bluuebunny/crossref_metadata_2025 huggingface dataset:
Key stakeholder perspectives on the development and real-world implementation of a home-based physical activity program for mothers at risk of postnatal depression: a qualitative study
Authors: Teychenne Megan , Apostolopoulos Maria , Ball Kylie , Olander Ellinor K. , Opie Rachelle S. , Rosenbaum Simon , Laws Rachel
Published: February 2021

Background

Physical activity (PA) is a modifiable risk factor for postnatal depression (PND) and programs are needed to enhance PA amongst women at risk of PND. Key stakeholder involvement in informing development and implementation of such programs is vital. However, little research demonstrates key stakeholder insights to inform the design and delivery of PA programs for improving PND. The aim of this study was to explore key stakeholder perspectives on the design and delivery of a home-based PA program for mothers with PND symptoms to inform future real-world implementation and scale-up.

Methods

A descriptive qualitative study was undertaken whereby semi-structured interviews were conducted with representatives from various key stakeholder organisations involved in postnatal PA and/or mental health, public health and policy in Australia (n = 11). Interviews were conducted between September to November 2019 and explored stakeholder perceptions on the design and delivery of a home-based PA program for mothers with PND symptoms. The interview schedule was informed by both the Consolidated Framework for Implementation Research (CFIR) and the PRACTical planning for Implementation and Scale-up (PRACTIS) guide. Data were analysed thematically using both deductive and inductive coding.

Results

The relative priority of PND and PA was high for most organisations involved, although none implemented PA programs supporting women at risk of PND. Most stakeholders perceived the program as appealing due to addressing barriers to postnatal PA, although identified some feasibility issues regarding funding and delivery mechanisms. Suggestions for program adaptations included an equity focus (e.g. providing socioeconomically disadvantaged women with a greater program dose; translating web-app based content into various languages). Planned components of the program were suggested to align (i.e. relative advantage) with existing initiatives (e.g. equipment hire for nurseries scheme) and screening systems for PND (timing of referral). Perceived barriers to scale-up included logistics/cost of equipment, organisational capacity demands and safety risks/liability. Perceived enablers to scale-up included linking the program with ‘adjunct’ programs and services.

Conclusions

While the program was appealing and most organisations could see a role in endorsing and/or referring to the program, funding and delivery mechanisms still need to be identified.
Evidence use in E-cigarettes debates: scientific showdowns in a ‘wild west’ of research
Authors: Smith Katherine E. , Ikegwuonu Theresa , Weishaar Heide , Hilton Shona
Published: February 2021

Background

Against a backdrop of declining tobacco use, e-cigarette markets are growing. The UK now has a higher percentage of e-cigarette users than any other European country. These developments have prompted fierce discussions in scientific, advocacy and policy communities about how best to respond. This article is one of the first to examine the role of evidence in these debates.

Methods

We analysed 121 submissions to two Scottish policy consultations on e-cigarettes (in 2014 and 2015) and undertook interviews with 26 key informants in 2015–2016, following up with a sub-set in 2019–2020. All data were thematically coded, and our analysis was informed by insights from policy studies and the sociology of science.

Results

First, we affirm previous research in suggesting that e-cigarettes appeared to have triggered a breakdown of old public health alliances. Second, we demonstrate that, amid concerns about research quality and quantity, actors are guided by normative outlooks (and/or economic interests) in their assessments of evidence. Third, we show that, despite describing e-cigarette debates as contentious and polarised, actors engaging in Scottish policy debates exhibit a spectrum of views, with most interviewees occupying an uncertain ‘middle ground’ that is responsive to new evidence. Fourth, we suggest that the perceived divisiveness of e-cigarette debates is attributed to recurrent media simplifications and tensions arising from the behaviours of some actors with settled positions working to promote particular policy responses (including by strategically enrolling supportive evidence). Fifth, we argue that the actions of these actors are potentially explained by the prospect that e-cigarettes could usher in a new tobacco ‘policy paradigm’. Finally, we show how scientific authority is employed as a tool within these debates.

Conclusions

E-cigarette debates are likely to reconcile only if a clear majority of participants in the uncertain ‘middle ground’ settle on a more fixed position. Our results suggest that many participants in Scottish e-cigarette debates occupy this ‘middle ground’ and express concerns that can be empirically assessed, implying evidence has the potential to play a more important role in settling e-cigarette debates than previous research suggests.
Identification of subgroup effect with an individual participant data meta-analysis of randomised controlled trials of three different types of therapist-delivered care in low back pain
Authors:   On behalf of the Repository Group, Hee Siew Wan , Mistry Dipesh , Friede Tim , Lamb Sarah E. , Stallard Nigel , Underwood Martin , Patel Shilpa
Published: February 2021

Background

Proven treatments for low back pain, at best, only provide modest overall benefits. Matching people to treatments that are likely to be most effective for them may improve clinical outcomes and makes better use of health care resources.

Methods

We conducted an individual participant data meta-analysis of randomised controlled trials of three types of therapist delivered interventions for low back pain (active physical, passive physical and psychological treatments). We applied two statistical methods (recursive partitioning and adaptive risk group refinement) to identify potential subgroups who might gain greater benefits from different treatments from our individual participant data meta-analysis.

