bluuebunny/crossref_metadata_2025 huggingface dataset:
B cell metabolism in autoimmune diseases: signaling pathways and interventions
Authors: Li Jingyue , Zhao Mingjiu , Luo Wenjun , Huang Jiaqi , Zhao Bin , Zhou Zhiguang
Published: August 2023

Autoimmune diseases are heterogeneous disorders believed to stem from the immune system’s inability to distinguish between auto- and foreign- antigens. B lymphocytes serve a crucial role in humoral immunity as they generate antibodies and present antigens. Dysregulation of B cell function induce the onset of autoimmune disorders by generating autoantibodies and pro-inflammatory cytokines, resulting in an imbalance in immune regulation. New research in immunometabolism shows that cellular metabolism plays an essential role in controlling B lymphocytes immune reactions by providing the energy and substrates for B lymphocytes activation, differentiation, and function. However, dysregulated immunometabolism lead to autoimmune diseases by disrupting self-tolerance mechanisms. This review summarizes the latest research on metabolic reprogramming of B lymphocytes in autoimmune diseases, identifying crucial pathways and regulatory factors. Moreover, we consider the potential of metabolic interventions as a promising therapeutic strategy. Understanding the metabolic mechanisms of B cells brings us closer to developing novel therapies for autoimmune disorders.
Bed level changes in the surf zone during post-storm beach recovery
Authors: Hu Pengpeng , Li Zhiqiang , Zeng Chunhua , Zhu Daoheng , Liu Run , Su Qianxin , Tang Jieping , Zhu Yamin
Published: August 2023

The study of post-storm beach recovery is important for economic development and the protection of life in coastal areas. In this study, field observations were conducted for 21 days in the surf zone of Dongdao Beach, Hailing Island, China, after tropical storm “Cempaka”. Data on depth, wave, Eulerian velocity, sediment, three-dimensional topography of the beach, and high-frequency variations in bed-level elevation were collected. The results showed that the beach experienced medium- to low- to medium-energy waves during field observations and covered two complete astronomical tide cycles. Contrary to the effect of wave energy conditions on beaches under normal wave conditions, a higher wave energy during beach recovery can promote silting and accelerate beach recovery. Tidal water level is an important factor affecting beach restoration, and a smaller tidal range is conducive to beach accretion. In a mixed semidiurnal tide, beach erosion and accretion occurred in the “highest tide” and “sub-highest tide” tidal cycles, respectively, and the combined effect of the two affected the change in the bed level in a mixed semidiurnal tide. After the storm, the hydrodynamic forcing mechanism and self-organization process of the sand bar jointly drove the formation of the topography of the bar channel in the surf zone. After the storm stopped, the spectral energy in free surface elevation was mainly distributed in the very low frequency and decayed rapidly at the infragravity band. The very low-frequency pulsation of the surf zone during recovery is a prominent feature of bed-level elevation, depth, and velocity. This study provides a good case for the study of hydrodynamic and bed level changes in the post-storm surf zone, as well as a reference for future studies of the intrinsic mechanisms post-storm beach recovery processes around the world.
Study on the growth mechanism of the internal oxide layer in 9% Ni cryogenic steel
Authors: Du Hegang , Sun Haoran , Cai Minghui , Zuo Xiurong
Published: August 2023

The oxidation behavior of the Ni-rich layer in the internal oxide layer (IOL) in 9% Ni cryogenic steel is investigated at 1,150°C for 0–240 min in the air atmosphere. The morphology and phase composition of the Ni—rich layer are analyzed with energy dispersive spectroscopy, scanning electron microscopy, metallographic microscopy, and X—ray diffraction. The results show that the Ni—rich layer mainly consists of gray Fe3O4/FeO and white Ni–Fe particles, with a small amount of black Fe2SiO4. The morphologies of Ni–Fe particles undergo the following changes with isothermal oxidation time: dot—like → strip—like → net-like; at the same time, layered Ni–Fe particles were formed at about 1/3 of the thickness of the Ni—rich layer. Compared with the dot-like Ni–Fe particle, the net-like and layered Ni–Fe particles provide a fast path for the diffusion of O in the Ni—rich layer. However, the experimental steel still has a much lower oxidation rate because of the hindrance of Ni–Fe particles on the out-diffusion of Fe. During the oxidation process, the Kirkendall effect induces pores/cavities in the IOL, which weakens the stability of the IOL. In the end, the spalling phenomenon of the layered Ni–Fe particle occurs at 1,150°C for 180 min.
The long and sinuous road to phage-based therapy of Clostridioides difficile infections
Authors: Umansky Andrew A. , Fortier Louis Charles
Published: August 2023

With the antibiotic crisis and the rise in antimicrobial resistance worldwide, new therapeutic alternatives are urgently needed. Phage therapy represents one of the most promising alternatives but for some pathogens, such as Clostridioides difficile, important challenges are being faced. The perspective of phage therapy to treat C. difficile infections is complicated by the fact that no strictly lytic phages have been identified so far, and current temperate phages generally have a narrow host range. C. difficile also harbors multiple antiphage mechanisms, and the bacterial genome is often a host of one or multiple prophages that can interfere with lytic phage infection. Nevertheless, due to recent advances in phage host receptor recognition and improvements in genetic tools to manipulate phage genomes, it is now conceivable to genetically engineer C. difficile phages to make them suitable for phage therapy. Other phage-based alternatives such as phage endolysins and phage tail-like bacteriocins (avidocins) are also being investigated but these approaches also have their own limitations and challenges. Last but not least, C. difficile produces spores that are resistant to phage attacks and all current antibiotics, and this complicates therapeutic interventions. This mini-review gives a brief historical overview of phage work that has been carried out in C. difficile, presents recent advances in the field, and addresses the most important challenges that are being faced, with potential solutions.
Grapevines escaping trunk diseases in New Zealand vineyards have a distinct microbiome structure
Authors: Adejoro Damola O. , Jones E. Eirian , Ridgway Hayley J. , Mundy Dion C. , Vanga Bhanupratap R. , Bulman Simon R.
Published: August 2023

