bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of credit on the climate adaptation utilization among food crop farmers in Southwest, Nigeria: application of endogenous treatment Poisson regression model
Authors: Olutumise Adewale Isaac
Published: March 2023

The importance of credit in agriculture and technology adoption is well researched, but little is known about its impact on the intensity of climate adaptation strategies (CAS) utilization. To contribute to the literature on climate change, the study examines the impact of credit status on the intensity of CAS utilization with its treatment effects. Unlike previous studies that investigated CAS as binary decisions or multi-class models, the study changed the narrative by measuring the number of CAS adopted and utilized by crop farmers. Farm-level data were collected from 150 crop farmers in Southwest Nigeria using a well-designed questionnaire. Descriptive statistics and the endogenous treatment Poisson regression (ETPR) model were used for the data analysis. The results revealed that credit status positively and significantly impacts the intensity of CAS utilization. Other farm-level factors that jointly impacted CAS utilization were education, experience, age, income, extension contacts and farm size. Likewise, the credit status co-joints with climate variables, such as access to climate information, perceived rainfall and temperature, to impact the intensity of CAS utilization in the area. Based on the treatment effects estimates, an average crop farmer will utilize 1.986 times CAS more when he is not being credit constrained, while the average crop farmer in the treated group will utilize 1.757 times CAS more than it would if s/he is credit constrained. Thus, the policy should focus on revamping credit institutions that prioritize requisite adaptation strategy resources.
A field-experiment testing the impact of a warrant service prioritization strategy for police patrol officers
Authors: Taniguchi Travis A. , Aagaard Brian , Baumgartner Peter , Young Amanda R.
Published: March 2023

The objective of this experiment was to test the efficacy of providing prioritized warrant lists to patrol officers. A field experiment was carried out with the Greensboro (NC) Police Department. Warrant risk profiles were calculated from an analysis of historical offending; historical risk factors were used to implement prospective risk assessment for committing a violent crime while having an outstanding warrant issued during the field experiment. During the period from March 01, through July 31, 2019, people with warrants were randomly allocated to treatment or control. Outcomes included: number of warrants served, time to service, and average risk score of warrants served. Prioritization was not effective in promoting additional warrant service. No differences were found in the risk scores of people served. However, assessment of time to service suggested that warrants were served more quickly during the experimental period. Implementation of warrant prioritization had limited impacts; the process evaluation demonstrated the difficulty in modifying police patrol behaviors.
Secretogranin II influences the assembly and function of MHC class I in melanoma
Authors: Steinfass Tamara , Poelchen Juliane , Sun Qian , Mastrogiulio Giovanni , Novak Daniel , Vierthaler Marlene , Pardo Sandra , Federico Aniello , Hüser Laura , Hielscher Thomas , Carretero Rafael , Offringa Rienk , Altevogt Peter , Umansky Viktor , Utikal Jochen
Published: March 2023

Melanoma is the deadliest form of skin cancer showing rising incidence over the past years. New insights into the mechanisms of melanoma progression contributed to the development of novel treatment options, such as immunotherapies. However, acquiring resistance to treatment poses a big problem to therapy success. Therefore, understanding the mechanisms underlying resistance could improve therapy efficacy. Correlating expression levels in tissue samples of primary melanoma and metastases revealed that secretogranin 2 (SCG2) is highly expressed in advanced melanoma patients with poor overall survival (OS) rates. By conducting transcriptional analysis between SCG2-overexpressing (OE) and control melanoma cells, we detected a downregulation of components of the antigen presenting machinery (APM), which is important for the assembly of the MHC class I complex. Flow cytometry analysis revealed a downregulation of surface MHC class I expression on melanoma cells that showed resistance towards the cytotoxic activity of melanoma-specific T cells. IFNγ treatment partially reversed these effects. Based on our findings, we suggest that SCG2 might stimulate mechanisms of immune evasion and therefore be associated with resistance to checkpoint blockade and adoptive immunotherapy.
Association of APP gene polymorphisms and promoter methylation with essential hypertension in Guizhou: a case–control study
Authors: Li Ruichao , Song Juhui , Zhao Ansu , Diao Xiaoyan , Zhang Ting , Qi Xiaolan , Guan Zhizhong , An Yu , Ren Lingyan , Wang Chanjuan , He Yan
Published: March 2023

Background

Single-nucleotide polymorphisms (SNPs) and DNA methylation are crucial regulators of essential hypertension (EH). Amyloid precursor protein (APP) mutations are implicated in hypertension development. Nonetheless, studies on the association of APP gene polymorphism and promoter methylation with hypertension are limited. Therefore, this case–control aims to evaluate the genetic association of APP gene polymorphism and promoter methylation with EH in Guizhou populations.

Objective and methods

We conducted a case–control study on 343 EH patients and 335 healthy controls (including Miao, Buyi, and Han populations) in the Guizhou province of China to analyze 11 single-nucleotide polymorphisms (rs2040273, rs63750921, rs2211772, rs2830077, rs467021, rs368196, rs466433, rs364048, rs364051, rs438031, rs463946) in the APP gene via MassARRAY SNP. The MassARRAY EpiTYPER was employed to detect the methylation levels of the promoters.

