bluuebunny/crossref_metadata_2025 huggingface dataset:
Circular RNA hsa_circ_0043278 inhibits breast cancer progression via the miR-455-3p/EI24 signalling pathway
Authors: Shi Yue , Liu Chong
Published: November 2021

Background

Breast cancer (BC) is one of the major malignancies worldwide. Circular ribonucleic acids (circRNAs) are a class of conserved ribonucleic acid (RNA) molecules that play important roles in various diseases. Recently, circRNAs have been suggested to have diagnostic value and may function as potential diagnostic biomarkers for BC. Previously, hsa_circ_0043278 was found to be downregulated in human BC. However, its role in human BC has not yet been identified.

Methods

The levels of hsa_circ_0043278 in BC cell lines were verified by quantitative reverse transcription–polymerase chain reaction (qRT–PCR). The overexpression vector and short hairpin RNA (shRNA) of hsa_circ_0043278 were transfected into MDA-MB-231 and MCF-7 cells, respectively. The effects of hsa_circ_0043278 on tumour cell growth, migration and invasion were measured by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT), colony formation, wound healing and Transwell assays in vitro. A xenograft experiment was conducted to validate the inhibitory effect of hsa_circ_0043278 on tumour growth. The interaction between hsa_circ_0043278 and miR-455-3p was confirmed by a dual-luciferase reporter assay. Mimics and inhibitors of miR-455-3p were designed to confirm the influence of hsa_circ_0043278 on the hsa_circ_0043278/miR-455-3p/etoposide-induced gene 24 (EI24) axis.

Results

Hsa_circ_0043278 was downregulated in BC cell lines. Furthermore, overexpression of hsa_circ_0043278 notably decreased BC cell viability and inhibited BC cell migration and invasion in vitro and suppressed tumour growth in vivo. Downregulation of hsa_circ_0043278 led to the opposite results. Hsa_circ_0043278 expression was negatively correlated with that of miR-455-3p. In addition, mechanistic investigation proved that hsa_circ_0043278 directly bound to miR-455-3p and regulated EI24 and NF-κB expression in BC cells.

Conclusion

Hsa_circ_0043278 acts as a tumour suppressor gene in BC through the hsa_circ_0043278/miR-455-3p/EI24 axis and may be regarded as a new prognostic predictor or potential therapeutic target in BC.
Identification of a novel RPGR mutation associated with X-linked cone-rod dystrophy in a Chinese family
Authors: Wang Yafang , Liu Shu , Zhai Yuanqi , Liu Yang , Wan Xiaoling , Wang Wenqiu , Wang Fenghua , Sun Xiaodong
Published: November 2021

Background

Cone-rod dystrophy (CORD) is a group of inherited retinal dystrophies, characterized by decreased visual acuity, color vision defects, photophobia, and decreased sensitivity in the central visual field. Our study has identified a novel pathogenic variant associated with X-linked cone-rod dystrophy (XLCORD) in a Chinese family.

Methods

All six family members, including the proband, affected siblings, cousins and female carriers, have underwent thorough ophthalmic examinations. The whole exome sequencing was performed for the proband, followed by Sanger sequencing for spilt-sample validation. A mammalian expression vector (AAV-MCS) with mutated retinitis pigmentosa GTPase regulator (RPGR) sequence was expressed in HEK293 T cells. The mutated protein was verified by Western blotting and immunohistochemistry.

Results

A novel mutation in the RPGR gene (c.2383G > T, p.E795X) is identified to be responsible for CORD pathogenesis.

Conclusions

Our findings have expanded the spectrum of CORD-associated mutations in RPGR gene and serve as a basis for genetic diagnosis for X-linked CORD.
Adolescent psychiatric outpatient care rapidly switched to remote visits during the COVID-19 pandemic
Authors: Savilahti Emma M. , Lintula Sakari , Häkkinen Laura , Marttunen Mauri , Granö Niklas
Published: November 2021

Background

The COVID-19-pandemic and especially the physical distancing measures drastically changed the conditions for providing outpatient care in adolescent psychiatry.

Methods

We investigated the outpatient services of adolescent psychiatry in the Helsinki University Hospital (HUH) from 1/1/2015 until 12/31/2020. We retrieved data from the in-house data software on the number of visits in total and categorized as in-person or remote visits, and analysed the data on a weekly basis. We further analysed these variables grouped according to the psychiatric diagnoses coded for visits. Data on the number of patients and on referrals from other health care providers were available on a monthly basis. We investigated the data descriptively and with a time-series analysis comparing the pre-pandemic period to the period of the COVID-19 pandemic.

Results

The total number of visits decreased slightly at the early stage of the COVID-19 pandemic in Spring 2020. Remote visits sharply increased starting in 3/2020 and remained at a high level compared with previous years. In-person visits decreased in Spring 2020, but gradually increased afterwards. The number of patients transiently fell in Spring 2020.

Conclusions

Rapid switch to remote visits in outpatient care of adolescent psychiatry made it possible to avoid a drastic drop in the number of visits despite the physical distancing measures during the COVID-19 pandemic.
Cultural adaptation of mental health first aid guidelines for depression for Sri Lanka: a Delphi expert consensus study
Authors: Fernando Madhawee , Chandrasiri Amila , Dayabandara Madhubhashinee , Reavley Nicola J.
Published: November 2021

Background

Family and friends can play a key role in supporting a person with depression to seek professional help. However, they may lack the knowledge to do so. English-language guidelines for high-income countries have been developed to assist with this. The aim of this study was to adapt the English mental health first aid guidelines for helping a person with depression to the Sri Lankan context.

