bluuebunny/crossref_metadata_2025 huggingface dataset:
Verticillium Species as an Ecofriendly Alternative to Manage the Invasive Tree Ailanthus altissima (Mill.) Swingle
Authors: Pisuttu Claudia
Published: March 2024

Environmental pollution, unintended harm to beneficial organisms, and the development of herbicide resistance among weeds are the main consequences of the massive and consistent use of chemical herbicides in recent decades. The growing need for alternative solutions has been reinforced by restrictive policies, leading to a search for natural herbicidal candidates. Mycoherbicides, formulations containing plant pathogenic fungi, are viewed as promising substitutes for chemical herbicides. In the case of Ailanthus altissima (Mill.) Swingle, one of the worst invasive alien tree species in the world, Verticillium-based mycoherbicides offer a viable method for control, inducing a lethal wilt disease and leading plants to death within a few years. The demonstrated significant effectiveness enables addressing challenges posed by other—conventional—approaches. The current analysis matches key internal (strengths and weaknesses) and external factors (opportunities and threats) of Verticillium Nees isolates as environmentally-friendly control agents against the invasive A. altissima, by listing each singularly and then crossing them among the categories, drawing from the collaborative efforts of American, Austrian, and Italian research teams.
Biodeterioration Field Test and Mechanical Properties of Maesopsis eminii Wood Treated with Boron Preservative and Plant Oils
Authors: Priadi Trisna , Badruzzaman Muhammad Hilmy , Sofiaturizkiyah Nurul , Hermawan Andi , Malik Jamaludin , Hartono Rudi
Published: March 2024

Boron preservatives have insecticidal and fungicidal effects. The leaching problem of boron preservative-treated wood can be overcome using oil treatment. This study evaluated the resistance in a biodeterioration field test and the mechanical properties of manii wood (Maesopsis eminii Engl.) treated with boric acid and plant oils. Manii wood samples were impregnated in two stages with boric acid and vegetable oils (neem, tamanu, and candlenut oils). The impregnation process was performed in a chamber at a pressure of 7 kg cm−2 for approximately 4 h. Next, the sample was heated at temperatures of 60 °C, 120 °C, and 180 °C. The biodeterioration field test was conducted in ground contact for 100 days. In addition, mechanical tests in terms of modulus of elasticity (MOE), modulus of rupture (MOR), and hardness were conducted using an Instron universal testing machine. The test results prove that the combination of boric acid preservation with neem, tamanu, or candlenut oil treatment increases the resistance of manii wood to subterranean termites, especially when the treatment is accompanied by heating at 120 °C. The combination treatment of boric acid and plant oils also increases the MOE, MOR, and hardness values of manii wood.
Filamentous Fungi as Bioremediation Agents of Industrial Effluents: A Systematic Review
Authors: Rosa Fernanda Maria , Mota Thaís Fernandes Mendonça , Busso Cleverson , Arruda Priscila Vaz de , Brito Patrícia Elena Manuitt , Miranda João Paulo Martins , Trentin Alex Batista , Dekker Robert F. H. , Cunha Mário Antônio Alves da
Published: March 2024

The industrial sector plays a significant role in global economic growth. However, it also produces polluting effluents that must be treated to prevent environmental damage and ensure the quality of life for future generations is not compromised. Various physical, chemical, and biological methods have been employed to treat industrial effluents. Filamentous fungi, in particular, have garnered attention as effective bioremediation agents due to their ability to produce enzymes capable of degrading recalcitrant compounds, and adsorb different pollutant molecules. The novelty of the work reported herein lies in its comprehensive assessment of the research surrounding the use of white- and brown-rot fungi for removing phenolic compounds from industrial effluents. This study employs a systematic review coupled with scientometric analysis to provide insights into the evolution of this technology over time. It scrutinizes geographical distribution, identifies research gaps and trends, and highlights the most studied fungal species and their applications. A systematic review of 464 publications from 1945 to 2023 assessed the use of these fungi in removing phenolic compounds from industrial effluents. White-rot fungi were predominant (96.3%), notably Phanerochaete chrysosporium, Pleurotus ostreatus, Trametes versicolor, and Lentinula edodes. The cultures employing free cells (64.15%) stand out over those using immobilized cells, just like cultures with isolated fungi regarding systems with microbial consortia. Geographically, Italy, Spain, Greece, India, and Brazil emerged as the most prominent countries in publications related to this area during the evaluated period.
An Interdisciplinary Approach to Enhancing Cyber Threat Prediction Utilizing Forensic Cyberpsychology and Digital Forensics
Authors: Rich Marshall S. , Aiken Mary P.
Published: March 2024

The Cyber Forensics Behavioral Analysis (CFBA) model merges Cyber Behavioral Sciences and Digital Forensics to improve the prediction and effectiveness of cyber threats from Autonomous System Numbers (ASNs). Traditional cybersecurity strategies, focused mainly on technical aspects, must be revised for the complex cyber threat landscape. This research proposes an approach combining technical expertise with cybercriminal behavior insights. The study utilizes a mixed-methods approach and integrates various disciplines, including digital forensics, cybersecurity, computer science, and forensic psychology. Central to the model are four key concepts: forensic cyberpsychology, digital forensics, predictive modeling, and the Cyber Behavioral Analysis Metric (CBAM) and Score (CBS) for evaluating ASNs. The CFBA model addresses initial challenges in traditional cyber defense methods and emphasizes the need for an interdisciplinary, comprehensive approach. This research offers practical tools and frameworks for accurately predicting cyber threats, advocating for ongoing collaboration in the ever-evolving field of cybersecurity.
Large-Scale Cytochrome C Oxidase Subunit I Gene Data Analysis for the Development of a Multiplex Polymerase Chain Reaction Test Capable of Identifying Biting Midge Vector Species and Haplotypes (Diptera: Ceratopogonidae) of the Culicoides Subgenus Avaritia Fox, 1955
Authors: Dähn Oliver , Werner Doreen , Mathieu Bruno , Kampen Helge
Published: March 2024

