bluuebunny/crossref_metadata_2025 huggingface dataset:
Triptolide Reduces Neoplastic Progression in Hepatocellular Carcinoma by Downregulating the Lipid Lipase Signaling Pathway
Authors: Chang Wei , Wang Jingjing , You Yuanqi , Wang Hongqian , Xu Shendong , Vulcano Stephen , Xu Changlu , Shen Chenlin , Li Zhi , Wang Jie
Published: January 2024

Hepatocellular carcinoma (HCC), which is the third leading cause of cancer-related mortality in the world, presents a significant medical challenge. Triptolide (TP) has been identified as an effective therapeutic drug for HCC. However, its precise therapeutic mechanism is still unknown. Understanding the mechanism of action of TP against HCC is crucial for its implementation in the field of HCC treatment. We hypothesize that the anti-HCC actions of TP might be related to its modulation of HCC lipid metabolism given the crucial role that lipid metabolism plays in promoting the progression of HCC. In this work, we first demonstrate that, both in vitro and in vivo, TP significantly reduces lipid accumulation in HCC cells. Additionally, we notice that lipoprotein lipase (LPL) expression is markedly upregulated in HCC, and that its levels are positively connected with the disease’s progression. It is interesting to note that TP dramatically reduces LPL activity, which in turn prevents HCC growth and reduces lipid accumulation. Additionally, the effect of TP on LPL is a direct correlation. These results definitely demonstrate that TP protects hepatocytes against abnormal accumulation of lipids by transcriptionally suppressing LPL, which reduces the development of HCC. This newly identified pathway provides insight into the process through which TP exerts its anti-HCC actions.
Dynamic Contrast-Enhanced Ultrasound in the Prediction of Advanced Hepatocellular Carcinoma Response to Systemic and Locoregional Therapies
Authors: Cerrito Lucia , Ainora Maria Elena , Cuccia Giuseppe , Galasso Linda , Mignini Irene , Esposto Giorgio , Garcovich Matteo , Riccardi Laura , Gasbarrini Antonio , Zocco Maria Assunta
Published: January 2024

Hepatocellular carcinoma (HCC) is the most frequent primary liver cancer and the sixth most common malignant tumor in the world, with an incidence of 2–8% per year in patients with hepatic cirrhosis or chronic hepatitis. Despite surveillance schedules, it is sometimes diagnosed at an advanced stage, requiring complex therapeutic efforts with both locoregional and systemic treatments. Traditional radiological tools (computed tomography and magnetic resonance) are used for the post-treatment follow-up of HCC. The first follow-up imaging is performed at 4 weeks after resection or locoregional treatments, or after 3 months from the beginning of systemic therapies, and subsequently every 3 months for the first 2 years. For this reason, these radiological methods do not grant the possibility of an early distinction between good and poor therapeutic response. Contrast-enhanced ultrasound (CEUS) and dynamic contrast-enhanced ultrasound (DCE-US) have gained the interest of several researchers for their potential role in the early assessment of response to locoregional treatments (chemoembolization) or antiangiogenic therapies in patients with advanced HCC. In fact, DCE-US, through a quantitative analysis performed by specific software, allows the construction of time–intensity curves, providing an evaluation of the parameters related to neoplastic tissue perfusion and its potential changes following therapies. It has the invaluable advantage of being easily repeatable, minimally invasive, and able to grant important evaluations regarding patients’ survival, essential for well-timed therapeutic changes in case of unsatisfying response, and eventual further treatment planning.
Macromutations Yielding Karyotype Alterations (and the Process(es) behind Them) Are the Favored Route of Carcinogenesis and Speciation
Authors: Schubert Ingo
Published: January 2024

It is argued that carcinogenesis and speciation are evolutionary events which are based on changes in the ‘karyotypic code’ through a phase of ‘genome instability’, followed by a bottleneck of selection for the viability and adaptability of the initial cells. Genomic (i.e., chromosomal) instability is caused by (massive) DNA breakage and the subsequent mis-repair of DNA double-strand breaks (DSBs) resulting in various chromosome rearrangements. Potential tumor cells are selected for rapid somatic proliferation. Cells eventually yielding a novel species need not only to be viable and proliferation proficient, but also to have a balanced genome which, after passing meiosis as another bottleneck and fusing with an identical gamete, can result in a well-adapted organism. Such new organisms should be genetically or geographically isolated from the ancestral population and possess or develop an at least partial sexual barrier.
The Role of Chemokines in Orchestrating the Immune Response to Pancreatic Ductal Adenocarcinoma
Authors: Lekan Alexander A. , Weiner Louis M.
Published: January 2024

Chemokines are small molecules that function as chemotactic factors which regulate the migration, infiltration, and accumulation of immune cells. Here, we comprehensively assess the structural and functional role of chemokines, examine the effects of chemokines that are present in the pancreatic ductal adenocarcinoma (PDAC) tumor microenvironment (TME), specifically those produced by cancer cells and stromal components, and evaluate their impact on immune cell trafficking, both in promoting and suppressing anti-tumor responses. We further explore the impact of chemokines on patient outcomes in PDAC and their role in the context of immunotherapy treatments, and review clinical trials that have targeted chemokine receptors and ligands in the treatment of PDAC. Lastly, we highlight potential strategies that can be utilized to harness chemokines in order to increase cytotoxic immune cell infiltration and the anti-tumor effects of immunotherapy.
Severe Acute Kidney Injury in Hospitalized Cancer Patients: Epidemiology and Predictive Model of Renal Replacement Therapy and In-Hospital Mortality
Authors: Calças Marques Roberto , Reis Marina , Pimenta Gonçalo , Sala Inês , Chuva Teresa , Coelho Inês , Ferreira Hugo , Paiva Ana , Costa José Maximino
Published: January 2024

