bluuebunny/crossref_metadata_2025 huggingface dataset:
The Activation of the Fibrodysplasia Ossificans Progressiva-Inducing ALK2-R206H Mutant Depends on the Distinct Homo-Oligomerization Patterns of ACVR2B and ACVR2A
Authors: Szilágyi Szabina Szófia , Burdzinski Wiktor , Jatzlau Jerome , Ehrlich Marcelo , Knaus Petra , Henis Yoav I.
Published: January 2024

Mutations in activin-like kinase 2 (ALK2), e.g., ALK2-R206H, induce aberrant signaling to SMAD1/5/8, leading to Fibrodysplasia Ossificans Progressiva (FOP). In spite of extensive studies, the underlying mechanism is still unclear. Here, we quantified the homomeric and heteromeric interactions of ACVR2A, ACVR2B, ALK2-WT, and ALK2-R206H by combining IgG-mediated immobilization of one receptor with fluorescence recovery after photobleaching (FRAP) measurements on the lateral diffusion of a co-expressed receptor. ACVR2B formed stable homomeric complexes that were enhanced by Activin A (ActA), while ACVR2A required ActA for homodimerization. ALK2-WT, but not ALK2-R206H, exhibited homomeric complexes unaffected by ActA. ACVR2B formed ActA-enhanced heterocomplexes with ALK2-R206H or ALK2-WT, while ACVR2A interacted mainly with ALK2-WT. The extent of the homomeric complex formation of ACVR2A or ACVR2B was reflected in their ability to induce the oligomerization of ALK2-R206H and ALK2-WT. Thus, ACVR2B, which forms dimers without ligand, induced ActA-independent ALK2-R206H clustering but required ActA for enhancing the oligomerization of the largely dimeric ALK2-WT. In contrast, ACVR2A, which undergoes homodimerization in response to ActA, required ActA to induce ALK2-R206H oligomerization. To investigate whether these interactions are translated into signaling, we studied signaling by the FOP-inducing hyperactive ALK2-R206H mutant, with ALK2-WT signaling as control. The activation of SMAD1/5/8 signaling in cells expressing ALK2-R206H alone or together with ACVR2A or ACVR2B was measured by blotting for pSMAD1/5/8 and by transcriptional activation assays using BRE-Luc reporter. In line with the biophysical studies, ACVR2B activated ALK2-R206H without ligand, while activation by ACVR2A was weaker and required ActA. We propose that the homodimerization of ACVR2B or ACVR2A dictates their ability to recruit ALK2-R206H into higher complexes, enabling the homomeric interactions of ALK2-R206H receptors and, subsequently, their activation.
Dementia with Lewy Bodies: Genomics, Transcriptomics, and Its Future with Data Science
Authors: Goddard Thomas R. , Brookes Keeley J. , Sharma Riddhi , Moemeni Armaghan , Rajkumar Anto P.
Published: January 2024

Dementia with Lewy bodies (DLB) is a significant public health issue. It is the second most common neurodegenerative dementia and presents with severe neuropsychiatric symptoms. Genomic and transcriptomic analyses have provided some insight into disease pathology. Variants within SNCA, GBA, APOE, SNCB, and MAPT have been shown to be associated with DLB in repeated genomic studies. Transcriptomic analysis, conducted predominantly on candidate genes, has identified signatures of synuclein aggregation, protein degradation, amyloid deposition, neuroinflammation, mitochondrial dysfunction, and the upregulation of heat-shock proteins in DLB. Yet, the understanding of DLB molecular pathology is incomplete. This precipitates the current clinical position whereby there are no available disease-modifying treatments or blood-based diagnostic biomarkers. Data science methods have the potential to improve disease understanding, optimising therapeutic intervention and drug development, to reduce disease burden. Genomic prediction will facilitate the early identification of cases and the timely application of future disease-modifying treatments. Transcript-level analyses across the entire transcriptome and machine learning analysis of multi-omic data will uncover novel signatures that may provide clues to DLB pathology and improve drug development. This review will discuss the current genomic and transcriptomic understanding of DLB, highlight gaps in the literature, and describe data science methods that may advance the field.
Campylobacter jejuni Surface-Bound Protease HtrA, but Not the Secreted Protease nor Protease in Shed Membrane Vesicles, Disrupts Epithelial Cell-to-Cell Junctions
Authors: Sharafutdinov Irshad , Tegtmeyer Nicole , Rohde Manfred , Olofsson Annelie , Rehman Zia ur , Arnqvist Anna , Backert Steffen
Published: January 2024

Fundamental functions of the intestinal epithelium include the digestion of food, absorption of nutrients, and its ability to act as the first barrier against intruding microbes. Campylobacter jejuni is a major zoonotic pathogen accounting for a substantial portion of bacterial foodborne illnesses. The germ colonizes the intestines of birds and is mainly transmitted to humans through the consumption of contaminated poultry meat. In the human gastrointestinal tract, the bacterium triggers campylobacteriosis that can progress to serious secondary disorders, including reactive arthritis, inflammatory bowel disease and Guillain–Barré syndrome. We recently discovered that C. jejuni serine protease HtrA disrupts intestinal epithelial barrier functions via cleavage of the tight and adherens junction components occludin, claudin-8 and E-cadherin. However, it is unknown whether epithelial damage is mediated by the secreted soluble enzyme, by HtrA contained in shed outer-membrane vesicles (OMVs) or by another mechanism that has yet to be identified. In the present study, we investigated whether soluble recombinant HtrA and/or purified OMVs induce junctional damage to polarized intestinal epithelial cells compared to live C. jejuni bacteria. By using electron and confocal immunofluorescence microscopy, we show that HtrA-expressing C. jejuni bacteria trigger efficient junctional cell damage, but not soluble purified HtrA or HtrA-containing OMVs, not even at high concentrations far exceeding physiological levels. Instead, we found that only bacteria with active protein biosynthesis effectively cleave junctional proteins, which is followed by paracellular transmigration of C. jejuni through the epithelial cell layer. These findings shed new light on the pathogenic activities of HtrA and virulence strategies of C. jejuni.
Chemically Functionalized Single-Walled Carbon Nanotubes Prevent the Reduction in Plasmalemmal Glutamate Transporter EAAT1 Expression in, and Increase the Release of Selected Cytokines from, Stretch-Injured Astrocytes in Vitro
Authors: Gržeta Krpan Nika , Harej Hrkać Anja , Janković Tamara , Dolenec Petra , Bekyarova Elena , Parpura Vladimir , Pilipović Kristina
Published: January 2024

