bluuebunny/crossref_metadata_2025_split huggingface dataset:
Drosophila expressing mutant human KCNT1 transgenes make an effective tool for targeted drug screening in a whole animal model of KCNT1-epilepsy
Authors: Hussain Rashid , Lim Chiao Xin , Shaukat Zeeshan , Islam Anowarul , Caseley Emily A. , Lippiat Jonathan D. , Rychkov Grigori Y. , Ricos Michael G. , Dibbens Leanne M. 
Published: February 2024

AbstractMutations in the KCNT1 potassium channel cause severe forms of epilepsy which are poorly controlled with current treatments. In vitro studies have shown that KCNT1-epilepsy mutations are gain of function, significantly increasing K+ current amplitudes. To investigate if Drosophila can be used to model human KCNT1 epilepsy, we generated Drosophila melanogaster lines carrying human KCNT1 with the patient mutation G288S, R398Q or R928C. Expression of each mutant channel in GABAergic neurons gave a seizure phenotype which responded either positively or negatively to 5 frontline epilepsy drugs most commonly administered to patients with KCNT1-epilepsy, often with little or no improvement of seizures. Cannabidiol showed the greatest reduction of the seizure phenotype while some drugs increased the seizure phenotype. Our study shows that Drosophila has the potential to model human KCNT1- epilepsy and can be used as a tool to assess new treatments for KCNT1- epilepsy.
Vascularised cardiac spheroids-on-a-chip for testing the toxicity of therapeutics
Authors: Di Cio Stefania , Marhuenda Emilie , Haddrick Malcolm , Gautrot Julien E. 
Published: February 2024

AbstractMicrofabricated organ-on-a-chips are rapidly becoming the gold standard for the testing of safety and efficacy of therapeutics. A broad range of designs has emerged, but recreating microvascularised tissue models remains difficult in many cases. This is particularly relevant to mimic the systemic delivery of therapeutics, to capture the complex multi-step processes associated with trans-endothelial transport or diffusion, uptake by targeted tissues and associated metabolic response. In this report, we describe the formation of microvascularised cardiac spheroids embedded in microfluidic chips. Different protocols used for embedding spheroids within vascularised multi-compartment microfluidic chips were investigated first to identify the importance of the spheroid processing, and co-culture with pericytes on the integration of the spheroid within the microvascular networks formed. The architecture of the resulting models, the expression of cardiac and endothelial markers and the perfusion of the system was then investigated. This confirmed the excellent stability of the vascular networks formed, as well as the persistent expression of cardiomyocyte markers such as cTNT and the assembly of striated F-actin, myosin and α-actinin cytoskeletal networks typically associated with contractility and beating. The ability to retain beating over prolonged periods of time was quantified, over 25 days, demonstrating not only perfusability but also functional performance of the tissue model. Finally, as a proof-of-concept of therapeutic testing, the toxicity of one therapeutic associated with cardiac disfunction was evaluated, identifying differences between direct in vitro testing on suspended spheroids and vascularised models.
Short tandem repeat mutations regulate gene expression in colorectal cancer
Authors: Verbiest Max A. , Lundström Oxana , Xia Feifei , Baudis Michael , Bilgin Sonay Tugce , Anisimova Maria 
Published: February 2024

AbstractShort tandem repeat (STR) mutations are prevalent in colorectal cancer (CRC), especially in tumours with the microsatellite instability (MSI) phenotype. While STR length variations are known to regulate gene expression under physiological conditions, the functional impact of STR mutations in CRC remains unclear. Here, we integrate STR mutation data with clinical information and gene expression data to study the gene regulatory effects of STR mutations in CRC. We confirm that STR mutability in CRC highly depends on the MSI status, repeat unit size, and repeat length. Furthermore, we present a set of 1244 putative expression STRs (eSTRs) for which the STR length is associated with gene expression levels in CRC tumours. The length of 73 eSTRs is associated with expression levels of cancer-related genes, nine of which are CRC-specific genes. We show that linear models describing eSTR-gene expression relationships allow for predictions of gene expression changes in response to eSTR mutations. Moreover, we found an increased mutability of eSTRs in MSI tumours. Our evidence of gene regulatory roles for eSTRs in CRC highlights a mostly overlooked way through which tumours may modulate their phenotypes. Future extensions of these findings could uncover new STR-based targets in the treatment of cancer.
Development of an indirect ELISA for the serodiagnosis of canine infection by Onchocerca lupi
Authors: Latrofa Maria Stefania , Louzada-Flores Viviane Noll , Maia Carla , Kelly Maureen A. , Verocai Guilherme G. , Cantacessi Cinzia , Otranto Domenico 
Published: February 2024