Results

In the Han population, the rs2211772 genotype distribution was significantly different between disease and control groups (χ2 = 6.343, P = 0.039). The CC genotype reduced the risk of hypertension compared to the TT or TC genotype (OR 0.105, 95%CI 0.012–0.914, P = 0.041). For rs2040273 in the Miao population, AG or GG genotype reduced the hypertension risk compared with the AA genotype (OR 0.533, 95%CI 0.294–0.965, P = 0.038). Haplotype TCC (rs364051–rs438031–rs463946) increased the risk of EH in Guizhou (OR 1.427, 95%CI 1.020–1.996, P = 0.037). Each 1% increase in CpG_19 (− 613 bp) methylation level was associated with a 4.1% increase in hypertension risk (OR 1.041, 95%CI 1.002–1.081, P = 0.039). Each 1% increase in CpG_1 (− 296 bp) methylation level was associated with an 8% decrease in hypertension risk in women (OR 0.920, 95%CI 0.860–0.984, P = 0.015). CpG_19 significantly correlated with systolic blood pressure (r = 0.2, P = 0.03). The methylation levels of CpG_19 in hypertensive patients with rs466433, rs364048, and rs364051 minor alleles were lower than that with wild-type alleles (P < 0.05). Moreover, rs467021 and rs364051 showed strong synergistic interaction with EH (χ2 = 7.633, P = 0.006). CpG_11, CpG_19, and rs364051 showed weak synergistic interaction with EH (χ2 = 19.874, P < 0.001).

Conclusion

In summary, rs2211772 polymorphism and promoter methylation level of APP gene may be linked to EH in Guizhou populations. Our findings will provide novel insights for genetic research of hypertension and Alzheimer's disease.
Localized assembly for long reads enables genome-wide analysis of repetitive regions at single-base resolution in human genomes
Authors: Ikemoto Ko , Fujimoto Hinano , Fujimoto Akihiro
Published: March 2023

Background

Long-read sequencing technologies have the potential to overcome the limitations of short reads and provide a comprehensive picture of the human genome. However, the characterization of repetitive sequences by reconstructing genomic structures at high resolution solely from long reads remains difficult. Here, we developed a localized assembly method (LoMA) that constructs highly accurate consensus sequences (CSs) from long reads.

Methods

We developed LoMA by combining minimap2, MAFFT, and our algorithm, which classifies diploid haplotypes based on structural variants and CSs. Using this tool, we analyzed two human samples (NA18943 and NA19240) sequenced with the Oxford Nanopore sequencer. We defined target regions in each genome based on mapping patterns and then constructed a high-quality catalog of the human insertion solely from the long-read data.

Results

The assessment of LoMA showed a high accuracy of CSs (error rate < 0.3%) compared with raw data (error rate > 8%) and superiority to a previous study. The genome-wide analysis of NA18943 and NA19240 identified 5516 and 6542 insertions (≥ 100 bp), respectively. Most insertions (~ 80%) were derived from tandem repeats and transposable elements. We also detected processed pseudogenes, insertions in transposable elements, and long insertions (> 10 kbp). Finally, our analysis suggested that short tandem duplications are associated with gene expression and transposons.

Conclusions

Our analysis showed that LoMA constructs high-quality sequences from long reads with substantial errors. This study revealed the true structures of the insertions with high accuracy and inferred the mechanisms for the insertions, thus contributing to future human genome studies. LoMA is available at our GitHub page: https://github.com/kolikem/loma.
Comprehensive analysis of cuproptosis-related long noncoding RNA for predicting prognostic and diagnostic value and immune landscape in colorectal adenocarcinoma
Authors: Liu Shichao , Zhang Shoucai , Liu Yingjie , Yang XiaoRong , Zheng Guixi
Published: March 2023

Background

Cuproptosis, as a copper-induced mitochondrial cell death, has attracted extensive attention recently, especially in cancer. Although some key regulatory genes have been identified in cuproptosis, the related lncRNAs have not been further studied. Exploring the prognostic and diagnostic value of cuproptosis-related lncRNAs (CRLs) in colon adenocarcinoma and providing guidance for individualized immunotherapy for patients are of great significance.

Results

A total of 2003 lncRNAs were correlated with cuproptosis genes and considered as CRLs. We screened 33 survival-associated CRLs and established a prognostic signature base on 7 CRLs in the training group. The patients in the low-risk group had better outcomes in both training group (P < 0.001) and test group (P = 0.016). More exciting, our model showed good prognosis prediction in both stage I–II (P = 0.020) and stage III–IV (P = 0.001). The nomogram model could further improve the accuracy of prognosis prediction. Interestingly, glucose-related metabolic pathways, which were closely related to cuproptosis, were enriched in the low-risk group. Meanwhile, the immune infiltration scores were lower in the high-risk group. The high-risk group was more sensitive to OSI.906 and ABT.888, while low-risk group was more sensitive to Sorafenib. Three lncRNAs, FALEC, AC083967.1 and AC010997.4, were highly expressed in serum of COAD patients, and the AUC was 0.772, 0.726 and 0.714, respectively, indicating their valuable diagnostic value.