Background: Acute kidney injury (AKI) is a common complication among cancer patients, often leading to longer hospital stays, discontinuation of cancer treatment, and a poor prognosis. This study aims to provide insight into the incidence of severe AKI in this population and identify the risk factors associated with renal replacement therapy (RRT) and in-hospital mortality. Methods: This retrospective cohort study included 3201 patients with cancer and severe AKI admitted to a Comprehensive Cancer Center between January 1995 and July 2023. Severe AKI was defined according to the KDIGO guidelines as grade ≥ 2 AKI with nephrological in-hospital follow-up. Data were analyzed in two timelines: Period A (1995–2010) and Period B (2011–2023). Results: A total of 3201 patients (1% of all hospitalized cases) were included, with a mean age of 62.5 ± 17.2 years. Solid tumors represented 75% of all neoplasms, showing an increasing tendency, while hematological cancer decreased. Obstructive AKI declined, whereas the incidence of sepsis-associated, prerenal, and drug-induced AKI increased. Overall, 20% of patients required RRT, and 26.4% died during hospitalization. A predictive model for RRT (AUC 0.833 [95% CI 0.817–0.848]) identified sepsis and hematological cancer as risk factors and prerenal and obstructive AKI as protective factors. A similar model for overall in-hospital mortality (AUC 0.731 [95% CI 0.71–0.752]) revealed invasive mechanical ventilation (IMV), sepsis, and RRT as risk factors and obstructive AKI as a protective factor. The model for hemato-oncological patients’ mortality (AUC 0.832 [95% CI 0.803–0.861]) included IMV, sepsis, hematopoietic stem cell transplantation, and drug-induced AKI. Mortality risk point score models were derived from these analyses. Conclusions: This study addresses the demographic and clinical features of cancer patients with severe AKI. The development of predictive models for RRT and in-hospital mortality, along with risk point scores, may play a role in the management of this population.
Breast-Conserving Surgery Guided with Magnetic Seeds vs. Wires: A Single-Institution Experience
Authors: Moreno-Palacios Elisa , Martí Covadonga , Frías Laura , Meléndez Marcos , Loayza Adolfo , Roca María José , Córdoba Vicenta , Oliver José María , Hernández Alicia , Sánchez-Méndez José Ignacio
Published: January 2024

Purpose: The aim of this study is to describe our initial experience using magnetic seeds (Magseed®) to guide breast-conserving surgery in non-palpable breast lesions and compare the use of magnetic seed with wires to guide breast-conserving surgery in terms of clinical and pathological characteristics. Methods: We performed a retrospective study including all breast-conserving surgeries for non-palpable breast lesions under 16 mm from June 2018 to May 2021. We compared breast-conserving surgeries guided with magnetic seeds (Magseed®) to those guided with wires, analyzing tumor and patient characteristics, surgical time, and pathological results of the surgical specimens. Results: Data from 225 cases were collected, including 149 cases guided by magnetic seeds and 76 cases guided by wires. The breast lesion was localized in every case. Both cohorts were similar regarding clinical and pathological characteristics. We found significant statistical differences (p < 0.02) in terms of the median volume (cm3) of the excised specimen, which was lower (29.3%) in the magnetic seed group compared with the wire group (32.5 [20.5–60.0]/46.0 [20.3–118.7]). We did not find significant differences regarding surgical time (min) or the affected or close margins. Conclusion: In our experience, the use of magnetic seed (Magseed®) is a feasible option to guide breast-conserving surgery of non-palpable lesions and enabled us to resect less breast tissue.
Emerging Roles of Small Extracellular Vesicles in Gastrointestinal Cancer Research and Therapy
Authors: Schneider Nora , Hermann Patrick Christian , Eiseler Tim , Seufferlein Thomas
Published: January 2024

Discovered in the late eighties, sEVs are small extracellular nanovesicles (30–150 nm diameter) that gained increasing attention due to their profound roles in cancer, immunology, and therapeutic approaches. They were initially described as cellular waste bins; however, in recent years, sEVs have become known as important mediators of intercellular communication. They are secreted from cells in substantial amounts and exert their influence on recipient cells by signaling through cell surface receptors or transferring cargos, such as proteins, RNAs, miRNAs, or lipids. A key role of sEVs in cancer is immune modulation, as well as pro-invasive signaling and formation of pre-metastatic niches. sEVs are ideal biomarker platforms, and can be engineered as drug carriers or anti-cancer vaccines. Thus, sEVs further provide novel avenues for cancer diagnosis and treatment. This review will focus on the role of sEVs in GI-oncology and delineate their functions in cancer progression, diagnosis, and therapeutic use.
Inhibition of Enhancer of Zeste Homolog 2 Induces Blast Differentiation, Impairs Engraftment and Prolongs Survival in Murine Models of Acute Myeloid Leukemia
Authors: Fobare Sydney , Elgamal Ola A. , Wunderlich Mark , Stahl Emily , Mehmood Abeera , Furby Casie , Lerma James R. , Sesterhenn Thomas M. , Pan Jianmin , Rai Jayesh , Johnstone Megan E. , Abdul-Aziz Amina , Johnson Mariah L. , Rai Shesh N. , Byrd John C. , Hertlein Erin
Published: January 2024

