bluuebunny/crossref_metadata_2025 huggingface dataset:
Preferential Genetic Pathways Lead to Relapses in Adult B-Cell Acute Lymphoblastic Leukemia
Authors: Navas-Acosta Josgrey , Hernández-Sánchez Alberto , González Teresa , Villaverde Ramiro Ángela , Santos Sandra , Miguel Cristina , Ribera Jordi , Granada Isabel , Morgades Mireia , Sánchez Ricardo , Such Esperanza , Barrena Susana , Ciudad Juana , Dávila Julio , de Las Heras Natalia , García-de Coca Alfonso , Labrador Jorge , Queizán José Antonio , Martín Sandra , Orfao Alberto , Ribera Josep-María , Benito Rocío , Hernández-Rivas Jesús María
Published: December 2024

Adult B-cell acute lymphoblastic leukemia (B-ALL) is characterized by genetic heterogeneity and a high relapse rate, affecting over 40% of adults. However, the mechanisms leading to relapse in adults are poorly understood. Forty-four adult B-ALL patients were studied at both diagnosis and relapse by next-generation sequencing (NGS). Four main genetic pathways leading to relapse in adults were identified: IKZF1plus genetic profile, RAS mutations and TP53 alterations in Ph-negative B-ALL and acquisition of ABL1 mutations in Ph-positive patients. The most frequently deleted gene at diagnosis was IKZF1 (52%), and 70% of these patients had IKZF1plus profile. Notably, 88% of patients with IKZF1plus at diagnosis retained this genetic profile at relapse. Conversely, the acquisition of RAS mutations or the expansion of subclones (normalized variant allele frequency < 25%) present from diagnosis were observed in 24% of Ph-negative patients at relapse. In addition, 24% of relapses in the Ph-negative cohort could potentially be driven by TP53 alterations. Of these cases, five presented from diagnosis, and four emerged at relapse, mostly as “double-hit” events involving both TP53 deletion and mutation. In Ph-positive B-ALL, the main genetic finding at relapse was the acquisition of ABL1 mutations (86%). Three clonal evolution patterns were identified: the persistent clone trajectory (25%), the expanding clone trajectory (11%) and the therapy-boosted trajectory (48%). Our results reveal the presence of preferential biological pathways leading to relapse in adult B-ALL. These findings underscore the need for personalized therapeutic strategies to improve clinical outcomes in adult patients with B-ALL.
Obesity, Physical Activity, and Cancer Incidence in Two Geographically Distinct Populations; The Gulf Cooperation Council Countries and the United Kingdom—A Systematic Review and Meta-Analysis
Authors: Gaskell Christine , Lutimba Stuart , Bendriss Ghizlane , Aleem Eiman
Published: December 2024

Background: The relationship between obesity, physical activity, and cancer has not been well studied across different countries. The age-standardized rate of cancer in the UK is double–triple that in the Gulf Cooperation Council Countries (GCCCs). Here, we study the association between obesity, physical activity, and cancer incidence with the aim to elucidate cancer epidemiology and risk factors in two geographically, ethnically, and climatically different parts of the world. Methods: Our systematic search (from 2016 to 2023) in PubMed, EMBASE, Scopus, and APA PsycINFO databases resulted in 64 studies totaling 13,609,578 participants. The Cochrane risk of bias tool, GRADE, R programming language, and the meta package were used. Results: Significant associations between obesity and cancer were found in both regions, with a stronger association in the UK (p ≤ 0.0001) than the GCCCs (p = 0.0042). While physical inactivity alone did not show a statistically significant association with cancer incidence, the pooled hazard ratio analysis revealed that the presence of both obesity and physical inactivity was associated with a significantly higher cancer incidence. The most common types of cancer were breast cancer in the UK and colorectal cancer across the GCCCs. Conclusion: Although both regions share similarities, advanced healthcare systems, genetic characteristics, dietary habits, and cultural practices may influence cancer incidence and types.
New Insights in Paediatric Dermatopathology—2nd Edition
Authors: Fraitag Sylvie
Published: December 2024

Paediatric dermatology is still an expanding subspeciality, which is well illustrated by the growing number of books and articles that have been published on this subject in recent years [...]
The Optimization and Application Research of the RRT-APF-Based Path Planning Algorithm
Authors: Zhang Bolin , Li Changyong
Published: December 2024

To address the shortcomings of the original rapidly-exploring random tree (RRT) algorithm, such as long and non-smooth paths, slow convergence to the goal region, and limited adaptability in dynamic environments, this paper proposes a hybrid path planning method combining the artificial potential field (APF) approach with the RRT algorithm. This integrated approach leverages the strengths of both methods to achieve efficient, collision-free path planning in both two-dimensional and three-dimensional environments. The algorithm overcomes the local minima problem inherent in APF while maintaining the RRT’s efficiency in high-dimensional spaces and complex environments. A dynamic adjustment strategy is introduced to adapt to specific application scenarios and varying environmental complexity. Additionally, Bezier curve fitting is applied to smooth the resulting paths. Simulations conducted in various environments demonstrate the effectiveness of the proposed method, highlighting its efficiency and robustness in generating collision-free paths. Compared to the original RRT algorithm, the proposed method reduces path length by 13.4% to 24.9% and decreases search time by 9.8% to 56.5%, improving both path quality and planning efficiency.
Data-Driven-Based Full Recovery Technology and System for Transformer Insulating Oil
Authors: Chen Feng , Wang Li , Zheng Zhiyao , Pan Bin , Hu Yujia , Zhang Kexin
Published: December 2024

