bluuebunny/crossref_metadata_2025 huggingface dataset:
Pathogenic mitochondrial DNA variants are associated with response to anti-VEGF therapy in ovarian cancer PDX models
Authors: Boso Daniele , Piga Ilaria , Trento Chiara , Minuzzo Sonia , Angi Eleonora , Iommarini Luisa , Lazzarini Elisabetta , Caporali Leonardo , Fiorini Claudio , D’Angelo Luigi , De Luise Monica , Kurelac Ivana , Fassan Matteo , Porcelli Anna Maria , Navaglia Filippo , Billato Ilaria , Esposito Giovanni , Gasparre Giuseppe , Romualdi Chiara , Indraccolo Stefano
Published: December 2024

Background

Mitochondrial DNA (mtDNA) pathogenic variants have been reported in several solid tumors including ovarian cancer (OC), the most lethal gynecologic malignancy, and raised interest as they potentially induce mitochondrial dysfunction and rewiring of cellular metabolism. Despite advances in recent years, functional characterization of mtDNA variants in cancer and their possible modulation of drug response remain largely uncharted.

Methods

Here, we characterized mtDNA variants in OC patient derived xenografts (PDX) and investigated their impact on cancer cells at multiple levels.

Results

Genetic analysis revealed that mtDNA variants predicted as pathogenic, mainly involving complex I and IV genes, were present in all but one PDX (n = 20) at different levels of heteroplasmy, including 7 PDXs with homoplasmic variants. Functional analyses demonstrated that pathogenic mtDNA variants impacted on respiratory complexes activity and subunits abundance as well as on mitochondrial morphology. Moreover, PDX cells bearing homoplasmic mtDNA variants behaved as glucose-addicted and could barely survive glucose starvation in vitro. RNA-seq analysis indicated that mtDNA mutated (heteroplasmy > 50%) PDXs were endowed with upregulated glycolysis and other pathways connected with cancer metabolism. These findings led us to investigate whether pathogenic mtDNA variants correlated with response to anti-VEGF therapy, since the latter was shown to reduce glucose availability in tumors. Strikingly, PDXs bearing homoplasmic pathogenic mtDNA variants associated with improved survival upon anti-VEGF treatment in mice, compared with mtDNA wild type or low heteroplasmy PDXs.

Conclusions

These results hint at mtDNA variants as potential biomarkers of response to antiangiogenic drugs.
SNAI1 promotes epithelial-mesenchymal transition and maintains cancer stem cell-like properties in thymic epithelial tumors through the PIK3R2/p-EphA2 Axis
Authors: E Haoran , Zhang Lei , Yang Zhenhua , Xu Long , Wang Tao , Guo Junhong , Xia Lang , Yu Juemin , Wang Heyong , She Yunlang , Wu Junqi , Zhao Yue , Chen Chang , Zhao Deping
Published: December 2024

Background

Thymic epithelial tumors (TETs) are infrequent malignancies that arise from the anterior mediastinum. Therapeutic options for TETs, especially thymic carcinoma (TC), remain relatively constrained. This study aims to investigate the oncogenic hub gene and its underlying mechanisms in TETs, as well as to identify potential therapeutic targets.

Methods

Weighted gene co-expression network analysis (WGCNA) and differential gene expression (DEG) analysis were utilized to identify significant oncogenes using The Cancer Genome Atlas (TCGA) database. LASSO logistic regression analysis was performed to assess the association between hub genes and clinical parameters. The influence of the hub gene on promoting epithelial-mesenchymal transition (EMT), tumor progression, and regulating cancer stem cell-like properties was assessed both in vitro and in vivo. Single-cell RNA sequencing (scRNA-seq) was utilized to analyze the alterations in the tumor and its microenvironment following the administration of the hub gene’s inhibitor. Multiplex immunohistochemistry (mIHC) was employed to validate the results. The potential mechanism was further elucidated through the utilization of Cleavage Under Targets and Tagmentation (CUT&Tag), RNA-sequencing, chromatin immunoprecipitation (ChIP), CUT&RUN, luciferase reporter assay, co-immunoprecipitation (Co-IP), mass spectrometry (MS) and phosphoproteomic assays.

Results

SNAI1 was identified as a hub transcription factor for TETs, and its positive correlation with the invasiveness of the disease was confirmed. Subsequent experiments revealed that the upregulation of SNAI1 augmented the migration, invasion, and EMT of TET cell lines. Furthermore, we observed that the overexpression of SNAI1 sustained cancer stem cell-like properties. ScRNA-seq demonstrated that the use of a SNAI1 inhibitor inhibited the transition of macrophages from M1 to M2 phenotype, a finding further validated by multiplex immunohistochemistry (mIHC). Phosphoinositide-3-kinase regulatory subunit 2 (PIK3R2) was identified as one of the downstream targets of SNAI1 through CUT&Tag and RNA-sequencing, a finding validated by ChIP-qPCR, CUT&RUN-qPCR, luciferase reporter and immunofluorescence assays. Co-IP, MS and phosphoproteomic assays further confirmed that PIK3R2 directly interacted with phosphorylated EphA2 (p-EphA2), facilitating downstream GSK3β/β-catenin signaling pathway.