Methods

A Delphi expert consensus study involving mental health professionals and people with lived experience (either their own or as carers) was conducted. Participants were recruited from inpatient, outpatient and community care settings. The English-language questionnaire was translated into Sinhala and participants were asked to rate the importance of each item for inclusion in the guidelines for Sri Lanka.

Results

Data were collected over two survey rounds. A total of 115 panellists (23% male) consisting of 92 mental health professionals and 23 consumers and carers completed the Round 1 questionnaire. A total of 165 items were included in the final guidelines, with 156 adopted from the guidelines for English-speaking countries and 9 generated from the comments of panellists.

Conclusions

The adapted guidelines were similar to the English-language guidelines. However, new items reflecting culturally relevant approaches to autonomy-granting, communication and culture-specific manifestations of depression were reflected in the adapted version. Further research should explore the use of the adapted guidelines, including their incorporation into Mental Health First Aid Training.
Layering of a health, nutrition and sanitation programme onto microfinance-oriented self-help groups in rural India: results from a process evaluation
Authors: Irani Laili , Schooley Janine , Supriya  , Chaudhuri Indrajit
Published: November 2021

Background

The state of Bihar has been lagging behind Indian national averages on indicators related to maternal and child health, primarily due to lack of knowledge among mothers of young children on lifesaving practices and on where to seek services when healthcare is needed. Hence, the JEEViKA Technical Support Programme was established in 101 blocks to support the state rural livelihood entity, JEEViKA, in order to increase demand for and link rural families to existing health, nutrition and sanitation services. Programme activities were geared to those engaged in JEEViKA’s microfinance-oriented self-help groups. These groups were facilitated by a village-based community mobilizer who was trained on health, nutrition and sanitation-related topics which she later shared in self-help group meetings monthly and during ad hoc home visits. Further, a block-level health, nutrition and sanitation integrator was introduced within JEEViKA to support community mobilizers. Also, indicators were added into the existing monitoring system to routinely capture the layering of health, nutrition and sanitation activities.

Methods

A process evaluation was conducted from August–November 2017 which comprised of conducting 594 quantitative surveys with community mobilizers, from program and non-programme intervention blocks. Linear and logistic regressions were done to capture the association of at least one training that the community mobilizers received on knowledge of the topics learned and related activities they carried out.

Results

Community mobilizers who had received at least one training were more likely to have higher levels of knowledge on the topics they learned and were also more likely to carry out related activities, such as interacting with block-level integrators for guidance and support, routinely collect data on health, nutrition and sanitation indicators and spend time weekly on related activities.

Conclusions

Successful integration of health, nutrition and sanitation programming within a non-health programme such as JEEViKA is possible through trainings provided to dedicated staff in decentralized positions, such as community mobilizers. The findings of this evaluation hold great promise for engaging existing non-health, nutrition and sanitation systems that are serving vulnerable communities to become partners in working towards ensuring stronger health, nutrition and sanitation outcomes for all.
Improving body image at scale among Brazilian adolescents: study protocol for the co-creation and randomised trial evaluation of a chatbot intervention
Authors: Matheson E. L. , Smith H. G. , Amaral A. C. S. , Meireles J. F. F. , Almeida M. C. , Mora G. , Leon C. , Gertner G. , Ferrario N. , Suarez Battan L. , Linardon J. , Fuller-Tyszkiewicz M. , Diedrichs P. C.
Published: November 2021

Background

Body image concerns are prevalent among Brazilian adolescents and can lead to poor psychological and physical health. Yet, there is a scarcity of culturally-appropriate, evidence-based interventions that have been evaluated and made widely available. Chatbot technology (i.e., software that mimics written or spoken human speech) offers an innovative method to increase the scalability of mental health interventions for adolescents. The present protocol outlines the co-creation and evaluation of a body image chatbot for Brazilian adolescents via a partnership between academics, industry organisations and the United Nations Children’s Fund (UNICEF).

Methods

A two-armed fully remote randomised controlled trial will evaluate the chatbot’s effectiveness at improving body image and well-being. Adolescent girls and boys (N = 2800) aged 13–18 years recruited online will be randomly allocated (1:1) into either: 1) a body image chatbot or 2) an assessment-only control condition. Adolescents will engage with the chatbot over a 72-hour period onFacebook Messenger. Primary outcomes will assess the immediate and short-term impact of the chatbot on state- and trait-based body image, respectively. Secondary outcomes will include state- and trait-based affect, trait self-efficacy and treatment adherence.

Discussion

This research is the first to develop an evidence-informed body image chatbot for Brazilian adolescents, with the proposed efficacy trial aiming to provide support for accessible, scalable and cost-effective interventions that address disparities in body image prevalence and readily available resources.