We tested the effects of water-soluble single-walled carbon nanotubes, chemically functionalized with polyethylene glycol (SWCNT-PEG), on primary mouse astrocytes exposed to a severe in vitro simulated traumatic brain injury (TBI). The application of SWCNT-PEG in the culture media of injured astrocytes did not affect cell damage levels, when compared to those obtained from injured, functionalization agent (PEG)-treated cells. Furthermore, SWCNT-PEG did not change the levels of oxidatively damaged proteins in astrocytes. However, this nanomaterial prevented the reduction in plasmalemmal glutamate transporter EAAT1 expression caused by the injury, rendering the level of EAAT1 on par with that of control, uninjured PEG-treated astrocytes; in parallel, there was no significant change in the levels of GFAP. Additionally, SWCNT-PEG increased the release of selected cytokines that are generally considered to be involved in recovery processes following injuries. As a loss of EAATs has been implicated as a culprit in the suffering of human patients from TBI, the application of SWCNT-PEG could have valuable effects at the injury site, by preventing the loss of astrocytic EAAT1 and consequently allowing for a much-needed uptake of glutamate from the extracellular space, the accumulation of which leads to unwanted excitotoxicity. Additional potential therapeutic benefits could be reaped from the fact that SWCNT-PEG stimulated the release of selected cytokines from injured astrocytes, which would promote recovery after injury and thus counteract the excess of proinflammatory cytokines present in TBI.
Significant Variations in Double-Stranded RNA Levels in Cultured Skin Cells
Authors: Sadeq Shaymaa , Chitcharoen Suwalak , Al-Hashimi Surar , Rattanaburi Somruthai , Casement John , Werner Andreas
Published: January 2024

Endogenous double-stranded RNA has emerged as a potent stimulator of innate immunity. Under physiological conditions, endogenous dsRNA is maintained in the cell nucleus or the mitochondria; however, if protective mechanisms are breached, it leaches into the cytoplasm and triggers immune signaling pathways. Ectopic activation of innate immune pathways is associated with various diseases and senescence and can trigger apoptosis. Hereby, the level of cytoplasmic dsRNA is crucial. We have enriched dsRNA from two melanoma cell lines and primary dermal fibroblasts, including a competing probe, and analyzed the dsRNA transcriptome using RNA sequencing. There was a striking difference in read counts between the cell lines and the primary cells, and the effect was confirmed by northern blotting and immunocytochemistry. Both mitochondria (10–20%) and nuclear transcription (80–90%) contributed significantly to the dsRNA transcriptome. The mitochondrial contribution was lower in the cancer cells compared to fibroblasts. The expression of different transposable element families was comparable, suggesting a general up-regulation of transposable element expression rather than stimulation of a specific sub-family. Sequencing of the input control revealed minor differences in dsRNA processing pathways with an upregulation of oligoadenylate synthase and RNP125 that negatively regulates the dsRNA sensors RIG1 and MDA5. Moreover, RT-qPCR, Western blotting, and immunocytochemistry confirmed the relatively minor adaptations to the hugely different dsRNA levels. As a consequence, these transformed cell lines are potentially less tolerant to interventions that increase the formation of endogenous dsRNA.
The Impact of Lens Epithelium-Derived Growth Factor p75 Dimerization on Its Tethering Function
Authors: Brouns Tine , Lux Vanda , Van Belle Siska , Christ Frauke , Veverka Václav , Debyser Zeger
Published: January 2024

The transcriptional co-activator lens epithelium-derived growth factor/p75 (LEDGF/p75) plays an important role in the biology of the cell and in several human diseases, including MLL-rearranged acute leukemia, autoimmunity, and HIV-1 infection. In both health and disease, LEDGF/p75 functions as a chromatin tether that interacts with proteins such as MLL1 and HIV-1 integrase via its integrase-binding domain (IBD) and with chromatin through its N-terminal PWWP domain. Recently, dimerization of LEDGF/p75 was shown, mediated by a network of electrostatic contacts between amino acids from the IBD and the C-terminal α6-helix. Here, we investigated the functional impact of LEDGF/p75 variants on the dimerization using biochemical and cellular interaction assays. The data demonstrate that the C-terminal α6-helix folds back in cis on the IBD of monomeric LEDGF/p75. We discovered that the presence of DNA stimulates LEDGF/p75 dimerization. LEDGF/p75 dimerization enhances binding to MLL1 but not to HIV-1 integrase, a finding that was observed in vitro and validated in cell culture. Whereas HIV-1 replication was not dependent on LEDGF/p75 dimerization, colony formation of MLLr-dependent human leukemic THP-1 cells was. In conclusion, our data indicate that intricate changes in the quaternary structure of LEDGF/p75 modulate its tethering function.
Ergothioneine Prevents Neuronal Cell Death Caused by the Neurotoxin 6-Hydroxydopamine
Authors: Yuzawa Saho , Nakashio Motonari , Ichimura Suzuna , Shimoda Mikako , Nakashima Ayaka , Marukawa-Hashimoto Yuka , Kawano Yusuke , Suzuki Kengo , Yoshitomi Kenichi , Kawahara Masahiro , Tanaka Ken-ichiro
Published: January 2024

