bluuebunny/crossref_metadata_2025 huggingface dataset:
Surgical Strategies for Recurrent Hepatocellular Carcinoma after Resection: A Review of Current Evidence
Authors: Milana Flavio , Polidoro Michela Anna , Famularo Simone , Lleo Ana , Boldorini Renzo , Donadon Matteo , Torzilli Guido
Published: January 2023

Hepatocellular carcinoma (HCC) is the most common primary liver cancer, and both liver resection and liver transplantation are considered potentially curative options. However, high recurrence rates affect the prognosis depending both on the primary HCC pathology characteristics or on the type and time of the relapse. While great attention has been usually posted on treatment algorithms for the first HCC, treatment algorithms for recurrent HCC (rHCC) are lacking. In these cases, surgery still represents a curative option with both redo hepatectomy and/or salvage liver transplantation, which are considered valid treatments in selected patients. In the current era of personalised medicine with promises of new systemic-targeted immuno-chemotherapies, we wished to perform a narrative review of the literature on the role of surgical strategies for rHCC.
Concurrent Inhibition of Akt and ERK Using TIC-10 Can Overcome Venetoclax Resistance in Mantle Cell Lymphoma
Authors: Granau Agnete Marie , Andersen Pilar Aarøe , Jakobsen Theresa , Taouxi Konstantina , Dalila Nawar , Mogensen Johanne Bay , Kristensen Lasse Sommer , Grønbæk Kirsten , Dimopoulos Konstantinos
Published: January 2023

Venetoclax, a BCL-2 inhibitor, has proven to be effective in several hematological malignancies, including mantle cell lymphoma (MCL). However, development of venetoclax resistance is inevitable and understanding its underlying molecular mechanisms can optimize treatment response. We performed a thorough genetic, epigenetic and transcriptomic analysis of venetoclax-sensitive and resistant MCL cell lines, also evaluating the role of the stromal microenvironment using human and murine co-cultures. In our model, venetoclax resistance was associated with abrogated TP53 activity through an acquired mutation and transcriptional downregulation leading to a diminished apoptotic response. Venetoclax-resistant cells also exhibited an upregulation of the PI3K/Akt pathway, and pharmacological inhibition of Akt and ERK with TIC-10 led to cell death in all venetoclax-resistant cell lines. Overall, we highlight the importance of targeted therapies, such as TIC-10, against venetoclax resistance-related pathways, which might represent future therapeutic prospects.
Trends in Overall Survival among Patients Treated for Sarcoma at a Large Tertiary Cancer Center between 1986 and 2014
Authors: Stricker Erik , Reed Damon R. , Schabath Matthew B. , Sok Pagna , Scheurer Michael E. , Lupo Philip J.
Published: January 2023

Sarcomas are relatively rare malignancies accounting for about 1% of all cancer diagnoses. Studies on sarcomas comprising large cohorts covering extended time periods are lacking. Therefore, this study aimed to evaluate the impact of demographic, behavioral, and clinical characteristics on overall survival (OS) among individuals diagnosed with soft tissue sarcoma (STS) or bone sarcoma at the Moffitt Cancer Center between 1986 and 2014. Unadjusted and multivariable Cox proportional hazard regression (CPHR) models were constructed to generate hazard ratios (HRs) and 95% confidence intervals (CIs) to evaluate associations between a range of demographic, behavioral, and clinical characteristics, and OS. Additionally, Kaplan–Meier survival curves, associated log-rank statistics, and adjusted CPHR models were generated by time periods based on the year of first contact (1986–1994, 1995–1999, 2000–2005, 2006–2010, 2011–2014) to evaluate for temporal differences in OS. Of the 2570 patients, 2037 were diagnosed with STS, whereas 533 were diagnosed with bone sarcoma. At the time of analysis, 50% of the population were alive. In multivariable analyses, we observed poorer survival for patients ≥ 40 years of age (HR = 1.54, 95% CI = 1.34–1.78), current smokers (HR = 1.18, 95% CI = 1.01–1.37), patients with metastasis (HR = 2.19, 95% CI = 1.95–2.47), and patients not receiving first-line surgery treatment (HR = 2.11, 95% CI = 1.82–2.45). We discovered limited improvements in OS over time among individuals diagnosed with STS or bone sarcomas with the exception of gastrointestinal stromal tumors (GIST), which showed a significant improvement in OS across time periods (p = 0.0034). Overall, we identified well-established characteristics associated with OS (e.g., metastasis) in addition to factors (e.g., smoking status) not previously reported to impact OS. Improvements in survival over time have been relatively modest, suggesting the need for improved therapeutic options, especially for those diagnosed with less frequent sarcomas.
Costs of Newly Funded Proton Therapy Using Time-Driven Activity-Based Costing in The Netherlands
Authors: Chen Yi Hsuan , Blommestein Hedwig M. , Klazenga Reinder , Uyl-de Groot Carin , van Vulpen Marco
Published: January 2023