The emergence of culicoid-transmitted bluetongue and Schmallenberg viruses in several European countries demonstrated the ability of indigenous biting midge species to transmit pathogens. Entomologic research programs identified members of the Obsoletus Group (Culicoides subgenus Avaritia) as keyplayers in disease epidemiology in Europe. However, morphological identification of potential vectors is challenging due to the recent discovery of new genetic variants (haplotypes) of C. obsoletus sensu stricto (s.s.), forming distinct clades. In this study, 4422 GenBank entries of the mitochondrial cytochrome c oxidase subunit I (COI) gene of subgenus Avaritia members of the genus Culicoides were analyzed to develop a conventional multiplex PCR, capable of detecting all vector species and clades of the Western Palearctic in this subgenus. Numerous GenBank entries incorrectly assigned to a species were identified, analyzed and reassigned. The results suggest that the three C. obsoletus clades represent independent species, whereas C. montanus should rather be regarded as a genetic variant of C. obsoletus s.s. Based on these findings, specific primers were designed and validated with DNA material from field-caught biting midges which achieved very high diagnostic sensitivity (100%) when compared to an established reference PCR (82.6%).
Is Interoception Deficit Linking Alexithymia and Eating Spectrum Symptoms? Study on a Non-Clinical Sample of Young Adults
Authors: Miniati Mario , Lippi Maria , Palagini Laura , Conversano Ciro , Orrù Graziella , Gemignani Angelo , Perugi Giulio
Published: March 2024

We investigated if interoceptive deficits could be the link between alexithymic traits and eating spectrum manifestations in a non-clinical sample. One-hundred sixty-one young adults (mean age: 23.2 ± 2.4 years) were evaluated with the Toronto Alexithymia Scale-20 (TAS-20), the Interoceptive Accuracy Scale (IAS), the Interoceptive Confusion Questionnaire (ICQ), and the Eating Attitudes Test-26 (EAT-26). Questionnaires were administered with an online procedure (Microsoft Form, Office 365 A1, Pisa, Italy) (Study Protocol #0012005/2023). We compared ICQ, IAS, and TAS-20 scores in subjects who met the threshold for a potential eating spectrum disorder according to EAT-26 scores ≥ 20 (n = 27) vs. subjects who scored <20 (n = 134), with an ANCOVA corrected for ‘age’ and ‘gender’. Subjects with EAT-26 ≥ 20, scored significantly higher at ICQ (54.4 ± 13.2 vs. 50.2 ± 6.8; p = 0.011), TAS-20 ‘Total Score’ (60.8 ± 11.9 vs. 58.1 ± 9.2; p = 0.006), and TAS-20 ‘Identifying Feelings’ (21.5 ± 7.6 vs. 17.3 ± 5.8; p = 0.0001). A binary logistic regression analysis, with EAT-26 scores < 20 vs. ≥20 as the dependent variable, and ICQ, IAS, TAS-20 total scores and dimensions, age, and gender (categorical) as covariates, showed that the only variable predicting eating spectrum symptomatology was ‘ICQ Total Score’ (OR = 1.075, 95% CI: 1.016–1.139; p = 0.013). Interoceptive confusion was the dimension linking the occurrence of alexithymic traits and eating spectrum manifestations.
Factors Influencing Abortion Decision-Making of Adolescents and Young Women: A Narrative Scoping Review
Authors: Koiwa Yui , Shishido Eri , Horiuchi Shigeko
Published: March 2024

Introduction: Globally, about half of all induced abortions have been estimated to be unsafe, which results in 13% of maternal deaths yearly. Of these induced abortions, 41% of unsafe abortions have been reported in young women who are dependent on their parents for their livelihood. They are often left in a vulnerable position and may have difficulty in making a decision regarding abortion. This study aimed to (1) characterize and map factors that influence abortion decision-making of adolescents and young women, and (2) identify the care and support that they need in their decision-making process. Methods: We conducted a scoping review following the JBI method and PRISMA-ScR checklist. We comprehensively searched MEDLINE (PubMed), Embase, Cochrane Library, CINAHL, and PsycInfo, and hand searched publications in the Google Scholar database between November 2021 and October 2023. The search included all English language qualitative and mixed methods research articles published on the database up to October 2023 that included participants aged 10–24 years. The CASP checklist was used as a guide for the qualitative analysis. NVivo was used to synthesize the findings. Results: There were 18 studies from 14 countries (N = 1543 young women) that met the inclusion criteria. Three domains and eleven categories were included as follows: personal (desire for self-realization and unwanted pregnancy), interpersonal (parental impact, reaction of partner, roles of peers and friends, existence of own child, and lack of support), and social circumstances (sexual crime, financial problem, limitation of choice, and underutilized healthcare services). Decision-making factors regarding abortions were also found across all three domains. Conclusion: The abortion decision-making of young women is influenced by various external factors regardless of country. Parents are especially influential and tend to force their daughters to make a decision. Young women experienced suffering, frustration, and lack of autonomy in making decisions based on their preference. This emphasizes the importance of autonomous decision-making. In this regard, healthcare services should be used. However, there are barriers to accessing these services. To improve such access, the following are required: staff training to provide adolescent and youth-friendly health services, counseling based on women’s needs, counseling including the parents or guardians that is confidential and ethical, promotion of decision aids, and affordable accessible care.
Community Pharmacy Needle Exchange Programme: What Can Analysis of the Data Tell Us about the Changing Drug Market in Ireland?
Authors: Evans David S. , Harnedy Norma , Keenan Eamon
Published: March 2024