Results

We pooled data from 19 randomised controlled trials, totalling 9328 participants. There were 5349 (57%) females with similar ratios of females in control and intervention arms. The average age was 49 years (standard deviation, SD, 14).

Participants with greater psychological distress and physical disability gained most benefit in improving on the mental component scale (MCS) of SF-12/36 from passive physical treatment than non-active usual care (treatment effects, 4.3; 95% confidence interval, CI, 3.39 to 5.15). Recursive partitioning method found that participants with worse disability at baseline gained most benefit in improving the disability (Roland Morris Disability Questionnaire) outcome from psychological treatment than non-active usual care (treatment effects, 1.7; 95% CI, 1.1 to 2.31). Adaptive risk group refinement did not find any subgroup that would gain much treatment effect between psychological and non-active usual care. Neither statistical method identified any subgroups who would gain an additional benefit from active physical treatment compared to non-active usual care.

Conclusions

Our methodological approaches worked well and may have applicability in other clinical areas. Passive physical treatments were most likely to help people who were younger with higher levels of disability and low levels of psychological distress. Psychological treatments were more likely to help those with severe disability. Despite this, the clinical importance of identifying these subgroups is limited. The sizes of sub-groups more likely to benefit and the additional effect sizes observed are small. Our analyses provide no evidence to support the use of sub-grouping for people with low back pain.
Treatment of non‐arthritic pseudoparetic shoulders with irreparable massive rotator cuff tears: arthroscopic procedures yield comparable midterm results to reverse arthroplasty
Authors: Plachel Fabian , Siegert Paul , Moroder Philipp , Pauzenberger Leo , Laky Brenda , Anderl Werner , Heuberer Philipp
Published: February 2021

Background

Irreparable massive rotator cuff tears (IMRCTs) are a well-known cause for functional limitation and difficult to treat. Although several joint-preserving as well as joint-replacing procedures were found to provide pain relief and gain of function, midterm results are scarce, particularly in pseudoparetic shoulder joints unaccompanied by severe osteoarthritis. The purpose of this study was to compare the midterm functional outcomes of arthroscopic procedures to those of reverse total shoulder arthroplasty (RTSA) in pseudoparetic shoulders with IMRCTs unaccompanied by severe osteoarthritis.

Methods

All patients who underwent either joint-preserving (group A) or joint-replacing (group B) procedures for IMRCT unaccompanied by severe osteoarthritis with a pseudoparetic shoulder function were retrospectively included. Clinical assessment included the Constant Score (CS), the Subjective Shoulder Value (SSV) and the Visual Analog Score (VAS) at baseline and at latest follow-up. Furthermore, the complication and revision rates were assessed.

Results

Overall, a total 56 patients were included of whom each 28 patients formed group A (male, 36%) and B (male, 53%) with a mean patient age at time of surgery of 70 ± 7 years and 72 ± 7 years, respectively. The mean follow-up period was 56 ± 17 months. At final follow-up, the total CS (group A: 66 ± 14 points; group B 54 ± 15 points) was significantly increased after arthroscopic treatment when compared to RTSA (p=0.011). However, no significant differences were detected with SSV (p=0.583) and VAS (p=0.536). Although complication rate (11% versus 18%) was not significantly different (p=0.705), number of revision surgeries was significantly higher in group B when compared to group A (p=0.041).

Conclusions

In non-arthritic pseudoparetic shoulders, both joint-preserving and joint-replacing procedures yielded good clinical midterm outcomes for the treatment of degenerative IMRCTs. Despite of comparable functional and satisfactory functional improvement, increased complication rates and surgical invasiveness outweigh the benefits of primary RTSA and therefore reserve this procedure to a second-line treatment in pseudoparetic patients without any signs of severe cuff arthropathy.
Reversals in initially denied Department of Veterans Affairs’ PTSD disability claims after 17 years: a cohort study of gender differences
Authors: Murdoch Maureen , Spoont Michele Roxanne , Sayer Nina Aileen , Kehle-Forbes Shannon Marie , Noorbaloochi Siamak
Published: February 2021

Background

In 2011, the Department of Veterans Affairs (VA) strengthened its disability claims processes for military sexual trauma, hoping to reduce gender differences in initial posttraumatic stress disorder (PTSD) disability awards. These process improvements should also have helped women reverse previously denied claims and, potentially, diminished gender discrepancies in appealed claims’ outcomes. Our objectives were to examine gender differences in reversals of denied PTSD claims’ outcomes after 2011, determine whether disability awards (also known as “service connection”) for other disorders offset any PTSD gender discrepancy, and identify mediating confounders that could explain any persisting discrepancy.

Methods

From a nationally representative cohort created in 1998, we examined service connection outcomes in 253 men and 663 women whose initial PTSD claims were denied. The primary outcome was PTSD service connection as of August 24, 2016. Secondary outcomes were service connection for any disorder and total disability rating. The total disability rating determines the generosity of Veterans’ benefits.

