bluuebunny/crossref_metadata_2025 huggingface dataset:
EpiMCI: Predicting Multi-Way Chromatin Interactions from Epigenomic Signals
Authors: Xu Jinsheng , Zhang Ping , Sun Weicheng , Zhang Junying , Zhang Wenxue , Hou Chunhui , Li Li
Published: September 2023

The recently emerging high-throughput Pore-C (HiPore-C) can identify whole-genome high-order chromatin multi-way interactions with an ultra-high output, contributing to deciphering three-dimensional (3D) genome organization. However, it also brings new challenges to relevant data analysis. To alleviate this problem, we proposed the EpiMCI, a model for multi-way chromatin interaction prediction based on a hypergraph neural network with epigenomic signals as the input. The EpiMCI integrated separate hyperedge representations with coupling hyperedge information and obtained AUCs of 0.981 and 0.984 in the GM12878 and K562 datasets, respectively, which outperformed the current available method. Moreover, the EpiMCI can be applied to denoise the HiPore-C data and improve the data quality efficiently. Furthermore, the vertex embeddings extracted from the EpiMCI reflected the global chromatin architecture accurately. The principal component analysis suggested that it was well aligned with the activities of genomic regions at the chromatin compartment level. Taken together, the EpiMCI can accurately predict multi-way chromatin interactions and can be applied to studies relying on chromatin architecture.
In Search of Disentanglement in Tandem Mass Spectrometry Datasets
Authors: Abram Krzysztof Jan , McCloskey Douglas
Published: September 2023

Generative modeling and representation learning of tandem mass spectrometry data aim to learn an interpretable and instrument-agnostic digital representation of metabolites directly from MS/MS spectra. Interpretable and instrument-agnostic digital representations would facilitate comparisons of MS/MS spectra between instrument vendors and enable better and more accurate queries of large MS/MS spectra databases for metabolite identification. In this study, we apply generative modeling and representation learning using variational autoencoders to understand the extent to which tandem mass spectra can be disentangled into their factors of generation (e.g., collision energy, ionization mode, instrument type, etc.) with minimal prior knowledge of the factors. We find that variational autoencoders can disentangle tandem mass spectra data with the proper choice of hyperparameters into meaningful latent representations aligned with known factors of variation. We develop a two-step approach to facilitate the selection of models that are disentangled, which could be applied to other complex and high-dimensional data sets.
MicroRNAs in the Regulation of RIG-I-like Receptor Signaling Pathway: Possible Strategy for Viral Infection and Cancer
Authors: Chen Dengwang , Ji Qinglu , Liu Jing , Cheng Feng , Zheng Jishan , Ma Yunyan , He Yuqi , Zhang Jidong , Song Tao
Published: September 2023

The retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) play a crucial role as pattern-recognition receptors within the innate immune system. These receptors, present in various cell and tissue types, serve as essential sensors for viral infections, enhancing the immune system’s capacity to combat infections through the induction of type I interferons (IFN-I) and inflammatory cytokines. RLRs are involved in a variety of physiological and pathological processes, including viral infections, autoimmune disorders, and cancer. An increasing body of research has examined the possibility of RLRs or microRNAs as therapeutic targets for antiviral infections and malignancies, despite the fact that few studies have focused on the regulatory function of microRNAs on RLR signaling. Consequently, our main emphasis in this review is on elucidating the role of microRNAs in modulating the signaling pathways of RLRs in the context of cancer and viral infections. The aim is to establish a robust knowledge base that can serve as a basis for future comprehensive investigations into the interplay between microRNAs and RIG-I, while also facilitating the advancement of therapeutic drug development.
Interaction of S100A6 Protein with the Four-Helical Cytokines
Authors: Kazakov Alexey S. , Deryusheva Evgenia I. , Rastrygina Victoria A. , Sokolov Andrey S. , Permyakova Maria E. , Litus Ekaterina A. , Uversky Vladimir N. , Permyakov Eugene A. , Permyakov Sergei E.
Published: September 2023

S100 is a family of over 20 structurally homologous, but functionally diverse regulatory (calcium/zinc)-binding proteins of vertebrates. The involvement of S100 proteins in numerous vital (patho)physiological processes is mediated by their interaction with various (intra/extra)cellular protein partners, including cell surface receptors. Furthermore, recent studies have revealed the ability of specific S100 proteins to modulate cell signaling via direct interaction with cytokines. Previously, we revealed the binding of ca. 71% of the four-helical cytokines via the S100P protein, due to the presence in its molecule of a cytokine-binding site overlapping with the binding site for the S100P receptor. Here, we show that another S100 protein, S100A6 (that has a pairwise sequence identity with S100P of 35%), specifically binds numerous four-helical cytokines. We have studied the affinity of the recombinant forms of 35 human four-helical cytokines from all structural families of this fold to Ca2+-loaded recombinant human S100A6, using surface plasmon resonance spectroscopy. S100A6 recognizes 26 of the cytokines from all families of this fold, with equilibrium dissociation constants from 0.3 nM to 12 µM. Overall, S100A6 interacts with ca. 73% of the four-helical cytokines studied to date, with a selectivity equivalent to that for the S100P protein, with the differences limited to the binding of interleukin-2 and oncostatin M. The molecular docking study evidences the presence in the S100A6 molecule of a cytokine-binding site, analogous to that found in S100P. The findings argue the presence in some of the promiscuous members of the S100 family of a site specific to a wide range of four-helical cytokines. This unique feature of the S100 proteins potentially allows them to modulate the activity of the numerous four-helical cytokines in the disorders accompanied by an excessive release of the cytokines.
Genomics of Wolfram Syndrome 1 (WFS1)
Authors: Kõks Sulev
Published: September 2023