Conclusions

Our research constructed a prognostic signature based on 7 CRLs and found three promising diagnostic markers for COAD patients. Our results provided a reference to the personalized immunotherapy strategies.
Biallelic variants in NOS3 and GUCY1A3, the two major genes of the nitric oxide pathway, cause moyamoya cerebral angiopathy
Authors: Guey Stéphanie , Hervé Dominique , Kossorotoff Manoëlle , Ha Guillaume , Aloui Chaker , Bergametti Françoise , Arnould Minh , Guenou Hind , Hadjadj Jessica , Dubois Teklali Fanny , Riant Florence , Balligand Jean-Luc , Uzan Georges , Villoutreix Bruno O. , Tournier-Lasserve Elisabeth
Published: March 2023

Background

Moyamoya angiopathy (MMA) is a rare cerebrovascular condition leading to stroke. Mutations in 15 genes have been identified in Mendelian forms of MMA, but they explain only a very small proportion of cases. Our aim was to investigate the genetic basis of MMA in consanguineous patients having unaffected parents in order to identify genes involved in autosomal recessive MMA.

Methods

Exome sequencing (ES) was performed in 6 consecutive consanguineous probands having MMA of unknown etiology. Functional consequences of variants were assessed using western blot and protein 3D structure analyses.

Results

Causative homozygous variants of NOS3, the gene encoding the endothelial nitric oxide synthase (eNOS), and GUCY1A3, the gene encoding the alpha1 subunit of the soluble guanylate cyclase (sGC) which is the major nitric oxide (NO) receptor in the vascular wall, were identified in 3 of the 6 probands. One NOS3 variant (c.1502 + 1G > C) involves a splice donor site causing a premature termination codon and leads to a total lack of eNOS in endothelial progenitor cells of the affected proband. The other NOS3 variant (c.1942 T > C) is a missense variant located into the flavodoxine reductase domain; it is predicted to be destabilizing and shown to be associated with a reduction of eNOS expression. The GUCY1A3 missense variant (c.1778G > A), located in the catalytic domain of the sGC, is predicted to disrupt the tridimensional structure of this domain and to lead to a loss of function of the enzyme. Both NOS3 mutated probands suffered from an infant-onset and severe MMA associated with posterior cerebral artery steno-occlusive lesions. The GUCY1A3 mutated proband presented an adult-onset MMA associated with an early-onset arterial hypertension and a stenosis of the superior mesenteric artery. None of the 3 probands had achalasia.

Conclusions

We show for the first time that biallelic loss of function variants in NOS3 is responsible for MMA and that mutations in NOS3 and GUCY1A3 are causing fifty per cent of MMA in consanguineous patients. These data pinpoint the essential role of the NO pathway in MMA pathophysiology.
Reduction in COVID-19 related resource loss and decline in prevalence of probable depression in Chinese adults: an application of the Conservation of Resource Theory
Authors: Yu Yanqiu , Lau Mason M. C. , Lau Joseph T. F.
Published: March 2023

Background

The levels of resource losses due to coronavirus disease 2019 (COVID-19) and mental distress may change during the pandemic period. Based on the Conservation of Resource (COR) Theory, this study investigated such changes and the mediation between survey time (Round 2 versus Round 1) and depression via resource losses.

Methods

Two serial random population-based telephone surveys interviewed 209 and 458 Hong Kong Chinese adults in April 2020 and May 2021, respectively. Probable depression was defined as 9-item Patient Health Questionnaire (PHQ-9) score ≥ 10. The validated Conservation of Resources Scale for COVID-19 (CORS-COVID-19) scale was used to assess resource losses due to COVID-19. Multivariable logistic regression analysis, hierarchical logistic regression analysis, and structural equation modeling (SEM) was conducted to test the association, interaction, and mediation hypotheses, respectively.

Results

The prevalence of probable depression declined from 8.6% to 1.0% over time, together with reductions in losses of financial resource (Cohen’s d = 0.88), future control (Cohen’s d = 0.39), social resource (Cohen’s d = 0.60), and family resource (Cohen’s d = 0.36) due to COVID-19. All the overall scale/subscales of the CORS-COVID-19 were positively and associated with probable depression [adjusted odds ratio (aOR) ranged from 2.72 to 42.30]. In SEM, the survey time was negatively associated with the latent variable of resource loss (β = − 0.46), which in turn was positively associated with probable depression (β = 0.73). In addition, the direct effect of survey time on probable depression was statistically non-significant (β = − 0.08), indicating a full mediation effect of resource losses.

Conclusions

The lessening of the resource losses might have fully accounted for the significant decline in probable depression from Month 3 to 15 since the first COVID-19 outbreak in Hong Kong, China. The level of depression might have increased during the first phase of the pandemic, but might decline in the later phases if resources losses could be lessened. All stakeholders should hence work together to minimize individuals’ COVID-19-related resource losses to prevent depression in the general population, as COVID-19 might be lasting.
The global COVID-19 vaccine surplus: tackling expiring stockpiles
Authors: Quan Nguyen Khoi , Anh Nguyen Le My , Taylor-Robinson Andrew W.
Published: March 2023

Background

A global surplus of coronavirus disease 2019 (COVID-19) vaccines exists as a result of difficulties in aligning the demand and supply for vaccine manufacturing and delivery. World leaders have accelerated vaccine development, approval, production and distribution as a pragmatic approach to addressing the immediate public health challenges of the first two and a half years of the pandemic.

