bluuebunny/crossref_metadata_2025_split huggingface dataset:
Complex drivers of primary production along an anthropised estuary (Seine estuary—France)
Authors: Serre-Fredj Léon , Chasselin Léo , Jolly Orianne , Claquin Pascal 
Published: June 2023

The Seine estuary is a typical model of a system in which phosphorus (P) inputs have been considerably reduced to reduce past eutrophication, with a parallel decrease in phytoplankton biomass. However, reducing P alone while concentrations of nitrate (N) remains high led to a dystrophic nutrient balance in the estuary (high N/P and N/Si). To identify the drivers of primary production and phytoplankton communities in the highly anthropised Seine estuary, sampling was performed along a 110-km stretch over a period of 3 years. Photosynthetic parameters were measured with a single turnover active fluorimeter and the phytoplankton community was assessed using a fluoroprobe and flow cytometry. The results revealed an annual primary production of 33 g C.m−2.y−1 which was largely controlled by light availability (turbidity) but also by nutrients in late spring and summer period. Massive blooms, not seen since 2002, were observed in a specific area of the estuary. None of the nutrients measured explained the particular location of the blooms but phytoplankton production and productivity indicators were higher in this specific zone excluding a biomass accumulation phenomenon. The local effect of tide slowdown increasing water residence time in this exact part of the estuary could explain the bloom area. The question thus arises: does phosphate play a role as a limiting nutrient? The diatom bloom led to total depletion of Si, but no clear limitation of P was observed. Nevertheless, the decrease in Si appears to have played a key role by triggering a succession from diatoms (microphytoplankton) to chlorophytes (nanophytoplankton) and hence affecting phytoplankton composition. The N/P balance appeared to be more important than the absolute concentration of P to explain the phytoplankton dynamics and the biomass decrease observed the last decades.
A chromosomal microarray analysis-based laboratory algorithm for the detection of genetic etiology of early pregnancy loss
Authors: Liao Na , Zhang Zhu , Liu Xijing , Wang Jiamin , Hu Rui , Xiao Like , Yang Yunyuan , Lai Yi , Zhu Hongmei , Li Lingping , Liu Shanling , Wang He , Hu Ting 
Published: June 2023

Background: Chromosomal abnormalities are a major cause of early pregnancy loss. However, models synthesizing existing genetic technologies to improve pregnancy outcomes are lacking. We aim to provide an integrated laboratory algorithm for the genetic etiology of couples who experienced pregnancy loss.Methods: Over a 6-year period, 3,634 products of conception (POCs) following early pregnancy loss were collected. The clinical outcomes from a laboratory algorithm based on single nucleotide polymorphism (SNP) array, fluorescence in situ hybridization (FISH), and parental chromosomal karyotyping assays were comprehensively evaluated.Results: In total, 3,445 of 3,634 (94.8%) POCs had no maternal-cell contamination. Of those POCs, the detection rate of abnormal results was 65.2% (2,247/3,445), of which 91.2% (2,050/2,247) had numerical chromosomal abnormalities, 2.7% (60/2,247) had copy-number variations (CNVs) ≥10 Mb, 2.7% (61/2,247) had CNVs of terminal deletion and duplication, 2.8% (62/2,247) had CNVs &lt;10 Mb, and 0.6% (14/2,247) had uniparental disomy. Furthermore, FISH confirmed 7 of the 60 POCs with mosaic aneuploids below 30% based on the SNP array results as tetraploid. Of the 52 POCs with CNVs of terminal deletion and duplication, 29 couples had balanced rearrangements based on chromosomal karyotyping.Conclusion: The integrated SNP array-based algorithm combined with optional FISH and parental chromosomal karyotyping is an effective laboratory testing strategy, providing a comprehensive and reliable genetic investigation for the etiology of miscarriage, regardless of the number of miscarriages and the method of conception.
Pan-cancer analysis shows that IBSP is a potential prognostic and immunotherapeutic biomarker for multiple cancer types including osteosarcoma
Authors: Pan Boyu , Cheng Xiaoyun , Tan Wei , Liu Renfeng , Wu Xin , He Jinpeng , Fan Qizhi , Zhang Yan , Cheng Jun , Deng Youwen 
Published: June 2023

