bluuebunny/crossref_metadata_2025 huggingface dataset:
Commonly used genomic arrays may lose information due to imperfect coverage of discovered variants for autism spectrum disorder
Authors: Yao Michael , Daniels Jason , Grosvenor Luke , Morrill Valerie , Feinberg Jason I. , Bakulski Kelly M. , Piven Joseph , Hazlett Heather C. , Shen Mark D. , Newschaffer Craig , Lyall Kristen , Schmidt Rebecca J. , Hertz-Picciotto Irva , Croen Lisa A. , Fallin M. Daniele , Ladd-Acosta Christine , Volk Heather , Benke Kelly
Published: September 2024

Background

Common genetic variation has been shown to account for a large proportion of ASD heritability. Polygenic scores generated for autism spectrum disorder (ASD-PGS) using the most recent discovery data, however, explain less variance than expected, despite reporting significant associations with ASD and other ASD-related traits. Here, we investigate the extent to which information loss on the target study genome-wide microarray weakens the predictive power of the ASD-PGS.

Methods

We studied genotype data from three cohorts of individuals with high familial liability for ASD: The Early Autism Risk Longitudinal Investigation (EARLI), Markers of Autism Risk in Babies-Learning Early Signs (MARBLES), and the Infant Brain Imaging Study (IBIS), and one population-based sample, Study to Explore Early Development Phase I (SEED I). Individuals were genotyped on different microarrays ranging from 1 to 5 million sites. Coverage of the top 88 genome-wide suggestive variants implicated in the discovery was evaluated in all four studies before quality control (QC), after QC, and after imputation. We then created a novel method to assess coverage on the resulting ASD-PGS by correlating a PGS informed by a comprehensive list of variants to a PGS informed with only the available variants.

Results

Prior to imputations, None of the four cohorts directly or indirectly covered all 88 variants among the measured genotype data. After imputation, the two cohorts genotyped on 5-million arrays reached full coverage. Analysis of our novel metric showed generally high genome-wide coverage across all four studies, but a greater number of SNPs informing the ASD-PGS did not result in improved coverage according to our metric.

Limitations.

The studies we analyzed contained modest sample sizes. Our analyses included microarrays with more than 1-million sites, so smaller arrays such as Global Diversity and the PsychArray were not included. Our PGS metric for ASD is only generalizable to samples of European ancestries, though the coverage metric can be computed for traits that have sufficiently large-sized discovery findings in other ancestries.

Conclusions

We show that commonly used genotyping microarrays have incomplete coverage for common ASD variants, and imputation cannot always recover lost information. Our novel metric provides an intuitive approach to reporting information loss in PGS and an alternative to reporting the total number of SNPs included in the PGS. While applied only to ASD here, this metric can easily be used with other traits.
Genetic parameters and genotype-by-environment interaction estimates for growth and feed efficiency related traits in Chinook salmon, Oncorhynchus tshawytscha, reared under low and moderate flow regimes
Authors: Prescott Leteisha A. , Scholtens Megan R. , Walker Seumas P. , Clarke Shannon M. , Dodds Ken G. , Miller Matthew R. , Semmens Jayson M. , Carter Chris G. , Symonds Jane E.
Published: September 2024

Background

A genotype-by-environment (G × E) interaction is defined as genotypes responding differently to different environments. In salmonids, G × E interactions can occur in different rearing conditions, including changes in salinity or temperature. However, water flow, an important variable that can influence metabolism, has yet to be considered for potential G × E interactions, although water flows differ across production stages. The salmonid industry is now manipulating flow in tanks to improve welfare and production performance, and expanding sea pen farming offshore, where flow dynamics are substantially greater. Therefore, there is a need to test whether G × E interactions occur under low and higher flow regimes to determine if industry should consider modifying their performance evaluation and selection criteria to account for different flow environments. Here, we used genotype-by-sequencing to create a genomic-relationship matrix of 37 Chinook salmon, Oncorhynchus tshawytscha, families to assess possible G × E interactions for production performance under two flow environments: a low flow regime (0.3 body lengths per second; bl s−1) and a moderate flow regime (0.8 bl s−1).

Results

Genetic correlations for the same production performance trait between flow regimes suggest there is minimal evidence of a G × E interaction between the low and moderate flow regimes tested in this study, for Chinook salmon reared from 82.9 ± 16.8 g ($${\overline{\text{x}}}$$

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 ± s.d.) to 583.2 ± 117.1 g ($${\overline{\text{x}}}$$

x
¯

 ± s.d.). Estimates of genetic and phenotypic correlations between traits did not reveal any unfavorable trait correlations for size- (weight and condition factor) and growth-related traits, regardless of the flow regime, but did suggest measuring feed intake would be the preferred approach to improve feed efficiency because of the strong correlations between feed intake and feed efficiency, consistent with previous studies.

Conclusion

This new information suggests that Chinook salmon families do not need to be selected separately for performance across different flow regimes. However, further studies are needed to confirm this across a wider range of fish sizes and flows. This information is key for breeding programs to determine if separate evaluation groups are required for different flow regimes that are used for production (e.g., hatchery, post smolt recirculating aquaculture system, or offshore).
Mild cognitive impairment prediction based on multi-stream convolutional neural networks
Authors: Lee Chien-Cheng , Chau Hong-Han , Wang Hsiao-Lun , Chuang Yi-Fang , Chau Yawgeng
Published: September 2024

Background

Mild cognitive impairment (MCI) is the transition stage between the cognitive decline expected in normal aging and more severe cognitive decline such as dementia. The early diagnosis of MCI plays an important role in human healthcare. Current methods of MCI detection include cognitive tests to screen for executive function impairments, possibly followed by neuroimaging tests. However, these methods are expensive and time-consuming. Several studies have demonstrated that MCI and dementia can be detected by machine learning technologies from different modality data. This study proposes a multi-stream convolutional neural network (MCNN) model to predict MCI from face videos.