Community Pharmacy Needle Exchanges are a harm reduction measure that have been established in a number of countries to provide access to sterile injecting equipment for people who inject drugs (PWID). To ensure that they are meeting needs, it is important to monitor the use of the services. This study aimed to determine patterns of needle distribution and return in community pharmacies in Ireland over time. The number of pharmacies, needle packs, clean needles and returned packs was obtained from the Health Service Executive (HSE) Planning and Business Information Unit (PBI). Yearly totals were calculated to show patterns from 2015 to 2022. There has been an 18% decline in the number of pharmacies providing the service since 2015, with a 19% decline in the number of packs provided and a 21% decline in the number of packs returned. The proportion of packs returned was 23% in 2015 and 18% in 2022. There has been a 16% decline in the number of sterile needles provided and a 6% reduction in the average number of needles per individual since 2017. Declining needle use and low rates of used needle return (against a backdrop of large numbers of PWID that have not significantly reduced over time) suggest that there is a need to investigate if community pharmacies in Ireland have the scope to improve their harm reduction impact. This raises questions in terms of the need to both improve and adapt the service against a backdrop of changing drug markets. Key recommendations include the need to review the harm reduction services employed by participating pharmacies when providing new equipment and organising the return of used equipment.
A Knowledge-Guided Intelligent Analysis Method of Geographic Digital Twin Models: A Case Study on the Diagnosis of Geometric Deformation in Tunnel Excavation Profiles
Authors: Liang Ce , Zhu Jun , Zhang Jinbin , Zhu Qing , Lu Jingyi , Lai Jianbo , Wu Jianlin
Published: March 2024

It is essential to establish a digital twin scene, which helps to depict the dynamically changing geographical environment accurately. Digital twins could improve the refined management level of intelligent tunnel construction; however, research on geographical twin models primarily focuses on modeling and visual description, which has low analysis efficiency. This paper proposes a knowledge-guided intelligent analysis method for the geometric deformation of tunnel excavation profile twins. Firstly, a dynamic data-driven knowledge graph of tunnel excavation twin scenes was constructed to describe tunnel excavation profile twin scenes accurately. Secondly, an intelligent diagnosis algorithm for geometric deformation of tunnel excavation contour twins was designed by knowledge guidance. Thirdly, multiple visual variables were jointly used to support scene fusion visualization of tunnel excavation profile twin scenes. Finally, a case was selected to implement the experimental analysis. The experimental results demonstrate that the method in this article can achieve an accurate description of objects and their relationships in tunnel excavation twin scenes, which supports rapid geometric deformation analysis of the tunnel excavation profile twin. The speed of geometric deformation diagnosis is increased by more than 90% and the cognitive efficiency is improved by 70%. The complexity and difficulty of the deformation analysis operation are reduced, and the diagnostic analysis ability and standardization of the geographic digital twin model are effectively improved.
Biomolecular Actions by Intestinal Endotoxemia in Metabolic Syndrome
Authors: Charitos Ioannis Alexandros , Aliani Maria , Tondo Pasquale , Venneri Maria , Castellana Giorgio , Scioscia Giulia , Castellaneta Francesca , Lacedonia Donato , Carone Mauro
Published: March 2024

Metabolic syndrome (MetS) is a combination of metabolic disorders that concurrently act as factors promoting systemic pathologies such as atherosclerosis or diabetes mellitus. It is now believed to encompass six main interacting conditions: visceral fat, imbalance of lipids (dyslipidemia), hypertension, insulin resistance (with or without impairing both glucose tolerance and fasting blood sugar), and inflammation. In the last 10 years, there has been a progressive interest through scientific research investigations conducted in the field of metabolomics, confirming a trend to evaluate the role of the metabolome, particularly the intestinal one. The intestinal microbiota (IM) is crucial due to the diversity of microorganisms and their abundance. Consequently, IM dysbiosis and its derivate toxic metabolites have been correlated with MetS. By intervening in these two factors (dysbiosis and consequently the metabolome), we can potentially prevent or slow down the clinical effects of the MetS process. This, in turn, may mitigate dysregulations of intestinal microbiota axes, such as the lung axis, thereby potentially alleviating the negative impact on respiratory pathology, such as the chronic obstructive pulmonary disease. However, the biomolecular mechanisms through which the IM influences the host’s metabolism via a dysbiosis metabolome in both normal and pathological conditions are still unclear. In this study, we seek to provide a description of the knowledge to date of the IM and its metabolome and the factors that influence it. Furthermore, we analyze the interactions between the functions of the IM and the pathophysiology of major metabolic diseases via local and systemic metabolome’s relate endotoxemia.
Bridging the Gap in Understanding Bone Metastasis: A Multifaceted Perspective
Authors: Elaasser Basant , Arakil Nour , Mohammad Khalid S.
Published: March 2024