Conclusion

The tumorigenic role of SNAI1 through the PIK3R2/p-EphA2 axis was preliminarily validated in TETs. A potential therapeutic strategy for TETs may involve the inhibition of SNAI1.
Cancer-associated fibroblasts, tumor and radiotherapy: interactions in the tumor micro-environment
Authors: Raaijmakers Kris T. P. M. , Adema Gosse J. , Bussink Johan , Ansems Marleen
Published: December 2024

Cancer-associated fibroblasts (CAFs) represent a group of genotypically non-malignant stromal cells in the tumor micro-environment (TME) of solid tumors that encompasses up to 80% of the tumor volume. Even though the phenotypic diversity and plasticity of CAFs complicates research, it is well-established that CAFs can affect many aspects of tumor progression, including growth, invasion and therapy resistance. Although anti-tumorigenic properties of CAFs have been reported, the majority of research demonstrates a pro-tumorigenic role for CAFs via (in)direct signaling to cancer cells, immunomodulation and extracellular matrix (ECM) remodeling. Following harsh therapeutic approaches such as radio- and/or chemotherapy, CAFs do not die but rather become senescent. Upon conversion towards senescence, many pro-tumorigenic characteristics of CAFs are preserved or even amplified. Senescent CAFs continue to promote tumor cell therapy resistance, modulate the ECM, stimulate epithelial-to-mesenchymal transition (EMT) and induce immunosuppression. Consequently, CAFs play a significant role in tumor cell survival, relapse and potentially malignant transformation of surviving cancer cells following therapy. Modulating CAF functioning in the TME therefore is a critical area of research. Proposed strategies to enhance therapeutic efficacy include reverting senescent CAFs towards a quiescent phenotype or selectively targeting (non-)senescent CAFs. In this review, we discuss CAF functioning in the TME before and during therapy, with a strong focus on radiotherapy. In the future, CAF functioning in the therapeutic TME should be taken into account when designing treatment plans and new therapeutic approaches.
Metformin protects prepubertal mice ovarian reserve against cyclophosphamide via regulation of the PI3K/Akt/mTOR signaling pathway and Yap-1
Authors: Zatalian Negin , Dalman Azam , Afsharian Parvaneh , Hezavehei Maryam , Gourabi Hamid
Published: December 2024

Background

Cyclophosphamide is a widely utilized chemotherapeutic agent for pediatric cancers, known to elicit adverse effects, including perturbation of the PI3K/Akt/mTOR and Hippo signaling pathways, thereby diminishing ovarian reserve and fertility potential in females. Consequently, this investigation delves into the mitigative effects of metformin on cyclophosphamide-induced ovarian impairment in prepubertal mice.

Methods

Twenty-four 14-day-old NMRI female mice were distributed into four groups: Control (Cont), Cyclophosphamide (Cyc), Metformin (Met), and Metformin plus Cyclophosphamide (Met-Cyc). The Met-Cyc group was given daily doses of 150 mg/kg metformin for 11 consecutive days and in parallel 3 intermittent doses of 65 mg/kg cyclophosphamide once every three days. The Met and Cyc groups were given identical doses of Met or Cyc alone. The control group received normal saline treatment. On the 12th day, mice were sacrificed for analysis. Stereological methods were employed to measure the overall volume of the ovaries, including the medulla, cortex, and follicles, along with measuring anti-Müllerian hormone (AMH) levels using an ELISA kit. Furthermore, qRT-PCR was utilized to quantify the expression levels of genes, including P53, Bax, Bcl-2, Rad-51, Pten, Mtor, and Yap-1.

Results

The findings demonstrate that metformin ameliorates cyclophosphamide-induced ovarian toxicity by increasing AMH levels and attenuating the excessive activation of primordial follicles, the ratio of growing to quiescent follicles, and follicular atresia. This protective effect is mediated by the downregulation of apoptosis-related genes, upregulation of the gene involved in a reparative pathway, and modulation of the PI3K/Akt/mTOR pathway evidenced by increased expression of Pten, Mtor and Hippo pathway by Yap-1 expression.

Conclusions

Our results advocate for the potential of metformin as a viable therapeutic option for preserving ovarian function in cyclophosphamide-treated adolescent girls, given its favorable side effect profile and ability to improve cyclophosphamide-induced ovarian damage.
HGVS Nomenclature 2024: improvements to community engagement, usability, and computability
Authors: Hart Reece K. , Fokkema Ivo F. A. C. , DiStefano Marina , Hastings Ros , Laros Jeroen F. J. , Taylor Rachel , Wagner Alex H. , den Dunnen Johan T.
Published: December 2024

Background

The Human Genome Variation Society (HGVS) Nomenclature is the global standard for describing and communicating variants in DNA, RNA, and protein sequences in clinical and research genomics. This manuscript details recent updates to the HGVS Nomenclature, highlighting improvements in governance, community engagement, website functionality, and underlying implementation of the standard.

Methods

The HGVS Variant Nomenclature Committee (HVNC) now operates under the Human Genome Organization (HUGO), facilitating broader community feedback and collaboration with related standards organizations. The website has been redesigned using modern documentation tools and practices. The specification was updated to include guidance for transcript selection and to align with recent cross-consortia recommendations for the representation of gene fusions. A formal computational grammar was introduced to improve the precision and consistency of variant descriptions.

Results

Major improvements in HGVS Nomenclature v. 21.1 include a redesigned website with enhanced navigation, search functionality, and mobile responsiveness; a new versioning policy aligned with software management practices; formal mechanisms for community feedback and change proposals; and adoption of Extended Backus-Naur Form (EBNF) for defining syntax. The specification now recommends MANE Select transcripts where appropriate and includes updated guidance for representing adjoined transcripts and gene fusions. All content is freely available under permissive licenses at hgvs-nomenclature.org.

