bluuebunny/crossref_metadata_2025 huggingface dataset:
The Targeted Degradation of BRAF V600E Reveals the Mechanisms of Resistance to BRAF-Targeted Treatments in Colorectal Cancer Cells
Authors: Chapdelaine Abygail G. , Ku Geng Chia , Sun Gongqin , Ayrapetov Marina K.
Published: December 2023

The BRAF V600E mutation is frequently found in cancer. It activates the MAPK pathway and promotes cancer cell proliferation, making BRAF an excellent target for anti-cancer therapy. While BRAF-targeted therapy is highly effective for melanoma, it is often ineffective against other cancers harboring the BRAF mutation. In this study, we evaluate the effectiveness of a proteolysis targeting chimera (PROTAC), SJF-0628, in directing the degradation of mutated BRAF across a diverse panel of cancer cells and determine how these cells respond to the degradation. SJF-0628 treatment results in the degradation of BRAF V600E and a decrease in Mek activation in all cell lines tested, but the effects of the treatment on cell signaling and cell proliferation are cell-line-specific. First, BRAF degradation killed DU-4475 and Colo-205 cells via apoptosis but only partially inhibited the proliferation of other cancer cell lines. Second, SJF-0628 treatment resulted in co-degradation of MEK in Colo-205 cells but did not have the same effect in other cell lines. Finally, cell lines partially inhibited by BRAF degradation also contain other oncogenic drivers, making them multi-driver cancer cells. These results demonstrate the utility of a PROTAC to direct BRAF degradation and reveal that multi-driver oncogenesis renders some colorectal cancer cells resistant to BRAF-targeted treatment.
Ontology-Based AI Design Patterns and Constraints in Cancer Registry Data Validation
Authors: Nicholson Nicholas , Giusti Francesco , Martos Carmen
Published: December 2023

Data validation in cancer registration is a critical operation but is resource-intensive and has traditionally depended on proprietary software. Ontology-based AI is a novel approach utilising machine reasoning based on axioms formally described in description logic. This is a different approach from deep learning AI techniques but not exclusive of them. The advantage of the ontology approach lies in its ability to address a number of challenges concurrently. The disadvantages relate to computational costs, which increase with language expressivity and the size of data sets, and class containment restrictions imposed by description logics. Both these aspects would benefit from the availability of design patterns, which is the motivation behind this study. We modelled the European cancer registry data validation rules in description logic using a number of design patterns and showed the viability of the approach. Reasoning speeds are a limiting factor for large cancer registry data sets comprising many hundreds of thousands of records, but these can be offset to a certain extent by developing the ontology in a modular way. Data validation is also a highly parallelisable process. Important potential future work in this domain would be to identify and optimise reusable design patterns, paying particular attention to avoiding any unintended reasoning efficiency hotspots.
HPV-Negative and HPV-Positive Oral Cancer Cells Stimulate the Polarization of Neutrophils towards Different Functional Phenotypes In Vitro
Authors: Martínez-Barajas Marcela Guadalupe , Jave-Suárez Luis Felipe , Ramírez-López Inocencia Guadalupe , García-Chagollán Mariel , Zepeda-Nuño José Sergio , Ramírez-de-Arellano Adrián , Ortiz-Lazareno Pablo César , Villegas-Pineda Julio César , Pereira-Suárez Ana Laura
Published: December 2023

High-risk human papillomavirus (HPV) infection is one of the leading causes of oropharyngeal squamous cell carcinoma (OPSCC), while the correlation between HPV and oral squamous cell carcinoma (OSCC) remains controversial. The inflammatory infiltrate involved in these epithelial neoplasms differs based on their association with HPV. HPV− tumors show higher tumor-associated neutrophil (TAN) infiltration. It is believed that TANs can play a dual role in cancer by exerting either anti-tumorigenic or pro-tumorigenic effects. However, the impact of HPV status on neutrophil polarization remains unknown. Therefore, this study aimed to investigate the effect of OSCC cells, both HPV− and HPV16+, on the functional phenotype of neutrophils. Peripheral blood neutrophils were stimulated with supernatants from OSCC cell lines and non-tumorigenic HaCaT keratinocytes transduced with HPV16 E6/E7 oncogenes. Subsequently, cytokine production, cell viability, metabolism, expression of degranulation markers, and PD-L1 expression were evaluated. Our findings demonstrate that in contrast to UPCI:SCC154 (HPV+ OSCC) cells, the SCC-9 (HPV− OSCC) cell line induced a highly activated functional state in neutrophils, which is potentially associated with a pro-tumorigenic effect. The HaCaT 16-E7 supernatant only stimulated the activation of some neutrophil functions. Understanding the complex interplay between neutrophils and their microenvironment has the potential to identify TANs as viable therapeutic targets.
Functional and Molecular Heterogeneity in Glioma Stem Cells Derived from Multiregional Sampling
Authors: Brynjulvsen Marit , Solli Elise , Walewska Maria , Zucknick Manuela , Djirackor Luna , Langmoen Iver A. , Mughal Awais Ahmad , Skaga Erlend , Vik-Mo Einar O. , Sandberg Cecilie J.
Published: December 2023

