bluuebunny/crossref_metadata_2025 huggingface dataset:
Multisite Validation of a Functional Assay to Adjudicate
SCN5A
Brugada Syndrome–Associated Variants
Authors: Ma Joanne G. , O’Neill Matthew J. , Richardson Ebony , Thomson Kate L. , Ingles Jodie , Muhammad Ayesha , Solus Joseph F. , Davogustto Giovanni , Anderson Katherine C. , Shoemaker M. Benjamin , Stergachis Andrew B. , Floyd Brendan J. , Dunn Kyla , Parikh Victoria N. , Chubb Henry , Perrin Mark J. , Roden Dan M. , Vandenberg Jamie I. , Ng Chai-Ann , Glazer Andrew M.
Published: July 2024

BACKGROUND:

Brugada syndrome is an inheritable arrhythmia condition that is associated with rare, loss-of-function variants in
SCN5A
. Interpreting the pathogenicity of
SCN5A
missense variants is challenging, and ≈79% of
SCN5A
missense variants in ClinVar are currently classified as variants of uncertain significance. Automated patch clamp technology enables high-throughput functional studies of ion channel variants and can provide evidence for variant reclassification.

METHODS:

An in vitro
SCN5A
–Brugada syndrome automated patch clamp assay was independently performed at Vanderbilt University Medical Center and Victor Chang Cardiac Research Institute. The assay was calibrated according to ClinGen Sequence Variant Interpretation recommendations using high-confidence variant controls (n=49). Normal and abnormal ranges of function were established based on the distribution of benign variant assay results. Odds of pathogenicity values were derived from the experimental results according to ClinGen Sequence Variant Interpretation recommendations. The calibrated assay was then used to study
SCN5A
variants of uncertain significance observed in 4 families with Brugada syndrome and other arrhythmia phenotypes associated with
SCN5A
loss-of-function.

RESULTS:

Variant channel parameters generated independently at the 2 research sites showed strong correlations, including peak
I
Na
density (
R
2
=0.86). The assay accurately distinguished benign controls (24/25 concordant variants) from pathogenic controls (23/24 concordant variants). Odds of pathogenicity values were 0.042 for normal function and 24.0 for abnormal function, corresponding to strong evidence for both American College of Medical Genetics and Genomics/Association for Molecular Pathology benign and pathogenic functional criteria (BS3 and PS3, respectively). Application of the assay to 4 clinical
SCN5A
variants of uncertain significance revealed loss-of-function for 3/4 variants, enabling reclassification to likely pathogenic.

CONCLUSIONS:

This validated high-throughput assay provides clinical-grade functional evidence to aid the classification of current and future
SCN5A
–Brugada syndrome variants of uncertain significance.
Rare Variant in
MRC2
Associated With Familial Supraventricular Tachycardia and Wolff-Parkinson-White Syndrome
Authors: Potter Adam S. , Miyake Christina Y. , Gonzaga-Jauregui Claudia , Aguilar-Sanchez Yuriana , Hulsurkar Mohit M. , Lahiri Satadru K. , Moreira Lucia M. , Mehta Neelam , Azamian Mahshid S. , Lupski James R. , Reilly Svetlana , Lalani Seema R. , Wehrens Xander H.T.
Published: July 2024

BACKGROUND:

Accessory pathways are a common cause of supraventricular tachycardia (SVT) and can lead to sudden cardiac death in otherwise healthy children and adults when associated with Wolff-Parkinson-White syndrome. The goal of this study was to identify genetic variants within a large family with structurally normal hearts affected by SVT and Wolff-Parkinson-White syndrome and determine causality of the gene deficit in a corresponding mouse model.

METHODS:

Whole exome sequencing performed on 2 distant members of a 3-generation family in which multiple members were affected by SVT or Wolff-Parkinson-White pattern (preexcitation) on ECG identified
MRC2
as a candidate gene. Serial electrocardiograms, intracardiac electrophysiology studies, echocardiography, optical mapping studies, and histology were performed on both
Mrc2
mutant and WT (wild-type) mice.

RESULTS:

A rare HET (heterozygous) missense variant c.2969A>G;p.Glu990Gly (E990G) in
MRC2
was identified as the leading candidate gene variant segregating with the cardiac phenotype following an autosomal-dominant Mendelian trait segregation pattern with variable expressivity. In vivo electrophysiology studies revealed reentrant SVT in E990G mice. Optical mapping studies in E990G mice demonstrated abnormal retrograde conduction, suggesting the presence of an accessory pathway. Histological analysis of E990G mouse hearts showed a disordered ECM (extracellular matrix) in the annulus fibrosus. Finally,
Mrc2
knockdown in human cardiac fibroblasts enhanced accelerated cell migration.