Results

The total effective data are 48 facial videos from 45 participants, including 35 videos from normal cognitive participants and 13 videos from MCI participants. The videos are divided into several segments. Then, the MCNN captures the latent facial spatial features and facial dynamic features of each segment and classifies the segment as MCI or normal. Finally, the aggregation stage produces the final detection results of the input video. We evaluate 27 MCNN model combinations including three ResNet architectures, three optimizers, and three activation functions. The experimental results showed that the ResNet-50 backbone with Swish activation function and Ranger optimizer produces the best results with an F1-score of 89% at the segment level. However, the ResNet-18 backbone with Swish and Ranger achieves the F1-score of 100% at the participant level.

Conclusions

This study presents an efficient new method for predicting MCI from facial videos. Studies have shown that MCI can be detected from facial videos, and facial data can be used as a biomarker for MCI. This approach is very promising for developing accurate models for screening MCI through facial data. It demonstrates that automated, non-invasive, and inexpensive MCI screening methods are feasible and do not require highly subjective paper-and-pencil questionnaires. Evaluation of 27 model combinations also found that ResNet-50 with Swish is more stable for different optimizers. Such results provide directions for hyperparameter tuning to further improve MCI predictions.
β-glucans, SAM, and GSH fluctuations in barley anther tissue culture conditions affect regenerants’ DNA methylation and GPRE
Authors: Orłowska Renata , Dynkowska Wioletta Monika , Niedziela Agnieszka , Zebrowski Jacek , Zimny Janusz , Androsiuk Piotr , Bednarek Piotr Tomasz
Published: September 2024

Background

Microspore embryogenesis is a process that produces doubled haploids in tissue culture environments and is widely used in cereal plants. The efficient production of green regenerants requires stresses that could be sensed at the level of glycolysis, followed by the Krebs cycle and electron transfer chain. The latter can be affected by Cu(II) ion concentration in the induction media acting as cofactors of biochemical reactions, indirectly influencing the production of glutathione (GSH) and S-adenosyl-L-methionine (SAM) and thereby affecting epigenetic mechanisms involving DNA methylation (demethylation—DM, de novo methylation—DNM). The conclusions mentioned were acquired from research on triticale regenerants, but there is no similar research on barley. In this way, the study looks at how DNM, DM, Cu(II), SAM, GSH, and β-glucan affect the ability of green plant regeneration efficiency (GPRE).

Results

The experiment involved spring barley regenerants obtained through anther culture. Nine variants (trials) of induction media were created by adding copper (CuSO4: 0.1; 5; 10 µM) and silver salts (AgNO3: 0; 10; 60 µM), with varying incubation times for the anthers (21, 28, and 35 days). Changes in DNA methylation were estimated using the DArTseqMet molecular marker method, which also detects cytosine methylation.

Phenotype variability in β-glucans, SAM and GSH induced by the nutrient treatments was assessed using tentative assignments based on the Attenuated Total Reflectance-Fourier Transform Infrared (ATR-FTIR) spectroscopy. The effectiveness of green plant regeneration ranged from 0.1 to 2.91 plants per 100 plated anthers. The level of demethylation ranged from 7.61 to 32.29, while de novo methylation reached values ranging from 6.83 to 32.27. The paper demonstrates that the samples from specific in vitro conditions (trials) formed tight groups linked to the factors contributing to the two main components responsible for 55.05% of the variance (to the first component DNM, DM, to the second component GSH, β-glucans, Cu(II), GPRE).

Conclusions

We can conclude that in vitro tissue culture conditions affect biochemical levels, DNA methylation changes, and GPRE. Increasing Cu(II) concentration in the IM impacts the metabolism and DNA methylation, elevating GPRE. Thus, changing Cu(II) concentration in the IM is fair to expect to boost GPRE.
Effect of defocus incorporated multiple segments (DIMS) spectacle lenses on myopia progression in children: a retrospective analysis in a German real-life clinical setting
Authors: Neller Birte , Neller Kai , Schwahn Hartmut , Mattern Ann-Isabel , Devenijn Machteld , Langenbucher Achim , Seitz Berthold , Kaymak Hakan
Published: September 2024

Objectives

This retrospective analysis evaluates the treatment success of “Defocus Incorporated Multiple Segments” (DIMS) spectacle lenses in a real-life clinical setting in Germany.

Materials and methods

Axial length (AL) and objective refraction of 166 eyes treated with DIMS at baseline and 12-month follow-up were analyzed. Annual AL growth rate within the range of physiological growth rate was considered a successful treatment. Myopia progression of ≥ -0.5 D/yr accounted as treatment success. Differences in percentages of treatment success of subgroups depending on baseline AL and age against treatment success of the total population were investigated.