Glioblastoma (GBM) is an aggressive and highly heterogeneous primary brain tumor. Glioma stem cells represent a subpopulation of tumor cells with stem cell traits that are presumed to be the cause of tumor relapse. There exists complex tumor heterogeneity in drug sensitivity patterns between glioma stem cell (GSC) cultures derived from different patients. Here, we describe that heterogeneity also exists between GSC cultures derived from multiple biopsies within a single tumor. From biopsies harvested within spatially distinct regions representing the entire tumor mass, we established seven GSC cultures and compared their stem cell properties, mutations, gene expression profiles, and drug sensitivity patterns against 115 different anticancer drugs. The results were compared to 14 GSC cultures derived from other patients. Between the multiregional-derived GSC cultures, we observed only minor differences in their phenotype, proliferative capacity, and global gene expression. Further, they displayed intratumoral heterogeneity in mutational profiles and sensitivity patterns to anticancer drugs. This heterogeneity, however, did not exceed the extensive heterogeneity found between GSC cultures derived from other GBM patients. Our results suggest that the use of GSC cultures from one single focal biopsy may underestimate the overall complexity of the GSC population and display the importance of including GSC cultures reflecting the entire tumor mass in drug screening strategies.
Imaging of Peritoneal Carcinomatosis in Advanced Ovarian Cancer: CT, MRI, Radiomic Features and Resectability Criteria
Authors: Miceli Valentina , Gennarini Marco , Tomao Federica , Cupertino Angelica , Lombardo Dario , Palaia Innocenza , Curti Federica , Riccardi Sandrine , Ninkova Roberta , Maccioni Francesca , Ricci Paolo , Catalano Carlo , Rizzo Stefania Maria Rita , Manganaro Lucia
Published: December 2023

PC represents the most striking picture of the loco-regional spread of ovarian cancer, configuring stage III. In the last few years, many papers have evaluated the role of imaging and therapeutic management in patients with ovarian cancer and PC. This paper summed up the literature on traditional approaches to the imaging of peritoneal carcinomatosis in advanced ovarian cancer, presenting classification systems, most frequent patterns, routes of spread and sites that are difficult to identify. The role of imaging in diagnosis was investigated, with particular attention to the reported sensitivity and specificity data—computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography-CT (PET-CT)—and to the peritoneal cancer index (PCI). In addition, we explored the therapeutic possibilities and radiomics applications that can impact management of patients with ovarian cancer. Careful staging is mandatory, and patient selection is one of the most important factors influencing complete cytoreduction (CCR) outcome: an accurate pre-operative imaging may allow selection of patients that may benefit most from primary cytoreductive surgery.
Integrated Analysis of lncRNA–miRNA–mRNA Regulatory Network in Rapamycin-Induced Cardioprotection against Ischemia/Reperfusion Injury in Diabetic Rabbits
Authors: Samidurai Arun , Olex Amy L. , Ockaili Ramzi , Kraskauskas Donatas , Roh Sean K. , Kukreja Rakesh C. , Das Anindita
Published: December 2023

The inhibition of mammalian target of rapamycin (mTOR) with rapamycin (RAPA) provides protection against myocardial ischemia/reperfusion (I/R) injury in diabetes. Since interactions between transcripts, including long non-coding RNA (lncRNA), microRNA(miRNA) and mRNA, regulate the pathophysiology of disease, we performed unbiased miRarray profiling in the heart of diabetic rabbits following I/R injury with/without RAPA treatment to identify differentially expressed (DE) miRNAs and their predicted targets of lncRNAs/mRNAs. Results showed that among the total of 806 unique miRNAs targets, 194 miRNAs were DE after I/R in diabetic rabbits. Specifically, eight miRNAs, including miR-199a-5p, miR-154-5p, miR-543-3p, miR-379-3p, miR-379-5p, miR-299-5p, miR-140-3p, and miR-497-5p, were upregulated and 10 miRNAs, including miR-1-3p, miR-1b, miR-29b-3p, miR-29c-3p, miR-30e-3p, miR-133c, miR-196c-3p, miR-322-5p, miR-499-5p, and miR-672-5p, were significantly downregulated after I/R injury. Interestingly, RAPA treatment significantly reversed these changes in miRNAs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis indicated the participation of miRNAs in the regulation of several signaling pathways related to I/R injury, including MAPK signaling and apoptosis. Furthermore, in diabetic hearts, the expression of lncRNAs, HOTAIR, and GAS5 were induced after I/R injury, but RAPA suppressed these lncRNAs. In contrast, MALAT1 was significantly reduced following I/R injury, with the increased expression of miR-199a-5p and suppression of its target, the anti-apoptotic protein Bcl-2. RAPA recovered MALAT1 expression with its sponging effect on miR-199-5p and restoration of Bcl-2 expression. The identification of novel targets from the transcriptome analysis in RAPA-treated diabetic hearts could potentially lead to the development of new therapeutic strategies for diabetic patients with myocardial infarction.
Flavonoids Regulate Redox-Responsive Transcription Factors in Glioblastoma and Microglia
Authors: Joma Natali , Zhang Issan , Righetto Germanna L. , McKay Laura , Gran Evan Rizzel , Kakkar Ashok , Maysinger Dusica
Published: December 2023