AbstractOnchocercalupi is a zoonotic filarioid parasite of dogs and cats with widespread distribution. A specific non-invasive diagnostic assay for the detection of O.lupi infections remains unavailable. This study aimed to assess the accuracy, specificity, and sensitivity of an ELISA test designed using nine peptides from two O.lupi proteins. Sera (n = 54) collected from O.lupi infected dogs from endemic areas (Portugal and USA), alongside sera from dogs positive for Dirofilariaimmitis, D.repens, Cercopithifilariabainae, and Acanthocheilonemareconditum (n = 53) from a non-endemic area for O.lupi, as well as from helminth-free dogs (n = 60), were tested. The checkerboard titration method was applied for the optimization of peptide concentrations and conjugate anti-dog dilutions. Sensitivity, specificity, and optimal cut-off values were calculated using ROC curve analysis. All peptides reacted against sera of O.lupi, with no correlation between optic density (OD) values and microfilariae (mfs) loads. Sensitivity and specificity values ranging from 85.45 to 100%, and 88.89% to 100%, respectively, were recorded for all peptides examined, with 100% specificity and sensitivity observed for peptides 40_3, 40_5, 130_3, 120_3 and 40_1, 130_5, respectively. The maximum cut-off value was observed for peptides 40_5 (0.765) and 40_3 (0.708). Testing of sera from dogs positive for other filarioids resulted in lower OD values (up to 1.565) for peptides 40_3 and 40_5 when compared with O.lupi (up to 2.929). The availability of this assay will be of value in epidemiological studies of canine O.lupi infection in both endemic and non-endemic areas, and in assessing the risk for zoonotic transmission.
Gut microbiota composition is altered in postural orthostatic tachycardia syndrome and post-acute COVID-19 syndrome
Authors: Hamrefors Viktor , Kahn Fredrik , Holmqvist Madlene , Carlson Katherine , Varjus Roosa , Gudjonsson Alexander , Fedorowski Artur , Ohlsson Bodil 
Published: February 2024

AbstractPostural Orthostatic Tachycardia Syndrome (POTS) reflects an autonomic dysfunction, which can occur as a complication to COVID-19. Our aim was to examine gastrointestinal symptoms and gut microbiota composition in patients with POTS and post-acute COVID-19 syndrome (PACS), compared with controls. POTS patients (n = 27), PACS patients (n = 32) and controls (n = 39) delivered fecal samples and completed a 4-day food diary, irritable bowel syndrome-severity scoring system (IBS-SSS), and visual analog scale for IBS (VAS-IBS). A total of 98 DNA aliquots were sequenced to an average depth of 28.3 million (M) read pairs (Illumina 2 × 150 PE) per sample. Diversity and taxonomic levels of the microbiome, as well as functional abundances were calculated for POTS and PACS groups, then compared with controls. There were several differences in taxonomic composition between POTS and controls, whereas only the abundance of Ascomycota and Firmicutes differed between PACS and controls. The clinical variables total IBS-SSS, fatigue, and bloating and flatulence significantly correlated with multiple individual taxa abundances, alpha diversity, and functional abundances. We conclude that POTS, and to a less extent PACS, are associated with differences in gut microbiota composition in diversity and at several taxonomic levels. Clinical symptoms are correlated with both alpha diversity and taxonomic and functional abundances.
Antimicrobial potential of Streptomyces coeruleofuscus SCJ isolated from microbiologically unexplored garden soil in Northwest Morocco
Authors: Rammali Said , Rahim Abdellatif , El Aalaoui Mohamed , Bencharki Bouchaib , Dari Khadija , Habach Aicha , Abdeslam Lamiri , khattabi Abdelkrim 
Published: February 2024

