bluuebunny/crossref_metadata_2025 huggingface dataset:
The impact of observers’ beliefs on the perceived contribution of a Research Lesson
Authors: Caballero Daniela , Mella-Defranchi Eliacim , Araya Roberto
Published: April 2024

Recently, Lesson Study (LS) has gained popularity in countries worldwide because of its potentially positive effects on teachers’ practices (e.g., reflection, cooperation, and pre-service development) and students’ learning. However, despite global interest in LS’s implementation, an important gap exists between Japanese LS and its implementation in other countries, which may be due to several reasons, such as differences in culture and educational systems or teachers’ beliefs. In this study, we examined the effect of teachers’ beliefs on their evaluation of LS in Chile. We administered a questionnaire to 94 teachers who participated in the Research Lesson (RL) as observers. The questionnaire assessed teachers’ beliefs and RL’s contributions to knowledge of the subject matter, instructional strategies, monitoring skills, lesson planning, and student understanding. Using a stepwise logistic regression, after controlling for sex and occupation, we found that the observers’ beliefs influenced their perceptions of RL’s contributions to monitoring, assessment, and instruction. Participants with student-focused beliefs were more likely to find that RL contributed to their monitoring skills and ability to assess students’ understanding of content. The results regarding instructional strategies were mixed. Our findings can help devise strategies to increase the effectiveness of LS implementation. For example, by designing two types of LS, one adapted to teachers with student-focused teaching beliefs and the other to teacher-focused teaching beliefs. To the best of our knowledge, this dual strategy is not part of LS implementation, at least in Chile. LS teams could easily explore this dual strategy, which could improve teachers’ professional development.
Techno-anxiety and techno-satisfaction during the COVID-19 pandemic: the case of special education teachers
Authors: Al Mulhim Ensaf Nasser , Almulhem Fatema Abdullah
Published: April 2024

The objective of this study was to assess the levels of techno-anxiety and techno-satisfaction that special education teachers in Saudi Arabia experienced during the COVID-19 pandemic. We used a survey to gather data from 286 teachers of students with special needs across from early intervention to secondary school (5–18 years) the Kingdom, and we interviewed 23 teachers (3 early intervention, 13 primary, 2 intermediate, 5 secondary). Quantitative analysis was employed to analyze the survey responses, while qualitative thematic analysis was used for the interview data. The findings showed that the teachers experienced moderate levels of anxiety (a mean of 2.33 out of 4). On the other hand, the teachers expressed satisfaction (a mean of 2.98 of 4) with the distance learning system they used. The study highlights the benefits and challenges associated with implementing distance learning for students with special needs. These findings could help inform the design of distance learning environments and identify the factors that influence teachers’ feelings of anxiety or satisfaction during the implementation of distance learning. Additionally, the study’s results could encourage parents of students with special needs to foster improved collaboration and cooperation with teachers.
Research progress in the treatment of chronic fatigue syndrome through interventions targeting the hypothalamus-pituitary-adrenal axis
Authors: Zhang Yi-Dan , Wang Li-Na
Published: April 2024

Chronic fatigue syndrome (CFS) causes great harm to individuals and society. Elucidating the pathogenesis of CFS and developing safe and effective treatments are urgently needed. This paper reviews the functional changes in the hypothalamus-pituitary-adrenal (HPA) axis in patients with CFS and the associated neuroendocrine mechanisms. Despite some controversy, the current mainstream research evidence indicates that CFS patients have mild hypocortisolism, weakened daily variation in cortisol, a weakened response to the HPA axis, and an increase in negative feedback of the HPA axis. The relationship between dysfunction of the HPA axis and the typical symptoms of CFS are discussed, and the current treatment methods are reviewed.
Associations of sex hormone ratios with metabolic syndrome and inflammation in US adult men and women
Authors: Dubey Pallavi , Singh Vishwajeet , Venishetty Nikit , Trivedi Meesha , Reddy Sireesha Y. , Lakshmanaswamy Rajkumar , Dwivedi Alok Kumar
Published: April 2024

Background

Sex hormones play a critical role in sex differences and cardiovascular disease risk associated with metabolic syndrome (MS) and inflammation. However, the associations of sex hormone ratios with metabolic and inflammatory markers are unclear according to sex and age differences. We evaluated the associations of sex hormone ratios with MS and inflammation among males and females.

Methods

A retrospective cross-sectional study was conducted by including all adults from the National Health and Nutrition Examination Survey cycles 2013-2016 and excluding any pregnant women, heart disease, diabetes, and those currently taking insulin. MS was defined using the National Cholesterol Education Program criteria and a high-sensitivity C-reactive protein (CRP) level>3 mg/L was defined as a high CRP. Measures of MS components and CRP concentrations were also analyzed. The primary exposures were testosterone to estradiol (excess androgen index), testosterone to sex hormone-binding globulin (free androgen index), and estradiol to sex hormone-binding globulin (free estradiol index). The adjusted associations were summarized with a relative risk (RR) and 95% confidence interval (CI).

