bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stigma as a barrier to early intervention among youth seeking mental health services in Ontario, Canada: a qualitative study
Authors: Sheikhan Natasha Y. , Henderson Jo L. , Halsall Tanya , Daley Mardi , Brownell Samantha , Shah Jai , Iyer Srividya N. , Hawke Lisa D. 
Published: January 2023

Abstract
Background
Stigma associated with mental health challenges is a major barrier to service seeking among youth. Understanding how stigma impacts service-seeking decisions from the perspectives of youth remains underexplored. Such research is necessary to inform effective stigma reduction.

Objective
This study aims to understand how stigma influences service seeking among youth with mental health challenges.

Methods
Qualitative inquiry was taken using youth engagement, underpinned by pragmatism. Data were collected via 4 virtual focus groups with 22 purposively selected youth participants with lived experience of mental health challenges in Ontario, Canada. Focus group guides were developed collaboratively among research team members, including youth co-researchers. Data were analyzed inductively using reflexive thematic analysis.

Results
Three main themes were constructed from the data: point of entry into the system, being biomedicalized or trivialized, and paving the way for non-stigmatizing services. Initial contact with the mental healthcare system was seen to be affected by stigma, causing participants to delay contact or be refused services if they do not fit with an expected profile. Participants described a constant negotiation between feeling ‘sick enough’ and ‘not sick enough’ to receive services. Once participants accessed services, they perceived the biomedicalization or trivialization of their challenges to be driven by stigma. Lastly, participants reflected on changes needed to reduce stigma’s effects on seeking and obtaining services.

Conclusion
A constant negotiation between being ‘sick enough’ or ‘not sick enough’ is a key component of stigma from the perspectives of youth. This tension influences youth decisions about whether to seek services, but also service provider decisions about whether to offer services. Building awareness around the invisibility of mental health challenges and the continuum of wellness to illness may help to break down stigma’s impact as a barrier to service seeking. Early intervention models of care that propose services across the spectrum of challenges may prevent the sense of stigma that deters youth from accessing and continuing to access services.
UK government’s new placement legislation is a ‘good first step’: a rapid qualitative analysis of consumer, business, enforcement and health stakeholder perspectives
Authors: Muir Sarah , Dhuria Preeti , Roe Emma , Lawrence Wendy , Baird Janis , Vogel Christina 
Published: January 2023

AbstractBackgroundThe current food system in England promotes a population diet that is high in fat, sugar and salt (HFSS). To address this, the UK government has implemented legislation to restrict the promotion of HFSS products in prominent locations (e.g. store entrances, checkouts) in qualifying retailers since October 2022. This study investigated the perceived impact of the legislation for affected stakeholders.MethodsA pre-implementation rapid qualitative evaluation of stakeholder interviews. One hundred eight UK stakeholders participated in the study including 34 consumers, 24 manufacturers and retailers, 22 local authority enforcement officers and 28 academic and charitable health representatives. A participatory conference was used to enable policy recommendations to be confirmed by stakeholders.ResultsStakeholders perceived the legislation to be a ‘good first step’ towards improving population diet but recognised this needed to be considered amongst a range of long-term obesity policies. Areas of further support were identified and these are presented as six recommendations for government to support the successful implementation of the legislation: (1) provide a free central HFSS calculator, (2) refine legislation to enhance intent and clarity, (3) conduct a robust evaluation to assess intended and unintended outcomes, (4) provide greater support for smaller businesses, (5) provide ring-fenced resources to local authorities and (6) create and communicate a long-term roadmap for food and health.ConclusionsThis legislation has the potential to reduce impulse HFSS purchases and makes a solid start towards creating healthier retail outlets for consumers. Immediate government actions to create a freely accessible HFSS calculator, support smaller businesses and provide additional resources to local authorities would support successful implementation and enforcement. Independent evaluation of the implementation of the legislation will enable monitoring of potential unintended consequences identified in this study and support refinement of the legislation. A long-term roadmap is necessary to outline strategies to support equal access to healthier and sustainable food across the whole food system within the next 20–30 years.
Simultaneous enzyme production, Levan-type FOS synthesis and sugar by-products elimination using a recombinant Pichia pastoris strain expressing a levansucrase-endolevanase fusion enzyme
Authors: Ávila-Fernández Ángela , Montiel Silvia , Rodríguez-Alegría María Elena , Caspeta Luis , López Munguía Agustín 
Published: January 2023

