bluuebunny/crossref_metadata_2025 huggingface dataset:
Requirements and special considerations for drug trials with children across six jurisdictions: 2. Ethics review in the regulatory approval process
Authors: Stewart Breanne , Lepola Pirkko , Egger Gunter F. , Ali Fahimeda , Allen Albert J. , Croker Alysha K. , Davidson Andrew J. , Dicks Pamela , Faust Saul N. , Green Dionna , Hovinga Collin , Klein Agnes V. , Langham Robyn , Nakamura Hidefumi , Pioppo Laura , Ramroop Shiva , Sakiyama Michiyo , Sanchez Vigil de la Villa Isabel , Sato Junko , Snyder Donna L. , Turner Mark A. , Zaidi Sarah , Zimmerman Kanecia , Lacaze-Masmonteil Thierry
Published: February 2025

Background

Conducting clinical drug trials (CTs) with children presents several challenges. A major challenge is the need to enroll participants at multiple sites across different jurisdictions. Recruiting the required number of children within a reasonable timeframe requires the study to be reviewed by Research Ethics Boards (REB) or Institutional Review Boards (IRB) at multiple sites across various jurisdictions. This work, undertaken by the Working Group (WG) on International Collaborations at the European Network of Pediatric Research at the European Medicines Agency (Enpr-EMA) aims to describe the research ethics review requirements including any pediatric specific requirements, as well as current or upcoming changes across six jurisdictions – the European Union (EU), United Kingdom (UK), United States of America (USA), Canada, Japan, and Australia.

Methods

An open questionnaire developed by the WG and directed at both the Competent Authorities (CA) and the national pediatric clinical trial networks arranged by jurisdictions.

Results

A synopsis of the current regulatory requirements covers centralized versus independent review, comparisons between investigator initiated and industry sponsored clinical trials, timelines, review board members requirements and the consenting/assent process for clinical trial (CT) applications, application submission processes and application requirements for each of the six jurisdictions. It also describes changes currently or soon to be implemented in some jurisdictions.

Conclusion

This environmental scan highlights the differences in ethics review for CTs in pediatric medicine development across six jurisdictions. While there is a growing trend for centralized ethics review, it is not universally permitted due to institutional, state/provincial, or national policies. Even where central review is allowed, local review may still be required for vulnerable populations like children. Harmonized and centralized ethics reviews offer advantages such as expert pediatric reviewers and efficient and consistent evaluations.
Trichoderma collection from Brazilian soil reveals a new species: T. cerradensis Sp. nov.
Authors: Peixoto Gustavo Henrique Silva , da Silva Rildo Alexandre Fernandes , Zacaroni Ana Beatriz , Silva Thais França , Chaverri Priscila , Pinho Danilo Batista , de Mello Sueli Corrêa Marques
Published: February 2025

Trichoderma spp. are important biological control agents and plant growth promoters. However, only a limited number of species are used in biological control even though the genus contains more than 400 species, with most of them being mycotrophic. In this study, 97 Trichoderma isolates preserved at the EMBRAPA collection (an important source for biocontrol agents) and previously collected from several areas in Brazil were characterized which were identified using various molecular markers (internal transcribed spacers (its), translation elongation factor (tef1α), RNA polymerase II subunit (rpb2), actin (act), and calmodulin (cal). Of these, 54 isolates were found to group in the Harzianum species complex and 32 in Sect. Trichoderma. Others were distributed in the following clades: Strictipilosa complex (one isolate), Longibrachiatum (four isolates), and Brevicompactum (seven isolates). Most of the isolates were identified within 17 known species, whereas Trichoderma inhamatum and T. dorothopsis were synonymized under T. lentiforme and T. koningiopsis, respectively, based on multi-locus phylogenetic analysis and GCPRS criteria. However, two isolates formed a clade apart from previously identified species from Sect. Trichoderma and identified as a new species: T. cerradensis sp. nov. The multigenic characterization of isolates deposited in fungal culture collections is crucial for accurate identification and reveals a diverse range of Trichoderma species in Brazil.
Large-scale screening of HIV-1 T-cell epitopes restricted by 12 prevalent HLA-A allotypes in Northeast Asia and universal detection of HIV-1-specific CD8+ T cells
Authors: Ding Yan , Yan Jialai , Huang Ling , Yu Jinhong , Wu Yandan , Shen Chuanlai , Fang Anning
Published: February 2025

Background

Although the immune response of host T cells to human immunodeficiency virus (HIV) significantly influences the progression of the infection, the development of T-cell-based vaccines and therapies, as well as the clinical evaluation of specific T-cell functions, is currently markedly hindered by the absence of broad-spectrum, functionally validated HIV T-cell epitopes that account for the polymorphisms of the human leukocyte antigen (HLA) within an indicated geographic population. This study aimed to identify T-cell epitopes derived from the GP160, GAG, and POL proteins of the HIV-1 strain, specifically linked to 12 prevalent HLA-A allotypes, that collectively represent approximately 91% of the total gene frequency in Northeast Asian populations.