BackgroundIBSP is a member of the small integrin-binding ligand N-linked glycoprotein (SIBLING) family that plays a vital role in bone formation, renewal and repair. Emerging evidence revealed that IBSP participated in the tumorigenesis and progression in some cancers. However, its significance in tumour prognosis and immunotherapy is still unknown.MethodsIn the current study, we studied the role of IBSP in tumorigenesis, tumor diagnosis, genomic heterogeneity, methylation modifications, immune infiltration, and therapy response in pan-cancer. In addition, we constructed a risk score model to assessed the prognostic classification efficiency of IBSP using the co-expression genes of IBSP in osteosarcoma (OS), and analyzed the expression and role of IBSP in OS through a series of assays in vitro.ResultsIBSP was upregulated in various cancers compared to the paired normal tissues, and it was strongly correlated with the prognosis, pathological stage, diagnostic accuracy, genomic heterogeneity, methylation modification, immune infiltration, immune and checkpoint. Moreover, the predictive model we established in combination with the clinical characteristics of OS patients showed high survival predictive power in these individuals. The assays in vitro showed that IBSP promoted the proliferation, migration and invasion of OS cells, which further confirmed IBSP’s role in cancers.ConclusionsOur research revealed the multifunctionality of IBSP in the tumorigenesis, progression and therapy in various cancers, which demonstrated that IBSP may serve as a potential prognostic biomarker and a novel immunotherapy target in pan-cancer.
Immunogenicity and protective efficacy of an RSV G S177Q central conserved domain nanoparticle vaccine
Authors: Bergeron Harrison C. , Murray Jackelyn , Juarez Maria G. , Nangle Samuel J. , DuBois Rebecca M. , Tripp Ralph A. 
Published: June 2023

IntroductionRespiratory syncytial virus (RSV) can cause lower respiratory tract disease in infants and elderly populations. Despite decades of research, there remains no safe and approved RSV vaccine. Previously, we showed that an RSV G glycoprotein subunit vaccine candidate with a single point mutation within the central conserved domain (CCD), i.e. S177Q, considerably improved immunogenicity.MethodsHere, we examine the development of nanoparticle (NP) vaccines having either an RSV G protein CCD with wild-type sequence (NPWT) or an S177Q mutation (NP-S177Q). The NP vaccine immunogens were adjuvanted with monophosphoryl lipid A (MPLA), a TLR4 agonist to improve Th1- type responses. BALB/c mice were primed with 10 μg of NP-WT vaccine, NPS177Q, or vehicle, rested, and then boosted with a high (25 μg) or low (10 μg) dose of the NP-WT or NP-S177Q homologous candidate and subsequently challenged with RSV A2.ResultsThe results showed that mice boosted with NP-S177Q developed superior immunogenicity and neutralizing antibodies compared to NP-WT boosting. IgG from either NP-S177Q or NP-WT vaccinated mice did not interfere with fractalkine (CX3CL1) binding to CX3CR1 and effectively blocked G protein CX3C-CX3CR1 binding. Both NP-WT and NP-S177Q vaccination induced similar neutralizing antibodies to RSV in challenged mice compared to vehicle control. NP-S177Q boosting improved correlates of protection including reduced BAL cell infiltration following RSV challenge. However, the NP vaccine platform will require improvement due to the poor solubility and the unexpectedly weaker Th1-type IgG2a response.DiscussionThe results from this study support further NP-S177Q vaccine candidate development.
Deep learning system for distinguishing optic neuritis from non-arteritic anterior ischemic optic neuropathy at acute phase based on fundus photographs
Authors: Liu Kaiqun , Liu Shaopeng , Tan Xiao , Li Wangting , Wang Ling , Li Xinnan , Xu Xiaoyu , Fu Yue , Liu Xiaoning , Hong Jiaming , Lin Haotian , Yang Hui 
Published: June 2023