Abstract
Background
Although Levan-type fructooligosaccharides (L-FOS) have been shown to exhibit prebiotic properties, no efficient methods for their large-scale production have been proposed. One alternative relies on the simultaneous levan synthesis from sucrose, followed by endolevanase hydrolysis. For this purpose, several options have been described, particularly through the synthesis of the corresponding enzymes in recombinant Escherichia coli. Major drawbacks still consist in the requirement of GRAS microorganisms for enzyme production, but mainly, the elimination of glucose and fructose, the reaction by-products.

Results
The expression of a fusion enzyme between Bacillus licheniformis endolevanase (LevB1) and B. subtilis levansucrase (SacB) in Pichia pastoris cultures, coupled with the simultaneous synthesis of L-FOS from sucrose and the elimination of the residual monosaccharides, in a single one-pot process was developed. The proof of concept at 250 mL flask-level, resulted in 8.62 g of monosaccharide-free L-FOS and 12.83 gDCW of biomass, after 3 successive sucrose additions (30 g in total), that is a 28.7% yield (w L-FOS/w sucrose) over a period of 288 h.
At a 1.5 L bioreactor-level, growth considerably increased and, after 59 h and two sucrose additions, 72.9 g of monosaccharide-free L-FOS and 22.77 gDCW of biomass were obtained from a total of 160 g of sucrose fed, corresponding to a 45.5% yield (w L-FOS/w sucrose), 1.6 higher than the flask system. The L-FOS obtained at flask-level had a DP lower than 20 fructose units, while at bioreactor-level smaller oligosaccharides were obtained, with a DP lower than 10, as a consequence of the lower endolevanase activity in the flask-level.

Conclusion
We demonstrate here in a novel system, that P. pastoris cultures can simultaneously be used as comprehensive system to produce the enzyme and the enzymatic L-FOS synthesis with growth sustained by sucrose by-products. This system may be now the center of an optimization strategy for an efficient production of glucose and fructose free L-FOS, to make them available for their application as prebiotics. Besides, P. pastoris biomass also constitutes an interesting source of unicellular protein.
Factors associated with the ownership and use of insecticide-treated nets in Guinea: an analysis of the 2018 Demographic and Health Survey
Authors: Diallo Ousmane Oumou , Ozodiegwu Ifeoma D. , Camara Alioune , Galatas Beatriz , Gerardin Jaline 
Published: January 2023

Abstract
Background
Malaria is a leading cause of outpatient visits and deaths among children in Guinea. Despite several mass distribution campaigns of insecticide-treated nets (ITNs) in Guinea, ITN ownership and use remain low. Identifying the underlying factors affecting household ITN ownership and ITN usage among those with access will allow the Guinea National Malaria Control Programme to develop targeted initiatives to improve bed net ownership and usage.

Methods
To understand national and regional drivers of ITN ownership and use, multivariable binary logistic regression models were applied to data from the 2018 Demographic and Health Survey to identify risk factors of household ITN ownership and risk factors of ITN use among individuals with access. Akaike Information Criterion (AIC) was used for model parameter selection. Odds ratios were estimated with corresponding 95% confidence intervals.

Results
The proportion of households in Guinea with at least one ITN was 44%, ranging from a low of 25% in Conakry to a high of 54% in Labé. Use of ITNs among those with access was 66.1% nationally, ranging from 35.2% in Labé to 89.7% in N'zérékoré. Risk factors for household ITN ownership were household size, marital status of the household head, education level of the household head, and region. For ITN use among those with access, risk factors were age, wealth quintile, marital status, and region. In the seven regions of Guinea and capital of Conakry, risk factors for household ITN ownership were household size in Boké, Faranah, and Kankan; education level of the household head in Boké, Faranah, and N’zérékoré; age of the household head in Conakry and Labé; children under five in the household in Kankan; and wealth quintile in Mamou. For ITN use among those with access, risk factors were marital status in Conakry, Faranah, Kindia, Labé, Mamou, and N’zérékoré; place of residence in Labé; children under five in the household in Labé; wealth quintile in Mamou; and age in Faranah and N’zérékoré.