This study aims to develop an efficient recovery solution for waste transformer insulating oil, addressing the challenge of incomplete separation of residual oil in existing recovery technologies. A multi-module integrated system is constructed, comprising a waste oil extraction module, a residual oil vaporization module, an exhaust gas treatment module, and an online monitoring module. By combining steps such as oil extraction, residual oil absorption, hot air circulation heating, and negative-pressure low-frequency induction heating, the complete recovery of waste oil is achieved. The recovery process incorporates oil–gas saturation monitoring and an oil–gas precipitation assessment algorithm based on neural networks to enable intelligent control, ensuring thorough recovery of residual oil from transformers. The proposed system and methods demonstrate excellent recovery efficiency and environmental protection effects during the pre-treatment of waste transformer oil. Experiments conducted on 50 discarded transformers showed an average recovery efficiency exceeding 99%, with 49 transformers exhibiting no damage to core components after the recovery process. From a theoretical perspective, this research introduces monitoring and control methods for transformer insulating oil recovery, providing significant support for the green processing and reutilization of discarded transformer insulating oil. From an application value perspective, the recovery process helps reduce environmental pollution and facilitates the disassembly of transformers. This enables better analysis of transformer operating characteristics, thereby enhancing the reliability and safety of power systems.
Dynamics of Soil N and P Nutrient Heterogeneity in Mixed Forest of Populus × Euramercana ‘Neva’ and Robinia pseucdoacacia in Coastal Saline–Alkali Land
Authors: Wang Shumei , Lv Changxiao , Tang Bingxiang , Wang Mengxiao , Cao Banghua , Wu Ke
Published: December 2024

The mixing of poplar and robinia in coastal saline land is a useful attempt at difficult site afforestation. Investigating the long–term mixing effects of nitrogen–fixing and non–nitrogen–fixing tree species on the spatial heterogeneity of N and P nutrients and their ecological stoichiometric characteristics in the coastal saline–alkali soil can provide a scientific basis for soil improvement and plantation management in the coastal saline–alkali soil. By replacing time with space, poplar and robinia mixed forests and corresponding pure forests with the ages of 3, 7 and 18 years were selected, and soil profiles of 0–20 cm, 20–40 cm and 40–60 cm were dug up to determine the contents of total nitrogen, hydrolyzed nitrogen, total phosphorus and available phosphorus, the activities of soil urease and phosphatase and the number of soil bacteria, fungi and actinomycetes in rhizosphere soil. The mixture of poplar and robinia and the increase in planting years led to the heterogeneity of soil N and P in a coastal saline–alkali forest, which could significantly increase the contents of soil total nitrogen, hydrolyzed nitrogen, total phosphorus and available phosphorus between soil layers. Compared with the pure forest of poplar and robinia at the same age, the soil urease activity in the 0–20 cm soil layer of an 18a poplar and robinia mixed forest increased by 94.75% and 73.36%, and the soil phosphatase activity increased by 30.36% and 70.27%. The mix of poplar and robinia significantly increased the abundance of soil microorganisms in saline–alkali soil. The number of bacteria, fungi and actinomycetes in the 0–20 cm soil layer of the 18a poplar and robinia mixed forest was the highest, which were 703,200, 31,297 and 1903, respectively. Redundancy analysis showed that there was a significant positive correlation between soil N and P nutrient contents, soil enzyme activities and microbial abundance. The soil depth of N and P nutrient decomposition and transformation in the mixed poplar and robinia plantation was expanded. The soil N and P nutrient contents, enzyme activities and microbial abundance in the 40–60 cm soil layer of the mixed forest were higher than those of the pure forest. With the increase in plantation years, the depth of soil that can be used in the forest land is increasing. The mixture of poplar and robinia plantation is an excellent choice for the construction of coastal saline–alkali land plantation, which has a significant mixed gain for the decomposition and transformation of N and P nutrients and increases the depth of the available soil layer in the forest land in coastal saline–alkali land. However, the coastal saline–alkali land soil N/P is < 14 and is still restricted by nitrogen, so the application of nitrogen fertilizer can be increased during the afforestation process.
Calcium Signaling and Molecular Adhesion Processes May Hold the Key to Genetic Risk for Autism: A Molecular Pathway Analysis on Two Independent Samples
Authors: Drago Antonio , Calabro Marco , Crisafulli Concetta
Published: December 2024

Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by limited interests, difficulties in social interactions, repetitive behaviors, and impairments in social communication. ASD tends to run in families, and twin studies suggest a strong genetic basis for the disorder. However, the definition of a genetic profile that indicates a risk for ASD remains unclear. Methods: This analysis includes an investigation (Autism Dataset 4 from the NIMH repository, n = 2890) and a replication (Autism Dataset 3 from the NIMH repository, n = 1233) of trio samples with GWAS data. In Phase 1, a molecular pathway analysis is conducted on the investigation sample to test for the enrichment of specific Gene Ontology (GO) terms associated with autism. In Phase 2, the identified pathways are tested for enrichment in the replication sample. Permutation tests are performed to reduce the risk of false-positive findings. Quality assessment is conducted using QQ-plots and λ values, with Plink and R utilized for the Transmission Disequilibrium Test (TDT) and permutation tests. Results: The GO term GO:0007417 was found to be enriched in both the investigation and replication samples. SNPs associated with this pathway were observed at a frequency higher than expected in the replication sample. Conclusions: The GO term GO:0007417 (development of the nervous system) was associated with autism in both trio samples. Variations in the genes TMPRSS4, TRPC4, and PCDH9 were consistently linked to autism across the two independent samples, highlighting the role of calcium signaling and cell adhesion molecules in the risk of autism-related disorders. The pathways and variations associated with autism are described in detail, which can contribute to the engineering of new pharmacological treatments for ASD.
The Finnic Peoples of Russia: Genetic Structure Inferred from Genome-Wide and Y-Chromosome Data
Authors: Agdzhoyan Anastasia , Ponomarev Georgy , Pylev Vladimir , Autleva (Kagazezheva) Zhaneta , Gorin Igor , Evsyukov Igor , Pocheshkhova Elvira , Koshel Sergey , Kuleshov Viacheslav , Adamov Dmitry , Kuznetsova Natalia
Published: December 2024

