in importance and applicability. Currently, sphingolipids and their metabolism are hotly debated topics in various biochemical fields. Similar to other macromolecular reactions, SL metabolism has important implications in health and disease in most cells. A plethora of SL-related genetic ailments has been described. Defects in SL catabolism can cause the accumulation of SLs, leading to many types of lysosomal storage diseases (LSDs) collectively called sphingolipidoses. These diseases mainly impact the neuronal and immune systems, but other systems can be affected as well. This review aims to present a comprehensive, up-to-date picture of the rapidly growing field of sphingolipid LSDs, their etiology, pathology, and potential therapeutic strategies. We first describe LSDs biochemically and briefly discuss their catabolism, followed by general aspects of the major diseases such as Gaucher, Krabbe, Fabry, and Farber among others. We conclude with an overview of the available and potential future therapies for many of the diseases. We strive to present the most important and recent findings from basic research and clinical applications, and to provide a valuable source for understanding these disorders.
Construction of nanomaterials as contrast agents or probes for glioma imaging
Authors: Zhao Wei , Yu Xiangrong , Peng Shaojun , Luo Yu , Li Jingchao , Lu Ligong
Published: May 2021

Malignant glioma remains incurable largely due to the aggressive and infiltrative nature, as well as the existence of blood–brain-barrier (BBB). Precise diagnosis of glioma, which aims to accurately delineate the tumor boundary for guiding surgical resection and provide reliable feedback of the therapeutic outcomes, is the critical step for successful treatment. Numerous imaging modalities have been developed for the efficient diagnosis of tumors from structural or functional aspects. However, the presence of BBB largely hampers the entrance of contrast agents (Cas) or probes into the brain, rendering the imaging performance highly compromised. The development of nanomaterials provides promising strategies for constructing nano-sized Cas or probes for accurate imaging of glioma owing to the BBB crossing ability and other unique advantages of nanomaterials, such as high loading capacity and stimuli-responsive properties. In this review, the recent progress of nanomaterials applied in single modal imaging modality and multimodal imaging for a comprehensive diagnosis is thoroughly summarized. Finally, the prospects and challenges are offered with the hope for its better development.
Human nuclear receptors (NRs) genes have prognostic significance in hepatocellular carcinoma patients
Authors: Sun Guangtao , Sun Kejian , Shen Chao
Published: May 2021

Background

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related mortality in the world.

Method

We downloaded the mRNA profiles and clinical information of 371 HCC patients from The Cancer Genome Atlas (TCGA) database. The consensus clustering analysis with the mRNA levels of 48 nuclear receptors (NRs) was performed by the “ConsensusClusterPlus.” The univariate Cox regression analysis was performed to predict the prognostic significance of NRs on HCC. The risk score was calculated by the prognostic model constructed based on eight optimal NRs. Then multivariate Cox regression analysis was performed to determine whether the risk score is an independent prognostic signature. Finally, the nomogram based on multiple independent prognostic factors was used to predict the long-term survival of HCC patients.

Results

The prognostic model constructed based on the eight optimal NRs (NR1H3, ESR1, NR1I2, NR2C1, NR6A1, PPARD, PPARG, and VDR) could effectively predict the prognosis of HCC patients as an independent prognostic signature. Moreover, the nomogram was constructed based on multiple independent prognostic factors including risk score and tumor node metastasis (TNM) stage and could better predict the long-term survival for 3- and 5-year of HCC patients.

Conclusion

Our results provided novel evidences that NRs could act as the potential prognostic signatures for HCC patients.
The utility of self-rated health in population surveys: the role of bodyweight
Authors: Bozick Robert
Published: May 2021

Background

Self-rated health (SRH) is one of the most commonly used summary measures of overall health and well-being available to population scientists due to its ease of administration in large-scale surveys and to its efficacy in predicting mortality. This paper assesses the extent to which SRH is affected by its placement before or after questions about bodyweight on a survey, and whether differences in placement on the questionnaire affects SRH’s predictive validity.

Methods

I assessed the validity of SRH in predicting the risk of mortality by comparing outcomes of sample members who were asked to rate their health before reporting on their bodyweight (the control group) and sample members who were asked to rate their health after reporting on their bodyweight (the treatment group). Both the control and treatment group were randomly assigned via an experiment administered as a module in a nationally representative sample of adults in the USA in 2019 (N = 2523).