Conclusions
This analysis identified national and region-specific factors that affect ownership and use among those with access in Guinea. Future ITN and social-behavioural change campaigns in Guinea may particularly want to target larger households, households without children, and areas with lower perceived risk of malaria if universal coverage and usage are to be achieved for optimal malaria prevention.
Inositol is an effective and safe treatment in polycystic ovary syndrome: a systematic review and meta-analysis of randomized controlled trials
Authors: Greff Dorina , Juhász Anna E. , Váncsa Szilárd , Váradi Alex , Sipos Zoltán , Szinte Julia , Park Sunjune , Hegyi Péter , Nyirády Péter , Ács Nándor , Várbíró Szabolcs , Horváth Eszter M. 
Published: January 2023

Abstract
Background
Metformin is the gold standard insulin sensitizer, which is widely used to treat insulin resistance in polycystic ovary syndrome (PCOS). However, metformin may induce gastrointestinal side effects.

Objective
Inositols have long been debated as a potential alternative for metformin in treating PCOS. Therefore, the present systematic review aimed to evaluate the efficacy and safety of inositols in treating PCOS.

Methods
The present systematic search was performed in CENTRAL, MEDLINE, and Embase from the inception until October 20th, 2021. Eligible randomized controlled trials (RCTs) included women diagnosed with PCOS and compared any inositols with metformin or placebo. Our primary outcome was cycle normalization, whereas secondary outcomes were body mass index (BMI), parameters of carbohydrate metabolism and clinical and laboratory hyperandrogenism. Results are reported as risk ratios or mean differences (MDs) with 95% confidence intervals (CIs).

Results
Twenty-six RCTs were identified, including data of 1691 patients (806 inositol, 311 with placebo, and 509 metformin groups). In patients treated with inositols, the risk (CI: 1.13; 2.85) of having a regular menstrual cycle was found by 1.79 higher than in the case of placebo. Moreover, the inositols showed non-inferiority compared to metformin in this outcome. In the case of BMI (MD = -0.45; CI: -0.89; -0.02), free testosterone (MD = -0,41, CI: -0.69; -0.13), total testosterone (MD = -20.39, CI: -40.12; -0.66), androstenedione (MD = -0.69, CI: -1,16; -0.22), glucose (MD = -3.14; CI: -5.75; -0.54) levels and AUC insulin (MD = -2081.05, CI: -2745.32; -1416.78) inositol treatment induced greater decrease compared to placebo. Inositol increased sex-hormone-binding globulin significantly compared to placebo (MD = 32.06, CI:1.27; 62.85).

Conclusion
Inositol is an effective and safe treatment in PCOS. Moreover, inositols showed non-inferiority in most outcomes compared to the gold standard treatment; metformin.

Trial registration
PROSPERO registration number: CRD42021283275.
Current and future strategies to monitor and manage coagulation in ECMO patients
Authors: Zeibi Shirejini Saeedreza , Carberry Josie , McQuilten Zoe K. , Burrell Aidan J. C. , Gregory Shaun D. , Hagemeyer Christoph E. 
Published: January 2023

AbstractExtracorporeal membrane oxygenation (ECMO) can provide life-saving support for critically ill patients suffering severe respiratory and/or cardiac failure. However, thrombosis and bleeding remain common and complex problems to manage. Key causes of thrombosis in ECMO patients include blood contact to pro-thrombotic and non-physiological surfaces, as well as high shearing forces in the pump and membrane oxygenator. On the other hand, adverse effects of anticoagulant, thrombocytopenia, platelet dysfunction, acquired von Willebrand syndrome, and hyperfibrinolysis are all established as causes of bleeding. Finding safe and effective anticoagulants that balance thrombosis and bleeding risk remains challenging. This review highlights commonly used anticoagulants in ECMO, including their mechanism of action, monitoring methods, strengths and limitations. It further elaborates on existing anticoagulant monitoring strategies, indicating their target range, benefits and drawbacks. Finally, it introduces several highly novel approaches to real-time anticoagulation monitoring methods including sound, optical, fluorescent, and electrical measurement as well as their working principles and future directions for research.
Traffic-light front-of-pack environmental labelling across food categories triggers more environmentally friendly food choices: a randomised controlled trial in virtual reality supermarket
Authors: Arrazat Laura , Chambaron Stéphanie , Arvisenet Gaëlle , Goisbault Isabelle , Charrier Jean-Christophe , Nicklaus Sophie , Marty Lucile 
Published: January 2023