AbstractResearch on microorganisms in various biotopes is required to identify new, natural potent molecules. These molecules are essential to control the development of multi-drug resistance (MDR). In the present study, a Streptomyces sp., namely SCJ, was isolated from a soil sample collected from a Moroccan garden. SCJ isolate was identified on the basis of a polyphasic approach, which included cultural, micro-morphological, biochemical, and physiological characteristics. The sequence of the 16S rRNA gene of the SCJ strain showed 99.78% similarity to strains of Streptomyces coeruleofuscus YR-T (KY753282.1). The preliminary screening indicated that the SCJ isolate exhibited activity against Candida albicans ATCC 60,193, Escherichia coli ATCC 25,922, Staphylococcus aureus CECT 976, Staphylococcus aureus ATCC 25,923, Bacillus cereus ATCC 14,579, Pseudomonas aeruginosa ATCC 27,853, as well as various other clinical MDR bacteria and five phytopathogenic fungi. The ethyl acetate extract of the isolated strain demonstrated highly significant (p < 0.05) antimicrobial activity against multi-resistant bacteria and phytopathogenic fungi. The absorption spectral analysis of the ethyl acetate extract of the SCJ isolate obtained showed no absorption peaks characteristic of polyene molecules. Moreover, no hemolytic activity against erythrocytes was observed in this extract. GC–MS analysis of the ethyl acetate extract of the SCJ isolate revealed the presence of 9 volatile compounds including 3,5-Dimethylpyrazole, and pyrrolizidine derivatives (Pyrrolo[1,2-a]pyrazine 1,4-dione, hexahydro-3-(2-methylpropyl)), which could potentially explain the antimicrobial activity demonstrated in this study.
Assortative mixing of opinions about COVID-19 vaccination in personal networks
Authors: Hâncean Marian-Gabriel , Lerner Jürgen , Perc Matjaž , Molina José Luis , Geantă Marius 
Published: February 2024

AbstractMany countries worldwide had difficulties reaching a sufficiently high vaccination uptake during the COVID-19 pandemic. Given this context, we collected data from a panel of 30,000 individuals, which were representative of the population of Romania (a country in Eastern Europe with a low 42.6% vaccination rate) to determine whether people are more likely to be connected to peers displaying similar opinions about COVID-19 vaccination. We extracted 443 personal networks, amounting to 4430 alters. We estimated multilevel logistic regression models with random-ego-level intercepts to predict individual opinions about COVID-19 vaccination. Our evidence indicates positive opinions about the COVID-19 vaccination cluster. Namely, the likelihood of having a positive opinion about COVID-19 vaccination increases when peers have, on average, a more positive attitude than the rest of the nodes in the network (OR 1.31, p < 0.001). We also found that individuals with higher education and age are more likely to hold a positive opinion about COVID-19 vaccination. With the given empirical data, our study cannot reveal whether this assortative mixing of opinions is due to social influence or social selection. However, it may nevertheless have implications for public health interventions, especially in countries that strive to reach higher uptake rates. Understanding opinions about vaccination can act as an early warning system for potential outbreaks, inform predictions about vaccination uptake, or help supply chain management for vaccine distribution.
Late spontaneous posterior capsule rupture with single-piece hydrophobic acrylic intraocular lens dislocation
Authors: Lee Soomin , Lee Gahye , Park Choul Yong 
Published: February 2024

AbstractIn this study, we described and discussed the late onset spontaneous posterior capsule rupture with intraocular lens (IOL) dislocation years after uncomplicated cataract surgery and implantation of hydrophobic acrylic IOLs. Eight patients presented with spontaneous posterior capsule rupture and IOL dislocation 5–20 years after uncomplicated phacoemulsification and IOL (AcrySof, Alcon, US) implantation. None of the patients had undergone posterior capsulotomy in the past. Four of the patients admitted habitual eye rubbing. An intact and well-centered continuous curvilinear capsulotomy edge was observed in all cases. IOLs were dislocated or displaced behind the anterior capsulotomy with a significant decrease in vision. A large rupture with a curled edge of the broken posterior capsule was visible. Dislocated IOLs were removed, and a three-piece IOL was inserted in the sulcus in six cases and suture fixated to the sclera in two cases. Improved vision was achieved in all cases. Although the mechanism underlying this late complication is unclear, habitual eye rubbing or IOL design may play a role. Further investigation is needed to prevent this complication in the future.
Time dependent dihedral angle oscillations of the spike protein of SARS-CoV-2 reveal favored frequencies of dihedral angle rotations
Authors: Bastidas Oscar H. , Sevarac Zoran 
Published: February 2024