Methods

A total of 134 epitopes were predicted in silico and selected as potential candidates for further validation. Subsequently, peripheral blood mononuclear cells (PBMCs) were collected from 96 individuals with HIV-1 and cocultured ex vivo with each epitope candidate peptide, followed by the detection of activated CD8+ T cells. Peripheral blood mononuclear cells (PBMCs) were collected from 96 individuals with HIV-1 and cocultured ex vivo with each candidate peptide epitope, followed by the detection of activated CD8+ T cells. A total of 69 epitopes were validated as real-world HIV T-cell epitopes presented by 12 dominant HLA-A allotypes. Furthermore, the HLA-A cross-restriction for each epitope candidate was identified through peptide competitive binding assays using 12 transfected HMy2.CIR cell lines.

Results

A total of 45 epitopes demonstrated high affinity, while 31 epitopes displayed intermediate affinity. A broad-spectrum CD8+ T-cell epitope library containing 141 validated epitope peptides was used to universally detect HIV-1-specific CD8+ T cells via peptide-PBMC ex vivo coculture and intracellular IFN-γ staining. In 52 people with HIV-1, the number of reactive HIV-1 specific CD8+ T cells was significantly higher in the CD4+ T-cell-high patient group compared to the CD4+ T-cell-low patient group, and it correlated with the CD4+ T-cell-low patient group (<200/μL).

Conclusion

This study provides a broad-spectrum CD8+ T-cell epitope library aimed at developing a T-cell-directed HIV vaccine that offers high population coverage in Northeast Asia. In addition, it establishes a universal detection method for the clinical assessment of HIV-1-specific CD8+ T-cell responses.
The occurrence of wheat crown rot correlates with the microbial community and function in rhizosphere soil
Authors: Wang Yajiao , Feng Jian , Gao Jianhai , Han Sen , Li Qiusheng , Kong Lingxiao , Wu Yuxing
Published: February 2025

Wheat crown rot (WCR) is a significant soil-borne disease affecting wheat production worldwide. Understanding the impact of wheat crown rot on the structure and function of microbial communities in the wheat rhizosphere soil can provide a theoretical basis for the mining biological control resources against WCR. In this study, rhizosphere soils with varying WCR severities (light, moderate, severe) were analyzed for chemical properties, microbial community composition and functions using high-throughput sequencing. The results revealed that WCR decreased rhizosphere soil pH, the content of available nitrogen and phosphorus, and the abundance of beneficial taxa such as Bacillus and Streptomyces. Additionally, functional predictions showed that microbial communities adapted to WCR by enhancing signaling pathways and reducing their anabolic activity. From soil with light WCR occurrence, we isolated Bacillus velezensis BF-237, whose abundance was reduced by WCR. Greenhouse experiments demonstrated that BF-237 achieved a control efficiency of 56.61% against WCR in artificially inoculated sterilized soil and 53.32% in natural soil. This study clarifies the impact of wheat crown rot on the community structure, and function of rhizosphere soil microorganisms, alongside identifying a promising biocontrol agent. These findings contribute to understanding WCR pathogenesis and offer practical resources for its management.
Relationships between the menstrual cycle and neuropsychiatric and physical symptoms in females with Tourette syndrome
Authors: Noriega-Makarskyy Daisy T. , Realbuto Evan , Kaylor Ariadne , Osiecki Lisa , Essa Angela , Yu Dongmei , Illmann Cornelia , Mathews Carol A. , Scharf Jeremiah M.
Published: February 2025

Background

The effects of the menstrual cycle on neuropsychiatric and physical symptoms have been examined in multiple psychiatric illnesses, but research on Tourette syndrome (TS) and menstruation is limited and inconclusive. One study published in 1992 reported that 34% of female respondents experienced tic fluctuations with their menstrual cycles; however, a subsequent 2001 study found no significant relationship between menstrual cycle-related hormonal changes and tic symptoms across participants. There has been no further published exploration of this topic in the intervening 20+ years, and thus these discrepant results have not been reconciled. The current study aimed to assess tic changes across the menstrual cycle and to explore clinical predictors of tic fluctuations in adult females with TS.

Methods

An online survey was completed by 112 of 315 eligible female adults with TS. Respondents were asked to share their age of TS symptom onset, history of OCD and ADHD diagnoses, and current tic symptoms and severity. Participants also retrospectively reported their experiences with fluctuations in tics and other physical and psychiatric symptoms over the course of the menstrual cycle.

Results

26% of the 112 respondents endorsed tic changes in relation to their menstrual cycles. Univariable and multivariable logistic regression demonstrated that higher current tic severity and impairment as well as co-occurring cycle-related mood and anxiety changes significantly predicted the presence of self-reported tic fluctuations during the menstrual cycle.

Discussion

Results suggest that some females with TS experience changes in tic symptoms during their menstrual cycles, although future research is required to clarify the complex relationships between the menstrual cycle, tics, and other psychiatric symptoms. The low response rate, retrospective recall of symptoms, and lack of information about hormonal influences such as contraceptives and menopause are notable study limitations.
A novel paradigm for fast training data generation in asynchronous movement-based BCIs
Authors: Crell Markus R. , Kostoglou Kyriaki , Sterk Kathrin , Müller-Putz Gernot R.
Published: February 2025

Introduction

Movement-based brain-computer interfaces (BCIs) utilize brain activity generated during executed or attempted movement to provide control over applications. By relying on natural movement processes, these BCIs offer a more intuitive control compared to other BCI systems. However, non-invasive movement-based BCIs utilizing electroencephalographic (EEG) signals usually require large amounts of training data to achieve suitable accuracy in the detection of movement intent. Additionally, patients with movement impairments require cue-based paradigms to indicate the start of a movement-related task. Such paradigms tend to introduce long delays between trials, thereby extending training times. To address this, we propose a novel experimental paradigm that enables the collection of 300 cued movement trials in 18 min.