The tumor microenvironment (TME) has emerged as a valuable therapeutic target in glioblastoma (GBM), as it promotes tumorigenesis via an increased production of reactive oxygen species (ROS). Immune cells such as microglia accumulate near the tumor and its hypoxic core, fostering tumor proliferation and angiogenesis. In this study, we explored the therapeutic potential of natural polyphenols with antioxidant and anti-inflammatory properties. Notably, flavonoids, including fisetin and quercetin, can protect non-cancerous cells while eliminating transformed cells (2D cultures and 3D tumoroids). We tested the hypothesis that fisetin and quercetin are modulators of redox-responsive transcription factors, for which subcellular location plays a critical role. To investigate the sites of interaction between natural compounds and stress-responsive transcription factors, we combined molecular docking with experimental methods employing proximity ligation assays. Our findings reveal that fisetin decreased cytosolic acetylated high mobility group box 1 (acHMGB1) and increased transcription factor EB (TFEB) abundance in microglia but not in GBM. Moreover, our results suggest that the most powerful modulator of the Nrf2-KEAP1 complex is fisetin. This finding is in line with molecular modeling and calculated binding properties between fisetin and Nrf2-KEAP1, which indicated more sites of interactions and stronger binding affinities than quercetin.
Beyond the Basics: Unraveling the Complexity of Coronary Artery Calcification
Authors: Hashmi Satwat , Shah Pashmina Wiqar , Aherrahrou Zouhair , Aikawa Elena , Aherrahrou Rédouane
Published: December 2023

Coronary artery calcification (CAC) is mainly associated with coronary atherosclerosis, which is an indicator of coronary artery disease (CAD). CAC refers to the accumulation of calcium phosphate deposits, classified as micro- or macrocalcifications, that lead to the hardening and narrowing of the coronary arteries. CAC is a strong predictor of future cardiovascular events, such as myocardial infarction and sudden death. Our narrative review focuses on the pathophysiology of CAC, exploring its link to plaque vulnerability, genetic factors, and how race and sex can affect the condition. We also examined the connection between the gut microbiome and CAC, and the impact of genetic variants on the cellular processes involved in vascular calcification and atherogenesis. We aimed to thoroughly analyze the existing literature to improve our understanding of CAC and its potential clinical and therapeutic implications.
Cholesteryl Hemiazelate Present in Cardiovascular Disease Patients Causes Lysosome Dysfunction in Murine Fibroblasts
Authors: Lopes Elizeth , Machado-Oliveira Gisela , Simões Catarina Guerreiro , Ferreira Inês S. , Ramos Cristiano , Ramalho José , Soares Maria I. L. , Melo Teresa M. V. D. Pinho e , Puertollano Rosa , Marques André R. A. , Vieira Otília V.
Published: December 2023

There is growing evidence supporting the role of fibroblasts in all stages of atherosclerosis, from the initial phase to fibrous cap and plaque formation. In the arterial wall, as with macrophages and vascular smooth muscle cells, fibroblasts are exposed to a myriad of LDL lipids, including the lipid species formed during the oxidation of their polyunsaturated fatty acids of cholesteryl esters (PUFA-CEs). Recently, our group identified the final oxidation products of the PUFA-CEs, cholesteryl hemiesters (ChE), in tissues from cardiovascular disease patients. Cholesteryl hemiazelate (ChA), the most prevalent lipid of this family, is sufficient to impact lysosome function in macrophages and vascular smooth muscle cells, with consequences for their homeostasis. Here, we show that the lysosomal compartment of ChA-treated fibroblasts also becomes dysfunctional. Indeed, fibroblasts exposed to ChA exhibited a perinuclear accumulation of enlarged lysosomes full of neutral lipids. However, this outcome did not trigger de novo lysosome biogenesis, and only the lysosomal transcription factor E3 (TFE3) was slightly transcriptionally upregulated. As a consequence, autophagy was inhibited, probably via mTORC1 activation, culminating in fibroblasts’ apoptosis. Our findings suggest that the impairment of lysosome function and autophagy and the induction of apoptosis in fibroblasts may represent an additional mechanism by which ChA can contribute to the progression of atherosclerosis.
Increased Digital Media Use in Preschool Children: Exploring the Links with Parental Stress and Their Problematic Media Use
Authors: Kattein Elena , Schmidt Hannah , Witt Stefanie , Jörren Hannah Lea , Menrath Ingo , Rumpf Hans-Jürgen , Wartberg Lutz , Pawils Silke
Published: December 2023

Background: Intense or problematic media use behavior of parents could serve as a role model for their children’s media use behavior. So far, knowledge is scarce about increased children’s media use (ICMU) and its association with parental stress (PS) and problematic parental media use (PPMU). Methods: ICMU was examined using a modified set of the DSM-5 criteria for Internet Gaming Disorder. PS was assessed via the widely used Parenting Stress Index, and PPMU was assessed using the Short Compulsive Internet Use Scale. A multiple linear regression analysis was conducted to evaluate the links between ICMU, PS, and PPMU. A mediation analysis was performed to examine if PPMU mediated the relationship between PS and ICMU. Results: In sum, 809 parents (M = 36.89 years; SD = 4.87; 81.4% female) of preschool children (average age: 44.75 months, SD = 13.68) participated in the study. ICMU was statistically significantly related to higher age of the parent, greater PPMU, and higher PS. Furthermore, we found that the association between PS and ICMU was partially mediated by PPMU. Conclusions: The results indicate that more pronounced PS and PPMU are associated with ICMU, highlighting the necessity of considering these parental variables when developing early prevention strategies for preschool-age children.
Advocacy of Precision Allergy Molecular Diagnosis in Decision Making for the Eligibility of Customized Allergen Immunotherapy
Authors: González-Pérez Ruperto , Poza-Guedes Paloma , Pineda Fernando , Sánchez-Machín Inmaculada
Published: December 2023