Grapevine trunk diseases (GTDs) are a substantial challenge to viticulture, especially with a lack of available control measures. The lack of approved fungicides necessitates the exploration of alternative controls. One promising approach is the investigation of disease escape plants, which remain healthy under high disease pressure, likely due to their microbiome function. This study explored the microbiome of grapevines with the disease escape phenotype. DNA metabarcoding of the ribosomal internal transcribed spacer 1 (ITS1) and 16S ribosomal RNA gene was applied to trunk tissues of GTD escape and adjacent diseased vines. Our findings showed that the GTD escape vines had a significantly different microbiome compared with diseased vines. The GTD escape vines consistently harbored a higher relative abundance of the bacterial taxa Pseudomonas and Hymenobacter. Among fungi, Aureobasidium and Rhodotorula were differentially associated with GTD escape vines, while the GTD pathogen, Eutypa, was associated with the diseased vines. This is the first report of the link between the GTD escape phenotype and the grapevine microbiome.
Co-circulation of Chikungunya virus, Zika virus, and serotype 1 of Dengue virus in Western Bahia, Brazil
Authors: de França Cirilo Marcus Vinicius , Pour Shahab Zaki , de Fatima Benedetti Viviane , Farias Jéssica Pires , Fogaça Mayanna Moreira Costa , da Conceição Simões Rafael , Vidal Paloma Oliveira , Birbrair Alexander , de Andrade Zanotto Paolo Marinho , Luiz Wilson Barros , Amorim Jaime Henrique
Published: August 2023

Chikungunya, mayaro, dengue, zika, and yellow fever are mosquito-borne viral diseases caused, respectively, by Chikungunya virus, Mayaro virus (CHIKV and MAYV, respectively: Togaviridae: Alphavirus), Dengue virus, Zika virus, and Yellow fever virus (DENV, ZIKV, and YFV, respectively: Flaviviridae: Flavivirus). These viruses have an important epidemiological impact worldwide, especially in Brazil. Western Bahia is one of the less studied regions in that country regarding the circulation of these pathogens. In this study, we aimed to apply molecular biology assays to better know the mosquito-borne viruses circulating in Barreiras and Luís Eduardo Magalhães, two main cities of Western Bahia. From March to June 2021, we enrolled 98 patients with the clinical diagnosis of dengue. Personal information (gender and age) were retrieved at the moment of enrollment. Serum samples were obtained from volunteers and used in molecular detection of CHIKV, MAYV, DENV, ZIKV, and YFV by reverse transcription followed by real-time polymerase chain reaction as well as in genome sequencing aiming phylogenetic analysis. As the main result, we found that from the 98 patients 45 were infected by CHIKV, 32 were infected by serotype 1 of DENV (DENV-1) and six were infected by ZIKV, while 15 were negative for all arboviruses tested. In addition, phylogenetic analysis revealed that all CHIKV-positive samples were of the East/Central/South African (ECSA) genotype, while all DENV-1-positive samples were of the V genotype. These results clearly show that epidemiological surveillance cannot be based only on clinical evaluations. Laboratory diagnosis is important in arbovirus infection that are prevalent in a particular area. These findings also demonstrate the co-circulation of many arboviruses in Western Bahia in 2021.
Assessing seizure liability in vitro with voltage-sensitive dye imaging in mouse hippocampal slices
Authors: Utsumi Yuichi , Taketoshi Makiko , Miwa Michiko , Tominaga Yoko , Tominaga Takashi
Published: August 2023

Non-clinical toxicology is a major cause of drug candidate attrition during development. In particular, drug-induced seizures are the most common finding in central nervous system (CNS) toxicity. Current safety pharmacology tests for assessing CNS functions are often inadequate in detecting seizure-inducing compounds early in drug development, leading to significant delays. This paper presents an in vitro seizure liability assay using voltage-sensitive dye (VSD) imaging techniques in hippocampal brain slices, offering a powerful alternative to traditional electrophysiological methods. Hippocampal slices were isolated from mice, and VSD optical responses evoked by stimulating the Schaffer collateral pathway were recorded and analyzed in the stratum radiatum (SR) and stratum pyramidale (SP). VSDs allow for the comprehensive visualization of neuronal action potentials and postsynaptic potentials on a millisecond timescale. By employing this approach, we investigated the in vitro drug-induced seizure liability of representative pro-convulsant compounds. Picrotoxin (PiTX; 1–100 μM), gabazine (GZ; 0.1–10 μM), and 4-aminopyridine (4AP; 10–100 μM) exhibited seizure-like responses in the hippocampus, but pilocarpine hydrochloride (Pilo; 10–100 μM) did not. Our findings demonstrate the potential of VSD-based assays in identifying seizurogenic compounds during early drug discovery, thereby reducing delays in drug development and providing insights into the mechanisms underlying seizure induction and the associated risks of pro-convulsant compounds.
Case report: A combination of nitroglycerin and adenosine proves effective in repairing a cerebral arteriovenous malformation
Authors: Rojas-Nieves Virginia , Rosa-Carrasquillo Cristian , Reyes-Sullivan Allan , Román Marie , Feliciano-Valls Caleb E. , Torres-Pérez Héctor M. , Fernández Pamela , Crespo María J.
Published: August 2023

