bluuebunny/crossref_metadata_2025_split huggingface dataset:
Classification of brain lesions using a machine learning approach with cross-sectional ADC value dynamics
Authors: Solar Peter , Valekova Hana , Marcon Petr , Mikulka Jan , Barak Martin , Hendrych Michal , Stransky Matyas , Siruckova Katerina , Kostial Martin , Holikova Klara , Brychta Jindrich , Jancalek Radim 
Published: July 2023

AbstractDiffusion-weighted imaging (DWI) and its numerical expression via apparent diffusion coefficient (ADC) values are commonly utilized in non-invasive assessment of various brain pathologies. Although numerous studies have confirmed that ADC values could be pathognomic for various ring-enhancing lesions (RELs), their true potential is yet to be exploited in full. The article was designed to introduce an image analysis method allowing REL recognition independently of either absolute ADC values or specifically defined regions of interest within the evaluated image. For this purpose, the line of interest (LOI) was marked on each ADC map to cross all of the RELs’ compartments. Using a machine learning approach, we analyzed the LOI between two representatives of the RELs, namely, brain abscess and glioblastoma (GBM). The diagnostic ability of the selected parameters as predictors for the machine learning algorithms was assessed using two models, the k-NN model and the SVM model with a Gaussian kernel. With the k-NN machine learning method, 80% of the abscesses and 100% of the GBM were classified correctly at high accuracy. Similar results were obtained via the SVM method. The proposed assessment of the LOI offers a new approach for evaluating ADC maps obtained from different RELs and contributing to the standardization of the ADC map assessment.
Modulation of toxicity effects of CuSO4 by sulfated polysaccharides extracted from brown algae (Sargassum tenerrimum) in Danio rerio as a model
Authors: Zargari Ashkan , Nejatian Mohammad , Abbaszadeh Sepideh , Jahanbin Kambiz , Bagheri Tahereh , Hedayati Aliakbar , Sheykhi Monireh 
Published: July 2023

AbstractCopper is widely used in agriculture and aquaculture due to its high disinfection properties and relatively low cost. However, the increase in copper concentration due to evaporation can lead to water reservoir pollution, which can harm the health of consumers. The present study aimed to determine the role of sulfated polysaccharides (SPs) extracted from Sargassum tenerimum algae in reducing lesions caused by the heavy metal copper. Zebrafish (Danio rerio) were used as a human model in five treatments. The negative and positive control groups were fed a diet containing zero percent of SPs, while the experimental groups were fed 0.5%, 1%, and 1.5% of SPs in three treatments for 56 days, finally CuSO4 was exposed only to the positive control group and the groups fed with SPs. Results showed a significant decrease in the activity level of ALT enzymes (39–16 U/mL), AST (67–46 U/mL), and ALP (485–237 U/mL), confirming the results obtained from histopathological studies in CuSO4 exposed groups. The addition of SPs to the diet resulted in a significant reduction (sig < 0.05) of mortalities due to the decrease of tissue damage. Additionally, due to the anti-inflammatory properties and the protective effect of SPs, a significant decrease (sig < 0.05) was observed in the relative expression of Il-1β and Tnf-α genes.
Spinal cord tethering and syringomyelia after trauma: impact of age and surgical outcome
Authors: Bratelj Denis , Stalder Susanne , Capone Crescenzo , Jaszczuk Phillip , Dragalina Cristian , Pötzel Tobias , Gebhard Catherine , Fiechter Michael 
Published: July 2023

AbstractPosttraumatic spinal cord tethering and syringomyelia frequently lead to progressive neurological loss. Although several studies demonstrated favourable outcome following spinal cord detethering with/without shunting, additional research is required as no clear consensus exists over the ideal treatment strategy and knowledge about prognostic demographic determinants is currently limited. In this investigation, we retrospectively investigated 67 patients (56 men, 11 women) who were surgically treated and followed for symptomatic spinal cord tethering and syringomyelia from 2012 to 2022 at our center. Age (B-coefficient 0.396) and severity of trauma to the spinal cord (B-coefficient − 0.462) have been identified as independent predictors for the rate of development of symptomatic spinal cord tethering and syringomyelia (p < 0.001). Following untethering surgery including expansion duraplasty with/without shunting, 65.9% of patients demonstrated an improvement of neurological loss (p < 0.001) whereas 50.0% of patients displayed amelioration of spasticity and/or neuropathic pain (p < 0.001). Conclusively, active screening for symptomatic spinal cord tethering and syringomyelia, particularly in younger patients with severe spinal trauma, is crucial as surgical untethering with/without shunting is able to achieve favourable clinical outcomes. This knowledge may enable clinicians to tailor treatment strategies in spinal cord injury patients suffering from progressive neurological loss towards a more optimal and personalized patient care.
Carvacrol attenuated lipopolysaccharide-induced intestinal injury by down-regulating TLRs gene expression and regulating the gut microbiota in rabbit
Authors: Wu Diange , Xia Miao , Yan An , Jiang Haotian , Fan Jiaqi , Zhou Siyuan , Wei Xu , Liu Shudong , Chen Baojiang 
Published: July 2023