Wolfram Syndrome (WFS) is a rare, autosomal, recessive neurogenetic disorder that affects many organ systems. It is characterised by diabetes insipidus, diabetes mellites, optic atrophy, and deafness and, therefore, is also known as DIDMOAD. Nearly 15,000–30,000 people are affected by WFS worldwide, and, on average, patients suffering from WFS die at 30 years of age, usually from central respiratory failure caused by massive brain atrophy. The more prevalent of the two kinds of WFS is WFS1, which is a monogenic disease and caused by the loss of the WFS1 gene, whereas WFS2, which is more uncommon, is caused by mutations in the CISD2 gene. Currently, there is no treatment for WFS1 to increase the life expectancy of patients, and the treatments available do not significantly improve their quality of life. Understanding the genetics and the molecular mechanisms of WFS1 is essential to finding a cure. The inability of conventional medications to treat WFS1 points to the need for innovative strategies that must address the fundamental cause: the deletion of the WFS1 gene that leads to the profound ER stress and disturbances in proteostasis. An important approach here is to understand the mechanism of the cell degeneration after the deletion of the WFS1 gene and to describe the differences in these mechanisms for the different tissues. The studies so far have indicated that remarkable clinical heterogeneity is caused by the variable vulnerability caused by WFS1 mutations, and these differences cannot be attributed solely to the positions of mutations in the WFS1 gene. The present review gives a broader overview of the results from genomic studies on the WFS1 mouse model.
Climate-Adaptive Design Strategies of Sports Stadia in a Hot Summer and Cold Winter Zone: A Case Study of Nanjing
Authors: Xiong Dongxu , Cheng Kai , Chen Jingjing
Published: September 2023

Urban planning and design, with the objectives of energy efficiency and climate adaptation, is receiving more and more attention as urban energy consumption keeps rising. As technical representatives with large spans and high difficulties, sports stadia have a broad range of energy conservation and emission reduction compared with traditional buildings and have an extremely close relationship with the energy consumption of the building environment and urban microclimate, so it is necessary to study the climate adaptation design strategy of sports stadia. However, climate adaptive design has not given much thought to sports stadia nowadays. And the energy-saving strategies of sports stadia rely mostly on engineering expertise without taking into account the effect of sports stadia layout, shape, and structure on the urban microclimate. This paper investigates the energy-saving and climate-adaptive design techniques of sports stadia in the hot summer and cold winter zone of China using the layout of sports stadia as the research object. Firstly, we construct a climate adaptive design framework of sports stadia of “layout-shape-structure” based on the characteristics of sports stadia. Secondly, combined with typical examples of large-scale sports stadia in hot summers and cold winters, we establish an abstract model of architectural layout, shape, and structure based on climatic environment. In order to provide climate-adaptive design methods for sports stadia in hot summer and cold winter zones, the ventilation of the external and internal spaces of sports stadia is simulated, quantified, and compared using CFD software. The study’s findings suggest that the layout of sports stadia should take into account the direction of the local wind, that the goal of low energy consumption should guide the choice of building form, and that the internal wind and temperature environment should be stabilized during construction. The study’s findings can serve as a guide for comparable designs that aim to construct sports stadia with reduced carbon footprints.
Toll-like Receptor Agonists Are Unlikely to Provide Benefits in Head and Neck Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis
Authors: Maddineni Sainiteesh , Chen Michelle , Baik Fred , Divi Vasu , Sunwoo John B. , Finegersh Andrey
Published: September 2023

Background: Recurrent and metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) has poor survival rates. Immunotherapy is the standard of care for R/M HNSCC, but objective responses occur in a minority of patients. Toll-like receptor (TLR) agonists promote antitumor immune responses and have been explored in clinical trials. Methods: A search for clinical trials using TLR agonists in HNSCC was performed under PRISMA guidelines. Data on patient characteristics, safety, and efficacy were collected and analyzed. Results: Three phase 1b trials with 40 patients and three phase 2 trials with 352 patients studying TLR8 and TLR9 agonists in combination with other treatment regimens for HNSCC were included. In phase 2 trials, there was no significant change in the objective response rate (RR = 1.13, CI 0.80–1.60) or association with increased grade 3+ adverse events (RR = 0.91, CI 0.76–1.11) associated with TLR agonist use. Conclusion: TLR agonists do not appear to provide additional clinical benefits or increase adverse events in the treatment of HNSCC. Given these results across multiple clinical trials and drug regimens, it is unlikely that additional trials of TLR agonists will demonstrate clinical benefits in HNSCC.
Automatic Segmentation with Deep Learning in Radiotherapy
Authors: Isaksson Lars Johannes , Summers Paul , Mastroleo Federico , Marvaso Giulia , Corrao Giulia , Vincini Maria Giulia , Zaffaroni Mattia , Ceci Francesco , Petralia Giuseppe , Orecchia Roberto , Jereczek-Fossa Barbara Alicja
Published: September 2023