The treatment of patients with advanced cancer poses clinical problems due to the complications that arise as the disease progresses. Bone metastases are a common problem that cancer patients may face, and currently, there are no effective drugs to treat these individuals. Prostate, breast, and lung cancers often spread to the bone, causing significant and disabling health conditions. The bone is a highly active and dynamic tissue and is considered a favorable environment for the growth of cancer. The role of osteoblasts and osteoclasts in the process of bone remodeling and the way in which their interactions change during the progression of metastasis is critical to understanding the pathophysiology of this disease. These interactions create a self-perpetuating loop that stimulates the growth of metastatic cells in the bone. The metabolic reprogramming of both cancer cells and cells in the bone microenvironment has serious implications for the development and progression of metastasis. Insight into the process of bone remodeling and the systemic elements that regulate this process, as well as the cellular changes that occur during the progression of bone metastases, is critical to the discovery of a cure for this disease. It is crucial to explore different therapeutic options that focus specifically on malignancy in the bone microenvironment in order to effectively treat this disease. This review will focus on the bone remodeling process and the effects of metabolic disorders as well as systemic factors like hormones and cytokines on the development of bone metastases. We will also examine the various therapeutic alternatives available today and the upcoming advances in novel treatments.
Phenotypic Analysis of Hematopoietic Stem and Progenitor Cell Populations in Acute Myeloid Leukemia Based on Spectral Flow Cytometry, a 20-Color Panel, and Unsupervised Learning Algorithms
Authors: Matthes Thomas
Published: March 2024

The analysis of hematopoietic stem and progenitor cell populations (HSPCs) is fundamental in the understanding of normal hematopoiesis as well as in the management of malignant diseases, such as leukemias, and in their diagnosis and follow-up, particularly the measurement of treatment efficiency with the detection of measurable residual disease (MRD). In this study, I designed a 20-color flow cytometry panel tailored for the comprehensive analysis of HSPCs using a spectral cytometer. My investigation encompassed the examination of forty-six samples derived from both normal human bone marrows (BMs) and patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) along with those subjected to chemotherapy and BM transplantation. By comparing my findings to those obtained through conventional flow cytometric analyses utilizing multiple tubes, I demonstrate that my innovative 20-color approach enables a more in-depth exploration of HSPC subpopulations and the detection of MRD with at least comparable sensitivity. Furthermore, leveraging advanced analytical tools such as t-SNE and FlowSOM learning algorithms, I conduct extensive cross-sample comparisons with two-dimensional gating approaches. My results underscore the efficacy of these two methods as powerful unsupervised alternatives for manual HSPC subpopulation analysis. I expect that in the future, complex multi-dimensional flow cytometric data analyses, such as those employed in this study, will be increasingly used in hematologic diagnostics.
Development of Fluorescence-Based Assays for Key Viral Proteins in the SARS-CoV-2 Infection Process and Lifecycle
Authors: Deng Mingzhenlong , Zhang Chuang , Yan Wanli , Chen Lei , He Bin , Li Yan
Published: March 2024

Since the appearance of SARS-CoV-2 in 2019, the ensuing COVID-19 (Corona Virus Disease 2019) pandemic has posed a significant threat to the global public health system, human health, life, and economic well-being. Researchers worldwide have devoted considerable efforts to curb its spread and development. The latest studies have identified five viral proteins, spike protein (Spike), viral main protease (3CLpro), papain-like protease (PLpro), RNA-dependent RNA polymerase (RdRp), and viral helicase (Helicase), which play crucial roles in the invasion of SARS-CoV-2 into the human body and its lifecycle. The development of novel anti-SARS-CoV-2 drugs targeting these five viral proteins holds immense promise. Therefore, the development of efficient, high-throughput screening methodologies specifically designed for these viral proteins is of utmost importance. Currently, a plethora of screening techniques exists, with fluorescence-based assays emerging as predominant contenders. In this review, we elucidate the foundational principles and methodologies underpinning fluorescence-based screening approaches directed at these pivotal viral targets, hoping to guide researchers in the judicious selection and refinement of screening strategies, thereby facilitating the discovery and development of lead compounds for anti-SARS-CoV-2 pharmaceuticals.
Prognostic Value of Circulating Cell-Free DNA Concentration and Neutrophil-to-Lymphocyte Ratio in Patients with Pancreatic Ductal Adenocarcinoma: A Prospective Cohort Study
Authors: Varzaru Bianca , Iacob Razvan Andrei , Bunduc Stefania , Manea Ioana , Sorop Andrei , Spiridon Andreea , Chelaru Raluca , Croitoru Adina , Topala Mihaela , Becheanu Gabriel , Dumbrava Mona , Dima Simona , Popescu Irinel , Gheorghe Cristian
Published: March 2024

