bluuebunny/crossref_metadata_2025 huggingface dataset:
Environment DNA Reveals Fish Diversity in a Canyon River within the Upper Pearl River Drainage
Authors: Luo Si , Wang Meng , Ma Weizhong , Gu Dangen , Jin Zhijun , Yang Ruiqi , Qian Zhen , Song Chengwen , Wang Zexin , Jin Shiyu
Published: August 2024

Investigating fish diversity in canyon rivers through conventional fish surveys is challenging due to precipitous conditions, including steep slopes, rapid water flow, and complex habitats. Additionally, intensive construction of dams has further complicated the understanding of contemporary fish diversity in these rivers. In this study, we used the environmental DNA (eDNA) technique to assess fish diversity and examine the effects of dams on fish diversity in the Mabiehe River, a canyon river in the upper reaches of the Pearl River drainage. Water samples from 15 sampling sites were collected, yielding 9,356,148 valid sequences. Utilizing the NCBI public database, a total of 60 freshwater fish species were identified, with Carassius auratus, Cyprinus carpio, and Pelteobagrus fulvidraco being the most dominant species in the Mabiehe River. We also detected one nationally protected fish species, three provincially protected fish species, and six exotic species in this river. Furthermore, eDNA analyses demonstrated that the lotic river sections harbor more species and greater diversity than dammed sections, suggesting that dams might exert significant impacts on local fish diversity. Overall, this study supports the effectiveness of the eDNA technique as a complementary tool to traditional field surveys for monitoring fish biodiversity in canyon rivers.
Detailed Comparison of Acoustic Signals from Rehabilitated and Wild Franciscanas (Pontoporia blainvillei) Dolphins
Authors: Giardino Gisela , Cosentino Mel , Macchi Agustina , Loureiro Juan , Heredia Sergio , Alvarez Karina , Moron Sergio , Rodriguez Diego
Published: August 2024

The franciscana dolphin is a small, vulnerable species often caught in artisanal gillnets. This study aims to provide a comprehensive assessment of their acoustic capabilities by using advanced equipment to collect a large dataset of wideband, continuous recordings. We examined the detailed acoustic signals of franciscana dolphins, comparing the sounds from rehabilitated dolphins in captivity with those of wild dolphins near fishing nets. Significant differences in acoustic characteristics were found between neonates and older dolphins, with juvenile and wild dolphins showing similar features. For the first time, repetition patterns in click production were identified, highlighting the importance of understanding the context of these sounds in regards to feeding and communication. This study emphasizes the need for detecting neonates for species protection and suggests the potential for developing acoustic classifiers specific to different age groups. Our findings offer valuable insights for conservation efforts and the development of protection strategies for franciscana dolphins.
The Role of Oxidative Stress in Hypomagnetic Field Effects
Authors: Tian Lanxiang , Luo Yukai , Ren Jie , Zhao Chenchen
Published: August 2024

The geomagnetic field (GMF) is crucial for the survival and evolution of life on Earth. The weakening of the GMF, known as the hypomagnetic field (HMF), significantly affects various aspects of life on Earth. HMF has become a potential health risk for future deep space exploration. Oxidative stress is directly involved in the biological effects of HMF on animals or cells. Oxidative stress occurs when there is an imbalance favoring oxidants over antioxidants, resulting in cellular damage. Oxidative stress is a double-edged sword, depending on the degree of deviation from homeostasis. In this review, we summarize the important experimental findings from animal and cell studies on HMF exposure affecting intracellular reactive oxygen species (ROS), as well as the accompanying many physiological abnormalities, such as cognitive dysfunction, the imbalance of gut microbiota homeostasis, mood disorders, and osteoporosis. We discuss new insights into the molecular mechanisms underlying these HMF effects in the context of the signaling pathways related to ROS. Among them, mitochondria are considered to be the main organelles that respond to HMF-induced stress by regulating metabolism and ROS production in cells. In order to unravel the molecular mechanisms of HMF action, future studies need to consider the upstream and downstream pathways associated with ROS.
The Implementation of Cloud and Vertical Velocity Relocation/Cycling System in the Vortex Initialization of the HAFS
Authors: Shin JungHoon , Zhang Zhan , Liu Bin , Weng Yonghui , Liu Qingfu , Mehra Avichal , Tallapragada Vijay
Published: August 2024

The first version operational Hurricane Analysis and Forecast System (HAFS) implemented the Vortex Initialization (VI) technique to optimize tropical cyclone structure and intensity, which was adopted from the Hurricane Weather Research and Forecasting system (HWRF) and does not initialize cloud hydrometeors and vertical velocity. This limitation in the VI caused the inconsistency issue between hurricane vortex and its cloud in the model initial condition. A new VI, which can relocate or cycle cloud hydrometeors and vertical velocity, has been developed to solve this issue. For the cold start, the VI simply relocates the cloud and vertical velocity fields of Global Forecasting System (GFS) analysis; for the warm start, the cloud and vertical velocity associated with a hurricane in the GFS analysis are replaced by the fields extracted from the 6 h HAFS forecast of a previous cycle. This new VI has been tested for the 2023 HAFS-A real-time experiment configuration, and another sensitivity experiment without relocating or cycling both cloud and vertical velocity is conducted to examine the effect of the new VI. A comparison of the results reveals that the new VI improves the intensity forecast and generates a very realistic initial cloud field in correct position. Validating the model initial conditions with observed radar data reveals that the new VI captures the secondary eyewall of major hurricanes and asymmetric convective structure of weak tropical storms. This improvement of the cloud field in the model initial condition through the new VI expects to provide a better background for further data assimilation. Additional sensitivity experiment that only relocates or cycles cloud hydrometeors without correcting the vertical velocity field results in poorer intensity forecasts, which highlights the importance of vertical velocity in the model initial condition.
VOCs Concentration, SOA Formation Contribution and Festival Effects during Heavy Haze Event: A Case Study in Zhengzhou, Central China
Authors: Yu Shijie , Xue Chaofang , Deng Fuwen , Xu Qixiang , Zhao Bingnan
Published: August 2024