This review provides a formal overview of current automatic segmentation studies that use deep learning in radiotherapy. It covers 807 published papers and includes multiple cancer sites, image types (CT/MRI/PET), and segmentation methods. We collect key statistics about the papers to uncover commonalities, trends, and methods, and identify areas where more research might be needed. Moreover, we analyzed the corpus by posing explicit questions aimed at providing high-quality and actionable insights, including: “What should researchers think about when starting a segmentation study?”, “How can research practices in medical image segmentation be improved?”, “What is missing from the current corpus?”, and more. This allowed us to provide practical guidelines on how to conduct a good segmentation study in today’s competitive environment that will be useful for future research within the field, regardless of the specific radiotherapeutic subfield. To aid in our analysis, we used the large language model ChatGPT to condense information.
Expanding the Clinical Utility of Targeted RNA Sequencing Panels beyond Gene Fusions to Complex, Intragenic Structural Rearrangements
Authors: Schieffer Kathleen M. , Moccia Amanda , Bucknor Brianna A. , Stonerock Eileen , Jayaraman Vijayakumar , Jenkins Heather , McKinney Aimee , Koo Selene C. , Mathew Mariam T. , Mardis Elaine R. , Lee Kristy , Reshmi Shalini C. , Cottrell Catherine E.
Published: September 2023

Gene fusions are a form of structural rearrangement well established as driver events in pediatric and adult cancers. The identification of such events holds clinical significance in the refinement, prognostication, and provision of treatment in cancer. Structural rearrangements also extend beyond fusions to include intragenic rearrangements, such as internal tandem duplications (ITDs) or exon-level deletions. These intragenic events have been increasingly implicated as cancer-promoting events. However, the detection of intragenic rearrangements may be challenging to resolve bioinformatically with short-read sequencing technologies and therefore may not be routinely assessed in panel-based testing. Within an academic clinical laboratory, over three years, a total of 608 disease-involved samples (522 hematologic malignancy, 86 solid tumors) underwent clinical testing using Anchored Multiplex PCR (AMP)-based RNA sequencing. Hematologic malignancies were evaluated using a custom Pan-Heme 154 gene panel, while solid tumors were assessed using a custom Pan-Solid 115 gene panel. Gene fusions, ITDs, and intragenic deletions were assessed for diagnostic, prognostic, or therapeutic significance. When considering gene fusions alone, we report an overall diagnostic yield of 36% (37% hematologic malignancy, 41% solid tumors). When including intragenic structural rearrangements, the overall diagnostic yield increased to 48% (48% hematologic malignancy, 45% solid tumor). We demonstrate the clinical utility of reporting structural rearrangements, including gene fusions and intragenic structural rearrangements, using an AMP-based RNA sequencing panel.
Safety and Efficacy of a Single-Stage versus Two-Stage Intramedullary Nailing for Synchronous Impending or Pathologic Fractures of Bilateral Femur for Oncologic Indications: A Systematic Review
Authors: Nian Patrick P. , Ganesan Vanathi , Baidya Joydeep , Marder Ryan S. , Maheshwari Krish , Kobryn Andriy , Maheshwari Aditya V.
Published: September 2023

Although intramedullary nail (IMN) fixation is the standard of care for most impending and/or complete pathologic fractures of the femur, the optimal timing/sequence of the IMN in cases of synchronous bilateral femoral disease in advanced cancer is not well established. Thus, we compared the outcomes of single-stage (SS) vs. two-stage (TS) IMN of the bilateral femur with a systematic review of the literature on this topic. Bilateral SS and TS IMN cases were identified from 14 studies extracted from four databases according to PRISMA guidelines. Safety (complications, reoperations, mortality, survival, blood loss, and transfusion) and efficacy (length of stay [LOS], time to start rehabilitation and adjuvant therapy, functional scores, and cost) were compared between the groups. A total of 156 IMNs in 78 patients (36 SS and 42 TS) were analyzed. There were one surgical (infection in TS requiring reoperation; p = 0.860) and fifteen medical complications (five in SS, ten in TS; p = 0.045), with SS being associated with lower rates of total and medical complications. Survival, intraoperative mortality, and postoperative same-admission mortality were similar. No cases of implant failure were reported. Data on LOS, rehabilitation, and adjuvant therapy were scarcely reported, although one study favored SS over TS. No study compared cost or functional scores. Our study is the largest and most comprehensive of its kind in supporting the safety and efficacy of a SS bilateral femur IMN approach in these select patients. Further investigations with higher levels of evidence are warranted to optimize treatment protocols for this clinical scenario.
DCIS and LCIS: Are the Risk Factors for Developing In Situ Breast Cancer Different?
Authors: Timbres Jasmine , Kohut Kelly , Caneppele Michele , Troy Maria , Schmidt Marjanka K. , Roylance Rebecca , Sawyer Elinor
Published: September 2023

Ductal carcinoma in situ (DCIS) is widely accepted as a precursor of invasive ductal carcinoma (IDC). Lobular carcinoma in situ (LCIS) is considered a risk factor for invasive lobular carcinoma (ILC), and it is unclear whether LCIS is also a precursor. Therefore, it would be expected that similar risk factors predispose to both DCIS and IDC, but not necessarily LCIS and ILC. This study examined associations with risk factors using data from 3075 DCIS cases, 338 LCIS cases, and 1584 controls aged 35–60, recruited from the UK-based GLACIER and ICICLE case-control studies between 2007 and 2012. Analysis showed that breastfeeding in parous women was protective against DCIS and LCIS, which is consistent with research on invasive breast cancer (IBC). Additionally, long-term use of HRT in post-menopausal women increased the risk of DCIS and LCIS, with a stronger association in LCIS, similar to the association with ILC. Contrary to findings with IBC, parity and the number of births were not protective against DCIS or LCIS, while oral contraceptives showed an unexpected protective effect. These findings suggest both similarities and differences in risk factors for DCIS and LCIS compared to IBC and that there may be justification for increased breast surveillance in post-menopausal women taking long-term HRT.
Is Computed-Tomography-Based Body Composition a Reliable Predictor of Chemotherapy-Related Toxicity in Pancreatic Cancer Patients?
Authors: Cefalì Marco , Scala Isabel , Pavone Giuliana , Helbling Daniel , Hussung Saskia , Fritsch Ralph , Reiner Cäcilia , Stocker Soleen , Koeberle Dieter , Kissling Marc , Chianca Vito , Del Grande Filippo , De Dosso Sara , Rizzo Stefania
Published: September 2023

