bluuebunny/crossref_metadata_2025_split huggingface dataset:
Defining research priorities for youth public mental health: reflections on a coproduction approach to transdisciplinary working
Authors: Taylor Andrea , McMellon Christina , French Tara , MacLachlan Alice , Evans Rhiannon , Lewis Ruth , McCann Mark , Moore Laurence , Murphy Simon , Simpson Sharon , Inchley Jo 
Published: June 2022

Abstract
Background
With most mental health problems established during childhood/adolescence, young people must be a key focus of public mental health approaches. Despite the range of factors known to influence mental health, evidence for effective interventions is lacking for this age group. This study aimed to define priorities for future public health intervention-focused research to support youth mental health by engaging with transdisciplinary stakeholder groups.

Methods
Our coproduction approach involved priority-setting workshops with young people, researchers, practitioners and policy-makers. Each workshop focused on three thematic areas: social connections and relationships; schools and other education settings; and key groups at greater risk of mental ill-health, specifically LGBTQ+ and care-experienced young people. Workshop outputs were synthesized to define research priorities.

Results
This paper presents the research priorities that were defined through the priority-setting workshops, and our reflections on the coproduction approach to guide future similar activities undertaken by others. Ten priorities for youth public mental health research were defined, covering the following areas: building supportive relationships; whole system approaches; social media; support at times of transition; improving links between different services; development and training for those who support young people; staff mental health; engaging with families; awareness of and access to services; and out-of-school and community settings.

Conclusions
These research priorities can inform future intervention development to support youth public mental health. Our transdisciplinary approach means the identified research priorities are likely to be relevant to young people’s experiences and needs, and to fit with the needs of those working in practice and policy to support young people.
Complement C3a activates astrocytes to promote medulloblastoma progression through TNF-α
Authors: Gong Biao , Guo Duancheng , Zheng Chaonan , Ma Zhen , Zhang Jie , Qu Yanghui , Li Xinhua , Li Gen , Zhang Li , Wang Yuan 
Published: June 2022

AbstractBackgroundMedulloblastoma (MB) is the most common malignant brain tumor in children. Approximately one-third of MB patients remain incurable. Understanding the molecular mechanism of MB tumorigenesis is, therefore, critical for developing specific and effective treatment strategies. Our previous work demonstrated that astrocytes constitute the tumor microenvironment (TME) of MB and play an indispensable role in MB progression. However, the underlying mechanisms by which astrocytes are regulated and activated to promote MB remain elusive.MethodsBy taking advantage ofMath1-Cre/Ptch1loxp/loxpmice, which spontaneously develop MB, primary MB cells and astrocytes were isolated and then subjected to administration and coculture in vitro. Immunohistochemistry was utilized to determine the presence of C3a in MB sections. MB cell proliferation was evaluated by immunofluorescent staining. GFAP and cytokine expression levels in C3a-stimulated astrocytes were assessed by immunofluorescent staining, western blotting, q-PCR and ELISA. C3a receptor and TNF-α receptor expression was determined by PCR and immunofluorescent staining. p38 MAPK pathway activation was detected by western blotting. Transplanted MB mice were treated with a C3a receptor antagonist or TNF-α receptor antagonist to investigate their role in MB progression in vivo.ResultsWe found that complement C3a, a fragment released from intact complement C3 following complement activation, was enriched in both human and murine MB tumor tissue, and its receptor was highly expressed on tumor-associated astrocytes (TAAs). We demonstrated that C3a activated astrocytes and promoted MB cell proliferation via the p38 MAPK pathway. Moreover, we discovered that C3a upregulated the production of proinflammatory cytokines, such as IL-6 and TNF-α in astrocytes. Application of the conditioned medium of C3a-stimulated astrocytes promoted MB cell proliferation, which was abolished by preincubation with a TNF-α receptor antagonist, indicating a TNF-α-dependent event. Indeed, we further demonstrated that administration of a selective C3a receptor or TNF-α receptor antagonist to mice subcutaneously transplanted with MB suppressed tumor progression in vivo.ConclusionsC3a was released during MB development. C3a triggered astrocyte activation and TNF-α production via the p38 pathway, which promoted MB cell proliferation. Our findings revealed the novel role of C3a-mediated TNF-α production by astrocytes in MB progression. These findings imply that targeting C3a and TNF-α may represent a potential novel therapeutic approach for human MB.
Apelin alleviated neuroinflammation and promoted endogenous neural stem cell proliferation and differentiation after spinal cord injury in rats
Authors: Liu Qing , Zhou Shuai , Wang Xiao , Gu Chengxu , Guo Qixuan , Li Xikai , Zhang Chunlei , Zhang Naili , Zhang Luping , Huang Fei 
Published: June 2022