Hemorrhage secondary to rupture of a brain arteriovenous malformations (AVM) is one of the initial manifestations, and the main cause of, morbidity and mortality in patients with this condition. Current treatment strategies include endovascular embolization with the goal of AVM obliteration and neurological preservation. In the transvenous endovascular embolization procedure, adenosine is the preferred agent to induce temporary hypotension and allow adequate AVM embolization. We describe the intraoperative management of an adenosine-resistant 38 year-old male who underwent a successful intracranial AVM embolization after concomitant administration of gradually increasing doses of nitroglycerin. This report suggests that nitroglycerin infusion can be combined with adenosine boluses to create a pronounced and dose-dependent hypotension in patients partially unresponsive to adenosine alone.
Microbleed clustering in thalamus sign in CADASIL patients with NOTCH3 R75P mutation
Authors: Takei Jun , Higuchi Yujiro , Ando Masahiro , Yoshimura Akiko , Yuan Jun-Hui , Fujisaki Natsumi , Tokashiki Takashi , Kanzato Naomi , Jonosono Manabu , Sueyoshi Takeshi , Kanda Naoaki , Matsuoka Hideki , Okubo Ryuichi , Suehara Masahito , Matsuura Eiji , Takashima Hiroshi
Published: August 2023

Background and objective

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited cerebral microvascular disease characterized by the development of vascular dementia and lacunar infarctions. This study aimed to identify the genetic and clinical features of CADASIL in Japan.

Methods

We conducted genetic analysis on a case series of patients clinically diagnosed with CADASIL. Clinical and imaging analyses were performed on 32 patients with pathogenic mutations in the NOTCH3 gene. To assess the presence of cerebral microbleeds (CMBs), we utilized several established rating scales including the Fazekas scale, Scheltens rating scale, and Microbleed Anatomical Rating Scale, based on brain MRI images.

Results

Among the 32 CADASIL patients, 24 cases were found carrying the R75P mutation in NOTCH3, whereas the remaining eight cases had other NOTCH3 mutations (R75Q, R110C, C134F, C144F, R169C, and R607C). The haplotype analysis of the R75P mutation uncovered the presence of a founder effect. A brain MRI analysis revealed that cases with the R75P mutation had a significantly higher total number of CMBs, particularly in the thalamus when compared to patients with other NOTCH3 mutations. Among 15 out of 24 cases with the R75P mutation, we observed a notable clustering of CMBs in the thalamus, termed microbleed clustering in thalamus sign (MCT sign).

Conclusion

We propose that the MCT sign observed in NOTCH3 R75P-related CADASIL patients may serve as a potentially characteristic imaging feature. This finding offers further insights into the interactions between genotypes and phenotypes between NOTCH3 and CADASIL.
Botulinum toxin use in patients with post-stroke spasticity: a nationwide retrospective study from France
Authors: Levy Jonathan , Karam Pierre , Forestier Anne , Loze Jean-Yves , Bensmail Djamel
Published: August 2023

Background

Current guidelines recommend intramuscular botulinum toxin type A (BoNT-A) injection as first-line treatment for spasticity, a frequent and impairing feature of various central nervous system (CNS) lesions such as stroke. Patients with spasticity commonly require BoNT-A injections once every 3 to 4 months. We conducted a nationwide, population-based, retrospective cohort study, using the French National Hospital Discharge Database (PMSI), to describe BoNT-A use for spasticity in clinical practice in France between 2014 and 2020. The PMSI database covers the whole French population, corresponding to over 66 million persons.

Methods

We first searched the PMSI database for healthcare facility discharge of patients who received BoNT-A injections between 2014 and 2020, corresponding to the first set. For each BoNT-A-treated patient, we identified the medical condition for which BoNT-A may have been indicated. Another search of the PMSI database focused on patients admitted for acute stroke between 2014 and 2016 and their spasticity-related care pathway (second set). Overall, two subpopulations were analysed: 138,481 patients who received BoNT-A injections between 2014 and 2020, and 318,025 patients who survived a stroke event between 2014 and 2016 and were followed up until 2020.

Results

Among the 138,481 BoNT-A-treated patients, 53.5% received only one or two BoNT-A injections. Most of these patients (N = 85,900; 62.0%) received BoNT-A because they had CNS lesions. The number of patients with CNS lesions who received ≥1 BoNT-A injection increased by a mean of 7.5% per year from 2014 to 2019, but decreased by 0.2% between 2019 and 2020, corresponding to the COVID-19 outbreak. In stroke survivors (N = 318,025), 10.7% were coded with post-stroke spasticity, 2.3% received ≥1 BoNT-A injection between 2014 and 2020, and only 0.8% received ≥3 injections within the 12 months following BoNT-A treatment initiation, i.e., once every 3 to 4 months.