Abstract
Background
Food systems highly contribute to anthropogenic greenhouse gas emissions and shifting towards more environmentally friendly diets is urgently needed. Enabling consumers to compare the environmental impact of food products at point-of-purchase with front-of-pack labelling could be a promising strategy to trigger more environmentally friendly food choices. This strategy remained to be tested.

Methods
The effect of a new traffic-light front-of-pack environmental label on food choices was tested in a 2-arm randomised controlled trial in a virtual reality supermarket. Participants (n = 132) chose food products to compose two main meals for an everyday meal scenario and for an environmentally friendly meal scenario with or without the label. The environmental label (ranging from A: green/lowest impact, to E: red/highest impact) was based on the Environmental Footprint (EF) single score calculation across food categories. The effect of the label on the environmental impact of food choices in each scenario was tested using linear mixed models.

Results
In the everyday meal scenario, the environmental impact of meals was lower in the label condition than in the no label condition (-0.17 ± 0.07 mPt/kg, p = 0.012). This reduction was observed at no nutritional, financial nor hedonic cost. The effectiveness of the label can be attributed to a change in the food categories chosen: less meat-based and more vegetarian meals were chosen with the label. In the environmentally friendly meal scenario, we demonstrated that the label provided new information to the participants as they were able to further reduce the environmental impact of their food choices with the label (-0.19 ± 0.07 mPt/kg, p = 0.005).

Conclusions
Implementing a front-of-pack environmental label on food products in real supermarkets could increase awareness of the environmental impact of food and contribute to drive more environmentally friendly food choices.

Trial registration
The study protocol was pre-registered prior to data collection at Clinicaltrials.gov (NCT04909372).
β-catenin-IRP2-primed iron availability to mitochondrial metabolism is druggable for active β-catenin-mediated cancer
Authors: Wu Yuting , Yang Shuhui , Han Luyang , Shang Kezhuo , Zhang Baohui , Gai Xiaochen , Deng Weiwei , Liu Fangming , Zhang Hongbing 
Published: January 2023

Abstract
Background
Although β-catenin signaling cascade is frequently altered in human cancers, targeting this pathway has not been approved for cancer treatment.

Methods
High-throughput screening of an FDA-approved drug library was conducted to identify therapeutics that selectively inhibited the cells with activated β-catenin. Efficacy of iron chelator and mitochondrial inhibitor was evaluated for suppression of cell proliferation and tumorigenesis. Cellular chelatable iron levels were measured to gain insight into the potential vulnerability of β-catenin-activated cells to iron deprivation. Extracellular flux analysis of mitochondrial function was conducted to evaluate the downstream events of iron deprivation. Chromatin immunoprecipitation, real-time quantitative PCR and immunoblotting were performed to identify β-catenin targets. Depletion of iron-regulatory protein 2 (IRP2), a key regulator of cellular iron homeostasis, was carried out to elucidate its significance in β-catenin-activated cells. Online databases were analyzed for correlation between β-catenin activity and IRP2-TfR1 axis in human cancers.

Results
Iron chelators were identified as selective inhibitors against β-catenin-activated cells. Deferoxamine mesylate, an iron chelator, preferentially repressed β-catenin-activated cell proliferation and tumor formation in mice. Mechanically, β-catenin stimulated the transcription of IRP2 to increase labile iron level. Depletion of IRP2-sequered iron impaired β-catenin-invigorated mitochondrial function. Moreover, mitochondrial inhibitor S-Gboxin selectively reduced β-catenin-associated cell viability and tumor formation.