Results

Considering all eyes, treatment success regarding AL growth and myopia progression was achieved in 46% and 65%, respectively. Male eyes with moderate AL showed treatment success in a higher proportion (73%, p < 0.01; 89%, p < 0.01); eyes with high AL showed treatment success in a lower proportion (25%, p < 0.01; 51%, n.s.). Female eyes showed the same trend but without statistical significance (moderate AL: 49%; 68%; high AL: 40%; 62%). Younger children showed treatment success in a lower proportion (male: 11%, p < 0.01; 38%, p < 0.05; female: 25%, p < 0.01; 42%, p < 0.01). Older children showed treatment success in a higher proportion (male: 60%, p < 0.05; 78% p < 0.05; female: 53%, n.s.; 77% p < 0.05).

Conclusions

Eyes with moderate baseline AL and of older children showed treatment success after 12 months of DIMS treatment. Eyes with a high baseline AL and of younger children showed treatment success in a smaller proportion, therefore combination treatment should be considered. In future studies, males and females should be assessed separately.
Health assessments of refugee minors arriving in Norway – a modified Delphi study among health professionals in primary care settings
Authors: Dangmann Cecilie , Kleppang Annette Løvheim , Leonhardt Marja
Published: September 2024

Background

Refugee minors are considered particularly vulnerable to negative health consequences from war, flight and resettlement. Offering health assessments after arrival in a host country could uncover unmet health needs and provide access to treatment. In Norway, a national guide describes these assessments, but little is known about its implementation especially for refugee minors. Thus, the aim of this study was first to explore how health assessments of refugee minors are carried out, second how health professionals perceive the needs of refugee minors and third, the competencies they perceive as necessary to meet the needs of refugee minors.

Method

A modified Delphi study in three rounds was conducted using online surveys and one focus group to collect data on the needs and resources of refugee minors, essential factors for a good and health assessment practice. Participants were 54 health professionals responsible for early health assessments of refugee minors, throughout the Norwegian municipalities, working in primary care settings. Quantitative data was analysed descriptively, and qualitative data with content analysis.

Results

Health assessments of refugee minors were predominantly conducted by public health nurses, but the organisational structures surrounding assessments varied greatly according to the size of the municipalities and to how much resources were allocated. The feeling of safety was found to be paramount to ensure a good start in a new country for refugee minors. The top four competences professionals should have, were ‘general communication skills’, a ‘health professional background’, ‘expertise in children’s health’ and ‘knowledge about the national guide’. To ensure good health services for refugee minors, improved, more comprehensive, and mandatory directives for children and young individuals was highlighted.

Conclusion

Although most refugee minors were invited and attend health assessments, one third of participating municipalities did not offer health assessments to all newcomers and the organisation and content of the assessments were diverse. Several topics, especially mental health, were postponed or not routinely addressed, contrasting with current knowledge of unmet health needs for this group. Missing documentation, practical barriers and providing general health information took time away from doing the actual assessments. The perceived needs of refugee minors were safety and stability, combined with meaningful activities, thus a coordinated effort from several services is necessary. Suggestions for improvements were more time given to assessments, better organisation and co-operation, improved competence and guidelines adjusted for age.
Internal fit and marginal adaptation of all-ceramic implant-supported hybrid abutment crowns with custom-milled screw-channels on Titanium-base: in-vitro study
Authors: Fakhr Marwa Wagih Zaky Fouad , Alansary Hesham , Hassanien Eman Ezzat Youssef
Published: September 2024

Background

Advancements in digital dentistry helped in custom-milling screw-channels in implant-supported restorations; however, the fit of these restorations is still unclear especially for contemporary computer aided designing/computer aided manufacturing (CAD/CAM) materials. This study aimed to compare the internal and marginal fit of Ultra translucent multilayered zirconia versus lithium disilicate implant-supported hybrid abutment crowns (HACs) constructed with custom-milled screw-channels on Titanium-base.

Materials and methods

A total of 24 HACs with custom-milled screw-channels were constructed from lithium disilicate (Group LDS) and Ultra translucent multilayered zirconia (Group UT) using digital workflow (n = 12). The internal and marginal gaps of HACs on their corresponding Titanium-bases were assessed using replica technique and stereomicroscope, respectively. After testing for normality, quantitative data were expressed as mean and standard deviation and compared using independent t-test at a level of significance (P ≤ 0.05).

Results

There was no statistically significant difference between Group LDS and Group UT in terms of marginal and internal fit. The internal and marginal gaps in both groups were within the accepted values reported in literature.

Conclusions

UT and LDS HACs with custom-milled screw-channels demonstrated comparable and acceptable internal fit and marginal adaptations to Ti-base, which lied within the range reported in literature.
Improving the quality of clinical training in maternal and neonatal health in undergraduate nursing students: a participatory action research
Authors: Hoseini Akramsadat Sadat , Ghasemi Fatemeh , Valizadeh Fatemeh , Nayeri Nahid Dehghan , Toulabi Tahereh , Hasanvand Shirin
Published: September 2024

Background

Improving the quality of clinical training is synonymous with accomplishing nursing education goals and improving the quality of nursing care. This study aimed to improve the quality of clinical training in Maternal and Neonatal Health (MNH) in nursing students.