Background: Eastern Finnic populations, including Karelians, Veps, Votes, Ingrians, and Ingrian Finns, are a significant component of the history of Finnic populations, which have developed over ~3 kya. Yet, these groups remain understudied from a genetic point of view. Methods: In this work, we explore the gene pools of Karelians (Northern, Tver, Ludic, and Livvi), Veps, Ingrians, Votes, and Ingrian Finns using Y-chromosome markers (N = 357) and genome-wide autosomes (N = 67) and in comparison with selected Russians populations of the area (N = 763). The data are analyzed using statistical, bioinformatic, and cartographic methods. Results: The autosomal gene pool of Eastern Finnic populations can be divided into two large categories based on the results of the PCA and ADMIXTURE modeling: (a) “Karelia”: Veps, Northern, Ludic, Livvi, and Tver Karelians; (b) “Ingria”: Ingrians, Votes, Ingrian Finns. The Y-chromosomal gene pool of Baltic Finns is more diverse and is composed of four genetic components. The “Northern” component prevails in Northern Karelians and Ingrian Finns, the “Karelian” in Livvi, Ludic, and Tver Karelians, the “Ingrian-Veps” in Ingrians and Veps (a heterogeneous cluster occupying an intermediate position between the “Northern” and the “Karelian” ones), and the “Southern” in Votes. Moreover, our phylogeographic analysis has found that the Y-haplogroup N3a4-Z1927 carriers are frequent among most Eastern Finnic populations, as well as among some Northern Russian and Central Russian populations. Conclusions: The autosomal clustering reflects the major areal groupings of the populations in question, while the Y-chromosomal gene pool correlates with the known history of these groups. The overlap of the four Y-chromosomal patterns may reflect the eastern part of the homeland of the Proto-Finnic gene pool. The carriers of the Y-haplogroup N3a4-Z1927, frequent in the sample, had a common ancestor at ~2.4 kya, but the active spread of N3a4-Z1927 happened only at ~1.7–2 kya, during the “golden” age of the Proto-Finnic culture (the archaeological period of the “typical” Tarand graves). A heterogeneous Y-chromosomal cluster containing Ingrians, Veps, and Northern Russian populations, should be further studied.
Using T-Cell Subsets to Better Characterize Immunoresiliency and Immunodeficiency in Patients with Recurrent Infections
Authors: Hung Justine , Vonasek Bryan , Rosenberg Daniel , Vo Tri , Striker Rob
Published: December 2024

Background/Objectives: Common Variable Immunodeficiency Disease (CVID) and other immunodeficiencies can present in subtle and variable ways. Whether or not a genetic lesion can be identified, there are not well understood biomarkers that quantitatively describe how severe a deficiency is. Here we discuss two possible ranking systems, CD4/CD8 T cell ratios and Immune Health Grades, and how such data maybe applicable to some immunodeficiencies. Methods: This is not a systematic review, but we identify papers relating to immunodeficiencies with enough data to comment on the CD4/CD8 and Immune Health Grade. We also summarized relevant data publicly available from USIDNET, a website that compiles data on immunodeficiencies, and provide two new cases that illustrate ways that this information can alter clinical assessment. Results: We review the HIV literature on CD4/CD8 T cell data and how this correlates with both immunologic function and comorbidity better than CD4 count alone. The ratio aslso relates to a new system called Immune Health Grades (IHG) derived from young adult to elderly subjects from many NIH cohorts without HIV. CVID is often thought of as an antibody problem, but in fact most patients also have low CD4/CD8 ratio and other cellular abnormalities. We review IDNET to categorize nine molecular immunodeficiencies including two subcategories of CVID into low, normal, or high ratios. Finally, we present two new cases in the literature of patients with recurrent infection and discuss how viewing the cases through the “lens” of CD4/CD8 ratio and IHG can facilitate clinical decisions. Conclusions: Emerging data suggests at least some immunodeficiencies can be grouped by how abnormal their CD4/CD8 ratio or IHG. This represents a clinically available biomarker that can be tracked to see if the condition is worsening or not.
Infection Rate and Risk Factors of SARS-CoV-2 Infection in Retail Workers at the Onset of the COVID-19 Pandemic, Quebec, Canada
Authors: Santerre Kim , Thériault Mathieu , Brousseau Nicholas , Langlois Marc-André , Arnold Corey , Pelletier Joelle N. , Gilbert Caroline , Masson Jean-François , Baz Mariana , Boudreau Denis , Trottier Sylvie
Published: December 2024