Allergen immunotherapy (AIT) with aeroallergens is the only disease-modifying treatment for patients with different allergic conditions. Despite the effectiveness of AIT having been proven in both randomized controlled trials and real-world studies, it remains underused in less than 10% of subjects with allergic rhinitis (AR) and/or asthma (A). We aimed to determine the current eligibility for house dust mite (HDM) AIT by means of a precision allergy molecular diagnosis (PAMD@) model in a selected cohort of youngsters with different allergic phenotypes according to the available evidence. A complex response to both HDM and storage mite allergens was depicted regardless of the subjects’ basal atopic condition. No solely specific IgE-binding responses to Der p 1, Der p 2, and/or Der p 23 were found in the studied cohort. Despite the patients with A and atopic dermatitis showing significantly higher serum titers to six mite allergens than subjects with AR, no specific molecular profile was regarded as disease specific. Given the increasing complexity of specific IgE responses to the local prevailing aeroallergens, the identification and presence of such molecules are needed in commercially available AIT in the era of precision medicine.
The Utilization of Plant-Material-Loaded Vesicular Drug Delivery Systems in the Management of Pulmonary Diseases
Authors: Lukhele Bongani Sannyboy , Bassey Kokoette , Witika Bwalya Angel
Published: December 2023

Medicinal plants have been utilized to treat a variety of conditions on account of the bioactive properties that they contain. Most bioactive constituents from plants are of limited effectiveness, due to poor solubility, limited permeability, first-pass metabolism, efflux transporters, chemical instability, and food–drug interactions However, when combined with vesicular drug delivery systems (VDDS), herbal medicines can be delivered at a predetermined rate and can exhibit site-specific action. Vesicular drug delivery systems are novel pharmaceutical formulations that make use of vesicles as a means of encapsulating and transporting drugs to various locations within the body; they are a cutting-edge method of medication delivery that combats the drawbacks of conventional drug delivery methods. Drug delivery systems offer promising strategies to overcome the bioavailability limitations of bioactive phytochemicals. By improving their solubility, protecting them from degradation, enabling targeted delivery, and facilitating controlled release, drug delivery systems can enhance the therapeutic efficacy of phytochemicals and unlock their full potential in various health conditions. This review explores and collates the application of plant-based VDDS with the potential to exhibit protective effects against lung function loss in the interest of innovative and effective treatment and management of respiratory illnesses.
Multi-Hazard Extreme Scenario Quantification Using Intensity, Duration, and Return Period Characteristics
Authors: Sfetsos Athanasios , Politi Nadia , Vlachogiannis Diamando
Published: December 2023

Many modern frameworks for community resilience and emergency management in the face of extreme hydrometeorological and climate events rely on scenario building. These scenarios typically cover multiple hazards and assess the likelihood of their occurrence. They are quantified by their main characteristics, including likelihood of occurrence, intensity, duration, and spatial extent. However, most studies in the literature focus only on the first two characteristics, neglecting to incorporate the internal hazard dynamics and their persistence over time. In this study, we propose a multidimensional approach to construct extreme event scenarios for multiple hazards, such as heat waves, cold spells, extreme precipitation and snowfall, and wind speed. We consider the intensity, duration, and return period (IDRP) triptych for a specific location. We demonstrate the effectiveness of this approach by developing pertinent scenarios for eight locations in Greece with diverse geographical characteristics and dominant extreme hazards. We also address how climate change impacts the scenario characteristics.
The Influence Mechanism of Molar Ratio on the Performance of Phosphogypsum-Modified Geopolymer Material
Authors: Xu Jin , Zhang Meixia , Lu Junqiu , Wang Kai , Yang Fan , Chen Shengying , Xu Fang
Published: December 2023

Comprising a relatively large amount of industrial solid waste, the high-value utilization of phosphogypsum (PG) is closely related to the sustainable development of resource materials and the protection of the ecological environment. PG can improve some of the shortcomings of geopolymers, but there is a lack of systematic research on the specific influencing factors as well as the mechanism of the two in a hydration reaction. In this study, the effects of the Si/Al, Na/Al and Ca/Al ratios on the micropores as well as the hydration products of phosphogypsum-modified geopolymer material (PMGM) are systematically explored via macroscopic and microscopic tests from the molar ratios of the raw material’s target components. By changing the molar ratio, the generation of hydration products is affected, thereby altering the properties of the material. The effects of each molar ratio on paste workability, capillary water absorption, drying shrinkage and self shrinkage are systematically analyzed, while the types, productions, and micropores of hydration products are analyzed via XRD and SEM. This study provides a new idea for the large-scale recycling of PG and makes a systematic investigation of its hydration mechanism, which can provide a reference for the reaction principle of PG with geopolymers.
Structure Optimization and Failure Mechanism of Metal Nitride Coatings for Enhancing the Sand Erosion Resistance of Aluminum Alloys
Authors: Yang Zhufang , Ren Yuxin , Zhang Yanli , Zhang Zilei , He Guangyu , Zhang Zhaolu
Published: December 2023