Background: Proton therapy (PT) has characteristics that enable the sparing of healthy, non-cancerous tissue surrounding the radiotherapy target volume better from radiation doses than conventional radiotherapy for patients with cancer. While this innovation entails investment costs, the information about the treatment costs per patient, especially during the start-up phase, is limited. This study aims to calculate the costs of PT at a single center during the start-up phase in the Netherlands. Methods: The cost of PT per patient was estimated for the treatment indications, head and neck cancer, breast cancer, brain cancer, thorax cancer, chordoma and eye melanoma. A time-driven activity-based costing analysis (TDABC), a methodology that calculates the costs of consumed healthcare resources by a patient, was conducted in a newly established PT center in the Netherlands (HPTC). Both direct (e.g., the human resource costs for medical staff) and indirect costs (e.g., the operating/interest costs, indirect human resource costs and depreciation costs) were included. A scenario analysis was conducted for short-term (2021), middle-term (till 2024) and long-term (after 2024) predicted patient numbers in the PT center. Results: The total cost of PT in 2020 at the center varied between EUR 12,062 for an eye melanoma course and EUR 89,716 for a head and neck course. Overall, indirect costs were the largest cost component. The high indirect costs implied the potential of the scale of economics; according to our estimation, the treatment cost could be reduced to 35% of the current cost when maximum treatment capacity is achieved. Conclusion: This study estimated the PT cost delivered in a newly operated treatment center. Scenario analysis for increased patient numbers revealed the potential for cost reductions. Nevertheless, to have an estimation that reflects the matured cost of PT which could be used in cost-effectiveness analysis, a follow-up study assessing the full-fledged situation is recommended.
The True Value of Quantitative Imaging for Adrenal Mass Characterization: Reality or Possibility?
Authors: Stanzione Arnaldo , Romeo Valeria , Maurea Simone
Published: January 2023

The widespread use of cross-sectional imaging modalities, such as computed tomography (CT) and magnetic resonance imaging (MRI), in the evaluation of abdominal disorders has significantly increased the number of incidentally detected adrenal abnormalities, particularly adrenal masses [...]
Diagnosis and Treatment Using Autologous Stem-Cell Transplantation in Primary Central Nervous System Lymphoma: A Systematic Review
Authors: Steffanoni Sara , Calimeri Teresa , Marktel Sarah , Nitti Rosamaria , Foppoli Marco , Ferreri Andrés J. M.
Published: January 2023

Background: Consolidation therapy has improved the outcome of newly diagnosed PCNSL patients. Whole-brain radiotherapy (WBRT) was the first consolidation strategy used and represented the gold standard for many years, but at the expense of a high risk of neurotoxicity. Thus, alternative strategies are being investigated in order to improve disease outcomes and to spare the neurocognitive side effects due to WBRT. Methods: We reviewed published studies on PCNSL patients treated with HDC/ASCT, focusing on the efficacy and safety of the conditioning regimens. Prospective and retrospective studies, published in the English language from 1992 to 2022, in high-quality international journals were identified in PubMed. Results: Consolidation with HDC containing highly CNS-penetrating agents (thiotepa, busulfan or BCNU) followed by ASCT provided long-term disease control and survival in PCNSL patients. Two prospective randomized studies, comparing HDC/ASCT versus WBRT, reported similar progression-free survival (PFS) and similar results on the decline in neurocognitive functions in a substantial proportion of patients after WBRT but not after HDC-ASCT. A recent randomized study comparing HDC/ASCT versus non-myeloablative consolidation reported a longer PFS in transplanted patients. Conclusion: ASCT conditioned with regimens, including highly CNS-penetrating agents, represents, to date, the best choice among the available consolidation strategies for fit newly diagnosed PCNSL patients.
Post-Translational Modifications of Histone Variants in the Absence and Presence of a Methionine-Depleting Enzyme in Normal and Cancer Cells
Authors: Montalbano Serena , Raboni Samanta , Sidoli Simone , Mozzarelli Andrea , Bettati Stefano , Buschini Annamaria
Published: January 2023

Methionine is an essential amino acid involved in the formation of polyamines and a precursor metabolite for DNA and protein methylation. The dependence of cancer cells on methionine has triggered extensive investigations aimed at its targeting for cancer therapy, including the exploitation as a therapeutic tool of methionine γ-lyase (MGL), a bacterial enzyme that degrades methionine, capable of inhibiting cancer cells growth due to methionine starvation. We have exploited the high-resolution power of mass spectrometry to compare the effects of reduced availability of the methyl donor SAM, induced by MGL treatment, on the post-translational modifications of the histone tails in normal Hs27 and cancer HT-29 cells. In the absence of MGL, our analysis detected a three-fold higher relative abundance of trimethylated K25 of H1.4 in HT-29 than Hs27 cells, and a complex pattern of methylated, unmethylated and acetylated peptides in H2 and H3.3. In the presence of MGL, in HT-29, the peptide H2A1_4_11 is predominantly unmodified with mono-methylated K5 increasing upon treatment, whereas in Hs27 cells, H2A1_4_11 is monomethylated at K5 and K9 with these marks decreasing upon treatment. The time dependence of the effects of MGL-mediated methionine depletion on PTMs of histone variants in HT-29 cancer cells was also monitored. Overall, our present data on histone variants H1, H2A, H2B as well as H3.3 integrated with our previous studies on histones H3 and H4, shed light on the epigenetic modifications associated with methionine starvation and associated cancer cell death.
Shallow Whole-Genome Sequencing of Cell-Free DNA (cfDNA) Detects Epithelial Ovarian Cancer and Predicts Patient Prognosis
Authors: Bak Seong Eun , Kim Hanwool , Ho Jung Yoon , Cho Eun-Hae , Lee Junnam , Youn Sung Min , Park Seong-Woo , Han Mi-Ryung , Hur Soo Young , Lee Sung Jong , Choi Youn Jin
Published: January 2023