Background/Objectives: During the pandemic, client-facing workers were perceived to be at greater risk of SARS-CoV-2 infection. This study investigated the risk factors for SARS-CoV-2 infection among a cohort of 304 retail workers in the Quebec City metropolitan area. Methods: After providing consent, participants were interviewed to gather information on demographic, socioeconomic, behavioural, and occupational variables. They were subsequently followed for up to five visits, scheduled every 12 ± 4 weeks. The study covered critical periods before and during the emergence of the Omicron variants and included retrospective reporting of COVID-19 symptoms and virus detection tests to capture the pandemic’s early stages. Results: During the observation period, 173 (57%) participants experienced a first episode of COVID-19. Serological evidence of recent infection was detected in 160 participants (53%), while 117 (38%) reported a positive virus detection test. In adjusted analyses, risk factors for infection included younger age, a diagnosis of lung disease, longer weekly working hours, more frequent social gatherings, and having received fewer than three doses of vaccine. Notably, the increased risk associated with younger age and longer working hours was observed only after the relaxation of public health measures in the spring of 2022. Conclusions: These data suggest that during the early years of the pandemic when strict public health measures were in place, retail work was not a significant risk factor for SARS-CoV-2 infection in Quebec City metropolitan area. These findings highlight the complex dynamics of COVID-19 transmission and the effectiveness of workplace protective measures.
Utilization of Participatory Research Theory and a National Framework to Advance a State Food Security Research Agenda: A Mixed-Methods Study
Authors: Gordon Barbara , Reader Jenifer , Larsen Benjamin G. , Cooper Kelsey
Published: December 2024

The 2022 White House National Strategy on Hunger, Nutrition, and Health outlined goals for ending hunger in the US. Actions fell into five areas, called pillars; the goal of Pillar 5 was to enhance nutrition and food security research. This study leveraged participatory research theory and the National Strategy for developing a statewide, evidence-informed food security research agenda. A mixed-methods study employing the Community Engagement in Research Continuum (CEnR) was implemented. Engagement strategies included collecting baseline data via a statewide survey and encouraging participants of a statewide Summit to participate in a collective prioritization process. Surveys were emailed to a purposive sample of 1575 contacts; 31 registered for the in-person session. A total of 197 records were included in the survey analysis; all 31 registrants attended the in-person session. The research agenda was to include two objectives for implementation over the next two years. Academic and nonacademic stakeholders interacted as peers during the prioritization exercise. The first research objective was to conduct food assistance usage gap analyses; the second was to investigate barriers to collaboration among Idaho’s food security programs. The CEnR proved efficacious for producing a stakeholder-generated research agenda. Leveraging a national framework helped facilitate asset-based, actionable strategies within a proposed timeline.
Biopsychosocial Factors Associated with Activities of Daily Living Limitations in Chronic Kidney Disease Patients: Insights from the Brazilian Population
Authors: Lima Hellen de Carvalho , Barbosa Joubert Vitor de Souto , Santos Adson Aragão de Araújo , Cavalcanti Rafael Limeira , Tenório Adirlene Pontes de Oliveira , Lopes Matheus Rodrigues , Guedes Thais Sousa Rodrigues , Andrade Achilles de Souza , Sanchis Geronimo José Bouzas , Pegado Rodrigo , Lopes Johnnatas Mikael , Guedes Marcello Barbosa Otoni Gonçalves
Published: December 2024

Chronic kidney disease (CKD) can impair activities of daily living (ADL), reducing quality of life. The influence of biopsychosocial factors on ADL limitations among CKD patients remains unclear. This study aims to investigate associations between these factors and ADL limitations among CKD patients in the Brazilian population. We analyzed data from 839 individuals diagnosed with CKD obtained from the National Health Survey. The outcome was the presence or absence of limitations in ADL caused by CKD. Biopsychosocial factors included clinical and health status, self-perceived behavior, contextual social support, lifestyle, and household characteristics. Cox regression was employed to adjust interactions between these factors, with the prevalence ratio used as a measure of effect (α ≤ 5%). From the analyzed sample, 373 CKD patients (40.7%; 95% CI: 35.4–46.1%) reported experiencing limitations in ADL. These limitations were associated with individual and contextual factors, including lack of private health insurance, residing in a rural area, poorer self-perceived health, presence of depressive symptoms, physical/mental disabilities, use of medications, and undergoing hemodialysis. Limitations in ADL among individuals with CKD are associated with biopsychosocial factors in the Brazilian population, emphasizing the necessity for public policies that support enhanced therapeutic management and address behavioral health.
Stumbles, Gait, and Cognition: Risk Factors Associated with Falls in Older Adults with Subjective Memory Complaints
Authors: Delgado Isabella , Camacho Miguel Angello , Pugliese Isabella , Clavijo Hugo Juan Camilo , Moreno Mabel , Muñoz Ospina Beatriz , Orozco Jorge
Published: December 2024

Falls are a public health problem, impacting quality of life, independence, and health costs. Subjective memory complaints (SMCs) and mild cognitive impairment (MCI) increase with age and may coexist. The risk of falls coinciding with SMCs is less understood. This study explored the risk factors associated with falls in adults with SMCs or MCI. A case–control study in adults over 50 was conducted. All participants underwent a neuropsychological assessment and a Timed Up and Go (TUG) test for gait analysis. Logistic regression calculated OR and p values, adjusting for demographic, clinical, cognitive, and gait variables. There was a total of 64 patients (47.06%) and 72 controls (52.94%). Fallers were older (70.76 ± 7.31) and had hypertension (29.63%), a history of stumbling (13.97%), slow TUG test performance (19.12%), and an asymmetric arm swing (19.85%). Fallers had lower verbal fluency (p = 0.043) and impairment on the Rey–Osterrieth figure copy (p = 0.047). Highest risk factors included female sex (OR 3.55, p = 0.006), older age (OR= 1.08, p = 0.006), hypertension (OR 3.33, p = 0.005), and stumbles (OR 5.65, p = 0.002). This study reconsiders clinical fall risk assessments in older adults with SMCs. Visuo-constructional abilities and executive dysfunction should be followed over time. Female sex, hypertension, and stumbles are risk factors. Integrated cognitive and motor assessments are crucial for detecting and proposing interventions for fall prevention in this population.
KOnezumi-AID: Automation Software for Efficient Multiplex Gene Knockout Using Target-AID
Authors: Taki Taito , Morimoto Kento , Mizuno Seiya , Kuno Akihiro
Published: December 2024