In this study, TiN/Ti coatings with various modulation ratios (TiN/Ti-4:1, TiN/Ti-1:1, and TiN/Ti-1:4) were deposited on 2A70 aluminum to improve its sand erosion performance. The structural design of ion implantation + high thickness Ti transition layer + TiN/Ti coatings was applied to alleviate the differences in physical properties between hard nitride coatings and 2A70 aluminum. Surface roughness, XRD, elastic modulus, hardness, and the sand erosion failure mechanism of each coating were evaluated. The hardness of TiN/Ti-4:1, TiN/Ti-1:1, and TiN/Ti-1:4 on aluminum was 26.99 GPa, 21.70 GPa, and 10.99 GPa. Sand erosion test results showed that TiN/Ti-1:1 had the highest erosion rates due to its rougher surface. Under a 90° incident angle, TiN/Ti-4:1 and TiN/Ti-1:4 both exhibited vertical cracks parallel to the coating growth direction in the bottom TiN layer at the initial erosion stage. Also, a lateral crack caused by TiN layer crack deflection emerged due to a higher crack resistance in the thicker Ti layer of TiN/Ti-1:4. Furthermore, in comparison with the layer-by-layer spalling failure behavior of TiN/Ti-1:4, overall spallation induced by the crack coalescence of the TiN layer was exhibited in TiN/Ti-4:1. In addition, cracks formed and intersected in the inner TiN layer in TiN/Ti-1:1 and TiN/Ti-4:1, resulting in layer-by-layer spallation under a 45° incident angle.
A New Type of White Nephrite from Limestone Replacement along the Kunlun–Altyn Tagh Mountains: A Case from the Mida Deposit, Qiemo County, Xinjiang, China
Authors: Jiang Tianlong , Shi Guanghai , Ye Danning , Zhang Xiaochong , Zhang Linjing , Han Hongwei
Published: December 2023

The recently discovered Mida nephrite deposit, located in the East Kunlun Mountains, Qiemo County, Xinjiang, Northwest China, contains new types of white and greenish white nephrite formed by limestone replacement, which shows microstructures, macroscopic features and country rocks typologies that are quite different from those of the other deposits along the Kunlun–Altyn Tagh Mountains. The gemological and mineralogical characteristics of Mida nephrite are presented here. These nephrites show an ivory white color and a porcelain-like appearance, with semitranslucent-to-opaque transparency and a porcelain-to-greasy luster. Petrographic study, electron probe microanalysis (EPMA) data and scanning electron microscopy (SEM) images have indicated that the nephrite is composed of tremolite, accompanied by minor quartz, calcite and diopside. Tremolite aggregates have shown different textures, like flaky, granular, fibrous–felted, bundle, radial and metasomatic relict textures. Quartz has appeared in granular or disseminated form, dispersed in the tremolite matrix. Calcite has shown a metasomatic relict texture in the white nephrite samples. Diopside has shown euhedral grains, with some distributed with a certain geometric appearance. Based on our observations, it is suggested that the quartz in the nephrite originated from Si-rich hydrothermal fluids. We propose that the substantial size difference of mineral grains, together with uncompacted grains with inter-particle pores, are the main reasons for the internal reflection and refraction under transmitted light, which allow less transmitted light to pass through the nephrite body and generate the appearance of a semitranslucent-to-opaque transparency, ivory white color and porcelain luster. Our study has unveiled that the Mida nephrite is not typical of the two known types (D-type: dolomite-related; S-type: serpentinite-related) and is overlapped by quartz grains dispersed throughout the less compact tremolite matrix. These observations would help set it apart from the majority of nephrite jades found in the Kunlun Mountains region and provide valuable insights for enhancing comprehension of the diversity of the nephrite deposits.
The Clinical Utility of FLT3 Mutation Testing in Acute Leukemia: A Canadian Consensus
Authors: Bergeron Julie , Capo-Chichi Jose-Mario , Tsui Hubert , Mahe Etienne , Berardi Philip , Minden Mark D. , Brandwein Joseph M. , Schuh Andre C.
Published: December 2023

FMS-like tyrosine kinase 3 (FLT3) mutations are detected in approximately 20–30% of patients with acute myeloid leukemia (AML), with the presence of a FLT3 internal tandem duplication (FLT3-ITD) mutation being associated with an inferior outcome. Assessment of FLT3 mutational status is now essential to define optimal upfront treatment in both newly diagnosed and relapsed AML, to support post-induction allogeneic hematopoietic stem cell transplantation (alloSCT) decision-making, and to evaluate treatment response via measurable (minimal) residual disease (MRD) evaluation. In view of its importance in AML diagnosis and management, the Canadian Leukemia Study Group/Groupe canadien d’étude sur la leucémie (CLSG/GCEL) undertook the development of a consensus statement on the clinical utility of FLT3 mutation testing, as members reported considerable inter-center variability across Canada with respect to testing availability and timing of use, methodology, and interpretation. The CLSG/GCEL panel identified key clinical and hematopathological questions, including: (1) which patients should be tested for FLT3 mutations, and when?; (2) which is the preferred method for FLT3 mutation testing?; (3) what is the clinical relevance of FLT3-ITD size, insertion site, and number of distinct FLT3-ITDs?; (4) is there a role for FLT3 analysis in MRD assessment?; (5) what is the clinical relevance of the FLT3-ITD allelic burden?; and (6) how should results of FLT3 mutation testing be reported? The panel followed an evidence-based approach, taken together with Canadian clinical and laboratory experience and expertise, to create a consensus document to facilitate a more uniform approach to AML diagnosis and treatment across Canada.
Traumatic Anterior Cervical Disc Herniation Presenting as Severe Dysphagia
Authors: Seo Jonghun , Oh Jeonghyun , Kim Pius , Ju Chang Il , Kim Seok Won
Published: December 2023