Results

The odds of reporting a more favorable appraisal of health are 30% lower for sample members who were in the treatment group when compared with the control group. Additionally, the SRH of treatment group members is significantly associated with their risk of mortality, while the SRH of control group members is not.

Conclusion

The findings from this study suggest that for researchers to maximize the utility of SRH, closer attention needs to be paid to the context of the survey within which it asked. SRH is highly sensitive to the questions that precede it, and this sensitivity may in turn mischaracterize the true health of the population that the survey is intending to measure.
Targeting the PI3K and MAPK pathways to improve response to HER2-targeted therapies in HER2-positive gastric cancer
Authors: Mezynski M. Janusz , Farrelly Angela M. , Cremona Mattia , Carr Aoife , Morgan Clare , Workman Julie , Armstrong Paul , McAuley Jennifer , Madden Stephen , Fay Joanna , Sheehan Katherine M. , Kay Elaine W. , Holohan Ciara , Elamin Yasir , Rafee Shereen , Morris Patrick G. , Breathnach Oscar , Grogan Liam , Hennessy Bryan T. , Toomey Sinead
Published: May 2021

Background

Aberrant PI3K signalling is implicated in trastuzumab resistance in HER2-positive gastric cancer (GC). The role of PI3K or MEK inhibitors in sensitising HER2-positive GCs to trastuzumab or in overcoming trastuzumab resistance is unclear.

Methods

Using mass spectrometry-based genotyping we analysed 105 hotspot, non-synonymous somatic mutations in PIK3CA and ERBB-family (EGFR, ERBB2, ERBB3 and ERBB4) genes in gastric tumour samples from 69 patients. A panel of gastric cell lines (N87, OE19, ESO26, SNU16, KATOIII) were profiled for anti-proliferative response to the PI3K inhibitor copanlisib and the MEK1/2 inhibitor refametinib alone and in combination with anti-HER2 therapies.

Results

Patients with HER2-positive GC had significantly poorer overall survival compared to HER2-negative patients (15.9 months vs. 35.7 months). Mutations in PIK3CA were only identified in HER2-negative tumours, while ERBB-family mutations were identified in HER2-positive and HER2-negative tumours. Copanlisib had anti-proliferative effects in 4/5 cell lines, with IC50s ranging from 23.4 (N87) to 93.8 nM (SNU16). All HER2-positive cell lines except SNU16 were sensitive to lapatinib (IC50s 0.04 µM–1.5 µM). OE19 cells were resistant to trastuzumab. The combination of lapatinib and copanlisib was synergistic in ESO-26 and OE-19 cells (ED50: 0.83 ± 0.19 and 0.88 ± 0.13, respectively) and additive in NCI-N87 cells (ED50:1.01 ± 0.55). The combination of copanlisib and trastuzumab significantly improved growth inhibition compared to either therapy alone in NCI-N87, ESO26 and OE19 cells (p < 0.05).

Conclusions

PI3K or MEK inhibition alone or in combination with anti-HER2 therapy may represent an improved treatment strategy for some patients with HER2-positive GC, and warrants further investigation in a clinical trial setting.
Identifying the functions of two biomarkers in human oligodendrocyte progenitor cell development
Authors: Zhou Haipeng , He Ying , Wang Zhaoyan , Wang Qian , Hu Caiyan , Wang Xiaohua , Lu Siliang , Li Ke , Yang Yinxiang , Luan Zuo
Published: May 2021

Background

Human oligodendrocyte precursor cells (hOPCs) are an important source of myelinating cells for cell transplantation to treat demyelinating diseases. Myelin oligodendrocytes develop from migratory and proliferative hOPCs. It is well known that NG2 and A2B5 are important biological markers of hOPCs. However, the functional differences between the cell populations represented by these two biomarkers have not been well studied in depth.

Objective

To study the difference between NG2 and A2B5 cells in the development of human oligodendrocyte progenitor cells.

Methods

Using cell sorting technology, we obtained NG2+/−, A2B5+/− cells. Further research was then conducted via in vitro cell proliferation and migration assays, single-cell sequencing, mRNA sequencing, and cell transplantation into shiverer mice.