With the groundbreaking advancements in genome editing technologies, particularly CRISPR-Cas9, creating knockout mutants has become highly efficient. However, the CRISPR-Cas9 system introduces DNA double-strand breaks, increasing the risk of chromosomal rearrangements and posing a major obstacle to simultaneous multiple gene knockout. Base-editing systems, such as Target-AID, are safe alternatives for precise base modifications without requiring DNA double-strand breaks, serving as promising solutions for existing challenges. Nevertheless, the absence of adequate tools to support Target-AID-based gene knockout highlights the need for a comprehensive system to design guide RNAs (gRNAs) for the simultaneous knockout of multiple genes. Here, we aimed to develop KOnezumi-AID, a command-line tool for gRNA design for Target-AID-mediated genome editing. KOnezumi-AID facilitates gene knockout by inducing the premature termination codons or promoting exon skipping, thereby generating experiment-ready gRNA designs for mouse and human genomes. Additionally, KOnezumi-AID exhibits batch processing capacity, enabling rapid and precise gRNA design for large-scale genome editing, including CRISPR screening. In summary, KOnezumi-AID is an efficient and user-friendly tool for gRNA design, streamlining genome editing workflows and advancing gene knockout research.
Genetically Engineered T Cells and Recombinant Antibodies to Target Intracellular Neoantigens: Current Status and Future Directions
Authors: Waaga-Gasser Ana Maria , Böldicke Thomas
Published: December 2024

Recombinant antibodies and, more recently, T cell receptor (TCR)-engineered T cell therapies represent two immunological strategies that have come to the forefront of clinical interest for targeting intracellular neoantigens in benign and malignant diseases. T cell-based therapies targeting neoantigens use T cells expressing a recombinant complete TCR (TCR-T cell), a chimeric antigen receptor (CAR) with the variable domains of a neoepitope-reactive TCR as a binding domain (TCR-CAR-T cell) or a TCR-like antibody as a binding domain (TCR-like CAR-T cell). Furthermore, the synthetic T cell receptor and antigen receptor (STAR) and heterodimeric TCR-like CAR (T-CAR) are designed as a double-chain TCRαβ-based receptor with variable regions of immunoglobulin heavy and light chains (VH and VL) fused to TCR-Cα and TCR-Cβ, respectively, resulting in TCR signaling. In contrast to the use of recombinant T cells, anti-neopeptide MHC (pMHC) antibodies and intrabodies neutralizing intracellular neoantigens can be more easily applied to cancer patients. However, different limitations should be considered, such as the loss of neoantigens, the modification of antigen peptide presentation, tumor heterogenicity, and the immunosuppressive activity of the tumor environment. The simultaneous application of immune checkpoint blocking antibodies and of CRISPR/Cas9-based genome editing tools to engineer different recombinant T cells with enhanced therapeutic functions could make T cell therapies more efficient and could pave the way for its routine clinical application.
Oncogenic Functions of Alternatively Spliced MDM2-ALT2 Isoform in Retroperitoneal Liposarcoma
Authors: de Faria Fernanda Costas C. , Khurshid Safiya , Sarchet Patricia , Tahara Sayumi , Casadei Lucia , Grignol Valerie , Karna Roma , Rentsch Sydney , Sp Nipin , Beane Joal D. , Mazzoccoli Luciano , Montes Matias , Nigita Giovanni , Sharick Joe T. , Leight Jennifer L. , Calore Federica , Chandler Dawn S. , Pollock Raphael E.
Published: December 2024

Retroperitoneal liposarcoma (RPLPS) is one of the most common histologic subtypes of soft tissue sarcoma (STS). Complete surgical resection remains the mainstay treatment, while the high rate of locoregional recurrence constitutes the predominant cause of mortality. Well-differentiated (WDLPS) and dedifferentiated (DDLPS) liposarcoma are the most frequent subtypes of RPLPS and present amplified MDM2 gene as a hallmark. However, there are few reports evaluating the role of alternatively spliced MDM2 transcripts in RPLPS. In this study, we assessed MDM2-ALT2 expression levels in a cohort of RPLPS patients and evaluated the biological functions of the MDM2-ALT2 isoform in vitro in DDLPS cell lines. Using BaseScope™ and qPCR, we demonstrated that MDM2-Full Length (MDM2-FL) and MDM2-ALT2 expression levels were upregulated in RPLPS patient-derived tissue samples compared to normal adjacent to tumor tissue (NAT). DDLPS cells overexpressing MDM2-FL or MDM2-ALT2 had higher proliferation rates and increased migration and invasion capacities, as well as increased protein levels of p-AKT, mTOR, p70S6K, MMP2, and cJun. Simultaneous overexpression of MDM2-ALT2 and AKT silencing showed that AKT inhibition impaired p-p70S6K and MMP2 protein increased levels and led to significantly decreased proliferation and migration rates compared to cells overexpressing MDM2-ALT2 only. Taken together, our data suggest that MDM2-ALT2 may promote RPLPS progression.
The Effect of Milk-Derived Extracellular Vesicles on Intestinal Epithelial Cell Proliferation
Authors: Reif Shimon , Birimberg-Schwartz Liron , Grunewald Myriam , Duran Deborah , Sebbag-Sznajder Naama , Toledano Tirtsa , Musseri Mirit , Golan-Gerstl Regina
Published: December 2024