Results

This study included 9167 subjects with 4360 males and 4807 females. Increases in free estradiol index were positively associated with MS (RR=1.48; 95%CI: 1.39, 1.58; RR=1.31; 95%CI: 1.22, 1.40) and high CRP (RR=1.49; 95%CI: 1.25, 1.77; RR=1.26; 95%CI: 1.06, 1.50) in men with age<50 years and age≥50 years, respectively. Similarly, higher free estradiol index was also robustly associated with increased prevalence of MS (RR=1.22; 95%CI: 1.15, 1.28) and high CRP (RR=1.68; 95%CI: 1.48, 1.90) in women with age ≥50 years. Among women with age<50 years, a higher free androgen index was associated with MS (RR=1.34; 95%CI: 1.25, 1.42) and high CRP (RR=1.13; 95%CI: 1.02, 1.25). These associations were unchanged even after adjusting for all sex hormones.

Conclusion

Free estradiol index was consistently and positively associated with MS and high CRP in males of all ages and older females. Free androgen index was positively associated with MS and high CRP in females with age<50 years.
The dynamics of neurobehavioral impairment and recovery sleep: improved biomathematical modeling for fatigue risk management in operational settings
Authors: McCauley Mark E. , McCauley Peter , Kalachev Leonid V. , Banks Siobhan , Dinges David F. , Van Dongen Hans P. A.
Published: April 2024

Adequate sleep is essential for maintaining health, safety, and neurobehavioral functioning in 24/7 operational settings. Loss of sleep causes fatigue, which results in neurobehavioral impairment. Neurobehavioral impairment builds up disproportionately under conditions of total sleep deprivation compared to sustained sleep restriction; and recuperation due to recovery sleep is disproportionately fast after total sleep deprivation compared to sustained sleep restriction. These sleep schedule-dependent dynamics have been captured in a previously published, biomathematical model of fatigue, which includes positive feedback regulation of a relatively fast (hours to days) sleep/wake homeostatic process by a slower (days to weeks) allostatic process—a feature that suggests adenosinergic mechanisms are involved. However, the previously published model underestimates the rate of recuperation due to recovery sleep after acute total sleep deprivation as well as after consecutive days of sleep restriction. The objective of the present research is to modify the model to improve the accuracy of its predictions for recuperation due to recovery sleep. This can be accomplished by including in the model an additional, reciprocal feedback mechanism, presumed to be predominantly adenosinergic in nature, which provides feedback from the faster homeostatic process back onto the slower allostatic process. Adding a single new model parameter and refitting three existing model parameters significantly improves the predictions for recuperation due to recovery sleep after both acute total sleep deprivation and sustained sleep restriction. This model modification also improves the predictions of the build-up of neurobehavioral impairment across days of sustained sleep restriction, without adversely affecting the accuracy of the model in other scenarios including circadian misalignment and sleep inertia. The modified model preserves the previously developed capability to predict the differential dynamics of fatigue for objective performance impairment and subjective sleepiness. With the improved predictions for recuperation due to recovery sleep, the expanded model can be used to provide quantitative estimates for potentially impactful work scheduling decisions, such as the duration of time off needed before workers would be safe to return to the work floor. This enhances the usefulness of the model as a tool for predicting and managing neurobehavioral functioning and safety in 24/7 operational settings.
Critical gene signature and immunological characterization in peripheral vascular atherosclerosis: novel insights from mendelian randomization and transcriptomics
Authors: Xie Wei , Chen Shumin , Luo Hanqing , Kong Chuiyu , Wang Dongjin
Published: April 2024

Introduction

Peripheral vascular atherosclerosis (PVA) is a chronic inflammatory disease characterized by lipid accumulation in blood vessel walls, leading to vessel narrowing and inadequate blood supply. However, the molecular mechanisms underlying PVA remain poorly understood. In this study, we employed a combination of Mendelian randomization (MR) analysis and integrated transcriptomics to identify the critical gene signature associated with PVA.

Methods

This study utilized three public datasets (GSE43292, GSE100927 and GSE28829) related to peripheral vascular atherosclerosis obtained from the Gene Expression Omnibus database. Instrumental variables (IVs) were identified through expression quantitative trait loci (eQTL) analysis, and two-sample MR analysis was performed using publicly available summary statistics. Disease critical genes were identified based on odds ratios and intersected with differentially expressed genes in the disease dataset. GSE28829 dataset was used to validate the screened disease critical genes. Functional enrichment analysis, GSEA analysis, and immune cell infiltration analysis were performed to further characterize the role of these genes in peripheral vascular atherosclerosis.

Results

A total of 26,152 gene-related SNPs were identified as IVs, and 242 disease-associated genes were identified through MR analysis. Ten disease critical genes (ARHGAP25, HCLS1, HVCN1, RBM47, LILRB1, PLAU, IFI44L, IL1B, IFI6, and CFL2) were significantly associated with peripheral vascular atherosclerosis. Functional enrichment analysis using KEGG pathways revealed enrichment in the NF-kappa B signaling pathway and osteoclast differentiation. Gene set enrichment analysis further demonstrated functional enrichment of these genes in processes related to vascular functions and immune system activation. Additionally, immune cell infiltration analysis showed differential ratios of B cells and mast cells between the disease and control groups. The correlations analysis highlights the intricate interplay between disease critical genes and immune cells associated with PVA.