Conclusions

These advancements establish a more sustainable foundation for maintaining and evolving the HGVS Nomenclature while improving its accessibility and utility. The introduction of formal computational grammar marks a crucial step toward unambiguous variant descriptions that can be reliably processed by both humans and machines. Combined with enhanced community engagement mechanisms and improved guidance, these changes position the HGVS Nomenclature to better serve the evolving needs of clinical and research genomics while maintaining the stability that users require.
ITC-MNP: a diverse dataset for image file fragment classification
Authors: Tavassoli Behnam , Naghshbandi Zhino , Teimouri Mehdi
Published: December 2024

Objectives

Image file fragment classification is a critical area of study in digital forensics. However, many publicly available datasets in this field are derived from a single source, often lacking consideration of the diversity in image settings and content. To demonstrate the effectiveness of a given methodology, it is essential to evaluate it using datasets that are sampled from varied data sources. Therefore, providing a sufficiently diverse dataset is crucial to enable a realistic assessment of any proposed method.

Data description

The dataset includes image file fragments of 4096 bytes from five formats (JPG, BMP, GIF, PNG, and TIFF), each processed with different conversion settings. The source images are categorized into three content types: Nature, People, and Medical. In total, the dataset contains 501,000 fragments. These fragments consist of file headers and incomplete end-of-file fragments, completed with random bytes to approximate how operating systems handle data when file sizes are not multiples of the sector size. This approach aims to simulate typical scenarios where fragments are recovered from a hard drive, though it may not capture all real-world complexities such as data corruption and complex file structures.
‘QuickDASH’ to find unique genes and biological processes associated with shoulder osteoarthritis: a prospective case–control study
Authors: Lynskey Samuel J. , Gill Stephen D. , McGee Sean L. , Ziemann Mark , Page Richard S.
Published: December 2024

Objective

Osteoarthritis (OA) is a disease impacting the synovial joint complex, yet transcriptional changes specific to shoulder OA remain underexplored. This study aims to profile transcriptomic changes in periarticular tissues from patients undergoing shoulder replacement for OA. By correlating these profiles with QuickDASH scores—a validated measure of worsening shoulder function—this research seeks to understand the gene expression changes associated with clinical decline. Capsular tissue biopsies from shoulder OA patients were compared with those from a control group undergoing shoulder stabilization for recurrent instability. This investigation forms part of a larger transcriptomic analysis of painful shoulder conditions which will address the current gap in knowledge regarding the molecular and genetic underpinnings of shoulder OA, rotator cuff tears and cuff-tear arthropathy.

Results

The analysis revealed that genes most strongly associated with increasing QuickDASH scores across tissues were linked to inflammation and stress response. Key pathways involved interleukins, chemokines, complement components, nuclear response factors, and immediate early response genes, reflecting a balance between pro- and anti-inflammatory signalling. Additionally, this study identified unique gene expression patterns in shoulder OA not previously observed in hip and knee OA, along with novel genes implicated in shoulder OA, highlighting areas for future targeted investigation.

Trial registration This investigation has been registered with the Australian New Zealand Clinical Trials Registry (ANZCTR), registered on the 26th of March 2018, registration number: 12618000431224, accessible from: https://anzctr.org.au/Trial/Registration/TrialReview.aspx?id=374665&isReview=true
Deep learning for opportunistic, end-to-end automated assessment of epicardial adipose tissue in pre-interventional, ECG-gated spiral computed tomography
Authors: Theis Maike , Garajová Laura , Salam Babak , Nowak Sebastian , Block Wolfgang , Attenberger Ulrike I. , Kütting Daniel , Luetkens Julian A. , Sprinkart Alois M.
Published: December 2024

Objectives

Recently, epicardial adipose tissue (EAT) assessed by CT was identified as an independent mortality predictor in patients with various cardiac diseases. Our goal was to develop a deep learning pipeline for robust automatic EAT assessment in CT.

Methods

Contrast-enhanced ECG-gated cardiac and thoraco-abdominal spiral CT imaging from 1502 patients undergoing transcatheter aortic valve replacement (TAVR) was included. Slice selection at aortic valve (AV)-level and EAT segmentation were performed manually as ground truth. For slice extraction, two approaches were compared: A regression model with a 2D convolutional neural network (CNN) and a 3D CNN utilizing reinforcement learning (RL). Performance evaluation was based on mean absolute z-deviation to the manually selected AV-level (Δz). For tissue segmentation, a 2D U-Net was trained on single-slice images at AV-level and compared to the open-source body and organ analysis (BOA) framework using Dice score. Superior methods were selected for end-to-end evaluation, where mean absolute difference (MAD) of EAT area and tissue density were compared. 95% confidence intervals (CI) were assessed for all metrics.

Results

Slice extraction using RL was slightly more precise (Δz: RL 1.8 mm (95% CI: [1.6, 2.0]), 2D CNN 2.0 mm (95% CI: [1.8, 2.3])). For EAT segmentation at AV-level, the 2D U-Net outperformed BOA significantly (Dice score: 2D U-Net 91.3% (95% CI: [90.7, 91.8]), BOA 85.6% (95% CI: [84.7, 86.5])). The end-to-end evaluation revealed high agreement between automatic and manual measurements of EAT (MAD area: 1.1 cm2 (95% CI: [1.0, 1.3]), MAD density: 2.2 Hounsfield units (95% CI: [2.0, 2.5])).