Methods

By obtaining measurements from ten participants, we demonstrate that the data produced by this paradigm exhibits characteristics similar to those observed during self-paced movement.

Results and discussion

We also show that classifiers trained on this data can be used to accurately detect executed movements with an average true positive rate of 31.8% at a maximum rate of 1.0 false positives per minute.
Combined morphology and radiomics of intravoxel incoherent movement as a predictive model for the pathologic complete response before neoadjuvant chemotherapy in patients with breast cancer
Authors: Zheng Yunyan , Zhang Hui , Chen Huijian , Song Yang , Lu Ping , Ma Mingping , Lin Mengbo , He Muzhen
Published: February 2025

Background

To develop a predictive model using baseline imaging of morphology and radiomics derived from intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) to determine the pathologic complete response (pCR) to neoadjuvant chemotherapy (NACT) in breast cancer patients.

Methods

A total of 265 patients who underwent 3.0 T MRI scans before NACT were examined. Among them, 113 female patients with stage II–III breast cancer were included. The training data set consisted of 79 patients (31/48=pCR/Non-PCR, npCR), while the remaining 34 cases formed the validation cohort (13/21=pCR/npCR). Radiomics and conventional magnetic resonance imaging features analysis were performed. To build a nomogram model that integrates the radiomics signature and conventional imaging, a logistic regression method was employed. The performance evaluation of the nomogram involved the area under the receiver operating characteristic curve (AUC), a decision curve analysis, and the calibration slope.

Results

In an assessment for predicting pCR, the radiomics model displayed an AUC of 0.778 and 0.703 for the training and testing cohorts, respectively. Conversely, the morphology model exhibited an AUC of 0.721 and 0.795 for the training and testing cohorts, respectively. The nomogram displayed superior predictive discrimination with an AUC of 0.862 for the training cohort and 0.861 for the testing cohort. Decision curve analyses indicated that the nomogram provided the highest clinical net benefit.

Conclusion

Performing a nomogram consisting of integrated morphology and radiomics assessment using IVIM-DWI before NACT enables effective prediction of pCR in breast cancer. This predictive model therefore can facilitate medical professionals in making individualized treatment decisions.
Co-modulation of a circular form of PCDH11Y during neuroendocrine differentiation of prostate cancer
Authors: Pecoraro Giovanni , Leone Ilaria , Nuzzo Silvia , Negueruela Santiago , Smaldone Giovanni , Buono Lorena
Published: February 2025

Introduction

Prostate cancer (PC) is a leading cause of cancer-related deaths among men, often progressing to castration-resistant prostate cancer (CRPC) after androgen deprivation therapy (ADT). A subset of CRPC evolves into treatment-emergent neuroendocrine prostate cancer (t-NEPC), an aggressive form characterized by poor prognosis. Currently, there is no reliable biomarker for early detection of t-NEPC. Circular RNAs (circRNAs) have emerged as potential biomarkers due to their stability and tissue-specific expression.

Methods

In this study, we investigated the circRNA landscape during neuroendocrine transdifferentiation (NED) of PC cells using the androgen-sensitive LNCaP and androgen-insensitive DU145 cell lines. To achieve that, we applied CirComPara2 pipeline to publicly available datasets to identify the differently expressed circRNAs in the LNCaP cell lines pre- and post-transdifferentiation. After that, validation and functional analysis by RNA-interference was applied to a selected circRNA to explore its role during NED.

Results

We identified over 6,200 circRNAs, of which 33 were differentially expressed during NED. Among them, a novel circRNA, circPCDH11Y, was highly upregulated during the transition of LNCaP cells from an epithelial to neuroendocrine phenotype, while its levels remained unchanged in DU145 cells. Functional assays demonstrated that circPCDH11Y plays a role in regulating the expression of key neuroendocrine markers, including synaptophysin (SYP), neuron-specific enolase (ENO2), prostate-specific antigen (PSA), Brain-Specific Homeobox/POU Domain Protein 2 (BRN2) and the linear form of Protocadherin 11 Y-Linked (PCDH11Y). Silencing circPCDH11Y delayed the expression of SYP, ENO2 and PCDH11Y, while increasing PSA and BRN2 transcriptional levels, indicating its involvement in promoting neuroendocrine differentiation. Additionally, circPCDH11Y was detected in extracellular vesicles (EVs) secreted by LNCaP cells post-NED, suggesting its potential as a circulating biomarker.