Conclusion

In conclusion, this study provides new insights into the molecular mechanisms underlying PVA by identifying ten disease critical genes associated with the disease. These findings, supported by differential expression, functional enrichment, and immune system involvement, emphasize the role of these genes in vascular function and immune cell interactions in the context of PVA. These findings contribute to a better understanding of PVA pathogenesis and offer potential targets for further mechanistic exploration and therapeutic interventions.
Combined metabolome and transcriptome analyses reveal that growing under Red shade affects secondary metabolite content in Huangjinya green tea
Authors: Shu Zaifa , Ji Qingyong , He Tianjun , Zhou Dayun , Zheng Shenghong , Zhou Huijuan , He Weizhong
Published: April 2024

Shading treatments impact the tea (Camellia sinensis L.) quality. The sunlight sensitive varieties can be grown under shading nets for better growth and secondary metabolite content. Here, we studied the responses of a sunlight sensitive green tea variety “Huangjinya” by growing under colored shading nets (red, yellow, blue, and black (75% and 95%) shading rates) to find out the most suitable color of the shading net. Red shading was the most promising treatment as it positively affected the weight and length of 100 one-bud-three leaves and reduced the degree and rate of new shoots burn compared to control (natural sunlight). We then explored the comparative metabolomic changes in response to red shading by using UPLC-ESI-MS/MS system. The amino acids and derivatives, flavonoids, and alkaloids were downaccumulated whereas lipids, organic acids, and lignans were upaccumulated in Red shade grown tea samples. The red shading nets caused a decreased catechin, epicatechin, dopamine, and L-tyramine contents but increased caffeine content. We then employed transcriptome sequencing to find key changes in expressions of related genes and pathways. Notably, key genes associated with the phenylpropanoid and flavonoid biosynthesis pathways exhibited complex regulation. These expression changes suggested a potential trend of polymerization or condensation of simple molecules like catechin or pelargonidin into larger molecules like glucoside or proanthocyanidins. Here, Red shading net triggered higher expression of genes enriched in lipid biosynthesis and jasmonic acid biosynthesis, suggesting an interplay of fatty acids and JA in improving tea performance. These findings contribute to the metabolic responses of Huangjinya tea to red shading nets which might have implications for flavor and health benefits. Our data provide a foundation for further exploration and optimization of cultivation practices for this unique tea variety.
A transformer-based method for correcting significant wave height numerical forecasting errors
Authors: Kang Xianbiao , Song Haijun , Zhang Zhanshuo , Yin Xunqiang , Gu Juan
Published: April 2024

Accurate significant wave height (SWH) forecasting is essential for various marine activities. While traditional numerical and mathematical-statistical methods have made progress, there is still room for improvement. This study introduces a novel transformer-based approach called the 2D-Geoformer to enhance SWH forecasting accuracy. The 2D-Geoformer combines the spatial distribution capturing capabilities of SWH numerical models with the ability of mathematical-statistical methods to identify intrinsic relationships among datasets. Using a comprehensive long time series of SWH numerical hindcast datasets as the numerical forecasting database and ERA5 reanalysis SWH datasets as the observational proxies database, with a focus on a 72-hour forecasting window, the 2D-Geoformer is designed. By training the potential connections between SWH numerical forecasting fields and forecasting errors, we can retrieve SWH forecasting errors for each numerical forecasting case. The corrected forecasting results can be obtained by subtracting the retrieved SWH forecasting errors from the original numerical forecasting fields. During long-term validation periods, this method consistently and effectively corrects numerical forecasting errors for almost every case, resulting in a significant reduction in root mean square error compared to the original numerical forecasting fields. Further analysis reveals that this method is particularly effective for numerical forecasting fields with higher errors compared to those with relatively smaller errors. This integrated approach represents a substantial advancement in SWH forecasting, with the potential to improve the accuracy of operational SWH forecasts. The 2D-Geoformer combines the strengths of numerical models and mathematical-statistical methods, enabling better capture of spatial distributions and intrinsic relationships in the data. The method's effectiveness in correcting numerical forecasting errors, particularly for cases with higher errors, highlights its potential for enhancing SWH forecasting accuracy in operational settings.
Unveiling APOL1 haplotypes in a predominantly African-American cohort of kidney transplant patients: a novel classification using probe-independent quantitative real-time PCR
Authors: Dogan Murat , Watkins Christine , Ingram Holly , Moore Nicholas , Rucker Grace M. , Gower Elizabeth G. , Eason James D. , Bhalla Anshul , Talwar Manish , Nezakatgoo Nosratollah , Eymard Corey , Helmick Ryan , Vanatta Jason , Bajwa Amandeep , Kuscu Canan , Kuscu Cem
Published: April 2024

Introduction

Apolipoprotein-L1 (APOL1) is a primate-specific protein component of high-density lipoprotein (HDL). Two variants of APOL1 (G1 and G2), provide resistance to parasitic infections in African Americans but are also implicated in kidney-related diseases and transplant outcomes in recipients. This study aims to identify these risk variants using a novel probe-independent quantitative real-time PCR method in a high African American recipient cohort. Additionally, it aims to develop a new stratification approach based on a haplotype-centric model.