Inflammatory bowel disease (IBD) is a chronic, relapsing inflammation disorder of the gastrointestinal tract characterized by disrupted intestinal epithelial barrier function. Despite advances in treatment, including biological agents, achieving sustained remission remains challenging for many patients with IBD. This highlights the urgent need for novel therapeutic strategies. Milk-derived extracellular vesicles (MDEs) have emerged as a promising therapeutic option. In this study, we isolated and characterized MDEs and evaluated their effects on the function of intestinal epithelial cells (IECs). Using a murine model of Dextran Sulfate Sodium (DSS)-induced colitis, we observed that MDEs significantly ameliorated disease symptoms. The upregulation of β-catenin, a crucial mediator of Wnt signaling, in colonic tissues suggests that MDEs may facilitate epithelial regeneration and restore barrier function. In patient-derived colon organoids (PDCOs), MDEs were internalized and modulated the expression of key signaling molecules, such as the upregulation of β-catenin, cyclin D1, and the proliferation marker Ki67, indicating their potential to promote IEC proliferation and intestinal barrier repair. Importantly, MDEs demonstrated selective activity by downregulating β-catenin and cyclin D1 in colon cancer cells, leading to reduced proliferation. This selectivity indicates a dual therapeutic potential of MDEs for promoting healthy IEC proliferation while potentially mitigating malignancy risks.
Vasculo-Protective Effects of Standardized Black Chokeberry Extracts in Mice Aorta
Authors: Buda Valentina , Sturza Adrian , Minda Daliana , Diaconeasa Zorița , Iuhas Cristian , Bădescu Bianca , Dehelean Cristina-Adriana , Danciu Corina , Muntean Mirela-Danina , Lighezan Rodica , Dănilă Maria-Daniela
Published: December 2024

Black chokeberry (Aronia melanocarpa  Elliot) represents a rich source of dietary polyphenols and other bioactive phytochemicals with pleiotropic beneficial cardiovascular effects. The present study was aimed at evaluating the ex vivo effects of two black chokeberry extracts (BChEs), obtained from either dry (DryAr) or frozen (FrozAr) berries, on oxidative stress and vascular function in mice aortic rings after incubation with angiotensin 2 (Ang 2), lipopolysaccharide (LPS) and glucose (GLUC) in order to mimic renin–angiotensin system activation, inflammation and hyperglycemia. The identification of phenolic compounds was performed by means of liquid chromatography with a diode array detector coupled with mass spectrometry using the electrospray ionization interface. The BChE obtained from the FrozAr was rich in cyanidin glucoside, rutin and caffeic acid, while the one obtained from the dried berries was rich in rutin, caffeic acid and chlorogenic acid. Mice aortas were dissected and acutely incubated (12 h) with Ang2 (100 nM), LPS (1 µg/mL) or GLUC (400 mg/dL) in the presence vs. absence of the two BChEs (1, 10, 50, 75, 100, 500 µg/mL). Subsequently, the tissues were used for the assessment of (i) hydrogen peroxide (H2O2) and superoxide production (using two methods, spectrophotometry and immunofluorescence), (ii) H2O2 scavenger effect and (iii) vascular reactivity (using the organ bath/myograph system). After exposure to Ang2, LPS or GLUC, both types of extracts decreased the H2O2 and superoxide levels in a concentration-dependent manner starting from either 50 µg/mL or 100 µg/mL. Also, in the highest concentrations (100 µg/mL, 150 µg/mL and 500 µg/mL), both extracts elicited a significant scavenger effect on H2O2 (similar to catalase, the classic H2O2 scavenger). Moreover, at 100 µg/mL, both extracts were able to significantly improve vascular relaxation in all stimulated aortic rings. In conclusion, in mice aortas, black chokeberry extracts in acute application elicited a concentration-dependent vasculo-protective effect through the reduction of oxidative stress and the alleviation of endothelial dysfunction in ex vivo conditions that mimic cardio-metabolic diseases.
Wanted: Dead or Alive Cells with Propidium Iodide Staining in Liver Tissue
Authors: Krapoth Tim Christopher , Henle Gina Sophie , Avdyli Mihrije , Bektić Berina , Schwarzkopf Katharina Maria , Bešić Larisa , Zeuzem Stefan , Welsch Christoph , Kraus Nico , Ortiz Cristina
Published: December 2024

This study demonstrates the effectiveness of propidium iodide as a reliable marker for detecting dead or dying cells in frozen liver tissue sections. By comparing propidium iodide staining with the widely used Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, both methods showed consistent results in disease models such as alcohol-induced fibrosis and Western diet-induced fatty liver. Additionally, propidium iodide was successfully co-stained with other fluorescent markers, like phalloidin (for actin filaments) and antibodies targeting collagen, enabling detailed spatial analysis of dying cells within tissue. This multiplex approach allows for a deeper understanding of tissue organization and cell death localization, particularly in complex conditions like liver fibrosis. Moreover, our results suggest that propidium iodide staining can be applied beyond current models, offering a more accessible and cost-effective alternative to traditional methods, like TUNEL. Furthermore, its integration with other markers enables simultaneous analysis of immune responses and tissue damage, making it a powerful tool for future studies on liver disease and other inflammatory conditions. This technique has the potential to advance research into disease mechanisms and improve the evaluation of novel therapeutic strategies targeting tissue regeneration and inflammation control.
WTSM-SiameseNet: A Wood-Texture-Similarity-Matching Method Based on Siamese Networks
Authors: Zhang Yizhuo , Wu Guanlei , Shi Shen , Yu Huiling
Published: December 2024

