bluuebunny/crossref_metadata_2025_split huggingface dataset:
Real-time ex vivo monitoring of NK cell migration toward obesity-associated oesophageal adenocarcinoma following modulation of CX3CR1
Authors: Mylod Eimear , O’Connell Fiona , Donlon Noel E. , Davern Maria , Marion Caroline , Butler Christine , Reynolds John V. , Lysaght Joanne , Conroy Melissa J. 
Published: February 2024

AbstractOesophagogastric adenocarcinomas (OAC) are poor prognosis, obesity-associated cancers which may benefit from natural killer (NK) cell-based immunotherapies. Cellular immunotherapies encounter two key challenges to their success in OAC, namely recruitment to extratumoural tissues such as the omentum at the expense of the tumour and an immunosuppressive tumour microenvironment (TME) which can hamper NK cell function. Herein, we examined approaches to overcome the detrimental impact of obesity on NK cells and NK cell-based immunotherapies. We have demonstrated that NK cells migrate preferentially to the chemotactic signals of OAC patient-derived omentum over tumour in an ex vivo model of immune cell migration. We have identified CX3CR1 modulation and/or tumour chemokine profile remodelling as approaches to skew NK cell migration towards tumour. We also report targetable immunosuppressive facets of the obese OAC TME which dampen NK cell function, in particular cytotoxic capabilities. These data provide insights into approaches to therapeutically overcome key challenges presented by obesity and will inform superior design of NK cell-based immunotherapies for OAC.
Targeting autophagy as a therapeutic strategy in pediatric acute lymphoblastic leukemia
Authors: Bwanika Henri Colyn , Leo Isabelle Rose , Struyf Nona , Talanti Asimina , Aswad Luay , Konnur Aishwarya , Björklund Ann-Charlotte , Heyman Mats , Rassidakis Georgios , Erkers Tom , Seashore-Ludlow Brinton , Jafari Rozbeh , Pokrovskaja Tamm Katja 
Published: February 2024

AbstractAutophagy is activated in response to a variety of stress conditions including anti-cancer therapies, and tumors cells often depend on autophagy for survival. In this study, we have evaluated inhibition of autophagy as therapeutic strategy in acute lymphoblastic leukemia (ALL) in children, both as a single treatment and in combination with glucocorticoid (GC) Dexamethasone (Dexa). Analysis of proteomics and RNA-seq of ALL cell lines and primary samples identified an upregulation of Vps34 and ATG14 proteins and autophagy and lysosomal pathway enrichment in a genetic subgroup with a recurrent t(12;21) translocation. Cells from this sugbroup were also significantly more sensitive to the selective autophagy or lysosomal inhibitors than cells with other genetic rearrangements. Further, combination of Dexa with either lysosomal or autophagy inhibitors was either synergistic or additive in killing leukemic cells across various genetic and lineage backgrounds, for both cell lines and primary samples, as assessed using viability assays and SynergyFinder as well as apoptotic caspase 3/7-based live-cell assays. Our data demonstrate that targeting autophagy represents a promising strategy for the treatment of pediatric ALL, both as a selective modality for the t(12;21) pre-B-ALL subgroup, and in combination treatments to sensitize to GC-induced cytotoxicity.
ATP6AP1 as a potential prognostic biomarker in CRC by comprehensive analysis and verification
Authors: Zhang Shijie , Wang Yan , Zhang Xiaodong , Wang Min , Wu Hao , Tao Yuwen , Fan Wentao , Liu Li , Wang Bangting , Gao Wenqing 
Published: February 2024

AbstractThe role of ATP6AP1 in colorectal cancer (CRC) remains elusive despite its observed upregulation in pan-cancer. Therefore, the current study aimed to assess the clinical significance of ATP6AP1 and its relationship with the immune infiltration in CRC. Transcriptome data of CRC were obtained from The Cancer Genome Atlas (TCGA) database and analyzed using the combination of R packages and tumor-related databases, including TIMER2, TISIDB, cBioPortal, and MethSurv. The tissue arrays and immunohistochemical staining were performed to verify the expression and clinical characteristics of ATP6AP1. The results revealed that ATP6AP1 expression was significantly elevated in CRC and associated with poor clinicopathological characteristics and prognosis. Furthermore, the analysis demonstrated ATP6AP1 expression was correlated with the infiltration of immune cells and cancer-associated fibroblasts in the microenvironment of CRC. Moreover, ATP6AP1 was found to be linked to various immune checkpoints and chemokines, with enrichment of cytoplasmic vesicle lumen, endopeptidase regulator activity, and endopeptidase inhibitor activity observed in the high ATP6AP1 expressional group. In conclusion, the findings of this study suggest that ATP6AP1 upregulation may serve as a biomarker for poor diagnosis in CRC and offer a potential target for immunotherapy in CRC.
Non-magnetic four-port electronic circulators based on $$90^\circ $$ non-reciprocal phase-shifters
Authors: Regev Dror , Regev Shaked , Shilo Shimi , Ezri Doron , Ginzberg Nimrod , Cohen Emanuel 
Published: February 2024