Neuronal cell death is a key mechanism involved in the development and exacerbation of Parkinson’s disease (PD). The excessive production of reactive oxygen species (ROS) is a major cause leading to neuronal death; therefore, compounds that prevent oxidative stress-dependent neuronal death may be promising as a preventive method for PD. Ergothioneine is a natural amino acid with antioxidant properties, and its protective functions in the body are attracting attention. However, there has been no investigation into the protective functions of ergothioneine using in vivo and in vitro PD models. Thus, in this study, we analyzed the efficacy of ergothioneine against 6-hydroxydopamine (6-OHDA)-dependent neuronal cell death using immortalized hypothalamic neurons (GT1-7 cells). First, we found that ergothioneine prevents 6-OHDA-dependent neuronal cell death by suppressing ROS overproduction in GT1-7 cells. The cytoprotective effect of ergothioneine was partially abolished by verapamil, an inhibitor of OCTN1, which is involved in ergothioneine uptake. Furthermore, ergothioneine-rich Rice-koji (Ergo-koji) showed cytoprotective and antioxidant effects similar to those of ergothioneine. Taken together, these results suggest that ergothioneine or foods containing ergothioneine may be an effective method for preventing the development and progression of PD.
The Opioid Receptor Influences Circadian Rhythms in Human Keratinocytes through the β-Arrestin Pathway
Authors: Bigliardi Paul , Junnarkar Seetanshu , Markale Chinmay , Lo Sydney , Bigliardi Elena , Kalyuzhny Alex , Ong Sheena , Dunn Ray , Wahli Walter , Bigliardi-Qi Mei
Published: January 2024

The recent emphasis on circadian rhythmicity in critical skin cell functions related to homeostasis, regeneration and aging has shed light on the importance of the PER2 circadian clock gene as a vital antitumor gene. Furthermore, delta-opioid receptors (DOPrs) have been identified as playing a crucial role in skin differentiation, proliferation and migration, which are not only essential for wound healing but also contribute to cancer development. In this study, we propose a significant association between cutaneous opioid receptor (OPr) activity and circadian rhythmicity. To investigate this link, we conducted a 48 h circadian rhythm experiment, during which RNA samples were collected every 5 h. We discovered that the activation of DOPr by its endogenous agonist Met-Enkephalin in N/TERT-1 keratinocytes, synchronized by dexamethasone, resulted in a statistically significant 5.6 h delay in the expression of the core clock gene PER2. Confocal microscopy further confirmed the simultaneous nuclear localization of the DOPr-β-arrestin-1 complex. Additionally, DOPr activation not only enhanced but also induced a phase shift in the rhythmic binding of β-arrestin-1 to the PER2 promoter. Furthermore, we observed that β-arrestin-1 regulates the transcription of its target genes, including PER2, by facilitating histone-4 acetylation. Through the ChIP assay, we determined that Met-Enkephalin enhances β-arrestin-1 binding to acetylated H4 in the PER2 promoter. In summary, our findings suggest that DOPr activation leads to a phase shift in PER2 expression via β-arrestin-1-facilitated chromatin remodeling. Consequently, these results indicate that DOPr, much like its role in wound healing, may also play a part in cancer development by influencing PER2.
Rapid Assessment of Extractability of Macronutrients from Yerba Mate (Illex paraguariensis) Leaves Based on Laser-Induced Breakdown Spectroscopy
Authors: Díaz Pace Diego , Molina Juan , Rodríguez Corina Iris
Published: January 2024

Leaves of yerba mate plant (Ilex paraguariensis) have a wealth of nutrients, ingested by people who drink them in the hot water infusion popularly known as mate. In the present work, the laser-induced breakdown spectroscopy (LIBS) technique was applied for the first time to analysis of the extractability of macronutrients, including Mg, Ca, Na, and K, in commercial samples of yerba mate. Powdered samples from leaves’ material were used to simulate the infusion process in the laboratory. To carry out LIBS analysis, the emission spectra were measured before and after the infusion from the samples prepared in pellets. The spectral data were processed and analyzed by a specially designed algorithm. A coefficient of extractability was calculated for each of the investigated macronutrients in the range 34–76%, showing a good correlation with the corresponding elemental concentrations leached into the water infusion, determined by Atomic Absorption Spectroscopy. The obtained results demonstrated the feasibility of our approach for the rapid analysis of extractable macronutrients present in yerba mate leaves.
Net Zero Dairy Farming—Advancing Climate Goals with Big Data and Artificial Intelligence
Authors: Neethirajan Suresh
Published: January 2024