Conclusions

We propose a method for robust automatic EAT assessment in spiral CT scans enabling opportunistic evaluation in clinical routine.

Critical relevance statement

Since inflammatory changes in epicardial adipose tissue (EAT) are associated with an increased risk of cardiac diseases, automated evaluation can serve as a basis for developing automated cardiac risk assessment tools, which are essential for efficient, large-scale assessment in opportunistic settings.

Key Points

Deep learning methods for automatic assessment of epicardial adipose tissue (EAT) have great potential.

A 2-step approach with slice extraction and tissue segmentation enables robust automated evaluation of EAT.

End-to-end automation enables large-scale research on the value of EAT for outcome analysis.

Graphical Abstract
Antioxidant mechanisms in salt-stressed Maize (Zea mays L.) seedlings: comparative analysis of tolerant and susceptible genotypes
Authors: Methela Nusrat Jahan , Islam Mohammad Shafiqul , Das Ashim Kumar , Raihan Hasan Uz Zaman , Rohman Md. Motiar , Chowdhury Abul Kashem , Mun Bong-Gyu
Published: December 2024

Recent anthropogenic activities have spurred unparalleled environmental changes, among which elevated salinity levels emerge as a substantial threat to plant growth and development. This threat is characterized by oxidative stress, marked by the excessive generation of reactive oxygen species (ROS), proline accumulation, and lipid peroxidation. This study investigated the response of four maize (Zea mays L.) genotypes - two tolerant (9120 and Super Gold) and two susceptible (Pacific 984 and PS999) - to salinity-induced oxidative stress. Seedlings aged seven days were exposed to 12 dSm− 1 salinity stress for five days, with various parameters including relative water content (RWC), ROS accumulation, proline levels, lipid peroxidation, lipoxigenase (LOX) activity, enzymatic and non-enzymatic antioxidants, and glyoxalases evaluated in fully expanded leaves. Susceptible genotypes exhibited higher RWC loss compared to tolerant genotypes, while proline accumulation was elevated in the latter. Enhanced ROS production (hydrogen peroxide and superoxide), melondialdehyde (MDA) levels, and LOX activity were observed in susceptible genotypes under salinity stress, along with increased oxidation of glutathione (GSH) and ascorbate (ASA) compared to tolerant genotypes. Enzymatic antioxidants such as superoxide dismutase (SOD), peroxidase (POD), glutathione peroxidase (GPX), and monodehydroascorbate reductase (MDHAR) displayed higher activity in tolerant genotypes, while catalase (CAT) activity was significantly different between tolerant and susceptible genotypes under salinity stress in maize. Conversely, elevated activities of ascorbate peroxidase (APX), glutathione S-transferase (GST), glutathione reductase (GR), and dehydroascorbate reductase (DHAR) were observed in both genotypes, indicating their crucial role in cellular protection against ROS and metabolites during salt stress. In short, plants have devised tactics to scavenge surplus Reactive Oxygen Species (ROS) and uphold cellular redox balance amidst oxidative stress. This study aims to offer basic knowledge regarding both enzymatic and nonenzymatic antioxidants, and the defense mechanisms they constitute against ROS detoxification upon salt stress conditions; furthermore, it also explores their interactions with cellular components.
Surface roughness impact of 3D Ti-alloy printed WR-10 waveguide and rectangular horn antenna at W-band (75-110 GHz)
Authors: Kim Cheolbok , Cadwell Ryan , Ngoma Anthony , Yang Zhong , Ahmad Md Mufassal , Kim Jungkwun , Kim Sung Jin
Published: December 2024

To investigate the effect of the surface roughness of 3D-metal-printed sub-THz components, the WR-10 3-inch-long waveguide and 24 dBi rectangular horn antenna were 3D-metal-printed using a titanium alloy powder and a high-resolution 3D metal printer. The characterized surface roughness of the printed components was 17.27 µm in RMS from a 3D optical surface profiler, and a nodule ratio of 7.89 µm and surface ratio of 1.52 for Huray model from the analyzed SEM images. The measured results of the 3D-metal-printed waveguide and rectangular horn antenna were compared with the ones of commercial waveguide and horn antenna having the same shapes. The 3D-metal-printed waveguide has 4.02 dB higher loss than the commercial waveguide, which may be caused by an ohmic loss of 0.85 dB and a surface roughness loss of 2.81 dB. The 3D-metal-printed horn antenna has 2 dB higher loss then the commercial horn antenna, which may be caused by an ohmic loss of 0.2 dB, surface roughness of 0.1 dB and fabrication tolerance loss of 1.7 dB. The loss separation was done from the EM simulation by changing the conductor material and surface roughness.
Numerical investigation on the influence of groundwater flow on long-term heat extraction performance of deep borehole heat exchanger array
Authors: Yang Xiong , Cai Wanlong , Li Yongpeng , Wang Ming , Kong Yanlong , Wang Fenghao , Chen Chaofan
Published: December 2024