Methods

Genomic DNA was extracted from recipient PBMCs using SDS lysis buffer and proteinase K. A quantitative PCR assay with modified forward primers and a common reverse primer enabled us to quantitatively identify single nucleotide polymorphisms (SNPs) and the 6-bp deletion. Additionally, we used Sanger sequencing to verify our QPCR findings.

Results

Our novel probe-independent qPCR effectively distinguished homozygous wild-type, heterozygous SNPs/deletions, and homozygous SNPs/deletions, with at least 4-fold differences. A high prevalence of APOL1 variants was observed (18% two-risk alleles, 34% one-risk allele) in our recipient cohort. Intriguingly, no significant impact of recipient APOL1 variants on transplant outcomes was observed up to 12-month of follow-ups. Ongoing research will encompass more time points and a larger patient cohort, allowing for a comprehensive evaluation of G1/G2 variant subgroups categorized by new haplotype scores, enriching our understanding.

Conclusion

Our cost-effective and rapid qPCR technique facilitates APOL1 genotyping within hours. Prospective and retrospective studies will enable comparisons with long-term allograft rejection, potentially predicting early/late-stage transplant outcomes based on haplotype evaluation in this diverse group of kidney transplant recipients.
Effect of manual osteopathic techniques on the autonomic nervous system, respiratory system function and head-cervical-shoulder complex—a systematic review
Authors: Stępnik Jakub , Czaprowski Dariusz , Kędra Agnieszka
Published: April 2024

Background

Osteopathic manual techniques are now widely used in medicine worldwide. At present, there are no clear conclusions regarding the possibility of affecting the function of the autonomic nervous system (ANS), respiratory system and head-cervical-shoulder complex by manual osteopathic techniques.

Objectives

The aim of the study was to review the current literature regarding the possible impact of osteopathic manual techniques on the state of the autonomic nervous system, spirometric parameters of the respiratory system and the state of the head-collar-shoulder complex.

Methods

Publications have been searched in the following databases: PubMed, Virtual Health Library and Cochrane Central Register of Controlled Trials. The search strategy included keywords related to manual osteopathic treatment, autonomic nervous system, spirometry, respiratory function and head, neck and shoulder pain. The methodological quality of the included studies was assessed. The PRISMA guidelines were used for the systematic review. Studies from 2010 to 2023 were selected.

Results

Using the proposed descriptions and manual searches from the literature of other works, 40 studies were found, out of which 22 were rejected because they did not meet the inclusion criteria. The analysis included: 15 randomized controlled trials, 3 pilot studies.

Conclusion

Studies clearly show the effect of OMT on both spirometric parameters and the condition of the head-collar-shoulder complex. Most often this translates into improved ANS performance, but there are exceptions.

Systematic review registration

https://www.crd.york.ac.uk/prospero/, CRD42023476963.
Transcriptomic analysis identifies the shared diagnostic biomarkers and immune relationship between Atherosclerosis and abdominal aortic aneurysm based on fatty acid metabolism gene set
Authors: Gu Xuefeng , Yu Zhongxian , Qian Tianwei , Jin Yiqi , Xu Guoxiong , Li Jiang , Gu Jianfeng , Li Ming , Tao Ke
Published: April 2024

Background:

Epidemiological research has demonstrated that there is a connection between lipid metabolism disorder and an increased risk of developing arteriosclerosis (AS) and abdominal aortic aneurysm (AAA). However, the precise relationship between lipid metabolism, AS, and AAA is still not fully understood. The objective of this study was to examine the pathways and potential fatty acid metabolism-related genes (FRGs) that are shared between AS and AAA.

Methods:

AS- and AAA-associated datasets were retrieved from the Gene Expression Omnibus (GEO) database, and the limma package was utilized to identify differentially expressed FRGs (DFRGs) common to both AS and AAA patients. Functional enrichment analysis was conducted on the (DFRGs), and a protein-protein interaction (PPI) network was established. The selection of signature genes was performed through the utilization of least absolute shrinkage and selection operator (LASSO) regression and random forest (RF). Subsequently, a nomogram was developed using the results of the screening process, and the crucial genes were validated in two separate external datasets (GSE28829 and GSE17901) as well as clinical samples. In the end, single-sample gene set enrichment analysis (ssGSEA) was utilized to assess the immune cell patterns in both AS and AAA. Additionally, the correlation between key crosstalk genes and immune cell was evaluated.

Results:

In comparison to control group, both AS and AAA patients exhibited a decrease in fatty acid metabolism score. We found 40 DFRGs overlapping in AS and AAA, with lipid and amino acid metabolism critical in their pathogenesis. PCBD1, ACADL, MGLL, BCKDHB, and IDH3G were identified as signature genes connecting AS and AAA. Their expression levels were confirmed in validation datasets and clinical samples. The analysis of immune infiltration showed that neutrophils, NK CD56dim cells, and Tem cells are important in AS and AAA development. Correlation analysis suggested that these signature genes may be involved in immune cell infiltration.