Despite the progress in diagnostics and therapeutics, epithelial ovarian cancer (EOC) remains a fatal disease. Using shallow whole-genome sequencing of plasma cell-free DNA (cfDNA), we investigated biomarkers that could detect EOC and predict survival. Plasma cfDNA from 40 EOC patients and 20 healthy subjects were analyzed by shallow whole-genome sequencing (WGS) to identify copy number variations (CNVs) and determine the Z-scores of genes. In addition, we also calculated the genome-wide scores (Gi scores) to quantify chromosomal instability. We found that the Gi scores could distinguish EOC patients from healthy subjects and identify various EOC histological subtypes (e.g., high-grade serous carcinoma). In addition, we characterized EOC CNVs and demonstrated a relationship between RAB25 amplification (alone or with CA125), and disease-free survival and overall survival. This study identified RAB25 amplification as a predictor of EOC patient survival. Moreover, we showed that Gi scores could detect EOC. These data demonstrated that cfDNA, detected by shallow WGS, represented a potential tool for diagnosing EOC and predicting its prognosis.
Distinct Cellular Origins and Differentiation Process Account for Distinct Oncogenic and Clinical Behaviors of Leiomyosarcomas
Authors: Darbo Elodie , Pérot Gaëlle , Darmusey Lucie , Le Guellec Sophie , Leroy Laura , Gaston Laëtitia , Desplat Nelly , Thébault Noémie , Merle Candice , Rochaix Philippe , Valentin Thibaud , Ferron Gwenaël , Chevreau Christine , Bui Binh , Stoeckle Eberhard , Ranchere-Vince Dominique , Méeus Pierre , Terrier Philippe , Piperno-Neumann Sophie , Collin Françoise , De Pinieux Gonzague , Duffaud Florence , Coindre Jean-Michel , Blay Jean-Yves , Chibon Frédéric
Published: January 2023

In leiomyosarcoma (LMS), a very aggressive disease, a relatively transcriptionally uniform subgroup of well-differentiated tumors has been described and is associated with poor survival. The question raised how differentiation and tumor progression, two apparently antagonist processes, coexist and allow tumor malignancy. We first identified the most transcriptionally homogeneous LMS subgroup in three independent cohorts, which we named ‘hLMS’. The integration of multi-omics data and functional analysis suggests that hLMS originate from vascular smooth muscle cells and show that hLMS transcriptional program reflects both modulations of smooth muscle contraction activity controlled by MYOCD/SRF regulatory network and activation of the cell cycle activity controlled by E2F/RB1 pathway. We propose that the phenotypic plasticity of vascular smooth muscle cells coupled with MYOCD/SRF pathway amplification, essential for hLMS survival, concomitant with PTEN absence and RB1 alteration, could explain how hLMS balance this uncommon interplay between differentiation and aggressiveness.
Dual Function of CCAT2 in Regulating Luminal Subtype of Breast Cancer Depending on the Subcellular Distribution
Authors: Xie Heying , Guo Yuefan , Xu Zhen , Wang Qiong , Wang Tao , Gu Yi , Li Danni , Liu Yu , Ma Wenjing , Liu Pengfei , Zhao Qian , Lü Jinhui , Liu Junjun , Yu Zuoren
Published: January 2023

Breast cancer is the most common cancer in women around the world. Emerging evidence has indicated the important roles that non-coding RNAs play in regulating tumor development and progression in breast cancer. Herein, we found a dual function of long non-coding RNA (LncRNA) CCAT2 in the luminal subtype of breast cancer, depending on its subcellular distribution. CCAT2 showed an overall downregulation in the tumor tissues from luminal breast cancer patients. Transient overexpression of CCAT2 in the luminal subtype of breast cancer cell MCF-7 or T47D significantly suppressed cell proliferation in vitro and inhibited tumor growth in vivo. Gene expression analysis of cancer stem cell markers including OCT4, NANOG, h-TERT, SOX2 and KLF4; flow cytometry analysis of breast cancer stem cell population, and mammosphere formation assay demonstrated inhibition of cancer cell stemness with transient transfection of CCAT2 in which exogenous CCAT2 mainly distributed in the cytoplasm and regulated miR-221-p27 signaling via RNA sequence interaction. However, overexpression of CCAT2 in MCF-7 cells through pMX retroviral nuclear expression vector accumulated CCAT2 in the nucleus, leading to upregulation of OCT4-PG1, a pseudogene of stem gene OCT4, thereby promoting the cancer cell stemness. In conclusion, the current study, for the first time, revealed a dual function of lncRNA CCAT2 as a tumor suppressor or oncogene depending upon its subcellular distribution. It also demonstrated the regulatory mechanism of cytoplasmic CCAT2 in suppressing tumorigenesis in the luminal subtype of breast cancer.
Efficacy of Liver Chemoembolization after Prior Cetuximab Monotherapy in Patients with Metastatic Colorectal Cancer
Authors: Szemitko Marcin , Golubinska-Szemitko Elzbieta , Sienko Jerzy , Falkowski Aleksander , Wiernicki Ireneusz
Published: January 2023