Trial registration number

NCT04825184, registered 30th March 2021.
Change in exposure of children to second-hand smoke with impact on children’s health and change in parental smoking habits after smoking ban in Bavaria – a multiple cross-sectional study
Authors: El Sharkawy Mohammed , Heinze Stefanie , Hendrowarsito Lana , Weinberger Alisa , Huß Jonas , Nennstiel Uta , Herr Caroline , Kutzora Susanne ,   for the GME Study Group, Doerk Wiltrud , Pfister Angelika , Sit-tig Ro S E Earie , Strauch Winfried , Thamm Heidi , Wunder Anita , FrießHesse Tatjana , Lang Franziska , Rudolph Dagmar , Schmid Roland , Winter Gudrun , Bockmann Isabella , Gampenrieder Christine , Motzet Margot , Schneider Elisabeth , Tontsch Traudl , Woelk Gerlinde , Kranebitter Sylvia , Mayrhofer Heidi , Rohrhirsch Gertraud , Weise Brigitte , Wolf Luisa , Baranek Kornelia , Koch-Singer Gitte , Kühnel Maximilian , Baghi Ladan , Bayer Otmar , von Kries Rüdiger , Bolte Gabriele , Fromme Hermann , Heißenhuber Annette , Hendrowarsito Lana , Herr Caroline , Kohlhuber Martina , Kuhn Joseph , Liebl Bernhard , Lüders Anja , Meyer Nicole , Mitschek Christine , Morlock Gabriele , Mosetter Michael , Nennstiel-Ratzel Uta , Twardella Dorothee , Wildner Manfred , Zirngibl Angelika
Published: November 2021

Background

Concerns about smoking displacement from public places to private amenities aroused following smoking ban implementation in Bavaria in 2008. We analysed children’s exposure to second-hand smoke (SHS) before and after the ban, its effect on children’s health and prevalence of active smoking in adults.

Methods

Six cross-sectional surveys (n = 32,443) on pre-school children in Bavaria were analysed, two surveys before the smoking ban in years 2004 and 2005 (S1 and S2) and four after the ban in 2008, 2012, 2014 and 2016 (S4, S6, S7 and S8). Using multivariable logistic regression, we analysed change in children’s intra- and extrauterine SHS exposure and its adverse health effects (Asthma, wheezing, bronchitis and neurodermatitis) as well as change in parental active smoking.

Results

The response rates were 78% for S1, 73% for S2, 61% for S4, 62% for S6, 56% for S7 and 54% for S8. Odds of parents never smoked at home in presence of children increased significantly from before to after the ban with odds ratios (OR) 1.17 (CI95%1.01–1.35), 1.65 (CI95%1.39–1.95), 2.85 (CI95%2.32–3.51), 2.24 (CI95%1.84–2.72) and 3.66 (CI95%2.89–4.63) for S2, S4, S6, S7 and S8, respectively with S1 as reference. Compared to S4, odds of parents who were not actively smoking is significantly higher in S7 (OR = 1.13 (CI95%1.03–1.24)) and S8 (OR = 1.24 (CI95%1.13–1.36)). The odds of mothers who never smoked during pregnancy increased over time with OR = 1.22 (CI95%1.06–1.40) for S2 and 1.57 (CI95%1.33–1.86) for S8 compared to S1. Adverse health effects related to children’s exposure to SHS are significantly less in S8 compared to S1.

Conclusion

After 11 years of smoking ban in Bavaria, smoking displacement to homes was disproved. Exposure of children to SHS intrauterine and at home is decreasing. Number of parents who are not actively smoking is increasing over time. Prevalence of health problems in children related to exposure to SHS is decreasing.
Methodological issues in economic evaluations of disease prevention and health promotion: an overview of systematic and scoping reviews
Authors: Seleznova Yana , Alayli Adrienne , Stock Stephanie , Müller Dirk
Published: November 2021

Background

We aimed to provide a comprehensive overview of methodological challenges in economic evaluations of disease prevention and health promotion (DPHP)-measures.

Methods

We conducted an overview of reviews searching MEDLINE, EMBASE, NHS Economic Evaluation Database, Database of Promoting Health Effectiveness Reviews, Cochrane Database of Systematic Reviews (CDSR) and Database of Promoting Health Effectiveness Reviews (DOPHER) (from their inception to October 2021). We included both systematic and scoping reviews of economic evaluations in DPHP addressing following methodological aspects: (i) attribution of effects, (ii) outcomes, (iii) inter-sectoral (accruing to non-health sectors of society) costs and consequences and (iv) equity. Data were extracted according to the associated sub-criteria of the four methodological aspects including study design economic evaluation (e.g. model-based), type/scope of the outcomes (e.g. outcomes beyond health), perspective, cost categories related to non-health sectors of society, and consideration of equity (method of inclusion). Two reviewers independently screened all citations, full-text articles, and extracted data. A narrative synthesis without a meta-analysis or other statistical synthesis methods was conducted.

Results

The reviewing process resulted in ten systematic and one scoping review summarizing 494 health economic evaluations. A lifelong time horizon was adopted in about 23% of DPHP evaluations, while 64% of trial-based evaluations had a time horizon up to 2 years. Preference-based outcomes (36%) and non-health outcomes (8%) were only applied in a minority of studies. Although the inclusion of inter-sectoral costs (i.e. costs accruing to non-health sectors of society) has increased in recent years, these were often neglected (between 6 and 23% depending on the cost category). Consideration to equity was barely given in economic evaluations, and only addressed in six of the eleven reviews.

Conclusions

Economic evaluations of DPHP measures give only little attention to the specific methodological challenges related to this area. For future economic DPHP evaluations a tool with structured guidance should be developed.

This overview of reviews was not registered and a published protocol does not exist.
Trends in socioeconomic inequalities in smoking in Turkey from 2008 to 2016
Authors: Hassoy Hur , Ergin Isil , Yararbas Gorkem
Published: November 2021

Background

Smoking inequalities in Turkey were previously demonstrated in an early stage of the smoking epidemic model. This paper aimed to assess the trends for socioeconomic inequalities in smoking in Turkey over the years in the context of the smoking epidemic model using data from the Global Adult Tobacco Survey (GATS) Turkey 2008–2012-2016.