Conclusion:

The fatty acid metabolism pathway appears to be linked to the development of both AS and AAA. Furthermore, PCBD1, ACADL, MGLL, BCKDHB, and IDH3G have the potential to serve as diagnostic markers for patients with AS complicated by AAA.
Biofluid biomarkers for Alzheimer’s disease
Authors: Wang Sensen , Xie Sitan , Zheng Qinpin , Zhang Zhihui , Wang Tian , Zhang Guirong
Published: April 2024

Alzheimer’s disease (AD) is a multifactorial neurodegenerative disease, with a complex pathogenesis and an irreversible course. Therefore, the early diagnosis of AD is particularly important for the intervention, prevention, and treatment of the disease. Based on the different pathophysiological mechanisms of AD, the research progress of biofluid biomarkers are classified and reviewed. In the end, the challenges and perspectives of future research are proposed.
Inhibiting presynaptic calcium channel motility in the auditory cortex suppresses synchronized input processing
Authors: Deane Katrina E. , Klymentiev Ruslan , Heck Jennifer , Mark Melanie D. , Ohl Frank W. , Heine Martin , Happel Max F. K.
Published: April 2024

Introduction

The emergent coherent population activity from thousands of stochastic neurons in the brain is believed to constitute a key neuronal mechanism for salient processing of external stimuli and its link to internal states like attention and perception. In the sensory cortex, functional cell assemblies are formed by recurrent excitation and inhibitory influences. The stochastic dynamics of each cell involved is largely orchestrated by presynaptic CAV2.1 voltage-gated calcium channels (VGCCs). Cav2.1 VGCCs initiate the release of neurotransmitters from the presynaptic compartment and are therefore able to add variability into synaptic transmission which can be partly explained by their mobile organization around docked vesicles.

Methods

To investigate the relevance of Cav2.1 channel surface motility for the input processing in the primary auditory cortex (A1) in vivo, we make use of a new optogenetic system which allows for acute, reversable cross-linking Cav2.1 VGCCs via a photo-cross-linkable cryptochrome mutant, CRY2olig. In order to map neuronal activity across all cortical layers of the A1, we performed laminar current-source density (CSD) recordings with varying auditory stimulus sets in transgenic mice with a citrine tag on the N-terminus of the VGCCs.

Results

Clustering VGCCs suppresses overall sensory-evoked population activity, particularly when stimuli lead to a highly synchronized distribution of synaptic inputs.

Discussion

Our findings reveal the importance of membrane dynamics of presynaptic calcium channels for sensory encoding by dynamically adjusting network activity across a wide range of synaptic input strength.
Treatment advances in high-grade gliomas
Authors: Chen Xi , Cui Yi , Zou Liqun
Published: April 2024

High-grade gliomas (HGG) pose significant challenges in modern tumour therapy due to the distinct biological properties and limitations of the blood-brain barrier. This review discusses recent advancements in HGG treatment, particularly in the context of immunotherapy and cellular therapy. Initially, treatment strategies focus on targeting tumour cells guided by the molecular characteristics of various gliomas, encompassing chemotherapy, radiotherapy and targeted therapy for enhanced precision. Additionally, technological enhancements are augmenting traditional treatment modalities. Furthermore, immunotherapy, emphasising comprehensive tumour management, has gained widespread attention. Immune checkpoint inhibitors, vaccines and CAR-T cells exhibit promising efficacy against recurrent HGG. Moreover, emerging therapies such as tumour treating fields (TTFields) offer additional treatment avenues for patients with HGG. The combination of diverse treatments holds promise for improving the prognosis of HGG, particularly in cases of recurrence.
Neurotype and participatory autism knowledge predict perceptions of an autistic employee in the workplace
Authors: Szechy Kathryn A. , O'Donnell Lisa A.
Published: April 2024

Introduction

Autistic adults are unemployed at much higher rates than the general population. Differences due to autistic traits, including social skills differences, are often barriers to autistic adults obtaining and retaining employment in non-autistic workplaces. The double empathy problem (DEP) posits that autistic social differences are not due to assumed autistic social impairment but to mutual misunderstandings within the autistic/non-autistic social interaction. Consistent with the DEP, autistic adults are more likely to accurately interpret the behavior of an autistic employee, compared to non-autistic adults. This study examined additional factors, beyond neurotype, that are associated with accurate interpretation of the behavior of an autistic employee.

Methods

A sample of 73 autistic and 140 non-autistic participants read a vignette about a hypothetical autistic employee in a non-autistic workplace having a difficult workday. Participants completed questions about their interpretation of the employee's behavior, an autism knowledge measure, autism experience questions, and demographic information.

Results

General autism knowledge, but not autism experience, was an influential predictor of accurate behavior interpretation toward the autistic employee and negated the predictive influence of education level, income, and gender identity of participants (OR = 1.12, p < 0.001). However, regardless of the level of autism knowledge, autistic participants continued to be significantly more likely to accurately interpret the behavior of the autistic employee, compared to non-autistic participants (OR = 2.94, p = 0.02).