Methods

This action research was conducted in two cycles from June 2017 to June 2018. The study setting was the School of Nursing and Midwifery of Lorestan University of Medical Sciences in southwest Iran. The participants were nursing students, faculty members, clinical trainers, educational managers, and teaching personnel. In the first cycle, semi-structured interviews were held with stakeholders to identify clinical problems and improvement strategies. Based on the results of these sessions, the changes needed to improve the quality of clinical training were planned and implemented. The weaknesses and strengths of the implemented changes were then identified through group discussions with the stakeholders. In the second cycle, a second plan was carried out to correct the weaknesses of the changes planned in the first cycle, and the modifications were implemented and evaluated.

Results

The main three categories extracted included an unsystematic curriculum and inadequate monitoring, inadequate resources and facilities, and the student’s lack of motivation. The measures taken for improvement included holding communication workshops, developing and internalizing logbooks, reducing the number of students in clinical training groups, using modern clinical training methods, and changing clinical evaluation methods.

Conclusion

Improving communication skills among the students, trainers, and hospital personnel and using modern clinical training methods, such as conceptual maps, triple jumps, and clinical skill centers, are the best strategies for improving clinical training in MNH nursing students.
“Economic exclusion and the health and wellbeing impacts of the oil industry in the Niger Delta region: a qualitative study of Ogoni experiences”
Authors: Nkem Augusta C. , Devine Susan , Ogaji Daprim S. , Topp Stephanie M.
Published: September 2024

Background

When managed effectively, oil wealth can drive economic development and improve wellbeing. Conversely, as has been the experience in Ogoniland in the Niger Delta, the presence of the oil industry can lead to environmental degradation and social and economic vulnerabilities with negative impacts on health and wellbeing. Few studies have explored the experiences and perceptions of these impacts among residents of host communities themselves.

Methods

This qualitative study explored Ogoni residents’ experiences and perceptions of oil-industry related economic exclusion and associated impacts on health and wellbeing. In-depth interviews with 22 participants from four Local Government Areas (LGAs) were analyzed with open (inductive) coding. Guided by constructivist philosophy, interpretation of emerging themes was informed by the concept of social exclusion which recognizes that multi-dimensional processes can deprive individuals or groups of resources, rights, goods, and services, thus limiting broader societal participation.

Results

Findings highlight the exclusionary impacts of the oil industry at the intersection of i) damaged livelihoods and family income, that increased economic vulnerability and reduced participants’ ability to meet basic needs including ability to pay for healthcare; ii) lack of progress on environmental remediation and non-transparent benefit sharing schemes that exacerbate economic displacement and contribute to ongoing exposures to air and water pollution; and iii) insufficient of investment in economic development and essential health services, limiting employment opportunities and ability to access adequate healthcare.

Conclusion

Addressing these issues requires integrated policy interventions focusing on equitable resource distribution, environmental restoration, and inclusive economic development to promote sustainable community resilience.
Caecal villi? A comparative histological and morphometric study of caecal and jejunal mucosa in adult rabbits
Authors: Gal Adrian Florin , Matei-Lațiu Maria-Cătălina , Lațiu Călin , Andrei Sanda , Rus Vasile
Published: September 2024

Background

Rabbits are herbivores with a distinctive digestive strategy that differs significantly from other caecal fermenters (e.g., horses, guinea pigs) and ruminants. In view of this, the current study aimed to highlight distinctive histological and morphometric features of the caecal mucosa in adult rabbits that accentuate its major role in digestion. The caecal and jejunal samples were harvested from five 1-year-old domestic rabbits and processed by regular paraffin-embedding histological technique followed by Goldner’s trichrome staining. A comprehensive morphological and morphometrical analysis of the jejunal mucosa vs. caecal mucosa was performed.

Results

Microscopically, as in the case of the jejunal mucosa, the caecal mucosa presents long and often branched finger-like villi covered by a simple columnar epithelium mostly made of enterocytes with a prominent microvillous brush border. Besides, the caecal villi include a lacteal along with the villous muscle. Statistically, except for villus length, all the parameters assessed in the caecal mucosa, including villus width, villus count, thickness of the brush border and enterocyte/goblet cells ratio, revealed a high grade of similarities with the jejunal villi.

Conclusions

According to the obtained results, the caecal mucosa in adult domestic rabbits includes unique features, namely caecal villi, structures infrequently presented in the large intestine of other adult mammals. Those structures once more emphasize the major role of the caecum not only in fermentation but also subliminally in local absorption. To our knowledge, this is the first reliable microanatomical and morphometric report of caecal villi in adult domestic rabbits.
Multilevel barriers to guideline implementation: a nationwide multi-professional cross-sectional study within child and adolescent psychiatry
Authors: Santesson Anna Helena Elisabeth , Holmberg Robert , Bäckström Martin , Gustafsson Peik , Perrin Sean , Jarbin Håkan
Published: September 2024

Background

Despite efforts to promote guideline use, guideline adoption is often suboptimal due to failure to identify and address relevant barriers. Barriers vary not only between guidelines but also between settings, intended users, and targeted patients. Multi-professional guidelines are often used in child and adolescent mental health services (CAMHS), making the implementation process more difficult. Despite this, there is a lack of knowledge about which barriers to consider or if barriers vary by profession. The aim of this study was to address these gaps by examining barriers to adopting a multi-professional depression guideline in the context of a nationwide implementation study.

Methods

440 CAMHS clinicians across Sweden (52%) completed the Barriers and Facilitators Assessment Instrument (BFAI) ahead of an implementation endeavour. BFAI is a widely used and validated measure of guideline implementation on four scales: Innovation, Provider, Context, and Patient. Barriers were calculated at scale and at item levels. ANOVA and chi-square tests were used to analyse differences by profession and effect sizes were calculated.