Purpose: Chemoembolization of liver lesions, metastatic from colorectal cancer (CRC), with irinotecan-loaded microspheres shows less efficacy if applied after previous systemic chemotherapy. This is because cancer cells acquire resistance to previously used chemotherapeutic agents, e.g., irinotecan or perhaps via, e.g., modulations of EGFR receptors after use of anti-EGFR antibodies. Objective: To evaluate the effects of prior treatment with anti-EGFR (cetuximab) antibodies on the efficacy of chemoembolization, with irinotecan-loaded microspheres, of liver lesions metastatic from CRC. Patients and methods: The study included 50 patients (27 female, 23 male) with inoperable liver metastases in the course of CRC who underwent a total of 192 chemoembolization procedures with microspheres loaded with 100 mg of irinotecan. Chemoembolization of the right or left liver lobes was performed alternately at three-week intervals. Patients were divided into two groups: group A (n = 26): patients who had previously received anti-EGFR (cetuximab) antibodies; and group B (n = 24): patients who had never received anti-EGFR antibodies. Response to treatment was assessed according to mRECIST criteria. Overall survival time (OS) was calculated using the Kaplan–Meier method. Evaluation of adverse effects was performed according to the Cancer Therapy Evaluation Program Common Terminology Criteria for Adverse Events (Version 5.0). Results: Analysis did not show a statistically significant difference in radiological response between the two groups: partial response: 36.2% in group A and 32.9% in group B (p = 0.139); and stable disease: 19.2% in group A and 21.7% in group B (p = 0.224). Post-treatment progression was comparable at 46.2% in group A and 41.6% in group B (p = 0.343). There was a significant difference in OS (p = 0.043 log-rank test), however, prior treatment with cetuximab showed no significant effect on OS in a Cox proportional hazards regression model HR 1.906 (0.977–3.716), p = 0.058. Mean OS was 15.2 months (95% confidence interval (Cl): 6 to 23 months) in group A and 13.1 months (95% Cl: 7 to 22 months) in group B. In both groups, there was a negative correlation between carcinoembryonic antigen (CEA) levels below 10 mg/mL before surgery and OS (hazard ratio (HR) 0.83 (0.47–8.43), p = 0.005 in group A and HR 1.02 (0.56–7.39), p = 0.003 in group B). There was no significant difference in the number of prominent complications between group A (7 complications) and group B (6 complications), p = 0.663. Conclusions: Previous therapy with anti-EGFR antibodies before treatment with irinotecan chemoembolization of liver metastatic lesions did not have a significant effect on radiological response to treatment or post-treatment progression. However, higher baseline levels of CEA (>10 ng/mL) were correlated with worse OS (p = 0.039).
Multimodal Deep Learning-Based Prognostication in Glioma Patients: A Systematic Review
Authors: Alleman Kaitlyn , Knecht Erik , Huang Jonathan , Zhang Lu , Lam Sandi , DeCuypere Michael
Published: January 2023

Malignant brain tumors pose a substantial burden on morbidity and mortality. As clinical data collection improves, along with the capacity to analyze it, novel predictive clinical tools may improve prognosis prediction. Deep learning (DL) holds promise for integrating clinical data of various modalities. A systematic review of the DL-based prognostication of gliomas was performed using the Embase (Elsevier), PubMed MEDLINE (National library of Medicine), and Scopus (Elsevier) databases, in accordance with PRISMA guidelines. All included studies focused on the prognostication of gliomas, and predicted overall survival (13 studies, 81%), overall survival as well as genotype (2 studies, 12.5%), and response to immunotherapy (1 study, 6.2%). Multimodal analyses were varied, with 6 studies (37.5%) combining MRI with clinical data; 6 studies (37.5%) integrating MRI with histologic, clinical, and biomarker data; 3 studies (18.8%) combining MRI with genomic data; and 1 study (6.2%) combining histologic imaging with clinical data. Studies that compared multimodal models to unimodal-only models demonstrated improved predictive performance. The risk of bias was mixed, most commonly due to inconsistent methodological reporting. Overall, the use of multimodal data in DL assessments of gliomas leads to a more accurate overall survival prediction. However, due to data limitations and a lack of transparency in model and code reporting, the full extent of multimodal DL as a resource for brain tumor patients has not yet been realized.
DHODH Inhibition Exerts Synergistic Therapeutic Effect with Cisplatin to Induce Ferroptosis in Cervical Cancer through Regulating mTOR Pathway
Authors: Jiang Mengying , Song Yizuo , Liu Hejing , Jin Yanshan , Li Ruyi , Zhu Xueqiong
Published: January 2023

Ferroptosis exhibits a potent antitumor effect and dihydroorotate dehydrogenase (DHODH) has recently been identified as a novel ferroptosis defender. However, the role of DHODH inhibition in cervical cancer cells is unclear, particularly in synergy with cisplatin via ferroptosis. Herein, shRNA and brequinar were used to knock down DHODH and directly inhibit DHODH, respectively. Immunohistochemistry and Western blotting assays were performed to measure the expression of proteins. CCK-8 and colony formation assays were employed to assess the cell viability and proliferation. Ferroptosis was monitored through flow cytometry, the malondialdehyde assay kit and JC-1 staining analyses. The nude mouse xenograft model was generated to examine the effect of combination of DHODH inhibition and cisplatin on tumor growth in vivo. The expression of DHODH was increased in cervical cancer tissues. DHODH inhibition inhibited the proliferation and promoted the ferroptosis in cervical cancer cells. A combination of DHODH inhibition and cisplatin synergistically induced both in vitro and in vivo ferroptosis and downregulated the ferroptosis defender mTOR pathway. Therefore, the combination of DHODH inhibition and cisplatin exhibits synergistic effects on ferroptosis induction via inhibiting the mTOR pathway could provide a promising way for cervical cancer therapy.
Degradation of Textile Dye by Bimetallic Oxide Activated Peroxymonosulphate Process
Authors: Rashid Hera , Nidheesh P. V.
Published: January 2023