Main body

The currently predominant, highly transmissible Omicron variant of severe acute respiratory syndrome coronavirus 2 has brought us closer to the threshold required to achieve herd immunity by greatly increasing rates of natural infection. Paradoxically, in parallel with rising vaccination levels in industrialized nations, this indirectly reduces the need for mass vaccine campaigns. Principal concerns that contribute to low vaccination rates which persist in several other countries, particularly of the Global South, are vaccine hesitancy and unequal access to vaccination. Social uncertainty fueled by fake news, misinformation, unfounded lay opinions and conspiracy theories has inevitably led to an erosion of public trust in vaccination.

Conclusion

To address the current mismatch between supply and demand of COVID-19 vaccines, there should be a focus on three principles: decelerating vaccine production, increasing distribution across communities, and optimizing cost-effectiveness of distribution logistics. Slowing down and switching from large-scale production to effectively ‘made to order’ is a feasible option, which should be commensurate with management capacity. Transparent and evidence-based data should be widely and freely disseminated to the public through multimedia channels to mitigate miscommunication and conspiracy theories. Use of soon-to-expire stockpiles should be prioritized not only to enhance booster dose rollouts in adults but to expand immunization campaigns to children (especially those aged 5–11 years), subject to national approval. Future research should ideally aim to develop vaccines that only require basic, affordable storage and maintenance procedures as opposed to sophisticated and expensive protocols.

Graphical Abstract
Survival, healing, and swim performance of juvenile migratory sea lamprey (Petromyzon marinus) implanted with a new acoustic microtransmitter designed for small eel-like fishes
Authors: Haas Taylor F. , Castro-Santos Theodore , Miehls Scott M. , Deng Zhiqun D. , Bruning Tyler M. , Wagner C. Michael
Published: March 2023

Background

Little is known about the transformer stage of the parasitic lampreys, a brief but critical period that encompasses juvenile out-migration from rivers to lakes or oceans to begin parasitic feeding. Information about this life stage could have significant conservation implications for both imperiled and invasive lampreys. We investigated tag retention, survival, wound healing, and swim performance of newly transformed sea lamprey (Petromyzon marinus) implanted with a new micro-acoustic transmitter, the eel–lamprey acoustic transmitter (ELAT), in a controlled laboratory environment.

Results

The 61-day survival of our tagged subjects was 71%, within the range reported in similar studies of juvenile lampreys. However, survival was significantly lower in the tagged animals (vs control), with no effect statistically attributable to measures of animal length, mass, condition, or population of origin (Great Lakes vs. Atlantic drainage). Mortality in tagged fish was concentrated in the first four days post-surgery, suggesting injury from the surgical process. An unusually long recovery time from anesthesia may have contributed to the increased mortality. In a simple burst swim assay, tagged animals swam significantly slower (− 22.5%) than untagged animals, but were not significantly different in endurance swim tests. A composite wound healing score at day four was a significant predictor of maximum burst swim speed at day 20, and wound condition was related to animal mass, but not length, at the time of tagging.

Conclusions

Impairments to survival and swim performance of juvenile sea lamprey implanted with the ELAT transmitter were within currently reported ranges for telemetry studies with small, difficult to observe fishes. Our results could be improved with more refined anesthesia and surgical techniques. The ability to track migratory movements of imperiled and pest populations of parasitic lampreys will improve our ability to estimate vital rates that underlie recruitment to the adult population (growth, survival) and to investigate the environmental factors that regulate the timing and rates of movement, in wild populations.
POD-Galerkin reduced order models and physics-informed neural networks for solving inverse problems for the Navier–Stokes equations
Authors: Hijazi Saddam , Freitag Melina , Landwehr Niels
Published: March 2023

We present a Reduced Order Model (ROM) which exploits recent developments in Physics Informed Neural Networks (PINNs) for solving inverse problems for the Navier–Stokes equations (NSE). In the proposed approach, the presence of simulated data for the fluid dynamics fields is assumed. A POD-Galerkin ROM is then constructed by applying POD on the snapshots matrices of the fluid fields and performing a Galerkin projection of the NSE (or the modified equations in case of turbulence modeling) onto the POD reduced basis. A POD-Galerkin PINN ROM is then derived by introducing deep neural networks which approximate the reduced outputs with the input being time and/or parameters of the model. The neural networks incorporate the physical equations (the POD-Galerkin reduced equations) into their structure as part of the loss function. Using this approach, the reduced model is able to approximate unknown parameters such as physical constants or the boundary conditions. A demonstration of the applicability of the proposed ROM is illustrated by three cases which are the steady flow around a backward step, the flow around a circular cylinder and the unsteady turbulent flow around a surface mounted cubic obstacle.
Provider perceptions of barriers and facilitators to care in eating disorder treatment for transgender and gender diverse patients: a qualitative study
Authors: Ferrucci Katarina A. , McPhillips Emily , Lapane Kate L. , Jesdale Bill M. , Dubé Catherine E.
Published: March 2023

Background

The prevalence of eating disorders is higher in transgender and non-binary compared to cisgender people. Gender diverse people who seek eating disorder treatment often report struggling to find affirming and inclusive treatment from healthcare clinicians. We sought to understand eating disorder care clinicians’ perceptions of facilitators of and barriers to effective eating disorder treatment for transgender and gender diverse patients.

Methods

In 2022, nineteen US-based licensed mental health clinicians who specialized in eating disorder treatment participated in semi-structured interviews. We used inductive thematic analysis to identify themes around perceptions and knowledge of facilitators and barriers to care for transgender and gender diverse patients diagnosed with eating disorders.