Results

Overall, clinicians were optimistic about guideline uptake, particularly about guideline characteristics and their own adoption ability. Barriers were related to the patient and the context domains, as well as to individual clinician knowledge and training. Perceptions differed across professions; psychiatrists were most, and counsellors were least positive about guideline embeddedness.

Conclusion

This large-scale quantitative study suggests that CAMHS clinicians have an overall favourable attitude towards guideline adoption but highlights the need for adaptations to certain patient groups. Strategies to improve guideline use should primarily address these patient issues while securing proper support to the implementation. Implementation efforts, particularly those targeting staff knowledge, training, and involvement, may benefit from being tailored to different professional needs. These findings may inform implementation projects in CAMHS and future research.
“I’m trying to take the lead from my child”: experiences Parenting Young Nonbinary Children
Authors: Sweder Noah , Garcia Lucinda , Salinas-Quiroz Fernando
Published: September 2024

Background

While research has emphasized the importance of parental support for LGBTQIA + youth wellbeing, there remains limited understanding of parental experiences with nonbinary children, particularly those prepubescent. This study aimed to explore how parents of nonbinary children ages 5–8 learn to support their child’s identity, examining initial reactions, emotional processes, supportive behaviors, societal responses, and associated challenges and rewards.

Methods

A qualitative study was conducted using Reflexive Thematic Analysis (RTA) within a framework of ontological relativism and epistemological constructivism. Nine parents of nonbinary children aged 5–8 from the Northeastern United States participated in semi-structured interviews lasting 60–80 min. Questions explored various aspects of parenting nonbinary children, including the child’s gender identity, parental feelings, experiences sharing the child’s identity, and challenges and rewards of raising a gender-diverse child. The research team, comprising individuals who identify as trans, genderqueer, and nonbinary, employed collaborative coding and thematic development.

Results

Four main themes were constructed: (1) Parents hear and support their child’s nonbinary identity, this theme highlights immediate acceptance and efforts parents make to affirm their child’s gender; (2) Parents learn about ways cisnormative society harms their child, here, parents recognize the societal pressures and barriers their children face; (3) Parents take significant and proactive steps to affirm their child, this theme documents the actions parents take to support their child in environments that invalidate their identity; and (4) Gender is just one aspect of who my child is, this theme reflects on parental insights of gender as just one part of their child’s overall personhood.

Conclusions

This study provides insights into the experiences of parents supporting young nonbinary children, emphasizing the importance of affirming expressed identity, the parent-child relationship, and proactive support in navigating cisnormative societal structures. Findings highlight the transformative experience of parenting nonbinary children, with parents often challenging their own preconceptions of gender and coming to more nuanced understandings. These results can inform supportive interventions and policies for nonbinary children and their families, and we hope to contribute to a growing body of research that shifts narratives towards joy, resilience, and community in trans and nonbinary experiences.
Design considerations for Factorial Adaptive Multi-Arm Multi-Stage (FAST) clinical trials
Authors: Beall Jonathan , Elm Jordan , Semler Matthew W. , Wang Li , Rice Todd , Kamel Hooman , Mack William , Mistry Akshitkumar M.
Published: September 2024

Background

Multi-Arm, Multi-Stage (MAMS) clinical trial designs allow for multiple therapies to be compared across a spectrum of clinical trial phases. MAMS designs fall under several overarching design groups, including adaptive designs (AD) and multi-arm (MA) designs. Factorial clinical trials designs represent a combination of factorial and MAMS trial designs and can provide increased efficiency relative to fixed, traditional designs. We explore design choices associated with Factorial Adaptive Multi-Arm Multi-Stage (FAST) designs, which represent the combination of factorial and MAMS designs.

Methods

Simulation studies were conducted to assess the impact of the type of analyses, the timing of analyses, and the effect size observed across multiple outcomes on trial operating characteristics for a FAST design. Given multiple outcomes types assessed within the hypothetical trial, the primary analysis approach for each assessment varied depending on data type.

Results

The simulation studies demonstrate that the proposed class of FAST trial designs can offer a framework to potentially provide improvements relative to other trial designs, such as a MAMS or factorial trial. Further, we note that the design implementation decisions, such as the timing and type of analyses conducted throughout trial, can have a great impact on trial operating characteristics.

Conclusions

Motivated by a trial currently under design, our work shows that the FAST category of trial can potentially offer benefits similar to both MAMS and factorial designs; however, the chosen design aspects which can be included in a FAST trial need to be thoroughly explored during the planning phase.
Factors related to the return to work of head and neck cancer patients diagnosed between 2004–2011 in Belgium: a multivariate Fine-Gray regression model analysis
Authors: Van den Broecke Maxim , de Jong Sarah , Vanthomme Katrien , Mbengi Régine Kiasuwa , Vanroelen Christophe
Published: September 2024

Background

This study aims to identify the key factors that underlie the return to work (RTW) of head and neck cancer (HNC) patients in Belgium.

Methods

We used data from the EMPCAN database linking data from the Belgian Cancer Registry and the Crossroads Bank for Social Security. We selected HNC patients aged 18–60 at diagnosis who became inactive on the labour market during the follow-up time observed (n = 398). Fine-Gray regression models were used to examine associations between clinical, socio-demographical and work-related factors and RTW over a follow-up of almost 8 years (2004–2011).