Discussion

These findings highlight circPCDH11Y as a promising candidate for early detection of t-NEPC and provide new insights into the molecular mechanisms underlying prostate cancer progression. Further validation in clinical samples is required to establish its diagnostic and therapeutic potential, which could significantly improve the management of treatment-resistant prostate cancer.
Integrating MAPK pathway inhibition into standard-of-care therapy for pediatric low-grade glioma
Authors: Crotty Erin E. , Sato Aimee A. , Abdelbaki Mohamed S.
Published: February 2025

Pediatric low-grade gliomas (pLGG) are a group of tumors largely driven by alterations in a single genetic pathway, known as the RAS-RAF-mitogen-activated protein kinase (MAPK) pathway. Recent biologic insights and therapeutic targeting of MAPK-alterations have dramatically shifted the treatment approach in pLGG. While chemotherapy remains front-line therapy for unresectable pLGG in most scenarios (with the notable exception of BRAFV600E-altered tumors), many patients recur following cytotoxic agents and require further treatment. Inhibitors of the MAPK pathway, primarily MEK and RAF kinase inhibitors, have emerged as effective and tolerable second-line or later therapy for pLGG. As familiarity with these targeted agents increases, their indications for use continue to expand and Phase 3 clinical trials investigating their utility in the front-line setting are ongoing. We have adopted mitigation strategies for their associated toxicities; skin toxicity, in particular, is now managed by prevention strategies and early dermatologic intervention. This review highlights current approaches for the clinical implementation of MEK and RAF kinase inhibitors for pLGG, focusing on the practical aspects of drug administration, toxicity management, response monitoring, and distribution to patients experiencing geographic or financial barriers to care. Additionally, we review important considerations for the off-label use of these agents while contemporaneous clinical trials assessing front-line efficacy are ongoing. We discuss the potential for more expansive or histology-agnostic tumor targeting using MEK inhibitors, harnessing their biologic relevance for other RAS-altered conditions.
Advances in small extracellular vesicles: roles in the tumor microenvironment and epithelial ovarian cancer diagnosis and treatment
Authors: Peng Liang , Lai Yi , Cao Baodi
Published: February 2025

Epithelial ovarian cancer (EOC), one of the most prevalent subtypes of ovarian cancer, has a 5-year survival rate of less than 30%, highlighting the urgent need for novel diagnostic and therapeutic strategies. The tumor microenvironment (TME), a critical regulator of tumor progression, includes various components, among which small extracellular vesicles (sEVs) serve as important molecular carriers, having gained attention as significant contributors to cancer biology. These vesicles, released by cells into the extracellular space, are pivotal in the pathogenesis of EOC. In addition, sEVs show significant promise as biomarkers and therapeutic agents for the treatment and management of this malignancy. This review explores recent advancements in the understanding of sEVs within the TME and their potential applications in the diagnosis and treatment of EOC.
Primary leiomyosarcoma of the scalp: a case report and review of the literature
Authors: Gao Shuo , Liu Pule , Liu Jixing , Yang Wenzhen , Yang Shude
Published: February 2025

Background and importance

Leiomyosarcoma is a rare and aggressive malignant tumor with a high potential for relapse and metastasis. Correct and timely diagnosis is critical for effective treatment, yet it is often challenging due to the diverse clinical presentations. This case report highlights the significance of early identification and the consequences of delayed diagnosis in scalp leiomyosarcoma.

Clinical presentation

We present the case of a 39-year-old woman with a scalp neoplasm. Initially, the diagnosis was missed, leading to a delay in surgical intervention. The tumor demonstrated a locally aggressive course, infiltrating the skull and dura mater. Upon admission, the scalp tumor was promptly excised. This case provides valuable insights into the varied symptoms and presentations of scalp leiomyosarcoma, which can aid in the recognition of this condition.

Conclusion

This report underscores the importance of considering leiomyosarcoma in the differential diagnosis of scalp masses, particularly when the etiology is unclear. Early recognition and intervention are essential to prevent locally invasive growth and potential metastasis, emphasizing the need for a high index of suspicion among healthcare professionals.
Association of blood manganese and selenium levels with hepatic steatosis among adolescents: a nationwide cross-sectional analysis
Authors: You Bin , Chen Zhiyuan
Published: February 2025

Objective

This study aimed to investigate the association between blood manganese and selenium levels and hepatic steatosis among adolescents, using data from the National Health and Nutrition Examination Survey (NHANES) 2017–2023.

Methods

A cross-sectional analysis was conducted using data from 2,459 adolescents (aged 12–19 years) with complete data on liver ultrasound transient elastography, blood manganese, and selenium levels. Hepatic steatosis was defined as a controlled attenuation parameter (CAP) score of ≥248 dB/m, a measure of liver steatosis, which is a primary characteristic and a less severe stage of hepatic steatosis, assessed by vibration-controlled transient elastography (VCTE). Multivariate logistic regression models were used to assess the associations between blood manganese and selenium levels and hepatic steatosis, while restricted cubic splines (RCS) were employed to examine the dose-response relationships.

Results

The mean age of the participants was 15.37 years, with 52.22% boy. Higher blood manganese and selenium levels were significantly associated with an increased prevalence of hepatic steatosis. In the fully adjusted model, adolescents in the highest quartile of blood manganese had more than twice the odds of hepatic steatosis compared to those in the lowest quartile (OR = 2.41, 95% CI: 1.55–3.75, P < 0.01). Similarly, the highest quartile of blood selenium was associated with a 57% increase in hepatic steatosis prevalence compared to the lowest quartile (OR = 1.57, 95% CI: 1.19–2.08, P < 0.01). RCS analysis confirmed a linear association between both blood manganese and selenium levels and hepatic steatosis prevalence. Subgroup analyses did not reveal statistically significant interactions by age, sex, or obesity status, although associations appeared stronger in younger adolescents.