Conclusion

Our analysis of the exhaustive PMSI database showed a suboptimal implementation of BoNT-A treatment recommendations in France. BoNT-A treatment initiation and re-administration are low, particularly in patients with post-stroke spasticity. Further investigations may help explain this observation, and may target specific actions to improve spasticity-related care pathway.
Publicly available ex vivo transcriptomics datasets to explore CNS physiology and neurodegeneration: state of the art and perspectives
Authors: Abdullatef Sandra , Farina Cinthia
Published: August 2023

The central nervous system (CNS) is characterized by an intricate composition of diverse cell types, including neurons and glia cells (astrocytes, oligodendrocytes, and microglia), whose functions may differ along time, between sexes and upon pathology. The advancements in high-throughput transcriptomics are providing fundamental insights on cell phenotypes, so that molecular codes and instructions are ever more described for CNS physiology and neurodegeneration. To facilitate the search of relevant information, this review provides an overview of key CNS transcriptomics studies ranging from CNS development to ageing and from physiology to pathology as defined for five neurodegenerative disorders and their relative animal models, with a focus on molecular descriptions whose raw data were publicly available. Accurate phenotypic descriptions of cellular states correlate with functional changes and this knowledge may support research devoted to the development of therapeutic strategies supporting CNS repair and function.
Integrative Bayesian tensor regression for imaging genetics applications
Authors: Liu Yajie , Chakraborty Nilanjana , Qin Zhaohui S. , Kundu Suprateek ,   The Alzheimer’s Disease Neuroimaging Initiative
Published: August 2023

Identifying biomarkers for Alzheimer's disease with a goal of early detection is a fundamental problem in clinical research. Both medical imaging and genetics have contributed informative biomarkers in literature. To further improve the performance, recently, there is an increasing interest in developing analytic approaches that combine data across modalities such as imaging and genetics. However, there are limited methods in literature that are able to systematically combine high-dimensional voxel-level imaging and genetic data for accurate prediction of clinical outcomes of interest. Existing prediction models that integrate imaging and genetic features often use region level imaging summaries, and they typically do not consider the spatial configurations of the voxels in the image or incorporate the dependence between genes that may compromise prediction ability. We propose a novel integrative Bayesian scalar-on-image regression model for predicting cognitive outcomes based on high-dimensional spatially distributed voxel-level imaging data, along with correlated transcriptomic features. We account for the spatial dependencies in the imaging voxels via a tensor approach that also enables massive dimension reduction to address the curse of dimensionality, and models the dependencies between the transcriptomic features via a Graph-Laplacian prior. We implement this approach via an efficient Markov chain Monte Carlo (MCMC) computation strategy. We apply the proposed method to the analysis of longitudinal ADNI data for predicting cognitive scores at different visits by integrating voxel-level cortical thickness measurements derived from T1w-MRI scans and transcriptomics data. We illustrate that the proposed imaging transcriptomics approach has significant improvements in prediction compared to prediction using a subset of features from only one modality (imaging or genetics), as well as when using imaging and transcriptomics features but ignoring the inherent dependencies between the features. Our analysis is one of the first to conclusively demonstrate the advantages of prediction based on combining voxel-level cortical thickness measurements along with transcriptomics features, while accounting for inherent structural information.
Novel role for non-invasive neuromodulation techniques in central respiratory dysfunction
Authors: Lv Lan , Cheng Xiaoping , Yang Jiaying , Chen Xinyuan , Ni Jun
Published: August 2023

Respiration is a crucial steady-state function of human life. Central nervous system injury can damage the central respiratory pattern generator (CRPG) or interrupt its outflow, leading to central respiratory paralysis and dysfunction, which can endanger the patient's life. At present, there is no effective means to reverse this process. Commonly used non-invasive neuromodulation techniques include repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS) and so forth, which have been widely applied in nervous system diseases and their various secondary symptoms, but rarely in respiratory function. Clinical and animal studies have confirmed that TMS is also suitable for investigating the excitability and plasticity of ascending corticospinal respiratory pathways. In addition, although rTMS and tDCS differ in their respective mechanisms, both can regulate respiratory networks in healthy individuals and in diseased states. In this review, we provide an overview of the physiology of respiration, the use of TMS to assess the excitability of corticophrenic pathways in healthy individuals and in central respiratory disorders, followed by an overview of the animal and clinical studies of rTMS, tDCS and so forth in regulating respiratory circuits and the possible mechanisms behind them. It was found that the supplementary motor area (SMA) and the phrenic motor neuron (PMN) may be key regulatory areas. Finally, the challenges and future research directions of neuroregulation in respiratory function are proposed. Through understanding how neuromodulation affects the respiratory neural circuit non-invasively, we can further explore the therapeutic potential of this neuromodulation strategy, so as to promote the recovery of respiratory function after central nervous system diseases or injury.
Topological analysis of functional connectivity in Parkinson’s disease
Authors: Zhang Weiwei , Xia Shengxiang , Tang Xinhua , Zhang Xianfu , Liang Di , Wang Yinuo
Published: August 2023