Groundwater convection is commonly observed in real-world projects, particularly in coastal and groundwater-abundant regions. To accurately evaluate the heat extraction capacity of the deep borehole heat exchanger (DBHE) considering groundwater flow, a conduction–convection coupled numerical model of the DBHE is established by OpenGeoSys (OGS) software. Then, the variation of the DBHE circulation temperature and the heat extraction capacity affected by different groundwater conditions, including Darcy velocity, location of the aquifer, and porosity of the aquifer, are quantitatively analyzed. The results show that the porosity and location of the aquifer have a limited effect on the heat extraction capacity of the DBHE. With the given scenario in this study, when the Darcy velocity reaches more than $$1\times 10^{-7}\,{{\textrm{m}}/{\textrm{s}}}$$

1
×

10

-
7

m
/
s

, it has a distinguishable effect on the heat extraction capacity of DBHE under the influence of groundwater. In addition, long-term simulations of multiple DBHEs considering the characteristics of the ground pipe network are performed in different directions of groundwater flow. The results indicate that groundwater flow can alleviate cold accumulation around the boreholes, and the thermal plume is pushed much towards the downstream direction. The cross-flow groundwater results in a higher circulation temperature than the parallel flow for the DBHE array. The maximum temperature difference between the two configurations is $${1.98}\,^{\circ }{\textrm{C}}$$

1.98

∘

C

, which occurs at the end of the 15th operating year based on the given parameters. The results of this study can be used as a guide for project engineers and decision-makers to accurately assess the heat extraction capacity of DBHE and strategize the layout of the DBHE array, taking into account the influence of groundwater flow.
Four functional genotoxic marker genes (Bax, Btg2, Ccng1, and Cdkn1a) discriminate genotoxic hepatocarcinogens from non-genotoxic hepatocarcinogens and non-genotoxic non-hepatocarcinogens in rat public toxicogenomics data, Open TG-GATEs
Authors: Furihata Chie , Suzuki Takayoshi
Published: December 2024

Background

Previously, Japanese Environmental Mutagen and Genome Society/Mammalian Mutagenicity Study Group/Toxicogenomics Study Group (JEMS/MMS toxicogenomic study group) proposed 12 genotoxic marker genes (Aen, Bax, Btg2, Ccnf, Ccng1, Cdkn1a, Gdf15, Lrp1, Mbd1, Phlda3, Plk2, and Tubb4b) to discriminate genotoxic hepatocarcinogens (GTHCs) from non-genotoxic hepatocarcinogens (NGTHCs) and non-genotoxic non-hepatocarcinogens (NGTNHCs) in mouse and rat liver using qPCR and RNA-Seq and confirmed in public rat toxicogenomics data, Open TG-GATEs, by principal component analysis (PCA). On the other hand, the U.S. Environmental Protection Agency (US EPA) suggested seven genotoxic marker genes (Bax, Btg2, Ccng1, Cgrrf1, Cdkn1a, Mgmt, and Tmem47) with Open TG-GATEs data. Four genes (Bax, Btg2, Ccng1, and Cdkn1a) were common in these two studies. In the present study, we examined the performance of these four genes in Open TG-GATEs data using PCA.

Results

The study's findings are of paramount significance, as these four genes proved to be highly effective in distinguishing five typical GTHCs (2-acetylaminofluorene, aflatoxin B1, 2-nitrofluorene, N-nitrosodiethylamine and N-nitrosomorpholine) from seven typical NGTHCs (clofibrate, ethanol, fenofibrate, gemfibrozil, hexachlorobenzene, phenobarbital, and WY-14643) and 11 NGTNHCs (allyl alcohol, aspirin, caffeine, chlorpheniramine, chlorpropamide, dexamethasone, diazepam, indomethacin, phenylbutazone, theophylline, and tolbutamide) by PCA at 24 h after a single administration with 100% accuracy. These four genes also effectively distinguished two typical GTHCs (2-acetylaminofluorene and N-nitrosodiethylamine) from seven NGTHCs and ten NGTNHCs by PCA on 29 days after 28 days-repeated administrations, with a similar or even better performance compared to the previous 12 genes. Furthermore, the study's analysis revealed that the three intermediate GTHC/NGTHCs (methapyrilene, monocrotaline, and thioacetamide, which were negative in the Salmonella test but positive in the in vivo rat liver test) were located in the intermediate region between typical GTHCs and typical NGTHCs by PCA.

Conclusions

The present results unequivocally demonstrate the availability of four genotoxic marker genes ((Bax, Btg2, Ccng1, and Cdkn1a) and PCA in discriminating GTHCs from NGTHCs and NGTNHCs in Open TG-GATEs. These findings strongly support our recommendation that future rat liver in vivo toxicogenomics tests prioritize these four genotoxic marker genes, as they have proven to be highly effective in discriminating between different types of hepatocarcinogens.
Hepatic artery stenting with Viabahn
Authors: Okumura Kenichiro , Ogi Takahiro , Matsumoto Junichi , Asato Nobuyuki , Sun Xiamin , Osanai Hirohito , Kozaka Kazuto , Kobayashi Satoshi
Published: December 2024

Background

The effect of vessel morphology on the technical success and patency of Viabahn stent-grafts in treating postoperative arterial injuries and bleeding (AIB) after hepatopancreatobiliary surgery is not well understood. Difficulties in stent insertion persist despite using stiff guidewires to straighten tortuous vessels. This study aimed to identify vessel morphologies linked to technical success and short-term patency and to explore effective management strategies.