Abstract
Background
Spinal cord injury (SCI) causes devastating neurological damage, including secondary injuries dominated by neuroinflammation. The role of Apelin, an endogenous ligand that binds the G protein-coupled receptor angiotensin-like receptor 1, in SCI remains unclear. Thus, our aim was to investigate the effects of Apelin in inflammatory responses and activation of endogenous neural stem cells (NSCs) after SCI.

Methods
Apelin expression was detected in normal and injured rats, and roles of Apelin in primary NSCs were examined. In addition, we used induced pluripotent stem cells (iPSCs) as a carrier to prolong the effective duration of Apelin and evaluate its effects in a rat model of SCI.

Results
Co-immunofluorescence staining suggested that Apelin was expressed in both astrocytes, neurons and microglia. Following SCI, Apelin expression decreased from 1 to 14 d and re-upregulated at 28 d. In vitro, Apelin promoted NSCs proliferation and differentiation into neurons. In vivo, lentiviral-transfected iPSCs were used as a carrier to prolong the effective duration of Apelin. Transplantation of transfected iPSCs in situ immediately after SCI reduced polarization of M1 microglia and A1 astrocytes, facilitated recovery of motor function, and promoted the proliferation and differentiation of endogenous NSCs in rats.

Conclusion
Apelin alleviated neuroinflammation and promoted the proliferation and differentiation of endogenous NSCs after SCI, suggesting that it might be a promising target for treatment of SCI.
Female education and maternal health care utilization: evidence from Uganda
Authors: Amwonya David , Kigosa Nathan , Kizza James 
Published: June 2022

Abstract
Background
Maternal health care is among the key indicators of population health and economic development. Therefore, the study attempted to explore female education and maternal healthcare utilization in Uganda. The study identified the causal effect of introduction of free education by exploiting the age as an instrument at the second stage model (BMC Health Serv Res. 2015. 10.1186/s12913-015-0943-8; Matern Child Health J. 2009;14:988–98). This instrument provided an exogenous source of variation in the years of schooling and allowed to implement a regression discontinuity design which accounted for heterogeneity in the cohort overtime.

Methods
The study used the Ordinary Least Squares (OLS) to help predict years of schooling that were used in the second stage model in the Two Stage Least Squares (2SLS). The study further used the Regression Discontinuity Design (RDD) model with a running variable of birth years to observe its effect on education. To control for heterogeneity in regions in the second stage model, a fixed effects model was used.

Results
Female education indeed had a positive impact on maternal health care utilization. It was further found out that age also influences maternal health care utilization.

Conclusions
Therefore, as an effort to improve professional maternal health care utilisation, there is need to focus on education beyond primary level. Uganda Government should also ensure that there is an improvement in community infrastructure and security across all regions and locations.
Penetrating renal injuries: an observational study of non-operative management and the impact of opening Gerota’s fascia
Authors: Clements Thomas W. , Ball Chad G. , Nicol Andrew J. , Edu Sorin , Kirkpatrick Andrew W. , Navsaria Pradeep 
Published: June 2022

Abstract
Background
Non-operative management has become increasingly popular in the treatment of renal trauma. While data are robust in blunt mechanisms, the role of non-operative management in penetrating trauma is less clear. Additionally, there is a paucity of data comparing gunshot and stab wounds.

Methods
A retrospective review of patients admitted to a high-volume level 1 trauma center (Groote Schuur Hospital, Cape Town) with penetrating abdominal trauma was performed. Patients with renal injuries were identified and compared based on mechanism [gunshot (GSW) vs. stab] and management strategy (operative vs. non-operative). Primary outcomes of interest were mortality and failure of non-operative management. Secondary outcomes of interest were nephrectomy rates, Clavien-Dindo complication rate, hospital length of stay, and overall morbidity rate.