This paper explores the transformative potential of Big Data and Artificial Intelligence (AI) in propelling the dairy industry toward net zero emissions, a critical objective in the global fight against climate change. Employing the Canadian dairy sector as a case study, the study extrapolates its findings to demonstrate the global applicability of these technologies in enhancing environmental sustainability across the agricultural spectrum. We begin by delineating the environmental challenges confronting the dairy industry worldwide, with an emphasis on greenhouse gas (GHG) emissions, including methane from enteric fermentation and nitrous oxide from manure management. The pressing need for innovative approaches in light of the accelerating climate crisis forms the crux of our argument. Our analysis delves into the role of Big Data and AI in revolutionizing emission management in dairy farming. This includes applications in optimizing feed efficiency, refining manure management, and improving energy utilization. Technological solutions such as predictive analytics for feed optimization, AI in herd health management, and sensor networks for real-time monitoring are thoroughly examined. Crucially, the paper addresses the wider implications of integrating these technologies in dairy farming. We discuss the development of benchmarking standards for emissions, the importance of data privacy, and the essential role of policy in promoting sustainable practices. These aspects are vital in supporting the adoption of technology, ensuring ethical use, and aligning with international climate commitments. Concluding, our comprehensive study not only suggests a pathway for the dairy industry towards environmental sustainability but also provides insights into the role of digital technologies in broader agricultural practices, aligning with global environmental sustainability efforts.
The Interplay between Mycobacterium tuberculosis and Human Microbiome
Authors: Nguyen Michelle , Ahn Phillip , Dawi John , Gargaloyan Areg , Kiriaki Anthony , Shou Tiffany , Wu Kevin , Yazdan Kian , Venketaraman Vishwanath
Published: January 2024

Tuberculosis (TB), a respiratory disease caused by Mycobacterium tuberculosis (Mtb), is a significant cause of mortality worldwide. The lung, a breeding ground for Mtb, was once thought to be a sterile environment, but has now been found to host its own profile of microbes. These microbes are critical in the development of the host immune system and can produce metabolites that aid in host defense against various pathogens. Mtb infection as well as antibiotics can shift the microbial profile, causing dysbiosis and dampening the host immune response. Additionally, increasing cases of drug resistant TB have impacted the success rates of the traditional therapies of isoniazid, rifampin, pyrazinamide, and ethambutol. Recent years have produced tremendous research into the human microbiome and its role in contributing to or attenuating disease processes. Potential treatments aimed at altering the gut-lung bacterial axis may offer promising results against drug resistant TB and help mitigate the effects of TB.
Study of the Industrial Application of Diamond-Like Carbon Coatings Deposited on Advanced Tool Steels
Authors: Barba Eneko , Claver Adrián , Montalà Francesc , Palacio José F. , Luis-Pérez Carmelo J. , Sala Neus , Colominas Carles , García José Antonio
Published: January 2024

The utilization of diamond-like carbon (DLC) coatings has emerged as a promising strategy to enhance the performance, durability, and functionality of industrial tools and components. Recognized for their exceptional attributes such as hardness, wear resistance, low friction, and biocompatibility, DLC coatings have achieved widespread acclaim for their potential to improve the capabilities of tool steels for different applications. This present study shows a comprehensive investigation into the application of DLC coatings on a diverse range of tool steel substrates, encompassing 1.2379, 1.2358, Caldie, K340, HWS, and Vanadis 4. The main aim is to show the effects of DLC coatings on these substrates and to provide an in-depth analysis of their properties during forming processes. Furthermore, this study explores the practical utilization of DLC-coated tool steel components, with a particular focus on their role in cold forming dies. Additionally, the study reviews the application of duplex treatments involving plasma nitriding to enhance DLC coating performance. To sum up, this study pursues a threefold objective: to investigate DLC coatings’ performance on diverse tool steel substrates; to assess the potential for improvement through nitriding; and to evaluate the behavior of DLC coatings in the cold stamping of S235 steel, which is of great technological and industrial interest to the cold forging sector.
The Influence of Angle of Attack on the Icing Distribution Characteristics of DU97 Blade Airfoil Surface for Wind Turbines
Authors: Wang Chuanxi , Lin Weirong , Lin Xuefeng , Wu Tong , Meng Zhe , Cai Anmin , Xu Zhi , Li Yan , Feng Fang
Published: January 2024

This study explores the influence of angle of attack (AOA) on the icing distribution characteristics of asymmetric blade airfoil (DU97) surfaces for wind turbines under icing conditions by numerical simulation. The findings demonstrate a consistence between the simulated ice shapes and experimental data. The ice thickness distribution on the lower surface of the leading edge exhibits a trend of first rising and then declining along the chord direction while showing a gradually decreasing trend on the upper surface. The ice distribution range on the upper surface of the trailing edge is broader than that on the lower surface. The peak ice thickness at the trailing edge rises significantly as AOA increases from 5° to 10°, and at the leading edge raises dramatically at droplet sizes of 30–40 μm and wind speeds of 5–10 m/s. The peak ice thickness is more significantly influenced by AOA than by ambient temperature due to the combined effect of airflow characteristics induced by AOA and latent heat (phase change) and sensible heat (thermal convection and thermal radiation) caused by ambient temperature. The findings offer valuable insights into the flow and heat transfer physics, and can operate as references for wind turbine anti/de-icing technology.
Effects of Surface Size and Shape of Evaporation Area on SiC Single-Crystal Growth Using the PVT Method
Authors: Zhang Yu , Wen Xin , Chen Nuofu , Zhang Fang , Chen Jikun , Hu Wenrui
Published: January 2024