CONCLUSIONS:

This study identified a rare nonsynonymous variant in the
MRC2
gene in individuals with familial reentrant SVT, Wolff-Parkinson-White ECG pattern, and structurally normal hearts. Furthermore,
Mrc2
knock-in mice revealed an increased incidence of reentrant SVT and bypass tract formation in the setting of preserved cardiac structure and function.
Genus Onobrychis (Fabaceae) in Tunisia: distribution, rediscovery, ecology, and description of two new variety with an updated identification key in the country
Authors: SAKHRAOUI ANIS , LTAEIF HELA BELHAJ , CASTILLO JESÚS M. , ROUZ SLIM
Published: July 2024

Long-term field surveys within Tunisian dorsal revealed the recollection of the poorly known North African endemic Onobrychis kabylica and O. conferta subsp. conferta. Two new varieties of O. conferta subsp. conferta are described and illustrated, a key to recognize the two varieties of the species and a distribution map of both taxa are included. IUCN Red List assessment shows that the species should be considered Critically Endangered and requires the implementation of immediate appropriate measurements to ensure their conservation.
Salvia glabrifolia (Lamiaceae), a new species from Hunan, China
Authors: CHENG KE-YI , ZHANG TING , XIE CHU-MIAO , DAI JING-MIN , HUANG MING-HAO , MENG YING , TIAN XIANG-RONG , ZHANG DAI-GUI , LONG XIU-JI , ZHANG MENG-HUA
Published: July 2024

Based on molecular and morphological evidence, a new species of Salvia (Lamiaceae), Salvia glabrifolia D.G. Zhang & X.J. Long, from Hunan Province, China, is described and illustrated. Salvia glabrifolia is morphologically similar to S. cavaleriei var. simplicifolia, S. daiguii, and S. cavaleriei var. cavaleriei but is distinct by its glabrous stem, petioles, veins, inflorescence axis, leaf margin repand, and glossy and subleathery leaf texture. Maximum likelihood (ML) analyses of the whole plastome dataset strongly supported S. glabrifolia as a sister to the S. japonica-S. liguliloba clade. Moreover, the chromosome number of S. glabrifolia, 2n = 16, is the same as other species in S. chinensis group.
Ceratopteris baguangensis (Pteridaceae), a new species of Ceratopteris from Guangdong, China
Authors: LI ZIXIANG , XIA ZENGQIANG , LIN LIN , HE CHUNMEI , LUO LIN , XING FUWU , WANG FAGUO
Published: July 2024

A new species of fern, Ceratopteris baguangensis was recently discovered in Shenzhen, Guangdong, China. Detailed morphological descriptions and photographs of the habitat are shown. C. baguangensis is similar to C. thalictroides and C. oblongiloba in the morphology of the fertile fronds but is distinct from them in the lobes of the sterile fronds. Furthermore, the chloroplast genome of C. baguangensis was sequenced and characterized. The annotated results revealed that the chloroplast genome had a conserved quadripartite structure, with a pair of inverted repeat regions (IRs) separating the large single copy (LSC) region and the small single copy (SSC) region, resulting in a total length of 149,755 base pairs (bp). The genome encodes a total of 120 unique genes, including 76 protein-coding genes, 36 tRNA genes, and 8 rRNA genes. Molecular evidence indicated that the C. baguangensis formed a distinct lineage and was sister to C. oblongiloba. Given the current population size of C. baguangensis in Baguang Heritiera littoralia Wetland Park, it is suggested C. baguangensis should be categorized as an Endangered (EN) species according to the criteria of IUCN. This study further enriches the diversity of the genus Ceratopteris and will help to elucidate their phylogenetic relationships.
Impact of Summer North Atlantic Sea Surface Temperature Tripole on Precipitation over Mid–High-Latitude Eurasia
Authors: Cheng Shanling , Yu Haipeng , Zhou Jie , Zhang Bofei , Ren Yu , Luo Hongyu , Chen Siyu , Gong Yongqi , Peng Ming , Zhu Yunsai
Published: July 2024

Eurasia is a sensitive and high-risk region for global climate changes, where climate anomalies significantly influence natural ecosystems, human health, and economic development. The North Atlantic tripole (NAT) sea surface temperature anomaly is crucial to interannual precipitation variations in Eurasia. Several studies have focused on the link between the NAT and climate anomalies in winter and spring. However, the mechanism by which the summer NAT impacts climate anomalies in Eurasia remains unclear. This study examines how the NAT impacts interannual variations of summer precipitation in mid–high-latitude Eurasia. Precipitation variations are associated with the atmospheric teleconnection triggered by the NAT. When the NAT is in its positive phase, the anomalous atmospheric diabatic heating over the North Atlantic excites an equivalent-barotropic Rossby wave train response that propagates eastward toward Eurasia, resulting in atmospheric circulation anomalies over the region. The combined effects of atmospheric circulation, radiative forcing, and water vapor transport anomalies lead to decreased precipitation across northern Europe and central Eurasia, with higher precipitation anomalies over northeast Asia. Finally, numerical experiments verify that the summer NAT excites atmospheric teleconnections that propagate downstream, affecting precipitation anomalies in mid–high-latitude Eurasia. This study provides a scientific basis for predicting Eurasian summer precipitation and strengthening disaster management strategies.
Greenhouse Gas Emissions from Thai and Japanese Restaurants for Reduction Management Strategies
Authors: Mungkung Rattanawan , Jaieim Piyatida , Chancharoonpong Panit
Published: July 2024