Conclusion

Elevated blood manganese and selenium levels are associated with a higher prevalence of hepatic steatosis in adolescents. These findings suggest a potential role of trace elements in the development of hepatic steatosis, highlighting the need for further research to better understand the underlying mechanisms involved in liver fat accumulation in this population.
Distance of interaction: a phenomenological analysis of elastic scattering data induced by light projectiles
Authors: Guimarães Valdir , Nistal Pierre Camilo , Olorunfunmi Sunday D. , Linares Roberto , Lubian Jesus
Published: February 2025

Introduction

A phenomenological analysis, based on distances, has been performed for elastic scattering data induced by tightly bound (11B, 12C, and 16O), weakly bound (6Li, 7Li, 7Be, and 9Be), and exotic (6He, 8B, 11Be, and 15C) nuclei on light (27Al), medium (58Ni and 120Sn), and heavy mass (208Pb) targets, respectively, at energies close to the Coulomb barrier.

Methods

The cross-section data on the angular distributions have been converted as a function of the distance of the closest approach.

Results

From a fitting analysis, critical interaction and strong absorption distances were extracted from the data.

Discussion

Correlation was observed with the projectile cluster configuration for the data on the target 208Pb.
Pan-genome analysis and expression verification of the maize ARF gene family
Authors: Man Quan-cai , Wang Yan-qun , Gao Shun-juan , Gao Zhi-chang , Peng Zheng-ping , Cui Jiang-hui
Published: February 2025

Auxin transcription factors regulate auxin responses and play crucial roles in plant growth, development, and responses to abiotic stress. Utilizing the maize pan-genome data, this study identified 35 ARF family members in maize, comprising 21 core genes, 10 near-core genes, and 4 non-essential genes; no private genes were detected. The construction of a phylogenetic tree using Arabidopsis thaliana revealed that the G3 subfamily comprises the highest number of core genes, with a total of 10, and exhibits relative stability throughout the evolution of maize. The calculation of the Ka/Ks ratios for ARF family members across 26 genomes indicated that, aside from ARF8 and ARF11, which were subjected to positive selection, the remaining genes underwent purifying selection. Analysis of structural variation revealed that the expression level of the ARF4 gene significantly differed as a result of this variation. Simultaneously, the structural variation also influenced the conserved domain and cis-acting elements of the gene. Further combining the transcriptome data and RT-qPCR found that, The expression levels of ARF family members in maize were higher at the early stage of embryo and grain development, and the expression levels of each member in embryo and grain were complementary, and the ARF4 plays an important role in abiotic stress. In summary, this study utilizes the maize pan-genome and bioinformatics methods to investigate the evolutionary relationships and functional roles of ARF family members in maize, thereby providing a novel theoretical framework for further research on the maize ARF family.
Transcriptomic reprogramming and epigenetic regulation underlying pollination-dependent and auxin-induced fruit set in tomato
Authors: Li Xiaohan , He Bing , Djari Anis , Frasse Pierre , Maza Elie , Regad Farid , Pirrello Julien , Hu Guojian , Bouzayen Mondher
Published: February 2025

The transition from flower to fruit, naturally triggered by flower pollination and known as fruit set, is instrumental for plant reproduction, seed formation, and crop yield. Notably, this developmental process can also proceed in the absence of flower fertilization, although it remains unclear whether pollination-dependent and pollination-independent fruit sets undergo similar transcriptomic reprogramming. Genome-wide transcriptomic profiling of the flower-to-fruit transition, either pollination-induced or triggered by auxin treatment, shows that both types of triggers modulate the expression of a common large set of genes primarily expressed in maternal tissues. These include genes related to auxin, gibberellin, brassinosteroid, and ethylene signaling. Furthermore, analysis of changes in histone marking during this transition phase indicated that gene reprogramming underlying both types of fruit set primarily correlated with dynamic changes in H3K9ac and H3K4me3 histone marks. Notably, MCM1, AG, DEFA and SRF (MADS)-box and NAM, ATAF1/2, and CUC2 (NAC) genes were extensively downregulated during the transition from flower to fruit, suggesting their negative roles in fruit initiation. In contrast, Teosinte branched1/Cincinnata/proliferating cell factor (TCP), SQUAMOSA -promoter binding proteins (SBP), Sucrose nonfermenting 2 (SNF2), Growth-regulating factor (GRF), and Su (var)3-9, Enhancer-of-zeste and Trithorax (SET) family genes were significantly upregulated in both pollinated and auxin-treated young developing fruits, suggesting their active roles in promoting fruit sets. Despite these similarities, a comparative analysis of the effects of natural pollination and auxin treatment revealed several differences, primarily related to seed development and hormone signaling. Taken together, the data support the idea that auxin serves as the central hormone orchestrating the extensive gene reprogramming associated with fruit initiation in tomato.
Identification of quantitative trait loci for yield traits and fine-mapping of qGW4 using the chromosome segment substitution line-Z708 and dissected single-segment substitution lines
Authors: Zhou Kai , Yu Jinjin , Yu Zhaopeng , Chi Chunyu , Ren Jialin , Zhao Zhuowen , Zhang Han , Ling Yinghua , Zhang Changwei , Zhao Fangming
Published: February 2025