Results

Two broad themes were identified: (1) factors affecting access to care; and (2) factors affecting care while in treatment. Within the first theme, the following subthemes were found: stigmatization, family support, financial factors, gendered clinics, scarcity of gender-competent care, and religious communities. Within the second theme, prominent subthemes included discrimination and microaggressions, provider lived experience and education, other patients and parents, institutions of higher education, family-centered care, gendered-centered care, and traditional therapeutic techniques.

Conclusion

Many barriers and facilitators have potential to be improved upon, especially those caused by clinicians’ lack of knowledge or attitudes towards gender minority patients in treatment. Future research is needed to identify how provider-driven barriers manifest and how they can be improved upon to better patient care experiences.
Effectiveness of interventions to improve employment for people released from prison: systematic review and meta-analysis
Authors: Connell Catriona , Birken Mary , Carver Hannah , Brown Tamara , Greenhalgh Jessica
Published: March 2023

Background

People released from prison experience complex health challenges in addition to challenges resettling into the community. Consequently, employment rates are low. Participating in good quality employment can support good health and is protective against future reoffending. Multiple interventions are provided to support people into employment on release. The effectiveness of interventions for improving employment outcomes has not previously been evaluated in a meta-analysis.

Aim

Our objective was to examine the effectiveness of interventions to improve employment following release from prison.

Method

We searched seven databases and three trial registries for peer reviewed randomised controlled trials (RCTs), published since 2010, that included adults and measured an employment outcome(s). We conducted meta-analysis using random effects models with sub-group and sensitivity analyses. We appraised bias risk per outcome, and incorporated this into an assessment of the certainty estimates for each outcome. A group of people with experience of imprisonment met with us throughout the project to inform our search strategy and interpretation of results.

Results

We included 12 RCTs (2,875 participants) which were all conducted in the USA. Few outcomes were of low risk of bias. Intervention participants were 2.5 times more likely to work at least one day (95% CI:1.82–3.43) and worked more days over 12 months (MD = 59.07, 95% CI:15.83–102.32) compared to controls. There was no effect on average employment status or employment at study end. There is moderate certainty in these estimates.

Conclusion

Interventions can improve some employment outcomes for people released from prison. More evidence is required to establish effective interventions for sustaining quality employment, particularly outside the USA, and which consider outcomes for different groups of people released, such as women or those with health or substance use needs.
Association between self-compassion and cyber aggression in the COVID-19 context: roles of attribution and public stigma
Authors: Wu Qinglu , Zhang Tian-Ming
Published: March 2023

Self-compassion is negatively associated with aggressive behaviors. However, the association between self-compassion and cyber aggression toward stigmatized people (e.g., people infected with COVID-19) has not been investigated in the COVID-19 context and the mechanism underlying this association remains underexplored. On the basis of emotion regulation theory and attribution theory, this study examined the indirect effects of self-compassion on cyber aggression toward people infected with COVID-19 through attribution and public stigma of COVID-19. Data were collected from 1162 Chinese college students (415 male, mean age = 21.61 years). Participants completed an online questionnaire including measurement of the key variables and basic demographic information. Results indicated that self-compassion was negatively associated with cyber aggression through the lower attribution of COVID-19 and lower public stigma of COVID-19. A sequential pathway from the attribution of COVID-19 to public stigma of COVID-19 was identified in the relationship between self-compassion and cyber aggression. Our findings are consistent with emotion regulation theory and attribution theory, which posit that emotion regulation strategies are associated with interpersonal mistreatment through cognitive pathways. These findings suggest that emotional self-regulation strategies can be used to reduce cyber aggression toward stigmatized people by reducing attribution and public stigma in the COVID-19 context. Self-compassion improvement could be target for the interventions aiming at alleviating public stigma and interpersonal mistreatment toward stigmatized people.
Evaluating programs for young people with a family member with mental health challenges: protocol for a mixed methods, longitudinal, collaborative evaluation
Authors: Reupert Andrea , Freeman Nerelie , Hine Rochelle , Lea Sophie , Nandakumar Nivedita , O’Grady Charlotte , Patlamazoglou Lefteris , Pettenuzzo Laura , Foster Kim
Published: March 2023

Background

Young people with a sibling or parent who experiences mental health challenges have their own support needs. Most programs designed for this population lack a strong evidence base, and the involvement of young people in the development and evaluation of programs designed to support them is unclear or lacking.

Methods

This paper describes a protocol for a mixed methods, longitudinal, collaborative evaluation of a suite of programs delivered by The Satellite Foundation, a not-for-profit organisation for young people (5–25 years) who have a family member with mental health challenges. Young people’s lived experience and knowledge will guide the research approach. Institutional ethics approval has been obtained. Over a three year period, approximately 150 young people will be surveyed online on various wellbeing outcome measures, prior to, six and twelve months following program participation with data analysed using multi-level modelling. Groups of young people will be interviewed after participating in different Satellite programs each year. An additional group of young people will be interviewed individually over time. Transcripts will be analysed using thematic analysis. Young people’s creative artworks on their experiences will be included as part of the evaluation data.

Discussion

This novel, collaborative evaluation will provide vital evidence on young people’s experiences and outcomes during their time with Satellite. Findings will be used to inform future program development and policy. The approach used here may guide other researchers engaging in collaborative evaluations with community organisations.
Effect of Chinese young children’s epidemic cognition on their coping behavior: mediating role of emotion
Authors: Wei Yonggang , Shi Yu , Zhou Qiao , Zhu Ruihan , Wang Lu
Published: March 2023

Introduction

Young children’s epidemic awareness and risk prevention about public health emergencies such as the COVID-19 are issues of great importance deserving research.