Background: Acute myeloid leukemia (AML) is the malignant proliferation of immature myeloid cells characterized by a block in differentiation. As such, novel therapeutic strategies to promote the differentiation of immature myeloid cells have been successful in AML, although these agents are targeted to a specific mutation that is only present in a subset of AML patients. In the current study, we show that targeting the epigenetic modifier enhancer of zeste homolog 2 (EZH2) can induce the differentiation of immature blast cells into a more mature myeloid phenotype and promote survival in AML murine models. Methods: The EZH2 inhibitor EPZ011989 (EPZ) was studied in AML cell lines, primary in AML cells and normal CD34+ stem cells. A pharmacodynamic assessment of H3K27me3; studies of differentiation, cell growth, and colony formation; and in vivo therapeutic studies including the influence on primary AML cell engraftment were also conducted. Results: EPZ inhibited H3K27me3 in AML cell lines and primary AML samples in vitro. EZH2 inhibition reduced colony formation in multiple AML cell lines and primary AML samples, while exhibiting no effect on colony formation in normal CD34+ stem cells. In AML cells, EPZ promoted phenotypic evidence of differentiation. Finally, the pretreatment of primary AML cells with EPZ significantly delayed engraftment and prolonged the overall survival when engrafted into immunodeficient mice. Conclusions: Despite evidence that EZH2 silencing in MDS/MPN can promote AML pathogenesis, our data demonstrate that the therapeutic inhibition of EZH2 in established AML has the potential to improve survival.
The Oncogenic Lipid Sphingosine-1-Phosphate Impedes the Phagocytosis of Tumor Cells by M1 Macrophages in Diffuse Large B Cell Lymphoma
Authors: Perry Tracey A. , Masand Navta , Vrzalikova Katerina , Pugh Matthew , Wei Wenbin , Hollows Robert , Bouchalova Katerina , Nohtani Mahdi , Fennell Eanna , Bouchal Jan , Kearns Pamela , Murray Paul G.
Published: January 2024

Background: A total of 30–40% of diffuse large B cell lymphoma (DLBCL) patients will either not respond to the standard therapy or their disease will recur. The first-line treatment for DLBCL is rituximab and combination chemotherapy. This treatment involves the chemotherapy-induced recruitment of tumor-associated macrophages that recognize and kill rituximab-opsonized DLBCL cells. However, we lack insights into the factors responsible for the recruitment and functionality of macrophages in DLBCL tumors. Methods: We have studied the effects of the immunomodulatory lipid sphingosine-1-phosphate (S1P) on macrophage activity in DLBCL, both in vitro and in animal models. Results: We show that tumor-derived S1P mediates the chemoattraction of both monocytes and macrophages in vitro and in animal models, an effect that is dependent upon the S1P receptor S1PR1. However, S1P inhibited M1 macrophage-mediated phagocytosis of DLBCL tumor cells opsonized with the CD20 monoclonal antibodies rituximab and ofatumumab, an effect that could be reversed by an S1PR1 inhibitor. Conclusions: Our data show that S1P signaling can modulate macrophage recruitment and tumor cell killing by anti-CD20 monoclonal antibodies in DLBCL. The administration of S1PR1 inhibitors could enhance the phagocytosis of tumor cells and improve outcomes for patients.
Automated Quantitative Analysis of CT Perfusion to Classify Vascular Phenotypes of Pancreatic Ductal Adenocarcinoma
Authors: Perik Tom , Alves Natália , Hermans John J. , Huisman Henkjan
Published: January 2024

CT perfusion (CTP) analysis is difficult to implement in clinical practice. Therefore, we investigated a novel semi-automated CTP AI biomarker and applied it to identify vascular phenotypes of pancreatic ductal adenocarcinoma (PDAC) and evaluate their association with overall survival (OS). Methods: From January 2018 to November 2022, 107 PDAC patients were prospectively included, who needed to undergo CTP and a diagnostic contrast-enhanced CT (CECT). We developed a semi-automated CTP AI biomarker, through a process that involved deformable image registration, a deep learning segmentation model of tumor and pancreas parenchyma volume, and a trilinear non-parametric CTP curve model to extract the enhancement slope and peak enhancement in segmented tumors and pancreas. The biomarker was validated in terms of its use to predict vascular phenotypes and their association with OS. A receiver operating characteristic (ROC) analysis with five-fold cross-validation was performed. OS was assessed with Kaplan–Meier curves. Differences between phenotypes were tested using the Mann–Whitney U test. Results: The final analysis included 92 patients, in whom 20 tumors (21%) were visually isovascular. The AI biomarker effectively discriminated tumor types, and isovascular tumors showed higher enhancement slopes (2.9 Hounsfield unit HU/s vs. 2.0 HU/s, p < 0.001) and peak enhancement (70 HU vs. 47 HU, p < 0.001); the AUC was 0.86. The AI biomarker’s vascular phenotype significantly differed in OS (p < 0.01). Conclusions: The AI biomarker offers a promising tool for robust CTP analysis. In PDAC, it can distinguish vascular phenotypes with significant OS prognostication.
In Silico and In Vitro Mapping of Receptor-Type Protein Tyrosine Phosphatase Receptor Type D in Health and Disease: Implications for Asprosin Signalling in Endometrial Cancer and Neuroblastoma
Authors: Orton Sophie , Karkia Rebecca , Mustafov Denis , Gharanei Seley , Braoudaki Maria , Filipe Alice , Panfilov Suzana , Saravi Sayeh , Khan Nabeel , Kyrou Ioannis , Karteris Emmanouil , Chatterjee Jayanta , Randeva Harpal S.
Published: January 2024