In this study, online ambient volatile organic compounds (VOCs) were collected at an urban site of Zhengzhou in Central China during February 2018. The VOCs characteristics, source contributions and the Chinese New Year (CNY) effects have been investigated. During the sampling period, three haze periods have been identified, with the corresponding VOCs concentrations of (92 ± 45) ppbv, (62 ± 18) ppbv and (83 ± 34) ppbv; in contrast, the concentration during non-haze days was found to be (57 ± 27) ppbv. In addition, the festival effects of the CNY were investigated, and the concentration of particulate matter precursor decreased significantly. Meanwhile, firework-displaying events were identified, as the emission intensity had been greatly changed. Both potential source contribution function (PSCF) and the concentration weighted trajectory (CWT) models results indicated that short-distance transportation was the main influencing factor of the local VOCs pollution, especially by transport from the northeast. Source contribution results by the positive matrix factorization (PMF) model showed that vehicle exhaust (24%), liquid petroleum gas and natural gas (LPG/NG, 23%), coal combustion (21%), industrial processes (16%) and solvent usages (16%) were the major sources of ambient VOCs. Although industry and solvents have low contribution to the total VOCs, their secondary organic aerosol (SOA) contribution were found to be relatively high, especially in haze-1 and haze-3 periods. The haze-2 period had the lowest secondary organic aerosol potential (SOAp) during the sampling period; this is mainly caused by the reduction of industrial and solvent emissions due to CNY.
Targeting Grb2 SH3 Domains with Affimer Proteins Provides Novel Insights into Ras Signalling Modulation
Authors: Tang Anna A. S. , Macdonald Andrew , McPherson Michael J. , Tomlinson Darren C.
Published: August 2024

Src homology 3 (SH3) domains play a critical role in mediating protein–protein interactions (PPIs) involved in cell proliferation, migration, and the cytoskeleton. Despite their abundance in the human proteome, the functions and molecular interactions of many SH3 domains remain unknown, and this is in part due to the lack of SH3-domain-specific reagents available for their study. Affimer proteins have been developed as affinity reagents targeting a diverse range of targets, including those involved in PPIs. In this study, Affimer proteins were isolated against both the N- and C-terminal SH3 domains (NSH3 and CSH3) of growth-factor-receptor-bound protein 2 (Grb2), an adapter protein that provides a critical link between cell surface receptors and Ras signalling pathways. Targeting the CSH3 alone for the inhibition of PPIs appeared sufficient for curtailing Ras signalling in mammalian cell lines stimulated with human epidermal growth factor (EGF), which conflicts with the notion that the predominant interactions with Ras activating Son of sevenless (SOS) occur via the NSH3 domain. This result supports a model in which allosteric mechanisms involved in Grb2-SOS1 interaction modulate Ras activation.
Bone Turnover Markers during Growth Hormone Therapy for Short Stature Children Born Small for Gestational Age
Authors: Korpysz Alicja , Jaworski Maciej , Skorupa Ewa , Szalecki Mieczysław , Walczak Mieczysław , Petriczko Elżbieta
Published: August 2024

Growth hormone therapy (GHT) can improve growth velocity and final height, but can also accelerate the process of bone growth, which is related to structural bone modeling in both formation and resorption. This study evaluated the capacity of bone turnover markers to predict early growth response to one year of GHT in short stature children born small for gestational age (SGA). This study included 25 prepubertal children born SGA. We estimated P1NP (N-terminal procollagen type 1), CTX (C-terminal telopeptide of collagen type 1), P3NP (N-terminal procollagen type 3), NT-pro-CNP (amino-terminal C-type natriuretic peptide) and Ca-P metabolism using standard ECLIA (electrochemiluminescence), RIA (radioimmunoassay), and ELISA (enzyme-linked immunosorbent assay) methods. A statistically significant increase in bone resorption markers (CTX) was found at both 6 and 12 months. P1NP bone markers were increased at 6 months and after 12 months of therapy. The P3NP marker for collagen synthesis also increased after 12 months of therapy. We obtained significant increases in phosphorus levels at 6 and 12 months, and similar ALP (alkaline phosphatase) increases. We found a significant correlation between height (cm) and CTX after 6–12 months, as well as a P1NP/height (SD) correlation after 12 months. Calcium levels significantly correlated with height (SD) after 12 months. We found strong reactions of bone resorption and bone formation markers during growth hormone therapy, which may determine their selection as predictors of GHT outcome in children born SGA. However, the issue requires further research.
NeuroAiDTM-II (MLC901) Promoted Neurogenesis by Activating the PI3K/AKT/GSK-3β Signaling Pathway in Rat Spinal Cord Injury Models
Authors: Anjum Anam , Yazid Muhammad Dain , Daud Muhammad Fauzi , Idris Jalilah , Ng Angela Min Hwei , Naicker Amaramalar Selvi , Rashidah Ismail Ohnmar Htwe , Athi Kumar Ramesh Kumar , Lokanathan Yogeswaran
Published: August 2024