The sulphate radical based advanced oxidation processes (AOPs) are highly in demand these days, owing to their numerous advantages. Herein, the Fe-Mn bimetallic oxide particle was used to activate peroxymonosulphate (PMS) for Rhodamine B (RhB) degradation. Three bimetallic catalysts were synthesized via the chemical precipitation method with different concentrations of metals; Fe-Mn (1:1), Fe-Mn (1:2) and Fe-Mn (2:1). The best performance was shown by Fe-Mn (2:1) system at optimized conditions; 96% of RhB was removed at optimized conditions. Scavenging experiments displayed the clear dominance of hydroxyl radical in pH 3, while sulphate radical was present in a large amount at pH 7 and 10. The monometallic Fe and Mn oxides were also synthesized to confirm the synergistic effect that was present in the bimetallic oxide system. The application of optimized condition in real textile wastewater was conducted, which revealed the system works efficiently at high concentrations of PMS and catalyst dosage.
Comparison of Catalytic Properties of the Easily Interconvertible, Water-Soluble [RuHCl(CO)(mtppms-Na)3] and [RuH(H2O)(CO)(mtppms-Na)3][BF4]
Authors: Horváth Henrietta , Papp Gábor , Joó Ferenc , Kathó Ágnes
Published: January 2023

The effect of the mobile interconversion of [RuHCl(CO)(mtppms-Na)3] 1, and [RuH(H2O)(CO)(mtppms-Na)3]+ 2, was studied in hydrogenation of phenylacetylene and cinnamaldehyde in aqueous–organic biphasic systems, as a function of the chloride concentration and the pH of the aqueous phase. Catalytic activity of the two complexes was also determined in homogeneous organic solvents without any additives. In the biphasic system, the rate of selective hydrogenation of phenylacetylene to styrene was strongly increased upon addition of NaCl, while the reaction of cinnamaldehyde slowed, with no change in product distribution. Both reactions responded with a rate decrease upon increasing the pH of the aqueous phase. It was concluded that hydrogenation of phenylacetylene was catalyzed by 1 with no chloride dissociation, while in the reduction of cinnamaldehyde, the aquo-complex 2 was the active catalytic species. Catalytic cycles were suggested to rationalize these findings.
High-Temperature-Treated LTX Zeolites as Heterogeneous Catalysts for the Hock Cleavage
Authors: Drönner Jan , Bijerch Karim , Hausoul Peter , Palkovits Regina , Eisenacher Matthias
Published: January 2023

Hydroxybenzene, commonly known as phenol, is one of the most important organic commodity chemicals. To produce phenol, the cumene process is the most used process worldwide. A crucial step in this process is the Hock rearrangement, which has a major impact on the overall cumene consumption rate and determines the safety level of the process. The most used catalyst for the cleavage of cumene hydroperoxide (CHP) is sulfuric acid. Besides its strong corrosive property, which increases plant investment costs, it also requires neutralization after the decomposition step to prevent side reactions. In this study, we show that high-temperature-treated Linde Type X (LTX) zeolites exhibit a high activity for the peroxide cleavage step. In addition, the structure–activity relationship responsible for this good performance in the reaction system of the HOCK rearrangement was investigated. XRPD analyses revealed the formation of a new phase after temperature treatment above 900 °C. The Si/Al ratio determined by EDX suggested the formation of extra-framework aluminum, which was confirmed by solid-state NMR analysis. The newly formed extra-framework aluminum was found to be responsible for the high catalytic activity. BET analyses showed that the surface area drops at higher calcination temperatures. This leads to a lower catalytic activity for most known reactions. However, for this study, no decrease in activity has been observed. The newfound material shows extraordinarily high activity as a catalyst in the HOCK cleavage and has the potential to be a heterogeneous alternative to sulfuric acid for this reaction.
Circular RNAs: Non-Canonical Observations on Non-Canonical RNAs
Authors: Stringer Brett W. , Gantley Laura , Conn Simon J.
Published: January 2023

The existence of circular RNA (circRNA) research in mainstream science can be attributed to the contemporary synergism of big data and keen attention to detail by several research groups worldwide. Since the re-emergence of these non-canonical RNA transcripts, seminal advances have been made in understanding their biogenesis, interactome, and functions in diverse fields and a myriad of human diseases. However, most research outputs to date have focused on the ability of highly stable circRNAs to interact with, and impact signalling through, microRNAs. This is likely to be the result of seminal papers in the field ascribing a few remarkable circRNAs as “miRNA sponges”. However, the stoichiometric ratio between the (often-lowly-expressed) circRNA and their (commonly-more-abundant) target is rarely in favour of a biologically relevant and functional consequence of these interactions. It is time for yet another revolution in circRNA research to uncover functions beyond their documented ability to bind miRNAs. This Special Issue aims to highlight non-canonical functions for this non-canonical family of RNA molecules.
Non-Steroidal Drug Interferences in a Quantitative Multisteroid LC-MS/MS Assay
Authors: Braun Valentin , Stuppner Hermann , Seger Christoph
Published: January 2023

Screening for possible interferences from steroidal compounds other than the target analytes (endogenous or exogenous) is well established in LC-MS/MS assay development for steroid quantification in a routine clinical setting. However, interferences from non-steroidal substances have, hitherto, not been explored. After screening more than 150 pharmaceuticals and their metabolites by analyzing commercial quality control samples from TDM analysis kits (Recipe, Chromsystems) with a multisteroid LC-MS/MS assay (protein precipitation followed by HybridSPE filtration, biphenyl column, methanol–water gradient with NH4F additive), we can report the finding of two newly discovered potential interferences from non-steroidal drugs. Antidepressant paroxetine (PX) was identified as an interference to 17-hydroxyprogesterone (17P), and α-hydroxytriazolam (α-OH-TZM)—a major metabolite of benzodiazepine triazolam (TZM)—was identified as an interference to aldosterone (ALDO). Despite different elemental and structural compositions and nominal masses, the M+1 isotopologues of PX and α-OH-TZM produced overlapping signals in ion traces monitored for the respective analytes (m/z 331 → 109/97 and 361→315/343, respectively). PX and TZM are frequently prescribed drugs, and their therapeutic ranges are far exceeding the reference ranges of 17P or ALDO (µmol vs nmol); therefore, these interferences should be considered clinically relevant. Striving for faster multi-analyte methods with high sample turnover, especially in the field of steroid quantification, can limit assay selectivity and specificity. Therefore, supported by the findings of this study, screening for potential interferences in multi-analyte LC-MS/MS method development should not cover only substances of the same class but also include a set of common drugs.
Towards a Better Understanding of the Interaction of Fe66Cr10Nb5B19 Metallic Glass with Aluminum: Growth of Intermetallics and Formation of Kirkendall Porosity during Sintering
Authors: Dudina Dina V. , Kvashnin Vyacheslav I. , Matvienko Alexander A. , Sidelnikov Anatoly A. , Gavrilov Alexander I. , Ukhina Arina V. , Jorge Alberto Moreira , Georgarakis Konstantinos
Published: January 2023