Background: Protein Tyrosine Phosphatase Receptor Type D (PTPRD) is involved in the regulation of cell growth, differentiation, and oncogenic transformation, as well as in brain development. PTPRD also mediates the effects of asprosin, which is a glucogenic hormone/adipokine derived following the cleavage of the C-terminal of fibrillin 1. Since the asprosin circulating levels are elevated in certain cancers, research is now focused on the potential role of this adipokine and its receptors in cancer. As such, in this study, we investigated the expression of PTPRD in endometrial cancer (EC) and the placenta, as well as in glioblastoma (GBM). Methods: An array of in silico tools, in vitro models, tissue microarrays (TMAs), and liquid biopsies were employed to determine the gene and protein expression of PTPRD in healthy tissues/organs and in patients with EC and GBM. Results: PTPRD exhibits high expression in the occipital lobe, parietal lobe, globus pallidus, ventral thalamus, and white matter, whereas in the human placenta, it is primarily localised around the tertiary villi. PTPRD is significantly upregulated at the mRNA and protein levels in patients with EC and GBM compared to healthy controls. In patients with EC, PTPRD is significantly downregulated with obesity, whilst it is also expressed in the peripheral leukocytes. The EC TMAs revealed abundant PTPRD expression in both low- and high-grade tumours. Asprosin treatment upregulated the expression of PTPRD only in syncytialised placental cells. Conclusions: Our data indicate that PTPRD may have potential as a biomarker for malignancies such as EC and GBM, further implicating asprosin as a potential metabolic regulator in these cancers. Future studies are needed to explore the potential molecular mechanisms/signalling pathways that link PTPRD and asprosin in cancer.
The Use of Gene Expression Profiling and Biomarkers in Melanoma Diagnosis and Predicting Recurrence: Implications for Surveillance and Treatment
Authors: Sun James , Karasaki Kameko M. , Farma Jeffrey M.
Published: January 2024

Cutaneous melanoma is becoming more prevalent in the United States and has the highest mortality among cutaneous malignancies. The majority of melanomas are diagnosed at an early stage and, as such, survival is generally favorable. However, there remains prognostic uncertainty among subsets of early- and intermediate-stage melanoma patients, some of whom go on to develop advanced disease while others remain disease-free. Melanoma gene expression profiling (GEP) has evolved with the notion to help bridge this gap and identify higher- or lower-risk patients to better tailor treatment and surveillance protocols. These tests seek to prognosticate melanomas independently of established AJCC 8 cancer staging and clinicopathologic features (sex, age, primary tumor location, thickness, ulceration, mitotic rate, lymphovascular invasion, microsatellites, and/or SLNB status). While there is a significant opportunity to improve the accuracy of melanoma prognostication and diagnosis, it is equally important to understand the current landscape of molecular profiling for melanoma treatment. Society guidelines currently do not recommend molecular testing outside of clinical trials for melanoma clinical decision making, citing insufficient high-quality evidence guiding indications for the testing and interpretation of results. The goal of this chapter is to review the available literature for GEP testing for melanoma diagnosis and prognostication and understand their place in current treatment paradigms.
PPIP5K2 Facilitates Proliferation and Metastasis of Non-Small Lung Cancer (NSCLC) through AKT Signaling Pathway
Authors: Yang Qi , Cao Chenhui , Wu Binghuo , Yang Haochi , Tan Tian , Shang Dan , Xu Chuan , Huang Xiaoyi
Published: January 2024

Through facilitating DNA homologous recombination repair, PPIP5K2 has been proven to be essential for improving colorectal cancer survival in our previous research. However, its function in the tumorigenesis of NSCLC, the most common cancer and the primary cause of cancer-related death globally, is still unknown. Here, we initially discovered that PPIP5K2 had significant effects on proliferation of NSCLC cells through loss- and gain-of-function assays in vitro and in vivo. Moreover, PPIP5K2 is capable of regulating NSCLC cells metastasis in an EMT-dependent manner. In terms of mechanism exploration, we found that PPIP5K2 knockdown can significantly inhibit the phosphorylation of AKT/mTOR signaling pathway, whereas the overexpression of PPIP5K2 resulted in converse effects. By employing AKT signaling related agonists or antagonists, we further demonstrated that PPIP5K2 regulates NSCLC tumorigenesis partly via the AKT/mTOR pathway. In conclusion, PPIP5K2 plays a key oncogenic role in NSCLC by the activation of the AKT/mTOR signaling axis. It is anticipated that targeting PPIP5K2 might emerge as a viable therapeutic approach for NSCLC patients.
Healthcare Costs and Resource Utilisation of Italian Metastatic Non-Small Cell Lung Cancer Patients
Authors: Gentili Nicola , Balzi William , Foca Flavia , Danesi Valentina , Altini Mattia , Delmonte Angelo , Bronte Giuseppe , Crinò Lucio , De Luigi Nicoletta , Mariotti Marita , Verlicchi Alberto , Burgio Marco Angelo , Roncadori Andrea , Burke Thomas , Massa Ilaria
Published: January 2024