Methods

Cross-sectional data were analyzed to calculate the association of smoking with, wealth, education, occupation and place of residence using age-standardized prevalence rates, odds ratios, relative index of inequality (RII) and slope index of inequality (SII). The analysis was performed separately for age groups (younger: 20–39 years/older: 40 and above years) and sex.

Results

Younger women with higher wealth and older women with higher wealth and education smoked more. For both age groups, smoking was increased for working class and urban women. Relative wealth inequalities in smoking narrowed and then showed a reversal for younger women (RII2008 = 3.37; 95% CI:1.64–3.40; RII2012 = 2.19; 95% CI:1.48–3.24; RII2016 = 0.80; 95% CI:0.58–1.10, p-for trend < 0.0001). Relative educational inequalities in smoking for older women also showed a narrowing (RII2008 = 21.45; 95% CI:11.74–39.19; RII2012 = 15.25; 95% CI:9.10–25.55; and RII2016 = 5.48; 95% CI:3.86–7.78, p-for trend < 0.0001). For older women, a similar narrowing was observed for wealth (RII2008 = 3.94; 95% CI:2.38–6.53; RII2012 = 2.79; 95% CI:1.80–4.32; and RII2016 = 1.34; 95% CI:0.94–1.91, p-for trend = 0.0001). The only significant trend for absolute inequalities was for younger women by wealth. This trend showed a narrowing and then a reversal (SII2008 = 0.14; 95% CI:0.09–1.20; SII2012 = 0.12; 95% CI:0.06–0.18; and SII2016 = -0.05; 95% CI:-0.12–0.02, p-for trend = 0.0001). Unlike women, smoking in men showed inverse associations for wealth and education, although not statistically confirmed for all years. Smoking was increased in working classes and unemployed men in 2012 and 2016. Inequalities did not show a trend in relative and absolute terms for men.

Conclusions

For smoking inequalities in Turkey, a transition to the next stage was observed, although the previously defined Southern European pattern also existed. Low socioeconomic women deserve special attention as well as stressors at work and drivers of smoking at urban settings.
Association of early-life undernutrition and risk of dyslipidemia in adulthood: a population-based cohort study
Authors: Wang Minmin , Liu Mengfei , Guo Chuanhai , Li Fenglei , Liu Zhen , Pan Yaqi , Liu Fangfang , Liu Ying , Bao Huanyu , Hu Zhe , Cai Hong , He Zhonghu , Ke Yang
Published: November 2021

Background

The association of early-life undernutrition and dyslipidemia found in previous studies may be confounded by the uncontrolled age difference between exposed and unexposed participants. The study aimed to investigate the association of early-life undernutrition and the risk of dyslipidemia in adulthood with good control of the age variable.

Methods

We took the Great Chinese Famine (1959–1961) as a natural experiment of severe undernutrition. This study was based on the baseline investigation of a population-based cohort in rural China. Undernutrition in early life was defined as being exposed to famine at younger than 3 years of age. Three approaches including Adjustment, Restriction, and Matching were applied to control the confounding effect of age. Logistic regression models were applied to evaluate the association between early-life famine and the presence of dyslipidemia. Stratified analysis by gender was also performed, and potential effect modification was tested by adding the interaction term of the famine exposure variable and gender into the model.

Results

Undernutrition in early life was associated with increased risk of borderline high and above (BHA) levels of total cholesterol (TC, ORAdjustment = 1.61; ORRestriction = 1.56; ORMatching = 1.87), triglycerides (TG, ORAdjustment = 1.33; ORRestriction = 1.30; ORMatching = 1.34), low-density lipoprotein cholesterol (LDL-C, ORAdjustment = 1.75; ORRestriction = 1.53; ORMatching = 1.77) and dyslipidemia (ORAdjustment = 1.52; ORRestriction = 1.45; ORMatching = 1.60), as well as high levels of TC, TG, LDL-C and dyslipidemia. An inverse association of undernutrition and risk of low high-density lipoprotein cholesterol (HDL-C) was found. Female participants with undernutrition experience had an increased risk of BHA TG and LDL-C (TG: ORAdjustment, female = 1.45; ORRestriction, female = 1.39; ORMatching, female = 1.51; LDL-C: ORAdjustment, female = 2.11; ORRestriction, female = 1.80; ORMatching, female = 2.15), but this association was not found in males.

Conclusion

Early-life undernutrition increased the risk of TC, TG, LDL-C, and dyslipidemia. Gender would significantly modify this effect for TG and LDL-C. These results emphasize the importance of nutritional conditions in the early stages of life to long-term health consequences.
Impact of COVID-19 on dental education- a scoping review
Authors: Farrokhi Farid , Mohebbi Simin Zahra , Farrokhi Farzaneh , Khami Mohammad Reza
Published: November 2021

Background

A new corona virus called COVID-19 and its epidemic has affected health care systems in many ways. There have also been significant changes in dental education. The present study summarizes the findings about dental education resulting from a scoping review of COVID-19 and dentistry.

Methods

First, a comprehensive search of five databases (Google Scholar, Medline through PubMed, Embase, Scopus, and Cochrane Central) was conducted with the keywords: COVID-19 and its equivalent terms, dentistry, education, oral, students, curriculum, and academics. Articles related to oral health and COVID-19 were searched. Then articles on the subject of dental education were screened and reviewed.