Parkinson’s disease (PD) is a clinically heterogeneous disorder, which mainly affects patients’ motor and non-motor function. Functional connectivity was preliminary explored and studied through resting state functional magnetic resonance imaging (rsfMRI). Through the topological analysis of 54 PD scans and 31 age-matched normal controls (NC) in the Neurocon dataset, leveraging on rsfMRI data, the brain functional connection and the Vietoris-Rips (VR) complex were constructed. The barcodes of the complex were calculated to reflect the changes of functional connectivity neural circuits (FCNC) in brain network. The 0-dimensional Betti number β0 means the number of connected branches in VR complex. The average number of connected branches in PD group was greater than that in NC group when the threshold δ ≤ 0.7. Two-sample Mann–Whitney U test and false discovery rate (FDR) correction were used for statistical analysis to investigate the FCNC changes between PD and NC groups. In PD group, under threshold of 0.7, the number of FCNC involved was significantly differences and these brain regions include the Cuneus_R, Lingual_R, Fusiform_R and Heschl_R. There are also significant differences in brain regions in the Frontal_Inf_Orb_R and Pallidum_R, when the threshold increased to 0.8 and 0.9 (p < 0.05). In addition, when the length of FCNC was medium, there was a significant statistical difference between the PD group and the NC group in the Neurocon dataset and the Parkinson’s Progression Markers Initiative (PPMI) dataset. Topological analysis based on rsfMRI data may provide comprehensive information about the changes of FCNC and may provide an alternative for clinical differential diagnosis.
Multi-phase-combined CECT radiomics models for Fuhrman grade prediction of clear cell renal cell carcinoma
Authors: Zhou Zhiyong , Qian Xusheng , Hu Jisu , Geng Chen , Zhang Yongsheng , Dou Xin , Che Tuanjie , Zhu Jianbing , Dai Yakang
Published: August 2023

Objective

This study aimed to evaluate the effectiveness of multi-phase-combined contrast-enhanced CT (CECT) radiomics methods for noninvasive Fuhrman grade prediction of clear cell renal cell carcinoma (ccRCC).

Methods

A total of 187 patients with four-phase CECT images were retrospectively enrolled and then were categorized into training cohort (n=126) and testing cohort (n=61). All patients were confirmed as ccRCC by histopathological reports. A total of 110 3D classical radiomics features were extracted from each phase of CECT for individual ccRCC lesion, and contrast-enhanced variation features were also calculated as derived radiomics features. These features were concatenated together, and redundant features were removed by Pearson correlation analysis. The discriminative features were selected by minimum redundancy maximum relevance method (mRMR) and then input into a C-support vector classifier to build multi-phase-combined CECT radiomics models. The prediction performance was evaluated by the area under the curve (AUC) of receiver operating characteristic (ROC).

Results

The multi-phase-combined CECT radiomics model showed the best prediction performance (AUC=0.777) than the single-phase CECT radiomics model (AUC=0.711) in the testing cohort (p value=0.039).

Conclusion

The multi-phase-combined CECT radiomics model is a potential effective way to noninvasively predict Fuhrman grade of ccRCC. The concatenation of first-order features and texture features extracted from corticomedullary phase and nephrographic phase are discriminative feature representations.
The impact of staging FDG-PET/CT on treatment for stage III NSCLC - an analysis of population-based data from Ontario, Canada
Authors: Beers Craig A. , Pond Gregory R. , Wright James R. , Tsakiridis Theodoros , Okawara Gordon S. , Swaminath Anand
Published: August 2023

Purpose

Fluoro-2-deoxyglucose positron-emission tomography (FDG-PET/CT) is now considered a standard investigation for the staging of new cases of stage III NSCLC. However, there is not published level 3 evidence demonstrating the impact of FDG-PET/CT on appropriate therapy in this setting. Using retrospective population-based data, we sought to examine the role and timing that FDG-PET/CT scans play in influencing treatment choice, as well as survival in patients diagnosed with stage III NSCLC.

Materials and methods

A retrospective cohort of patients diagnosed with stage III NSCLC from 2009-2017 in Ontario were identified from the IC/ES (formerly Institute of Clinical Evaluative Sciences) database. FDG-PET/CT utilization over time, trends in mediastinal biopsy technique and usage, the impact of FDG-PET/CT on overall survival (OS), and its influence on use of concurrent chemoradiotherapy (CRT) were explored. The impact of timing of pre-treatment FDG-PET/CT on OS was also analyzed (≤28 days prior to treatment, 29-56 days prior, and >56 days prior).

Results

Between 2007 and 2017, a total of 13 796 people were diagnosed with stage III NSCLC in Ontario. FDG-PET/CT utilization increased over time with 0% of cases in 2007 and 74% in 2017 with pre-treatment FDG-PET/CT scans. The number of patients who received a mediastinal biopsy similarly increased in this timeframe increasing from 41% to 53%. More patients with pre-treatment FDG-PET/CT scans received curative-intent therapy than those who did not: 23% vs 13% for CRT (p<0.001), and 23% vs 10% for surgery (p<0.001). Median OS was longer in those with FDG-PET/CT scans prior to treatment (17 vs 11 months), as was 5-year survival (22% vs 14%, p<0.001), and this held true on both univariate and multivariate analyses. Timing of FDG-PET/CT scan relative to treatment was not associated with differences in OS.

Conclusion

Improvements in OS were seen in this cohort of stage III NSCLC patients who underwent a pre-treatment FDG-PET/CT scan. This can likely be attributed to stage-appropriate therapy due to more complete staging using FDG-PET/CT. This study stresses the importance of complete staging for suspected stage III NSCLC using FDG-PET/CT, and a need for continued advocacy for increased access to FDG-PET/CT scans.
Identification and validation of SERPINE1 as a prognostic and immunological biomarker in pan-cancer and in ccRCC
Authors: Li Lingqin , Li Fan , Xu Zhehao , Li Liyang , Hu Haiyi , Li Yang , Yu Shicheng , Wang Mingchao , Gao Lei
Published: August 2023

Background:SERPINE1, a serine protease inhibitor involved in the regulation of the plasminogen activation system, was recently identified as a cancer-related gene. However, its clinical significance and potential mechanisms in pan-cancer remain obscure.