In tasks such as wood defect repair and the production of high-end wooden furniture, ensuring the consistency of the texture in repaired or jointed areas is crucial. This paper proposes the WTSM-SiameseNet model for wood-texture-similarity matching and introduces several improvements to address the issues present in traditional methods. First, to address the issue that fixed receptive fields cannot adapt to textures of different sizes, a multi-receptive field fusion feature extraction network was designed. This allows the model to autonomously select the optimal receptive field, enhancing its flexibility and accuracy when handling wood textures at different scales. Secondly, the interdependencies between layers in traditional serial attention mechanisms limit performance. To address this, a concurrent attention mechanism was designed, which reduces interlayer interference by using a dual-stream parallel structure that enhances the ability to capture features. Furthermore, to overcome the issues of existing feature fusion methods that disrupt spatial structure and lack interpretability, this study proposes a feature fusion method based on feature correlation. This approach not only preserves the spatial structure of texture features but also improves the interpretability and stability of the fused features and the model. Finally, by introducing depthwise separable convolutions, the issue of a large number of model parameters is addressed, significantly improving training efficiency while maintaining model performance. Experiments were conducted using a wood texture similarity dataset consisting of 7588 image pairs. The results show that WTSM-SiameseNet achieved an accuracy of 96.67% on the test set, representing a 12.91% improvement in accuracy and a 14.21% improvement in precision compared to the pre-improved SiameseNet. Compared to CS-SiameseNet, accuracy increased by 2.86%, and precision improved by 6.58%.
Endoscopic Ultrasonography-Guided Drainage of the Pancreatic Duct (EUS-PD)—Indications and Results with a Literature Review
Authors: Will Uwe , Fueldner Frank , Buechner Theresa , Meyer Frank
Published: December 2024

Background/Objectives: Drawing upon over twenty years of clinical experience in endoscopic and endosonographic procedures, along with comprehensive literature research, we present an overview on EUS-guided pancreatography and pancreatic duct drainage (EUS-PD) as an alternative approach, encompassing indications, procedural methods, and outcomes, including complications and the success rate. Methods: Narrative review. Results: (corner points): EUS-PD is indicated for cases, for which conventional methods are ineffective due to altered abdominal anatomy of the upper gastrointestinal (GI) tract, such as congenital or postoperative conditions that prevent access to the papilla or pancreatoenteric anastomosis. It is also considered if there is symptomatic retention of the pancreatic duct due to pathological changes in the papillary region or stenosis of the pancreatic duct or anastomosis, especially if surgery is not feasible or poses higher risks. EUS-PD has a technical success rate ranging from 25 to 92%, albeit with a complication rate spanning from 14 to 40%, primarily comprising bleeding, perforation, pancreatitis, and pain. Long-term clinical success, measured by pain and symptom relief, falls within a range of 65–85%. Conclusions: The method offers advantages such as minimal invasiveness, enhanced quality of life, the potential for endoscopic revision in the case of complications, and compatibility with most conventional endoscopic instruments requiring extensive expertise in interventional endoscopy and endosonography.
Additions to Dictyosporiaceae: Neoxylochrysis typhicola comb. et gen. nov., Two New Species and Four New Host Records from Medicinal Plants in Southwestern China
Authors: Wu Na , Du Hong-Zhi , Chethana Kandawatte Wedaralalage Thilini , Khongphinitbunjong Kitiphong , Maharachchikumbura Sajeewa S. N. , Hyde Kevin D. , Liu Jian-Kui
Published: December 2024

Medicinal plants serve as vital resources for preventing and treating diseases, with their flowers, fruits, leaves, roots, or entire plants being utilized in the pharmaceutical industry or as direct therapeutic agents. During our investigation of microfungi associated with medicinal plants in Guizhou and Sichuan Provinces, China, several asexual and sexual fungal morphs were collected. Multi-locus phylogenetic analysis based on combined ITS, LSU, SSU and TEF1-α datasets revealed that these taxa are related to the family Dictyosporiaceae. Morphological characteristics, along with multi-locus phylogenetic analysis, supported the establishment of Dictyocheirospora alangii sp. nov. and Pseudocoleophoma rosae sp. nov., as well as the introduction of a novel genus Neoxylochrysis, which accommodates Neoxylochrysis typhicola comb. nov. (≡Pseudocoleophoma typhicola). In addition, four new host records are introduced for Aquadictyospora lignicola from Periploca forrestii, Dendryphiella eucalyptorum from Leonurus japonicus, Ophiopogon japonicus and Sambucus javanica, D. vinosa from Phytolacca americana, and Dictyocheirospora rotunda from Euonymus japonicus and Prinsepia utilis. Detailed descriptions, micrographs of the new taxa and a phylogenetic tree are provided.
Nanopore Data-Driven T2T Genome Assemblies of Colletotrichum lini Strains
Authors: Sigova Elizaveta A. , Dvorianinova Ekaterina M. , Arkhipov Alexander A. , Rozhmina Tatiana A. , Kudryavtseva Ludmila P. , Kaplun Antoniy M. , Bodrov Yakov V. , Pavlova Valeria A. , Borkhert Elena V. , Zhernova Daiana A. , Pushkova Elena N. , Melnikova Nataliya V. , Dmitriev Alexey A.
Published: December 2024