Materials and methods

This retrospective study examined 12 consecutive cases of hepatic artery stenting in 11 patients, using Viabahn grafts for postoperative AIB from 2017 to 2024. Patient data, angiographic outcomes, and stent placement details were reviewed. Different types of guidewires, including stiff and soft guidewires, were utilized to facilitate stent deployment. Vessel tortuosity and vessel narrowing before stent placement were evaluated both qualitatively and quantitatively. Outcomes measured included technical and clinical success rates, stent patency at one month, and the time from surgery to stent placement.

Results

Final technical and clinical success was achieved in all cases (100%). Vessel tortuosity often led to the emergence of accordion-like appearances upon vessel straightening, necessitating additional technical adaptations due to the formation of steps (p = 0.005). One-month stent patency was observed in 10/12 cases (83%). Among cases with severe vessel narrowing distal to the bleeding point, 2/3 (67%) experienced stent occlusion, significantly higher than those with less severe narrowing (p = 0.045). All occluded cases involved the extension of stent length by overlapping stent-grafts.

Conclusions

Steps created by the accordion-like appearance in the hepatic artery resulting from the straightening of tortuous vessels can complicate stent insertion, and severe narrowing distal to the bleeding point increases the risk of short-term occlusion.
Antimicrobial and enzymatic potential of Pterocarpus erinaceus Poir. endophytes used in Benin (West Africa)
Authors: Aliou Sophia , Fanou Brice , Klotoé Jean Robert , Agbodjento Eric , Dougnon Victorien , Gbesso Norbert , Yangambele Toussaint , Hinnilo Curiace , Sovègnon Toussaint , Akotègnon Remi , Yemadje Alda , Nonviho Guevara , Fagbohoun Louis , Baba-Moussa Lamine
Published: December 2024

Background

Pterocarpus erinaceus Poir. is a plant widely used in traditional medicine in Benin, treating various diseases such as diabetes, ulcers, parasitic infections, hypertension, and infertility. This plant is under strong anthropogenic pressure due to its overexploitation, putting it in danger of extinction. The study aims to explore the antimicrobial and enzymatic activities of endophytes produced by Pterocarpus erinaceus.

Methods

Fresh leaves, stems, and roots of P. erinaceus, collected in two phytogeographical zones of Benin, Savalou and Abomey-Calavi of Benin, were sterilized to eliminate surface microorganisms prior to cultivation and isolation of endophytes. Isolated endophytes were tested for various enzymatic activities (catalase, cellulase, protease, lipase, and amylase), and their antimicrobial activities were evaluated by measuring inhibition diameters. The content of total polyphenols and flavonoids was determined by spectrophotometry.

Results

The results showed that bacterial endophytes have a higher colonization (80.55%) and isolation (69.44%) rates than fungal endophytes (44.44% and 50%, respectively). Bacterial endophytes expressed more enzymatic activities such as lecithinase and amylase, whereas fungal endophytes showed little. Only two fungal isolates (HT1a and HF2b) showed antibacterial activity, and one isolate (HF2b) showed antifungal action against Candida albicans, while no bacterial isolate demonstrated significant antimicrobial activity. Fungal isolates show significant variation in polyphenol content, while bacterial isolates show similar levels. As far as flavonoids are concerned, bacterial strains such as F3b and SR2C have high levels, unlike fungal endophytes which contain very few.

Conclusion

These results underscore the importance of conserving P. erinaceus while exploring its endophytes for potential therapeutic applications.
Delayed optical feedback-regulated artificial soliton molecule in a femtosecond optical parametric oscillator
Authors: Cai Yu , Fan Jintao , Meng Fanchao , Song Youjian , Hu Minglie
Published: December 2024

Soliton molecules (SMs) play a crucial role in nonlinear optical systems, enriching our understanding of nonlinear science through the study of their interaction dynamics. While passively mode-locked fiber lasers offer an efficient platform for generating diverse types of SMs, the complex internal dynamics of the laser often pose challenges in achieving predetermined temporal separations between SMs. Here, we implement a delayed optical feedback technique within a femtosecond optical parametric oscillator, enabling the generation of SMs with precise and controllable temporal separations. A theoretical model, which models the intracavity iterations of the signal with a simplified Ikeda map, is proposed to study the impact of parametric gain, intracavity feedback delay, and cavity length on the internal separations of the SMs. Our experimental results confirm that adjusting the cavity length allows for producing desired temporal separations within SMs. To reveal the evolution dynamics of the SMs, we further develop a rigorous numerical model using the carrier-resolved Forward Maxwell Equation, which is capable of modeling ultra-broadband complex dynamics based on a single equation without relying on the slowly-varying envelope approximation. The numerical model unveils the rich formation dynamics of the SMs at various separations, which confirms the critical role of the gain window provided by the pump. This work opens up new opportunities for the on-demand generation of SMs and provides valuable insights into the complex dynamics in femtosecond optical parametric oscillator systems with optical delayed feedback.
Impact of liquidity on capital structure and financial performance of non-financial-listed companies in the vietnam stock market
Authors: Nam Nguyen Hoang Phi , Tuyen Tran Thi My
Published: December 2024