Due to the anatomical characteristics of the cervical spine, few cases of traumatic anterior cervical disc herniation have been reported in the literature. Here, we present a rare case of a traumatic anterior cervical disc herniation presenting as severe dysphagia. A 75-year-old male patient presented with severe dysphagia following an accident three days prior when he fell from a height of stairs. Cervical magnetic resonance (MR) imaging revealed a 1.3 × 1.0 cm extruded disc in the anterior aspect of the C4 level with the base at the C3–4 disc, which displaced the esophagus anteriorly. Esophagography revealed an extrinsic esophageal lesion that was considered to be responsible for the obstruction of the airway at the same level. He underwent a ruptured disc removal via the anterior approach. Preoperative dysphagia was resolved gradually after surgery, and he remained asymptomatic six months after surgery.
An Intra-Individual Comparison of Low-keV Photon-Counting CT versus Energy-Integrating-Detector CT Angiography of the Aorta
Authors: Hennes Jan-Lucca , Huflage Henner , Grunz Jan-Peter , Hartung Viktor , Augustin Anne Marie , Patzer Theresa Sophie , Pannenbecker Pauline , Petritsch Bernhard , Bley Thorsten Alexander , Gruschwitz Philipp
Published: December 2023

This retrospective study aims to provide an intra-individual comparison of aortic CT angiographies (CTAs) using first-generation photon-counting-detector CT (PCD-CT) and third-generation energy-integrating-detector CT (EID-CT). High-pitch CTAs were performed with both scanners and equal contrast-agent protocols. EID-CT employed automatic tube voltage selection (90/100 kVp) with reference tube current of 434/350 mAs, whereas multi-energy PCD-CT scans were generated with fixed tube voltage (120 kVp), image quality level of 64, and reconstructed as 55 keV monoenergetic images. For image quality assessment, contrast-to-noise ratios (CNRs) were calculated, and subjective evaluation (overall quality, luminal contrast, vessel sharpness, blooming, and beam hardening) was performed independently by three radiologists. Fifty-seven patients (12 women, 45 men) were included with a median interval between examinations of 12.7 months (interquartile range 11.1 months). Using manufacturer-recommended scan protocols resulted in a substantially lower radiation dose in PCD-CT (size-specific dose estimate: 4.88 ± 0.48 versus 6.28 ± 0.50 mGy, p < 0.001), while CNR was approximately 50% higher (41.11 ± 8.68 versus 27.05 ± 6.73, p < 0.001). Overall image quality and luminal contrast were deemed superior in PCD-CT (p < 0.001). Notably, EID-CT allowed for comparable vessel sharpness (p = 0.439) and less pronounced blooming and beam hardening (p < 0.001). Inter-rater agreement was good to excellent (0.58–0.87). Concluding, aortic PCD-CTAs facilitate increased image quality with significantly lower radiation dose compared to EID-CTAs.
Diffusion-Weighted MR Imaging of the Thymus in Children with Non-Thymic Neoplasms
Authors: Hwang Sook Min , Park Ji Eun , Yoo So-Young , Kim Ji Hye , Baek Sun-Young , Moon Sung-Hoon , Jeon Tae Yeon
Published: December 2023

Purpose: To investigate the diffusion-weighted imaging (DWI) findings and apparent diffusion coefficient (ADC) value of the thymus in children under the age of 13 who have non-thymic neoplasms. Materials and Methods: From January 2021 to April 2023, a single-center retrospective study analyzed consecutive 191 thoracic MRI scans with DWI from 67 children (<13 years) with non-thymic neoplasms. The scans were categorized based on the presence of restricted diffusion on DWI. We analyzed the demographics, laboratory data, and MR findings of the thymus. Statistical differences were assessed using generalized estimating equations. Results: Forty-five percent (86/191) of the scans exhibited restricted diffusion in the thymus: multifocal (n = 65; 76%), focal (n = 19; 22%), and diffuse (n = 2; 2%) patterns. The restricted diffusion group demonstrated higher absolute lymphocyte counts, more prominent thymus sizes, and higher frequency of off-treatment status compared to the unrestricted diffusion group (p>0.05). The mean ADC value across all 191 scans was 1.80 × 10−3 mm2/s. No significant difference was observed in the ADC value related to restricted diffusion patterns, the MRI vendors, or the age at the time of the scan. Conclusions: Restricted diffusion was observed in 45% of the thymus in children with non-thymic neoplasms, with a mean ADC value of 1.80 × 10−3 mm2/s. Recognizing the DWI findings can prevent unnecessary invasive procedures, alleviating concerns for patients and families.
Diagnosis and Treatment of Leprosy in Taiwan during the COVID-19 Pandemic: A Retrospective Study in a Tertiaty Center
Authors: Hsieh Chin-Ling , Hsiao Pa-Fan
Published: December 2023

Currently, over 200,000 new cases of leprosy are reported annually worldwide. Although leprosy was thought to have been eradicated in Taiwan, a few new cases still occur annually. Protean clinical manifestations of leprosy and immunological reactions result in delayed diagnoses. In addition, drug-resistant leprosy is emerging and poses treatment challenges. In this retrospective study, we collected and analyzed the clinicopathological features, leprosy type, treatment response, and relapse rate of patients with leprosy in our hospital between January 2009 and November 2022. We found that 54% of patients were Indonesian, and borderline lepromatous leprosy was predominant (39%); moreover, histoid leprosy and the Lucio phenomenon were also reported. Polymerase chain reaction analysis identified four positive cases, including a dapsone-resistant (4%) case. Our findings indicated good control of leprosy and a lower rate of dapsone resistance than that reported by the World Health Organization (4% vs. 13%) from 2009 to 2015. We found that the patient profile in terms of the treatment duration, recurrence rate, systemic symptoms, and neurological symptoms did not differ between before and during the pandemic. We report the recent advances in leprosy diagnosis, drug-resistant gene mutations, post-exposure prophylaxis, vaccination, and the effect of coronavirus disease 2019 on leprosy to facilitate updated leprosy diagnosis and management.
Low Vitamin D Levels Are Associated with Increased Cardiac Iron Uptake in Beta-Thalassemia Major
Authors: Meloni Antonella , Pistoia Laura , Vassalle Cristina , Spasiano Anna , Fotzi Ilaria , Bagnato Sergio , Putti Maria Caterina , Cossu Antonella , Massei Francesco , Giovangrossi Piera , Maffei Silvia , Positano Vincenzo , Cademartiri Filippo
Published: December 2023