Silicon carbide (SiC) polycrystalline powder. As the raw material for SiC single-crystal growth through the physical vapor transport (PVT) method, its surface size and shape have a great influence on growth of crystal. The surface size and shape of the evaporation area filled with polycrystalline powder were investigated by numerical simulation in this study. Firstly, the temperature distribution and deposition rate distribution for the PVT system were calculated by global numerical simulation, and the optimal ratio of polycrystalline powder surface diameter to seed crystal diameter was determined to be 1.6. Secondly, the surface of the evaporation area filled with polycrystalline powder was covered by a graphite ring and a graphite disc, respectively, to change its surface shape. The results show that adjusting the surface size and shape of the evaporation area filled with polycrystalline powder is an effective method to control the growth rate, growth stability, and growth surface shape of the single crystal. Finally, the result obtained by selecting appropriate covered structures for actual growth indicates that this process can act as a reference for improving the quality of single crystals.
Study of the Long-Range Exchange Coupling in Nd-Fe-B/Ti/Fe Multilayered Structure
Authors: Yazdani Saeed , Phillips Jared , Mosey Aaron , Bsaibes Thomas , Decca Ricardo , Cheng Ruihua
Published: January 2024

The exchange coupling between two ferromagnetic thin films, one with magnetically hard and the other with soft phases, separated by a thin non-magnetic layer, is studied. Nd-Fe-B/Ti/Fe thin film heterostructures were fabricated using DC magnetron sputtering on Si substrates, which were heated in situ at 650 °C using a house-built vacuum-compatible heater. The effect of the thickness of the Ti buffer layer and the annealing temperature on the formation of various phases of Nd-Fe-B was investigated. The effect of the thickness of the non-magnetic Ti spacer layer on the exchange coupling strength between the hard phase Nd-Fe-B ferromagnetic thin layer and the soft phase transition metal Fe layer was experimentally investigated. Hysteresis loops of multilayer thin films indicate an antiferromagnetic coupling was observed when the thickness of the spacer layer was 2 nm. This is within the range of an antiferromagnetic coupling calculation based on RKKY theory predictions.
Paclitaxel as HIPEC-Drug after Surgical Cytoreduction for Ovarian Peritoneal Metastases: A Randomized Phase III Clinical Trial (HIPECOVA)
Authors: Villarejo Campos Pedro , Sánchez García Susana , Amo-Salas Mariano , García Santos Esther , López de la Manzanara Carlos , Alberca Ana , Padilla-Valverde David , Redondo Calvo Francisco Javier , Martín Jesús
Published: January 2024

Multidisciplinary strategies have transformed the management of advanced ovarian cancer. We aimed to evaluate the effectiveness of paclitaxel in hyperthermic intraperitoneal chemotherapy (HIPEC) following surgical cytoreduction for ovarian peritoneal metastases in a randomized phase III trial conducted between August 2012 and December 2019. Seventy-six patients were randomized to either the HIPEC or no HIPEC group. Although median values for the primary endpoints (recurrence-free survival (RFS) and overall survival (OS)) revealed superior outcomes for the HIPEC (RFS: 23 months, OS: 48 months) over the control group (RFS: 19 months, OS: 46 months), these differences were not statistically significant (p = 0.22 and p = 0.579). Notably, the HIPEC group demonstrated significantly higher 5-year OS and 3-year RFS rates (47.2% and 47.5%) compared to patients without HIPEC (34.5% and 21.3%). Stratification according to Peritoneal Surface Disease Severity Score (PSDSS) showed improved OS and RFS for patients with lower PSDSS (I–II) in the HIPEC-treated group (p = 0.033 and p = 0.042, respectively). The Clavien–Dindo classification of adverse event grades revealed no significant differences between HIPEC and controls (p = 0.482). While overall results were not statistically significant, our long-term follow-up emphasized the potential benefit of HIPEC-associated cytoreduction with paclitaxel, particularly in selected ovarian cancer patients with lower PSDSS indices.
Discordance of Biomarker Expression Profile between Primary Breast Cancer and Synchronous Axillary Lymph Node Metastasis in Preoperative Core Needle Biopsy
Authors: Marletta Stefano , Giorlandino Alexandra , Cavallo Enrico , Dello Spedale Venti Michele , Leone Giorgia , Tranchina Maria Grazia , Gullotti Lucia , Bonanno Claudia Lucia , Spoto Graziana , Falzone Giusi , Tornabene Irene , Trovato Carmelina , Baron Marco Maria , Di Mauro Giuseppe , Falsaperna Lucia , Angelico Giuseppe , Pafumi Sarah , Rizzo Antonio
Published: January 2024

Background: Breast cancer (BC) is a heterogeneous disease made up of clones with different metastatic potential. Intratumoral heterogeneity may cause metastases to show divergent biomarker expression, potentially affecting chemotherapy response. Methods: We investigated the immunohistochemical (IHC) and FISH profile of estrogen receptors (ER), progesterone (PR) receptors, Ki67, and HER2 in a series of BC-matched primary tumors (PTs) and axillary lymph node (ALN) metastases in pre-operative core needle biopsies (CNBs). Phenotypical findings were correlated to morphological features and their clinical implications. Results: Divergent expression between PTs and ALNs was found in 10% of the tumors, often involving multiple biomarkers (12/31, 39%). Most (52%) displayed significant differences in ER and PR staining. HER2 divergences were observed in almost three-quarters of the cases (23/31, 74%), with five (16%) switching from negativity to overexpression/amplification in ALNs. Roughly 90% of disparities reflected significant morphological differences between PTs and ALN metastases. Less than half of the discrepancies (12/31, 39%) modified pre/post-operative treatment options. Conclusions: We observed relevant discrepancies in biomarker expression between PTs and metastatic ALNs in a noteworthy proportion (10%) of preoperative BC CNBs, which were often able to influence therapies. Hence, our data suggest routine preoperative assessment of biomarkers in both PTs and ALNs in cases showing significant morphological differences.
Spatial Position and Anatomical Characteristics Associated with Impacted Third Molars Using a Map-Reading Strategy on Cone-Beam Computed Tomography Scans: A Retrospective Analysis
Authors: Lima Djalma Maciel de , Estrela Cyntia Rodrigues de Araújo , Bernardes Cristiane Martins Rodrigues , Estrela Lucas Rodrigues de Araújo , Bueno Mike Reis , Estrela Carlos
Published: January 2024