AbstractThis paper presents a family of four-port electronic circulators adhering to a new topology symmetry that enables linear, low-loss transistor-based circuit implementations. The underlying principle of operation employs a property of the$$90^\circ $$90∘non-reciprocal phase shifter (NRPS) derived in this article. Under quadrature excitation, the NRPS transfers or reflects exciting signals depending on their respective phase lead. The fundamental topology consists of two back-to-back quadrature hybrid couplers with a$$90^\circ $$90∘NRPS connected in parallel over the line of symmetry, interrupting the circuit’s reciprocity to achieve circular propagation by bypassing or reflecting at the NRPS but not through. We break down the circuit into three fundamental four-port sub-circuits. The transfer function of the cascaded sub-circuits enables an analysis with specific hybrid couplers. It also allows a synthesis of other four-port passive sub-circuits that, with an NRPS, achieve a four-port circulator transfer function by solving a matrix equation. Some of the mathematical solutions have circuit realizations, which are adjusted quadrature hybrid structures that differ from each other by the characteristic impedance of their arms. Two familiar solutions, including the standard quadrature hybrid and a modified design with equal$$Z_0$$Z0,$$\lambda /4$$λ/4arms, are simulated utilizing lossless lumped element arms and a 4-Path, 65-nm NMOS$$90^\circ $$90∘NRPS. The simulation results verify the theoretical analysis and enable a comparison between the performance of the two circuit solutions around 1 GHz. The four-port circulator with equal arms is implemented on a PCB and measured, yielding better than 1.5 dB insertion loss between the circulator ports, over 17 dB port-to-port reverse isolation, and better than 20 dBr port matching around 1 GHz.
Efficient content caching for 5G assisted vehicular networks
Authors: Ahmed Faareh , Alsamani Badr , Alkhathami Mohammed , Alsadie Deafallah , Alosaimi Norah , Alenzi Badriya , Nkenyereye Lewis 
Published: February 2024

AbstractTraffic congestion is one of the major challenges faced by daily commuters in smart cities. An autonomous transportation system with a 5 G-based Cellular Vehicle-to-Everything (C-V2X) communication system is the solution to meet the traffic challenges faced in smart cities. Vehicular networks provide wireless connectivity to enable a large number of connected vehicle applications. Vehicular networks allow vehicles to share their emergency and infotainment traffic by following vehicle-to-vehicle (V2V) or by using vehicle-to-infrastructure (V2I) communication. The infrastructure of vehicular networks mainly comprises multiple Road Side Units (RSUs). Fog computing nodes are placed adjacent to these RSUs to provide quick access to vehicles. For infotainment traffic, vehicles intend to download their required content from the content provider. Caching the same contents from the nearby fog computing node significantly reduces delay with improved quality of service. As there are millions of contents with varying sizes, caching all demanded contents on these fog nodes is not possible due to their limited caching capacity. In this work, we propose an improved content caching scheme for fog nodes to satisfy vehicles and content providers for fair content placement. The proposed algorithm is based on a modified Gale–Shapley technique that considers factors such as content popularity, vehicle connectivity, and quality of the communication channel to optimize the content caching process. Simulation results show that the proposed technique caches a higher number of popular contents with lower downloading time.
Circadian characteristics of term and preterm labors
Authors: Moškon Miha , Kovač Urša , Raspor Dall’Olio Lucija , Geršak Ksenija , Kavšek Gorazd , Bojc Šmid Eva , Trojner Bregar Andreja , Rozman Damjana 
Published: February 2024