Traumatic damage to the spinal cord (SCI) frequently leads to irreversible neurological deficits, which may be related to apoptotic neurodegeneration in nerve tissue. The MLC901 treatment possesses neuroprotective and neuroregenerative activity. This study aimed to explore the regenerative potential of MLC901 and the molecular mechanisms promoting neurogenesis and functional recovery after SCI in rats. A calibrated forceps compression injury for 15 s was used to induce SCI in rats, followed by an examination of the impacts of MLC901 on functional recovery. The Basso, Beattie, and Bresnahan (BBB) scores were utilized to assess neuronal functional recovery; H&E and immunohistochemistry (IHC) staining were also used to observe pathological changes in the lesion area. Somatosensory Evoked Potentials (SEPs) were measured using the Nicolet® Viking Quest™ apparatus. Additionally, we employed the Western blot assay to identify PI3K/AKT/GSK-3β pathway-related proteins and to assess the levels of GAP-43 and GFAP through immunohistochemistry staining. The study findings revealed that MLC901 improved hind-limb motor function recovery, alleviating the pathological damage induced by SCI. Moreover, MLC901 significantly enhanced locomotor activity, SEPs waveform, latency, amplitude, and nerve conduction velocity. The treatment also promoted GAP-43 expression and reduced reactive astrocytes (GFAP). MLC901 treatment activated p-AKT reduced p-GSK-3β expression levels and showed a normalized ratio (fold changes) relative to β-tubulin. Specifically, p-AKT exhibited a 4-fold increase, while p-GSK-3β showed a 2-fold decrease in T rats compared to UT rats. In conclusion, these results suggest that the treatment mitigates pathological tissue damage and effectively improves neural functional recovery following SCI, primarily by alleviating apoptosis and promoting neurogenesis. The underlying molecular mechanism of this treatment mainly involves the activation of the PI3K/AKT/GSK-3β pathway.
Xenografting Human Musculoskeletal Sarcomas in Mice, Chick Embryo, and Zebrafish: How to Boost Translational Research
Authors: Giusti Veronica , Miserocchi Giacomo , Sbanchi Giulia , Pannella Micaela , Hattinger Claudia Maria , Cesari Marilena , Fantoni Leonardo , Guerrieri Ania Naila , Bellotti Chiara , De Vita Alessandro , Spadazzi Chiara , Donati Davide Maria , Torsello Monica , Lucarelli Enrico , Ibrahim Toni , Mercatali Laura
Published: August 2024

Musculoskeletal sarcomas pose major challenges to researchers and clinicians due to their rarity and heterogeneity. Xenografting human cells or tumor fragments in rodents is a mainstay for the generation of cancer models and for the preclinical trial of novel drugs. Lately, though, technical, intrinsic and ethical concerns together with stricter regulations have significantly curbed the employment of murine patient-derived xenografts (mPDX). In alternatives to murine PDXs, researchers have focused on embryonal systems such as chorioallantoic membrane (CAM) and zebrafish embryos. These systems are time- and cost-effective hosts for tumor fragments and near-patient cells. The CAM of the chick embryo represents a unique vascularized environment to host xenografts with high engraftment rates, allowing for ease of visualization and molecular detection of metastatic cells. Thanks to the transparency of the larvae, zebrafish allow for the tracking of tumor development and metastatization, enabling high-throughput drug screening. This review will focus on xenograft models of musculoskeletal sarcomas to highlight the intrinsic and technically distinctive features of the different hosts, and how they can be exploited to elucidate biological mechanisms beneath the different phases of the tumor’s natural history and in drug development. Ultimately, the review suggests the combination of different models as an advantageous approach to boost basic and translational research.
Heart Transplant Rejection: From the Endomyocardial Biopsy to Gene Expression Profiling
Authors: Farcas Anca Otilia , Stoica Mihai Ciprian , Maier Ioana Maria , Maier Adrian Cornel , Sin Anca Ileana
Published: August 2024

Heart transplant prolongs life for patients with end-stage heart failure but rejection remains a complication that reduces long-term survival. The aim is to provide a comprehensive overview of the current status in HT rejection. EMB is an invasive diagnostic tool, consisting in the sampling of a fragment of myocardial tissue from the right ventricular septum using fluoroscopic guidance. This tissue can later be subjected to histopathological, immunohistochemical or molecular analysis, providing valuable information for cardiac allograft rejection, but this procedure is not without complications. To increase the accuracy of the rejection diagnosis, EMB requires a systematic evaluation of endocardium, myocardium, interstitium and intramural vessels. There are three types of rejection: hyperacute, acute or chronic, diagnosed by the histopathological evaluation of EMB as well as by new diagnostic methods such as DSA, ddcfDNA and gene expression profiling, the last having a high negative predictive value. More than 50 years after the introduction of EMB in medical practice, it still remains the “gold standard” in monitoring rejection in HT recipients but other new, less invasive diagnostic methods reduce the number of EMBs required.
Selective COX-2 Inhibitors as Neuroprotective Agents in Traumatic Brain Injury
Authors: Hiskens Matthew I. , Schneiders Anthony G. , Fenning Andrew S.
Published: August 2024