Objective

To explore the effect of young children’s epidemic cognition on their coping behavior, and the mediating role of emotion.

Method

An online anonymous survey was administrated on 2221 Chinese parents of young children aged three to six during the COVID-19 overwhelming period.

Results

(1) The epidemic cognition (M = 4.17, SD = 0.73), the coping behavior (M = 4.16, SD = 0.65), and the emotion (M = 3.99, SD = 0.81) were at a relatively high level. (2) Young children’s epidemic cognition significantly predicted their coping behavior (β = 0.71, t = 45.29, P < 0.001). The positive prediction effect of epidemic cognition on young children’s emotion was significant (β = 0.19, t = 8.56, P < 0.001), and emotion had a significant positive predictive effect on young children’s coping behavior (β = 0.20, t = 4.89, P < 0.001).

Conclusion

Young children’s epidemic cognition can significantly predict their coping behavior, and emotion plays a significant mediating role in their relation. It is necessary for practitioners to optimize the contents and methods of epidemic education on young children.
Changing positive and negative affects through music experiences: a study with university students
Authors: Blasco-Magraner José Salvador , Bernabé-Valero Gloria , Marín-Liébana Pablo , Botella-Nicolás Ana María
Published: March 2023

Background

Currently, there are few empirical studies that demonstrate the effects of music on specific emotions, especially in the educational context. For this reason, this study was carried out to examine the impact of music to identify affective changes after exposure to three musical stimuli.

Methods

The participants were 71 university students engaged in a music education course and none of them were musicians. Changes in the affective state of non-musical student teachers were studied after listening to three pieces of music. An inter-subject repeated measures ANOVA test was carried out using the Positive and Negative Affect Schedule (PANAS) to measure their affective state.

Results

The results revealed that: (i) the three musical experiences were beneficial in increasing positive affects and reducing negative affects, with significant differences between the interaction of Music Experiences × Moment (pre-post); (ii) listening to Mahler’s sad fifth symphony reduced more negative affects than the other experimental conditions; (iii) performing the blues had the highest positive effects.

Conclusions

These findings provide applied keys aspects for music education and research, as they show empirical evidence on how music can modify specific affects of personal experience.
RNA demethylase ALKBH5 promotes tumorigenesis of t (8;21) acute myeloid leukemia via ITPA m6A modification
Authors: Li Ran , Wu Xiaolu , Xue Kai , Feng Dandan , Li Jianyong , Li Junmin
Published: March 2023

Background

Although t (8;21) is in fact considered a good risk acute myeloid leukemia (AML), only 60% of the patients live beyond 5 years after diagnosis. Studies have shown that RNA demethylase ALKBH5 promotes leukemogenesis. However, the molecular mechanism and clinical significance of ALKBH5 in t (8;21) AML have not been elucidated.

Methods

The expression of ALKBH5 was assessed in t (8;21) AML patients via qRT-PCR and western blot. The proliferative activity of these cells was examined through CCK-8 or colony-forming assays, while flow cytometry approaches were used to examine apoptotic cell rates. The in vivo role of ALKBH5 promoting leukemogenesis was assessed using t (8;21) murine model, CDX, and PDX models. RNA sequencing, m6A RNA methylation assay, RNA immunoprecipitation, and luciferase reporter assay were used to explore the molecular mechanism of ALKBH5 in t (8;21) AML.

Results

ALKBH5 is highly expressed in t (8;21) AML patients. Silencing ALKBH5 suppresses the proliferation and promotes the apoptosis of patient-derived AML cells and Kasumi-1 cells. With integrated transcriptome analysis and wet-lab confirmation, we found that ITPA is a functionally important target of ALKBH5. Mechanistically, ALKBH5 demethylates ITPA mRNA and increases its mRNA stability, leading to enhanced ITPA expression. Furthermore, transcription factor TCF15, specifically expressed in leukemia stem/initiating cells (LSCs/LICs), is responsible for the dysregulated expression of ALKBH5 in t (8;21) AML.

Conclusion

Our work uncovers a critical function for the TCF15/ALKBH5/ITPA axis and provides insights into the vital roles of m6A methylation in t (8;21) AML.
BCL7A is silenced by hypermethylation to promote acute myeloid leukemia
Authors: Patiño-Mercau Juan Rodrigo , Baliñas-Gavira Carlos , Andrades Alvaro , Benitez-Cantos Maria S. , Rot Ana Ercegovič , Rodriguez Maria Isabel , Álvarez-Pérez Juan Carlos , Cuadros Marta , Medina Pedro P.
Published: March 2023

Background

Recent massive sequencing studies have revealed that SWI/SNF complexes are among the most frequently altered functional entities in solid tumors. However, the role of SWI/SNF in acute myeloid leukemia is poorly understood. To date, SWI/SNF complexes are thought to be oncogenic in AML or, at least, necessary to support leukemogenesis. However, mutation patterns in SWI/SNF genes in AML are consistent with a tumor suppressor role. Here, we study the SWI/SNF subunit BCL7A, which has been found to be recurrently mutated in lymphomas, but whose role in acute myeloid malignancies is currently unknown.