Methods: In pan-cancer multi-omics data from public datasets, including The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx), and online web tools were used to analyze the expression of SERPINE1 in different cancers and its correlation with prognosis, genetic alteration, DNA promoter methylation, biological processes, immunoregulator expression levels, immune cell infiltration into tumor, tumor mutation burden (TMB), microsatellite instability (MSI), immunotherapy response and drug sensitivity. Further, two single-cell databases, Tumor Immune Single-cell Hub 2 (TISCH2) and CancerSEA, were used to explore the expression and potential roles of SERPINE1 at a single-cell level. The aberrant expression of SERPINE1 was further verified in clear cell renal cell carcinoma (ccRCC) through qRT-PCR of clinical patient samples, validation in independent cohorts using The Gene Expression Omnibus (GEO) database, and proteomic validation using the Clinical Proteomic Tumor Analysis Consortium (CPTAC) database.

Results: The expression of SERPINE1 was dysregulated in cancers and enriched in endothelial cells and fibroblasts. Copy number amplification and low DNA promoter methylation could be partly responsible for high SERPINE1 expression. High SERPINE1 expression was associated with poor prognosis in 21 cancers. The results of gene set enrichment analysis (GSEA) indicated SERPINE1 involvement in the immune response and tumor malignancy. SERPINE1 expression was also associated with the expression of several immunoregulators and immune cell infiltration and could play an immunosuppression role. Besides, SERPINE1 was found to be related with TMB, MSI, immunotherapy response and sensitivity to several drugs in cancers. Finally, the high expression of SERPINE1 in ccRCC was verified using qRT-PCR performed on patient samples, six independent GEO cohorts, and proteomic data from the CPTAC database.

Conclusion: The findings of the present study revealed that SERPINE1 exhibits aberrant expression in various types of cancers and is associated with cancer immunity and tumor malignancy, providing novel insights for individualized cancer treatment.
Differential impact of 5-lipoxygenase-activating protein antagonists on the biosynthesis of leukotrienes and of specialized pro-resolving mediators
Authors: Dahlke Philipp , Peltner Lukas K. , Jordan Paul M. , Werz Oliver
Published: August 2023

Lipoxygenases (LOX) transform arachidonic acid (AA, C20:4) and docosahexaenoic acid (DHA, C22:6) into bioactive lipid mediators (LMs) that comprise not only pro-inflammatory leukotrienes (LTs) but also the specialized pro-resolving mediators (SPMs) that promote inflammation resolution and tissue regeneration. The 5-LOX-activating protein (FLAP) is known to provide AA as a substrate to 5-LOX for generating LTs, such as LTB4, a potent chemoattractant and activator of phagocytes. Notably, 5-LOX is also involved in the biosynthesis of certain SPMs, namely, lipoxins and D-resolvins, implying a role of FLAP in SPM formation. FLAP antagonists have been intensively developed as LT biosynthesis inhibitors, but how they impact SPM formation is a matter of debate. Here, we show that FLAP antagonism suppresses the conversion of AA by 5-LOX to LT and lipoxins, while the conversion of DHA to SPM is unaffected. Screening of multiple prominent FLAP antagonists for their effects on LM formation in human M1- and M2-monocyte-derived macrophages by comprehensive LM profiling showed that all nine compounds reduced the production of 5-LOX-derived LTs but increased the formation of SPMs from DHA, e.g., resolvin D5. Some FLAP antagonists, especially those that contain an indole or benzimidazole moiety, even elicited SPM formation in resting M2-monocyte-derived macrophages. Intriguingly, in coincubations of human neutrophils and platelets that produce substantial AA-derived lipoxin and DHA-derived RvD5, FLAP antagonism abolished lipoxin formation, but resolvin D5 levels remained unaffected. Conclusively, antagonism of FLAP suppresses the conversion of AA by 5-LOX to LTs and lipoxins but not the conversion of DHA by 5-LOX to SPM, which should be taken into account for the development of such compounds as anti-inflammatory drugs.
Rapid test to detect insecticide resistance in field populations of Spodoptera frugiperda (Lepidoptera: Noctuidae)
Authors: Mao Kai-Kai , Li Hong-Ran , Zhu Jing-Yun , Jin Ming-Hui , Wang Peng , Peng Yan , Xiao Yu-Tao
Published: August 2023

Introduction: The development of insecticide resistance in Spodoptera frugiperda populations is a serious threat to the crop industry. Given the spread of invasive resistant populations, prospective monitoring should be accelerated, and the development of diagnostic tools for rapid and accurate assessments of insecticide resistance is essential.

Methods: First, the discriminating dose and diagnostic time of the kit were determined by the glass vial method based on a susceptible strain. Then, pests that were collected from field populations were used to determine their susceptibility to seven insecticides by using the diagnostic kit. Finally, the accuracy of the kit was verified based on correlation analyses and the likelihood of insecticide control failure was assessed.