Quantifying the total greenhouse gas (GHG) emissions along the whole value chain is essential for effective greenhouse gas management. Two types of the most popular restaurants in Thailand were included in this study: 1) a restaurant that specialized in northeastern Thai cuisine with an area of 94 m2 and 41 000 clients per year and 2) a restaurant serving Japanese–Thai fusion meals with an area of 284 m2 with 59 000 clients per year. Notably, the scope 3 GHG emissions were the highest (76%–81% of total emissions). The main contributors at both restaurants were raw material acquisition, followed by transportation of raw materials and waste management. It was suggested that the restaurants should not overlook the major sources of scope 3 GHG emissions, especially in food procurement, transportation from suppliers, and waste management. GHG management measures that could be applied include using local food ingredients, buying raw materials from nearby locations, simulating transport routes to minimize the distance of transport, and separating food wastes and sorting recyclable packaging wastes for further use. In addition, the restaurants could flag low-carbon footprint meals on their menus to engage their customers in contributing to GHG reductions.
Are Millennials Spearheading SDG 12 in Sustainable Workplaces?
Authors: Kaur Mandeep , Mittal Shweta , Kaur Amarjeet
Published: July 2024

This article offers insights for companies and managers to understand how millennials’ traits contribute to fostering an environmentally sustainable workplace, ultimately aiding in achieving environmental sustainability. Employing mindful learning theory as its foundation, the article proposes a framework that leverages millennials’ characteristics to create a sustainable workplace. It highlights how millennials’ inclinations towards sustainability can shape eco-friendly work environments, allowing companies to align individual and organisational goals. This alignment, focused on responsible production and consumption (SDG 12), can drive progress towards environmental sustainability. The significance of this article lies in succinctly explaining millennial traits and their potential use by companies in cultivating sustainable workplaces, ultimately contributing to the pursuit of SDG 12.
The Writing in the Sand. Introducing Sandtray Work in Futures Research Supervision
Authors: Westacott Marguerite , Flynn Trudi
Published: July 2024

This paper presents an open inquiry that embraces curiosity and vulnerability in the anticipatory space of an art-led, Futures orientated PhD supervisory relationship. We use sandtray work to elicit an anticipatory aesthetic, recording emergent data and processes through the dialogical method of duoethnography, and the visual format of photography. We seek to generate an environment that rouses imagination, creativity and futures consciousness implicit in the Australian Research Council’s definition of research. We use a duoethnographic method to collaborate, reflect and provide dialogical ways to surface deep meanings. There is a shared equity of understanding of the research process as a vehicle for engaging with the unknown. Both supervisor and supervisee hold explicit and implicit referent knowledge in relation to person and process. Therefore, it is a collaborative, reciprocal and fluid environment, where 1 + 1 = ∞ possibilities. We use sandtray to provide the location of open inquiry, dialogical reciprocation, reflection, and improvisation. This gives voice to the meaning that is made in the meandering paths between the words and an opportunity to loosen the shackles of business as usual. The sandtray moves not-known material into conscious awareness via somatic/intuitive symbol selection, engagement with metaphor, and projection; each privileging the unconscious. Introducing sandtray process into the supervisory relationship provides an alternative and adjunct modality of non-verbal inquiry that can support the calling of an anticipatory aesthetic through the Futures Senses. While there is rich, though sparse, literature describing the facilitation of sandtray work within the context of clinical supervision of mental health professionals, the introduction of such an approach within research supervision appears rare, or unique in relation to published research.
Recent advances in two-dimensional perovskite materials for light-emitting diodes
Authors: Tyagi Deepika , Laxmi Vijay , Basu Nilanjan , Reddy Leelakrishna , Tian Yibin , Ouyang Zhengbiao , Nayak Pramoda K.
Published: July 2024

Light-emitting diodes (LEDs) are an indispensable part of our daily life. After being studied for a few decades, this field still has some room for improvement. In this regard, perovskite materials may take the leading role. In recent years, LEDs have become a most explored topic, owing to their various applications in photodetectors, solar cells, lasers, and so on. Noticeably, they exhibit significant characteristics in developing LEDs. The luminous efficiency of LEDs can be significantly enhanced by the combination of a poor illumination LED with low-dimensional perovskite. In 2014, the first perovskite-based LED was illuminated at room temperature. Furthermore, two-dimensional (2D) perovskites have enriched this field because of their optical and electronic properties and comparatively high stability in ambient conditions. Recent and relevant advancements in LEDs using low-dimensional perovskites including zero-dimensional to three-dimensional materials is reported. The major focus of this article is based on the 2D perovskites and their heterostructures (i.e., a combination of 2D perovskites with transition metal dichalcogenides, graphene, and hexagonal boron nitride). In comparison to 2D perovskites, heterostructures exhibit more potential for application in LEDs. State-of-the-art perovskite-based LEDs, current challenges, and prospects are also discussed.

Graphical Abstract
Breed of origin analysis in genome-wide association studies: enhancing SNP-based insights into production traits in a commercial Brangus population
Authors: Zayas Gabriel A. , Rodriguez Eduardo , Hernandez Aakilah , Rezende Fernanda M. , Mateescu Raluca G.
Published: July 2024

Background

Carcass weight (HCW) and marbling (MARB) are critical for meat quality and market value in beef cattle. In composite breeds like Brangus, which meld the genetics of Angus and Brahman, SNP-based analyses have illuminated some genetic influences on these traits, but they fall short in fully capturing the nuanced effects of breed of origin alleles (BOA) on these traits. Focus on the impacts of BOA on phenotypic features within Brangus populations can result in a more profound understanding of the specific influences of Angus and Brahman genetics. Moreover, the consideration of BOA becomes particularly significant when evaluating dominance effects contributing to heterosis in crossbred populations. BOA provides a more comprehensive measure of heterosis due to its ability to differentiate the distinct genetic contributions originating from each parent breed. This detailed understanding of genetic effects is essential for making informed breeding decisions to optimize the benefits of heterosis in composite breeds like Brangus.