Methods

Data mining and bioinformatic approaches were used to study the mutational status of BCL7A and the correlation between BCL7A expression and promoter hypermethylation. Methylation-specific PCR, bisulfite sequencing, and 5-aza-2'-deoxycytidine treatment assays were used to determine if BCL7A expression was silenced due to promoter hypermethylation. Cell competition assays after BCL7A expression restoration were used to assess the role of BCL7A in AML cell line models. Differential expression analysis was performed to determine pathways and genes altered after BCL7A expression restoration. To establish the role of BCL7A in tumor development in vivo, tumor growth was compared between BCL7A-expressing and non-expressing mouse xenografts using in vivo fluorescence imaging.

Results

BCL7A expression was inversely correlated with promoter methylation in three external cohorts: TCGA-LAML (N = 160), TARGET-AML (N = 188), and Glass et al. (2017) (N = 111). The AML-derived cell line NB4 silenced the BCL7A expression via promoter hypermethylation. Ectopic BCL7A expression in AML cells decreased their competitive ability compared to control cells. Additionally, restoration of BCL7A expression reduced tumor growth in an NB4 mouse xenograft model. Also, differential expression analysis found that BCL7A restoration altered cell cycle pathways and modified significantly the expression of genes like HMGCS1, H1-0, and IRF7 which can help to explain its tumor suppressor role in AML.

Conclusions

BCL7A expression is silenced in AML by promoter methylation. In addition, restoration of BCL7A expression exerts tumor suppressor activity in AML cell lines and xenograft models.
Ballooned neurons in semi-recent severe traumatic brain injury
Authors: Michaud Jean , Plu Isabelle , Parai Jacqueline , Bourgault André , Tanguay Caroline , Seilhean Danielle , Woulfe John
Published: March 2023

Traumatic brain injury (TBI) is now recognized as an insult triggering a dynamic process of degeneration and regeneration potentially evolving for years with chronic traumatic encephalopathy (CTE) as one major complication. Neurons are at the center of the clinical manifestations, both in the acute and chronic phases. Yet, in the acute phase, conventional neuropathology detects abnormalities predominantly in the axons, if one excludes contusions and hypoxic ischemic changes. We report the finding of ballooned neurons, predominantly in the anterior cingulum, in three patients who sustained severe TBI and remained comatose until death, 2 ½ weeks to 2 ½ months after the traumatic impact. All three cases showed severe changes of traumatic diffuse axonal injury in line with acceleration/deceleration forces. The immunohistochemical profile of the ballooned neurons was like that described in neurodegenerative disorders like tauopathies which were used as controls. The presence of αB-crystallin positive ballooned neurons in the brain of patients who sustained severe craniocerebral trauma and remained comatose thereafter has never been reported. We postulate that the co-occurrence of diffuse axonal injury in the cerebral white matter and ballooned neurons in the cortex is mechanistically reminiscent of the phenomenon of chromatolysis. Experimental trauma models with neuronal chromatolytic features emphasized the presence of proximal axonal defects. In our three cases, proximal swellings were documented in the cortex and subcortical white matter. This limited retrospective report should trigger further studies in order to better establish, in recent/semi-recent TBI, the frequency of this neuronal finding and its relationship with the proximal axonal defects.
Roles of neuropathology-associated reactive astrocytes: a systematic review
Authors: Lawrence Jill M. , Schardien Kayla , Wigdahl Brian , Nonnemacher Michael R.
Published: March 2023

In the contexts of aging, injury, or neuroinflammation, activated microglia signaling with TNF-α, IL-1α, and C1q induces a neurotoxic astrocytic phenotype, classified as A1, A1-like, or neuroinflammatory reactive astrocytes. In contrast to typical astrocytes, which promote neuronal survival, support synapses, and maintain blood–brain barrier integrity, these reactive astrocytes downregulate supportive functions and begin to secrete neurotoxic factors, complement components like C3, and chemokines like CXCL10, which may facilitate recruitment of immune cells across the BBB into the CNS. The proportion of pro-inflammatory reactive astrocytes increases with age through associated microglia activation, and these pro-inflammatory reactive astrocytes are particularly abundant in neurodegenerative disorders. As the identification of astrocyte phenotypes progress, their molecular and cellular effects are characterized in a growing array of neuropathologies.
Exceptionally rare IDH1-mutant adult medulloblastoma with concurrent GNAS mutation revealed by in vivo magnetic resonance spectroscopy and deep sequencing
Authors: Liserre Roberto , Branzoli Francesca , Pagani Francesca , Gryzik Magdalena , Cominelli Manuela , Miele Evelina , Marjańska Małgorzata , Doglietto Francesco , Poliani Pietro Luigi
Published: March 2023