Traumatic brain injury (TBI) is a significant contributor to mortality and morbidity in people, both young and old. There are currently no approved therapeutic interventions for TBI. Following TBI, cyclooxygenase (COX) enzymes generate prostaglandins and reactive oxygen species that perpetuate inflammation, with COX-1 and COX-2 isoforms providing differing responses. Selective COX-2 inhibitors have shown potential as neuroprotective agents. Results from animal models of TBI suggest potential treatment through the alleviation of secondary injury mechanisms involving neuroinflammation and neuronal cell death. Additionally, early clinical trials have shown that the use of celecoxib improves patient mortality and outcomes. This review aims to summarize the therapeutic effects of COX-2 inhibitors observed in TBI animal models, highlighting pertinent studies elucidating molecular pathways and expounding upon their mechanistic actions. We then investigated the current state of evidence for the utilization of COX-2 inhibitors for TBI patients.
Applying a Fluorescence Polarization Assay for Detection of Brucellosis in Animals Using the Fluorescently Labeled Synthetic Oligosaccharides as Biosensing Tracer
Authors: Mukhametova Liliya I. , Zherdev Dmitry O. , Eremin Sergei A. , Kuznetsov Anton N. , Yudin Viktor I. , Sclyarov Oleg D. , Babicheva Olesia V. , Motorygin Anton V. , Tsvetkov Yury E. , Krylov Vadim B. , Nifantiev Nikolay E.
Published: August 2024

Brucellosis in animals is an infectious disease caused by bacteria of the genus Brucella. Known methods for diagnosing brucellosis face some challenges, due to the difficulties in isolating and standardizing the natural brucellosis antigen. In this work, we investigated the possibility of using the fluorescence polarization assay (FPA) with synthetic glycoconjugate biosensing tracers to detect antibodies against Brucella as a new methodology for diagnosing brucellosis. Based on the received results, the synthetic fluorescein-labeled trisaccharide tracer is most effective for Brucellosis detection. This tracer is structurally related to the immune determinant fragment of the Brucella LPS buildup of N-formyl-d-perosamine units, connected via α-(1→3)-linkage at the non-reducing end and α-(1→2)-linkage at the reducing end. The sensitivity and specificity in the case of the use of trisaccharide tracer 3b were 71% and 100% (Yuden’s method) and 87% and 88% (Euclidean method), respectively, which is comparable with the diagnostic efficiency of traditionally used serological methods, such as the agglutination test (AT), complement fixation test (CFT), and Rose Bengal test (RBT). Given the known advantages of FPA (e.g., speed, compactness of the equipment, and standard reagents) and the increased specificity of the developed test system, it would be appropriate to consider its widespread use for the diagnosis of brucellosis in animals, including rapid testing in the field.
The Daylighting Optimization of Integrated Suspended Particle Devices Glazing in Different School Typologies
Authors: Mesloub Abdelhakim , Alnaim Mohammed Mashary , Albaqawy Ghazy , Elkhayat Khaled , Hafnaoui Rim , Ghosh Aritra , Mayhoub Mohammed Salah
Published: August 2024

The design of school building typologies, along with the use of advanced glazing systems such as suspended particle devices (SPD), is crucial for determining visual comfort for students. Recent research has focused on integrating SPD in architectural elements such as skylights, clerestories, and windows. In hot desert climates, minimizing window areas, employing shading mechanisms, and utilizing daylighting features such as courtyards and atriums are practical. This study explores the optimization of various architectural components in classroom designs, including Window Wall Ratios (WWR), Skylight Ratios (SR), floor levels, cardinal orientation, and SPD switching states. Using a detailed and comprehensive radiance simulation via Rhino-Grasshopper and Colibri 2.0, we conducted a thorough analysis and optimization of the SPD glazing system across different states on both annual and hourly bases. The results indicate that optimizing SPD transmittance states between 30–40%, maintaining WWRs from 20–40%, and incorporating a large skylight ratio significantly enhances the recommended work plane illuminance (WPI) and the uniformity index (Ui) of the tested typologies. This optimization improves glare control across various building typologies and provides a roadmap for architects aiming to design learning spaces that prioritize visual comfort and overall student well-being.
Embracing Artificial Intelligence (AI) in Architectural Education: A Step towards Sustainable Practice?
Authors: Komatina Dragan , Miletić Mirjana , Mosurović Ružičić Marija
Published: August 2024

This study explores the impact of artificial intelligence (AI) on the behavior and knowledge of final-year architectural students in Serbia and Montenegro. It aims to describe how students approach sustainability in architecture and their use of AI tools within this context. The primary objective is to analyze how AI affects students’ understanding of sustainable architecture indicators and how sustainability challenges and concerns influence AI applications. Using a comparative analysis approach across the two countries, this research employs surveys to test various hypotheses regarding the effects of AI on students’ perceptions of sustainability and their use of AI to achieve sustainable outcomes. The findings highlight a significant relationship between students’ knowledge of sustainability and their use of AI, revealing different influencing factors. These insights are essential for predicting future AI usage in architectural practice and provide a theoretical foundation for assumptions about sustainability in architecture. This study’s findings offer valuable guidance for refining curricula at the universities involved, aiming to enhance the integration of AI and sustainability in architectural education.
Research on New Method for Safety Testing of Steel Structures—Combining 3D Laser Scanning Technology with FEA
Authors: Wang Kaichao , Zhang Guojie , Yi Tianqi , Zha Xiaoxiong
Published: August 2024