Circulating cell-free DNA (ccfDNA) quantity correlates with the clinical characteristics and prognosis of various cancer types. We investigated whether ccfDNA levels and the neutrophil-to-lymphocyte ratio (NLR) have prognostic value in patients with pancreatic ductal adenocarcinoma (PDAC). Peripheral blood was collected from 82 patients with PDAC prior to any diagnostic procedure or the administration of chemotherapy. Plasma DNA was isolated, and ccfDNA concentration and NLR were determined. We found that ccfDNA levels were correlated with age and tumor burden. Moreover, higher values of NLR (≥3.31) were linked with worse overall survival (OS) (4 vs. 10 months; log rank p = 0.011), and an elevated ccfDNA concentration (≥25.79 ng/mL) was strongly associated with shorter OS (4 vs. 8 months; log rank p = 0.009). According to the results of the multivariable Cox regression analysis, the baseline concentration of ccfDNA was an independent prognostic factor for OS (HR 0.45, 95% CI 0.21–0.97, p = 0.041). Furthermore, the combination of ccfDNA levels with NLR greatly enhanced the prognostic accuracy of PDAC patients. Our study demonstrates that ccfDNA concentration and NLR are independent predictors of survival in PDAC. Subsequent studies should validate this combination as a prognostic indicator in PDAC patients and assess its utility for guiding therapeutic decisions.
Relationship between the Expression of Matrix Metalloproteinases and Their Tissue Inhibitors in Patients with Brain Tumors
Authors: Dibdiakova Katarina , Majercikova Zuzana , Galanda Tomas , Richterova Romana , Kolarovszki Branislav , Racay Peter , Hatok Jozef
Published: March 2024

Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) play critical roles in regulating processes associated with malignant behavior. These endopeptidases selectively degrade components of the extracellular matrix (ECM), growth factors, and their receptors, contributing to cancer cell invasiveness and migratory characteristics by disrupting the basal membrane. However, the expression profile and role of various matrix metalloproteinases remain unclear, and only a few studies have focused on differences between diagnoses of brain tumors. Using quantitative real-time PCR analysis, we identified the expression pattern of ECM modulators (n = 10) in biopsies from glioblastoma (GBM; n = 20), astrocytoma (AST; n = 9), and meningioma (MNG; n = 19) patients. We found eight deregulated genes in the glioblastoma group compared to the benign meningioma group, with only MMP9 (FC = 2.55; p = 0.09) and TIMP4 (7.28; p < 0.0001) upregulated in an aggressive form. The most substantial positive change in fold regulation for all tumors was detected in matrix metalloproteinase 2 (MNG = 30.9, AST = 4.28, and GBM = 4.12). Notably, we observed an influence of TIMP1, demonstrating a positive correlation with MMP8, MMP9, and MMP10 in tumor samples. Subsequently, we examined the protein levels of the investigated MMPs (n = 7) and TIMPs (n = 3) via immunodetection. We confirmed elevated levels of MMPs and TIMPs in GBM patients compared to meningiomas and astrocytomas. Even when correlating glioblastomas versus astrocytomas, we showed a significantly increased level of MMP1, MMP3, MMP13, and TIMP1. The identified metalloproteases may play a key role in the process of gliomagenesis and may represent potential targets for personalized therapy. However, as we have not confirmed the relationship between mRNA expression and protein levels in individual samples, it is therefore natural that the regulation of metalloproteases will be subject to several factors.
Clinical and Preclinical Targeting of Oncogenic Pathways in PDAC: Targeted Therapeutic Approaches for the Deadliest Cancer
Authors: Jiménez Diego J. , Javed Aadil , Rubio-Tomás Teresa , Seye-Loum Ndioba , Barceló Carles
Published: March 2024

Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer-related death worldwide. It is commonly diagnosed in advanced stages and therapeutic interventions are typically constrained to systemic chemotherapy, which yields only modest clinical outcomes. In this review, we examine recent developments in targeted therapy tailored to address distinct molecular pathway alteration required for PDAC. Our review delineates the principal signaling pathways and molecular mechanisms implicated in the initiation and progression of PDAC. Subsequently, we provide an overview of prevailing guidelines, ongoing investigations, and prospective research trajectories related to targeted therapeutic interventions, drawing insights from randomized clinical trials and other pertinent studies. This review focus on a comprehensive examination of preclinical and clinical data substantiating the efficacy of these therapeutic modalities, emphasizing the potential of combinatorial regimens and novel therapies to enhance the quality of life for individuals afflicted with PDAC. Lastly, the review delves into the contemporary application and ongoing research endeavors concerning targeted therapy for PDAC. This synthesis serves to bridge the molecular elucidation of PDAC with its clinical implications, the evolution of innovative therapeutic strategies, and the changing landscape of treatment approaches.
NOTCH1-Related Leukoencephalopathy: A Novel Variant and Literature Review
Authors: Della Vecchia Stefania , Tessa Alessandra , Pasquariello Rosa , Seabra Luis , Crow Yanick J. , Battini Roberta
Published: March 2024