We evaluated the association of vitamin D and parathormone (PTH) levels with cardiac iron and function in beta-thalassemia major (β-TM) patients. Two-hundred and seventy-eight TM patients (39.04 ± 8.58 years, 56.8% females) underwent magnetic resonance imaging for the assessment of iron overload (T2* technique), biventricular function parameters (cine images), and replacement myocardial fibrosis (late gadolinium enhancement technique). Vitamin D levels were deficient (<20 ng/dL) in 107 (38.5%) patients, insufficient (20–30 ng/dL) in 96 (34.5%) patients, and sufficient (≥30 ng/dL) in 75 (27.0%) patients. Deficient vitamin D patients had a significantly higher frequency of myocardial iron overload (MIO; global heart T2* < 20 ms) than patients with sufficient and insufficient vitamin D levels and a significantly higher left ventricular end-diastolic volume index and mass index than patients with sufficient vitamin D levels. PTH was not associated with cardiac iron, function, or fibrosis. In the multivariate regression analysis, vitamin D, serum ferritin, and pancreatic iron levels were the strongest predictors of global heart T2* values. In receiver operating characteristic curve analysis, a vitamin D level ≤ 17.3 ng/dL predicted MIO with a sensitivity of 81.5% and a specificity of 75.3% (p < 0.0001). In TM, the periodic and regular assessment of vitamin D levels can be beneficial for the prevention of cardiac iron accumulation and subsequent overt dysfunction.
The Capabilities of Boltzmann Machines to Detect and Reconstruct Ising System’s Configurations from a Given Temperature
Authors: Valle Mauricio A.
Published: December 2023

The restricted Boltzmann machine (RBM) is a generative neural network that can learn in an unsupervised way. This machine has been proven to help understand complex systems, using its ability to generate samples of the system with the same observed distribution. In this work, an Ising system is simulated, creating configurations via Monte Carlo sampling and then using them to train RBMs at different temperatures. Then, 1. the ability of the machine to reconstruct system configurations and 2. its ability to be used as a detector of configurations at specific temperatures are evaluated. The results indicate that the RBM reconstructs configurations following a distribution similar to the original one, but only when the system is in a disordered phase. In an ordered phase, the RBM faces levels of irreproducibility of the configurations in the presence of bimodality, even when the physical observables agree with the theoretical ones. On the other hand, independent of the phase of the system, the information embodied in the neural network weights is sufficient to discriminate whether the configurations come from a given temperature well. The learned representations of the RBM can discriminate system configurations at different temperatures, promising interesting applications in real systems that could help recognize crossover phenomena.
Revolutionizing Target Detection in Intelligent Traffic Systems: YOLOv8-SnakeVision
Authors: Liu Qi , Liu Yang , Lin Da
Published: December 2023

Intelligent traffic systems represent one of the crucial domains in today’s world, aiming to enhance traffic management efficiency and road safety. However, current intelligent traffic systems still face various challenges, particularly in the realm of target detection. These challenges include adapting to complex traffic scenarios and the lack of precise detection for multiple objects. To address these issues, we propose an innovative approach known as YOLOv8-SnakeVision. This method introduces Dynamic Snake Convolution, Context Aggregation Attention Mechanisms, and the Wise-IoU strategy within the YOLOv8 framework to enhance target detection performance. Dynamic Snake Convolution assists in accurately capturing complex object shapes and features, especially in cases of target occlusion or overlap. The Context Aggregation Attention Mechanisms allow the model to better focus on critical image regions and effectively integrate information, thus improving its ability to recognize obscured targets, small objects, and complex patterns. The Wise-IoU strategy combines dynamic non-monotonic focusing mechanisms, aiming to more precisely regress target bounding boxes, particularly for low-quality examples. We validate our approach on the BDD100K and NEXET datasets. Experimental results demonstrate that YOLOv8-SnakeVision excels in various complex road traffic scenarios. It not only enhances small object detection but also strengthens the ability to recognize multiple targets. This innovative method provides robust support for the development of intelligent traffic systems and holds the promise of achieving further breakthroughs in future applications.
DiffQuant: Reducing Compression Difference for Neural Network Quantization
Authors: Zhang Ming , Xu Jian , Li Weijun , Ning Xin
Published: December 2023