Results

The proportion of PDGFR-α + cells in the negative cell population was higher than that in the positive cell population. The migration ability of the NG2+/−, A2B5+/− cells was inversely proportional to their myelination ability. The migration, proliferation, and myelination capacities of the negative cell population were stronger than those of the positive cell population. The ability of cell migration and proliferation of the four groups of cells from high to low was: A2B5− > NG2− > NG2+ > A2B5+. The content of PDGFR-α+ cells and the ability of cell differentiation from high to low was: NG2− > A2B5− > A2B5+ > NG2+.

Conclusion

In summary, NG2+  and A2B5+ cells have poor myelination ability due to low levels of PDGFR-α+ cells. Therefore, hOPCs with a higher content of PDGFR-α+ cells may have a better effect in the cell transplantation treatment of demyelinating diseases.
Electronic forms for patient reported outcome measures (PROMs) are an effective, time-efficient, and cost-minimizing alternative to paper forms
Authors: Yu Jennifer Y. , Goldberg Talia , Lao Nicholas , Feldman Brian M. , Goh Y. Ingrid
Published: May 2021

Background

Patient reported outcome measures (PROMs) provide valuable insight on patients’ well-being and facilitates communication between healthcare providers and their patients. The increased integration of the technology within the healthcare setting presents the opportunity to collect PROMs electronically, rather than on paper. The Childhood Health Assessment Questionnaire (CHAQ) and Quality of My Life (QoML) are common PROMs collected from pediatric rheumatology patients. The objectives of this study are to (a) determine the equivalence of the paper and electronic forms (e-form) of CHAQ and QoML questionnaires; (b) identify potential benefits and barriers associated with using an e-form to capture PROMs; and (c) gather feedback on user experience.

Methods

Participants completed both a paper and an e-form of the questionnaires in a randomized order, following which they completed a feedback survey. Agreement of the scores between the forms were statistically analyzed using the intraclass correlation coefficient (ICC) (95 % Confidence Interval (CI)) and bias was assessed using a Bland-Altman plot. Completion and processing times of the forms were compared using mean and median measures. Quantitative analysis was performed to assess user experience ratings, while comments were qualitatively analyzed to identify important themes.

Results

196 patients participated in this project. Scores on the forms had high ICC agreement > 0.9. New patients took longer than returning patients to complete the forms. Overall, the e-form was completed and processed in a shorter amount of time than the paper form. 83 % of survey respondents indicated that they either preferred the e-form or had no preference. Approximately 10 % of respondents suggested improvements to improve the user interface.

Conclusions

E-forms collect comparable information in an efficient manner to paper forms. Given that patients and caregivers indicated they preferred completing PROMs in this manner, we will implement their suggested changes and incorporate e-forms as standard practice for PROMs collection in our pediatric rheumatology clinic.
Myoelectric prosthesis users and non-disabled individuals wearing a simulated prosthesis exhibit similar compensatory movement strategies
Authors: Williams Heather E. , Chapman Craig S. , Pilarski Patrick M. , Vette Albert H. , Hebert Jacqueline S.
Published: May 2021

Background

Research studies on upper limb prosthesis function often rely on the use of simulated myoelectric prostheses (attached to and operated by individuals with intact limbs), primarily to increase participant sample size. However, it is not known if these devices elicit the same movement strategies as myoelectric prostheses (operated by individuals with amputation). The objective of this study was to address the question of whether non-disabled individuals using simulated prostheses employ the same compensatory movements (measured by hand and upper body kinematics) as individuals who use actual myoelectric prostheses.

Methods

The upper limb movements of two participant groups were investigated: (1) twelve non-disabled individuals wearing a simulated prosthesis, and (2) three individuals with transradial amputation using their custom-fitted myoelectric devices. Motion capture was used for data collection while participants performed a standardized functional task. Performance metrics, hand movements, and upper body angular kinematics were calculated. For each participant group, these measures were compared to those from a normative baseline dataset. Each deviation from normative movement behaviour, by either participant group, indicated that compensatory movements were used during task performance.

Results

Results show that participants using either a simulated or actual myoelectric prosthesis exhibited similar deviations from normative behaviour in phase durations, hand velocities, hand trajectories, number of movement units, grip aperture plateaus, and trunk and shoulder ranges of motion.

Conclusions

This study suggests that the use of a simulated prosthetic device in upper limb research offers a reasonable approximation of compensatory movements employed by a low- to moderately-skilled transradial myoelectric prosthesis user.