Results

51.4% of men and 31.3% of women were service connected for PTSD by study’s end (p < 0.001). At inception, 54.2% of men and 63.2% of women had any service connection—i.e., service connection for disorders other than PTSD (p = 0.01) and similar total disability ratings (p = 0.50). However, by study’s end, more men than women had any service connection (88.5% versus 83.5%, p = 0.05), and men’s mean total disability rating was substantially greater than women’s (77.1 ± 26.2 versus 66.8 ± 30.7, p < 0.001). History of military sexual assault had the largest effect modification on men’s versus women’s odds of PTSD service connection.

Conclusion

Even after 2011, cohort men were more likely than the women to reverse initially denied PTSD claims, and military sexual assault history accounted for much of this difference. Service connection for other disorders initially offset women’s lower rate of PTSD service connection, but, ultimately, men’s total disability ratings exceeded women’s. Gender discrepancies in service connection should be monitored beyond the initial claims period.
Implementation of sustainable complex interventions in health care services: the triple C model
Authors: Khalil Hanan , Kynoch Kathryn
Published: February 2021

Background

The changing and evolving healthcare environment means organisations are under increasing pressure to deliver value-based, high quality care to patients through enabling access, reducing costs and improving outcomes. These factors result in an increased pressure to deliver efficient and beneficial interventions to improve patient care and support sustainability beyond the scope of the implementation of such interventions. Additionally, the literature highlights the importance of coordination, cooperation and working together across areas is critical to achieving implementation success. This paper discusses the development of a triple C model for implementation that supports sustainability of complex interventions in health care services.

Methods

In order to develop the proposed implementation model, we adapted the formal tradition of theory building that is described in sociology. Firstly, we conducted a review of the literature on complex interventions and the available implementation models used to embed these interventions to identify the key aspects relating to successful implementation. Secondly, we devised a framework that encompassed these findings into a simple and workable model that can be easily embedded into everyday practice. This proposed model uses clear, systemic explanation, adds to the current knowledge in this area and is fit for purpose, providing healthcare workers with a simple easy-to-follow framework to embed practice change.

Results

A three-stage implementation model was devised based on the findings of the literature and named the Triple C model (Consultation, Collaboration and Consolidation). The three stages are interconnected and overlap to support sustainability is considered at all levels of the project ensuring its greater success. This model considers the sustainability within any implementation project. Sustainability of interventions are a key consideration for continuous and successful change in any health care organisation. A set of criteria were developed for each of the three stages to support adaptability and sustainment of interventions are maintained throughout the life of the intervention.

Conclusion

Ensuring sustainability of interventions requires continuing effort and embedding the need for sustainability throughout all stages of an implementation project. The Triple C model offers a new approach for healthcare clinicians to support sustainability of organizational change.
Patient preferences for using technology in communication about symptoms post hospital discharge
Authors: Alexander Kim E. , Ogle Theodora , Hoberg Hana , Linley Libbie , Bradford Natalie
Published: February 2021

Background

Technology is increasingly transforming the way we interact with others and undertake activities in our daily lives. The healthcare setting has, however, not yet realised the potential of technology solutions to facilitate communication between patients and healthcare providers. While the procedural and policy requirements of healthcare systems will ultimately drive such solutions, understanding the preferences and attitudes of patients is essential to ensure that technology implemented in the healthcare setting facilitates communication in safe, acceptable, and appropriate ways. Therefore, the purpose of this study was to examine patient preferences for using technology to communicate with health service providers about symptoms experienced following discharge from the hospital.

Methods

Primary data were collected from patients admitted to a large metropolitan hospital in Australia during three consecutive months in 2018. Participants were asked about their daily use of technology including use of computers, email, phone, text messaging, mobile applications, social media, online discussion forums, and videoconference. They were then asked about their use of technologies in managing their health, and preferences for use when communicating about symptoms with health service providers following discharge from hospital.

Results

Five hundred and twenty-five patients with a wide range of differing clinical conditions and demographics participated. Patients indicated they used a range of technologies in their everyday lives and to manage their health. Almost 60% of patients would prefer to return to hospital if they were experiencing symptoms of concern. However, if patients experienced symptoms that were not of concern, over 60% would prefer to communicate with the hospital via telephone or using technology. Admitting condition, income, and age were significantly associated with preferences for communication about symptoms following hospital discharge.

Conclusions

Patients have varied preferences for communicating with their health service providers post-hospital discharge. Findings suggest that some, but not all patients, would prefer to use technology to traditional methods of communicating with the healthcare team. Health services should offer patients multiple options for communicating about their recovery to ensure individual needs are appropriately met.
Quality assessment with diverse studies (QuADS): an appraisal tool for methodological and reporting quality in systematic reviews of mixed- or multi-method studies
Authors: Harrison Reema , Jones Benjamin , Gardner Peter , Lawton Rebecca
Published: February 2021

Background

In the context of the volume of mixed- and multi-methods studies in health services research, the present study sought to develop an appraisal tool to determine the methodological and reporting quality of such studies when included in systematic reviews. Evaluative evidence regarding the design and use of our existing Quality Assessment Tool for Studies with Diverse Designs (QATSDD) was synthesised to enhance and refine it for application across health services research.