(1) Background: This study assessed the spatial position and anatomical features associated with impacted third molars through a map-reading strategy employing cone-beam computed tomography (CBCT). (2) Methods: The positioning of impacted third molars on CBCT was assessed using Winter’s and Pell and Gregory’s classifications. External root resorption in mandibular second molars was categorized according to Herman’s classification. Additionally, the relationship between the mandibular third molar root apex and the mandibular canal was examined. Comparative statistical analysis was conducted using Fisher’s exact test, with a significance level considered as 5%. (3) Results: The results indicated that, based on Winter’s classification, 48.06 % of impacted teeth were positioned mesioangularly. Employing Pell and Gregory’s classification, 43.22% of the impacted molars fell into positions B and C, with 54.2% classified as Class II. A notable 69.7% of teeth exhibited no contact between the root apex and the mandibular canal, and external root resorption in the distal aspect of the second molar was absent in 88.7% of cases. (4) Conclusions: Utilizing the map-reading strategy with CBCT scans to assess the anatomical positions and characteristics of impacted third molars enhances professional confidence and sets a standard for quality and safety in the surgical procedure for patients.
Artificial Intelligence in Transcatheter Aortic Valve Replacement: Its Current Role and Ongoing Challenges
Authors: Benjamin Mina M. , Rabbat Mark G.
Published: January 2024

Transcatheter aortic valve replacement (TAVR) has emerged as a viable alternative to surgical aortic valve replacement, as accumulating clinical evidence has demonstrated its safety and efficacy. TAVR indications have expanded beyond high-risk or inoperable patients to include intermediate and low-risk patients with severe aortic stenosis. Artificial intelligence (AI) is revolutionizing the field of cardiology, aiding in the interpretation of medical imaging and developing risk models for at-risk individuals and those with cardiac disease. This article explores the growing role of AI in TAVR procedures and assesses its potential impact, with particular focus on its ability to improve patient selection, procedural planning, post-implantation monitoring and contribute to optimized patient outcomes. In addition, current challenges and future directions in AI implementation are highlighted.
Assessment of the Performance of Lactate Dehydrogenase-Based Rapid Diagnostic Test for Malaria in Djibouti in 2022–2023
Authors: Abdi Moussa Rahma , Papa Mze Nasserdine , Yonis Arreh Houssein , Abdillahi Hamoud Aicha , Mohamed Alaleh Kahiya , Mohamed Aden Fatouma , Yonis Omar Abdoul-Razak , Osman Abdi Warsama , Kayad Guelleh Samatar , Ahmed Abdi Abdoul-Ilah , Basco Leonardo K. , Abdi Khaireh Bouh , Bogreau Hervé
Published: January 2024

Until 2020, Djiboutian health authorities relied on histidine-rich protein-2 (HRP2)-based rapid diagnostic tests (RDTs) to establish the diagnosis of Plasmodium falciparum. The rapid spread of P. falciparum histidine-rich protein-2 and -3 (pfhrp2/3) gene-deleted parasite strains in Djibouti has led the authorities to switch from HRP2-based RDTs to lactate dehydrogenase (LDH)-based RDTs targeting the plasmodial lactate dehydrogenase (pLDH) specific for P. falciparum and P. vivax (RapiGEN BIOCREDIT Malaria Ag Pf/Pv pLDH/pLDH) in 2021. This study was conducted with the primary objective of evaluating the diagnostic performance of this alternative RDT. Operational constraints related, in particular, to the implementation of this RDT during the COVID-19 pandemic were also considered. The performance of BIOCREDIT Malaria Ag Pf/Pv (pLDH/pLDH) RDT was also compared to our previously published data on the performance of two HRP2-based RDTs deployed in Djibouti in 2018–2020. The diagnosis of 350 febrile patients with suspected malaria in Djibouti city was established using two batches of RapiGEN BIOCREDIT Malaria Ag Pf/Pv (pLDH/pLDH) RDT over a two-year period (2022 and 2023) and confirmed by real-time quantitative polymerase chain reaction. The sensitivity and specificity for the detection of P. falciparum were 88.2% and 100%, respectively. For P. vivax, the sensitivity was 86.7% and the specificity was 100%. Re-training and closer supervision of the technicians between 2022 and 2023 have led to an increased sensitivity to detect P. falciparum (69.8% in 2022 versus 88.2% in 2023; p < 0.01). The receiver operating characteristic curve analysis highlighted a better performance in the diagnosis of P. falciparum with pLDH-based RDTs compared with previous HRP2-based RDTs. In Djibouti, where pfhrp2-deleted strains are rapidly gaining ground, LDH-based RDTs seem to be more suitable for diagnosing P. falciparum than HRP2-based RDTs. Awareness-raising and training for technical staff have also been beneficial.
Impact of Enhanced Recovery after Surgery® Protocol Compliance on Length of Stay, Bowel Recovery and Complications after Radical Cystectomy
Authors: Grilo Nuno , Crettenand François , Bohner Perrine , Rodrigues Dias Sonia Cristina , Cerantola Yannick , Lucca Ilaria
Published: January 2024