Results
A total of 150 patients with renal injuries were identified (82 GSW, 68 stab). Overall, 55.2% of patients required emergent/urgent laparotomy. GSWs were more likely to cause grade V injury and concurrent intra-abdominal injuries (p > 0.05). The success rate of non-operative management was 91.6% (89.9% GSW, 92.8% stab, p = 0.64). The absence of hematuria on point of care testing demonstrated a negative predictive value of 98.4% (95% CI 96.8–99.2%). All but 1 patient who failed non-operative management had associated intra-abdominal injuries requiring surgical intervention. Opening of Gerota’s fascia resulted in nephrectomy in 55.6% of cases. There were no statistically significant risk factors for failure of non-operative management identified on univariate logistic regression.

Conclusions
NOM of penetrating renal injuries can be safely and effectively instituted in both gunshot and stab wounds with a very low number of patients progressing to laparotomy. Most patients fail NOM for associated injuries. During laparotomy, the opening of Gerota’s fascia may lead to increased risk of nephrectomy. Ongoing study with larger populations is required to develop effective predictive models of patients who will fail NOM.
In-hospital mortality of patients with severe left ventricular dysfunction undergoing coronary artery bypass grafting in Iranian population
Authors: Khalili Ahmadali , Rahimi Mehran , Khezerlouy-aghadam Naser , Akbarzadeh Fariborz , Taban-sadeghi Mohammadreza 
Published: June 2022

Abstract
Background
Historically, coronary artery bypass grafting is associated with a higher mortality rate in patients with severe heart failure. This study aimed to assess the in-hospital mortality of CABG in patients with severe heart failure in Iranian patients and to identify factors associated with adverse outcomes.

Methods
This retrospective descriptive study enrolled patients with severe heart failure who underwent coronary artery bypass surgery from 2015 to 2020 in Madani Hospital, affiliated with Tabriz University of Medical Sciences.

Results
A total of 865 consecutive patients with a mean age of 60.65 ± 10.00 were enrolled in the study. Of all participants, 175 were female (20.4%), and 684 were male. The overall mortality rate was 9.5%. In the univariate analysis, predictors of ICU mortality were age, female sex, DM, and renal failure (P value < 0.05). None of the factors studied was an independent predictor of ICU mortality in the multivariate analysis.

Conclusion
This study established that although coronary artery bypass surgery is reported to have low mortality and postoperative morbidity in patients with severe heart failure, there are still centers that face higher mortality rates in these patients. Improving these patients' outcomes would be possible through identifying the associated risk factors and pre-and postoperative management.
SeqScreen: accurate and sensitive functional screening of pathogenic sequences via ensemble learning
Authors: Balaji Advait , Kille Bryce , Kappell Anthony D. , Godbold Gene D. , Diep Madeline , Elworth R. A. Leo , Qian Zhiqin , Albin Dreycey , Nasko Daniel J. , Shah Nidhi , Pop Mihai , Segarra Santiago , Ternus Krista L. , Treangen Todd J. 
Published: June 2022

AbstractThe COVID-19 pandemic has emphasized the importance of accurate detection of known and emerging pathogens. However, robust characterization of pathogenic sequences remains an open challenge. To address this need we developed SeqScreen, which accurately characterizes short nucleotide sequences using taxonomic and functional labels and a customized set of curated Functions of Sequences of Concern (FunSoCs) specific to microbial pathogenesis. We show our ensemble machine learning model can label protein-coding sequences with FunSoCs with high recall and precision. SeqScreen is a step towards a novel paradigm of functionally informed synthetic DNA screening and pathogen characterization, available for download atwww.gitlab.com/treangenlab/seqscreen.
Open problems in human trait genetics
Authors: Brandes Nadav , Weissbrod Omer , Linial Michal 
Published: June 2022

AbstractGenetic studies of human traits have revolutionized our understanding of the variation between individuals, and yet, the genetics of most traits is still poorly understood. In this review, we highlight the major open problems that need to be solved, and by discussing these challenges provide a primer to the field. We cover general issues such as population structure, epistasis and gene-environment interactions, data-related issues such as ancestry diversity and rare genetic variants, and specific challenges related to heritability estimates, genetic association studies, and polygenic risk scores. We emphasize the interconnectedness of these problems and suggest promising avenues to address them.
An analysis of proteogenomics and how and when transcriptome-informed reduction of protein databases can enhance eukaryotic proteomics
Authors: Fancello Laura , Burger Thomas 
Published: June 2022