This study evaluated the economic burden of metastatic non-small cell lung cancer patients before and after the availability of an immuno-oncology (IO) regimen as a first-line (1L) treatment. Patients from 2014 to 2020 were categorized according to mutational status into mutation-positive and negative/unknown groups, which were further divided into pre-1L IO and post-1L IO sub-groups depending on the availability of pembrolizumab monotherapy in 1L. Healthcare costs and HCRU for a 1L treatment and overall follow-up were reported as the mean total and per-month cost per patient by groups. Of 644 patients, 125were mutation-positive and 519 negative/unknown (229 and 290 in pre- and post-1L IO, respectively). The mean total per-patient cost in 1L was lower in pre- (EUR 7804) and post-1L IO (EUR 19,301) than the mutation-positive group (EUR 45,247), persisting throughout overall disease follow-up. However, this difference was less when analyzing monthly costs. Therapy costs were the primary driver in 1L, while hospitalization costs rose during follow-up. In both mutation-positive and post-IO 1L groups, the 1L costs represented a significant portion (70.1% and 66.3%, respectively) of the total costs in the overall follow-up. Pembrolizumab introduction increased expenses but improved survival. Higher hospitalisation and emergency room occupation rates during follow-up reflected worsening clinical conditions of the negative/unknown group than the mutation-positive population.
Molecular Basis of XRN2-Deficient Cancer Cell Sensitivity to Poly(ADP-ribose) Polymerase Inhibition
Authors: Viera Talysa , Abfalterer Quinn , Neal Alyssa , Trujillo Richard , Patidar Praveen L.
Published: January 2024

R-loops (RNA–DNA hybrids with displaced single-stranded DNA) have emerged as a potent source of DNA damage and genomic instability. The termination of defective RNA polymerase II (RNAPII) is one of the major sources of R-loop formation. 5′-3′-exoribonuclease 2 (XRN2) promotes genome-wide efficient RNAPII termination, and XRN2-deficient cells exhibit increased DNA damage emanating from elevated R-loops. Recently, we showed that DNA damage instigated by XRN2 depletion in human fibroblast cells resulted in enhanced poly(ADP-ribose) polymerase 1 (PARP1) activity. Additionally, we established a synthetic lethal relationship between XRN2 and PARP1. However, the underlying cellular stress response promoting this synthetic lethality remains elusive. Here, we delineate the molecular consequences leading to the synthetic lethality of XRN2-deficient cancer cells induced by PARP inhibition. We found that XRN2-deficient lung and breast cancer cells display sensitivity to two clinically relevant PARP inhibitors, Rucaparib and Olaparib. At a mechanistic level, PARP inhibition combined with XRN2 deficiency exacerbates R-loop and DNA double-strand break formation in cancer cells. Consistent with our previous findings using several different siRNAs, we also show that XRN2 deficiency in cancer cells hyperactivates PARP1. Furthermore, we observed enhanced replication stress in XRN2-deficient cancer cells treated with PARP inhibitors. Finally, the enhanced stress response instigated by compromised PARP1 catalytic function in XRN2-deficient cells activates caspase-3 to initiate cell death. Collectively, these findings provide mechanistic insights into the sensitivity of XRN2-deficient cancer cells to PARP inhibition and strengthen the underlying translational implications for targeted therapy.
Postnatal Dynamic Ciliary ARL13B and ADCY3 Localization in the Mouse Brain
Authors: Brewer Katlyn K. , Brewer Kathryn M. , Terry Tiffany T. , Caspary Tamara , Vaisse Christian , Berbari Nicolas F.
Published: January 2024

Primary cilia are hair-like structures found on nearly all mammalian cell types, including cells in the developing and adult brain. A diverse set of receptors and signaling proteins localize within cilia to regulate many physiological and developmental pathways, including the Hedgehog (Hh) pathway. Defects in cilia structure, protein localization, and function lead to genetic disorders called ciliopathies, which present with various clinical features that include several neurodevelopmental phenotypes and hyperphagia-associated obesity. Despite their dysfunction being implicated in several disease states, understanding their roles in central nervous system (CNS) development and signaling has proven challenging. We hypothesize that dynamic changes to ciliary protein composition contribute to this challenge and may reflect unrecognized diversity of CNS cilia. The proteins ARL13B and ADCY3 are established markers of cilia in the brain. ARL13B is a regulatory GTPase important for regulating cilia structure, protein trafficking, and Hh signaling, and ADCY3 is a ciliary adenylyl cyclase. Here, we examine the ciliary localization of ARL13B and ADCY3 in the perinatal and adult mouse brain. We define changes in the proportion of cilia enriched for ARL13B and ADCY3 depending on brain region and age. Furthermore, we identify distinct lengths of cilia within specific brain regions of male and female mice. ARL13B+ cilia become relatively rare with age in many brain regions, including the hypothalamic feeding centers, while ADCY3 becomes a prominent cilia marker in the mature adult brain. It is important to understand the endogenous localization patterns of these proteins throughout development and under different physiological conditions as these common cilia markers may be more dynamic than initially expected. Understanding regional- and developmental-associated cilia protein composition signatures and physiological condition cilia dynamic changes in the CNS may reveal the molecular mechanisms associated with the features commonly observed in ciliopathy models and ciliopathies, like obesity and diabetes.
Wavy Ice Patterns as a Result of Morphological Instability of an Ice–Water Interface with Allowance for the Convective–Conductive Heat Transfer Mechanism
Authors: Alexandrov Dmitri V. , Makoveeva Eugenya V. , Pashko Alina D.
Published: January 2024