Background: Despite existing standardized surgical techniques and the development of new perioperative care protocols, radical cystectomy (RC) morbidity remains a serious challenge for urologists. Postoperative ileus (POI) is one of the most common postoperative complications, often leading to a longer length of stay (LOS). The aim of our study was to assess the impact of compliance to the Enhanced Recovery After Surgery (ERAS®) protocol on bowel recovery, 30-day complications and LOS after RC for bladder cancer (BC). Methods: Data from consecutive patients undergoing RC for BC within an ERAS® dedicated protocol were analyzed. Exclusion criteria were urinary diversion other than ileal conduit and palliative RC. Patients were divided into two groups according to their compliance (A: low-compliance and B: high-compliance). ERAS® compliance was extracted from the ERAS® Interactive Audit System (EIAS) database. Postoperative complications were prospectively recorded by a dedicated study nurse 30 days after RC. POI was defined as the placement of a nasogastric tube. Logistic regression analysis was used to identify predictors of 30-day complications and POI. Results: After considering the exclusion criteria, 108 patients were included for the final analysis. The median global compliance to the ERAS® protocol was 61%. A total of 78 (72%) patients had a compliance <65% (group A), while the remaining 30 (28%) had a compliance >65% (group B). No significant differences were found among the two groups regarding the 30-day complication rate (86% in group A versus 73% in group B, p = 0.82) and LOS (14 days in group A versus 15 days in group B, p = 0.82). The time to stool was significantly shorter in group B (4 days versus 6 days, p = 0.02), and the time to tolerate solid food was slightly faster in group B but not significant (8 versus 7 days, p = 0.23). The POI rate was significantly lower in patients with a higher ERAS® compliance (20% versus 46%, p = 0.01). A multivariate analysis showed that ERAS® compliance was not significantly associated with 30-day total complications. However, a lower compliance to the ERAS® protocol and age > 75 years were significant independent predictors of POI. Conclusions: Our study provides further evidence to support the beneficial effect of the ERAS® protocol in patients undergoing RC, particularly in terms of facilitating a faster recovery of bowel function and preventing POI. Future research should focus on investigating novel approaches and interventions to improve compliance with the ERAS® protocol. This may involve patient education, multidisciplinary teamwork, and continuous quality improvement initiatives.
Non-Invasive Serum Biomarkers for the Diagnosis of Cirrhosis in Patients with Autoimmune Hepatitis (AIH) and AIH-Primary Biliary Cholangitis Overlap Syndrome (AIH-PBC): Red Cell Distribution Width to Platelet Ratio (RPR) Yielded the Most Promising Result
Authors: Nawalerspanya Siwanon , Tantipisit Jarukit , Assawasuwannakit Suraphon , Kaewdech Apichat , Chamroonkul Naichaya , Sripongpun Pimsiri
Published: January 2024

Several serum biomarkers for fibrosis assessment have been proposed in various liver diseases, but in autoimmune hepatitis (AIH) or overlap with primary biliary cholangitis (PBC; AIH-PBC) patients, the data are scarce. This retrospective cross-sectional study was conducted to validate six non-invasive biomarkers in the diagnosis of cirrhosis (F4 fibrosis) in such patients. We included adult patients diagnosed with AIH or AIH-PBC overlap syndrome who underwent a liver biopsy between 2011 and 2021. Laboratory data were collected to calculate the following scores: red cell distribution width to platelet ratio (RPR), aspartate aminotransferase/platelet ratio index (APRI), Fibrosis-4 index (FIB-4), aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio (AAR), neutrophil-to-lymphocyte ratio (NLR), and lymphocyte-to-platelet ratio (LPR). A total of 139 patients were eligible (111 AIH and 28 AIH-PBC). The prevalence of cirrhosis was 35.3% (36% in AIH and 32.1% in AIH-PBC). The AUROCs of the RPR, FIB-4, APRI, AAR, LPR, and NLR in all patients were 0.742, 0.724, 0.650, 0.640, 0.609, and 0.585, respectively. RPR was significantly superior to APRI, NLR, and LPR. Moreover, RPR showed the highest AUROC (0.915) in the overlap AIH-PBC subgroup. In conclusion, RPR yielded the highest diagnostic accuracy to predict cirrhosis in AIH and AIH-PBC overlap syndrome patients, while FIB-4 was considerably optimal.
A Study of the Effects of a Structured Daily Physical Activity Intervention in Schools in Malta
Authors: Attard Charles , Kerr-Cumbo Renzo , Muscat-Inglott Matthew , Darmanin Melanie , Schembri Heathcliff
Published: January 2024

The measurement of daily step counts is a widely adopted and efficacious approach for assessing children’s physical activity levels. With the aim of finding out the effect of daily PA sessions in schools on the total PA levels in terms of steps taken, two (treatment and control) Year Four classrooms (with students aged from eight to nine years old) in three participating schools in Malta participated in this study. A random sample of 45 children across all the treatment and control groups wore pedometers for five continuous school days. Additional data were logged to facilitate data analysis. Statistical analysis was conducted on data from 18 participants, as incomplete data were eliminated. The findings show that a daily physical activity programme was sufficient to make a significant difference in the number of steps taken at school. It also made the difference between Maltese schools being either under par (if not engaged in daily PA at school) or among high-performing nations (if engaged in daily PA at school) in terms of the proportional contribution of steps taken at school to children’s total PA. However, the capacity for school-based activity to exert wider effects on total steps taken throughout the entire day appears to be limited. Reported engagement in additional formal sports activities outside school also had limited effects on steps overall. Finally, a statistical model incorporating sex, daily PA, sports participation, and BMI as exogenous variables accounted only for around a quarter of the variation in average daily pedometer-measured PA, leaving approximately 75% of the variation unexplained. Implications of the findings are discussed, including recommendations for alternative ways of conceptualising and promoting health-related physical activity and exercise.
Academic Motivation of Students Experiencing Person-Environment Misfit in Social Work Educational Settings: The Role of Social Dominance Orientation
Authors: Tesi Alessio , Di Santo Daniela , Aiello Antonio
Published: January 2024