PurposeTo develop a deep learning system to differentiate demyelinating optic neuritis (ON) and non-arteritic anterior ischemic optic neuropathy (NAION) with overlapping clinical profiles at the acute phase.MethodsWe developed a deep learning system (ONION) to distinguish ON from NAION at the acute phase. Color fundus photographs (CFPs) from 871 eyes of 547 patients were included, including 396 ON from 232 patients and 475 NAION from 315 patients. Efficientnet-B0 was used to train the model, and the performance was measured by calculating the sensitivity, specificity, and area under the receiver operating characteristic curve (AUC). Also, Cohen’s kappa coefficients were obtained to compare the system’s performance to that of different ophthalmologists.ResultsIn the validation data set, the ONION system distinguished between acute ON and NAION achieved the following mean performance: time-consuming (23 s), AUC 0.903 (95% CI 0.827–0.947), sensitivity 0.796 (95% CI 0.704–0.864), and specificity 0.865 (95% CI 0.783–0.920). Testing data set: time-consuming (17 s), AUC 0.902 (95% CI 0.832–0.944), sensitivity 0.814 (95% CI 0.732–0.875), and specificity 0.841 (95% CI 0.762–0.897). The performance (κ = 0.805) was comparable to that of a retinal expert (κ = 0.749) and was better than the other four ophthalmologists (κ = 0.309–0.609).ConclusionThe ONION system performed satisfactorily distinguishing ON from NAION at the acute phase. It might greatly benefit the challenging differentiation between ON and NAION.
Effect of biochar and bioorganic fertilizer on the microbial diversity in the rhizosphere soil of Sesbania cannabina in saline-alkaline soil
Authors: Gu Yin-yu , Liang Xiao-yan , Zhang Hai-yang , Fu Rao , Li Meng , Chen Chuan-jie 
Published: June 2023

IntroductionBiochar and bioorganic fertilizer (BOF) application in agriculture has garnered increasing interest recently. However, the effects of biochar and BOF on rhizosphere soil microecology, especially in a region with saline-alkaline soil, remain largely unexplored.MethodsIn this study, we performed Illumina-based 16S rRNA sequencing to investigate the effects of biochar with or without BOF addition, as well as at different addition rates and particles sizes, on the microecology of saline-alkaline rhizosphere soil.ResultsIn the field experiment, biochar and BOF application altered the rhizosphere soil microecology. Actinobacteriota, Proteobacteria, and Chloroflexi accounted for &gt;60% of the total bacterial population in each treatment. In the different treatments, Actinobacteria and Alphaproteobacteria were the predominant classes; Micromonosporales and Vicinamibacterales were the dominant orders; norank_f__Geminicoccaceae and Micromonosporaceae were the most abundant families; and Micromonospora and norank_f_Geminicoccaceae were the predominant genera. Application of biochar with or without BOF decreased soil electrical conductivity (EC) by 7% -11.58% only at the depth of 10 cm below the surface, again, soil EC can be significantly reduced by an average of 4% at 10 cm depth soil after planting Sesbania cannabina. Soil organic carbon, organic matter, available potassium, and available phosphorus contents had significant effects on the soil bacterial community structure.ConclusionCo-application of biochar and BOF resulted in the greatest improvement of rhizosphere soil microecology, either by promoting plant growth or improving the nutrition and physicochemical properties of soil, followed by BOF alone and biochar alone. Additionally, higher application rate of biochar was better than lower application rate, and fine biochar had a stronger effect than coarse biochar. These results provide guidance for the development of new saline-alkaline soil remediation strategies.
Investigation of multidrug-resistant plasmids from carbapenemase-producing Klebsiella pneumoniae clinical isolates from Pakistan
Authors: Lascols Christine , Cherney Blake , Conley Andrew B. , Rishishwar Lavanya , Crawford Matthew A. , Morse Stephen A. , Fisher Debra J. , Anderson Kevin , Hodge David R. , Pillai Segaran P. , Hughes Molly A. , Khan Erum , Sue David 
Published: June 2023