AbstractBackgroundProteogenomics aims to identify variant or unknown proteins in bottom-up proteomics, by searching transcriptome- or genome-derived custom protein databases. However, empirical observations reveal that these large proteogenomic databases produce lower-sensitivity peptide identifications. Various strategies have been proposed to avoid this, including the generation of reduced transcriptome-informed protein databases, which only contain proteins whose transcripts are detected in the sample-matched transcriptome. These were found to increase peptide identification sensitivity. Here, we present a detailed evaluation of this approach.ResultsWe establish that the increased sensitivity in peptide identification is in fact a statistical artifact, directly resulting from the limited capability of target-decoy competition to accurately model incorrect target matches when using excessively small databases. As anti-conservative false discovery rates (FDRs) are likely to hamper the robustness of the resulting biological conclusions, we advocate for alternative FDR control methods that are less sensitive to database size. Nevertheless, reduced transcriptome-informed databases are useful, as they reduce the ambiguity of protein identifications, yielding fewer shared peptides. Furthermore, searching the reference database and subsequently filtering proteins whose transcripts are not expressed reduces protein identification ambiguity to a similar extent, but is more transparent and reproducible.ConclusionsIn summary, using transcriptome information is an interesting strategy that has not been promoted for the right reasons. While the increase in peptide identifications from searching reduced transcriptome-informed databases is an artifact caused by the use of an FDR control method unsuitable to excessively small databases, transcriptome information can reduce the ambiguity of protein identifications.
Safety, reactogenicity, and immunogenicity of a 2-dose Ebola vaccine regimen of Ad26.ZEBOV followed by MVA-BN-Filo in healthy adult pregnant women: study protocol for a phase 3 open-label randomized controlled trial
Authors: Karita Etienne , Nyombayire Julien , Ingabire Rosine , Mazzei Amelia , Sharkey Tyronza , Mukamuyango Jeannine , Allen Susan , Tichacek Amanda , Parker Rachel , Priddy Frances , Sayinzoga Felix , Nsanzimana Sabin , Robinson Cynthia , Katwere Michael , Anumendem Dickson , Leyssen Maarten , Schaefer Malinda , Wall Kristin M. 
Published: June 2022

Abstract
Background
Risks to mother and fetus following Ebola virus infection are very high. Evaluation of safety and immunogenicity of non-replicating Ebola vaccine candidates is a priority for use in pregnant women. This is the protocol for a randomized, open-label, single-center phase 3 clinical trial of the safety, reactogenicity, and immunogenicity of the 2-dose Ebola vaccine regimen in healthy adult pregnant women. This 2-dose regimen has been shown to be safe, judged effective, and approved in non-pregnant populations.

Methods
A total of 2000 adult (≥ 18 years of age) pregnant women will be enrolled from antenatal care facilities in Western Rwanda and randomized (1:1) to receive the 2-dose Ebola vaccine regimen (Ad26.ZEBOV, MVA-BN-Filo (group A)) or control (unvaccinated pregnant women (group B)). The primary objectives are to (1) assess adverse maternal/fetal outcomes in randomized pregnant women up to 1.5 months after delivery and (2) assess adverse neonatal/infant outcomes in neonates/infants born to randomized women up to 3.5 months after birth. The frequency and relatedness of all serious adverse events in women and newborns from randomization or birth, respectively, until study end will be reported. The reactogenicity and unsolicited adverse events of the 2-dose Ebola vaccine regimen in all vaccinated pregnant women (group A) will be reported. We will also assess the immunogenicity of the 2-dose Ebola vaccine regimen in 150 pregnant women who are anticipated to receive both vaccine doses within the course of their pregnancy (a subset of the 1000 pregnant vaccinated women from group A) compared to 150 non-pregnant women vaccinated after delivery (a subset of group B). The persistence of maternal antibodies in 75 infants born to women from the group A subset will be assessed. Exploratory analyses include assessment of acceptability of the 2-dose Ebola vaccine regimen among group A and assessment of maternal antibodies in breast milk in 50 women from group A and 10 controls (women from group B prior to vaccination).

Discussion
This study is intended to support a label variation to relax restrictions on use in pregnant women, a vulnerable population with high medical need.