Methods

Secondary data were collected through a literature review of all articles identified using Google Scholar that had cited the QATSDD tool from its inception in 2012 to December 2019. First authors of all papers that had cited the QATSDD (n=197) were also invited to provide further evaluative data via a qualitative online survey. Evaluative findings from the survey and literature review were synthesised narratively and these data used to identify areas requiring refinement. The refined tool was subject to inter-rater reliability, face and content validity analyses.

Results

Key limitations of the QATSDD tool identified related to a lack of clarity regarding scope of use of the tool and in the ease of application of criteria beyond experimental psychological research. The Quality Appraisal for Diverse Studies (QuADS) tool emerged as a revised tool to address the limitations of the QATSDD. The QuADS tool demonstrated substantial inter-rater reliability (k=0.66), face and content validity for application in systematic reviews with mixed, or multi-methods health services research.

Conclusion

Our findings highlight the perceived value of appraisal tools to determine the methodological and reporting quality of studies in reviews that include heterogeneous studies. The QuADS tool demonstrates strong reliability and ease of use for application to multi or mixed-methods health services research.
Seniors don’t use Medicare.Gov: how do eligible beneficiaries obtain information about Medicare Advantage Plans in the United States?
Authors: Rivera-Hernandez Maricruz , Blackwood Kristy L. , Mercedes Marquisele , Moody Kyle A.
Published: February 2021

Background

Managed care programs in the US are becoming a preferred alternative among low-income individuals in the US. Every year during open enrollment, seniors can enroll in Medicare Advantage (MA) or switch MA plans. However, there is very limited information about how seniors obtain information to help them make their choices. While the Centers for Medicaid and Medicare offer online resources that are designed to enable potential beneficiaries to make informed coverage decisions, there is no information as to whether seniors use these resources, and therefore whether these resources are effective compared to other information retrieval methods.

Methods

The purpose of the present study was to qualitatively explore how seniors obtain information about insurance plans in MA. We conducted semi-structured interviews with 26 MA beneficiaries from Rhode Island.

Results

We found that most seniors have strong preferences for obtaining information in-person regarding benefits, cost and other plan information. Some seniors relied heavily on insurance brokers or representatives, and considered the information provided to them without questioning the potential for bias. Others consulted with family and/or friends for guidance, or to compare costs and benefits. Only a few of these seniors used the available internet resources, and in fact most of them mentioned that they did not have a computer/smart device with internet capabilities. However, among those who used and appeared to be comfortable with navigating the internet,www.medicare.govwas not discussed as a useful resource for making decisions regarding health insurance.

Conclusions

This study suggests that existing online medical resource usage and effects among senior citizens in the United States may need supplementing with in-person communication among influential agents.
What are the risk factors for avoidable transitions in the last year of life? A qualitative exploration of professionals’ perspectives for improving care in Germany
Authors:   on behalf of CoRe Net, Kasdorf Alina , Dust Gloria , Vennedey Vera , Rietz Christian , Polidori Maria C. , Voltz Raymond , Strupp Julia
Published: February 2021

Background

Little is known about the nature of patients’ transitions between healthcare settings in the last year of life (LYOL) in Germany. Patients often experience transitions between different healthcare settings, such as hospitals and long-term facilities including nursing homes and hospices. The perspective of healthcare professionals can therefore provide information on transitions in the LYOL that are avoidable from a medical perspective. This study aims to explore factors influencing avoidable transitions across healthcare settings in the LYOL and to disclose how these could be prevented.

Methods

Two focus groups (n = 11) and five individual interviews were conducted with healthcare professionals working in hospitals, hospices and nursing services from Cologne, Germany. They were asked to share their observations about avoidable transitions in the LYOL. The data collection continued until the point of information power was reached and were audio recorded and analysed using qualitative content analysis.

Results

Four factors for potentially avoidable transitions between care settings in the LYOL were identified: healthcare system, organization, healthcare professional, patient and relatives. According to the participants, the most relevant aspects that can aid in reducing unnecessary transitions include timely identification and communication of the LYOL; consideration of palliative care options; availability and accessibility of care services; and having a healthcare professional taking main responsibility for care planning.

Conclusions

Preventing avoidable transitions by considering the multicomponent factors related to them not only immediately before death but also in the LYOL could help to provide more value-based care for patients and improving their quality of life.
Factors associated with access to healthcare in Burkina Faso: evidence from a national household survey
Authors: Zon Hilaire , Pavlova Milena , Groot Wim
Published: February 2021

Background

Burkina Faso has undertaken major reforms, the cornerstone of which has been the decentralization of the health system to increase access to primary healthcare and to increase the effectiveness, efficiency, financial viability and equity of health services. This study aims to analyze the socio-demographic determinants of households’ access to healthcare in Burkina Faso.

Methods

We used data from a national household survey conducted in 2014 in Burkina Faso. We carried out binary logistic and linear regression analysis using data from a national household survey. The statistical analysis explored the associations between socio-demographic characteristics on the one side, and the use of health services, satisfaction with health services and expenditures on health services, on the other side.