This paper introduces a novel approach to assessing structural safety, specifically aimed at evaluating the safety of existing structures. Firstly, a point cloud model of the existing commercial complex was captured utilizing three-dimensional (3D) laser scanning technology. Subsequently, an intelligent method for identifying holes within the point cloud model was proposed, built upon a YOLO v5-based framework, to ascertain the dimensions and locations of holes within the commercial complex. Secondly, Poisson surface reconstruction, coupled with partially self-developed algorithms, was employed to reconstruct the surface of the structure, facilitating the three-dimensional geometric reconstruction of the commercial complex. Lastly, a finite element model of the framed structure with holes was established using the reconstructed 3D model, and a safety analysis was conducted. The research findings reveal that the YOLO v5-based intelligent hole identification method significantly enhances the level of intelligence in point cloud data processing, reducing manual intervention time and boosting operational efficiency. Furthermore, through Poisson surface reconstruction and the self-developed algorithms, we have successfully achieved automated surface reconstruction, where the resulting geometric model accurately reflects the dimensional information of the commercial complex. Additionally, the maximum uniformly distributed surface load that the floor slabs within the framed structure with holes can withstand should not exceed 17.7 kN/m2, and its vertical deformation resistance stiffness is approximately 71.6% of that of a frame without holes.
Systems Engineering in the Business Case Phase to Reduce Risk in Megaprojects
Authors: Serrano Will
Published: August 2024

One of the main Frequently Asked Questions (FAQs) in project management for built environment or physical infrastructure projects is “How will this project scope be delivered on time and under budget, addressing health and safety in a sustainable way?” This article presents a parallel point of view summarised in a competing question: “Have you followed a systems engineering methodology to detail interfaces and integrations in the business case?” Megaprojects face multiple risks that incur project delays and cost overruns; hence, this article proposes a simple but nevertheless innovative model that incorporates a systems engineering framework at the start of the built environment or physical infrastructure project: the business case phase. This proposed approach seeks to derisk megaprojects composed of complex systems of systems (SoSs) in their earliest stage when financial decisions based on cost estimations have to be made. The scope of this article covers built environment and physical infrastructure projects and their associated ICT, digital, and technology programmes, rather than purely IT developments. The inconvenient truth is this additional systems engineering task embedded in the business case comes at a further project CAPEX cost that decision makers or stakeholders should be willing to accept as it provides a wider technical vision of the project and better quantifies the Return on Investment (ROI).
Influence of the Mass Percentage of Bottom Ash and Its State of Maturation on the Mechanical Performance of a Bio-Composite
Authors: Taleb-Ahmed Asmahan , Montrelay Nicolas , Houessou Koffi Justin , Quéneudec-t’Kint Michèle , Sebaibi Nassim , Dheilly Rose-Marie
Published: August 2024

This study examines the influence of the mass percentage and maturation stage of bottom ash on bio-composite mechanical strength. Two kinds of bottom ash were used: matured and non-matured. To elaborate the composites, several different percentages of bottom ash were mixed with an organic matrix. Casein, starch, alginate, polyethylene glycol, pre-vulcanized natural latex, and water are the components of matrix. The idea was to use as much bottom ash as possible, since it can be used as 80% or more as the main charge, which was in prismatic form for mechanical testing after drying. The results show that whatever the state of maturation of the bottom ash, the resistances present a maximum for a percentage of bottom ash equal to 85%. It could also be noticed that non-matured bottom ash composites have better mechanical strengths than composites with matured bottom ash. This is due to the decrease in porosity of the composites and to the improvement in their structural integrity. These new composites could solve some of the solid waste problems created by bottom ash production. As the matrix is made from organic resources, it saves energy and reduces the carbon footprint. This bio-composite contributes to the circular economy by giving waste a second life.
Effect of Cyclin-Dependent Kinase 4/6 Inhibitors on Circulating Cells in Patients with Metastatic Breast Cancer
Authors: Lobo-Martins Soraia , Corredeira Patrícia , Cavaco Ana , Rodrigues Carolina , Piairo Paulina , Lopes Cláudia , Fraga Joana , Silva Madalena , Alves Patrícia , Wachholz Szeneszi Lisiana , Barradas Ana , Castro Duran Camila , Antunes Marília , Nogueira-Costa Gonçalo , Sousa Rita , Pinto Conceição , Ribeiro Leonor , Abreu Catarina , Torres Sofia , Quintela António , Mata Gadea , Megías Diego , Ribot Julie , Serre Karine , Casimiro Sandra , Silva-Santos Bruno , Diéguez Lorena , Costa Luís
Published: August 2024