AbstractCarvacrol (CAR) is a plant extract that has been reported to enhance antioxidant activity in animals. However, the effect of CAR on the intestinal health of rabbits is poorly understood. Here, we investigated whether CAR exerts protective effects on the intestinal health of rabbits following lipopolysaccharide (LPS) challenge and whether these effects were mediated via the reduction of intestinal inflammation and the regulation of the intestinal flora. Intestinal damage was assessed in LPS-challenged rabbits treated or not with CAR. The serum levels of inflammatory factors were assessed by enzyme-linked immunosorbent assay. Histopathological changes in the ileum and cecum were examined using hematoxylin and eosin staining. The relative gene expression levels of inflammatory factors and tight junction proteins in the rabbit cecum were determined by qRT-PCR. High-throughput sequencing analysis of the microbial 16S rRNA gene was performed using the Illumina NovaSeq Platform. The results showed that CAR can prevent intestinal inflammation and damage as well as mitigate gut dysbiosis in rabbits following LPS challenge. Our study provides a theoretical reference for the application of dietary CAR in rabbit production.
Complexity synchronization: a measure of interaction between the brain, heart and lungs
Authors: Mahmoodi Korosh , Kerick Scott E. , Grigolini Paolo , Franaszczuk Piotr J. , West Bruce J. 
Published: July 2023

AbstractHerein we address the measurable consequences of the network effect (NE) on time series generated by different parts of the brain, heart, and lung organ-networks (ONs), which are directly related to their inter-network and intra-network interactions. Moreover, these same physiologic ONs have been shown to generate crucial event (CE) time series, and herein are shown, using modified diffusion entropy analysis (MDEA) to have scaling indices with quasiperiodic changes in complexity, as measured by scaling indices, over time. Such time series are generated by different parts of the brain, heart, and lung ONs, and the results do not depend on the underlying coherence properties of the associated time series but demonstrate a generalized synchronization of complexity. This high-order synchrony among the scaling indices of EEG (brain), ECG (heart), and respiratory time series is governed by the quantitative interdependence of the multifractal behavior of the various physiological ONs’ dynamics. This consequence of the NE opens the door for an entirely general characterization of the dynamics of complex networks in terms of complexity synchronization (CS) independently of the scientific, engineering, or technological context. CS is truly a transdisciplinary effect.
A two-sample mendelian randomization analysis investigates associations between gut microbiota and infertility
Authors: Li Taozhi , Shao Wenbo , Wang Yukun , Zhou Rui , Yun Zhangjun , He Yalin , Wu Yu 
Published: July 2023

AbstractObservational studies have provided evidence of a correlation between alterations in gut microbiota composition and infertility. However, concrete proof supporting the causal relationship is still lacking. We performed a Mendelian randomization study to assess whether genetically gut microbiota composition influences the risk of infertility. The genetic data pertaining to gut microbiota were obtained from a genome-wide association study meta-analysis, which was conducted among 24 cohorts (18,340 participants) from the international MiBioGen consortium. By the primary method of assessing causality, we have identified 2 family taxa, 2 genus taxa, and 1 order taxa that were linked to a low risk of male infertility, while 1 genus taxa were associated with a high risk of male infertility. Furthermore, we have discovered 6 genus taxa, 1 phylum taxa, 1 class taxa, 1 order taxa, and 1 family taxa that were associated with a low risk of female infertility, while 1 genus taxa were linked to a high risk of female infertility. This study successfully confirmed that there was a causal link between gut microbiota and infertility. The identification of these specific strains through genetic prediction offers a valuable insight for early diagnosis, prevention, and treatment of infertility.
The human acetylcholinesterase C-terminal T30 peptide activates neuronal growth through alpha 7 nicotinic acetylcholine receptors and the mTOR pathway
Authors: Graur Alexandru , Sinclair Patricia , Schneeweis Amanda K. , Pak Daniel T. , Kabbani Nadine 
Published: July 2023