Deep neural network quantization is a widely used method in the deployment of mobile or edge devices to effectively reduce memory overhead and speed up inference. However, quantization inevitably leads to a reduction in the performance and equivalence of models. Moreover, access to labeled datasets is often denied as they are considered valuable assets for companies or institutes. Consequently, performing quantization training becomes challenging without sufficient labeled datasets. To address these issues, we propose a novel quantization pipeline named DiffQuant, which can perform quantization training using unlabeled datasets. The pipeline includes two cores: the compression difference (CD) and model compression loss (MCL). The CD can measure the degree of equivalence loss between the full-precision and quantized models, and the MCL supports fine-tuning the quantized models using unlabeled data. In addition, we design a quantization training scheme that allows the quantization of both the batch normalization (BN) layer and the bias. Experimental results show that our method outperforms state-of-the-art methods on ResNet18/34/50 networks, maintaining performance with a reduced CD. We achieve Top-1 accuracies of 70.08%, 74.11%, and 76.16% on the ImageNet dataset for the 8-bit quantized ResNet18/34/50 models and reduce the gap to 0.55%, 0.61%, and 0.71% with the full-precision network, respectively. We achieve CD values of only 7.45%, 7.48%, and 8.52%, which allows DiffQuant to further exploit the potential of quantization.
Multi-Label Diagnosis of Arrhythmias Based on a Modified Two-Category Cross-Entropy Loss Function
Authors: Zhu Junjiang , Ma Cheng , Zhang Yihui , Huang Hao , Kong Dongdong , Ni Wangjin
Published: December 2023

The 12-lead resting electrocardiogram (ECG) is commonly used in hospitals to assess heart health. The ECG can reflect a variety of cardiac abnormalities, requiring multi-label classification. However, the diagnosis results in previous studies have been imprecise. For example, in some previous studies, some cardiac abnormalities that cannot coexist often appeared in the diagnostic results. In this work, we explore how to realize the effective multi-label diagnosis of ECG signals and prevent the prediction of cardiac arrhythmias that cannot coexist. In this work, a multi-label classification method based on a convolutional neural network (CNN), long short-term memory (LSTM), and an attention mechanism is presented for the multi-label diagnosis of cardiac arrhythmia using resting ECGs. In addition, this work proposes a modified two-category cross-entropy loss function by introducing a regularization term to avoid the existence of arrhythmias that cannot coexist. The effectiveness of the modified cross-entropy loss function is validated using a 12-lead resting ECG database collected by our team. Using traditional and modified cross-entropy loss functions, three deep learning methods are employed to classify six types of ECG signals. Experimental results show the modified cross-entropy loss function greatly reduces the number of non-coexisting label pairs while maintaining prediction accuracy. Deep learning methods are effective in the multi-label diagnosis of ECG signals, and diagnostic efficiency can be improved by using the modified cross-entropy loss function. In addition, the modified cross-entropy loss function helps prevent diagnostic models from outputting two arrhythmias that cannot coexist, further reducing the false positive rate of non-coexisting arrhythmic diseases, thereby demonstrating the potential value of the modified loss function in clinical applications.
Machine Learning-Based Soft-Error-Rate Evaluation for Large-Scale Integrated Circuits
Authors: Song Ruiqiang , Shao Jinjin , Chi Yaqing , Liang Bin , Chen Jianjun , Wu Zhenyu
Published: December 2023

Transient pulses generated by high-energy particles can cause soft errors in circuits, resulting in spacecraft malfunctions and posing serious threats to the normal operation of spacecraft. For integrated circuits used in space applications, it is necessary to first evaluate soft errors caused by transient pulses. Conventional soft-error-rate evaluation tools are designed to simulate the generation of transient pulses using many accurate models, while the propagation of transient pulses is primarily simulated by circuit-level simulation tools. Due to the limitations of simulation tools, conventional evaluation approaches are limited to the circuit scale. The simulation runtime is unbearable for large-scale integrated circuits. This paper presents an approach for evaluating the soft error rate using machine learning. A back propagation neural network is implemented in the proposed approach. It helps to determine the probability of transient pulse propagation. Compared with the conventional soft-error-rate evaluation results, the proposed approach demonstrates a strong correlation in both trend and magnitude. The average difference between the results obtained using the proposed evaluation method and the experimental results is 23.5%, which is 7.5% higher than that between the results obtained using the conventional evaluation method and the experimental results. Compared to the conventional evaluation method, the proposed approach improves the runtime by an order of magnitude. The proposed approach also benefits the locating of highly sensitive circuit nodes in large-scale integrated circuits. Circuit design and radiation hardening are both useful applications.
A Ka-Band Silicon-Based Antenna-in-Package Design Using Characteristic Mode Analysis for Bandwidth Enhancement
Authors: Zhao Yu , Liang Lin , Hu Yali , Xiao Yu , Sun Houjun
Published: December 2023

With the emergence of 5G and satellite communication applications, where millimeter-wave (mm-wave) active phased arrays play an important role, the demand for a highly integrated and cost-effective method to achieve mm-wave antennas is an inevitable trend. Antenna-in-package (AiP) design is therefore becoming a hotspot. This paper presents the design procedure for a broadband silicon-based stacked patch antenna in Ka-band, which realizes a practical AiP structure for phased-array module integration requirements. A stacked-patch antenna on a high-resistivity silicon (HRSi) substrate is demonstrated to effectively extend the bandwidth with the guidance of characteristic mode analysis (CMA).The proposed antenna element and its 2 × 2 array were designed and fabricated using silicon bulk micromachining and wafer-level bonding technology. The measured results from the fabricated antenna prototypes showed that (1) the antenna element had an impedance bandwidth of 13.8% from 26.2 to 30.1 GHz, and the peak gain was 6.1 dBi at 28.9 GHz; (2) the 2 × 2 array realized an impedance bandwidth of 11.4% from 27.2 to 30.5 GHz, and the peak gain was 9.3 dBi at 28.5 GHz.