Results

The findings indicate an association between age, education, income and use of services (p < 0.0005). The results show that healthcare users’ satisfaction is influenced by age, the association is stronger with the age group under 24 (p < 0.0005) than the age group of 25–39 (p < 0.005). An association was found between the age group under 15 (p < 0.005), the type of health facility used (p < 0.0005), the distance traveled to health facilities (p < 0.005) and households’ individuals’ health expenditure.

Conclusion

Specific policies are needed to enhance geographical access to healthcare, financial access to and satisfaction with healthcare in moving towards universal health coverage (UHC).
Conceptual approach to developing quality measures for transgender patients
Authors: Rose Adam J. , Dunbar Michael S. , Hughto Jaclyn M. W. , Jasuja Guneet K.
Published: February 2021

Background

Valid and reliable quality measures can help catalyze improvements in health care. The care of transgender patients is ripe for quality measurement, as there is increasing awareness of the increasing prevalence of this population and the urgency of improving the health care they receive. While best practices may not exist for some aspects of transgender health care, other aspects are characterized by well-developed and highly evidence-based recommendations. Our objective was to create a list of potential quality measures for transgender care.

Methods and results

In consultation with our advisory panel, which consisted of clinical and academic experts in transgender medicine, we selected eight prominent clinical practice guidelines of transgender health care for review. Our four team investigators carefully reviewed all eight clinical practice guidelines. Through the course of multiple consensus-building meetings, we iteratively refined items until we had agreed upon a list of forty potential quality measures, all of which met the criteria for quality measures set forth in the Center for Medicare and Medicaid Services Blueprint for developing quality measures.

Conclusions

This manuscript explains the origin of the quality measures we developed, and also provides a useful roadmap to any group hoping to develop quality measures for a field that has not previously had any.
Evaluation of fasting plasma insulin and proxy measurements to assess insulin sensitivity in horses
Authors: Lindåse Sanna , Nostell Katarina , Bergsten Peter , Forslund Anders , Bröjer Johan
Published: February 2021

Background

Proxies are mathematical calculations based on fasting glucose and/or insulin concentrations developed to allow prediction of insulin sensitivity (IS) and β-cell response. These proxies have not been evaluated in horses with insulin dysregulation. The first objective of this study was to evaluate how fasting insulin (FI) and proxies for IS (1/Insulin, reciprocal of the square root of insulin (RISQI) and the quantitative insulin sensitivity check index (QUICKI)) and β-cell response (the modified insulin-to-glucose ratio (MIRG) and the homeostatic model assessment of β-cell function (HOMA-β)) were correlated to measures of IS (M index) using the euglycemic hyperinsulinemic clamp (EHC) in horses with insulin resistance (IR) and normal IS. A second objective was to evaluate the repeatability of FI and proxies in horses based on sampling on consecutive days. The last objective was to investigate the most appropriate cut-off value for the proxies and FI.

Results

Thirty-four horses were categorized as IR and 26 as IS based on the M index. The proxies and FI had coefficients of variation (CVs) ≤ 25.3 % and very good reliability (intraclass correlation coefficients ≥ 0.89). All proxies and FI were good predictors of the M index (r = 0.76–0.85; P < 0.001). The proxies for IS had a positive linear relationship with the M index whereas proxies for β-cell response and FI had an inverse relationship with the M index. Cut-off values to distinguish horses with IR from horses with normal IS based on the M index were established for all proxies and FI using receiver operating characteristic curves, with sensitivity between 79 % and 91 % and specificity between 85 % and 96 %. The cut-off values to predict IR were < 0.32 (RISQI), < 0.33 (QUICKI) and > 9.5 µIU/mL for FI.

Conclusions

All proxies and FI provided repeatable estimates of horses’ IS. However, there is no advantage of using proxies instead of FI to estimate IR in the horse. Due to the heteroscedasticity of the data, proxies and FI in general are more suitable for epidemiological studies and larger clinical studies than as a diagnostic tool for measurement of IR in individual horses.
Assessing the role of livestock and sympatric wild ruminants in spreading antimicrobial resistant Campylobacter and Salmonella in alpine ecosystems
Authors: Espunyes Johan , Cabezón Oscar , Dias-Alves Andrea , Miralles Pol , Ayats Teresa , Cerdà-Cuéllar Marta
Published: February 2021

Background

Livestock play an important role as reservoir of enteric pathogens and antimicrobial resistance (AMR), a health and economic concern worldwide. However, little is known regarding the transmission and maintenance of these pathogens at the wildlife-livestock interface. In this study, we assessed the occurrence, genetic diversity and AMR of Campylobacter spp. and Salmonella spp. shed by sympatric free-ranging livestock and a wild herbivore in an alpine ecosystem.

Results

Campylobacter spp. was isolated from 23.3 % of cattle and 7.7 % of sheep but was not isolated from horses nor Pyrenean chamois (Rupicapra pyrenaica). Campylobacter jejuni was the most frequent species. A high genetic diversity and certain host specificity of C. jejuni isolates was observed. The main AMR detected in Campylobacter isolates was to nalidixic acid (88.2 %), ciprofloxacin (82.4 %) and tetracycline (82.4 %); only 11.7 % of the isolates were pan-susceptible and 17.6 % were multi-resistant. Salmonella ser. Newport was isolated only from one Pyrenean chamois and was pan-susceptible.