ObjectivesThe study aim was to investigate multidrug-resistant (MDR) plasmids from a collection of 10 carbapenemase-producing Klebsiella pneumoniae clinical isolates identified within the same healthcare institution in Pakistan. Full characterization of the MDR plasmids including structure, typing characteristics, and AMR content as well as determination of their plasmid-based antimicrobial susceptibility profiles were carried out.MethodsPlasmids were isolated from 10 clinical isolates of Klebsiella pneumoniae, and from a corresponding set of Escherichia coli transconjugants, then sequenced using Nanopore/Illumina technology to generate plasmid hybrid assemblies. Full characterization of MDR plasmids, including determination of next generation sequencing (NGS)-based AMR profiles, plasmid incompatibility groups, and types, was carried out. The structure of MDR plasmids was analyzed using the Galileo AMR platform. For E. coli transconjugants, the NGS-based AMR profiles were compared to NGS-predicted AMR phenotypes and conventional broth microdilution (BMD) antimicrobial susceptibility testing (AST) results.ResultsAll carbapenemase-producing K. pneumoniae isolates (carrying either blaNDM-1, or/and blaOXA-48) carried multiple AMR plasmids encoding 34 antimicrobial resistance genes (ARGs) conferring resistance to antimicrobials from 6 different classes. The plasmid incompatibility groups and types identified were: IncC (types 1 and 3), IncFIA (type 26) IncFIB, IncFII (types K1, K2, K7, and K9), IncHI1B, and IncL. None of the blaNDM-1 and blaESBL-plasmids identified in this study were previously described. Most blaNDM-1-plasmids shared identical AMR regions suggesting potential genetic material/plasmid exchange between K. pneumoniae isolates of this collection. The majority of NGS-based AMR profiles from the E. coli transconjugants correlated well with both NGS-based predicted and conventional AST results.ConclusionThis study highlights the complexity and diversity of the plasmid-based genetic background of carbapenemase-producing clinical isolates from Pakistan. This study emphasizes the need for characterization of MDR plasmids to determine their complete molecular background and monitor AMR through plasmid transmission between multi-resistant bacterial pathogens.
APOE ε4 allele, along with G206D-PSEN1 mutation, alters mitochondrial networks and their degradation in Alzheimer’s disease
Authors: Costa-Laparra Irene , Juárez-Escoto Elena , Vicario Carlos , Moratalla Rosario , García-Sanz Patricia 
Published: June 2023

IntroductionAlzheimer’s disease remains the most common neurodegenerative disorder, depicted mainly by memory loss and the presence in the brain of senile plaques and neurofibrillary tangles. This disease is related to several cellular alterations like the loss of synapses, neuronal death, disruption of lipid homeostasis, mitochondrial fragmentation, or raised oxidative stress. Notably, changes in the autophagic pathway have turned out to be a key factor in the early development of the disease. The aim of this research is to determine the impact of the APOE allele ε4 and G206D-PSEN1 on the underlying mechanisms of Alzheimer’s disease.MethodsFibroblasts from Alzheimer’s patients with APOE 3/4 + G206D-PSEN1 mutation and homozygous APOE ε4 were used to study the effects of APOE polymorphism and PSEN1 mutation on the autophagy pathway, mitochondrial network fragmentation, superoxide anion levels, lysosome clustering, and p62/SQSTM1 levels.ResultsWe observed that the APOE allele ε4 in homozygosis induces mitochondrial network fragmentation that correlates with an increased colocalization with p62/SQSTM1, probably due to an inefficient autophagy. Moreover, G206D-PSEN1 mutation causes an impairment of the integrity of mitochondrial networks, triggering high superoxide anion levels and thus making APOE 3/4 + PSEN1 fibroblasts more vulnerable to cell death induced by oxidative stress. Of note, PSEN1 mutation induces accumulation and clustering of lysosomes that, along with an increase of global p62/SQSTM1, could compromise lysosomal function and, ultimately, its degradation.ConclusionThe findings suggest that all these modifications could eventually contribute to the neuronal degeneration that underlies the pathogenesis of Alzheimer’s disease. Further research in this area may help to develop targeted therapies for the treatment of Alzheimer’s disease.
Correlation analysis between subtest scores of CERAD-K and a newly developed tablet computer-based digital cognitive test (Inbrain CST)
Authors: Na Seunghee , Seo Sang Won , Kim Young Ju , Yoo Heejin , Lee Eek-Sung 
Published: June 2023