AbstractThe spike protein of SARS-CoV-2 is critical to viral infection of human host cells which ultimately results in COVID-19. In this study we analyzed the behavior of dihedral angles (phi and psi) of the wild-type spike protein over time from molecular dynamics and identified that their oscillations are dominated by a few discrete, relatively low frequencies in the 23–63 MHz range with 42.969 MHz being the most prevalent frequency sampled by the oscillations. We thus observed the spike protein to favor certain frequencies more than others. Gaps in the tally of all observed frequencies for low-abundance amino acids also suggests that the frequency components of dihedral angle oscillations may be a function of position in the primary structure since relatively more abundant amino acids lacked gaps. Lastly, certain residues identified in the literature as constituting the inside of a druggable pocket, as well as others identified as allosteric sites, are observed in our data to have distinctive time domain profiles. This motivated us to propose additional residues with similar time domain profiles, which may be of potential interest to the vaccine and drug design communities for further investigation. Thus these findings indicate that there is a particular frequency domain profile for the spike protein hidden within the time domain data and this information, perhaps with the suggested residues, might provide additional insight into therapeutic development strategies for COVID-19 and beyond.
The therapeutic effect of hyperbaric oxygen therapy in patients with severe to profound idiopathic sudden sensorineural hearing loss
Authors: Choi Yeso , Han Sung Jun , Kim Sung Kyun , Hong Seok Min 
Published: February 2024

AbstractThe optimal treatment for sudden sensorineural hearing loss (SSNHL) is unclear. Hyperbaric oxygen therapy (HBOT) has been suggested as a viable option for treatment of SSNHL as it improves vascular dysfunction. In this study, we evaluated the therapeutic effects of HBOT by retrospectively reviewing the records of 2206 patients with SSNHL. 54 who had received HBOT were selected for the HBOT groups, while 59 age-matched controls who had not were selected for the control groups. The HBOT and control groups were divided into subgroups according to intratympanic steroid (ITS) use. Groups A–D had received oral steroids + HBOT, oral steroids only, oral steroids + ITS + HBOT, and oral steroids + ITS, respectively. Of the 113 SSNHL patients, 21 had diabetes mellitus (DM) (2, 0, 9, and 10 patients in Groups A–D, respectively). There was no notable difference in hearing improvement between patients receiving HBOT and those in the control group. However, among diabetic patients, those who underwent HBOT demonstrated a significant improvement in hearing when compared to the control group. The combination of HBOT and steroids could potentially be beneficial for treating severe to profound SSNHL patients with DM.
Association of UGT1A1 gene variants, expression levels, and enzyme concentrations with 2,3,7,8-TCDD exposure in individuals exposed to Agent Orange/Dioxin
Authors: Van Quang Ha , Vuong Nguyen Ba , Trang Bui Ngoc Linh , Toan Nguyen Linh , Van Tong Hoang 
Published: February 2024

AbstractAmong the congener of dioxin, 2,3,7,8-TCDD is the most toxic, having a serious long-term impact on the environment and human health. UDP-glucuronosyltransferase 1A1 (UGT1A1) plays a crucial role in the detoxification and excretion of endogenous and exogenous lipophilic compounds, primarily in the liver and gastrointestinal tract. This study aimed to investigate the association of UGT1A1 gene polymorphisms, expression levels, and enzyme concentration with Agent Orange/Dioxin exposure. The study included 100 individuals exposed to Agent Orange/Dioxin nearby Da Nang and Bien Hoa airports in Vietnam and 100 healthy controls. UGT1A1 SNP rs10929303, rs1042640 and rs8330 were determined by Sanger sequencing, mRNA expression was quantified by RT-qPCR and plasma UGT1A1 concentrations were measured by ELISA. The results showed that UGT1A1 polymorphisms at SNPs rs10929303, rs1042640 and rs8330 were associated with Agent Orange/Dioxin exposure (OR = 0.55, P = 0.018; OR = 0.55, P = 0.018 and OR = 0.57, P = 0.026, respectively). UGT1A1 mRNA expression levels and enzyme concentration were significantly elevated in individuals exposed to Agent Orange/Dioxin compared to controls (P < 0.0001). Benchmark dose (BMD) analyses showed that chronic exposure to 2,3,7,8-TCDD contamination affects the UGT1A1 mRNA and protein levels. Furthermore, UGT1A1 polymorphisms affected gene expression and enzyme concentrations in individuals exposed to Agent Orange/Dioxin. In conclusion, UGT1A1 gene polymorphisms, UGT1A gene expression levels and UGT1A1 enzyme concentrations were associated with Agent Orange/Dioxin exposure. The metabolism of 2,3,7,8-TCDD may influence UGT1A gene expression and enzyme concentrations.
Vertical accretion trends project doughnut-like fragmentation of saltmarshes
Authors: Hein Christopher J. , Connell Jennifer E. , FitzGerald Duncan M. , Georgiou Ioannis Y. , Hughes Zoe J. , King Kendall 
Published: February 2024