Identifying quantitative trait loci (QTL) for yield traits using single-segment substitution lines (SSSL) is essential for both targeted breeding and functional analysis of key genes. Here, a wide-grain rice chromosome segment substitution line (CSSL), Z708, carrying four substitution segments from Jinhui35 in the genetic background of Xihui18, was used to identify the QTL associated with grain size. Seven QTL for yield-related traits (qGW4, qRLW4, qGWT4, qGW5, qRLW5, qGWT5, and qGPP5) were identified on the substitution segments of the fourth and fifth chromosomes of Z708. Subsequently, four SSSLs (S1-S4), which harbored 16 QTL for yield traits, were constructed using molecular marker-assisted selection. These lines (S1-S4) exhibited a significant increase in yield per plant compared to that of Xihui18. Among them, qGW4, which controls wide grains, belongs to a single dominant gene action in S1 based on the frequency distribution of grain width and chi-square test analysis. Finally, qGW4 was fine-mapped to the interval of 80-kb (minimum) and 310-kb (maximum) using both traditional fine mapping and overlapping substitution mapping of the newly constructed secondary SSSLs (S5-S8). Within this interval, four previously unreported candidate genes were predicted.
Analysis of the composition, characteristics, and antifungal properties of cutin in goji berry fruits at different developmental stages
Authors: Zhou Yueli , Chen Dayuan , Wang Cong , Zhang Huaiyu , Zhao Lunaike , Wang Junjie , Peng Qiding
Published: February 2025

Cutin is the main component of the fruit cuticle framework and plays a role in resisting biological stress. However, little is known about the cutin composition and antifungal properties of goji berry (Lycium barbarum L.). In the current study, paraffin sections and gas chromatography/mass spectrometry (GC/MS) techniques were used to identify differences in cuticle structure and chemical composition of Ningqi-1 and Ningqi-5 goji berries at different developmental stages. Meanwhile, cutin extracts from goji berries at four developmental stages were evaluated for their effects on spore germination, germ tube elongation, and mycelial growth of A. alternata. Twenty-six cutin compounds were identified in Ningqi-1 and Ningqi-5. Fatty acids, alkanes, aromatic acids, and small molecule acids were the main components of goji berry cutin, which are related to the formation of cutin structures. Spore germination and germ tube elongation in A. alternata were significantly inhibited by treatment with cutin extracts from goji berries at different developmental stages. Moreover, the cutin monomer content in goji berries may be closely related to antifungal properties. This study provides a research basis for further investigation of the accumulation mechanism of natural antifungal substances during the growth and development of goji berries.
Assessing the role of genotype by environment interaction of winter wheat cultivars using envirotyping techniques in North China
Authors: Yue Haiwang , Wang Yanbing , Chen Zhaoyang , Zhu Jiashuai , Behera Partha Pratim , Liu Pengcheng , Yang Haoxiang , Wei Jianwei , Bu Junzhou , Jiang Xuwen , Ma Wujun
Published: February 2025

Introduction

Winter wheat is a crucial crop extensively cultivated in northern China, where its grain yield is influenced by genetic factors (G), environmental conditions (E), and their interactions (GEI). Accurate yield estimation depends on understanding the patterns of GEI in multi-environment trials (METs).

Methods

From 2014 to 2018, continuous experiments were conducted in the Heilonggang region of the North China Plain (NCP), evaluating 71 winter wheat genotypes across 16 locations over five years. Leveraging 30 years of environmental data, including 19 meteorological parameters and 6 soil physicochemical properties, the study analyzed GEI and identified four distinct mega-environments (MEs) using advanced environmental classification techniques.

Results

Variance analysis of genotype-year combinations at individual locations revealed significant differences among genotypes. Furthermore, the joint analysis showed that GEI variance exceeded the variance attributed to genotypic effects alone. The Additive Main Effects and Multiplicative Interaction (AMMI) model indicates that the first three interaction principal component axes (IPCAs) account for over 70% of the GEI variance, thereby demonstrating the relevance of this model to the current study. Principal Component Analysis (PCA) across the five-year study period revealed positive correlations between grain yield and vapor pressure deficit (VPD), evapotranspiration potential (ETP), temperature range (TRANGE), available soil water (ASKSW), and sunshine duration. Conversely, negative correlations were observed with relative humidity at 2 meters (RH2M), total precipitation (PRECTOT), potential evapotranspiration (PETP), and dew point temperature at 2 meters (T2MDEW). Among the meteorological and soil variables, minimum temperature (TMIN), fruiting rate (FRUE), temperature at 2 meters (T2M), and clay content (CLAY) emerged as the most significant contributors to yield variation during the study period. Based on GGE biplot analysis, superior genotypes were identified for their respective regions: JM196, WN4176, and HN6119 in 2014; ZX4899, H9966, and LM22 in 2015; BM7, KN8162, and KM3 in 2016; HH14-4019, HM15-1, and HH1603 in 2017; and S14-6111 and JM5172 in 2018. Feixiang and Shenzhou were identified as the most discriminative and representative locations.