Objective

This study aims to identify quantitative trait loci (QTL) influencing HCW and MARB by utilizing SNP and BOA information, incorporating additive, dominance, and overdominance effects within a multi-generational Brangus commercial herd.

Methods

We analyzed phenotypic data from 1,066 genotyped Brangus steers. BOA inference was performed using LAMP-LD software using Angus and Brahman reference sets. SNP-based and BOA-based GWAS were then conducted considering additive, dominance, and overdominance models.

Results

The study identified numerous QTLs for HCW and MARB. A notable QTL for HCW was associated to the SGCB gene, pivotal for muscle growth, and was identified solely in the BOA GWAS. Several BOA GWAS QTLs exhibited a dominance effect underscoring their importance in estimating heterosis.

Conclusions

Our findings demonstrate that SNP-based methods may not detect all genetic variation affecting economically important traits in composite breeds. BOA inclusion in genomic evaluations is crucial for identifying genetic regions contributing to trait variation and for understanding the dominance value underpinning heterosis. By considering BOA, we gain a deeper understanding of genetic interactions and heterosis, which is integral to advancing breeding programs. The incorporation of BOA is recommended for comprehensive genomic evaluations to optimize trait improvements in crossbred cattle populations.
Identification and expression analysis of Sox family genes in echinoderms
Authors: Li Xiaojing , Cao Tiangui , Liu Hui , Fu Longhai , Wang Quanchao
Published: July 2024

The Sox gene family, a collection of transcription factors widely distributed throughout the animal kingdom, plays a crucial role in numerous developmental processes. Echinoderms occupy a pivotal position in many research fields, such as neuroscience, sex determination and differentiation, and embryonic development. However, to date, no comprehensive study has been conducted to characterize and analyze Sox genes in echinoderms. In the present study, the evolution and expression of Sox family genes across 11 echinoderms were analyzed using bioinformatics methods. The results revealed a total of 70 Sox genes, with counts ranging from 5 to 8 across different echinoderms. Phylogenetic analysis revealed that the identified Sox genes could be categorized into seven distinct classes: the SoxB1 class, SoxB2 class, SoxC class, SoxD class, SoxE class, SoxF class and SoxH class. Notably, the SoxB1, SoxB2, and SoxF genes were ubiquitously present in all the echinoderms studied, which suggests that these genes may be conserved in echinoderms. The spatiotemporal expression patterns observed for Sox genes in the three echinoderms indicated that various Sox members perform distinct functional roles. Notably, SoxB1 is likely involved in echinoderm ovary development, while SoxH may play a crucial role in testis development in starfish and sea cucumber. In general, the present investigation provides a molecular foundation for exploring the Sox gene in echinoderms, providing a valuable resource for future phylogenetic and genomic studies.
Analysis of risk factors for long-term mortality in patients with stage II and III tuberculous meningitis
Authors: Wang Ling , Gu Zhihan , Chen Xiaoli , Yu Xiaomin , Meng Xiandong
Published: July 2024

Objective

To investigate risk factors associated with long-term mortality in patients with stage II and III tuberculous meningitis (TBM).

Methods

This retrospective analysis examined patients who were first diagnosed with stage II and III TBM at West China Hospital of Sichuan University between January 1, 2018 and October 1, 2019. Patients were followed via telephone and categorized into survival and mortality groups based on 4-year outcomes. Multivariate logistic regression identified independent risk factors for long-term mortality in stage II and III TBM.

Results

In total, 178 patients were included, comprising 108 (60.7%) males and 36 (20.2%) non-survivors. Mean age was 36 ± 17 years. Compared to survivors, non-survivors demonstrated significantly higher age, heart rate, diastolic blood pressure, blood glucose, rates of headache, neurological deficits, cognitive dysfunction, impaired consciousness, hydrocephalus, and basal meningeal inflammation. This group also exhibited significantly lower Glasgow Coma Scale (GCS) scores, blood potassium, albumin, and cerebrospinal fluid chloride. Multivariate analysis revealed age (OR 1.042; 95% CI 1.015–1.070; P = 0.002), GCS score (OR 0.693; 95% CI 0.589–0.814; P < 0.001), neurological deficits (OR 5.204; 95% CI 2.056–13.174; P < 0.001), and hydrocephalus (OR 2.680; 95% CI 1.081–6.643; P = 0.033) as independent mortality risk factors. The ROC curve area under age was 0.613 (95% CI 0.506–0.720; P = 0.036) and 0.721 (95% CI 0.615–0.826; P < 0.001) under GCS score.

Conclusion

Advanced age, reduced GCS scores, neurological deficits, and hydrocephalus were identified as independent risk factors for mortality in stage II and III TBM patients.
Azithromycin sequential therapy plus inhaled terbutaline for Mycoplasma Pneumoniae pneumonia in children: a systematic review and meta-analysis
Authors: Sheng Yongcheng , Liang Yi , Zhao Chongyang , Kang Deying , Liu Xueting
Published: June 2024

Background

An improper host immune response to Mycoplasma pneumoniae generates excessive inflammation, which leads to the impairment of pulmonary ventilation function (PVF). Azithromycin plus inhaled terbutaline has been used in the treatment of Mycoplasma pneumoniae pneumonia (MPP) in children with impaired pulmonary function, but previous randomized controlled trials (RCTs) showed inconsistent efficacy and safety. This study is aimed to firstly provide a systematic review of the combined therapy.