The primary objective of this study is to conduct a comprehensive analysis of the relationships between liquidity (LIQ), capital structure (LEV), and financial performance (FIP). Additionally, we seek to investigate the indirect effect of liquidity (LIQ) on financial performance (FIP) by examining the intermediary role of the capital structure (LEV) of non-financial-listed companies in the Vietnamese stock market. This study utilizes PLS-SEM with a robust sample of 644 non-financial-listed companies in the Vietnamese stock market. The findings suggest that liquidity positively influences financial performance but negatively impacts capital structure. Conversely, capital structure negatively affects financial performance. Thus, liquidity indirectly enhances financial performance through capital structure mediation. This research result can provide suggestions for non-financial enterprises in making financial decisions to increase financial efficiency by increasing the holdings of highly liquid assets to prevent risks and take advantage of new investment opportunities in the future. In addition, increasing the holding of highly liquid assets also reduces debt pressure and reduces interest costs, thereby increasing financial efficiency. Our research shows that the relationship between economic factors is extremely complex; specifically, our research shows the true nature of the positive impact of liquidity on financial performance, including direct positive effects and indirect positive effects through capital structure. In addition, our research results also show that non-financial enterprises that want to increase financial efficiency need to pay attention to revenue growth, and non-financial companies with larger total assets (size) will have more advantages in increasing financial performance.
Could hematological indices predict the response of rheumatoid arthritis patients to biological drugs?
Authors: Elnemr Rehab Abd El-AL , Elshatby Nehad Mohamed
Published: December 2024

Background

The present cohort study with a control group aimed to evaluate the predictive value of hematological indices in assessing treatment response to biological drugs, including Janus Kinase (JAK) inhibitors, and their impact on these indices.

Methods

The study included 115 RA patients with active disease and 67 age- and sex-matched healthy volunteers. All patients were assessed at baseline and after 6 months of biological treatment. The disease Activity Score of 28 joints using the erythrocyte sedimentation rate (DAS28-ESR) and Clinical Disease Activity Index (CDAI) were evaluated. The hematological indices used were the neutrophil-to-lymphocyte ratio (NLR), neutrophil-to-hemoglobin and lymphocyte (NHL) score, platelet-to-lymphocyte ratio (PLR), platelet-to-hemoglobin ratio (PHR), monocyte-to-lymphocyte ratio (MLR), and Systemic Immune-Inflammation Index (SII).

Results

At baseline, The RA patients had significantly lower hemoglobin levels, a greater monocyte count, a greater platelet count, a significantly greater MLR, PLR PHR, NHL score, and SII than the control group (p ≤ 0.05). Neutrophil and lymphocyte percentages were positively correlated with the DAS28-ESR and CDAI. The PHR and NHL ratios were correlated with the ESR and CDAI. Biological treatment significantly decreased neutrophil, monocyte, and platelet counts, the MLR, the PHR, the NHL score, and the SII (p ≤ 0.05). Changes in the SII and NHL scores were associated with changes in the DAS28-ESR during treatment. No hematological indices showed predictive potential for nonresponse to biological treatment.

Conclusion

Hematological indices, such as MLR, PHR, NHL score, and SII, remain valuable despite not predicting non-response to treatment. These indices are cost-effective and widely available tools that correlate with RA disease activity, offering clinicians actionable insights into the inflammatory status of patients. Their utility lies in tracking treatment efficacy and guiding adjustments in therapeutic strategies, ensuring better disease management and improving patient outcomes.
Efficacy and Safety of Denileukin Diftitox-Cxdl, an Improved Purity Formulation of Denileukin Diftitox, in Patients With Relapsed or Refractory Cutaneous T-Cell Lymphoma
Authors: Foss Francine M. , Kim Youn H. , Prince H. Miles , Akilov Oleg E. , Querfeld Christiane , Seminario-Vidal Lucia , Fisher David C. , Kuzel Timothy M. , Yannakou Costas K. , Geskin Larisa J. , Feldman Tatyana , Sokol Lubomir , Allen Pamela Blair , Dang Nam Hoang , Cabanillas Fernando , Wong Henry K. , Ooi Chean Eng , Xing Dongyuan , Sauter Nicholas , Singh Preeti , Czuczman Myron , Duvic Madeleine
Published: December 2024

PURPOSE

Denileukin diftitox (DD)-cxdl is a fusion protein comprising diphtheria toxin fragments A and B and human interleukin-2. This phase III, multicenter, open-label, single-arm registrational trial evaluated the efficacy and safety of DD-cxdl in patients with relapsed/refractory (R/R) cutaneous T-cell lymphoma (CTCL).

PATIENTS AND METHODS

In the main study, which followed a dose-finding lead-in, DD-cxdl was administered intravenously daily (5 days; 9 µg/kg/d once daily) every 21 days for up to eight cycles. Patients in the primary efficacy analysis set (PEAS) were required to have stage IA-IIIB CTCL (mycosis fungoides and/or Sézary syndrome) and at least ≥one previous systemic therapy. The primary efficacy end point was objective response rate (ORR) using the Global Response Score. Secondary end points were duration of response (DOR), time to response (TTR), skin tumor burden, and safety and tolerability.

RESULTS

The PEAS included 69 patients (median age, 64.0 years). The ORR was 36.2% (95% CI, 25.0 to 48.7), including 8.7% with complete response. The median DOR was 8.9 months (95% CI, 5.0 to not estimable), and the median (Q1-Q3) TTR was 1.4 (0.7-2.1) months. A total of 84.4% of patients showed decreased skin tumor burden, with 48.4% showing a ≥50% decrease. Treatment-emergent adverse events (TEAEs) of special interest, most of which were grade 1 or 2, included infusion reaction (73.9%), hypersensitivity (68.1%), hepatotoxicity (36.2%), and capillary leak syndrome (20.3% [grade ≥3, 5.8%]). Other common TEAEs were nausea (43.5%) and fatigue (31.9%).