Results

The overall RTW was 21.6%. Stage IV at diagnosis and the use of chemoradiation were associated with a decreased RTW probability but this effect was attenuated by age-adjusted analyses. Multivariate analysis shows that the probability of RTW decreases with age and depends on the household composition. Patients who live alone (SHR 2.2, 95% CI 1.0 – 4.5) and patients who live with another adult and child(ren) (SHR 2.1, 95% CI 1.1 – 4.0) are more likely to RTW than patients who live with another adult without children.

Conclusions

The cumulative incidence of RTW in HNC patients is associated with age and household composition but not with treatment modalities or stage. In future research, this model could be applied to larger cancer patient groups for more accurate estimations. These insights are of importance to better support patients and for informing tailored policy measures which should take into account the sociodemographic profile of HNC patients to tackle societal and health-related inequities and burden of work inactivity.
TwinF interface inhibitor FP802 prevents retinal ganglion cell loss in a mouse model of amyotrophic lateral sclerosis
Authors: Wang Yu Meng , Yan Jing , Williams Sarah K. , Fairless Richard , Bading Hilmar
Published: September 2024

Motor neuron loss is well recognized in amyotrophic lateral sclerosis (ALS), but research on retinal ganglion cells (RGCs) is limited. Ocular symptoms are generally not considered classic ALS symptoms, although RGCs and spinal motor neurons share certain cell pathologies, including hallmark signs of glutamate neurotoxicity, which may be triggered by activation of extrasynaptic NMDA receptors (NMDARs). To explore potential novel strategies to prevent ALS-associated death of RGCs, we utilized inhibition of the TwinF interface, a new pharmacological principle that detoxifies extrasynaptic NMDARs by disrupting the NMDAR/TRPM4 death signaling complex. Using the ALS mouse model SOD1G93A, we found that the small molecule TwinF interface inhibitor FP802 prevents the loss of RGCs, improves pattern electroretinogram (pERG) performance, increases the retinal expression of Bdnf, and restores the retinal expression of the immediate early genes, Inhibin beta A and Npas4. Thus, FP802 not only prevents, as recently described, death of spinal motor neurons in SOD1G93A mice, but it also mitigates ALS-associated retinal damage. TwinF interface inhibitors have great potential for alleviating neuro-ophthalmologic symptoms in ALS patients and offer a promising new avenue for therapeutic intervention.
Recurrent partial resetting of quartz OSL signal by earthquakes: a thermochronological study on fault gouges from the Atotsugawa Fault, Japan
Authors: Tsukamoto Sumiko , Guralnik Benny , Prince Erick , Oohashi Kiyokazu , Otsubo Makoto
Published: September 2024

Optically stimulated luminescence (OSL) dating utilises the detection of trapped charge in minerals, and has an ultralow closure temperature. There is the potential for direct dating of fault movement using fault gouges, because frictional heating caused by large earthquakes can reduce the OSL signal intensity of minerals within gouges. In this study, we conducted quartz OSL dating on four fault gouge and breccia samples from a surface outcrop of the Atotsugawa Fault, one of the most active dextral strike-slip faults in central Japan, where the last large earthquake occurred in AD1858, with an estimated magnitude of 7. The natural OSL signal intensity of fine-grained quartz was clearly below the signal saturation level, with the fraction of saturation (n/N) between 0.30 ± 0.02 and 0.39 ± 0.03, indicating there was signal resetting by past earthquakes. However, the apparent OSL ages ranged from 22 ± 1 to 72 ± 4 ka, two orders of magnitude older than the age of the last earthquake. To explain the significant age overestimation, we measured the thermal stability of the OSL signal, and used a thermal model with punctuated episodic losses to constrain the average shear heating temperature experienced during an individual faulting event. For an independently known recurrence interval of 2.5 ka and a presumed shear heating duration of 1 s, the observed n/N and the measured thermal stability of the OSL signals correspond to a resetting temperature of ~ 300 °C during a single earthquake event.

Graphical Abstract
Neuropsychiatric manifestations of hospitalized patients with coronavirus disease 2019 during the second wave in Egypt
Authors: Nagy Nahla , Fayez Fiby , Hashem Reem ElSayed , Antaky Marco , Rabie Eman. S.
Published: September 2024

Background

Studies suggested that COVID-19 virus causes neurological and psychiatric manifestations with different mechanisms. However, prevalence of neurological and psychiatric manifestations among COVID-19 patients varies across studies from 18.1%: 82.3%. The objective of this study was to determine neuropsychiatric manifestations in a sample of Egyptian COVID-19 hospitalized patients during the second wave of the pandemic and to detect factors affecting neurological and psychiatric prevalence. This cross-sectional study was conducted at Ain Shams university isolation hospitals and included 110 hospitalized COVID-19 patients, over a 2-month period from June 2021 to August 2021. Patients underwent a careful history taking, full neurological examination including Mini-Mental State Examination, the Structured Clinical Interview for DSM-IV (SCID I), COVID-19 severity criteria. Any available imaging and laboratory tests were recorded.