The combination of cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) with endocrine therapy (ET) is the standard-of-care for estrogen receptor (ER)-positive, HER2-negative (ER+/HER2− advanced/metastatic breast cancer (mBC). However, the impact of CDK4/6i on circulating immune cells and circulating tumor cells (CTCs) in patients receiving CDK4/6i and ET (CDK4/6i+ET) remains poorly understood. This was a prospective cohort study including 44 patients with ER+/HER2− mBC treated with CDK4/6i+ET in either first or second line. Peripheral blood samples were collected before (baseline) and 3 months (t2) after therapy. Immune cell’s subsets were quantified by flow cytometry, and microfluidic-captured CTCs were counted and classified according to the expression of cytokeratin and/or vimentin. Patients were categorized according to response as responders (progression-free survival [PFS] ≥ 6.0 months; 79.1%) and non-responders (PFS < 6.0 months; 20.9%). CDK4/6i+ET resulted in significant changes in the hematological parameters, including decreased hemoglobin levels and increased mean corpuscular volume, as well as reductions in neutrophil, eosinophil, and basophil counts. Specific immune cell subsets, such as early-stage myeloid-derived suppressor cells, central memory CD4+ T cells, and Vδ2+ T cells expressing NKG2D, decreased 3 months after CDK4/6i+ET. Additionally, correlations between the presence of CTCs and immune cell populations were observed, highlighting the interplay between immune dysfunction and tumor dissemination. This study provides insights into the immunomodulatory effects of CDK4/6i+ET, underscoring the importance of considering immune dynamics in the management of ER+/HER2− mBC.
Ageing-Related Changes to H3K4me3, H3K27ac, and H3K27me3 in Purified Mouse Neurons
Authors: Signal Brandon , Phipps Andrew J. , Giles Katherine A. , Huskins Shannon N. , Mercer Timothy R. , Robinson Mark D. , Woodhouse Adele , Taberlay Phillippa C.
Published: August 2024

Neurons are central to lifelong learning and memory, but ageing disrupts their morphology and function, leading to cognitive decline. Although epigenetic mechanisms are known to play crucial roles in learning and memory, neuron-specific genome-wide epigenetic maps into old age remain scarce, often being limited to whole-brain homogenates and confounded by glial cells. Here, we mapped H3K4me3, H3K27ac, and H3K27me3 in mouse neurons across their lifespan. This revealed stable H3K4me3 and global losses of H3K27ac and H3K27me3 into old age. We observed patterns of synaptic function gene deactivation, regulated through the loss of the active mark H3K27ac, but not H3K4me3. Alongside this, embryonic development loci lost repressive H3K27me3 in old age. This suggests a loss of a highly refined neuronal cellular identity linked to global chromatin reconfiguration. Collectively, these findings indicate a key role for epigenetic regulation in neurons that is inextricably linked with ageing.
De Novo Cancer Mutations Frequently Associate with Recurrent Chromosomal Abnormalities during Long-Term Human Pluripotent Stem Cell Culture
Authors: Al Delbany Diana , Ghosh Manjusha S. , Krivec Nuša , Huyghebaert Anfien , Regin Marius , Duong Mai Chi , Lei Yingnan , Sermon Karen , Olsen Catharina , Spits Claudia
Published: August 2024

Human pluripotent stem cells (hPSCs) are pivotal in regenerative medicine, yet their in vitro expansion often leads to genetic abnormalities, raising concerns about their safety in clinical applications. This study analyzed ten human embryonic stem cell lines across multiple passages to elucidate the dynamics of chromosomal abnormalities and single-nucleotide variants (SNVs) in 380 cancer-related genes. Prolonged in vitro culture resulted in 80% of the lines acquiring gains of chromosome 20q or 1q, both known for conferring an in vitro growth advantage. 70% of lines also acquired other copy number variants (CNVs) outside the recurrent set. Additionally, we detected 122 SNVs in 88 genes, with all lines acquiring at least one de novo SNV during culture. Our findings showed higher loads of both CNVs and SNVs at later passages, which were due to the cumulative acquisition of mutations over a longer time in culture, and not to an increased rate of mutagenesis over time. Importantly, we observed that SNVs and rare CNVs followed the acquisition of chromosomal gains in 1q and 20q, while most of the low-passage and genetically balanced samples were devoid of cancer-associated mutations. This suggests that recurrent chromosomal abnormalities are potential drivers for the acquisition of other mutations.
Harnessing Machine Learning to Decode the Mediterranean’s Climate Canvas and Forecast Sea Level Changes
Authors: Radin Cristina , Nieves Veronica , Vicens-Miquel Marina , Alvarez-Morales Jose Luis
Published: August 2024

Climate change and rising sea levels pose significant threats to coastal regions, necessitating accurate and timely forecasts. Current methods face limitations due to their inability to fully capture nonlinear complexities, high computational costs, gaps in historical data, and bridging the gap between short-term and long-term forecasting intervals. Our study addresses these challenges by combining advanced machine learning techniques to provide region-specific sea level predictions in the Mediterranean Sea. By integrating high-resolution sea surface temperature data spanning 40 years, we employed a tailored k-means clustering technique to identify regions of high variance. Using these clusters, we developed RNN-GRU models that integrate historical tide gauge data and sea surface height data, offering regional sea level predictions on timescales ranging from one month to three years. Our approach achieved the highest predictive accuracy, with correlation values ranging from 0.65 to 0.84 in regions with comprehensive datasets, demonstrating the model’s robustness. In areas with fewer tide gauge stations or shorter time series, our models still performed moderately well, with correlations between 0.51 and 0.70. However, prediction accuracy decreases in regions with complex geomorphology. Yet, all regional models effectively captured sea level variability and trends. This highlights the model’s versatility and capacity to adapt to different regional characteristics, making it invaluable for regional planning and adaptation strategies. Our methodology offers a powerful tool for identifying regions with similar variability and providing sub-regional scale predictions up to three years in advance, ensuring more reliable and actionable sea level forecasts for Mediterranean coastal communities.
Comprehensive Analysis of Fullerene- and Non-Fullerene-Based Bulk Heterojunction Solar Cells Using Numerical Simulation
Authors: Khan Muhammad Raheel , Jarząbek Bożena
Published: August 2024