Discussion

These findings provide a scientific basis for optimizing winter wheat cultivation strategies in northern regions. Based on long-term data from the North China Plain, future work can further validate their applicability in other regions.
Mobile stance-taking in nature: an exploration of gaze patterns during assessments of objects in nature
Authors: Laner Barbara
Published: February 2025

In this paper, I examine the interactional dynamics of walkers assessing entities in nature, focusing on gaze behavior during these sequences. The analysis is based on a corpus of 10 hiking pairs who walked through the Black Forest National Park while wearing mobile eye-tracking glasses to record their gaze behavior and verbal practices. Using a combined quantitative and qualitative approach, the research identifies gaze patterns in 127 sequences and highlights the role of bodily-visual practices. Contrary to existing literature, the findings indicate that mutual gaze in this setting is not used to mark affiliation but instead occurs only during strong disagreements about initial assessments. During agreements, walkers maintain a triangular position, both gazing at the assessable object without looking at each other. Thus, in this context, gazing at each other serves different interactional purposes, as this study will demonstrate.
Preschoolers' prosocial behavior in groups—Testing effects of dominance, popularity, and friendship
Authors: Katerkamp Anne , Horn Lisa
Published: February 2025

Prosocial, other-benefitting behavior is a fundamental aspect of human social behavior. In the microsystem of their natural social groups, preschool children have to decide not only whether, but also whom to share with and help on a daily basis. In a study with 108 preschool children from five different childcare facilities in Vienna, we examined how individual measures of dominance and popularity of both the actor and the recipient, as well as their friendship influenced their prosocial behavior in a group setting. We assessed popularity and friendship with age-appropriate sociometric interviews and tested two types of dominant behavior (i.e., contest and scramble) as well as two types of prosocial behavior (i.e., sharing and helping) in groups of familiar peers. Participants were tested in their regular socio-ecological niches, thereby preserving and taking into account social dynamics that influence—and are influenced by—interactions within the group. We found that both types of prosocial behavior were directed more often toward friends than toward children that were not considered as friends. Likelihood to share was increased by both the actor's and the recipient's dominance in the contest game. Furthermore, we found that helping was preferentially performed by as well as directed toward older children and that dominant children more frequently received help. Group size and testing sequence had some additional effects on sharing and helping. Our findings suggest that sharing and helping have similar as well as different antecedents and underlying motivations and depend on social relationships between the children. Such effects can be examined more effectively when taking a developmental-ecological approach and investigating prosocial behavior in children's natural social environment.
The relationship between social support and depression among older adults with hypertension in urban communities: mediating effects of coping styles
Authors: Li Dan , Jie Jin-Hua , Li Hong , Xia Xue-Mei , Zhang Yilin , Yang Yan , Xiang Jianjun , Zhuang Hai-Lin
Published: February 2025

Background

Older adults with hypertension are at an increased risk of depression. Social support and coping style significantly influence this risk, with social cognitive theory suggesting that social support can affect an individual’s coping style, and coping style can affect the effective use of social support. However, the mediating role of coping style in the relationship between social support and depression in older hypertensive patients remains unclear. This study aimed to explore the inter-relationships between social support, coping style and depression in older hypertensive patients within a community setting, and to investigate the mediating effects of coping style.

Methods

A cross-sectional questionnaire survey was conducted with 4211 older hypertensive patients from Fuzhou, Fujian Province, China. Participants were assessed for depression, social support, coping styles, and general demographic information. Pearson correlation analysis was employed to test the correlation between variables. Mediation effect test was conducted using SPSS macro program PROCESS with Bootstrap based Model 4, after controlling for confounding factors.

Results

A total of 4211 valid questionnaires were collected, yielding an effective response rate of 98.6%. The average depression score among participants was 7.99 ± 4.92 points, with 29.5% of respondents experiencing varying degrees of depression. Both social support and coping style were associated with depression in older hypertensive patients. Specifically, objective support, subjective support, support utilization, and positive coping style were negatively correlated with depression, with correlation coefficients of -0.159, -0.160, -0.145, and -0.163, respectively. Conversely, negative coping style was positively correlated with depression, with a correlation coefficient of 0.170. Mediating effect analysis showed that coping style played a mediating role between social support and depression. Social support negatively moderated depression through positive coping style (moderating effect =-0.020, Bootstrap 95%CI [-0.027, -0.138], mediating effect value was 15.87%), while it positively influenced depression through negative coping style (moderating effect =0.012, Bootstrap 95%CI [0.008,0.017], intermediate effect value =9.52%).

Conclusion

Social support exerts a direct negative effect on depression, while coping styles mediate the relationship between social support and depression. Interventions to reduce depression in this population should focus on enhancing social support (across objective, subjective, and utilization aspects) and promoting positive coping strategies, thus strengthening psychological resilience and improving overall health and quality of life for older adults with hypertension.
Association of only-child status and household pet ownership with attention-deficit/hyperactivity disorder among Chinese preschool children: a population-based study
Authors: Zhang Yuying , Qiu Shuangyan , Guo Vivian Yawei , Chen Weiqing , Han Xiaomei , Yang Weikang
Published: February 2025

Background

The associations of only-child status and household pet ownership with the risk of attention-deficit/hyperactivity disorder (ADHD) are inconclusive, and the joint effects of only-child status and household pet ownership on ADHD have not been thoroughly investigated.