Discussion

Results continue to contribute support for the DEP within the context of autistic employment challenges. Findings also point to autism education as a promising autism workplace support in addressing the DEP and barriers autistic adults face with obtaining and retaining employment.
Current genetic diagnostics in inborn errors of immunity
Authors: von Hardenberg Sandra , Klefenz Isabel , Steinemann Doris , Di Donato Nataliya , Baumann Ulrich , Auber Bernd , Klemann Christian
Published: April 2024

New technologies in genetic diagnostics have revolutionized the understanding and management of rare diseases. This review highlights the significant advances and latest developments in genetic diagnostics in inborn errors of immunity (IEI), which encompass a diverse group of disorders characterized by defects in the immune system, leading to increased susceptibility to infections, autoimmunity, autoinflammatory diseases, allergies, and malignancies. Various diagnostic approaches, including targeted gene sequencing panels, whole exome sequencing, whole genome sequencing, RNA sequencing, or proteomics, have enabled the identification of causative genetic variants of rare diseases. These technologies not only facilitated the accurate diagnosis of IEI but also provided valuable insights into the underlying molecular mechanisms. Emerging technologies, currently mainly used in research, such as optical genome mapping, single cell sequencing or the application of artificial intelligence will allow even more insights in the aetiology of hereditary immune defects in the near future. The integration of genetic diagnostics into clinical practice significantly impacts patient care. Genetic testing enables early diagnosis, facilitating timely interventions and personalized treatment strategies. Additionally, establishing a genetic diagnosis is necessary for genetic counselling and prognostic assessments. Identifying specific genetic variants associated with inborn errors of immunity also paved the way for the development of targeted therapies and novel therapeutic approaches. This review emphasizes the challenges related with genetic diagnosis of rare diseases and provides future directions, specifically focusing on IEI. Despite the tremendous progress achieved over the last years, several obstacles remain or have become even more important due to the increasing amount of genetic data produced for each patient. This includes, first and foremost, the interpretation of variants of unknown significance (VUS) in known IEI genes and of variants in genes of unknown significance (GUS). Although genetic diagnostics have significantly contributed to the understanding and management of IEI and other rare diseases, further research, exchange between experts from different clinical disciplines, data integration and the establishment of comprehensive guidelines are crucial to tackle the remaining challenges and maximize the potential of genetic diagnostics in the field of rare diseases, such as IEI.
Access to a tailored mobile application enhances medication adherence among young users of antidepressants
Authors: Larsen Rønnaug Eline , Hole Kristine , Selle Maria Lie , Johannessen Landmark Cecilie , Krogstad Tonje , Holm Lene Berge
Published: April 2024

Introduction:

Patients’ adherence to antidepressants is generally reported to be poor. This study examined whether users of selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) enhance medication adherence following access to a mobile application (app) tailored for this patient group. The study addresses the implementation phase of medication adherence.

Methods:

The study was a single group pre-post intervention design. Data were collected using the validated OsloMet Adherence-to-medication Survey tool (OMAS-37) before and after app access. Pre-app access survey (Survey 1) was conducted via social media and online newspapers, encompassing 445 SSRI/SNRI users aged 18 years and above. Post-app access survey (Survey 2) was sent to 103 SSRI/SNRI users from Survey 1. Wilcoxon Signed Rank Test compared pre- and post-intervention adherence measurements. Pearson’s chi-square tests and Fisher’s exact tests compared study population categories.

Results:

Forty-two SSRI/SNRI users, median age 26 (IQR 17), 93% identifying as female, used the app while using the same antidepressant during the 2-month period between gaining access to the app and Survey 2. There was a statistically significant reduction in non-adherence score post-app access (z = 3.57, n = 42, p < 0.001) with medium effect size (r = 0.39), indicating enhanced adherence. Total non-adherence score decreased by 39% from pre-to post-access, and there was a 12% decrease in users scoring equivalent with poor adherence (score <2) post-access. Twenty-nine of 37 non-adherence causes improved, with three showing statistical significance. Of 42 responders, 50% (n = 21) indicated using the app one to two times, while 50% (n = 21) more than three times. Approximately 69% (n = 28) found it useful, and 43% (n = 18) felt safer in their use of antidepressants after access to the app. No significant preference was observed for the app over alternative sources of information.

Discussion:

Enhanced medication adherence was observed among antidepressant users following access to the tailored app. Further studies are warranted to evaluate the app applicability to a broader range of antidepressants users or other patient groups, encompassing those in the initiation phase of medication adherence. The app is intended as an easily accessible supplement to the information and advice provided by prescribing physicians and dispensing pharmacists.
Magnesium in hypertension: mechanisms and clinical implications
Authors: AlShanableh Zain , Ray Evan C.
Published: April 2024

Hypertension is associated with increased risk of cardiovascular disease and death. Evidence suggests that Mg2+ depletion contributes to hypertension. It is estimated that 25% or more of the United States population experiences chronic, latent Mg2+ depletion. This review explores mechanisms by which Mg2+ influences blood pressure, modifying risk of hypertension and complicating its treatment. Mechanisms addressed include effects upon i) sympathetic tone, via the modulation of N-methyl-D-aspartate (NMDA) receptor and N-type Ca2+ channel activity, influencing catecholamine release from sympathetic nerve endings; ii) vascular tone, via alteration of L-type Ca2+ and endothelial nitric oxide synthase (eNOS) activity and prostacyclin release; iii) renal K+ handling, influencing systemic K+ balance and potentially indirectly influencing blood pressure; iv) aldosterone secretion from the adrenal cortex; and v) modulation of pro-hypertensive inflammatory processes in dendritic cells and macrophages, including activation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome and stimulation of isolevuglandin (IsoLG) production. Discovery of these mechanisms has furthered our understanding of the pathogenesis of hypertension, with implications for treatment and has highlighted the role of Mg2+ balance in hypertension and cardiovascular disease.
Physiology of deep closed circuit rebreather mixed gas diving: vascular gas emboli and biological changes during a week-long liveaboard safari
Authors: Balestra Costantino , Lévêque Clément , Mrakic-Sposta Simona , Vezzoli Alessandra , Wauthy Pierre , Germonpré Peter , Tillmans Frauke , Guerrero François , Lafère Pierre
Published: April 2024