Conclusions
β-catenin/IRP2/iron stimulation of mitochondrial energetics is targetable vulnerability of β-catenin-potentiated cancer.
A pilot study to estimate the population size of endangered Galápagos marine iguanas using drones
Authors: Varela-Jaramillo Andrea , Rivas-Torres Gonzalo , Guayasamin Juan M. , Steinfartz Sebastian , MacLeod Amy 
Published: January 2023

Abstract
Background
Large-scale species monitoring remains a significant conservation challenge. Given the ongoing biodiversity crisis, the need for reliable and efficient methods has never been greater. Drone-based techniques have much to offer in this regard: they allow access to otherwise unreachable areas and enable the rapid collection of non-invasive field data. Herein, we describe the development of a drone-based method for the estimation of population size in Galápagos marine iguanas, Amblyrhynchus cristatus. As a large-bodied lizard that occurs in open coastal terrain, this endemic species is an ideal candidate for drone surveys. Almost all Amblyrhynchus subspecies are Endangered or Critically Endangered according to the IUCN yet since several colonies are inaccessible by foot, ground- based methods are unable to address the critical need for better census data. In order to establish a drone-based approach to estimate population size of marine iguanas, we surveyed in January 2021 four colonies on three focal islands (San Cristobal, Santa Fe and Espanola) using three techniques: simple counts (the standard method currently used by conservation managers), capture mark-resight (CMR), and drone-based counts. The surveys were performed within a 4-day window under similar ambient conditions. We then compared the approaches in terms of feasibility, outcome and effort.

Results
The highest population-size estimates were obtained using CMR, and drone-based counts were on average 14% closer to CMR estimates—and 17–35% higher—than those obtained by simple counts. In terms of field-time, drone-surveys can be faster than simple counts, but image analyses were highly time consuming.

Conclusion
Though CMR likely produces superior estimates, it cannot be performed in most cases due to lack of access and knowledge regarding colonies. Drone-based surveys outperformed ground-based simple counts in terms of outcome and this approach is therefore suitable for use across the range of the species. Moreover, the aerial approach is currently the only credible solution for accessing and surveying marine iguanas at highly remote colonies. The application of citizen science and other aids such as machine learning will alleviate the issue regarding time needed to analyze the images.
Prevalence of depression and anxiety, and their relationship to social support among patients and family caregivers of rare bone diseases
Authors: Lai Xuefeng , Jiang Yuling , Sun Yue , Zhang Zhijun , Wang Shengfeng 
Published: January 2023

Abstract
Background
Rare bone diseases (RBDs) are a set of inherited rare diseases that can cause disability and have a devastating impact on families affected, which may lead to a particular high prevalence of psychological disorders in patients and caregivers. Social support plays a role in the well-being of families with rare disease patients, but its effect on psychology of RBD families remains unclear. The purpose of the current cross-sectional quantitative study was to investigate the frequency of depression and anxiety, and their relationship with social support among RBD patients and family caregivers.

Results
A total of 196 participants responded to the questionnaire, including 72 patients and 124 caregivers. Depression was detected among 33.8% of patients and 57% of caregivers, and anxiety disorder was presented in 28.6% of patients and 50% of caregivers. Higher depression scores and anxiety scores were found in both patients and caregivers with an education level of ≤ middle school and monthly income of ≤ ￥2000 (all P < 0.05). The mean (SD) scores of Social Support Rating Scales in patients and caregivers were 37.06 (8.05) and 38.31 (5.76), respectively. After adjusting for gender, age, monthly income, education, employment and marital status, the reverse associations between depression scores, anxiety scores and social support were found merely in caregivers (depression & social support: β = − 0. 46, P < 0.001, anxiety & social support: β = − 0. 44, P < 0.001), specifically for subjective support (depression & subjective support: β = − 0.94, P < 0.001, anxiety & subjective support: β = − 0.87, P < 0.001).

Conclusions
The study identified a high prevalence of depression and anxiety among RBD patients and caregivers, and pointed out the significance of social support in alleviating psychological distress. In order to provide RBD families with comprehensive assistance, the government should actively develop programs aimed at psychological aid, policy advocacy and tangible support.