Results

Of the 1389 articles investigating COVID-19 and dentistry, 135 articles were related to dental education and its relationship with COVID-19. The most articles in this field were from the United States, India, and Saudi Arabia. Most of the articles were cross-sectional and then review articles. Based on the review the articles were divided into two main categories of changes and concerns, and opportunities and solutions. Moreover, the following themes were extracted: teaching-learning quality and methods, study career and how students are prepared, infection control policies, theses, exams and assessments, financial and economic security, students and staff’s mental health, school’s policies and curricula, knowledge of students and staff about COVID-19.

Conclusions

Dental education now faces big challenges, some of which have never been experienced before. On the other hand, the epidemic has created opportunities for dental education as well. Most of these challenges and opportunities are the same around the world, and the findings of the present study can be a good help to overcome the challenges ahead as well as a good reference to find the right questions to be answered in future studies.
Overbooking for physical examination considering late cancellation and set-resource relationship
Authors: Ho Te-Wei , Kung Ling-Chieh , Huang Hsin-Ya , Lai Jui-Fen , Chiu Han-Mo
Published: November 2021

Background

Late cancellations of physical examination has severe impact on the operations of a physical examination center since it is often too late to fill vacancy. A booking control policy that considers overbooking is then one natural solution. Unlike appointment scheduling problems for clinics and hospitals, in which treating a patient mostly requires only one type of resource, a physical examination set typically requires multiple types of resources. Traditional methods that do not consider set-resource relationship thus may be inapplicable.

Methods

We formulate a stochastic mathematical programming model that maximizes the expected net reward, which is the examination revenue minus overage cost. A complete search algorithm and a greedy search algorithm are designed to search for optimal booking limits for all examination sets. To estimate the late cancellation probability for each individual consumer, we apply logistic regression to identify significant factors affecting the probability. After clustering is used to estimate individual probabilities, Monte Carlo simulation is conducted to generate probability distributions for the number of consumers without late cancellations. A discrete-event simulation is performance to evaluate the effectiveness of our proposed solution.

Results

We collaborate with a leading physical examination center to collect real data to evaluate our proposed overbooking policies. We show that the proposed overbooking policy may significantly increase the expected net reward. Our simulation results also help us understand the impact of overbooking on the expected number of customers and expected overage. A sensitivity analysis is conducted to demonstrate that the benefit of overbooking is insensitive to the accuracy of cost estimation. A Pareto efficiency analysis gives practitioners suggestions regarding policy determination considering multiple performance indications.

Conclusions

Our proposed overbooking policies may greatly enhance the overall performance of a physical examination center.
A cost utility analysis alongside a cluster-randomised trial evaluating a minor ailment service compared to usual care in community pharmacy
Authors: Amador-Fernández Noelia , Benrimoj Shalom I. , García-Mochón Leticia , García-Cárdenas Victoria , Dineen-Griffin Sarah , Gastelurrutia Miguel Ángel , Gómez-Martínez Jesús Carlos , Colomer-Molina Vicente , Martínez-Martínez Fernando
Published: November 2021

Background

Minor ailments are “self-limiting conditions which may be diagnosed and managed without a medical intervention”. A cluster randomised controlled trial (cRCT) was designed to evaluate the clinical, humanistic and economic outcomes of a Minor Ailment Service (MAS) in community pharmacy (CP) compared with usual care (UC).

Methods

The cRCT was conducted for 6 months from December 2017. The pharmacist-patient intervention consisted of a standardised face-to-face consultation on a web-based program using co-developed protocols, pharmacists’ training, practice change facilitators and patients’ educational material. Patients requesting a non-prescription medication (direct product request) or presenting minor ailments received MAS or UC and were followed-up by telephone 10-days after the consultation.

The primary economic outcomes were incremental cost-utility ratio (ICUR) of the service and health related quality of life (HRQoL). Total costs included health system, CPs and patient direct costs: health professionals’ consultation time, medication costs, pharmacists’ training costs, investment of the pharmacy and consultation costs within the 10 days following the initial consultation. The HRQoL was obtained using the EuroQoL 5D-5L at the time of the consultation and at 10-days follow up. A sensitivity analysis was carried out using bootstrapping. There were two sub-group analyses undertaken, for symptom presentation and direct product requests, to evaluate possible differences.

Results

A total of 808 patients (323 MAS and 485 UC) were recruited in 27 CPs with 42 pharmacists (20 MAS and 22 UC). 64.7% (n = 523) of patients responded to follow-up after their consultation in CP. MAS patients gained an additional 0.0003 QALYs (p = 0.053). When considering only MAS patients presenting with symptoms, the ICUR was 24,733€/QALY with a 47.4% probability of cost-effectiveness (willingness to pay of 25,000€/QALY). Although when considering patients presenting for a direct product request, MAS was the dominant strategy with a 93.69% probability of cost-effectiveness.

Conclusions

Expanding community pharmacists’ scope through MAS may benefit health systems. To be fully cost effective, MAS should not only include consultations arising from symptom presentation but also include an oversight of self-selected products by patients. MAS increase patient safety through the appropriate use of non-prescription medication and through the direct referral of patients to GP.

Trial registration

ISRCTN, ISRCTN17235323. Registered 07/05/2021 - Retrospectively registered
Telomerase subunit Est2 marks internal sites that are prone to accumulate DNA damage
Authors: Pandey Satyaprakash , Hajikazemi Mona , Zacheja Theresa , Schalbetter Stephanie , Neale Matthew J. , Baxter Jonathan , Guryev Victor , Hofmann Andreas , Heermann Dieter W. , Juranek Stefan A. , Paeschke Katrin
Published: November 2021

Background

The main function of telomerase is at the telomeres but under adverse conditions telomerase can bind to internal regions causing deleterious effects as observed in cancer cells.