Results

83 (75.5%) patients had neurological manifestations. The most common neurological manifestations were headache (50.9%), hypogeusia (24.5%), hyposmia, paresthesia (23.6% each) and coma (15.5%). After exclusion of 17 patients who could not be examined by Mini-Mental State Examination, psychiatric manifestations were seen in 56 patients (61.5%) out of the remaining 91 patients. The most prevalent psychiatric disorders were delirium (30.8%), depression (19%), and adjustment disorder (17.5%). Moreover, hypertension, COVID-19 severity, place of admission, and high levels of LDH and ALT affected neurological manifestations prevalence.

Conclusions

COVID-19 infection and its immune reaction along with its social and psychological effects have a great impact on mental and physical health. Hence, neuropsychiatric evaluation cannot be ignored in any case with COVID-19 infection.
Three-phase balance relay using numerical techniques experimentally verified on synchronous machines
Authors: Mahmoud R. A. , Elwakil E. S.
Published: September 2024

In this paper, a multifunction three-phase balance relay based on normalized correlation coefficients is proposed to detect and estimate imbalances and perturbations in synchronous machine output signals. Furthermore, fresh definitions of imbalance and disturbance indicators derived using the correlation estimators are introduced, taking into account the changes in the waveform phase displacement, frequency, amplitude, and shape of the machine three-phase waves. Experimental tests are performed on a motor–generator set connected to a three-phase load, which is used to identify and evaluate the imbalance and disturbance conditions of the voltage and current measurements. Extensive tests for different fault types have been presented. The practical results show that the proposed protection can respond quickly to faults, and assess online the level of the imbalance/disturbance with high accuracy. Its running time is within one cycle. In addition, the proposed algorithm’s reliability and accuracy are its most significant attributes, whose percentages exceed 96.6%. The present algorithm considers the impact of both negative and zero sequence components when measuring di-symmetry factors, while some conventional approaches merely rely on the negative sequence component computed for the machine voltages and currents.
Toward Expanded Access to Cancer Care With Cost Awareness: An Optimization Modeling Analysis of Rwanda
Authors: Sapirstein Abel , Steimle Lauren N. , Stefan D. Cristina
Published: September 2024

PURPOSE

Cancers are a growing cause of mortality especially in low- and middle-income countries in Africa. Rwanda is no exception. Two cancer centers currently provide care to the public, but there are both political and human interest in expanding access to tertiary cancer care. Improved geographic access could lead to both better patient outcomes and a better understanding of the existing cancer burden across Rwanda.

METHODS

To identify cost-aware ways of expanding geographic access, we adopt an optimization approach and identify expansion plans that minimize the average travel time to a cancer center across the country while remaining under a given monetary budget.

RESULTS

Three additional hospitals could reduce average travel times by 40%, with the largest decrease in travel times observed in populations with long travel times. However, such an expansion would require a 50% increase in the number of in-country oncologists. We find that oncologist scarcity, as opposed to monetary constraints, is likely to be a limiting factor for improved access to cancer care.

CONCLUSION

We present an array of expansion plans and suggest that further modeling approaches that incorporate oncologist scarcity can help deliver better policy recommendations.
Efficient Delivery of Gold Nanoparticles and miRNA-33a Via Cationic PEGylated Niosomal Formulation to MCF-7 Breast Cancer Cells
Authors: Ahmadi Seyedeh Melika , Seyedabadi Mohammad , Ebrahimnejad Pedram , Abasi Mozhgan , Nokhodchi Ali
Published: September 2024

To overcome the challenges associated with the co-delivery of AuNPs (gold nanoparticles) and miRNA as an anti-breast cancer combination therapy, niosomal systems were developed using Span 60, cholesterol, and a cationic lipid (CTAB), and the formulations were optimized using Box-Behnken experimental design. The niosomal formulations with the smallest size were selected for further optimization of size, surface charge, entrapment efficiency, and stability. To achieve this, AuNPs and DSPE-PEG2000 (2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000)were added to the formulation. The optimized niosomal formulation could effectively encapsulate AuNPs with an entrapment efficiency of 34.49% ± 0.84 and a spherical particle size of 153.6 ± 4.62 nm. The incorporation of PEG and CTAB led to notable enhancements in the overall characteristics of the delivery system. To evaluate the effectiveness of the combination therapy, various assessments such as cytotoxicity, apoptosis, and gene expression properties were conducted. The results demonstrated that the combination delivery using the new C-PEG-Nio-AuNPs (cationic pegylated niosomal gold nanoparticles) system and miRNA had the lowest IC50, the highest apoptosis rate, and the most significant upregulation of miRNA and BAX/BCL2 expression in MCF-7 cell growth. In conclusion, this innovative co-delivery approach represents a promising breakthrough in the development of therapeutic agents for breast cancer treatment. By combining multiple therapeutic agents within a single delivery system, this method has the potential to enhance treatment efficacy, reduce side effects, and improve patient outcomes.