Background: Malnutrition, loss of weight and of skeletal muscle mass are frequent in pancreatic cancer patients, a majority of which will undergo chemotherapy over the course of their disease. Available data suggest a negative prognostic role of these changes in body composition on disease outcomes; however, it is unclear whether tolerance to chemotherapeutic treatment is similarly and/or negatively affected. We aimed to explore this association by retrospectively assessing changes in body composition and chemotherapy-related toxicity in a cohort of advanced pancreatic cancer patients. Methods: Body composition was evaluated through clinical parameters and through radiological assessment of muscle mass, skeletal muscle area, skeletal muscle index and skeletal muscle density; and an assessment of fat distribution by subcutaneous adipose tissue and visceral adipose tissue. We performed descriptive statistics, pre/post chemotherapy comparisons and uni- and multivariate analyses to assess the relation between changes in body composition and toxicity. Results: Toxicity risk increased with an increase of skeletal muscle index (OR: 1.03) and body mass index (OR: 1.07), whereas it decreased with an increase in skeletal muscle density (OR: 0.96). Multivariate analyses confirmed a reduction in the risk of toxicity only with an increase in skeletal muscle density (OR: 0.96). Conclusions: This study suggests that the retrospective analysis of changes in body composition is unlikely to be useful to predict toxicity to gemcitabine—nab-paclitaxel.
Management of Metastatic Pancreatic Cancer—Comparison of Global Guidelines over the Last 5 Years
Authors: Pajewska Monika , Partyka Olga , Czerw Aleksandra , Deptała Andrzej , Cipora Elżbieta , Gąska Izabela , Wojtaszek Marek , Sygit Katarzyna , Sygit Marian , Krzych-Fałta Edyta , Schneider-Matyka Daria , Cybulska Anna M. , Grochans Elżbieta , Asendrych-Woźniak Alicja , Romanowicz Agnieszka , Drobnik Jarosław , Bandurska Ewa , Ciećko Weronika , Maciuszek-Bartkowska Barbara , Curyło Mateusz , Wróbel Kacper , Kozłowski Remigiusz , Marczak Michał
Published: September 2023

Pancreatic cancer (PC) is usually diagnosed at an advanced stage of its development, which results in lower overall survival (OS). Prognosis is also poor even with curative-intent surgery. Approximately 80% of patients with localized PDAC have micrometastases at the time of diagnosis, which leads to a worse prognosis than in other cancers. The objective of this study is to present the progress in the treatment of metastatic pancreatic cancer based on the recommendations of oncological scientific societies, such as ESMO, NCCN, ASCO, NICE and SEOM, over the last 5 years. Combined FOLFIRINOX therapy is mostly a recommended therapy among patients with good performance statuses, while gemcitabine is recommended for more fragile patients as a first-line treatment. The newest guidelines suggest that molecular profiling of the tumor should be the first step in determining the course of treatment. The use of modern molecular therapies in patients with specific gene mutations should extend the survival of patients with this disease.
A Real-World Comparative Analysis of Atezolizumab Plus Bevacizumab and Transarterial Chemoembolization Plus Radiotherapy in Hepatocellular Carcinoma Patients with Portal Vein Tumor Thrombosis
Authors: Lee Soon Kyu , Kwon Jung Hyun , Lee Sung Won , Lee Hae Lim , Kim Hee Yeon , Kim Chang Wook , Song Do Seon , Chang U Im , Yang Jin Mo , Nam Soon Woo , Kim Seok-Hwan , Song Myeong Jun , Kim Ji Hoon , Lee Ahlim , Yang Hyun , Bae Si Hyun , Han Ji Won , Nam Heechul , Sung Pil Soo , Jang Jeong Won , Choi Jong Young , Yoon Seung Kew , Shim Dong Jae , Kim Doyoung , Kim Myungsoo
Published: September 2023

This study aimed to compare the treatment outcomes of atezolizumab-plus-bevacizumab (Ate/Bev) therapy with those of transarterial chemoembolization plus radiotherapy (TACE + RT) in hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT) and without metastasis. Between June 2016 and October 2022, we consecutively enrolled 855 HCC patients with PVTT. After excluding 758 patients, 97 patients (n = 37 in the Ate/Bev group; n = 60 in the TACE + RT group) were analyzed. The two groups showed no significant differences in baseline characteristics and had similar objective response and disease control rates. However, the Ate/Bev group showed a significantly higher one-year survival rate (p = 0.041) compared to the TACE + RT group, which was constantly displayed in patients with extensive HCC burden. Meanwhile, the clinical outcomes were comparable between the two groups in patients with unilobar intrahepatic HCC. In Cox-regression analysis, Ate/Bev treatment emerged as a significant factor for better one-year survival (p = 0.049). Finally, in propensity-score matching, the Ate/Bev group demonstrated a better one-year survival (p = 0.02) and PFS (p = 0.01) than the TACE + RT group. In conclusion, Ate/Bev treatment demonstrated superior clinical outcomes compared to TACE + RT treatment in HCC patients with PVTT. Meanwhile, in patients with unilobar intrahepatic HCC, TACE + RT could also be considered as an alternative treatment option alongside Ate/Bev therapy.
Photocatalytic Reduction Efficiency of CO2 Depending on ZnO Particle Size
Authors: Morawski Antoni W. , Gano Marcin , Ćmielewska Katarzyna , Kusiak-Nejman Ewelina , Pełech Iwona , Staciwa Piotr , Ekiert Ewa , Narkiewicz Urszula
Published: September 2023