Conclusions

Results show that free-ranging cattle and sheep are spreaders of Campylobacter as well as their AMR strains in the alpine environment. Therefore, contaminated alpine pastures or streams may constitute a source for the dissemination of AMR enteropathogens. However, apparently, alpine wild ungulates such as Pyrenean chamois play a negligible role in the epidemiology of zoonotic enteropathogens and AMR, and are not potential bioindicators of the burden of alpine environments.
G1-like M and PB2 genes are preferentially incorporated into H7N9 progeny virions during genetic reassortment
Authors: Li Xiuli , Gu Min , Wang Xiaoquan , Gao Ruyi , Bu Xinxin , Hao Xiaoli , Ma Jing , Hu Jiao , Hu Shunlin , Liu Xiaowen , Chen Sujuan , Peng Daxin , Jiao Xinan , Liu Xiufan
Published: February 2021

Background

Genotype S H9N2 viruses have become predominant in poultry in China since 2010. These viruses frequently donate their whole internal gene segments to other emerging influenza A subtypes such as the novel H7N9, H5N6, and H10N8 viruses. We recently reported that the PB2 and M genes of the genotype S H9N2 virus, which are derived from the G1-like virus, enhance the fitness of H5Nx and H7N9 avian influenza viruses in chickens and mice. However, whether the G1-like PB2 and M genes are preferentially incorporated into progeny virions during virus reassortment remains unclear; whether the G1-like PB2 and M genes from different subtypes are differentially incorporated into new virion progeny remains unknown.

Results

We conducted a reassortment experiment with the use of a H7N9 virus as the backbone and found that G1-like M/PB2 genes were preferentially incorporated in progeny virions over F/98-like M/PB2 genes. Importantly, the preference varied among G1-like M/PB2 genes of different subtypes. When competing with F/98-like M/PB2 genes during reassortment, both the M and PB2 genes from the H7N9 virus GD15 showed an advantage, whereas only the PB2 gene from the H9N2 virus CZ73 and the M gene from the H9N2 virus AH320 displayed the advantage.

Conclusion

Our findings highlight the preferential and variable advantages of H9N2-derived G1-like M and PB2 genes in incorporating them into H7N9 progeny virions over SH14-derived F/98-like M/PB2 genes.
A novel prognostic prediction model based on seven immune-related RNAs for predicting overall survival of patients in early cervical squamous cell carcinoma
Authors: Qin Rui , Cao Lu , Ye Cong , Wang Junrong , Sun Ziqian
Published: February 2021

Background

In this study, we aimed to mine immune-related RNAs expressed in early cervical squamous cell carcinoma to construct prognostic prediction models.

Methods

The RNA sequencing data of 309 cervical squamous cell carcinoma (CSCC) cases, including data of individuals with available clinical information, were obtained from The Cancer Genome Atlas (TCGA) database. We included 181 early-stage CSCC tumor samples with clinical survival and prognosis information (training dataset). Then, we downloaded the GSE44001 gene expression profile data from the National Center for Biotechnology Information Gene Expression Omnibus (validation dataset). Gene ontology annotation and the Kyoto Encyclopedia of Genes and Genomes pathway analyses were used to analyze the biological functions of differentially expressed immune-related genes (DEIRGs). We established protein–protein interactions and competing endogenous RNA networks using Cytoscape. Using the Kaplan–Meier method, we evaluated the association between the high- and low-risk groups and the actual survival and prognosis information. Our univariate and multivariate Cox regression analyses screened for independent prognostic factors.

Results

We identified seven prognosis-related signature genes (RBAKDN, CXCL2, ZAP70, CLEC2D, CD27, KLRB1, VCAM1), the expression of which was markedly associated with overall survival (OS) in CSCC patients. Also, the risk score of the seven-gene signature discripted superior ability to categorize CSCC patients into high-risk and low-risk groups, with a observablydifferent OS in the training and validation datasets. We screened two independent prognostic factors (Pathologic N and prognostic score model status) that correlated significantly by univariate and multivariate Cox regression analyses in the TCGA dataset. To further explore the potential mechanism of immune-related genes, we observed associated essential high-risk genes with a cytokine–cytokine receptor interaction.

Conclusions

This study established an immune-related RNA signature, which provided a reliable prognostic tool and may be of great significance for determining immune-related biomarkers in CSCC.
An optimized growth medium for increased recombinant protein secretion titer via the type III secretion system
Authors: Burdette Lisa Ann , Wong Han Teng , Tullman-Ercek Danielle
Published: February 2021

Background

Protein secretion in bacteria is an attractive strategy for heterologous protein production because it retains the high titers and tractability of bacterial hosts while simplifying downstream processing. Traditional intracellular production strategies require cell lysis and separation of the protein product from the chemically similar cellular contents, often a multi-step process that can include an expensive refolding step. The type III secretion system of Salmonella enterica Typhimurium transports proteins from the cytoplasm to the extracellular environment in a single step and is thus a promising solution for protein secretion in bacteria. Product titer is sensitive to extracellular environmental conditions, however, and T3SS regulation is integrated with essential cellular functions. Instead of attempting to untangle a complex web of regulatory input, we took an “outside-in” approach to elucidate the effect of growth medium components on secretion titer.