AbstractAcetylcholinesterase (AChE) is a highly conserved enzyme responsible for the regulation of acetylcholine signaling within the brain and periphery. AChE has also been shown to participate in non-enzymatic activity and contribute to cellular development and aging. In particular, enzymatic cleavage of the synaptic AChE isoform, AChE-T, is shown to generate a bioactive T30 peptide that binds to the ⍺7 nicotinic acetylcholine receptor (nAChR) at synapses. Here, we explore intracellular mechanisms of T30 signaling within the human cholinergic neural cell line SH-SY5Y using high performance liquid chromatography (HPLC) coupled to electrospray ionization mass spectrometry (ESI–MS/MS). Proteomic analysis of cells exposed to (100 nM) T30 for 3-days reveals significant changes within proteins important for cell growth. Specifically, bioinformatic analysis identifies proteins that converge onto the mammalian target of rapamycin (mTOR) pathway signaling. Functional experiments confirm that T30 regulates neural cell growth via mTOR signaling and ⍺7 nAChR activation. T30 was found promote mTORC1 pro-growth signaling through an increase in phosphorylated elF4E and S6K1, and a decrease in the autophagy LC3B-II protein. These findings are corroborated in hippocampal neurons and show that T30 promotes dendritic arborization. Taken together, our findings define mTOR as a novel pathway activated by T30 interaction with the nAChR and suggest a role for this process in human disease.
Functional characterization of the transient receptor potential melastatin 2 (TRPM2) cation channel from Nematostella vectensis reconstituted into lipid bilayer
Authors: Szollosi Andras , Almássy János 
Published: July 2023

AbstractTransient receptor potential melastatin 2 (TRPM2) cation channel activity is required for insulin secretion, immune cell activation and body heat control. Channel activation upon oxidative stress is involved in the pathology of stroke and neurodegenerative disorders. Cytosolic Ca2+, ADP-ribose (ADPR) and phosphatidylinositol-4,5-bisphosphate (PIP2) are the obligate activators of the channel. Several TRPM2 cryo-EM structures have been resolved to date, yet functionality of the purified protein has not been tested. Here we reconstituted overexpressed and purified TRPM2 from Nematostella vectensis (nvTRPM2) into lipid bilayers and found that the protein is fully functional. Consistent with the observations in native membranes, nvTRPM2 in lipid bilayers is co-activated by cytosolic Ca2+ and either ADPR or ADPR-2′-phosphate (ADPRP). The physiological metabolite ADPRP has a higher apparent affinity than ADPR. In lipid bilayers nvTRPM2 displays a large linear unitary conductance, its open probability (Po) shows little voltage dependence and is stable over several minutes. Po is high without addition of exogenous PIP2, but is largely blunted by treatment with poly-l-Lysine, a polycation that masks PIP2 headgroups. These results indicate that PIP2 or some other activating phosphoinositol lipid co-purifies with nvTRPM2, suggesting a high PIP2 binding affinity of nvTRPM2 under physiological conditions.
Electrotaxis evokes directional separation of co-cultured keratinocytes and fibroblasts
Authors: Leal José , Shaner Sebastian , Jedrusik Nicole , Savelyeva Anna , Asplund Maria 
Published: July 2023

AbstractBioelectric communication plays a significant role in several cellular processes and biological mechanisms, such as division, differentiation, migration, cancer metastasis, and wound healing. Ion flow across cellular walls leads to potential gradients and subsequent formation of constant or time-varying electric fields(EFs), which regulate cellular processes. An EF is natively generated towards the wound center during epithelial wound healing, aiming to align and guide cell migration, particularly of macrophages, fibroblasts, and keratinocytes. While this phenomenon, known as electrotaxis or galvanotaxis, has been extensively investigated across many cell types, it is typically explored one cell type at a time, which does not accurately represent cellular interactions during complex biological processes. Here we show the co-cultured electrotaxis of epidermal keratinocytes and dermal fibroblasts with a salt-bridgeless microfluidic approach for the first time. The electrotactic response of these cells was first assessed in mono-culture to establish a baseline, resulting in the characteristic cathodic migration for keratinocytes and anodic for fibroblasts. Both cell types retained their electrotactic properties in co-culture leading to clear cellular partition even in the presence of cellular collisions. The methods leveraged here pave the way for future co-culture electrotaxis experiments where the concurrent influence of cell types can be thoroughly investigated.
Understanding the hindrance factor of bacterial proliferation and γ-aminobutyric acid-producing capability of nondairy strains of Lactiplantibacillus plantarum in milk fermentation
Authors: Phirom-on Konlarat , Po-ngern Anuchida , Jaikhan Somchai , Sirichon Sasiwan , Vichitphan Sukanda , Vichitphan Kanit , Apiraksakorn Jirawan 
Published: July 2023