In the face of increasing global carbon dioxide emissions and the urgent need to mitigate climate change, the development of efficient and sustainable strategies for CO2 conversion has gained significant attention. One of the methods of eliminating the harmful effects of CO2 is its photoreduction. In this paper, ZnO was used as an effective photocatalyst for the photoreduction of CO2 in a gas-phase system. The influence of particle size on the process efficiency was investigated. The ZnO materials applied in the studies were characterized using XRD, SEM, and low-temperature nitrogen adsorption (BET) methods. The pore volume distribution was calculated based on the DFT method. The investigation confirmed that it had a significant impact on the formation of the product of photocatalysis carbon dioxide. The main identified product was carbon monoxide. Hydrogen and methane were detected as well. Based on the results, it was found that the process efficiency was enhanced with decreasing ZnO particle size, and the most effective catalyst for the photoreduction of CO2 was the ZnO sample with the smallest particle size (18 nm).
Lysophosphatidic Acid Signalling Regulates Human Sperm Viability via the Phosphoinositide 3-Kinase/AKT Pathway
Authors: Liao Hao-Yu , O’Flaherty Cristian
Published: September 2023

Lysophosphatidic acid (LPA) signalling is essential for maintaining germ cell viability during mouse spermatogenesis; however, its role in human spermatozoa is unknown. We previously demonstrated that peroxiredoxin 6 (PRDX6) calcium-independent phospholipase A2 (iPLA2) releases lysophospholipids such as LPA or arachidonic acid (AA) and that inhibiting PRDX6 iPLA2 activity impairs sperm cell viability. The exogenous addition of LPA bypassed the inhibition of PRDX6 iPLA2 activity and maintained the active phosphoinositide 3-kinase (PI3K)/AKT pathway. Here, we aimed to study PI3K/AKT pathway regulation via LPA signalling and protein kinases in maintaining sperm viability. The localization of LPARs in human spermatozoa was determined using immunocytochemistry, and P-PI3K and P-AKT substrate phosphorylations via immunoblotting. Sperm viability was determined using the hypo-osmotic swelling test. LPAR1, 3, 5 and 6 were located on the sperm plasma membrane. The inhibition of LPAR1-3 with Ki16425 promoted the impairment of sperm viability and decreased the phosphorylation of PI3K AKT substrates. Inhibitors of PKC, receptor-type PTK and PLC impaired sperm viability and the PI3K/AKT pathway. Adding 1-oleoyl-2-acetyl-snglycerol (OAG), a cell-permeable analog of diacylglycerol (DAG), prevented the loss of sperm viability and maintained the phosphorylation of PI3K. In conclusion, human sperm viability is supported by LPAR signalling and regulated by PLC, PKC and RT-PTK by maintaining phosphorylation levels of PI3K and AKT substrates.
Morphology of Neutrophils during Their Activation and NETosis: Atomic Force Microscopy Study
Authors: Sergunova Viktoria , Inozemtsev Vladimir , Vorobjeva Nina , Kozlova Elena , Sherstyukova Ekaterina , Lyapunova Snezhanna , Chernysh Aleksandr
Published: September 2023

Confocal microscopy and fluorescence staining of cellular structures are commonly used to study neutrophil activation and NETosis. However, they do not reveal the specific characteristics of the neutrophil membrane surface, its nanostructure, and morphology. The aim of this study was to reveal the topography and nanosurface characteristics of neutrophils during activation and NETosis using atomic force microscopy (AFM). We showed the main stages of neutrophil activation and NETosis, which include control cell spreading, cell fragment formation, fusion of nuclear segments, membrane disruption, release of neutrophil extracellular traps (NETs), and final cell disintegration. Changes in neutrophil membrane nanosurface parameters during activation and NETosis were quantified. It was shown that with increasing activation time there was a decrease in the spectral intensity of the spatial periods. Exposure to the activator A23187 resulted in an increase in the number and average size of cell fragments over time. Exposure to the activators A23187 and PMA (phorbol 12-myristate 13-acetate) caused the same pattern of cell transformation from spherical cells with segmented nuclei to disrupted cells with NET release. A23187 induced NETosis earlier than PMA, but PMA resulted in more cells with NETosis at the end of the specified time interval (180 min). In our study, we used AFM as the main research tool. Confocal laser-scanning microscopy (CLSM) images are provided for identification and detailed analysis of the phenomena studied. In this way, we exploited the advantages of both techniques.
Modeling the Mechanical Properties of a Polymer-Based Mixed-Matrix Membrane Using Deep Learning
Neural Networks
Authors: Alhulaybi Zaid , Martuza Muhammad , Rushd Sayeed
Published: September 2023

Polylactic acid (PLA), the second most produced biopolymer, was selected for the fabrication of mixed-matrix membranes (MMMs) via the incorporation of HKUST-1 metal–organic framework (MOF) particles into a PLA matrix with the aim of improving mechanical characteristics. A deep learning neural network (DLNN) model was developed on the TensorFlow 2 backend to predict the mechanical properties, stress, strain, elastic modulus, and toughness of the PLA/HKUST-1 MMMs with different input parameters, such as PLA wt%, HKUST-1 wt%, casting thickness, and immersion time. The model was trained and validated with 1214 interpolated datasets in stratified fivefold cross validation. Dropout and early stopping regularizations were applied to prevent model overfitting in the training phase. The model performed consistently for the unknown interpolated datasets and 26 original experimental datasets, with coefficients of determination (R2) of 0.93–0.97 and 0.78–0.88, respectively. The results suggest that the proposed method can build effective DLNNmodels using a small dataset to predict material properties.
Development and Validation of a Solvent-Free Headspace GC-MS Method for the Screening of Benzyl Chloride in Pharmaceutical Products
Authors: Song Eunchae , Min Chanhong , Kim Eunjae , Han Sang Beom , Lee Yong-Moon , Liu Kwang-Hyeon , Hong Jongki , Oh Han Bin
Published: September 2023