Colletotrichum lini is a pathogenic fungus that infects flax and causes significant yield losses. In this study, we assembled the genomes of four highly virulent C. lini strains using the Oxford Nanopore Technologies (ONT, R10.4.1 flow cells) and Illumina platforms. The performance of two tools developed for telomere-to-telomere (T2T) genome assembly was compared: Verkko and Hifiasm. Prior to the assembly, ONT reads were corrected using the HERRO algorithm. Verkko generated genome assemblies of high completeness but low contiguity, while Hifiasm allowed the generation of T2T assemblies. Despite significantly different genome coverage with ONT data (25–100×), four assemblies of equal contiguity were obtained: 53.6–54.7 Mb, ten core chromosomes, and two or three accessory chromosomes. A comparative analysis of different polishing tools showed that at a certain genome coverage with the corrected ONT data (≥35×), the additional polishing of the assembly did not improve its accuracy, even with the Illumina data. An analysis of the genome structures of the four C. lini strains revealed a high similarity between the core chromosomes. Thus, our approach enabled assembling T2T Colletotrichum genomes only from the ONT data obtained using R10.4.1 flow cells and may be promising for other fungal genera. These assemblies will allow the accurate identification of strain-specific differences at the chromosome level and will aid in the development of effective strategies to protect flax from anthracnose.
Identification and Characterization of Endophytic Fungus DJE2023 Isolated from Banana (Musa sp. cv. Dajiao) with Potential for Biocontrol of Banana Fusarium Wilt
Authors: Jin Longqi , Huang Rong , Zhang Jia , Li Zifeng , Li Ruicheng , Li Yunfeng , Kong Guanghui , Xi Pinggen , Jiang Zide , Li Minhui
Published: December 2024

This study characterized an endophytic fungus, DJE2023, isolated from healthy banana sucker of the cultivar (cv.) Dajiao. Its potential as a biocontrol agent against banana Fusarium wilt was assessed, aiming to provide a novel candidate strain for the biological control of the devastating disease. The fungus was isolated using standard plant tissue separation techniques and fungal culture methods, followed by identification through morphological comparisons, multi-gene phylogenetic analyses, and molecular detection targeting Fusarium oxysporum f. sp. cubense (Foc) race 1 and race 4. Furthermore, assessments of its characteristics and antagonistic effects were conducted through pathogenicity tests, biological trait investigations, and dual-culture experiments. The results confirmed isolate DJE2023 to be a member of the Fusarium oxysporum species complex but distinct from Foc race 1 or race 4, exhibiting no pathogenicity to banana plantlets of cv. Fenza No.1 or tomato seedlings cv. money maker. Only minute and brown necrotic spots were observed at the rhizomes of banana plantlets of ‘Dajiao’ and ‘Baxijiao’ upon inoculation, contrasting markedly with the extensive necrosis induced by Foc tropical race 4 strain XJZ2 at those of banana cv Baxijiao. Notably, co-inoculation with DJE2023 and XJZ2 revealed a significantly reduced disease severity compared to inoculation with XJZ2 alone. An in vitro plate confrontation assay showed no significant antagonistic effects against Foc, indicating a suppressive effect rather than direct antagonism of DJE2023. Research on the biological characteristics of DJE2023 indicated lactose as the optimal carbon source for its growth, while maltose favored sporulation. The optimal growth temperature for this strain is 28 °C, and its spores can germinate effectively within the range of 25–45 °C and pH 4–10, demonstrating a strong alkali tolerance. Collectively, our findings suggest that DJE2023 exhibits weak or non-pathogenic properties and lacks direct antagonism against Foc, yet imparts a degree of resistance against banana Fusarium wilt. The detailed information provides valuable insight into the potential role of DJE2023 in integrated banana disease control, presenting a promising candidate for biocontrol against banana Fusarium wilt.
Uncertainty Modelling of Groundwater-Dependent Vegetation
Authors: Robinson Todd P. , Trotter Lewis , Wardell-Johnson Grant W.
Published: December 2024

Groundwater-dependent vegetation (GDV) is threatened globally by groundwater abstraction. Water resource managers require maps showing its distribution and habitat preferences to make informed decisions on its protection. This study, conducted in the southeast Pilbara region of Western Australia, presents a novel approach based on metrics summarising seasonal phenology (phenometrics) derived from Sentinel-2 imagery. We also determined the preferential habitat using ecological niche modelling based on land systems and topographic derivatives. The phenometrics and preferential habitat models were combined using a framework that allows for the expression of different levels of uncertainty. The large integral (LI) phenometric was capable of discriminating GDV and reduced the search space to 111 ha (<1%), requiring follow-up monitoring. Suitable habitat could be explained by a combination of land systems and negative topographic positions (e.g., valleys). This designated 13% of the study area as requiring protection against the threat of intense bushfires, invasive species, land clearing and other disturbances. High uncertainty represents locations where GDV appears to be absent but the habitat is suitable and requires further field assessment. Uncertainty was lowest at locations where the habitat is highly unsuitable (87%) and requires infrequent revisitation. Our results provide timely geospatial intelligence illustrating what needs to be monitored, protected and revisited by water resource managers.
Ethyl 4H-Pyran-4-one-2-carboxylate
Authors: Aitken R. Alan , Nelson Alexander J. B. , Slawin Alexandra M. Z.
Published: December 2024

The title compound was characterised for the first time by 13C NMR, including the determination of CH coupling constants, and its X-ray structure was determined, showing double ribbons of molecules in the crystal held together by weak CH to O=C hydrogen bonds.