Graphical Abstract
Social and auditory experience shapes forebrain responsiveness in zebra finches before the sensitive period of vocal learning
Authors: Schroeder Katie M. , Remage-Healey Luke
Published: September 2024

Early-life experiences with signals used in communication are instrumental in shaping an animal's social interactions. In songbirds, which use vocalizations for guiding social interactions and mate choice, recent studies show that sensory effects on development occur earlier than previously expected, even in embryos and nestlings. Here, we explored the neural dynamics underlying experience-dependent song categorization in young birds prior to the traditionally studied sensitive period of vocal learning that begins around 3 weeks post-hatch. We raised zebra finches either with their biological parents, cross-fostered by Bengalese finches beginning at embryonic day 9, or with only the non-singing mother from 2 days post-hatch. Then, 1–5 days after fledging, we conducted behavioral experiments and extracellular recordings in the auditory forebrain to test responses to zebra finch and Bengalese finch songs. Auditory forebrain neurons in cross-fostered and isolated birds showed increases in firing rate and decreases in responsiveness and selectivity. In cross-fostered birds, decreases in responsiveness and selectivity relative to white noise were specific to conspecific song stimuli, which paralleled behavioral attentiveness to conspecific songs in those same birds. This study shows that auditory and social experience can already impact song ‘type’ processing in the brains of nestlings, and that brain changes at this age can portend the effects of natal experience in adults.
Improving Endurance Exercise Performance at High Altitude: Traditional and Nontraditional Approaches
Authors: Salgado Roy M. , Ryan Benjamin J. , Seeley Afton D. , Charkoudian Nisha
Published: September 2024

Acute exposure to terrestrial altitude (hypobaric hypoxia) causes decrements in endurance performance relative to sea level. Altitude acclimatization consistently results in partial attenuation of these decrements, but due to logistical challenges, it is not readily implemented. We discuss mechanisms and impact (or lack thereof) of other non-acclimatization interventions to improve endurance performance and provide suggestions for future research directions.
Οι Αντιλήψεις των Εκπαιδευτικών Πρωτοβάθμιας Εκπαίδευσης του Νομού Λασιθίου για τον Ρόλο των Τμημάτων Ένταξης στην Πρωτοβάθμια Εκπαίδευση
Authors: Κωνσταντίνου Ματθαίος , Δαλακούρα Παρασκευή
Published: September 2024

Καταλυτικό ρόλο στην ένταξη μαθητών με ειδικές εκπαιδευτικές ανάγκες στο σχολικό περιβάλλον, αλλά και στην κοινωνία διαδραματίζουν τα τμήματα ένταξης με τους εκπαιδευτικούς ειδικής και γενικής εκπαίδευσης να αναλαμβάνουν ευθύνες και να συνεργάζονται για να υλοποιηθούν τα εξειδικευμένα και εξατομικευμένα προγράμματα στο πλαίσιο του τμήματος ένταξης. Η παρούσα εργασία έχει ως στόχο να διερευνήσει τις απόψεις των εκπαιδευτικών πρωτοβάθμιας εκπαίδευσης του νομού Λασιθίου για τον ρόλο των τμημάτων ένταξης και τις προτάσεις τους για βελτίωση του θεσμού. Στην έρευνα συμμετείχαν 60 εκπαιδευτικοί πρωτοβάθμιας εκπαίδευσης. Τα αποτελέσματα της έρευνας ανέδειξαν τη θετική στάση των εκπαιδευτικών προς τη λειτουργία των τμημάτων ένταξης, αλλά και την εξειδίκευση στην ειδική αγωγή. Επιπλέον, οι απόψεις των εκπαιδευτικών για τη βελτίωση του θεσμού συνοψίζονται σε 4 πυλώνες: την επιμόρφωση των εκπαιδευτικών, την πλαισίωση των σχολείων με εξειδικευμένο προσωπικό, την υποστήριξη από το Υπουργείο με εξειδικευμένη υλικοτεχνική υποδομή και τη συμπερίληψη στο πλαίσιο της γενικής τάξης.
Τέχνη, Τεχνολογία και Κοινότητα: Ενσωμάτωση AI για την αειφόρο προώθηση της Κρητικής Διατροφής
Authors: Τρικάλης Κωνσταντίνος Κωνσταντίνος
Published: September 2024

Η τεχνολογία προσφέρει δυνατότητες για την ανάπτυξη βιώσιμων λύσεων για την αντιμετώπιση των προκλήσεων που θέτει η περιβαλλοντική βιωσιμότητα. Ωστόσο, οι εκπαιδευτικοί συναντούν εμπόδια στην εκπαίδευση για την προώθηση της κρητικής διατροφής. Ο στόχος αυτής της μελέτης είναι να διερευνήσει τους τρόπους με τους οποίους η τεχνολογία τεχνητής νοημοσύνης (artificial intelligence AI) μπορεί να βελτιώσει την πρόσβαση στη δια βίου μάθηση και να διευκολύνει την κοινωνική κινητικότητα μέσω της εκπαίδευσης και της κατάρτισης. Για να επιτευχθεί αυτό, διερευνώνται βιώσιμες περιβαλλοντικές στρατηγικές που μπορούν να εφαρμοστούν μέσω της κοινοτικής εκπαίδευσης, χρησιμοποιώντας την τέχνη ως καθολική μορφή επικοινωνίας. Η μεθοδολογία που χρησιμοποιήθηκε αφορούσε τη χρήση πλεγμάτων ρεπερτορίου RGT σε ένα Γυμνάσιο στο Ηράκλειο, με έμφαση στην ανάλυση των εννοιών της απόλαυσης, της συμμετοχής και της ανάπτυξης δεξιοτήτων και γνώσεων στην κοινότητα. Οι συνεντεύξεις με μαθητές επιβεβαίωσαν την ικανότητα δημιουργίας μιας δυναμικής εκπαιδευτικής κοινότητας που μεταφέρει αποτελεσματικά τη γνώση και ενθαρρύνει τον προβληματισμό μεταξύ γονέων και εκπαιδευτικών.