Methods

This study was registered at the International Prospective Register of Systematic Reviews (PROSPERO CRD42023452139). A PRISMA-compliant systematic review and meta-analysis was performed. Six English and four Chinese databases were comprehensively searched up to June, 2023. RCTs of azithromycin sequential therapy plus inhaled terbutaline were selected. The revised Cochrane risk of bias tool for randomized trials (RoB2) was used to evaluate the methodological quality of all studies, and meta-analysis was performed using Stata 15.0 with planned subgroup and sensitivity analyses. Publication bias was evaluated by a funnel plot and the Harbord’ test. Certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation recommendations.

Results

A total of 1,938 pediatric patients from 20 RCTs were eventually included. The results of meta-analysis showed that combined therapy was able to significantly increase total effectiveness rate (RR = 1.20, 95%CI 1.15 to 1.25), forced expiratory volume in one second (SMD = 1.14, 95%CIs, 0.98 to 1.29), the ratio of forced expiratory volume in one second/forced vital capacity (SMD = 2.16, 95%CIs, 1.46 to 2.86), peak expiratory flow (SMD = 1.17, 95%CIs, 0.91 to 1.43). The combined therapy was associated with a 23% increased risk of adverse reactions compared to azithromycin therapy alone, but no significant differences were found. Harbord regression showed no publication bias (P = 0.148). The overall quality of the evidence ranged from moderate to very low.

Conclusions

This first systematic review and meta-analysis suggested that azithromycin sequential therapy plus inhaled terbutaline was safe and beneficial for children with MPP. In addition, the combined therapy represented significant improvement of PVF. Due to lack of high-quality evidence, our results should be confirmed by adequately powered RCTs in the future.
Mental health outcomes of offspring exposed to parental intimate partner violence in Rwanda
Authors: Bahati Claire , Nyiranteziryayo Amina , Izabayo Josias , Atete Pauline , Sezibera Vincent , Mutesa Leon
Published: July 2024

Background

Children who witness parental intimate partner violence (IPV) are more likely to develop mental health issues compared to those who do not witness such violence.

Objective

The main objective of this study is to assess the association between parental intimate partner violence and child mental health outcomes.

Methodology

This cross-sectional study involved 548 participants divided into two groups: parents (N = 304) and offspring (N = 244). The participants were recruited from Mageragere Sector in the City of Kigali (urban), as well as Mbazi and Ruhashya sectors in Huye District (rural). To assess the difference about mental difficulties reported by the offspring, a Mann-Whitney U test was employed to compare the responses of parents and their children on mental health outcomes. Additionally, multiple linear regression analysis was conducted to explore the association between parental intimate partner violence (IPV) and the mental health outcomes of their offspring.

Results

The results highlighted significant levels of mental and emotional challenges in children, as reported by both parents and the children themselves. Depression and youth conduct problems were more prevalent among the children compared to their parents, whereas anxiety and irritability were more commonly reported by parents than by their children. Intimate partner violence showed to be a predictor of irritability and anxiety symptoms in offspring. In terms of irritability, depression, and youth conduct problems they were identified as predictors of anxiety symptoms. Particularly, anxiety and irritability were revealed to predict youth conduct problems.

Conclusion

The study indicates that parental intimate partner violence (IPV) has an impact on the mental well-being of their offspring. Furthermore, it was observed that there is not only a correlation between IPV and poor mental health outcomes, but also a connection between different mental conditions, implying that children exposed to IPV are more prone to experiencing a range of mental issues. As a result, intervention programs should place emphasis on addressing the mental disorders of both parents and children.
Examining the relationship between physical literacy and resilience against COVID-19-induced negative mental states in Chinese adolescents
Authors: Wu Jiarun , Kuan Garry , Wang Yishuai , Liu Zhutang , Hu Xiaoyu , Kueh Yee Cheng , Zhang Xinding
Published: July 2024

Research indicates that COVID-19 has had adverse effects on the mental health of adolescents, exacerbating their negative psychological states. The purpose of this study is to investigate the impact of Physical Literacy (PL) on Negative Mental State caused by COVID-19 (NMSC) and identify potential factors related to NMSC and PL in Chinese adolescents. This cross-sectional study involved a total of 729 Chinese high school students with an average age of 16.2 ± 1.1 years. Participants’ demographic data, PL data, and NMSC data were collected. PL and NMSC were measured using the self-reported Portuguese Physical Literacy Assessment Questionnaire (PPLA-Q), the Stress and Anxiety to Viral Epidemics-6 (SAVE-6), and the Fear of COVID-19 Scale (FCV-19). Adolescents in the current study demonstrated higher levels of NMSC and lower PL, with average scores of 3.45 and 2.26, respectively (on a scale of 5). Through multiple linear regression analysis, Motivation (MO), Confidence (CO), Emotional Regulation (ER), and Physical Regulation (PR) were identified as factors influencing NMSC in adolescents. The study findings contribute to providing guidance for actions aimed at alleviating NMSC among adolescents.
Insights into treatment-specific prognostic somatic mutations in NSCLC from the AACR NSCLC GENIE BPC cohort analysis
Authors: Liu Yi , Yalavarthi Sindhu , Yang Fan , Abdul-Rashid Yusif , Tang Shenkun , Long Zihe , Qin Yongkai , Wu Kerui , Wang Zhifei
Published: July 2024

Background

Treatment of non-small lung cancer (NSCLC) has evolved in recent years, benefiting from advances in immunotherapy and targeted therapy. However, limited biomarkers exist to assist clinicians and patients in selecting the most effective, personalized treatment strategies. Targeted next-generation sequencing–based genomic profiling has become routine in cancer treatment and generated crucial clinicogenomic data over the last decade. This has made the development of mutational biomarkers for drug response possible.