Interweaving social dominance, person-environment fit, and self-determination theories, the present study sought to understand whether the attrition between students’ levels of social dominance orientation and the hierarchy-attenuating function of the social work faculty in which they study may influence students’ academic motivational pathways. A total of 221 undergraduate social work students participated in the study and completed a self-report questionnaire. Participants’ social dominance orientation, person-environment misfit, and academic intrinsic and extrinsic motivation were measured. Results indicated that students’ social dominance orientation was associated with an external rather than an internal regulation of their academic motivation, mediated by their perceived person-environment misfit. For those students who personally support group-based inequalities, exposure to hierarchy-attenuating contexts would lead to regulating their academic behavior toward the pursuit of extrinsic (vs. intrinsic) goals, that is, studying to gain financial benefits and social prestige, in accordance with the pursuit of their beliefs of social dominance.
Modeling and Operating Characteristics of Excitation System for Variable Speed Pumped Storage Unit with Full-Size Converter
Authors: Pan Pengyu , Shi Huabo , Chen Gang , Ding Lijie , Zhang Yuanzhi , Zha Xiaoming
Published: January 2024

The variable speed pumped storage unit with a full-size converter (FSC-VSPSU) can provide fast and flexible regulation capacity for the power grid, assisting the rapid development of the new energy-dominated power systems, and its application is gradually becoming widespread. The excitation system of FSC-VSPSU is crucial for maintaining the motor-port voltage and further supports the stable operation of the entire unit. However, there is currently no research on excitation system modeling, and their essential operating characteristics have not been discussed in detail, which needs further study. With this aim, this paper firstly establishes a detailed transfer function model for FSC-VSPSU, which is then used to study the influence rules of FSC-VSPSU parameters on the operating characteristics. In addition, based on the summarized operating characteristics, the excitation system can be optimized, and its complexity is greatly reduced while ensuring the original performance of the unit. Finally, the results of the simulation can verify the correctness of the established model and the explored operating characteristics.
Identification Method for XRF Spectral Analysis Based on an AGA-BP-Attention Neural Network
Authors: Chang Zeyuan , Zhang Qi , Li Yuanfeng , Xin Xiangjun , Gao Ran , Teng Yun , Rao Lan , Sun Meng
Published: January 2024

X-ray fluorescence (XRF) spectroscopy is a non-destructive differential measurement technique widely utilized in elemental analysis. However, due to its inherent high non-linearity and noise issues, it is challenging for XRF spectral analysis to achieve high levels of accuracy. In response to these challenges, this paper proposes a method for XRF spectral analysis that integrates an adaptive genetic algorithm with a backpropagation neural network, enhanced by an attention mechanism, termed as the AGA-BP-Attention method. By leveraging the robust feature extraction capabilities of the neural network and the ability of the attention mechanism to focus on significant features, spectral features are extracted for elemental identification. The adaptive genetic algorithm is subsequently employed to optimize the parameters of the BP neural network, such as weights and thresholds, which enhances the model’s accuracy and stability. The experimental results demonstrate that, compared to traditional BP neural networks, the AGA-BP-Attention network can more effectively address the non-linearity and noise issues of XRF spectral signals. In XRF spectral analysis of air pollutant samples, it achieved superior prediction accuracy, effectively suppressing the impact of background noise on spectral element recognition.
Driving Efficiency and Competitiveness: Trends and Innovations in ERP Systems for the Wood Industry
Authors: Vukman Karla , Klarić Kristina , Greger Krešimir , Perić Ivana
Published: January 2024

Enterprise Resource Planning (ERP) systems offer various functionalities to support an organization’s core functions. However, many anticipated benefits often need to materialize due to business context changes and users’ high expectations. Continuous adaptation and improvement are necessary to address user disappointments. This research focuses on ERP systems, exploring key factors influencing the success of their implementation. Recognizing challenges in ERP system implementation, this study provides a comprehensive literature review, identifying essential and contemporary Critical Success Factors (CSFs) influenced by technological advancements. Addressing challenges specific to the wood industry, this research introduces additional industry-adapted CSFs, including industry adaptability, integration with production machinery, effective warehouse management, and supply chain tracking. Furthermore, this paper emphasizes the need for continuous adaptation and improvement of ERP systems, especially in light of current trends and technological achievements. This study recommends a holistic approach, considering traditional or essential CSFs while adapting to new trends. Critical success factors in ERP implementation in the next decade involve considering cloud technology, artificial intelligence and machine learning, data security, mobile access, IoT integration, user experience, and training. The main objective of this paper is to identify the latest CSFs in ERP implementation. This research highlights essential success factors in ERP implementation, and contemporary trends in ERP implementation with a particular focus on the specifics of wood industry. While organizations should aim to maximize the potential of ERP systems, they should also acknowledge the crucial role played by human intervention in the effective and responsible implementation of artificial intelligence.