In recent years, two-dimensional (2D) materials have been widely used for various applications due to their low cost, high charge carrier mobility, and tunable electronic structure. Here, in this study, we present the application of molybdenum disulfide (MoS2) used as a hole transport layer (HTL) material for fullerene (FA) and non-fullerene (NFA)-based organic photovoltaic (OPV) devices. A numerical simulation is carried out for these types of solar cells, and the SCAPS-1D software tool is used. Our study is specifically focused on the impact of thickness, the optimization of interface engineering, and the effect of high-temperature analysis to improve the output characteristics. The influence of interface defects between the HTL/active layer and the active layer/ETL (electron transport layer) is also contemplated. After optimization, the obtained power conversion efficiency (PCE) of these NFA- and FA-based devices is reported as 16.38% and 9.36%, respectively. A reflection coating study is also carried out to improve the power conversion efficiency of these devices. Here, the presented results demonstrate that molybdenum disulfide (MoS2) as a 2D material can be successfully used as an HTL material for high-efficiency OPV devices, both for fullerene (FA)- and non-fullerene (NFA)-based solar cells.
SOD: A Corpus for Saudi Offensive Language Detection Classification
Authors: Asiri Afefa , Saleh Mostafa
Published: August 2024

Social media platforms like X (formerly known as Twitter) are integral to modern communication, enabling the sharing of news, emotions, and ideas. However, they also facilitate the spread of harmful content, and manual moderation of these platforms is impractical. Automated moderation tools, predominantly developed for English, are insufficient for addressing online offensive language in Arabic, a language rich in dialects and informally used on social media. This gap underscores the need for dedicated, dialect-specific resources. This study introduces the Saudi Offensive Dialectal dataset (SOD), consisting of over 24,000 tweets annotated across three levels: offensive or non-offensive, with offensive tweets further categorized as general insults, hate speech, or sarcasm. A deeper analysis of hate speech identifies subtypes related to sports, religion, politics, race, and violence. A comprehensive descriptive analysis of the SOD is also provided to offer deeper insights into its composition. Using machine learning, traditional deep learning, and transformer-based deep learning models, particularly AraBERT, our research achieves a significant F1-Score of 87% in identifying offensive language. This score improves to 91% with data augmentation techniques addressing dataset imbalances. These results, which surpass many existing studies, demonstrate that a specialized dialectal dataset enhances detection efficacy compared to mixed-language datasets.
Self-Adaptive Evolutionary Info Variational Autoencoder
Authors: Emm Toby A. , Zhang Yu
Published: August 2024

With the advent of increasingly powerful machine learning algorithms and the ability to rapidly obtain accurate aerodynamic performance data, there has been a steady rise in the use of algorithms for automated aerodynamic design optimisation. However, long training times, high-dimensional design spaces and rapid geometry alteration pose barriers to this becoming an efficient and worthwhile process. The variational autoencoder (VAE) is a probabilistic generative model capable of learning a low-dimensional representation of high-dimensional input data. Despite their impressive power, VAEs suffer from several issues, resulting in poor model performance and limiting optimisation capability. Several approaches have been proposed in attempts to fix these issues. This study combines the approaches of loss function modification with evolutionary hyperparameter tuning, introducing a new self-adaptive evolutionary info variational autoencoder (SA-eInfoVAE). The proposed model is validated against previous models on the MNIST handwritten digits dataset, assessing the total model performance. The proposed model is then applied to an aircraft image dataset to assess the applicability and complications involved with complex datasets such as those used for aerodynamic design optimisation. The results obtained on the MNIST dataset show improved inference in conjunction with increased generative and reconstructive performance. This is validated through a thorough comparison against baseline models, including quantitative metrics reconstruction error, loss function calculation and disentanglement percentage. A number of qualitative image plots provide further comparison of the generative and reconstructive performance, as well as the strength of latent encodings. Furthermore, the results on the aircraft image dataset show the proposed model can produce high-quality reconstructions and latent encodings. The analysis suggests, given a high-quality dataset and optimal network structure, the proposed model is capable of outperforming the current VAE models, reducing the training time cost and improving the quality of automated aerodynamic design optimisation.
Line-Field Confocal Optical Coherence Tomography: A New Skin Imaging Technique Reproducing a “Virtual Biopsy” with Evolving Clinical Applications in Dermatology
Authors: Cappilli Simone , Paradisi Andrea , Di Stefani Alessandro , Palmisano Gerardo , Pellegrino Luca , D’Onghia Martina , Ricci Costantino , Tognetti Linda , Verzì Anna Elisa , Rubegni Pietro , Del Marmol Veronique , Lacarrubba Francesco , Cinotti Elisa , Suppa Mariano , Peris Ketty
Published: August 2024