Trial registration
Clinicaltrials.gov NCT04556526. September 21, 2020.
Protocol paper: multi-Centre randomised controlled trial evaluating a pre-clinic diabetes assessment and mapped care planning intervention amongst adults with type 1, type 2 or pre-diabetes
Authors: Kelly Ryan Charles , Phiri Peter , Price Hermione , Ali Amar , Stratton Irene , Austin Kayleigh , Neave Alice , Barnard-Kelly Katharine 
Published: June 2022

Abstract
Background
Existing therapeutic interventions to treat diabetes are well known, yet the majority of people with diabetes do not consistently achieve blood glucose targets (even individual therapy targets) for optimal health, despite the large range of treatment options available. Such outcomes have remained stubbornly poor for decades with <25% adults with diabetes achieving glycaemic targets. Patient behaviour, individually supported in routine clinical care, is an important missing component to improved outcomes, in a medical healthcare model not ideally suited to supporting successful diabetes management.

Methods
A multi-centre, parallel group, individually randomised trial comparing consultation duration in adults with type 1, type 2 or pre-diabetes using the Spotlight Consultations pre-clinic assessment compared to usual care in the Spotlight-AQ study. Two hundred adults with type 1, type 2 or pre-diabetes attending routine care outpatient appointments across up to ten participating sites will be invited to participate.

Intervention
An outpatient pre-clinic intervention delivered within 1 week prior to scheduled routine outpatient appointment.

Primary outcome measure
Duration of routine outpatient consultation.

Secondary outcome measures

Functional health status

Diabetes distress

Depression

Treatment satisfaction

Impact on self-care behaviours

HCP burnout

HCP treatment satisfaction and burden

Hypoglycaemia (time less than 70mg/dL)

Hyperglycaemia (time above 180 mg/dL)

Change in weight

Change in HbA1c

Cost effectiveness of intervention

Discussion
Results from the study will provide valuable insights into patient-professional communication practices within routine care and recommendations will be made, as necessary, for improvements to that. If the intervention is shown to be clinically and cost-effective, the feedback from participants and healthcare professionals will be used to make any improvements prior to its deployment to support improved communication and associated health outcomes.

Ethics and dissemination
The trial was approved by the Wales REC7 Research Ethics Committee (21/WA/0020). Results will be disseminated through national and international conferences, scientific journals, newsletters, magazines and social media. Target audiences include consultants and other clinicians in diabetes, and medical professionals or scientists overall.

Trial registration
ISRCTN15511689. Registered on 10 November 2021
Mapping the deformability of natural and designed cellulosomes in solution
Authors: Dorival Jonathan , Moraïs Sarah , Labourel Aurore , Rozycki Bartosz , Cazade Pierre-Andre , Dabin Jérôme , Setter-Lamed Eva , Mizrahi Itzhak , Thompson Damien , Thureau Aurélien , Bayer Edward A. , Czjzek Mirjam 
Published: June 2022

Abstract
Background
Natural cellulosome multi-enzyme complexes, their components, and engineered ‘designer cellulosomes’ (DCs) promise an efficient means of breaking down cellulosic substrates into valuable biofuel products. Their broad uptake in biotechnology relies on boosting proximity-based synergy among the resident enzymes, but the modular architecture challenges structure determination and rational design.

Results
We used small angle X-ray scattering combined with molecular modeling to study the solution structure of cellulosomal components. These include three dockerin-bearing cellulases with distinct substrate specificities, original scaffoldins from the human gut bacterium Ruminococcus champanellensis (ScaA, ScaH and ScaK) and a trivalent cohesin-bearing designer scaffoldin (Scaf20L), followed by cellulosomal complexes comprising these components, and the nonavalent fully loaded Clostridium thermocellum CipA in complex with Cel8A from the same bacterium. The size analysis of Rg and Dmax values deduced from the scattering curves and corresponding molecular models highlight their variable aspects, depending on composition, size and spatial organization of the objects in solution.

Conclusions
Our data quantifies variability of form and compactness of cellulosomal components in solution and confirms that this native plasticity may well be related to speciation with respect to the substrate that is targeted. By showing that scaffoldins or components display enhanced compactness compared to the free objects, we provide new routes to rationally enhance their stability and performance in their environment of action.