AbstractThe labor is a physiological event considered to have its own circadian (diurnal) rhythm, but some of the data remain conflicting, especially for preterm births. In this retrospective study, we analyzed the circadian trends of labor onset times in the Slovenian birth cohort from 1990 to 2018 with over 550,000 cases of singleton births. The number of term and preterm labor onsets was calculated for each hour in a day and circadian trends were evaluated for each of the study groups by modeling with a generalized Poisson distribution linked with the cosinor regression model using logarithmic link function. The induced labors were taken as the control group since the timing of labor depends mostly on the working schedule of personnel and not on the intrinsic rhythmic characteristics. For induced labors, the main peak in the number of labor cases was observed in the late morning hours (around 10 AM) for all gestational ages. The prominence of this peak becomes smaller in spontaneous premature labors with gradually disrupting rhythmicity in very preterm and extremely preterm cases. Labors starting with spontaneous contractions peak between 6 and 7 AM and lose the rhythmicity at 35 weeks of gestation while labors starting with a spontaneous rupture of membranes peak at 1 AM and lose the rhythmicity at 31 weeks of gestation, suggesting differences in underlying mechanisms. According to our knowledge, this is the first study that shows differences of circadian trends between different types of spontaneous labors, i.e., labors initiated with contraction and labors initiated with a spontaneous rupture of membranes. Moreover, the obtained results represent evidence of gradual disruption of rhythmicity from mild to extreme prematurity.
Quercetin-crosslinked chitosan nanoparticles: a potential treatment for allergic rhinitis
Authors: Mu Dehong , Zhou Li , Shi Lingyu , Liu Ting , Guo Ying , Chen Hao , Luo Hongping , Ma Junhao , Zhang Hui , Xiong Peizheng , Tian Li 
Published: February 2024

AbstractAllergic rhinitis (AR) remains a major health problem worldwide. Compared with traditional oral drugs, nasal administration avoids first-pass metabolism and achieve faster and more effective efficacy. In this study, we used the ion crosslinking method to prepare quercetin–chitosan nasal adaptive nanomedicine (QCS) delivery system and evaluated in the treatment of allergic rhinitis mice models. The obtained positively charged nanoparticles with a particle size of 229.2 ± 0.2 nm have excellent characteristics in encapsulation efficiency (79.604%), drug loading rate (14.068%), drug release (673.068 μg) and stability(> 7 days). Excitingly, QCS treatment significantly reduced the number of sneezing and nasal rubbing events in AR mice, while reducing the levels of inflammatory factors such as immunoglobulin E (IgE), interleukin (IL)-17, tumor necrosis factor (TNF)-α, and (IL)-6 to alleviate AR symptoms. Hematoxylin–eosin (HE) staining also showed the damaged nasal mucosa was improved. These experimental results suggest that QCS can effectively suppress allergic inflammation in a mouse model and hold promise as a therapeutic option for allergic rhinitis.
The complete plastome sequences of invasive weed Parthenium hysterophorus: genome organization, evolutionary significance, structural features, and comparative analysis
Authors: Lubna  , Asaf Sajjad , Jan Rahmatullah , Asif Saleem , Bilal Saqib , Khan Abdul Latif , Al-Rawahi Ahmed N. , Kim Kyung-Min , AL-Harrasi Ahmed 
Published: February 2024

AbstractParthenium hysterophorus, a globally widespread weed, poses a significant threat to agricultural ecosystems due to its invasive nature. We investigated the chloroplast genome of P. hysterophorus in this study. Our analysis revealed that the chloroplast genome of P. hysterophorus spans a length of 151,881 base pairs (bp). It exhibits typical quadripartite structure commonly found in chloroplast genomes, including inverted repeat regions (IR) of 25,085 bp, a small single copy (SSC) region of 18,052 bp, and a large single copy (LSC) region of 83,588 bp. A total of 129 unique genes were identified in P. hysterophorus chloroplast genomes, including 85 protein-coding genes, 36 tRNAs, and eight rRNAs genes. Comparative analysis of the P. hysterophorus plastome with those of related species from the tribe Heliantheae revealed both conserved structures and intriguing variations. While many structural elements were shared among the species, we identified a rearrangement in the large single-copy region of P. hysterophorus. Moreover, our study highlighted notable gene divergence in several specific genes, namely matK, ndhF, clpP, rps16, ndhA, rps3, and ndhD. Phylogenetic analysis based on the 72 shared genes placed P. hysterophorus in a distinct clade alongside another species, P. argentatum. Additionally, the estimated divergence time between the Parthenium genus and Helianthus (sunflowers) was approximately 15.1 million years ago (Mya). These findings provide valuable insights into the evolutionary history and genetic relationships of P. hysterophorus, shedding light on its divergence and adaptation over time.
Antigenicity and immunogenicity of different morphological forms of Borrelia burgdorferi sensu lato spirochetes
Authors: Sloupenska Kristyna , Koubkova Barbora , Horak Pavel , Dolezilkova Jana , Hutyrova Beata , Racansky Mojmir , Miklusova Martina , Mares Jan , Raska Milan , Krupka Michal 
Published: February 2024