Results: Here, we describe a diagnostic kit that enables the rapid detection of resistance to chlorpyrifos, bifenthrin, deltamethrin, lambda-cyhalothrin, phoxim, chlorantraniliprole and chlorfenapyr within 1-2 h in S. frugiperda at diagnostic doses of 0.98, 0.84, 0.38, 1.64, 0.0082, 1.75 and 0.65 μg/cm2, respectively. The linear equation between mortalities under diagnostic doses and actual resistance ratios measured by the diet-overlay bioassay was determined. The high correlation indicates that the insecticide resistance levels diagnosed by the kit were consistent with the results of the diet-overlay bioassay. Moreover, we found a significant negative correlation between diagnostic mortality and the likelihood of control failure for bifenthrin (r = −0.899, p = 0.001), deltamethrin (r = −0.737, p = 0.024) and lambda-cyhalothrin (r = −0.871, p = 0.002).

Discussion: The insecticide resistance diagnostic kit for S. frugiperda is a user-friendly tool (portable, short detection time). Its excellent performance qualifies the kit as a reliable screening tool for identifying effective insecticides in sustainable resistance management.
Comparative analysis of the medicinal plant Polygonatum kingianum (Asparagaceae) with related verticillate leaf types of the Polygonatum species based on chloroplast genomes
Authors: Shi Naixing , Yang Zefen , Miao Ke , Tang Lilei , Zhou Nian , Xie Pingxuan , Wen Guosong
Published: August 2023

Background

Polygonatum kingianum has been widely used as a traditional Chinese medicine as well as a healthy food. Because of its highly variable morphology, this medicinal plant is often difficult to distinguish from other related verticillate leaf types of the Polygonatum species. The contaminants in P. kingianum products not only decrease the products’ quality but also threaten consumer safety, seriously inhibiting the industrial application of P. kingianum.

Methods

Nine complete chloroplast (cp) genomes of six verticillate leaf types of the Polygonatum species were de novo assembled and systematically analyzed.

Results

The total lengths of newly sequenced cp genomes ranged from 155,437 to 155,977 bp, including 86/87 protein-coding, 38 tRNA, and 8 rRNA genes, which all exhibited well-conserved genomic structures and gene orders. The differences in the IR/SC (inverted repeats/single-copy) boundary regions and simple sequence repeats were detected among the verticillate leaf types of the Polygonatum cp genomes. Comparative cp genomes analyses revealed that a higher similarity was conserved in the IR regions than in the SC regions. In addition, 11 divergent hotspot regions were selected, providing potential molecular markers for the identification of the Polygonatum species with verticillate leaf types. Phylogenetic analysis indicated that, as a super barcode, plastids realized a fast and efficient identification that clearly characterized the relationships within the verticillate leaf types of the Polygonatum species. In brief, our results not only enrich the data on the cp genomes of the genus Polygonatum but also provide references for the P. kingianum germplasm resource protection, herbal cultivation, and drug production.

Conclusion

This study not only accurately identifies P. kingianum species, but also provides valuable information for the development of molecular markers and phylogenetic analyses of the Polygonatum species with verticillate leaf types.
Transcriptome and metabolome analysis reveals the effect of flavonoids on flower color variation in Dendrobium nobile Lindl.
Authors: Qiu Yujie , Cai Chengcheng , Mo Xu , Zhao Xinyi , Wu Lijuan , Liu Fan , Li Rui , Liu Chen , Chen Ji , Tian Mengliang
Published: August 2023

Introduction

Dendrobium nobile L. is a rare orchid plant with high medicinal and ornamentalvalue, and extremely few genetic species resources are remaining in nature. In the normal purple flower population, a type of population material with a white flower variation phenotype has been discovered, and through pigment component determination, flavonoids were preliminarily found to be the main reason for the variation.

Methods

This study mainly explored the different genes and metabolites at different flowering stages and analysed the flower color variation mechanism through transcriptome- and flavonoid-targeted metabolomics. The experimental materials consisted of two different flower color phenotypes, purple flower (PF) and white flower (WF), observed during three different periods.

Results and discussion

The results identified 1382, 2421 and 989 differentially expressed genes (DEGs) in the white flower variety compared with the purple flower variety at S1 (bud stage), S2 (chromogenic stage) and S3 (flowering stage), respectively. Among these, 27 genes enriched in the ko00941, ko00942, ko00943 and ko00944 pathways were screened as potential functional genes affecting flavonoid synthesis and flower color. Further analysis revealed that 15 genes are potential functional genes that lead to flavonoid changes and flower color variations. The metabolomics results at S3 found 129 differentially accumulated metabolites (DAMs), which included 8 anthocyanin metabolites, all of which (with the exception of delphinidin-3-o-(2’’’-o-malonyl) sophoroside-5-o-glucoside) were found at lower amounts in the WF variety compared with the PF variety, indicating that a decrease in the anthocyanin content was the main reason for the inability to form purple flowers. Therefore, the changes in 19 flavone and 62 flavonol metabolites were considered the main reasons for the formation of white flowers. In this study, valuable materials responsible for flower color variation in D. nobile were identified and further analyzed the main pathways and potential genes affecting changes in flavonoids and the flower color. This study provides a material basis and theoretical support for the hybridization and molecular-assisted breeding of D. nobile.
Uptake and accumulation of emerging contaminants in processing tomato irrigated with tertiary treated wastewater effluent: a pilot-scale study
Authors: Denora Michele , Candido Vincenzo , Brunetti Gennaro , De Mastro Francesco , Murgolo Sapia , De Ceglie Cristina , Salerno Carlo , Gatta Giuseppe , Giuliani Marcella Michela , Mehmeti Andi , Bartholomeus Ruud P. , Perniola Michele
Published: August 2023