Results

By mapping the global occupancy of the catalytic subunit of telomerase (Est2) in the budding yeast Saccharomyces cerevisiae, we reveal that it binds to multiple guanine-rich genomic loci, which we termed “non-telomeric binding sites” (NTBS). We characterize Est2 binding to NTBS. Contrary to telomeres, Est2 binds to NTBS in G1 and G2 phase independently of Est1 and Est3. The absence of Est1 and Est3 renders telomerase inactive at NTBS. However, upon global DNA damage, Est1 and Est3 join Est2 at NTBS and telomere addition can be observed indicating that Est2 occupancy marks NTBS regions as particular risks for genome stability.

Conclusions

Our results provide a novel model of telomerase regulation in the cell cycle using internal regions as “parking spots” of Est2 but marking them as hotspots for telomere addition.
Influence of number of ingredients, use of supplement and vegetarian or vegan preparation on the composition of homemade diets for dogs and cats
Authors: Pedrinelli Vivian , Zafalon Rafael Vessecchi Amorim , Rodrigues Roberta Bueno Ayres , Perini Mariana Pamplona , Conti Renata Maria Consentino , de Carvalho Balieiro Júlio Cesar , Brunetto Márcio Antonio
Published: November 2021

Background

Homemade diets are a worldwide trend, and many recipes are currently available on websites but may not be considered balanced. This study aimed to evaluate if the number of ingredients, supplement, or vegetarian/vegan-only ingredients included in a recipe influence the nutrient content of homemade diets for dogs and cats. Chemical analyses were performed on 75 diets for dogs and 25 for cats prepared according to websites’ recipes, and minerals were analyzed by inductively coupled plasma optical emission spectrometry (ICP-OES).

Results

Canine diets that met fat requirements had more ingredients than those below recommendations. None of the cat diets met iron requirements, and feline diets that met requirements of manganese had fewer ingredients and those that supplied requirements of protein and sodium had more ingredients than the diets below recommendations (p < 0.05). Non-supplemented canine and feline diets had calcium and calcium:phosphorus ratio below recommendations (p < 0.05). Non-supplemented feline diets had lower sodium and iron, and zinc levels were below recommendation in diets for both species. Diets with animal products for dogs had higher levels of protein and zinc, although zinc was deficient in both groups, and there were higher amounts of crude fiber, magnesium, and manganese in vegetarian/vegan diets (p < 0.05). Diets with animal products for cats had higher levels of protein (p = 0.003), but there was a higher amount of crude fiber (p = 0.014) in vegetarian/vegan diets.

Conclusion

The number of ingredients and vegetarian/vegan preparation did not guarantee nutritional adequacy of diets, and the presence of supplement did not ensure a balanced diet.
Association of single nucleotide polymorphisms with insulin secretion, insulin sensitivity, and diabetes in women with a history of gestational diabetes mellitus
Authors: Prasad Rashmi B. , Kristensen Karl , Katsarou Anastasia , Shaat Nael
Published: November 2021

Background

This study investigated whether single nucleotide polymorphisms (SNPs) reported by previous genome-wide association studies (GWAS) to be associated with impaired insulin secretion, insulin resistance, and/or type 2 diabetes are associated with disposition index, the homeostasis model assessment of insulin resistance (HOMA-IR), and/or development of diabetes following a pregnancy complicated by gestational diabetes mellitus (GDM).

Methods

Seventy-two SNPs were genotyped in 374 women with previous GDM from Southern Sweden. An oral glucose tolerance test was performed 1–2 years postpartum, although data on the diagnosis of diabetes were accessible up to 5 years postpartum. HOMA-IR and disposition index were used to measure insulin resistance and secretion, respectively.

Results

The risk A-allele in the rs11708067 polymorphism of the adenylate cyclase 5 gene (ADCY5) was associated with decreased disposition index (beta = − 0.90, SE 0.38,p = 0.019). This polymorphism was an expression quantitative trait loci (eQTL) in islets for bothADCY5and its antisense transcript. The risk C-allele in the rs2943641 polymorphism, near the insulin receptor substrate 1 gene (IRS1), showed a trend towards association with increased HOMA-IR (beta = 0.36, SE 0.18,p = 0.050), and the T-allele of the rs4607103 polymorphism, near the ADAM metallopeptidase with thrombospondin type 1 motif 9 gene (ADAMTS9), was associated with postpartum diabetes (OR = 2.12, SE 0.22,p = 0.00055). The genetic risk score (GRS) of the top four SNPs tested for association with the disposition index using equal weights was associated with the disposition index (beta = − 0.31, SE = 0.29,p = 0.00096). In addition, the GRS of the four SNPs studied for association with HOMA-IR using equal weights showed an association with HOMA-IR (beta = 1.13, SE = 0.48,p = 9.72874e−11). All analyses were adjusted for age, body mass index, and ethnicity.

Conclusions

This study demonstrated the genetic susceptibility of women with a history of GDM to impaired insulin secretion and sensitivity and, ultimately, to diabetes development.
Impact of COVID-19 and lockdowns on pulmonary embolism in hospitalized patients in France: a nationwide study
Authors: Tankere Pierre , Cottenet Jonathan , Tubert-Bitter Pascale , Mariet Anne-Sophie , Beltramo Guillaume , Cadranel Jacques , Piroth Lionel , Bonniaud Philippe , Quantin Catherine
Published: November 2021

Background

This study assessed the impact of the COVID-19 epidemic on overall hospitalizations for pulmonary embolism (PE) in France in comparison with previous years, and by COVID-19 and non-COVID-19 status.