AbstractBorrelia burgdorferi sensu lato is a species complex of pleomorphic spirochetes, including species that cause Lyme disease (LD) in humans. In addition to classic spiral forms, these bacteria are capable of creating morphological forms referred to as round bodies and aggregates. The subject of discussion is their possible contribution to the persistence of infection or post-infection symptoms in LD. This study investigates the immunological properties of these forms by monitoring reactivity with early (n = 30) and late stage (n = 30) LD patient sera and evaluating the immune response induced by vaccination of mice. In patient sera, we found a quantitative difference in reactivity with individual morphotypes, when aggregates were recognized most intensively, but the difference was statistically significant in only half of the tested strains. In post-vaccination mouse sera, we observed a statistically significant higher reactivity with antigens p83 and p25 (OspC) in mice vaccinated with aggregates compared to mice vaccinated with spiral forms. The importance of the particulate nature of the antigen for the induction of a Th1-directed response has also been demonstrated. In any of morphological forms, the possibility of inducing antibodies cross-reacting with human nuclear and myositis specific/associated autoantigens was not confirmed by vaccination of mice.
Impact of the diet in the gut microbiota after an inter-species microbial transplantation in fish
Authors: Ruiz Alberto , Gisbert Enric , Andree Karl B. 
Published: February 2024

AbstractInter-species microbial transplantations offer the possibility of transferring species-specific microbes and their associated functionality. As a conceptual approach, an intestinal microbiota transplant (IMT) between two marine carnivorous fish species that thrive in different environmental conditions was conducted: from donor Atlantic salmon (Salmo salar) to recipient gilthead seabream (Sparus aurata), after obliterating its basal microbiota with an antibiotic treatment. To confirm that the gut microbiota was able to recover after antibiotics without the influence of the diet, a group of gilthead seabream not submitted to the IMT was kept fasted as an internal control. To assess the effect of the diet after the IMT, two groups of gilthead seabream were respectively fed with their typical diet and with Atlantic salmon diet. At 36 days post-IMT, the gut of the individuals fed with their typical diet was dominated by the feed-associated bacteria, while those fed with the salmon diet had developed a unique microbiota from the convergence of the diet, donor, and recipient microbiota. These results suggested that an intestinal microbiota transplantation may be effective if the basal microbiota from the gut is first cleared and a targeted dietary modification is provided to maintain and enrich the novel bacteria species over time.
Multi-omics resources for the Australian southern stuttering frog (Mixophyes australis) reveal assorted antimicrobial peptides
Authors: Tang Simon , Peel Emma , Belov Katherine , Hogg Carolyn J. , Farquharson Katherine A. 
Published: February 2024

AbstractThe number of genome-level resources for non-model species continues to rapidly expand. However, frog species remain underrepresented, with up to 90% of frog genera having no genomic or transcriptomic data. Here, we assemble the first genomic and transcriptomic resources for the recently described southern stuttering frog (Mixophyes australis). The southern stuttering frog is ground-dwelling, inhabiting naturally vegetated riverbanks in south-eastern Australia. Using PacBio HiFi long-read sequencing and Hi-C scaffolding, we generated a high-quality genome assembly, with a scaffold N50 of 369.3 Mb and 95.1% of the genome contained in twelve scaffolds. Using this assembly, we identified the mitochondrial genome, and assembled six tissue-specific transcriptomes. We also bioinformatically characterised novel sequences of two families of antimicrobial peptides (AMPs) in the southern stuttering frog, the cathelicidins and β-defensins. While traditional peptidomic approaches to peptide discovery have typically identified one or two AMPs in a frog species from skin secretions, our bioinformatic approach discovered 12 cathelicidins and two β-defensins that were expressed in a range of tissues. We investigated the novelty of the peptides and found diverse predicted activities. Our bioinformatic approach highlights the benefits of multi-omics resources in peptide discovery and contributes valuable genomic resources in an under-represented taxon.
Assessment of area and structural irregularity of retinal layers in diabetic retinopathy using machine learning and image processing techniques
Authors: Riazi-Esfahani Hamid , Jafari Behzad , Azimi Hossein , Rahimi Masoud , Saeidian Jamshid , Pouya Parnia , Faghihi Hooshang , Mirzaei Arash , Asadi Khameneh Esmaeil , Khalili Pour Elias 
Published: February 2024