IntroductionThe prevalence of Alzheimer’s disease (AD) and other dementias is increasing; therefore, identifying individuals at risk for dementia is crucial. Traditional neuropsychological assessments are expensive and time-consuming; however, computerized cognitive testing is becoming popular in clinical and research settings, particularly during the COVID-19 pandemic. This study aimed to investigate the correlation between the computerized cognitive test, Inbrain cognitive screening test (CST), and the traditional neuropsychological battery, the consortium to establish a registry for Alzheimer’s disease assessment packet (CERAD-K).MethodsWe enrolled 166 participants from five districts in Republic of Korea, including cognitively unimpaired individuals and those with mild cognitive impairment (MCI) diagnosed by experienced neurologists. We used the Inbrain CST and CERAD-K to evaluate the cognitive function of the participants, and the scores of each subtest of the Inbrain CST and CERAD-K were compared.ResultsA significant correlation was found between the Inbrain CST and CERAD-K subtests. Furthermore, multivariate analysis revealed a significant correlation between the Inbrain CST and the CERAD-K test pairs after adjusting for age, educational level, and sex.DiscussionIn conclusion, this study demonstrates that the Inbrain CST is a reliable tool for detecting cognitive impairment in cognitively unimpaired individuals and patients with MCI, because it has a high correlation and agreement with CERAD-K. Therefore, the Inbrain CST can be a useful, time-efficient, and cost-effective computer-based cognitive test for individuals at risk for cognitive impairment.
Placebo effect after visual restitution training: no eye-tracking controlled perimetric improvement after visual border stimulation in late subacute and chronic visual field defects after stroke
Authors: Leitner Michael Christian , Ladek Anja-Maria , Hutzler Florian , Reitsamer Herbert , Hawelka Stefan 
Published: June 2023

IntroductionA significant number of Restitution Training (RT) paradigms claim to ameliorate visual field loss after stroke by re-activating neuronal connections in the residual visual cortex due to repeated bright light-stimulation at the border of the blind and intact fields. However, the effectiveness of RT has been considered controversial both in science and clinical practice for years. The main points of the controversy are (1) the reliability of perimetric results which may be affected by compensatory eye movements and (2) heterogeneous samples consisting of patients with visual field defects and/or visuospatial neglect.MethodsBy means of our newly developed and validated Virtual Reality goggles Salzburg Visual Field Trainer (SVFT) 16 stroke patients performed RT on a regular basis for 5  months. By means of our newly developed and validated Eye Tracking Based Visual Field Analysis (EFA), we conducted a first-time full eye-movement-controlled perimetric pre-post intervention study. Additionally, patients subjectively rated the size of their intact visual field.ResultsAnalysis showed that patients’ mean self-assessment of their subjective visual field size indicated statistically significant improvement while, in contrast, objective eye tracking controlled perimetric results revealed no statistically significant effect.DiscussionBright-light detection RT at the blind-field border solely induced a placebo effect and did not lead to training-induced neuroplasticity in the visual cortex of the type needed to ameliorate the visual field size of stroke patients.
Emerging V1 neuronal ensembles with enhanced connectivity after associative learning
Authors: Si Yue-Guang , Su Wen-Xin , Chen Xing-Dong , Li Ze-Yu , Yan Biao , Zhang Jia-Yi 
Published: June 2023

IntroductionThe visual stimulus-specific responses in the primary visual cortex (V1) undergo plastic changes after associative learning. During the learning process, neuronal ensembles, defined as groups of coactive neurons, are well known to be related to learning and memory. However, it remains unclear what effect learning has on ensembles, and which neuronal subgroups within those ensembles play a key role in associative learning.MethodsWe used two-photon calcium imaging in mice to record the activity of V1 neurons before and after fear conditioning associated with a visual cue (blue light). We first defined neuronal ensembles by thresholding their functional connectivity in response to blue (conditioned) or green (control) light. We defined neurons that existed both before and after conditioning as stable neurons. Neurons which were recruited after conditioning were defined as new neurons. The graph theory-based analysis was performed to quantify the changes in connectivity within ensembles after conditioning.ResultsA significant enhancement in the connectivity strength (the average correlation with other neurons) was observed in the blue ensembles after conditioning. We found that stable neurons within the blue ensembles showed a significantly smaller clustering coefficient (the value represented the degree of interconnectedness among a node's neighbors) after conditioning than they were before conditioning. Additionally, new neurons within the blue ensembles had a larger clustering coefficient, similar relative degree (the value represented the number of functional connections between neurons) and connectivity strength compared to stable neurons in the same ensembles.DiscussionOverall, our results demonstrated that the plastic changes caused by conditioning occurred in subgroups of neurons in the ensembles. Moreover, new neurons from conditioned ensembles may play a crucial role in memory formation, as they exhibited not only similar connection competence in relative degree and connectivity strength as stable neurons, but also showed a significantly larger clustering coefficient compared to the stable neurons within the same ensembles after conditioning.