This study presents a solvent-free headspace gas chromatography–mass spectrometry (SF-HS-GC/MS) method for robustly screening benzyl chloride, a mutagenic carcinogen, impurities in active pharmaceutical ingredients (APIs) and drug products. The SF-HS-GC/MS method simplifies analysis by eliminating solvent use, reducing matrix interference. Optimized headspace parameters include incubation temperature, time, and sample amount. Validation, aligned with Q2(R1) ICH guidelines and ICH M7 recommendations, covers selectivity, linearity, limit of detection (LOD), limit of quantification (LOQ), precision, accuracy, system suitability, and robustness. Employing a DB-5MS column (30 m × 0.25 mm, 0.25 µm) with solvent-free split injection, the method’s calibration curve (0.05–5 μg/g) exhibits a strong correlation (>0.9998). The LOQ was 0.1 μg/g, with precision (%CV) consistently <5% and accuracy within 95–105%. Furthermore, an investigation confirmed the absence of artefactual benzyl chloride formation in drug products under headspace conditions. The developed SF-HS-GC/MS method successfully screened benzyl chloride in cinnarizine drug substances and products.
Macadamia Nut Bio-Waste: An Agricultural Waste with Potential to Be Used as Carbon Support Material in Fuel Cell Applications
Authors: Mojapelo Nakedi Albert , Seroka Ntalane Sello , Khotseng Lindiwe
Published: September 2023

Nutrient resources account for an enormous quantity of the world’s waste materials. According to recent research, nuts and their byproducts are good for a variety of applications and are important natural resources for nutrition. Waste and nut residues in the environment could cause environmental problems. A critical issue is how this waste is employed in various applications. Nuts contain important chemicals that could be used to build catalytic nanomaterials. A variety of heterogeneous catalysts can be created directly from different parts of nuts, such as the shell, kernel, extracts, and so on, or they can be used as nanoparticle stabilizing and reducing agents. Nuts and their wastes can be particularly essential in evolution reactions, oxidation reactions, hydrolysis, pollutant degradation, and so on due to their extraordinary chemical properties. Natural substances such as biopolymers, zeolites, diatomites, agricultural wastes (such as rice husk, bagasse pith, coconut shell, and so on), and nut wastes are used to make inexpensive catalysts. This review focuses on the industrial benefits and future applications of these commercially feasible green resources to change, for the first time, the production of nanomaterials from nuts as environmentally friendly resources and their catalytic applications.
Predicting the Occurrence of Metabolic Syndrome Using Machine Learning Models
Authors: Trigka Maria , Dritsas Elias
Published: September 2023

The term metabolic syndrome describes the clinical coexistence of pathological disorders that can lead to the development of cardiovascular disease and diabetes in the long term, which is why it is now considered an initial stage of the above clinical entities. Metabolic syndrome (MetSyn) is closely associated with increased body weight, obesity, and a sedentary lifestyle. The necessity of prevention and early diagnosis is imperative. In this research article, we experiment with various supervised machine learning (ML) models to predict the risk of developing MetSyn. In addition, the predictive ability and accuracy of the models using the synthetic minority oversampling technique (SMOTE) are illustrated. The evaluation of the ML models highlights the superiority of the stacking ensemble algorithm compared to other algorithms, achieving an accuracy of 89.35%; precision, recall, and F1 score values of 0.898; and an area under the curve (AUC) value of 0.965 using the SMOTE with 10-fold cross-validation.
Transition Metals Meet Scorpiand-like Ligands
Authors: Blasco Salvador , Verdejo Begoña , Clares María Paz , García-España Enrique
Published: September 2023

Scorpiand-like ligands combine the preorganization of the donor atoms of macrocycles and the degrees of freedom of the linear ligands. We prepared the complexes of several of these ligands with transition metal ions and made a crystallographic and water solution speciation studies. The analysis of the resulting crystal structures show that the ligands have the ability to accommodate several metal ions and that the coordination geometry is mostly determined by the ligand. Ligand 6-[3,7-diazaheptyl]-3,6,9–triaza-1-(2,6)-pyridinacyclodecaphane (L3) is an hexadentate ligand that affords a family of isostructural crystals with Cu(II), Mn(II), Ni(II) and Zn(II). The attempts to obtain Co(II) crystals afforded the Co(III) structures instead. Ligand 6-[4-(2-pyridyl)-3-azabutyl]-3,6,9-triaza-1(2,6)-pyridinacyclodecaphane (L2) is very similar to L3 and yields structures similar to it, but its behavior in solution is very different due to the different interaction with protons. Ligand 6-(2-aminoethyl)-3,6,9–triaza-1-(2,6)-pyridinacyclodecaphane (L1) is pentadentate and its complexes allow the metal to be more accessible from the solvent. A Zn(II) structure with L1 shows the species [ZnBrHL1]2+, which exists in a narrow pH range.
Calibration Technique for MBE Growth of Long Wavelength InAlAs/InGaAs Quantum Cascade Lasers
Authors: Gutowski Piotr , Sankowska Iwona , Bugajski Maciej , Sobczak Grzegorz , Kuźmicz Aleksandr , Pierściński Kamil
Published: September 2023