Results

We dissected the individual and combined effects of carbon sources, buffers, and salts in a rich nutrient base on secretion titer. Carbon sources alone decreased secretion titer, secretion titer increased with salt concentration, and the combination of a carbon source, buffer, and high salt concentration had a synergistic effect on secretion titer. Transcriptional activity measured by flow cytometry showed that medium composition affected secretion system activity, and prolonged secretion system activation correlated strongly with increased secretion titer. We found that an optimal combination of glycerol, phosphate, and sodium chloride provided at least a fourfold increase in secretion titer for a variety of proteins. Further, the increase in secretion titer provided by the optimized medium was additive with strain enhancements.

Conclusions

We leveraged the sensitivity of the type III secretion system to the extracellular environment to increase heterologous protein secretion titer. Our results suggest that maximizing secretion titer via the type III secretion system is not as simple as maximizing secreted protein expression—one must also optimize secretion system activity. This work advances the type III secretion system as a platform for heterologous protein secretion in bacteria and will form a basis for future engineering efforts.
Pediococcus pentosaceus, a future additive or probiotic candidate
Authors: Jiang Shiman , Cai Lingzhi , Lv Longxian , Li Lanjuan
Published: February 2021

Background

Pediococcus pentosaceus, a promising strain of lactic acid bacteria (LAB), is gradually attracting attention, leading to a rapid increase in experimental research. Due to increased demand for practical applications of microbes, the functional and harmlessP. pentosaceusmight be a worthwhile LAB strain for both the food industry and biological applications.

Results

As an additive,P. pentosaceusimproves the taste and nutrition of food, as well as the storage of animal products. Moreover, the antimicrobial abilities ofPediococcusstrains are being highlighted. Evidence suggests that bacteriocins or bacteriocin-like substances (BLISs) produced byP. pentosaceusplay effective antibacterial roles in the microbial ecosystem. In addition, various strains ofP. pentosaceushave been highlighted for probiotic use due to their anti-inflammation, anticancer, antioxidant, detoxification, and lipid-lowering abilities.

Conclusions

Therefore, it is necessary to continue studyingP. pentosaceusfor further use. Thorough study of severalP. pentosaceusstrains should clarify the benefits and drawbacks in the future.
Long noncoding RNAs as tumorigenic factors and therapeutic targets for renal cell carcinoma
Authors: Shen Haiyan , Luo Guomin , Chen Qingjuan
Published: February 2021

Approximately 338,000 patients are diagnosed with kidney cancer worldwide each year, and renal cell carcinoma (RCC), which is derived from renal epithelium, accounts for more than ninety percent of the malignancy. Next generation RNA sequencing has enabled the identification of novel long noncoding RNAs (lncRNAs) in the past 10 years. Recent studies have provided extensive evidence that lncRNAs bind to chromatin modification proteins, transcription factors, RNA-binding proteins and microRNAs, and thereby modulate gene expression through regulating chromatin status, gene transcription, pre-mRNA splicing, mRNA decay and stability, protein translation and stability. In vitro and in vivo studies have demonstrated that over-expression of oncogenic lncRNAs and silencing of tumor suppressive lncRNAs are a common feature of human RCC, and that aberrant lncRNA expression is a marker for poor patient prognosis, and is essential for the initiation and progression of RCC. Because lncRNAs, compared with mRNAs, are expressed in a tissue-specific manner, aberrantly expressed lncRNAs can be better targeted for the treatment of RCC through screening small molecule compounds which block the interaction between lncRNAs and their binding proteins or microRNAs.
CircMED13L_012 promotes lung adenocarcinoma progression by upregulation of MAPK8 mediated by miR-433-3p
Authors: Chen Wenshu , Zheng Guanying , Huang Jianyuan , Zhu Lihuan , Li Wujin , Guo Tianxing , Huang Yangyun , Pan Xiaojie
Published: February 2021

Background

Metastasis and disease refractoriness remain as major challenges for non-small cell lung cancer (NSCLC) treatment and understanding the underlying molecular mechanisms is of scientific and clinical value. Therefore, in this study, we aimed to explore the effects of circMED13L_012 on the proliferation, migration, invasion and drug-resistance of NSCLC tumor cells.

Methods

In this study, we utilized clinical samples and NSCLC cell lines to explore the association between circMED13L_012 expressions and tumor cell metastasis and chemo resistance. CCK8 and transwell assay were conducted to explore the impact of circMED13_012 on NSCLC tumor proliferation and migrative capabilities. Dual-luciferase reporter gene assay was conducted to validate the circMED13L_012 interaction network.

Results

Our results demonstrated that circMED13L_012 exhibited significantly elevated average level in our clinical samples of NSCLC, compared with normal tissues. circMED13L_012 level was positively correlated with disease stage and metastatic status. Increased circMED13L_012 expression was associated with the enhanced migration, proliferation and chemo resistance of NSCLC cell lines. Further experiments indicated that circMED13L_012 promoted malignant behavior of NSCLC tumor cells by targeting MAPK8 through modulation miR-433-3p expression.