CONCLUSION

Efficacy and safety results show that DD-cxdl would potentially fulfill a serious, unmet medical need for patients with R/R CTCL.
Data-Driven Decision Support Tool Co-Development with a Primary Health Care Practice Based Learning Network
Authors: Kueper Jacqueline , Rayner Jennifer , Bhatti Sara , Angevaare Kelly , Fitzpatrick Sandra , Lucamba Paulino , Sutherland Eric , Lizotte Daniel
Published: December 2024

Background The Alliance for Healthier Communities is a learning health system that supports Community Health Centres (CHCs) across Ontario, Canada to provide team-based primary health care to people who otherwise experience barriers to care. This case study describes the ongoing process and lessons learned from the first Alliance for Healthier Communities’ Practice Based Learning Network (PBLN) data-driven decision support tool co-development project. Methods We employ an iterative approach to problem identification and methods development for the decision support tool, moving between discussion sessions and case studies with CHC electronic health record (EHR) data. We summarize our work to date in terms of six stages: population-level descriptive-exploratory study, PBLN team engagement, decision support tool problem selection, sandbox case study 1: individual-level risk predictions, sandbox case study 2: population-level planning predictions, project recap and next steps decision. Results The population-level study provided an initial point of engagement to consider how clients are (not) represented in EHR data and to inform problem selection and methodological decisions thereafter. We identified three initial meaningful types of decision support, with target application areas: risk prediction/screening, triaging specialized program referrals, and identifying care access needs. Based on feasibility and expected impact, we started with the goal to support earlier identification of mental health decline after diabetes diagnosis. As discussions deepened around clinical use cases associated with example prediction task set ups, the target problem evolved towards supporting the upstream task of organizational planning and advocacy for adequate mental health care service capacity to meet incoming needs. Conclusions This case study contributes towards a tool to support diabetes and mental health care, as well as lays groundwork for future CHC EHR-based decision support tool initiatives. We share lessons learned and reflections from our process that other primary health care organizations may use to inform their own co-development initiatives while we continue to work on advancing the population-level capacity planning model.
Intracellular dry mass density increases under growth-induced pressure
Authors: Kim Hyojun , Alric Baptiste , Chan Nolan , Roul Julien , Delarue Morgan
Published: December 2024

Cells that proliferate in confined environments develop mechanical compressive stress, referred to as growth-induced pressure, which inhibits growth and division across various organisms. Recent studies have shown that in these confined spaces, the diffusivity of intracellular nanoparticles decreases. However, the physical mechanisms behind this reduction remain unclear. In this study, we use quantitative phase imaging to measure the refractive index and dry mass density of Saccharomyces cerevisiae cells proliferating under confinement in a microfluidic bioreactor. Our results indicate that the observed decrease in diffusivity could be attributed to the intracellular accumulation of macromolecules. Furthermore, the linear scaling between cell content and growth-induced pressure suggests that the concentrations of macromolecules and osmolytes are maintained proportionally under such pressure in S. cerevisiae.
FEDECOM: Enabling cross-border energy exchange by federating energy communities
Authors: Lennard Zia
Published: December 2024

The FEDECOM project (Federated-system approach for flexible and interoperable energy communities) is a European Union-funded project aimed at fostering the integration and flexibility of local energy systems by demonstrating the potential of cross-border energy exchange by energy sector coupling through a federation of energy communities. The project seeks to provide economic benefits, improve grid stability and reliability, and contribute to the decarbonisation of the energy system. FEDECOM combines direct and indirect electrification strategies to leverage synergies and offers a cloud-based platform for managing local energy systems, including power, gas, thermal energy, industry, and mobility sectors. This paper discusses FEDECOM’s approach to energy management at multiple pilot sites, seeking to optimize resource use, enhance grid stability, and promote sustainable energy practices. It presents an overview of the FEDECOM project's goals, structure, pilot sites, and technical innovations, including peer-to-peer trading, semantic data modeling, and a novel platform architecture.
Reliability Analysis of Bucket-Wheel Excavator Parts – Application of Critical Position Selection Algorithm
Authors: Branković Dejan , Milovanović Zdravko , Janièić-Milovanović Valentina
Published: December 2024

Mining machines represent complex technical systems exposed to very difficult and demanding working conditions. The requirement of a high degree of effectiveness of technical systems in surface mines conditions a special organization of maintenance. The maintenance imperative is to ensure high reliability of parts of technical systems. For the maintenance of complex systems, made up of a large number of components, the parts whose failures cause the greatest negative consequences for the complete production system are particularly important. Analysis of the criticality of parts of technical systems directs maintenance activities to the prevention of failure states on key elements and ensuring the highest possible degree of their reliability. The paper presents the methodology of defining the critical position of the technical system Bucket-Wheel Excavator – belt conveyor – dumper on the open pit using the critical position selection algorithm. The basic criterion for choosing a critical position is a comparison of the frequency of failure and the reliability of individual components of technical systems. The results of the analysis confirm the connection of the statistical data analysis of the number of failure states of the working positions of the technical system with empirically determined reliability functions according to the methodology of non-parametric determination of reliability. The presented algorithm represents a methodology for recognizing the critical elements of technical systems whose operation has the greatest impact on the stability of the functioning of the complete technical system. Optimizing critical positions reduces total system downtime, increases productivity and improves overall business results.