Abstractγ-aminobutyric-acid (GABA) is a mental health-supporting substance that helps release anxiety and depression and improves memory. Lactiplantibacillus plantarum SKKL1, a GABA-producing bacterium, has been introduced to formulate a gut-brain axis product. However, growth and sugar consumption of L. plantarum SKKL1 in milk were ineffective. This obstacle was investigated by varying different types of milk, sugars, fermentation temperatures, and times. The results revealed that none of these parameters improved growth and bacterial metabolism in milk, except addition of soluble protein as found in yeast extract and malt extract. Although a protease deficiency of L. plantarum SKKL1 was discovered, it was not a primary barrier to cell propagation. Insight of this study showed clearly that soluble protein was an essential metabolic activator for growth, nutrient consumption, and protease synthesis, then stimulated lactic acid and GABA productions. While, milk casein and casein hydrolysate, a complex protein structure with low solubility, were not utilized by L. plantarum SKKL1. The novelty of this study is the first in-depth investigation to confirm a significant effect of soluble protein on enrich-GABA milk fermentation by L. plantarum SKKL1 as the sole starter without protease and monosodium glutamate addition.
Refining skin lesions classification performance using geometric features of superpixels
Authors: Moldovanu Simona , Miron Mihaela , Rusu Cristinel-Gabriel , Biswas Keka C. , Moraru Luminita 
Published: July 2023

AbstractThis paper introduces superpixels to enhance the detection of skin lesions and to discriminate between melanoma and nevi without false negatives, in dermoscopy images. An improved Simple Linear Iterative Clustering (iSLIC) superpixels algorithm for image segmentation in digital image processing is proposed. The local graph cut method to identify the region of interest (i.e., either the nevi or melanoma lesions) has been adopted. The iSLIC algorithm is then exploited to segment sSPs. iSLIC discards all the SPs belonging to image background based on assigned labels and preserves the segmented skin lesions. A shape and geometric feature extraction task is performed for each segmented SP. The extracted features are fed into six machine learning algorithms such as: random forest, support vector machines, AdaBoost, k-nearest neighbor, decision trees (DT), Gaussian Naïve Bayes and three neural networks. These include Pattern recognition neural network, Feed forward neural network, and 1D Convolutional Neural Network for classification. The method is evaluated on the 7-Point MED-NODE and PAD-UFES-20 datasets and the results have been compared to the state-of-art findings. Extensive experiments show that the proposed method outperforms the compared existing methods in terms of accuracy.
Integer time series models for tuberculosis in Africa
Authors: Ojo Oluwadare O. , Nadarajah Saralees , Kebe Malick 
Published: July 2023

AbstractTuberculosis, an airborne disease, is the deadliest human infectious disease caused by one single agent. The African region is among the most affected and most burdensome area in terms of tuberculosis cases. In this paper, we modeled the number of new cases of tuberculosis for 2000–2021 by integer time series. For each African country, we fitted twenty different models and selected the model that best fitted the data. The twenty models were mostly based on the number of new cases following either the Poisson or negative binomial distribution with the rate parameter allowed to vary linearly or quadratically with respect to year. The best fitted models were used to give predictions for 2022–2031.
Correlation of N-acetyltransferase 2 genotype and acetylation status with plasma isoniazid concentration and its metabolic ratio in ethiopian tuberculosis patients
Authors: Sileshi Tesemma , Telele Nigus Fikrie , Burkley Victoria , Makonnen Eyasu , Aklillu Eleni 
Published: July 2023