NOTCH1-related leukoencephalopathy is a new diagnostic entity linked to heterozygous gain-of-function variants in NOTCH1 that neuroradiologically show some overlap with the inflammatory microangiopathy Aicardi-Goutières syndrome (AGS). To report a 16-year-old boy harbouring a novel NOTCH1 mutation who presented neuroradiological features suggestive of enhanced type I interferon signalling. We describe five years of follow-up and review the current literature on NOTCH1-related leukoencephalopathy. Clinical evaluation, standardised scales (SPRS, SARA, CBCL, CDI-2:P, WISCH-IV and VABS-2) and neuroradiological studies were performed, as well as blood DNA analysis. For the literature review, a search was performed on Pubmed, Scopus and Web of Science up to December 2023 using the following text word search strategy: (NOTCH1) AND (leukoencephalopathy). Our patient presents clinical features consistent with other reported cases with NOTCH1 mutations but is among the minority of patients with an onset after infancy. During the five-year follow-up, we observed an increase in the severity of spasticity and ataxia. However, at the age of 16 years, our proband is still ambulatory. As for other reported patients, he manifests psychiatric features ranging from hyperactivity during childhood to anxiety and depression during adolescence. The neuroradiological picture remained essentially stable over five years. In addition to the typical findings of leukoencephalopathy with cysts and calcifications already described, we report the presence of T2-hyperintensity and T1-hypotensity of the transverse pontine fibres, enhancement in the periventricular white matter after gadolinium administration and decreased NAA and Cho peaks in the periventricular white matter on MRS. We identified a novel heterozygous variant in NOTCH1 (c.4788_4799dup), a frame insertion located in extracellular negative regulatory region (NRR)-domain as in previously published cases. Blood interferon signalling was not elevated compared to controls. This case provides further data on a new diagnostic entity, i.e., NOTCH1-related leukoencephalopathy. By describing a standardised five-year follow-up in one case and reviewing the other patients described to date, we outline recommendations relating to monitoring in this illness, emphasising the importance of psychiatric and gastroenterological surveillance alongside neurological and neuropsychological management. Studies are needed to better understand the factors influencing disease onset and severity, which are heterogeneous.
PHA-665752’s Antigrowth and Proapoptotic Effects on HSC-3 Human Oral Cancer Cells
Authors: Yadav Anil Kumar , Wang Saini , Shin Young-Min , Jang Byeong-Churl
Published: March 2024

c-Met is a tyrosine-kinase receptor, and its aberrant activation plays critical roles in tumorigenesis, invasion, and metastatic spread in many human tumors. PHA-665752 (PHA) is an inhibitor of c-Met and has antitumor effects on many hematological malignancies and solid cancers. However, the activation and expression of c-Met and its role and the antitumor effect of PHA on human oral squamous cell carcinoma (OSCC) cells remain unclear. Here, we investigated the activation and expression of c-Met and the effects of PHA on the growth of a highly tumorigenic HSC-3 human OSCC cell line with high c-Met phosphorylation and expression. Of note, c-Met was highly expressed and phosphorylated on Y1234/1235 in HSC-3 cells, and PHA treatment significantly suppressed the growth and induced apoptosis of these cells. Moreover, PHA that inhibited the phosphorylation (activation) of c-Met further caused the reduced phosphorylation and expression levels of Src, protein kinase B (PKB), mammalian target of rapamycin (mTtor), and myeloid cell leukemia-1 (Mcl-1) in HSC-3 cells. In addition, the antiangiogenic property of PHA in HSC-3 cells was shown, as evidenced by the drug’s suppressive effect on the expression of hypoxia-inducible factor-1α (HIF-1α), a critical tumor angiogenic transcription factor. Importantly, genetic ablation of c-Met caused the reduced growth of HSC-3 cells and decreased Src phosphorylation and HIF-1α expression. Together, these results demonstrate that c-Met is highly activated in HSC-3 human oral cancer cells, and PHA exhibits strong antigrowth, proapoptotic, and antiangiogenic effects on these cells, which are mediated through regulation of the phosphorylation and expression of multiple targets, including c-Met, Src, PKB, mTOR, Mcl-1, and HIF-1α.
Comprehensive Atlas of Alternative Splicing Reveals NSRP1 Promoting Adipogenesis through CCDC18
Authors: Liu Lei , Wang Wei , Liu Weiwei , Li Xingzheng , Yi Guoqiang , Adetula Adeyinka Abiola , Huang Haibo , Tang Zhonglin
Published: March 2024

Alternative splicing (AS) plays a crucial role in regulating gene expression, function, and diversity. However, limited reports exist on the identification and comparison of AS in Eastern and Western pigs. Here, we analyzed 243 transcriptome data from eight tissues, integrating information on transcription factors (TFs), selection signals, splicing factors (SFs), and quantitative trait loci (QTL) to comprehensively study alternative splicing events (ASEs) in pigs. Five ASE types were identified, with Mutually Exclusive Exon (MXE) and Skipped Exon (SE) ASEs being the most prevalent. A significant portion of genes with ASEs (ASGs) showed conservation across all eight tissues (63.21–76.13% per tissue). Differentially alternative splicing genes (DASGs) and differentially expressed genes (DEGs) exhibited tissue specificity, with blood and adipose tissues having more DASGs. Functional enrichment analysis revealed coDASG_DEGs in adipose were enriched in pathways associated with adipose deposition and immune inflammation, while coDASG_DEGs in blood were enriched in pathways related to immune inflammation and metabolism. Adipose deposition in Eastern pigs might be linked to the down-regulation of immune-inflammation-related pathways and reduced insulin resistance. The TFs, selection signals, and SFs appeared to regulate ASEs. Notably, ARID4A (TF), NSRP1 (SF), ANKRD12, IFT74, KIAA2026, CCDC18, NEXN, PPIG, and ROCK1 genes in adipose tissue showed potential regulatory effects on adipose-deposition traits. NSRP1 could promote adipogenesis by regulating alternative splicing and expression of CCDC18. Conducting an in-depth investigation into AS, this study has successfully identified key marker genes essential for pig genetic breeding and the enhancement of meat quality, which will play important roles in promoting the diversity of pork quality and meeting market demand.
Exposure to Light of the Abaxial versus Adaxial Side of Detached Kalanchoë blossfeldiana Leaves Affects Anthocyanin Content and Composition Differently
Authors: Wiczkowski Wiesław , Saniewski Marian , Marasek-Ciołakowska Agnieszka , Góraj-Koniarska Justyna , Mitrus Joanna , Horbowicz Marcin
Published: March 2024