Methods

To investigate the association between a patient’s responses to a specific somatic mutation treatment, we analyzed the NSCLC GENIE BPC cohort, which includes 2,004 tumor samples from 1,846 patients.

Results

We identified somatic mutation signatures associated with response to immunotherapy and chemotherapy, including carboplatin-, cisplatin-, pemetrexed- or docetaxel-based chemotherapy. The prediction power of the chemotherapy-associated signature was significantly affected by epidermal growth factor receptor (EGFR) mutation status. Therefore, we developed an EGFR wild-type–specific mutation signature for chemotherapy selection.

Conclusion

Our treatment-specific gene signatures will assist clinicians and patients in selecting from multiple treatment options.
Nanostructured ZnO thin film to enhance gutta-percha’s adhesion to endodontic sealers
Authors: Ferreira Inês , Lopes Cláudia , Ferreira Armando , Braga Ana Cristina , Vaz Filipe , Pina-Vaz Irene , Martin-Biedma Benjamin
Published: July 2024

Background

Gutta-percha (GP) combined with an endodontic sealer is still the core material most widely used for tridimensional obturation. The sealer acts as a bonding agent between the GP and the root dentinal walls. However, one of the main drawbacks of GP core material is the lack of adhesiveness to the sealer. ZnO thin films have many remarkable features due to their considerable bond strength, good optical quality, and excellent piezoelectric, antibacterial, and antifungal properties, offering many potential applications in various fields. This study aimed to explore the influence of GP surface’s functionalization with a nanostructured ZnO thin film on its adhesiveness to endodontic sealers.

Methods

Conventional GP samples were divided randomly into three groups: (a) Untreated GP (control); (b) GP treated with argon plasma (PT); (c) Functionalized GP (PT followed by ZnO thin film deposition). GP’s surface functionalization encompassed a multi-step process. First, a low-pressure argon PT was applied to modify the GP surface, followed by a ZnO thin film deposition via magnetron sputtering. The surface morphology was assessed using SEM and water contact angle analysis. Further comprehensive testing included tensile bond strength assessment evaluating Endoresin and AH Plus Bioceramic sealers’ adhesion to GP. ANOVA procedures were used for data statistical analysis.

Results

The ZnO thin film reproduced the underlying surface topography produced by PT. ZnO thin film deposition decreased the water contact angle compared to the control (p < 0.001). Endoresin showed a statistically higher mean bond strength value than AH Plus Bioceramic (p < 0.001). There was a statistically significant difference between the control and the ZnO-functionalized GP (p = 0.006), with the latter presenting the highest mean bond strength value.

Conclusions

The deposition of a nanostructured ZnO thin film on GP surface induced a shift towards hydrophilicity and an increased GP’s adhesion to Endoresin and AH Bioceramic sealers.
Variance due to the examination conditions and factors associated with success in objective structured clinical examinations (OSCEs): first experiences at Paris-Saclay medical school
Authors: Amadou Coralie , Veil Raphael , Blanié Antonia , Nicaise Claire , Rouquette Alexandra , Gajdos Vincent
Published: July 2024

Background

We aimed to measure the variance due to examination conditions during the first sessions of objective structured clinical examinations (OSCEs) performed at a French medical school and identify factors associated with student success.

Methods

We conducted a retrospective, observational study using data from the first three OSCEs sessions performed at Paris-Saclay medical school in 2021 and 2022. For all sessions (each organized in 5 parallel circuits), we tested a circuit effect using a linear mixed-effects model adjusted for sex and the average academic level of students (according to written tests). Then, we studied the factors associated with student success at one station using a multivariate linear mixed-effects model, including the characteristics of students, assessors, and standardized patients.

Results

The study included three OSCEs sessions, with 122, 175, and 197 students and a mean (± SD) session score of 13.7(± 1.5)/20, 12.7(± 1.7)/20 and 12.7(± 1.9)/20, respectively. The percentage of variance due to the circuit was 6.5%, 18.2% (statistically significant), and 3.8%, respectively. For all sessions, the student’s average level and station scenario were significantly associated with the score obtained in a station. Still, specific characteristics of assessors or standardized patients were only associated with the student’s score in April 2021 (first session).

Conclusion

The percentage of the variance of students’ performance due to the examination conditions was significant in one out of three of the first OSCE sessions performed at Paris-Saclay medical school. This result seems more related to individual behaviors rather than specific characteristics of assessors or standardized patients, highlighting the need to continue training teaching teams.