AbstractCoastal saltmarshes keep pace with sea-level rise through in-situ production of organic material and incorporation of allochthonous inorganic sediment. Here we report rates of vertical accretion of 16 new sediment cores collected proximal to platform edges within saltmarshes located behind four barrier islands along the southeast United States coast. All but two of these exceed the contemporaneous rate of relative sea-level rise, often by a factor of 1.5 or more. Comparison with 80 additional measurements compiled across the Georgia Bight reveals that marshes situated closer to inlets and large bays generally accrete faster than those adjacent to small creeks or within platform interiors. These results demonstrate a spatial dichotomy in the resilience of backbarrier saltmarshes: marsh interiors are near a tipping point, but allochthonous mineral sediment fluxes allow enhanced local resilience along well-exposed and platform-edge marshes. Together, this suggests that backbarrier marshes are trending towards rapid, doughnut-like fragmentation.
Diffusion‐UDA: Diffusion‐based unsupervised domain adaptation for submersible fault diagnosis
Authors: Zhao Penghui , Wang Xindi , Zhang Yi , Li Yang , Wang Hongjun , Yang Yang 
Published: February 2024

AbstractDeep learning has demonstrated notable success in mechanical signal processing with a large amount labelled data. However, the systems of the Jiaolong deep‐sea submersible prone to malfunction are typically diverse, due to the high complexity of its structure and operational environment. Consequently, this diversity gives rise to variations in the types of sensor signals and their associated data distributions that require analysis. Unsupervised domain adaptation (UDA) uses transferable knowledge derived from the source domain and applies it to an unlabelled target domain in order to improve the reusability of pre‐existing models and data. Inspired by the diffusion models that have the robust capabilities to transform data distributions across a large gap, we propose a novel diffusion‐based unsupervised domain adaptation (diffusion‐UDA) model, which leverages contrastive learning to alleviate the challenges of cross‐domain analysis for fault diagnosis within different systems of the deep‐sea submersible. Experimental results show the proposed method achieves state‐of‐the‐art performance on various benchmarks.
A Conv‐GEMM reconfigurable accelerator with WS‐RS dataflow for high throughput processing
Authors: Wang Feihu , Zhang Chi , Deng Yongchao , Yang Xu , Yu Shuangming , Dou Runjiang , Wu Nanjian , Liu Liyuan 
Published: February 2024

AbstractConvolution and matrix operations are both important computations in Deep Neural Networks (DNNs). However, the significant differences between convolution and matrix computation patterns have posed a challenge in efficiently supporting both convolution (Conv) and general matrix multiplication (GEMM) on hardware design. This paper proposes a Conv‐GEMM reconfigurable accelerator architecture for high throughput edge processing. A weight stationary‐row streaming (WS‐RS) dataflow scheme is proposed, which maximizes data reuse through hierarchical memory structures and flexible PE connections, and supports high throughput edge‐based deep learning algorithms. Based on the proposed dataflow, multi‐scale memory access network (MMAN), reconfigurable accumulator array (RAA), and configurable instruction set architecture (ISA) are designed to optimize computation throughput and energy efficiency. The accelerator is designed under 65 nm technology, achieves peak performance of 1.15 TOPS at 250 MHz, with an energy efficiency of 1.14 TOPS/W. The GEMM computation achieves 85.7% latency improvement and the Mobilenet‐V1 processing achieves a throughput of 529 fps under a 256 × 224 image size and an 87.15% (top‐5) accuracy on the ImageNet dataset.