The accumulation and composition of anthocyanins in leaves of Kalanchoë blossfeldiana, detached and kept for five days under natural light conditions, were investigated. The presence of fifteen derivatives of cyanidin, petunidin, and delphinidin was found. Changes in the content of each anthocyanin in the leaves before and after exposure to light on the abaxial (naturally upper) and adaxial (naturally lower) sides of the leaves were compared. When the adaxial side was exposed to light, the anthocyanin contents of the leaves did not change. In contrast, when the abaxial side of detached leaves was exposed to light, there was enhanced accumulation of delphinidin-rhamnoside-glucoside, cyanidin-rhamnoside-glucoside, cyanidin-glucoside-glucoside, and two unknown derivatives of petunidin and delphinidin. Application of methyl jasmonate (JA-Me) on the abaxial side exposed to light inhibited the accumulation of these anthocyanins. This effect could probably be due to the presence of these anthocyanins in the epidermal cells of K. blossfeldiana leaves and was visible in the microscopic view of its cross-section. These anthocyanins were directly exposed to JA-Me, leading to inhibition of their formation and/or accumulation. The lack of significant effects of JA-Me on anthocyanin mono- and tri-glycosides may indicate that they are mainly present in the mesophyll tissue of the leaf.
Special Issue “Molecular Biology in Forensic Science: Past, Present and Future”
Authors: Sessa Francesco , Salerno Monica
Published: March 2024

Molecular biology has always represented an enviable tool in the fields of biosciences, diagnostics, and forensic sciences [...]
Exploring the Potential of Exosomes as Biomarkers in Tuberculosis and Other Diseases
Authors: Arya Rakesh , Jit Bimal Prasad , Kumar Vijay , Kim Jong Joo
Published: March 2024

Tuberculosis (TB) is a major cause of morbidity and mortality and remains an important public health issue in developing countries worldwide. The existing methods and techniques available for the diagnosis of TB are based on combinations of laboratory (chemical and biological), radiological, and clinical tests. These methods are sophisticated and laborious and have limitations in terms of sensitivity, specificity, and accuracy. Clinical settings need improved diagnostic biomarkers to accurately detect biological changes due to pathogen invasion and pharmacological responses. Exosomes are membrane-bound vesicles and mediators of intercellular signaling processes that play a significant role in the pathogenesis of various diseases, such as tuberculosis, and can act as promising biomarkers for the monitoring of TB infection. Compared to conventional biomarkers, exosome-derived biomarkers are advantageous because they are easier to detect in different biofluids, are more sensitive and specific, and may be useful in tracking patients’ reactions to therapy. This review provides insights into the types of biomarkers, methods of exosome isolation, and roles of the cargo (proteins) present in exosomes isolated from patients through omics studies, such as proteomics. These findings will aid in developing new prognostic and diagnostic biomarkers and could lead to the identification of new therapeutic targets in the clinical setting.
Leucine-Rich Repeat in Polycystin-1 Suppresses Cystogenesis in a Zebrafish (Danio rerio) Model of Autosomal-Dominant Polycystic Kidney Disease
Authors: Padhy Biswajit , Amir Mohammad , Xie Jian , Huang Chou-Long
Published: March 2024

Mutations of PKD1 coding for polycystin-1 (PC1) account for most cases of autosomal-dominant polycystic kidney disease (ADPKD). The extracellular region of PC1 contains many evolutionarily conserved domains for ligand interactions. Among these are the leucine-rich repeats (LRRs) in the far N-terminus of PC1. Using zebrafish (Danio rerio) as an in vivo model system, we explored the role of LRRs in the function of PC1. Zebrafish expresses two human PKD1 paralogs, pkd1a and pkd1b. Knockdown of both genes in zebrafish by morpholino antisense oligonucleotides produced phenotypes of dorsal-axis curvature and pronephric cyst formation. We found that overexpression of LRRs suppressed both phenotypes in pkd1-morphant zebrafish. Purified recombinant LRR domain inhibited proliferation of HEK cells in culture and interacted with the heterotrimeric basement membrane protein laminin-511 (α5β1γ1) in vitro. Mutations of amino acid residues in LRRs structurally predicted to bind laminin-511 disrupted LRR–laminin interaction in vitro and neutralized the ability of LRRs to inhibit cell proliferation and cystogenesis. Our data support the hypothesis that the extracellular region of PC1 plays a role in modulating PC1 interaction with the extracellular matrix and contributes to cystogenesis of PC1 deficiency.
Retinal Ciliopathies and Potential Gene Therapies: A Focus on Human iPSC-Derived Organoid Models
Authors: McDonald Andrew , Wijnholds Jan
Published: March 2024