In this research, the wavy ice patterns that form due to the evolution of morphological perturbations on the water–ice phase transition interface in the presence of a fluid flow are studied. The mathematical model of heat transport from a relatively warm fluid to a cold wall includes the mechanism of convective–conductive heat transfer in liquid and small sinusoidal perturbations of the water–ice interface. The analytical solutions describing the main state with a flat phase interface as well as its small morphological perturbations are derived. Namely, the migration velocity of perturbations and the dispersion relation are found. We show that the amplification rate of morphological perturbations changes its sign with variation of the wavenumber. This confirms the existence of two different crystallization regimes with (i) a stable (flat) interfacial boundary and (ii) a wavy interfacial boundary. The maximum of the amplification rate representing the most dangerous (quickly growing) perturbations is found. The theory is in agreement with experimental data.
Insights in the Structural Hierarchy of Statically Crystallized Palm Oil
Authors: De Witte Fien , Penagos Ivana A. , Rondou Kato , Moens Kim , Lewille Benny , Tzompa-Sosa Daylan A. , Van de Walle Davy , Van Bockstaele Filip , Skirtach Andre G. , Dewettinck Koen
Published: January 2024

Palm oil (PO) is still widely used for the production of all types of food products. Due to its triacylglycerol (TG) composition, PO is semisolid at ambient temperature, offering possibilities for many applications. In order to tailor the fat crystal network for certain applications, it remains imperative to understand the structural build-up of the fat crystal network at the full-length scale and to understand the effect of processing conditions. In this study, PO was crystallized under four temperature protocols (fast (FC) or slow (SC) cooling to 20 °C or 25 °C) and was followed for one hour of isothermal time. A broad toolbox was used to fundamentally unravel the structural build-up of the fat crystal network at different length scales. Wide-angle and small-angle X-ray scattering (WAXS and SAXS) showed transitions from α-2L to β’-2L over time. Despite the presence of the same polymorphic form (β’), chain length structure (2L), and domain size, ultra-small-angle X-ray scattering (USAXS) showed clear differences in the mesoscale. For all samples, the lamellar organization was confirmed. Both cooling speed and isothermal temperature were found to affect the size of the crystal nanoplatelets (CNPs), where the highest cooling speed and lowest isothermal temperature (FC and 20 °C) created the smallest CNPs. The microstructure was visualized with polarized light microscopy (PLM) and cryo-scanning electron microscopy (cryo-SEM), showing clear differences in crystallite size, clustering, and network morphology. Raman spectroscopy was applied to confirm differences in triglyceride distribution in the fat crystal network. This study shows that both cooling rate and isothermal temperature affect the fat crystal network formed, especially at the meso- and microscale.
RE0.01Sr0.99Co0.5Fe0.5O3 (RE = La, Pr, and Sm) Cathodes for SOFC
Authors: Díaz-González Selene , Campana Roberto , Andújar Rocío , Pardo Adrián , Gil-Hernández Beatriz , Lozano-Gorrín Antonio D.
Published: January 2024

This study focuses on the synthesis, characterization, and study of new perovskite-type materials as cathodes in SOFC. The doped perovskites were successfully synthesized with high purity. The electrochemical performance of these materials was extensively examined through the characterization of I-V-P and EIS curves at the three temperatures, 750, 800, and 850 °C, where it reveals a substantial reduction in total resistances, accompanied by an impressive increase in power densities. The cell featuring La0.01Sr0.99Co0.5Fe0.5O3 exhibited the most commendable electrochemical properties at each temperature, following which were SrCo0.5Fe0.5O3, Pr0.01Sr0.99Co0.5Fe0.5O3, and Sm0.01Sr0.99Co0.5Fe0.5O3.
Assessment of Sessile Benthic Communities in Jeju Island, Republic of Korea, Using Autonomous Reef Monitoring Structures (ARMS)
Authors: Lee Kyeong-Tae , Kim Taihun , Park Gun-Hoo , Oh Chulhong , Park Heung-Sik , Kang Do-Hyung , Kang Hyun-Sil , Yang Hyun-Sung
Published: January 2024

Assessing the effectiveness of artificial structures as a monitoring tool for benthic diversity in temperate reefs is crucial to determining their relevance in reef conservation and management. In this study, we utilized Autonomous Reef Monitoring Structures (ARMS) to evaluate sessile benthic communities that colonized ARMS units after 12 and 34 months of immersion within distinct habitats (coral-dominated and macroalgae-dominated habitats) in Jeju Island, Korea. We used two methods: image analysis of the ARMS plates and DNA metabarcoding of the ARMS units. We found significant differences in the sessile benthic community between the plate faces, installation periods, and habitats. DNA metabarcoding also revealed differences in sessile benthic diversity among habitats. Additionally, we identified the Lithophyllum genus within the crustose coralline algae community, whose dominance might trigger a transition to coral-dominated habitats in Jeju Island. We recommend integrating ARMS image analysis with DNA metabarcoding to enhance and complement studies focusing on benthic diversity. By utilizing ARMS, this study provides valuable information for understanding sessile benthic communities and biodiversity, contributing to an enhanced understanding of the responses of ecological communities to climate change.
Diverse Communities of Endemic and Cosmopolitan Lineages at Local Sites in the Lecanora polytropa Aggregate (Ascomycota)
Authors: Woodhouse John , Pérez-Ortega Sergio , Roux Claude , Bertrand Michel , Leavitt Steven D.
Published: January 2024