AbstractDiabetes retinopathy prevention necessitates early detection, monitoring, and treatment. Non-invasive optical coherence tomography (OCT) shows structural changes in the retinal layer. OCT image evaluation necessitates retinal layer segmentation. The ability of our automated retinal layer segmentation to distinguish between normal, non-proliferative (NPDR), and proliferative diabetic retinopathy (PDR) was investigated in this study using quantifiable biomarkers such as retina layer smoothness index (SI) and area (S) in horizontal and vertical OCT images for each zone (fovea, superior, inferior, nasal, and temporal). This research includes 84 eyes from 57 individuals. The study shows a significant difference in the Area (S) of inner nuclear layer (INL) and outer nuclear layer (ONL) in the horizontal foveal zone across the three groups (p < 0.001). In the horizontal scan, there is a significant difference in the smoothness index (SI) of the inner plexiform layer (IPL) and the upper border of the outer plexiform layer (OPL) among three groups (p < 0.05). There is also a significant difference in the area (S) of the OPL in the foveal zone among the three groups (p = 0.003). The area (S) of the INL in the foveal region of horizontal slabs performed best for distinguishing diabetic patients (NPDR and PDR) from normal individuals, with an accuracy of 87.6%. The smoothness index (SI) of IPL in the nasal zone of horizontal foveal slabs was the most accurate at 97.2% in distinguishing PDR from NPDR. The smoothness index of the top border of the OPL in the nasal zone of horizontal slabs was 84.1% accurate in distinguishing NPDR from PDR. Smoothness index of IPL in the temporal zone of horizontal slabs was 89.8% accurate in identifying NPDR from PDR patients. In conclusion, optical coherence tomography can assess the smoothness index and irregularity of the inner and outer plexiform layers, particularly in the nasal and temporal regions of horizontal foveal slabs, to distinguish non-proliferative from proliferative diabetic retinopathy. The evolution of diabetic retinopathy throughout severity levels and its effects on retinal layer irregularity need more study.
A systematic review and meta-analysis of the effects of long-term antibiotic use on cognitive outcomes
Authors: Ye Yongqin , Tong Hor Yee Kimberley , Chong Wai Hong , Li Zhiqian , Tam Paul Kwong Hang , Baptista-Hon Daniel T. , Monteiro Olivia 
Published: February 2024

AbstractAntibiotics are indispensable to infection management. However, use of antibiotics can cause gut microbiota dysbiosis, which has been linked to cognitive impairment by disrupting communication between the gut microbiota and the brain. We conducted a systematic review and meta-analysis on the effects of long-term antibiotic use on cognitive outcomes. We have searched PubMed, Web of Science, Embase, Cochrane Library and Scopus for English publications before March 2023 following the PRISMA guidelines. Screening, data extraction, and quality assessment were performed in duplicate. 960 articles were screened and 16 studies which evaluated the effect of any antibiotic compared to no antibiotics or placebo were included. Case-reports, in vitro and animal studies were excluded. We found that antibiotic use was associated with worse cognitive outcomes with a pooled effect estimate of − 0.11 (95% CI − 0.15, − 0.07, Z = 5.45; P < 0.00001). Subgroup analyses performed on adult vs pediatric patients showed a similar association of antibiotic on cognition in both subgroups. Antibiotic treatment was not associated with worse cognition on subjects with existing cognitive impairment. On the other hand, antibiotic treatment on subjects with no prior cognitive impairment was associated with worse cognitive performance later in life. This calls for future well-designed and well-powered studies to investigate the impact of antibiotics on cognitive performance.