Metallic-glass-reinforced metal matrix composites are a novel class of composite materials, in which particles of alloys with an amorphous structure play the role of reinforcement. During the fabrication of these composites, a crystalline metal is in contact with a multicomponent alloy of an amorphous structure. In the present work, the morphological features of the reaction products formed upon the interaction of Fe66Cr10Nb5B19 metallic glass particles with aluminum were studied. The composites were processed via spark plasma sintering (SPS), hot pressing or a combination of SPS and furnace annealing. The reaction products in composites with different concentrations of the metallic glass and different transformation degrees were examined. The products of the interaction of the Fe66Cr10Nb5B19 metallic glass with Al were observed as dense layers covering the residual alloy cores, needles of FeAl3 protruding from the dense shells as well as needles and platelets of FeAl3 distributed in the residual Al matrix. The possible role of the liquid phase in the structure formation of the reaction products is discussed. The formation of needle- and platelet-shaped particles presumably occurred via crystallization from the Al-Fe-based melt, which formed locally due to the occurrence of the exothermic reactions between aluminum and iron. At the same time, aluminum atoms diffused into the solid Fe-based alloy particles, forming an intermetallic layer, which could grow until the alloy was fully transformed. When aluminum melted throughout the volume of the composite during heating of the sample above 660 °C, a similar microstructure developed. In both Al–Fe66Cr10Nb5B19 and Al–Fe systems, upon the reactive transformation, pores persistently formed in locations occupied by aluminum owing to the occurrence of the Kirkendall effect.
A New Unnatural Amino Acid Derived from the Modification of 4′-(p-tolyl)-2,2′:6′,2″-terpyridine and Its Mixed-Ligand Complexes with Ruthenium: Synthesis, Characterization, and Photophysical Properties
Authors: Ypsilantis Konstantinos , Garypidou Antonia , Gikas Andreas , Kiapekos Alexandros , Plakatouras John C. , Garoufis Achilleas
Published: January 2023

The modification of the methyl group of 4′-(p-tolyl)-2,2′:6′,2″-terpyridine produced the novel unnatural amino acid 3-(4-([2,2′:6′,2″-terpyridin]-4′-yl)phenyl)-2-aminopropanoic acid (phet). Mononuclear heteroleptic ruthenium complexes of the general formulae [Ru(L1)(L2)](PF6)2 (L1 = 2-acetylamino-2-(4-[2,2′:6′,2″]terpyridine-4′-yl-benzyl)-malonic acid diethyl ester, (phem), 3-(4-([2,2′:6′,2″-terpyridin]-4′-yl)phenyl)-2-aminopropanoic acid, (phet), and L2 = 2,2′:6′,2″-terpyridine (tpy), 4′-phenyl-2,2′:6′,2″-terpyridine (ptpy), 4′-(p-tolyl)-2,2′:6′,2″-terpyridine (mptpy)), as well as the homoleptic [Ru(phem)2](PF6)2 and [Ru(phet)2](PF6)2, were synthesized and characterized by means of NMR spectroscopic techniques, elemental analysis, and high-resolution mass spectrometry. The photophysical properties of the synthesized complexes were also studied.
Direct Current Reactive Sputtering Deposition and Plasma Annealing of an Epitaxial TiHfN Film on Si (001)
Authors: Wu Ping-Hsun , Chiu Kun-An , Shih Fu-Han , Fang Yu-Siang , Do Thi-Hien , Chen Wei-Chun , Chang Li
Published: January 2023

Deposition of a heteroepitaxial TiHfN film with a growth rate of about 1 μm/h was successfully achieved on a Si (001) substrate at a temperature above 700 °C by direct current magnetron reactive sputtering of a Ti0.6Hf0.4 (in atomic fraction) target with an Ar/N2 gas mixture. Annealing of the as-deposited TiHfN/Si sample at a temperature above 1000 °C using microwave plasma with H2/N2 gas was performed to further improve the TiHfN film’s quality. X-ray diffraction results show that the heteroepitaxial TiHfN film on Si exhibits a cube-on-cube relationship as {001}TiHfN//{001}Si and <110>TiHfN//<110>Si. X-ray rocking curve measurements show that the full width at half maximum of (200)TiHfN is 1.36° for the as-deposited TiHfN film, while it is significantly reduced to 0.53° after microwave plasma annealing. The surface morphologies of the as-deposited and annealed TiHfN films are smooth, with a surface roughness of around ~2 nm. Cross-sectional scanning/transmission electron microscopy (S/TEM) shows a reduction in defects in the annealed film, and X-ray photoelectron spectroscopy shows that the film composition remains unchanged. Additionally, S/TEM examinations with atomic resolution illustrate domain matching epitaxy (DME) between TiHfN and Si at the interface. The TiHfN films have good electrical conducting properties with resistivities of 40–45 μΩ·cm.
Application of Somatosensory Computer Game for Nutrition Education in Preschool Children
Authors: Chang Ing-Chau , Yen Chin-En
Published: January 2023