Methods

A population-based study was conducted in 2021 involving preschool children aged 3–6 years attending kindergartens in Longhua District, Shenzhen, China. Parents were invited to complete questionnaires providing information on socio-demographic and family-environmental factors. ADHD symptoms were assessed using the 26-item Swanson, Nolan, and Pelham Rating Scale as reported by parents.

Results

This study included 63,282 children (mean age: 4.86 ± 0.85 years, 53.6% boys), representing 72.6% of all preschool children in this district in 2021. Among them, 34.4% were only-child and 9.6% were identified as having ADHD. Only-child status was associated with an increased risk of ADHD [adjusted odds ratio: 1.30 (95%CI: 1.23–1.38). Compared to children without a pet (cats or dogs) at ages 0–3 years, pet ownership at ages only 0–1 year, only 1–3 years, and both ages were associated with increased odds of ADHD: 1.59 (1.30–1.95), 1.58 (1.28–1.93), and 1.66 (1.42–1.92), respectively, after controlling for potential confounders. A significant interaction between pet ownership at only 1–3 years and only-child status was observed (adjusted P for interaction = 0.028). Similar findings were observed when the analyses were performed separately for boys and girls.

Conclusion

Both only-child status and household pet ownership are associated with an increased risk of ADHD; however, the detrimental effect of pet ownership appears to be mitigated among only children when pet exposure occurs at ages 1–3 years, providing new insight into reducing family-related risk factors of ADHD.
Clinical efficacy and safety of proton radiotherapy for ocular conjunctival malignancies: a systematic review and meta-analysis
Authors: Zheng Tingwei , Wang Dandan , Miao Yuxin , Dong Meng , Liu Qin , Zhang Qiuning , Bai Huiling , Luo Hongtao , Li Meixuan
Published: February 2025

Objective

The use of proton beam therapy (PBT) for treating ocular conjunctival malignancies is on the rise across numerous medical centers. This study conducts a systematic review and meta-analysis to assess the effectiveness and safety of PBT in treating malignant conjunctival tumors.

Methods

We searched for studies on PBT for ocular conjunctival malignancies in PubMed, Embase, Cochrane Library, and Web of Science (WoS) databases up to November 25, 2023. Studies were selected and data were extracted by two independent reviewers based on pre-established inclusion and exclusion criteria. The quality of evidence was assessed using the GRADE method. Meta-analysis was performed using STATA version 16.0.

Results

An initial search yielded 586 articles, from which six retrospective case series studies were selected involving 291 patients with ocular conjunctival malignancies, including 240 cases of conjunctival melanoma and 51 cases of conjunctival squamous cell carcinoma (SCC). Meta-analysis with a random-effects model showed that PBT is effective and relatively safe, with 2-, 4-, and 5-year overall survival (OS) rates of 98% (95% CI 95–102%), 87% (95% CI 69–104%), and 78% (95% CI 70–87%) respectively. Reported toxicity rates included 19% for cataracts, 10% for glaucoma, 5% for lacrimal stenosis, 52% for sicca symptoms, and 11% for limbal stem cell deficiency. The GRADE assessment yielded a low certainty of evidence.

Conclusions

Proton therapy offers a viable alternative treatment for patients with conjunctival malignancies, with acceptable treatment-related toxicity rates.
Relationship between albumin-corrected anion gap and lumbar spine bone mineral density: a cross-sectional study
Authors: Liu Aiguo , Ying Ting , Deng Shuang , Wang Chenxu , Zhao Ziwen , Zhang Sitong , Xiao Han , Yi Chengqing , Li Dejian
Published: February 2025

Objectives

This study aimed to investigate the relationship between albumin-corrected anion gap (ACAG) and lumbar spine bone mineral density (BMD) in a diverse population, assessing how variations in ACAG levels correlate with changes in lumbar spine BMD and the potential implications for osteoporosis risk.

Methods

A cross-sectional analysis was conducted involving 3,057 participants (1,555 males and 1,502 females). Participants were stratified into quartiles based on baseline ACAG levels. Demographic and clinical characteristics were analyzed, including age, sex, education level, body mass index (BMI), and prevalence of diabetes and hypertension. The association between ACAG and lumbar spine BMD was evaluated using multiple regression models, and a generalized additive model was employed to identify potential nonlinear relationships.

Results

The analysis revealed a significant negative correlation between ACAG and lumbar spine BMD (P < 0.001). For each 1-unit increase in ACAG, BMD decreased with β coefficients of −0.004 to −0.005 across various models. Quartile analysis indicated that participants in the highest ACAG quartile (≥19.55) experienced the most substantial reductions in BMD (β coefficients ranging from −0.034 to −0.036, P < 0.001). Furthermore, a U-shaped relationship was identified, with a turning point at an ACAG value of 22.15, indicating that lower ACAG levels were associated with decreased BMD, while higher levels showed a positive effect. Subgroup analyses by sex demonstrated consistent findings, with significant associations in both males and females.

Conclusion

The findings underscore a significant association between elevated ACAG levels and reduced lumbar spine BMD, suggesting that ACAG may serve as a valuable biomarker for assessing osteoporosis risk. The identified nonlinear relationship further emphasizes the complexity of metabolic influences on bone health. These results warrant further investigation into the mechanisms underlying ACAG’s impact on bone density and its potential role in osteoporosis prevention strategies.