Methods

Hospitalization data (2017–2020) were extracted from the French National Discharge database (all public and private hospitals).

We included all patients older than 18 years hospitalized during the 3 years and extracted PE status and COVID-19 status (from March 2020). Age, sex and risk factors for PE (such as obesity, cancer) were identified. We also extracted transfer to an intensive care unit (ICU) and hospital death. The number of PE and the frequency of death in patients in 2019 and 2020 were described by month and by COVID-19 status. Logistic regressions were performed to identify the role of COVID-19 among other risk factors for PE in hospitalized patients.

Results

The overall number of patients hospitalized with PE increased by about 16% in 2020 compared with 2019, and mortality also increased to 10.3% (+ 1.2%). These increases were mostly linked to COVID-19 waves, which were associated with PE hospitalization in COVID-19 patients (PE frequency was 3.7%; 2.8% in non-ICU and 8.8% in ICU). The final PE odds ratio for COVID-19 hospitalized patients was 4 compared with other hospitalized patients in 2020.

The analyses of PE in non-COVID-19 patients showed a 2.7% increase in 2020 compared with the previous three years.

Conclusion

In 2020, the overall number of patients hospitalized with PE in France increased compared to the previous three years despite a considerable decrease in scheduled hospitalizations. Nevertheless, proactive public policy focused on the prevention of PE in all patients should be encouraged.
Construction of circRNA-miRNA-mRNA network and identification of novel potential biomarkers for non-small cell lung cancer
Authors: Yang Jia , Hao Ran , Zhang Yunlong , Deng Haibin , Teng Wenjing , Wang Zhongqi
Published: November 2021

Background

The underlying circular RNAs (circRNAs)-related competitive endogenous RNA (ceRNA) mechanisms of pathogenesis and prognosis in non-small cell lung cancer (NSCLC) remain unclear.

Methods

Differentially expressed circRNAs (DECs) in two Gene Expression Omnibus datasets (GSE101684 and GSE112214) were identified by utilizing R package (Limma). Circinteractome and StarBase databases were used to predict circRNA associated-miRNAs and mRNAs, respectively. Then, protein–protein interaction (PPI) network of hub genes and ceRNA network were constructed by STRING and Cytoscape. Also, analyses of functional enrichment, genomic mutation and diagnostic ROC were performed. TIMER database was used to analyze the association between immune infiltration and target genes. Kaplan–Meier analysis, cox regression and the nomogram prediction model were used to evaluate the prognostic value of target genes. Finally, the expression of potential circRNAs and target genes was validated in cell lines and tissues by quantitative real-time PCR (qRT-PCR) and Human Protein Atlas (HPA) database.

Results

In this study, 15 DECs were identified between NSCLC tissues and adjacent-normal tissues in two GEO datasets. Following the qRT-PCR corroboration, 7 DECs (hsa_circ_0002017, hsa_circ_0069244, hsa_circ_026337, hsa_circ_0002346, hsa_circ_0007386, hsa_circ_0008234, hsa_circ_0006857) were dramatically downregulated in A549 and SK-MES-1 compared with HFL-1 cells. Then, 12 circRNA-sponged miRNAs were screened by Circinteractome and StarBase, especially, hsa-miR-767-3p and hsa-miR-767-5p were significantly up-regulated and relevant to the prognosis. Utilizing the miRDB and Cytoscape, 12 miRNA-target genes were found. Functional enrichment, genomic mutation and diagnostic analyses were also performed. Among them, FNBP1, AKT3, HERC1, COL4A1, TOLLIP, ARRB1, FZD4 and PIK3R1 were related to the immune infiltration via TIMER database. The expression of ARRB1, FNBP1, FZD4, and HERC1 was correlated with poor overall survival (OS) in NSCLC patients by cox regression and nomogram. Furthermore, the hub-mRNAs were validated in cell lines and tissues.

Conclusion

We constructed the circRNA-miRNA-mRNA network that might provide novel insights into the pathogenesis of NSCLC and reveal promising immune infiltration and prognostic biomarkers.
Remodeling of the tumor microenvironment via disrupting Blimp1+ effector Treg activity augments response to anti-PD-1 blockade
Authors: Dixon Michael L. , Luo Lin , Ghosh Sadashib , Grimes Jeffrey M. , Leavenworth Jonathan D. , Leavenworth Jianmei W.
Published: November 2021

Background

Accumulation of Foxp3+ regulatory T (Treg) cells in the tumor often represents an important mechanism for cancer immune evasion and a critical barrier to anti-tumor immunity and immunotherapy. Many tumor-infiltrating Treg cells display an activated phenotype and express the transcription factor Blimp1. However, the specific impact of these Blimp1+ Treg cells and their follicular regulatory T (TFR) cell subset on tumor and the underlying mechanisms of action are not yet well-explored.

Methods

Various transplantable tumor models were established in immunocompetent wild-type mice and mice with a Foxp3-specific ablation of Blimp1. Tumor specimens from patients with metastatic melanoma and TCGA datasets were analyzed to support the potential role of Treg and TFR cells in tumor immunity. In vitro culture assays and in vivo adoptive transfer assays were used to understand how Treg, TFR cells and antibody responses influence tumor control. RNA sequencing and NanoString analysis were performed to reveal the transcriptome of tumor-infiltrating Treg cells and tumor cells, respectively. Finally, the therapeutic effects of anti-PD-1 treatment combined with the disruption of Blimp1+ Treg activity were evaluated.