Conclusions

Our study for the first time demonstrated that circMED13L_012–miR-433-3p–MAPK8 axis played important role for NSCLC pathogenesis, which could be potential therapeutic target for the development of future NSCLC treatment.
Vγ9Vδ2 T cells strengthen cisplatin inhibition activity against breast cancer MDA-MB-231 cells by disrupting mitochondrial function and cell ultrastructure
Authors: Huang Xin , Wang Cunchuan , Wang Ningxia
Published: February 2021

Background

Breast cancer ranks second of new cases and fifth of death in 2018 worldwide. Cis-platinum (CDDP) has been used as a chemotherapy to treat breast cancer for years. However, CDDP can adversely disrupt immune function of host. Thus, development of new protocol that can minimize side effect and meanwhile elevate clinical efficacy of CDDP will eventually benefit cancer patients. Since Vγ9Vδ2 T cells can up-regulate immune function of cancer patients, therefore, our hypothesis is that introduction of Vγ9Vδ2 T cells could potentiate CDDP efficacy against breast cancer.

Methods

We used breast cancer cell line MDA-MB-231 as model cell to test our hypothesis. The cancer cell viability in vitro in the context of different dose of CDDP was analyzed by flow cytometry. The cytoskeleton alteration was visualized by confocal microscopy, and the ultrastructure of cell membrane was observed by atomic force microscopy. The mitochondrial function of MDA-MB-231 cells was detected as well by flow cytometry.

Results

Comparing to either Vγ9Vδ2 T cells or CDDP alone, Vγ9Vδ2 T cells plus CDDP could more strikingly induce MDA-MB-231 cell membrane ultrastructure disruption and cytoskeleton disorder, and more significantly enhance the inhibition of CDDP on proliferation of MDA-MB-231 cells. At the same time, Vγ9Vδ2 T cells strengthened CDDP-induced mitochondrial dysfunction of cancer cells.

Conclusion

This work revealed that Vγ9Vδ2 T cells could synergistically enhance the inhibition activity of CDDP against breast cancer cells. Meanwhile, this in vitro proof-of-concept study implied the clinical prospect of the combining application of Vγ9Vδ2 T cells and CDDP in breast cancer therapy.
Influence of cytochrome P450 (CYP) 2C8 polymorphisms on the efficacy and tolerability of artesunate‐amodiaquine treatment of uncomplicated Plasmodium falciparum malaria in Zanzibar
Authors: Pernaute-Lau Leyre , Morris Ulrika , Msellem Mwinyi , Mårtensson Andreas , Björkman Anders , Gil Jose Pedro
Published: February 2021

Background

The anti-malarial drug, amodiaquine, a commonly used, long-acting partner drug in artemisinin-based combination therapy, is metabolized to active desethyl-amodiaquine (DEAQ) by cytochrome P450 2C8 (CYP2C8). The CYP2C8 gene carries several polymorphisms including the more frequent minor alleles, CYP2C8*2 and CYP2C8*3. These minor alleles have been associated with decreased enzymatic activity, slowing the amodiaquine biotransformation towards DEAQ. This study aimed to assess the influence of these CYP2C8 polymorphisms on the efficacy and tolerability of artesunate–amodiaquine (AS–AQ) treatment for uncomplicated Plasmodium falciparum malaria in Zanzibar.

Methods

Dried blood spots on filter paper were collected from 618 children enrolled in two randomized clinical trials comparing AS–AQ and artemether-lumefantrine in 2002–2005 in Zanzibar. Study participant were under five years of age with uncomplicated falciparum malaria. Human CYP2C8*2 and CYP2C8*3 genotype frequencies were determined by PCR-restriction fragment length polymorphism. Statistical associations between CYP2C8*2 and/or CYP2C8*3 allele carriers and treatment outcome or occurrence of adverse events were assessed by Fisher’s exact test.

Results

The allele frequencies of CYP2C8*2 and CYP2C8*3 were 17.5 % (95 % CI 15.4–19.7) and 2.7 % (95 % CI 1.8–3.7), respectively. There was no significant difference in the proportion of subjects carrying either CYP2C8*2 or CYP2C8*3 alleles amongst those with re-infections (44.1 %; 95 % CI 33.8–54.8) or those with recrudescent infections (48.3 %; 95 % CI 29.4–67.5), compared to those with an adequate clinical and parasitological response (36.7 %; 95 % CI 30.0-43.9) (P = 0.25 and P = 0.31, respectively). However, patients carrying either CYP2C8*2 or CYP2C8*3 alleles were significantly associated with an increased occurrence of non-serious adverse events, when compared with CYP2C8 *1/*1 wild type homozygotes (44.9 %; 95 % CI 36.1–54.0 vs. 28.1 %; 95 % CI 21.9–35.0, respectively; P = 0.003).

Conclusions

CYP2C8 genotypes did not influence treatment efficacy directly, but the tolerability to AS–AQ may be reduced in subjects carrying the CYP2C8*2 and CYP2C8*3 alleles. The importance of this non-negligible association with regard to amodiaquine-based malaria chemotherapy warrants further investigation.