The reuse of treated wastewater for crop irrigation is vital in water-scarce semi-arid regions. However, concerns arise regarding emerging contaminants (ECs) that persist in treated wastewater and may accumulate in irrigated crops, potentially entering the food chain and the environment. This pilot-scale study conducted in southern Italy focused on tomato plants (Solanum lycopersicum L. cv Taylor F1) irrigated with treated wastewater to investigate EC uptake, accumulation, and translocation processes. The experiment spanned from June to September 2021 and involved three irrigation strategies: conventional water (FW), treated wastewater spiked with 10 target contaminants at the European average dose (TWWx1), and tertiary WWTP effluent spiked with the target contaminants at a triple dose (TWWx3). The results showed distinct behavior and distribution of ECs between the TWWx1 and TWWx3 strategies. In the TWWx3 strategy, clarithromycin, carbamazepine, metoprolol, fluconazole, and climbazole exhibited interactions with the soil-plant system, with varying degradation rates, soil accumulation rates, and plant accumulation rates. In contrast, naproxen, ketoprofen, diclofenac, sulfamethoxazole, and trimethoprim showed degradation. These findings imply that some ECs may be actively taken up by plants, potentially introducing them into the food chain and raising concerns for humans and the environment.
The association of alcohol use and positive and negative urgency to same day objective binge eating in emerging adults
Authors: Fischer Sarah , Wonderlich Joseph , Miller Leo A. , Breithaupt Lauren , Frietchen Rachel , Cao Li , Nelson Jillian D. , Izquierdo Alyssa
Published: August 2023

Introduction

Objective binge eating and problematic alcohol use often co-occur and are common behaviors in emerging adults. Both behaviors are thought to be driven by affect regulation processes. Objective binge eating often occurs in the context of increasing or acute negative affect, and often occurs in solitude. Alcohol use in emerging adults can also be associated with negative affect regulation. However, in contrast to objective binge eating, a large body of research indicates that there are positively valenced pathways to alcohol use in this age group. Emerging adults often drink socially, to enhance enjoyment, and in the context of positive mood. We propose that one pathway to objective binge eating in this developmental period is through alcohol use itself, such that emerging adults who consume alcohol and who are more likely to act impulsively in the context of positive emotion (i.e., have high levels of positive urgency) may be more likely to binge eat following drinking.

Methods

We collected data using ecological momentary assessment in 106 undergraduates on positive and negative affect, motives for drinking and eating, and alcohol use and objective binge eating, in addition to baseline questionnaires of impulsivity.

Results

There were no significant changes in affect prior to drinking in this sample. Alcohol use at one time point significantly increased odds of objective binge eating at a later time point in the same day. Individual differences in positive urgency, the tendency to act rashly while experiencing positive affect, were also associated with increased odds of objective binge eating that occurred after alcohol use. Individual differences in negative urgency, the tendency to act rashly after experiencing negative affect, did not have a main effect on objective binge episodes, but did interact with alcohol use to increase the odds of objective binge eating following drinking. The vast majority of drinking episodes prior to objective binge eating were social drinking episodes, and participants most commonly endorsed "to have fun" as a reason for drinking.

Discussion

Results suggest that alcohol consumption may increase risk for objective binge eating in emerging adults.
Stability and genetic insights of the co-existence of blaCTX-M-65, blaOXA-1, and mcr-1.1 harboring conjugative IncI2 plasmid isolated from a clinical extensively-drug resistant Escherichia coli ST744 in Shanghai
Authors: Feng Jun , Wu Huanyu , Zhuang Yuan , Luo Jiayuan , Chen Yong , Wu Yitong , Fei Jiayi , Shen Qi , Yuan Zhengan , Chen Min
Published: August 2023

Background

Co-existence of colistin, β-lactam and carbapenem in multidrug-resistant Enterobacteriaceae isolates poses a serious threat to public health. In this study, we investigated and characterized the co-occurrence of blaCTX-M-65, blaOXA-1, and mcr-1.1 strain isolated from a clinical extensively-drug-resistant Escherichia coli ST744 in Shanghai.

Methods

Antimicrobial susceptibility test was carried out by agar dilution methods. Whole genome sequencing was conducted, and resistance genes, and sequence types of colistin in E. coli isolates were analyzed. Plasmid stability and amino acid mutations were assessed in E. coli isolates.

Results

A colistin resistant E. coli ST744, named ECPX221, was identified out of 145 fecal samples collected. The strain carries a 60,168 IncI2 plasmid with the mcr-1.1 gene. The strain also has blaCTX-M-65, blaOXA-1, dfrA14, qnrS1, cmlA5, arr2, ampC, aph(4)-Ia, sul1, and aadA5 resistance genes. The plasmid pECPX221 was capable of conjugation with an efficiency of 2.6 × 10−2. Notably, 45% of the transconjugants were determined as mcr-1.1-harboring in the colistin-free environment after 60 generation of passage. No mutations occurred in pmrB, mgrB, and phoPQ gene in the mcr-1.1-harboring transconjugants. Bioinformatic analysis indicated pECPX221 shared highly similar backbone with the previously reported mcr-1.1-harboring pAH62-1, pMFDS1339.1, pSCZE4, and p2018-10-2CC. Furthermore, sequencing and phylogenetic analyses revealed a similarity between other MCR-1-homolog proteins, indicating that ECPX221 was colistin resistant.

Conclusion

The stable transferable mcr-1.1-harboring plasmid found in the E. coli ST744 strain indicated the high risk to disseminate the extensively-drug-resistance phenotype among Enterobacteriaceae.