Results

Blimp1+ Treg and TFR cells were enriched in the tumors, and higher tumoral TFR signatures indicated increased risk of melanoma metastasis. Deletion of Blimp1 in Treg cells resulted in impaired suppressive activity and a reprogramming into effector T-cells, which were largely restricted to the tumor-infiltrating Treg population. This destabilization combined with increased anti-tumor effector cellular responses, follicular helper T-cell expansion, enhanced tumoral IgE deposition and activation of macrophages secondary to dysregulated TFR cells, remodeled the tumor microenvironment and delayed tumor growth. The increased tumor immunogenicity with MHC upregulation improved response to anti-PD-1 blockade. Mechanistically, Blimp1 enforced intratumoral Treg cells with a unique transcriptional program dependent on Eomesodermin (Eomes) expression; deletion of Eomes in Blimp1-deficient Treg cells restored tumor growth and attenuated anti-tumor immunity.

Conclusions

These findings revealed Blimp1 as a new critical regulator of tumor-infiltrating Treg cells and a potential target for modulating Treg activity to treat cancer. Our study has also revealed two FCERIA-containing immune signatures as promising diagnostic or prognostic markers for melanoma patients.
Levels of pretreatment blood lipids are prognostic factors in advanced NSCLC patients treated with anlotinib
Authors: Tang Mengqiu , Song Chao , Zhang Yaowen , Xu Xiaoyu , Wang Chen , Zhang Zhanchun , Chen Tian
Published: November 2021

Background

Anlotinib, a small molecule for multi-target tyrosine kinase inhibition, is the third or further line of defense for treatment of non-small cell lung cancer (NSCLC). Findings from an ALTER0303 phase III trial revealed that this drug confers significant survival benefits in patients. Although numerous inflammatory biomarkers have been shown to play vital roles in treatment, the clinical significance of blood lipid levels before treatment has not been evaluated. Here, this research aims to explore the relationship between blood lipids and efficacy of anlotinib, with a view of generating insights to guide future development of convenient and individualized treatment therapies.

Methods

This study analyzed basal blood lipids levels, including triglycerides (TG), total cholesterol (TC), low density lipoprotein (LDL), and high density lipoprotein (HDL), among other variables before treatment, in 137 patients with advanced NSCLC who received anlotinib as third or further-line treatment at the Ningbo Medical Center Lihuili Hospital, between July 2018 and December 2020. We determined the best cut off value for predicting treatment responses, generated survival curves using the Kaplan–Meier method, then applied univariate and multivariate Cox regression analyses to assess predictors of survival.

Results

The entire study population recorded median progression-free survival (PFS) and overall survival (OS) of 4 (95% CI 3.142–4.858) and 8.3 (95% CI 6.843–9.757) months, respectively. Researchers observed statistically significant differences across subgroups, between blood lipid indexes with different efficacies, except in the HDL subgroup. The low disease control rate (DCR) was associated with significantly elevated TG, TC and LDL levels (P = 0.000). Multivariate analysis demonstrated that elevated TC and LDL levels were independently associated with poor PFS or OS (P ≤ 0.003). Then, we established a prediction model, and set high TC or high LDL as the risk factor, respectively. There were significant differences in PFS (p = 0.000) and OS (p = 0.012) between 0 and ≥ 1 scores.

Conclusions

Prior to anlotinib therapy, TC and LDL levels, are independent prognostic indicators for patients with advanced NSCLC treated with this drug as a third or further-line treatment option. In addition, a risk score of 0 was attributed to a combination of low TC and low LDL, and these patients were exhibited excellent efficacies and survival rates.
Hybrid membrane-coated nanosuspensions for multi-modal anti-glioma therapy via drug and antigen delivery
Authors: Hao Wenyan , Cui Yuexin , Fan Yueyue , Chen Mengyu , Yang Guobao , Wang Yuli , Yang Meiyan , Li Zhiping , Gong Wei , Yang Yang , Gao Chunsheng
Published: November 2021

Background

Glioma is one of the deadliest human cancers. Although many therapeutic strategies for glioma have been explored, these strategies are seldom used in the clinic. The challenges facing the treatment of glioma not only involve the development of chemotherapeutic drugs and immunotherapeutic agents, but also the lack of a powerful platform that could deliver these two moieties to the targeted sites. Herein, we developed chemoimmunotherapy delivery vehicles based on C6 cell membranes and DC membranes to create hybrid membrane-coated DTX nanosuspensions (DNS-[C6&DC]m).

Results

Results demonstrated successful hybrid membrane fusion and nanosuspension functionalization, and DNS-[C6&DC]m could be used for different modes of anti-glioma therapy. For drug delivery, membrane coating could be applied to target the source cancer cells via a homotypic-targeting mechanism of the C6 cell membrane. For cancer immunotherapy, biomimetic nanosuspension enabled an immune response based on the professional antigen-presenting characteristic of the dendritic cell membrane (DCm), which carry the full array of cancer cell membrane antigens and facilitate the uptake of membrane-bound tumor antigens for efficient presentation and downstream immune n.

Conclusion

DNS-[C6&DC]m is a multifunctional biomimetic nano-drug delivery system with the potential to treat gliomas through tumor-targeted drug delivery combined with immunotherapy, thereby presenting a promising approach that may be utilized for multiple modes of cancer therapy.

Graphical Abstract