In this paper, we present the methodology for precise calibration of the Molecular Beam Epitaxy (MBE) growth process and achieving run-to-run stability of growth parameters. We present the analysis of the influence of fluxes stability during the growth of long wavelength quantum cascade laser structures designed for the range λ ~ 12–16 µm on wavelength accuracy with respect to desired emission wavelength. The active region of the lasers has a complex structure of nanometer thickness InxGa1−xAs/InyAl1−yAs superlattice. As a consequence, the compositional and thickness control of the structure via bulk growth parameters is rather difficult. To deal with this problem, we employ a methodology based on double-superlattice test structures that precede the growth of the actual structures. The test structures are analyzed by High Resolution X-ray Diffraction, which allows calibration of the growth of the complex active region of quantum cascade laser structures. We also theoretically studied the effect of individual flux changes on the emission wavelength and gain parameters of the laser. The results of simulations allow for the determination of flux stability tolerance, preserving acceptable parameters of the laser and providing means of emission wavelength control. The proposed methodology was verified by the growth of laser structures for emission at around 13.5 μm.
Synthesis of Silver Nanocubes@Cobalt Ferrite/Graphitic Carbon Nitride for Electrochemical Water Splitting
Authors: Zabielaite Ausrine , Eicher-Lorka Olegas , Kuodis Zenonas , Levinas Ramunas , Simkunaite Dijana , Tamasauskaite-Tamasiunaite Loreta , Norkus Eugenijus
Published: September 2023

This study presents the synthesis of graphitic carbon nitride (g-C3N4) and its nanostructures with cobalt ferrite (CoFe2O4) and silver nanocubes (Ag) when using the combined pyrolysis of melamine and the polyol method. The resulted nanostructures were tested as electrocatalysts for hydrogen and oxygen evolution reactions in alkaline media. It was found that Ag@CoFe2O4/g-C3N4 showed the highest current density and gave the lowest overpotential of −259 mV for HER to reach a current density of 10 mA cm−2 in a 1 M KOH. The overpotentials for reaching the current density of 10 mA·cm−2 for OER were 370.2 mV and 382.7 mV for Ag@CoFe2O4/g-C3N4 and CoFe2O4/g-C3N4, respectively. The above results demonstrated that CoFe2O4/g-C3N4 and Ag@CoFe2O4/g-C3N4 materials could act as bifunctional catalysts due to their notable performances and high stabilities toward hydrogen and oxygen evolution reactions (HER and OER). Total water splitting in practical applications is a promising alternative to noble-metal-based electrocatalysts.
Eastern Canadian Gastrointestinal Cancer Consensus Conference 2023
Authors: Al-Mansor Essa , Mahoney Meghan , Chenard-Poirier Maxime , Ramjeesingh Ravi , Nair Vimoj , Kennedy Erin , Locke Gordon , Welch Stephen , Berry Scott , Couture Felix , Elimova Elena , Pollett Aaron , Mahmud Aamer , Wilson Brooke , Armstrong Dawn , Falkson Conrad , Asmis Timothy , Vickers Michael , Goodwin Rachel
Published: September 2023

The annual Eastern Canadian Gastrointestinal Cancer Consensus Conference 2023 was held in Quebec City, Quebec 2–4 February 2023. The purpose of the conference was to develop consensus statements on emerging and evolving treatment paradigms. Participants included Canadian medical oncologists, radiation oncologists, pathologists and surgical oncologists from across Ontario, Quebec, and the Atlantic provinces. Consensus statements were developed following rapid review presentations and discussion of available literature. The recommendations proposed here represent the consensus opinions of physicians involved in the care of patients with gastrointestinal malignancies who participated in this meeting.
Risk Factors and Interpretation of Inconclusive Endoscopic Ultrasound-Guided Fine Needle Aspiration Cytology in the Diagnosis of Solid Pancreatic Lesions
Authors: Bor Renáta , Vasas Béla , Fábián Anna , Szűcs Mónika , Bősze Zsófia , Bálint Anita , Rutka Mariann , Farkas Klaudia , Tóth Tibor , Resál Tamás , Bacsur Péter , Molnár Tamás , Szepes Zoltán
Published: September 2023

Background: The inconclusive cytological findings of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) remain a major clinical challenge and often lead to treatment delays. Methods: Patients who had undergone EUS-FNA sampling for solid pancreas lesions between 2014 and 2021 were retrospectively enrolled. The “atypical” and “non-diagnostic” categories of the Papanicolaou Society of Cytopathology System were considered inconclusive and the “negative for malignancy” category of malignancy was suspected clinically. We determined the frequency and predictors of inconclusive cytological finding. Results: A total of 473 first EUS-FNA samples were included, of which 108 cases (22.83%) were inconclusive. Significant increases in the odds of inconclusive cytological findings were observed for lesions with a benign final diagnosis (OR 11.20; 95% CI 6.56–19.54, p < 0.001) as well as with the use of 25 G FNA needles (OR 2.12; 95% CI 1.09–4.01, p = 0.023) compared to 22 G needles. Furthermore, the use of a single EUS-FNA technique compared to the combined use of slow-pull and standard suction techniques (OR 1.70; 95% CI 1.06–2.70, p = 0.027) and less than three punctures per procedure led to an elevation in the risk of inconclusive cytology (OR 2.49; 95% CI 1.49–4.14, p < 0.001). Risk reduction in inconclusive cytology findings was observed in lesions between 2–4 cm (OR 0.40; 95% CI 0.23–0.68, p = 0.001) and >4 cm (OR 0.16; 95% CI 0.08–0.31, p < 0.001) compared to lesions ≤2 cm. Conclusions: The more than two punctures per EUS-FNA sampling with larger-diameter needle (19 G or 22 G) using the slow-pull and standard suction techniques in combination may decrease the probability of inconclusive cytological findings.
Migraine Aura—Catch Me If You Can with EEG and MRI—A Narrative Review
Authors: Riederer Franz , Beiersdorf Johannes , Scutelnic Adrian , Schankin Christoph J.
Published: September 2023