The human photoreceptor function is dependent on a highly specialised cilium. Perturbation of cilial function can often lead to death of the photoreceptor and loss of vision. Retinal ciliopathies are a genetically diverse range of inherited retinal disorders affecting aspects of the photoreceptor cilium. Despite advances in the understanding of retinal ciliopathies utilising animal disease models, they can often lack the ability to accurately mimic the observed patient phenotype, possibly due to structural and functional deviations from the human retina. Human-induced pluripotent stem cells (hiPSCs) can be utilised to generate an alternative disease model, the 3D retinal organoid, which contains all major retinal cell types including photoreceptors complete with cilial structures. These retinal organoids facilitate the study of disease mechanisms and potential therapies in a human-derived system. Three-dimensional retinal organoids are still a developing technology, and despite impressive progress, several limitations remain. This review will discuss the state of hiPSC-derived retinal organoid technology for accurately modelling prominent retinal ciliopathies related to genes, including RPGR, CEP290, MYO7A, and USH2A. Additionally, we will discuss the development of novel gene therapy approaches targeting retinal ciliopathies, including the delivery of large genes and gene-editing techniques.
OsOFP6 Overexpression Alters Plant Architecture, Grain Shape, and Seed Fertility
Authors: Zhu Xuting , Li Yuan , Zhao Xiangqian , Feng Yukai , Bao Zhengkai , Liu Wenzhen , Li Feifei
Published: March 2024

OVATE family proteins (OFPs) play important roles in plant growth and development, hormone signaling, and stress response pathways. However, the functions of OsOFPs in rice are largely unknown. In this study, a novel gain-of-function rice mutant, Osofp6-D, was identified. This mutant exhibited decreased plant height, erect leaves, reduced panicle size, short and wide seeds, delayed seed germination time, and reduced fertility. These phenotypic changes were attributed to the increased expression of OsOFP6, which was caused by a T-DNA insertion. Complementation of the Osofp6-D phenotype by knockout of OsOFP6 using the CRISPR/Cas9 system confirmed that the Osofp6-D phenotype was caused by OsOFP6 overexpression. In addition, transgenic plants overexpressing OsOFP6 with the 35S promoter mimicked the Osofp6-D phenotype. Cytological observations of the glumes showed that OsOFP6 overexpression altered the grain shape, mainly by altering the cell shape. Hormone response experiments showed that OsOFP6 was involved in the gibberellin (GA) and brassinolide (BR) signaling responses. Further studies revealed that OsOFP6 interacts with E3BB, which is orthologous to the Arabidopsis central organ size-control protein BIG BROTHER (BB). This study further elucidates the regulation mechanism of the rice OFP family on plant architecture and grain shape.
Single Cell High Dimensional Analysis of Human Peripheral Blood Mononuclear Cells Reveals Unique Intermediate Monocyte Subsets Associated with Sex Differences in Coronary Artery Disease
Authors: Chatterjee Nandini , Komaravolu Ravi K. , Durant Christopher P. , Wu Runpei , McSkimming Chantel , Drago Fabrizio , Kumar Sunil , Valentin-Guillama Gabriel , Miller Yury I. , McNamara Coleen A. , Ley Klaus , Taylor Angela , Alimadadi Ahmad , Hedrick Catherine C.
Published: March 2024

Monocytes are associated with human cardiovascular disease progression. Monocytes are segregated into three major subsets: classical (cMo), intermediate (iMo), and nonclassical (nMo). Recent studies have identified heterogeneity within each of these main monocyte classes, yet the extent to which these subsets contribute to heart disease progression is not known. Peripheral blood mononuclear cells (PBMC) were obtained from 61 human subjects within the Coronary Assessment of Virginia (CAVA) Cohort. Coronary atherosclerosis severity was quantified using the Gensini Score (GS). We employed high-dimensional single-cell transcriptome and protein methods to define how human monocytes differ in subjects with low to severe coronary artery disease. We analyzed 487 immune-related genes and 49 surface proteins at the single-cell level using Antibody-Seq (Ab-Seq). We identified six subsets of myeloid cells (cMo, iMo, nMo, plasmacytoid DC, classical DC, and DC3) at the single-cell level based on surface proteins, and we associated these subsets with coronary artery disease (CAD) incidence based on Gensini score (GS) in each subject. Only frequencies of iMo were associated with high CAD (GS > 32), adj.p = 0.024. Spearman correlation analysis with GS from each subject revealed a positive correlation with iMo frequencies (r = 0.314, p = 0.014) and further showed a robust sex-dependent positive correlation in female subjects (r = 0.663, p = 0.004). cMo frequencies did not correlate with CAD severity. Key gene pathways differed in iMo among low and high CAD subjects and between males and females. Further single-cell analysis of iMo revealed three iMo subsets in human PBMC, distinguished by the expression of HLA-DR, CXCR3, and CD206. We found that the frequency of immunoregulatory iMo_HLA-DR+CXCR3+CD206+ was associated with CAD severity (adj.p = 0.006). The immunoregulatory iMo subset positively correlated with GS in both females (r = 0.660, p = 0.004) and males (r = 0.315, p = 0.037). Cell interaction analyses identified strong interactions of iMo with CD4+ effector/memory T cells and Tregs from the same subjects. This study shows the importance of iMo in CAD progression and suggests that iMo may have important functional roles in modulating CAD risk, particularly among females.