Recent work has suggested exceptional species-level diversity in the lichen-forming Lecanora polytropa complex (Lecanoraceae, Ascomycota). However, biogeographic patterns and the spatial structuring of this diversity remains poorly known. To investigate diversity across multiple spatial scales, we sampled members of this species complex from two distinct regions—the Pacific Coast Ranges in southern Alaska, USA, and montane habitats in Spain. We also included sequence data from several species within this complex that were recently described from populations in France. Using the standard DNA barcoding marker and a sequence-based species delimitation approach (ASAP), we inferred a total of 123 candidate species (SHs) within the Lecanora polytropa complex, 32 of which were sampled for the first time here. Of 123 SHs, 21 had documented intercontinental distributions, while the vast majority were found at much smaller spatial scales. From our samples collected from Alaska, USA, and Spain, representing 36 SHs, we found high genetic diversity occurring within each sampled site, but limited overlap among all sites. Mountain ranges in both regions had high proportions of endemic lineages, with the highest diversity and endemism occurring in mountain ranges in Spain. Our sequence data generally support the recent taxonomic proposals, and an integrative taxonomy may help partly resolve the taxonomic conundrums within this hyper-diverse lineage.
Co-Evolution of Iolana Blues with Their Host Plants and the Higher Phylogeny of Subtribe Scolitantidina (Lepidoptera, Lycaenidae)
Authors: Nazari Vazrick , Montagud Alario Sergio , Spilani Loukia , Dincă Vlad , Naderi Alireza , ten Hagen Wolfgang , Vila Roger
Published: January 2024

We investigated the evolutionary relationships between the taxa in the butterfly genus Iolana Bethune-Baker, 1914 and others in the subtribe Scolitantidina using information from nine DNA markers (COI-COII, ND1, ITS2, 28S, CAD, EF-1α, wg, and H3). We show that the genus Iolana originated about 10 mya in Central Asia and gradually expanded to the west to reach Europe about 5 mya. We then compared our inferred phylogeny with that of the Iolana larval host plants in the genus Colutea, reconstructed using three DNA markers (ITS, matK, and rpl32). Although the host plant phylogeny was weakly resolved, the close spatiotemporal correlation between Iolana butterflies and their larval hosts suggests that they may have co-evolved. Based on the molecular results and the morphology of male and female genitalia, we confirm nine species in the genus Iolana, which are distributed in allopatry from Europe and North Africa to Central Asia. We synonymize I. andreasi andreasi Sheljuzhko, 1919 (=I. andreasi khayyami Bernardi, 1964 syn. nov.) and I. iolas wullschlegeli Oberthür, 1914 (=I. iolas protogenes Fruhstorfer, 1917 syn. nov.).
Wolf–Parkinson–White Syndrome: Diagnosis, Risk Assessment, and Therapy—An Update
Authors: Vătășescu Radu Gabriel , Paja Cosmina Steliana , Șuș Ioana , Cainap Simona , Moisa Ștefana María , Cinteză Eliza Elena
Published: January 2024

Wolf–Parkinson–White (WPW) syndrome is a disorder characterized by the presence of at least one accessory pathway (AP) that can predispose people to atrial/ventricular tachyarrhythmias and even sudden cardiac death. It is the second most common cause of paroxysmal supraventricular tachycardia in most parts of the world, affecting about 0.1–0.3% of the general population. Most patients with WPW syndrome have normal anatomy, but it may be associated with concomitant congenital heart disease or systemic diseases. Although many individuals are asymptomatic, during supraventricular arrhythmia episodes, they may experience severe symptoms, including syncope or even sudden cardiac death (mainly due to pre-excited atrial fibrillation over rapidly conducting AP). In addition to arrhythmia-related symptoms, for some specific locations of the APs with overt anterograde conduction, there might be a reduction in exercise capacity mediated by a reduction in LV systolic performance due to anomalous LV depolarization. Although it is typically diagnosed through electrocardiography (ECG), additional tests are necessary for risk assessment. Management of WPW syndrome may be quite challenging and can vary from only acknowledging the presence of the accessory pathway to pharmacological treatment or radiofrequency ablation. Early diagnosis, risk assessment, and appropriate treatment are critical steps in the management of WPW syndrome, aiming to improve the quality of life and reduce the risk of life-threatening arrhythmias.
Quantifying the Impact of Avian Influenza on the Northern Gannet Colony of Bass Rock Using Ultra-High-Resolution Drone Imagery and Deep Learning
Authors: Tyndall Amy A. , Nichol Caroline J. , Wade Tom , Pirrie Scott , Harris Michael P. , Wanless Sarah , Burton Emily
Published: January 2024