Introduction: Diving decompression theory hypothesizes inflammatory processes as a source of micronuclei which could increase related risks. Therefore, we tested 10 healthy, male divers. They performed 6–8 dives with a maximum of two dives per day at depths ranging from 21 to 122 msw with CCR mixed gas diving.

Methods: Post-dive VGE were counted by echocardiography. Saliva and urine samples were taken before and after each dive to evaluate inflammation: ROS production, lipid peroxidation (8-iso-PGF2), DNA damage (8-OH-dG), cytokines (TNF-α, IL-6, and neopterin).

Results: VGE exhibits a progressive reduction followed by an increase (p < 0.0001) which parallels inflammation responses. Indeed, ROS, 8-iso-PGF2, IL-6 and neopterin increases from 0.19 ± 0.02 to 1.13 ± 0.09 μmol.min−1 (p < 0.001); 199.8 ± 55.9 to 632.7 ± 73.3 ng.mg−1 creatinine (p < 0.0001); 2.35 ± 0.54 to 19.5 ± 2.96 pg.mL−1 (p < 0.001); and 93.7 ± 11.2 to 299 ± 25.9 μmol·mol−1 creatinine (p = 0.005), respectively. The variation after each dive was held constant around 158.3% ± 6.9% (p = 0.021); 151.4% ± 5.7% (p < 0.0001); 176.3% ± 11.9% (p < 0.0001); and 160.1% ± 5.6% (p < 0.001), respectively.

Discussion: When oxy-inflammation reaches a certain level, it exceeds hormetic coping mechanisms allowing second-generation micronuclei substantiated by an increase of VGE after an initial continuous decrease consistent with a depletion of “first generation” pre-existing micronuclei.
Mitochondrial genome variation and intergenomic sequence transfers in Hevea species
Authors: Niu Yingfeng , Gao Chengwen , Liu Jin
Published: April 2024

Among the Hevea species, rubber tree (Hevea brasiliensis) is the most important source of natural rubber. In previous studies, we sequenced the complete nuclear and chloroplast genomes of Hevea species, providing an invaluable resource for studying their phylogeny, disease resistance, and breeding. However, given that plant mitochondrial genomes are more complex and more difficult to assemble than that of the other organelles, little is known about their mitochondrial genome, which limits the comprehensive understanding of Hevea genomic evolution. In this study, we sequenced and assembled the mitochondrial genomes of four Hevea species. The four mitochondrial genomes had consistent GC contents, codon usages and AT skews. However, there were significant differences in the genome lengths and sequence repeats. Specifically, the circular mitochondrial genomes of the four Hevea species ranged from 935,732 to 1,402,206 bp, with 34–35 unique protein-coding genes, 35–38 tRNA genes, and 6–13 rRNA genes. In addition, there were 17,294–46,552 bp intergenomic transfer fragments between the chloroplast and mitochondrial genomes, consisting of eight intact genes (psaA, rrn16S, tRNA-Val, rrn5S, rrn4.5S, tRNA-Arg, tRNA-Asp, and tRNA-Asn), intergenic spacer regions and partial gene sequences. The evolutionary position of Hevea species, crucial for understanding its adaptive strategies and relation to other species, was verified by phylogenetic analysis based on the protein-coding genes in the mitochondrial genomes of 21 Malpighiales species. The findings from this study not only provide valuable insights into the structure and evolution of the Hevea mitochondrial genome but also lay the foundation for further molecular, evolutionary studies, and genomic breeding studies on rubber tree and other Hevea species, thereby potentially informing conservation and utilization strategies.
Genome-wide identification of Shaker K+ channel family in Nicotiana tabacum and functional analysis of NtSKOR1B in response to salt stress
Authors: Yuan Guang , Nong Tongjia , Hunpatin Oluwaseyi Setonji , Shi Chuhan , Su Xiaoqing , Xu Fangzheng , Wang Yihui , Zhang Zhaoting , Ning Yang , Liu Haobao , Wang Qian
Published: April 2024