Roughly one-third of migraine patients suffer from migraine with aura, characterized by transient focal neurological symptoms or signs such as visual disturbance, sensory abnormalities, speech problems, or paresis in association with the headache attack. Migraine with aura is associated with an increased risk for stroke, epilepsy, and with anxiety disorder. Diagnosis of migraine with aura sometimes requires exclusion of secondary causes if neurological deficits present for the first time or are atypical. It was the aim of this review to summarize EEG an MRI findings during migraine aura in the context of pathophysiological concepts. This is a narrative review based on a systematic literature search. During visual auras, EEG showed no consistent abnormalities related to aura, although transient focal slowing in occipital regions has been observed in quantitative studies. In contrast, in familial hemiplegic migraine (FHM) and migraine with brain stem aura, significant EEG abnormalities have been described consistently, including slowing over the affected hemisphere or bilaterally or suppression of EEG activity. Epileptiform potentials in FHM are most likely attributable to associated epilepsy. The initial perfusion change during migraine aura is probably a short lasting hyperperfusion. Subsequently, perfusion MRI has consistently demonstrated cerebral hypoperfusion usually not restricted to one vascular territory, sometimes associated with vasoconstriction of peripheral arteries, particularly in pediatric patients, and rebound hyperperfusion in later phases. An emerging potential MRI signature of migraine aura is the appearance of dilated veins in susceptibility-weighted imaging, which may point towards the cortical regions related to aura symptoms (“index vein”). Conclusions: Cortical spreading depression (CSD) cannot be directly visualized but there are probable consequences thereof that can be captured Non-invasive detection of CSD is probably very challenging in migraine. Future perspectives will be elaborated based on the studies summarized.
Age Matters: A Comparative Study of RF Heating of Epicardial and Endocardial Electronic Devices in Pediatric and Adult Phantoms during Cardiothoracic MRI
Authors: Jiang Fuchang , Henry Kaylee R. , Bhusal Bhumi , Sanpitak Pia , Webster Gregory , Popescu Andrada , Laternser Christina , Kim Daniel , Golestanirad Laleh
Published: September 2023

This study focused on the potential risks of radiofrequency-induced heating of cardiac implantable electronic devices (CIEDs) in children and adults with epicardial and endocardial leads of varying lengths during cardiothoracic MRI scans. Infants and young children are the primary recipients of epicardial CIEDs, though the devices have not been approved as MR conditional by the FDA due to limited data, leading to pediatric hospitals either refusing the MRI service to most pediatric CIED patients or adopting a scan-all strategy based on results from adult studies. The study argues that risk–benefit decisions should be made on an individual basis. We used 120 clinically relevant epicardial and endocardial device configurations in adult and pediatric anthropomorphic phantoms to determine the temperature rise during RF exposure at 1.5 T. The results showed that there was significantly higher RF heating of epicardial leads than endocardial leads in the pediatric phantom, but not in the adult phantom. Additionally, body size and lead length significantly affected RF heating, with RF heating up to 12 °C observed in models based on younger children with short epicardial leads. The study provides evidence-based knowledge on RF-induced heating of CIEDs and highlights the importance of making individual risk–benefit decisions when assessing the potential risks of MRI scans in pediatric CIED patients.
Precision in Dermatology: Developing an Optimal Feature Selection Framework for Skin Lesion Classification
Authors: Akram Tallha , Junejo Riaz , Alsuhaibani Anas , Rafiullah Muhammad , Akram Adeel , Almujally Nouf Abdullah
Published: September 2023

Melanoma is widely recognized as one of the most lethal forms of skin cancer, with its incidence showing an upward trend in recent years. Nonetheless, the timely detection of this malignancy substantially enhances the likelihood of patients’ long-term survival. Several computer-based methods have recently been proposed, in the pursuit of diagnosing skin lesions at their early stages. Despite achieving some level of success, there still remains a margin of error that the machine learning community considers to be an unresolved research challenge. The primary objective of this study was to maximize the input feature information by combining multiple deep models in the first phase, and then to avoid noisy and redundant information by downsampling the feature set, using a novel evolutionary feature selection technique, in the second phase. By maintaining the integrity of the original feature space, the proposed idea generated highly discriminant feature information. Recent deep models, including Darknet53, DenseNet201, InceptionV3, and InceptionResNetV2, were employed in our study, for the purpose of feature extraction. Additionally, transfer learning was leveraged, to enhance the performance of our approach. In the subsequent phase, the extracted feature information from the chosen pre-existing models was combined, with the aim of preserving maximum information, prior to undergoing the process of feature selection, using a novel entropy-controlled gray wolf optimization (ECGWO) algorithm. The integration of fusion and selection techniques was employed, initially to incorporate the feature vector with a high level of information and, subsequently, to eliminate redundant and irrelevant feature information. The effectiveness of our concept is supported by an assessment conducted on three benchmark dermoscopic datasets: PH2, ISIC-MSK, and ISIC-UDA. In order to validate the proposed methodology, a comprehensive evaluation was conducted, including a rigorous comparison to established techniques in the field.