Drones are an increasingly popular choice for wildlife surveys due to their versatility, quick response capabilities, and ability to access remote areas while covering large regions. A novel application presented here is to combine drone imagery with neural networks to assess mortality within a bird colony. Since 2021, Highly Pathogenic Avian Influenza (HPAI) has caused significant bird mortality in the UK, mainly affecting aquatic bird species. The world’s largest northern gannet colony on Scotland’s Bass Rock experienced substantial losses in 2022 due to the outbreak. To assess the impact, RGB imagery of Bass Rock was acquired in both 2022 and 2023 by deploying a drone over the island for the first time. A deep learning neural network was subsequently applied to the data to automatically detect and count live and dead gannets, providing population estimates for both years. The model was trained on the 2022 dataset and achieved a mean average precision (mAP) of 37%. Application of the model predicted 18,220 live and 3761 dead gannets for 2022, consistent with NatureScot’s manual count of 21,277 live and 5035 dead gannets. For 2023, the model predicted 48,455 live and 43 dead gannets, and the manual count carried out by the Scottish Seabird Centre and UK Centre for Ecology and Hydrology (UKCEH) of the same area gave 51,428 live and 23 dead gannets. This marks a promising start to the colony’s recovery with a population increase of 166% determined by the model. The results presented here are the first known application of deep learning to detect dead birds from drone imagery, showcasing the methodology’s swift and adaptable nature to not only provide ongoing monitoring of seabird colonies and other wildlife species but also to conduct mortality assessments. As such, it could prove to be a valuable tool for conservation purposes.
A Hands-On Collaboration-Ready Single- or Interdisciplinary Computational Exercise in Molecular Recognition and Drug Design
Authors: Allen Patrick , Nguyen Nguyet , Humphrey Nicholas D. , Mao Jia , Chavez-Bonilla Daniel , Sorin Eric J.
Published: January 2024

Molecular docking plays an increasingly necessary role in interdisciplinary research, particularly in modern drug design. Pharmaceutical companies compose a trillion dollar per year industry and the public is generally unaware of how beneficial pharmaceutics come to be. Despite this increasing relevance in contemporary research, docking and, by extension, computational science, have been under-represented in undergraduate education in the chemical, biochemical, and biophysical sciences. We describe herein how a multidisciplinary approach is used to design novel inhibitors of the butyrylcholinesterase enzyme (BChE), an upregulated protein in patients suffering from Alzheimer’s disease. Students will then be able to compare their designed inhibitors to known BChE inhibitors via molecular docking using this easily adapted hands-on computational laboratory exercise or at-home activity that provides users with a module in which to learn the fundamentals of computer-aided drug design. While being well suited for upper-division courses in biology/biochemistry and physics/physical chemistry, the accessibility of this module allows for its incorporation into college curricula as early as second-term organic chemistry. Highly portable freeware makes this an ideal learning tool by which to infuse single- or multidisciplinary drug design reasoning into college level curricula at no cost to the student or instructor.
A Mixed Study of Beliefs about Critical Thinking in a Sample of Trainee Teachers in Argentina and Spain
Authors: Garcia-Moro Francisco Jose , Gadea-Aiello Walter Federico , Nicoletti Javier Augusto , Gomez-Baya Diego
Published: January 2024

Critical thinking is a competence that is recommended to be learned with increasing emphasis from different national and international organizations in the fields of education and employability. The aim of this study was to analyze and describe the beliefs that Argentine and Spanish teachers who have received training in socioeducational intervention have about critical competence. A mixed-methods research study was developed by administering questionnaires and conducting focus group sessions in a sample of 153 trainee secondary school teachers holding different degrees. The results indicated that the sample subjects unanimously considered critical thinking to be essential for their professional development, but few teachers considered these skills to have been sufficiently developed. There were no significant differences between nationalities or between genders except for some variables linked to the role of universities. As a practical implication of these results, the importance of developing specific teaching–learning programs about critical competence in universities must be emphasized, especially in the degree programs whose ultimate aim is to educate individuals and groups.
Discrete-Time Adaptive Control for Uncertain Scalar Multiagent Systems with Coupled Dynamics: A Lyapunov-Based Approach
Authors: Aly Islam A. , Dogan Kadriye Merve
Published: January 2024

Discrete-time architectures offer a distinct advantage over their continuous counterparts, as they can be seamlessly implemented on embedded hardware without the necessity for discretization processes. Yet, because of the difficulty of ensuring Lyapunov difference expressions, their designs, which are based on quadratic Lyapunov-based frameworks, are highly complex. As a result, various existing continuous-time results using adaptive control methods to deal with system uncertainties and coupled dynamics in agents of a multiagent system cannot be directly applied to the discrete-time context. Furthermore, compared to their continuous-time equivalent, discrete-time information exchange based on periodic time intervals is more practical in the control of multiagent systems. Motivated by these standpoints, in this paper, we first introduce a discrete-time adaptive control architecture designed for uncertain scalar multiagent systems without coupled dynamics as a preliminary result. We then introduce another discrete-time adaptive control approach for uncertain multiagent systems in the presence of coupled dynamics. Our approach incorporates observer dynamics to manage unmeasurable coupled dynamics, along with a user-assigned Laplacian matrix to induce cooperative behaviors among multiple agents. Our solution includes Lyapunov analysis with logarithmic and quadratic Lyapunov functions for guaranteeing asymptotic stability with both controllers. To demonstrate the effectiveness of the proposed control architectures, we provide an illustrative example. The illustrative numerical example shows that the standard discrete-time adaptive control in the absence of observer dynamics cannot guarantee the reference state vector tracking, while the proposed discrete-time adaptive control can ensure the tracking objective.