National clinical trial number

Not applicable.
Trainees’ perspectives on sickle cell education: a qualitative needs assessment
Authors: Prince Elizabeth J. , Feder Katherine J. , Calhoun Cecelia , Lee Alfred I. , Carroll C. Patrick , Restrepo Valentina , Van Doren Layla
Published: July 2024

Background

Sickle cell disease (SCD) exemplifies many of the social, racial, and healthcare equity issues in the United States. Despite its high morbidity, mortality, and cost of care, SCD has not been prioritized in research and clinical teaching, resulting in under-trained clinicians and a poor evidence base for managing complications of the disease. This study aimed to perform a needs assessment, examining the perspectives of medical trainees pursuing hematology/oncology subspecialty training regarding SCD-focused education and clinical care.

Method

Inductive, iterative thematic analysis was used to explore qualitative interviews of subspecialty hematology-oncology trainees’ attitudes and preferences for education on the management of patients with SCD. Fifteen trainees from six programs in the United States participated in 4 focus groups between April and May 2023.

Results

Thematic analysis resulted in 3 themes: 1. Discomfort caring for patients with SCD. 2. Challenges managing complications of SCD, and 3. Desire for SCD specific education. Patient care challenges included the complexity of managing SCD complications, limited evidence to guide practice, and healthcare bias. Skill-building challenges included lack of longitudinal exposure, access to expert clinicians, and didactics.

Conclusions

Variations in exposure, limited formal didactics, and a lack of national standardization for SCD education during training contributes to trainees' discomfort and challenges in managing SCD, which in turn, contribute to decreased interest in entering the SCD workforce. The findings underscore the need for ACGME competency amendments, dedicated SCD rotations, and standardized didactics to address the gaps in SCD education.

Graphical Abstract
Application of the “Plan-Do-Check-Action” plan in improving the pass rate of the “National Medical Licensing Examination”
Authors: Zhou Shu , Zhang Xian , Zhang Hao , Zhang Donglei , Wei Renxiong , Yang Miao
Published: July 2024

Background

The National Medical Licensing Examination (NMLE) is the only objective, standardized metric to evaluate whether a medical student possessing the professional knowledge and skills necessary to work as a physician. However, the overall pass rate of NMLE in our hospital in 2021 was much lower than that of Peking Union Medical College Hospital, which was required to be further improved.

Methods

To find the reasons for the unsatisfactory performance in 2021, the quality improvement team (QIT) organized regular face-to-face meetings for in-depth discussion and questionnaire, and analyzed the data by “Plato analysis” and “Brainstorming method”. After finding out the reasons, the “Plan-Do-Check-Action” (PDCA) cycle was continued to identify and solve problems, which included the formulation and implementation of specific training plans by creating the “Gantt charts”, the check of effects, and continuous improvements from 2021 to 2022. Detailed information about the performance of students in 2021 and 2022, and the attendance, assessment, evaluation and suggestions from our hospital were provided by the relevant departments, and the pass rate-associated data was collected online.

Results

After the PDCA plan, the pass rate of NMLE in our hospital increased by 10.89% from 80.15% in 2021 to 91.04% in 2022 (P = 0.0109), with the pass rate of skill examination from 95.59% in 2021 to 99.25% in 2022 (P = 0.0581) and theoretical examination from 84.5% in 2021 to 93.13% in 2022 (P = 0.027). Additionally, the mean scores of all examinees increased with the theoretical examination score increasing from 377.0 ± 98.76 in 2021 to 407.6 ± 71.94 in 2022 (P = 0.004).

Conclusions

Our results showed a success application of the PDCA plan in our hospital which improved the pass rate of the NMLE in 2022, and the PDCA plan may provide a practical framework for future medical education and further improve the pass rate of NMLE in the next year.
Myeloid-specific Hdac10 deletion protects against LPS-induced acute lung injury via P62 acetylation at lysine 165
Authors: Xiang Yuanyuan , Zhong Yu , Lai Xianwen , Fang Zhenfu , Su Guomei , Lv Yingying , Tang Xiantong , Ouyang Lihuan , Gao Xiao , Zheng Hongying , He Lilin , Chen Jialong , Huang Jiewen , Lai Tianwen
Published: July 2024

Background

Aberrant activation of macrophages is associated with pathogenesis of acute lung injury (ALI). However, the potential pathogenesis has not been explored.

Objectives

We aimed to identify whether histone deacetylase (HDAC) 10 is involved in lipopolysaccharide (LPS)-exposed ALI and reveal the underlying pathogenesis by which it promotes lung inflammation in LPS-exposed ALI via modifying P62 with deacetylation.

Methods

We constructed an ALI mice model stimulated with LPS to determine the positive effect of Hdac10 deficiency. Moreover, we cultured murine alveolar macrophage cell line (MH-S cells) and primary bone marrow-derived macrophages (BMDMs) to explore the pro-inflammatory activity and mechanism of HDAC10 after LPS challenge.

Results

HDAC10 expression was increased both in mice lung tissues and macrophage cell lines and promoted inflammatory cytokines production exposed to LPS. Hdac10 deficiency inhibited autophagy and inflammatory response after LPS stimulation. In vivo, Hdac10fl/fl-LysMCre mice considerably attenuated lung inflammation and inflammatory cytokines release exposed to LPS. Mechanistically, HDAC10 interacts with P62 and mediates P62 deacetylation at lysine 165 (K165), by which it promotes P62 expression and increases inflammatory cytokines production. Importantly, we identified that Salvianolic acid B (SAB), an HDAC10 inhibitor, reduces lung inflammatory response in LPS-stimulated ALI.