Soil salinization poses a mounting global ecological and environmental threat. The identification of genes responsible for negative regulation of salt tolerance and their utilization in crop improvement through gene editing technologies emerges as a swift strategy for the effective utilization of saline-alkali lands. One efficient mechanism of plant salt tolerance is maintaining the proper intracellular K+/Na+ ratio. The Shaker K+ channels play a crucial role in potassium absorption, transport, and intracellular potassium homeostasis in plant cells. Here, the study presents the first genome-wide identification of Shaker K+ channels in Nicotiana tabacum L., along with a detailed bioinformatic analysis of the 20 identified members. Transcriptome analysis revealed a significant up-regulation of NtSKOR1B, an outwardly-rectifying member predominantly expressed in the root tissue of tobacco seedlings, in response to salt stress. This finding was then confirmed by GUS staining of ProNtSKOR1B::GUS transgenic lines and RT-qPCR analysis. Subsequently, NtSKOR1B knockout mutants (ntskor1) were then generated and subjected to salt conditions. It was found that ntskor1 mutants exhibit enhanced salt tolerance, characterized by increased biomass, higher K+ content and elevated K+/Na+ ratios in both leaf and root tissues, compared to wild-type plants. These results indicate that NtSKOR1B knockout inhibits K+ efflux in root and leaf tissues of tobacco seedlings under salt stress, thereby maintaining higher K+/Na+ ratios within the cells. Thus, our study identifies NtSKOR1B as a negative regulator of salt tolerance in tobacco seedlings.
Endogenous cell wall degrading enzyme LytD is important for the biocontrol activity of Bacillus subtilis
Authors: Wang Luotao , Huang Jianquan , Chen Si , Su Xin , Zhang Xun , Wang Lujun , Zhang Wei , Wang Zhenshuo , Zeng Qingchao , Wang Qi , Li Yan
Published: April 2024

Autolysins are endogenous cell wall degrading enzymes (CWDEs) in bacteria that remodel the peptidoglycan layer of its own cell wall. In the Bacillus subtilis genome, at least 35 autolysin genes have been identified. However, the study of their roles in bacterial physiology has been hampered by their complexity and functional redundancy. B. subtilis GLB191 is an effective biocontrol strain against grape downy mildew disease, the biocontrol effect of which results from both direct effect against the pathogen and stimulation of the plant defense. In this study, we show that the autolysin N-acetylglucosaminidase LytD, a major autolysin of vegetative growth in B. subtilis, plays an important role in its biocontrol activity against grape downy mildew. Disruption of lytD resulted in reduced suppression of the pathogen Plasmopara viticola and stimulation of the plant defense. LytD is also shown to affect the biofilm formation and colonization of B. subtilis on grape leaves. This is the first report that demonstrates the role of an endogenous CWDE in suppressing plant disease infection of a biological control microorganism. These findings not only expand our knowledge on the biological function of autolysins but also provide a new target to promote the biocontrol activity of B. subtilis.
Relationship between teachers’ professional identity and career satisfaction among college teachers: role of career calling
Authors: Wu Jinshun , Ghayas Saba , Aziz Aiman , Adil Adnan , Niazi Sadia
Published: April 2024

Objectives

Professional identity has been found an important determinant of career satisfaction of employees working in various fields. Teachers’ professional identity is a relatively less explored domain. Considering the importance of teacher’s career satisfaction, the current study was designed to test the role of career calling in the relationship between teachers’ professional identity and career satisfaction.

Methods

A sample of teachers (N = 300) with (n = 115) men and (n = 185) women was recruited from the colleges of Sargodha City, Pakistan with an age range from 24 to 45 (M = 31.3, SD = 6.4). A purposive sampling technique was employed for data collection. Variables of the present study were operationalized through the Professional Identity Scale, Brief Calling Scale, and Career Satisfaction Scale.

Results

Path analysis revealed that normative identity did not have any direct or indirect effects on career satisfaction and career calling. Whereas affective and efficacy identity demonstrated significant positive direct effects on career calling whereas career calling had significant positive direct effect on career satisfaction. Efficacy identity also had a significant positive direct effect on career satisfaction. Finally, both affective and efficacy identity had significant positive indirect effects on career satisfaction via career calling.

Conclusion

The findings of the current study may help in devising plans to improve the career satisfaction of teachers working in the higher education sector.
Understanding the patient and supporter journey in cocaine use disorder
Authors: Leclair Denise , Waye Katherine M. , Gomez-Mancilla Baltazar , Kiluk Brian D. , Karanam Ananda Krishna , Banerjee Partha S. , Muthusamy Velusamy Shanmuganathan , Maahs Suzanne
Published: April 2024

Background

There is a paucity of literature describing experiences and journey of individuals with cocaine use disorder (CUD) and supporters who care for them. The aim of this study was to understand and document the journey of individuals with current CUD, those in CUD remission, and supporters.

Methods

The online bulletin board (OBB) is a qualitative tool where participants engage in an interactive discussion on a virtual forum. After completing a 15-minute screening questionnaire determining eligibility, individuals in CUD remission and supporters participated in an OBB for 60 minutes, split across 8 days over 2 weeks. Individuals with current CUD participated in a one-time virtual focus group discussion for 90 minutes.

Results

Individuals in CUD remission (n=35) were from Brazil, France, Spain, the UK, and the US; those with current CUD (n=5) and supporters (n=6) were from the US. Key insights were that individuals with current CUD were seeking a ‘euphoric high’ that cocaine provides. Those in CUD remission described a ‘euphoric high’ when they first tried cocaine, but over time it became harder to re-create this feeling. Individuals in CUD remission expressed a ‘rollercoaster’ of emotions from when they first started using cocaine to when they stopped. Supporters were sad, isolated, and worried about a potential cocaine overdose for their loved ones with CUD.

Conclusion

The study provides valuable insights into the experiences and journey of individuals with CUD and their supporters. Data generated from this study gives insights into this under-served and growing population.