With the popularization of technological products, people’s everyday lives are now full of 3C (computer, communication, and consumer electronics) products. Children have gradually become acquainted with these new technological products. In recent years, more somatosensory games have been introduced along with the development of new media puzzle games for children. Several studies have shown that somatosensory games can improve physical, brain, and sensory integrated development in children, as well as promoting parent–child and peer interactions and enhancing children’s attention and cooperation in play. The purpose of this study is to assess the effect of integrating somatosensory computer games into early childhood nutrition education. The subjects of this study were 15 preschool children (aged 5–6 years old) from a preschool in Taichung City, Taiwan. We used the somatosensory game “Arno’s Fruit and Vegetable Journey” as an intervention tool for early childhood nutrition education. The somatosensory game production uses the Scratch software combined with Rabboni sensors. The somatosensory game education intervention was carried out for one hour a week over two consecutive weeks. We used questionnaires and nutrition knowledge learning sheets to evaluate the early childhood nutrition knowledge and learning status and satisfaction degree in the first and second weeks of this study. The results showed that there were no statistically significant differences between the preschool children’s game scores and times, as well as nutritional knowledge scores, before and after the intervention. Most of the preschool children highly enjoyed the somatosensory game educational activities. We reveal some problems in the teaching activities of somatosensory games, which can provide a reference for future research on designing and producing somatosensory games for preschool children and somatosensory game-based education.
Understanding the Challenges of HPV-Based Cervical Screening: Development and Validation of HPV Testing and Self-Sampling Attitudes and Beliefs Scales
Authors: Tatar Ovidiu , Haward Ben , Zhu Patricia , Griffin-Mathieu Gabrielle , Perez Samara , McBride Emily , Lofters Aisha , Smith Laurie , Mayrand Marie-Hélène , Daley Ellen , Brotherton Julia , Zimet Gregory , Rosberger Zeev
Published: January 2023

The disrupted introduction of the HPV-based cervical screening program in several jurisdictions has demonstrated that the attitudes and beliefs of screening-eligible persons are critically implicated in the success of program implementation (including the use of self-sampling). As no up-to-date and validated measures exist measuring attitudes and beliefs towards HPV testing and self-sampling, this study aimed to develop and validate two scales measuring these factors. In October-November 2021, cervical screening-eligible Canadians participated in a web-based survey. In total, 44 items related to HPV testing and 13 items related to HPV self-sampling attitudes and beliefs were included in the survey. For both scales, the optimal number of factors was identified using Exploratory Factor Analysis (EFA) and parallel analysis. Item Response Theory (IRT) was applied within each factor to select items. Confirmatory Factor Analysis (CFA) was used to assess model fit. After data cleaning, 1027 responses were analyzed. The HPV Testing Attitudes and Beliefs Scale (HTABS) had four factors, and twenty items were retained after item reduction. The HPV Self-sampling Attitudes and Beliefs Scale (HSABS) had two factors and seven items were retained. CFA showed a good model fit for both final scales. The developed scales will be a valuable resource to examine attitudes and beliefs in anticipation of, and to evaluate, HPV test-based cervical screening.
Very High Food Plant Diversity among Ethnic Groups in Northern Thailand
Authors: Panyadee Prateep , Wangpakapattanawong Prasit , Inta Angkhana , Balslev Henrik
Published: January 2023

The combination of the high biodiversity and many ethnicities in Thailand results in extensive ethnobotanical studies, especially in the northern part of the country. Here we have assembled 7620 records from 60 references regarding how plants are used for food among 14 ethnicities in northern Thailand. The uses are based on 1182 different plant species. Vegetables are the most common food category, which contributed more than 60% of all use-reports and involved nearly 900 species. This was followed by the dessert fruit category, which included about 350 species and over 1800 use-reports. The similarity among the different ethnicities was low and the number of uses and species recorded among different ethnicities were significantly related to the number of studies that had been conducted for each group. This implies that additional ethnobotanical studies are still needed in order to conserve and compile the valuable traditional knowledge related to food plants. Many exotic species are now an important part of traditional knowledge, whereas rare endemic species are uncommon among wild food plants. This situation leads to a loss of traditional knowledge about food plants and reduced awareness of their importance. As a key to using this great reservoir of food for local people, traditional knowledge related to local wild food plants can contribute to the zero-hunger goal of the Sustainable Development Goal (SDG). More studies on the nutrient content and health properties of these plants could lead to the development of new crops to meet present consumer demands.
No Tail No Fail: Life Cycles of the Zoogonidae (Digenea)
Authors: Kremnev Georgii , Gonchar Anna , Uryadova Alexandra , Krapivin Vladimir , Skobkina Olga , Gubler Arseniy , Krupenko Darya
Published: January 2023