AbstractUnfavorable treatment outcomes for tuberculosis (TB) treatment might result from altered plasma exposure to antitubercular drugs in TB patients. The present study investigated the distribution of the N-Acetyltransferase 2 (NAT2) genotype, isoniazid acetylation status, genotype–phenotype concordance of NAT2, and isoniazid plasma exposure among Ethiopian tuberculosis patients. Blood samples were collected from newly diagnosed TB patients receiving a fixed dose combination of first-line antitubercular drugs daily. Genotyping of NAT2 was done using TaqMan drug metabolism assay. Isoniazid and its metabolite concentration were determined using validated liquid chromatography-tandem mass spectrometry (LC–MS/MS). A total of 120 patients (63 male and 57 female) were enrolled in this study. The mean daily dose of isoniazid was 4.71 mg/kg. The frequency of slow, intermediate, and fast NAT2 acetylators genotypes were 74.2%, 22.4%, and 3.3% respectively. The overall median isoniazid maximum plasma concentration (Cmax) was 4.77 µg/mL and the AUC0–7 h was 11.21 µg.h/mL. The median Cmax in slow, intermediate, and fast acetylators were 5.65, 3.44, and 2.47 μg/mL, respectively. The median AUC0–7 h hour in slow, intermediate, and fast acetylators were 13.1, 6.086, and 3.73 mg•h/L, respectively. The majority (87.5%) of the study participants achieved isoniazid Cmax of above 3 µg/mL, which is considered a lower limit for a favorable treatment outcome. There is 85% concordance between the NAT2 genotype and acetylation phenotypes. NAT2 genotype, female sex, and dose were independent predictors of Cmax and AUC0–7 h (p < 0.001). Our finding revealed that there is a high frequency of slow NAT2 genotypes. The plasma Cmax of isoniazid was higher in the female and slow acetylators genotype group. The overall target plasma isoniazid concentrations in Ethiopian tuberculosis patients were achieved in the majority of the patients. Therefore, it is important to monitor adverse drug reactions and the use of a higher dose of isoniazid should be closely monitored.
Cryptic kin discrimination during communal lactation in mice favours cooperation between relatives
Authors: Green Jonathan P. , Franco Catarina , Davidson Amanda J. , Lee Vicki , Stockley Paula , Beynon Robert J. , Hurst Jane L. 
Published: July 2023

AbstractBreeding females can cooperate by rearing their offspring communally, sharing synergistic benefits of offspring care but risking exploitation by partners. In lactating mammals, communal rearing occurs mostly among close relatives. Inclusive fitness theory predicts enhanced cooperation between related partners and greater willingness to compensate for any partner under-investment, while females are less likely to bias investment towards own offspring. We use a dual isotopic tracer approach to track individual milk allocation when familiar pairs of sisters or unrelated house mice reared offspring communally. Closely related pairs show lower energy demand and pups experience better access to non-maternal milk. Lactational investment is more skewed between sister partners but females pay greater energetic costs per own offspring reared with an unrelated partner. The choice of close kin as cooperative partners is strongly favoured by these direct as well as indirect benefits, providing a driver to maintain female kin groups for communal breeding.
High resolution structures define divergent and convergent mechanisms of archaeal proteasome activation
Authors: Chuah Janelle J. Y. , Rexroad Matthew S. , Smith David M. 
Published: July 2023

AbstractConsidering the link between neurodegenerative diseases and impaired proteasome function, and the neuro-protective impact of enhanced proteasome activity in animal models, it’s crucial to understand proteasome activation mechanisms. A hydrophobic-tyrosine-any residue (HbYX) motif on the C-termini of proteasome-activating complexes independently triggers gate-opening of the 20S core particle for protein degradation; however, the causal allosteric mechanism remains unclear. Our study employs a structurally irreducible dipeptide HbYX mimetic to investigate the allosteric mechanism of gate-opening in the archaeal proteasome. High-resolution cryo-EM structures pinpoint vital residues and conformational changes in the proteasome α-subunit implicated in HbYX-dependent activation. Using point mutations, we simulated the HbYX-bound state, providing support for our mechanistic model. We discerned four main mechanistic elements triggering gate-opening: 1) back-loop rearrangement adjacent to K66, 2) intra- and inter- α subunit conformational changes, 3) occupancy of the hydrophobic pocket, and 4) a highly conserved isoleucine-threonine pair in the 20S channel stabilizing the open and closed states, termed the "IT switch." Comparison of different complexes unveiled convergent and divergent mechanism of 20S gate-opening among HbYX-dependent and independent activators. This study delivers a detailed molecular model for HbYX-dependent 20S gate-opening, enabling the development of small molecule proteasome activators that hold promise to treat neurodegenerative diseases.