Conclusion

These results uncover a previously unknown role for HDAC10 in regulating P62 deacetylation and aggravating lung inflammation in LPS-induced ALI, implicating that targeting HDAC10 is an effective therapy for LPS-exposed ALI.
Natural killer cell-derived exosome-based cancer therapy: from biological roles to clinical significance and implications
Authors: Si Chaohua , Gao Jianen , Ma Xu
Published: July 2024

Natural killer (NK) cells are important immune cells in the organism and are the third major type of lymphocytes besides T cells and B cells, which play an important function in cancer therapy. In addition to retaining the tumor cell killing function of natural killer cells, natural killer cell-derived exosomes cells also have the characteristics of high safety, wide source, easy to preserve and transport. At the same time, natural killer cell-derived exosomes are easy to modify, and the engineered exosomes can be used in combination with a variety of current cancer therapies, which not only enhances the therapeutic efficacy, but also significantly reduces the side effects. Therefore, this review summarizes the source, isolation and modification strategies of natural killer cell-derived exosomes and the combined application of natural killer cell-derived engineered exosomes with other antitumor therapies, which is expected to accelerate the clinical translation process of natural killer cell-derived engineered exosomes in cancer therapy.
Activity-based detection of synthetic cannabinoid receptor agonists in plant materials
Authors: Timmerman Axelle , Balcaen Margot , Coopman Vera , Degreef Maarten , Pottie Eline , Stove Christophe P.
Published: July 2024

Background

Since late 2019, fortification of ‘regular’ cannabis plant material with synthetic cannabinoid receptor agonists (SCRAs) has become a notable phenomenon on the drug market. As many SCRAs pose a higher health risk than genuine cannabis, recognizing SCRA-adulterated cannabis is important from a harm reduction perspective. However, this is not always an easy task as adulterated cannabis may only be distinguished from genuine cannabis by dedicated, often expensive and time-consuming analytical techniques. In addition, the dynamic nature of the SCRA market renders identification of fortified samples a challenging task. Therefore, we established and applied an in vitro cannabinoid receptor 1 (CB1) activity-based procedure to screen plant material for the presence of SCRAs.

Methods

The assay principle relies on the functional complementation of a split-nanoluciferase following recruitment of β-arrestin 2 to activated CB1. A straightforward sample preparation, encompassing methanolic extraction and dilution, was optimized for plant matrices, including cannabis, spiked with 5 µg/mg of the SCRA CP55,940.

Results

The bioassay successfully detected all samples of a set (n = 24) of analytically confirmed authentic Spice products, additionally providing relevant information on the ‘strength’ of a preparation and whether different samples may have originated from separate batches or possibly the same production batch. Finally, the methodology was applied to assess the occurrence of SCRA adulteration in a large set (n = 252) of herbal materials collected at an international dance festival. This did not reveal any positives, i.e. there were no samples that yielded a relevant CB1 activation.

Conclusion

In summary, we established SCRA screening of herbal materials as a new application for the activity-based CB1 bioassay. The simplicity of the sample preparation, the rapid results and the universal character of the bioassay render it an effective and future-proof tool for evaluating herbal materials for the presence of SCRAs, which is relevant in the context of harm reduction.
Caesarean section on maternal request: a qualitative study of conflicts related to shared decision-making and person-centred care in Sweden
Authors: Fredriksson Mio , Holmström Inger K , Höglund Anna T , Fleron Emma , Mattebo Magdalena
Published: July 2024

Background

Today, person-centred care is seen as a cornerstone of health policy and practice, but accommodating individual patient preferences can be challenging, for example involving caesarean section on maternal request (CSMR). The aim of this study was to explore Swedish health professionals’ perspectives on CSMR and analyse them with regard to potential conflicts that may arise from person-centred care, specifically in relation to shared decision-making.

Methods

A qualitative study using both inductive and deductive content analysis was conducted based on semi-structured interviews. It was based on a purposeful sampling of 12 health professionals: seven obstetricians, three midwives and two neonatologists working at different hospitals in southern and central Sweden. The interviews were recorded either in a telephone call or in a video conference call, and audio files were deleted after transcription.

Results

In the interviews, twelve types of expressions (sub-categories) of five types of conflicts (categories) between shared decision-making and CSMR emerged. Most health professionals agreed in principle that women have the right to decide over their own body, but did not believe this included the right to choose surgery without medical indications (patient autonomy). The health professionals also expressed that they had to consider not only the woman’s current preferences and health but also her future health, which could be negatively impacted by a CSMR (treatment quality and patient safety). Furthermore, the health professionals did not consider costs in the individual decision, but thought CSMR might lead to crowding-out effects (avoiding treatments that harm others). Although the health professionals emphasised that every CSMR request was addressed individually, they referred to different strategies for avoiding arbitrariness (equality and non-discrimination). Lastly, they described that CSMR entailed a multifaceted decision being individual yet collective, and the use of birth contracts in order to increase a woman’s sense of security (an uncomplicated decision-making process).

Conclusions

The complex landscape for handling CSMR in Sweden, arising from a restrictive approach centred on collective and standardised solutions alongside a simultaneous shift towards person-centred care and individual decision-making, was evident in the health professionals’ reasoning. Although most health professionals emphasised that the mode of delivery is ultimately a professional decision, they still strived towards shared decision-making through information and support. Given the different views on CSMR, it is of utmost importance for healthcare professionals and women to reach a consensus on how to address this issue and to discuss what patient autonomy and shared decision-making mean in this specific context.