Medulloblastoma (MB) is the most common malignant brain tumor occurring in childhood and rarely found in adults. Based on transcriptome profile, MB are currently classified into four major molecular groups reflecting a considerable biological heterogeneity: WNT-activated, SHH-activated, group 3 and group 4. Recently, DNA methylation profiling allowed the identification of additional subgroups within the four major molecular groups associated with different clinic-pathological and molecular features. Isocitrate dehydrogenase-1 and 2 (IDH1 and IDH2) mutations have been described in several tumors, including gliomas, while in MB are rarely reported and not routinely investigated. By means of magnetic resonance spectroscopy (MRS), we unequivocally assessed the presence the oncometabolite D-2-hydroxyglutarate (2HG), a marker of IDH1 and IDH2 mutations, in a case of adult MB. Immunophenotypical work-up and methylation profiling assigned the diagnosis of MB, subclass SHH-A, and molecular testing revealed the presence of the non-canonical somatic IDH1(p.R132C) mutation and an additional GNAS mutation, also rarely described in MB. To the best of our knowledge, this is the first reported case of MB simultaneously harboring both mutations. Of note, tumor exhibited a heterogeneous phenotype with a tumor component displaying glial differentiation, with robust GFAP expression, and a component with conventional MB features and selective presence of GNAS mutation, suggesting co-existence of two different major tumor subclones. These findings drew attention to the need for a deeper genetic characterization of MB, in order to get insights into their biology and improve stratification and clinical management of the patients. Moreover, our results underlined the importance of performing MRS for the identification of IDH mutations in non-glial tumors. The use of throughput molecular profiling analysis and advanced medical imaging will certainly increase the frequency with which tumor entities with rare molecular alterations will be identified. Whether these findings have any specific therapeutic implications or prognostic relevance requires further investigations.
Clinical and functional characterization of a long survivor congenital titinopathy patient with a novel metatranscript-only titin variant
Authors: Cardone Nastasia , Moula Melissa , Baelde Rianne J. , Biquand Ariane , Villanova Marcello , Metay Corinne , Fiorillo Chiara , Baratto Serena , Merlini Luciano , Sabatelli Patrizia , Romero Norma B. , Relaix Frederic , Authier François Jérôme , Taglietti Valentina , Savarese Marco , de Winter Josine , Ottenheijm Coen , Richard Isabelle , Malfatti Edoardo
Published: March 2023

Congenital titinopathies are an emerging group of a potentially severe form of congenital myopathies caused by biallelic mutations in titin, encoding the largest existing human protein involved in the formation and stability of sarcomeres. In this study we describe a patient with a congenital myopathy characterized by multiple contractures, a rigid spine, non progressive muscular weakness, and a novel homozygous TTN pathogenic variant in a metatranscript-only exon: the c.36400A > T, p.Lys12134*. Muscle biopsies showed increased internalized nuclei, variability in fiber size, mild fibrosis, type 1 fiber predominance, and a slight increase in the number of satellite cells. RNA studies revealed the retention of intron 170 and 171 in the open reading frame, and immunoflourescence and western blot studies, a normal titin content. Single fiber functional studies showed a slight decrease in absolute maximal force and a cross-sectional area with no decreases in tension, suggesting that weakness is not sarcomere-based but due to hypotrophy. Passive properties of single fibers were not affected, but the observed increased calcium sensitivity of force generation might contribute to the contractural phenotype and rigid spine of the patient. Our findings provide evidence for a pathogenic, causative role of a metatranscript-only titin variant in a long survivor congenital titinopathy patient with distal arthrogryposis and rigid spine.
Loss of MBNL1-mediated retrograde BDNF signaling in the myotonic dystrophy brain
Authors: Wang Pei-Ying , Kuo Ting-Yu , Wang Lee-Hsin , Liang Wen-Hsing , Wang Guey-Shin
Published: March 2023

Reduced brain volume including atrophy in grey and white matter is commonly seen in myotonic dystrophy type 1 (DM1). DM1 is caused by an expansion of CTG trinucleotide repeats in the 3’ untranslated region (UTR) of the Dystrophia Myotonica Protein Kinase (DMPK) gene. MutantDMPKmRNA containing expanded CUG RNA (DMPK-CUGexp) sequesters cytoplasmic MBNL1, resulting in morphological impairment. HowDMPK-CUGexpand loss of MBNL1 cause histopathological phenotypes in the DM1 brain remains elusive. Here, we show that BDNF-TrkB retrograde transport is impaired in neurons expressingDMPK-CUGexpdue to loss of cytoplasmic MBNL1 function. We reveal that mature BDNF protein levels are reduced in the brain of the DM1 mouse model EpA960/CaMKII-Cre. Exogenous BDNF treatment did not rescue impaired neurite outgrowth in neurons expressingDMPK-CUGexp, whereas overexpression of the cytoplasmic MBNL1 isoform inDMPK-CUGexp-expressing neurons improved their responsiveness to exogenous BDNF. We identify dynein light chain LC8-type 2, DYNLL2, as an MBNL1-interacting protein and demonstrate that their interaction is RNA-independent. Using time-lapse imaging, we show that overexpressed MBNL1 and DYNLL2 move along axonal processes together and that MBNL1-knockdown impairs the motility of mCherry-tagged DYNLL2, resulting in a reduced percentage of retrograde DYNLL2 movement. Examination of the distribution of DYNLL2 and activated phospho-TrkB (pTrkB) receptor in EpA960/CaMKII-Cre brains revealed an increase in the postsynaptic membrane fraction (LP1), indicating impaired retrograde transport. Finally, our neuropathological analysis of postmortem DM1 tissue reveals that reduced cytoplasmic MBNL1 expression is associated with an increase in DYNLL2 and activated pTrkB receptor levels in the synaptosomal fraction. Together, our results support that impaired MBNL1-mediated retrograde BDNF-TrkB signaling may contribute to the histopathological phenotypes of DM1.