The Zoogonidae is the only digenean family where known cercariae lack the tail but actively search for the second intermediate host. However, the data on the zoogonid life cycles are scarce. In the present study, we elucidated and verified life cycles of the Zoogonidae from the White Sea. Using rDNA data, we showed that Pseudozoogonoides subaequiporus utilizes gastropods from the family Buccinidae as the first intermediate host and protobranch bivalves as the second one. This life cycle can be facultatively truncated: some cercariae of P. subaequiporus encyst within the daughter sporocysts. Molecular data also confirmed previous hypotheses on Zoogonoides viviapus life cycle with buccinid gastropods acting as the first intermediate hosts, and annelids and bivalves as the second intermediate hosts. We demonstrated the presence of short tail primordium in the developing cercariae of both species. Based on the reviewed and our own data, we hypothesize that the emergence of tailless cercariae in the evolution of the Zoogonidae is linked to the switch to non-arthropod second intermediate hosts, and that it possibly happened only in the subfamily Zoogoninae. Basally branching zoogonids have retained the ancestral second intermediate host and might have also retained the tail.
The ‘Edge Effect’ Phenomenon in Plants: Morphological, Biochemical and Mineral Characteristics of Border Tissues
Authors: Golubkina Nadezhda , Skrypnik Liubov , Logvinenko Lidia , Zayachkovsky Vladimir , Smirnova Anna , Krivenkov Leonid , Romanov Valery , Kharchenko Viktor , Poluboyarinov Pavel , Sekara Agnieszka , Tallarita Alessio , Caruso Gianluca
Published: January 2023

The ‘edge’ effect is considered one of the fundamental ecological phenomena essential for maintaining ecosystem integrity. The properties of plant outer tissues (root, tuber, bulb and fruit peel, tree and shrub bark, leaf and stem trichomes) mimic to a great extent the ‘edge’ effect properties of different ecosystems, which suggests the possibility of the ‘edge’ effect being applicable to individual plant organisms. The most important characteristics of plant border tissues are intensive oxidant stress, high variability and biodiversity of protection mechanisms and high adsorption capacity. Wide variations in morphological, biochemical and mineral components of border tissues play an important role in the characteristics of plant adaptability values, storage duration of roots, fruit, tubers and bulbs, and the diversity of outer tissue practical application. The significance of outer tissue antioxidant status and the accumulation of polyphenols, essential oil, lipids and minerals, and the artificial improvement of such accumulation is described in connection with plant tolerance to unfavorable environmental conditions. Methods of plant ‘edge’ effect utilization in agricultural crop breeding, production of specific preparations with powerful antioxidant value and green nanoparticle synthesis of different elements have been developed. Extending the ‘edge’ effect phenomenon from ecosystems to individual organisms is of fundamental importance in agriculture, pharmacology, food industry and wastewater treatment processes.
Barrett’s Esophagus: An Updated Review
Authors: Stawinski Peter , Dziadkowiec Karolina , Kuo Lily , Echavarria Juan , Saligram Shreyas
Published: January 2023

Barrett’s esophagus (BE) is a change in the distal esophageal mucosal lining, whereby metaplastic columnar epithelium replaces squamous epithelium of the esophagus. This change represents a pre-malignant mucosal transformation which has a known association with the development of esophageal adenocarcinoma. Gastroesophageal reflux disease is a risk factor for BE, other risk factors include patients who are Caucasian, age > 50 years, central obesity, tobacco use, history of peptic stricture and erosive gastritis. Screening for BE remains selective based on risk factors, a screening program in the general population is not routinely recommended. Diagnosis of BE is established with a combination of endoscopic recognition, targeted biopsies, and histologic confirmation of columnar metaplasia. We aim to provide a comprehensive review of the epidemiology, pathogenesis, screening and advanced techniques of detecting and eradicating Barrett’s esophagus.
Deep Learning in Optical Coherence Tomography Angiography: Current Progress, Challenges, and Future Directions
Authors: Yang Dawei , Ran An Ran , Nguyen Truong X. , Lin Timothy P. H. , Chen Hao , Lai Timothy Y. Y. , Tham Clement C. , Cheung Carol Y.
Published: January 2023

Optical coherence tomography angiography (OCT-A) provides depth-resolved visualization of the retinal microvasculature without intravenous dye injection. It facilitates investigations of various retinal vascular diseases and glaucoma by assessment of qualitative and quantitative microvascular changes in the different retinal layers and radial peripapillary layer non-invasively, individually, and efficiently. Deep learning (DL), a subset of artificial intelligence (AI) based on deep neural networks, has been applied in OCT-A image analysis in recent years and achieved good performance for different tasks, such as image quality control, segmentation, and classification. DL technologies have further facilitated the potential implementation of OCT-A in eye clinics in an automated and efficient manner and enhanced its clinical values for detecting and evaluating various vascular retinopathies. Nevertheless, the deployment of this combination in real-world clinics is still in the “proof-of-concept” stage due to several limitations, such as small training sample size, lack of standardized data preprocessing, insufficient testing in external datasets, and absence of standardized results interpretation. In this review, we introduce the existing applications of DL in OCT-A, summarize the potential challenges of the clinical deployment, and discuss future research directions.
Cooperative Truck–Drone Delivery Path Optimization under Urban Traffic Restriction
Authors: Weng Ying-Ying , Wu Rong-Yu , Zheng Yu-Jun
Published: January 2023

In the traditional express delivery sector, trucks are the most available and efficient transportation mode in urban areas. However, due to the pressures of traffic congestion and air pollution problems, many cities have implemented strict measures to restrict trucks’ access to many zones during specified time periods, which has caused significant effects on the business of the industry. Due to their advantages, which include high speed, flexibility, and environmental friendliness, drones have great potential for being combined with trucks for efficient delivery in restricted traffic zones. In this paper, we propose a cooperative truck and drone delivery path optimization problem, in which a truck carrying cargo travels along the outer boundary of the restricted traffic zone to send and receive a drone, and the drone is responsible for delivering the cargo to customers. The objective of the problem is to minimize the completion time of all delivery tasks. To efficiently solve this problem, we propose a hybrid metaheuristic optimization algorithm to cooperatively optimize the outer path of the truck and the inner path of the drone. We conduct experiments on a set of test instances; the results demonstrate that the proposed algorithm exhibits a competitive performance compared to other selected popular optimization algorithms.