Background: Line-field confocal optical coherence tomography is a novel technology able to reproduce a “virtual biopsy” of the skin. The aim of this review is to explore the application of line-field confocal optical coherence tomography (LC-OCT) in various skin diseases, covering skin cancers, inflammatory and infectious skin diseases, genetic diseases, cosmetic procedures, and less common disorders. Methods: Study selection was conducted based on LC-OCT and using pertinent MeSh terms, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines from inception to March 2024; to evaluate the quality and risk of bias of studies, Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) was used. Results: the search retrieved 154 papers according to the selection criteria; after removing publications by one or more of the exclusion criteria, a total of 96 studies were found to be suitable for the analysis. Conclusions: Increasing evidence supports the use of LC-OCT as an adjunctive diagnostic tool for the in vivo diagnosis of a variety of skin tumors. As this device can be considered a “bridge” between dermoscopy and histopathology, widening applications in numerous fields of clinical dermatology, including inflammatory skin disease treatment, presurgical mapping, cosmetic procedures, and monitoring of non-invasive therapies, have been explored.
Kidney Dysfunction, Hepatic Impairment, and Lipid Metabolism Abnormalities in Patients with Precapillary Pulmonary Hypertension
Authors: Iancu Dragos Gabriel , Varga Andreea , Cristescu Liviu , Dumbrava Robert Adrian , Stoica Florin , Moldovan Diana Andreea , Suteu Radu Adrian , Tilea Ioan
Published: August 2024

Background: Pulmonary hypertension (PH) is a global health issue that has profound medical and research implications. Methods: This retrospective study examined changes in renal and liver function, as well as lipid metabolism, over a 12-month period in 49 adult patients with pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). All cases were admitted, managed, and followed up with in the PH Center, County Emergency Clinical Hospital of Targu Mures, Romania. Results: Kidney dysfunction was observed in 12.24% of cases at baseline, decreasing to 8.16% at 12 months, and CTEPH patients were more affected. In particular, CTEPH patients exhibited an improvement in renal function, confirmed by an increase in their glomerular filtration rates. Hepatic impairment was present in 57.14% of subjects at baseline, declining to 42.86% at 12 months, with significant improvements noted in the PAH group. Lipid metabolic dysregulations were experienced by 22.45% of all patients at baseline, decreasing to 16.33% at 6 months, with a slow elevation to 24.49% at 12 months, but with no statistically significant differences. Pharmacological regimens were adjusted in accordance with the PH groups, a patient’s functional and clinical response, and laboratory tests. Conclusions: Our results demonstrate the multi-organ damage in PH and the importance of individualized treatment approaches.
AI Digital Pathology Using qFibrosis Shows Heterogeneity of Fibrosis Regression in Patients with Chronic Hepatitis B and C with Viral Response
Authors: Liu Feng , Sun Yameng , Tai Dean , Ren Yayun , Chng Elaine L. K. , Wee Aileen , Bedossa Pierre , Huang Rui , Wang Jian , Wei Lai , You Hong , Rao Huiying
Published: August 2024

This study aimed to understand the dynamic changes in fibrosis and its relationship with the evaluation of post-treatment viral hepatitis using qFibrosis. A total of 158 paired pre- and post-treatment liver samples from patients with chronic hepatitis B (CHB; n = 100) and C (CHC; n = 58) were examined. qFibrosis was employed with artificial intelligence (AI) to analyze the fibrosis dynamics in the portal tract (PT), periportal (PP), midzonal, pericentral, and central vein (CV) regions. All patients with CHB achieved a virological response after 78 weeks of treatment, whereas patients with CHC achieved a sustained viral response after 24 weeks. For patients initially staged as F5/6 (Ishak system) at baseline, the post-treatment cases exhibited a significant reduction in the collagen proportionate area (CPA) (25–69%) and number of collagen strings (#string) (9–72%) across all regions. In contrast, those initially staged as F3/4 at baseline showed a similar CPA and #string trend at 24 weeks. For regression patients, 27 parameters (25 in the CV region) in patients staged as F3/4 and 15 parameters (three in the PT and 12 in the PP regions) in those staged as F5/6 showed significant differences between the CHB and CHC groups at baseline. Following successful antiviral treatment, the pre- and post-treatment liver samples provided quantitative evidence of the heterogeneity of fibrotic features. qFibrosis has the potential to provide new insights into the characteristics of fibrosis regression in both patients with CHB and CHC as early as 24 weeks after antiviral therapy.
Multi-Agent DRL-Based Resource Scheduling and Energy Management for Electric Vehicles
Authors: Zhang Zhewei , Yu Chengbo , Tian Bingxin
Published: August 2024

With the emergence of vehicular edge computing (VEC) and electric vehicles (EVs), integrating computation and charging tasks presents challenges due to limited resources and dynamic vehicular networks. This research focuses on the joint optimization of computation offloading and charging scheduling in VEC networks. Specifically, we optimize the offloading factor, charging association variable, and charging rates to minimize the system delay and energy consumption by leveraging the multi-attributes of EVs in both information and energy networks. Considering the dynamic environment, we model the problem as a Markov Decision Process, and use the Multi-Agent Reinforcement Learning (MARL) algorithm MADDPG, with its centralized training and distributed execution mechanisms. Simulation results demonstrate that this approach significantly improves utility while reducing energy consumption and latency.