bluuebunny/crossref_metadata_2025 huggingface dataset:
Status assessment and probabilistic health risk modeling of polycyclic aromatic hydrocarbons (PAHs) in surface soil across China
Authors: He Mingjiang , Shangguan Yuxian , Zhou Zijun , Guo Song , Yu Hua , Chen Kun , Zeng Xiangzhong , Qin Yusheng
Published: February 2023

Polycyclic aromatic hydrocarbon (PAH) accumulation in topsoil is getting particular concern with the rapid development of urbanization and industrialization, while the overall pollution status and related risk posed by PAHs received limited attentions at the national scale. This study conducted an overview of published data on 16 priority control PAHs by USEPA on the related peer-reviewed 207 research papers between 2000 and 2020 in 30 provinces of China. Based on that, the pollution levels, composition status, spatial distribution pattern, ecological risk, and human health risk posed by soil PAHs were evaluated. Monte Carlo simulation was adopted to model the probabilistic health risk and identify the contributor of such risks. Results demonstrated the concentrations of ∑16PAHs in soil varied from “undetected” to 261 μg g−1 with a mean value of 0.63 μg g−1, indicating the obvious accumulation of PAHs in topsoil of most provinces in China compared with the guideline value (0.2 μg g−1). The concentrations of ∑16PAHs in surface soil of China has obvious regional characteristics. Higher concentrations of soil PAHs are mainly distributed in north, northwest, and eastern regions, especially in Xinjiang, Shandong, Jiangsu, Sichuan, and Guangxi Province. Risk assessment indicates potential ecological and human health risk were posed by soil PAHs, therefore, reducing soil PAHs concentration and exposure frequency are the most effective pathways to protect human health. Despite the fact that risks posed by soil PAHs are generally low, concentrations of PAHs in some sites are relatively high. It is necessary to take effective measures to remediate soil PAHs pollution in certain areas to reduce concentration and associated risks.
Considering strategies for SNP selection in genetic and polygenic risk scores
Authors: St.-Pierre Julien , Zhang Xinyi , Lu Tianyuan , Jiang Lai , Loffree Xavier , Wang Linbo , Bhatnagar Sahir , Greenwood Celia M. T. ,   CANSSI team on Improving Robust High-Dimensional Causal Inference and Prediction Modelling
Published: February 2023

Genetic risk scores (GRS) and polygenic risk scores (PRS) are weighted sums of, respectively, several or many genetic variant indicator variables. Although they are being increasingly proposed for clinical use, the best ways to construct them are still actively debated. In this commentary, we present several case studies illustrating practical challenges associated with building or attempting to improve score performance when there is expected to be heterogeneity of disease risk between cohorts or between subgroups of individuals. Specifically, we contrast performance associated with several ways of selecting single nucleotide polymorphisms (SNPs) for inclusion in these scores. By considering GRS and PRS as predictors that are measured with error, insights into their strengths and weaknesses may be obtained, and SNP selection approaches play an important role in defining such errors.
Application of an angiogenesis-related genes risk model in lung adenocarcinoma prognosis and immunotherapy
Authors: Wang Jinsong , Cui Xue , Weng Yiming , Wei Jiayan , Chen Xinyi , Wang Peiwei , Wang Tong , Qin Jian , Peng Min
Published: February 2023

Lung adenocarcinoma (LUAD) is an essential pathological subtype of non-small cell lung cancer and offers a severe problem for worldwide public health. There is mounting proof that angiogenesis is a crucial player in LUAD progression. Consequently, the purpose of this research was to construct a novel LUAD risk assessment model based on genetic markers related to angiogenesis. We accessed The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases for LUAD mRNA sequencing data and clinical information. Based on machine algorithms and bioinformatics, angiogenic gene-related risk scores (RS) were calculated. Patients in the high-risk category had a worse prognosis (p < 0.001) in the discovery TCGA cohort, and the results were confirmed by these three cohorts (validation TCGA cohort, total TCGA cohort, and GSE68465 cohort). Moreover, risk scores for genes involved in angiogenesis were independent risk factors for lung cancer in all four cohorts. The low-risk group was associated with better immune status and lower tumor mutational load. In addition, the somatic mutation study revealed that the low-risk group had a lower mutation frequency than the high-risk group. According to an analysis of tumor stem cell infiltration, HLA expression, and TIDE scores, the low-risk group had higher TIDE scores and HLA expression levels than the high-risk group, and the amount of tumor stem cell infiltration correlated with the risk score. In addition, high-risk groups may benefit from immune checkpoint inhibitors and targeted therapies. In conclusion, we developed an angiogenesis-related gene risk model to predict the prognosis of LUAD patients, which may aid in the classification of patients with LUAD and select medications for LUAD patients.
Genome-wide identification, evolution and expression analysis of bone morphogenetic protein (BMP) gene family in chinese soft-shell turtle (Pelodiscus sinensis)
Authors: Lei Luo , Zhu Junxian , Chen Chen , Wang Yongchang , Wu Congcong , Qi Ming , Wang Yakun , Liu Xiaoli , Hong Xiaoyou , Yu Lingyun , Chen Haigang , Wei Chengqing , Liu Yihui , Li Wei , Zhu Xinping
Published: February 2023

Introduction: Bone morphogenetic proteins (BMPs) play a crucial role in bone formation and differentiation. Recent RNA-Seq results suggest that BMPs may be involved in the sex differentiation of P. sinensis, yet more relevant studies about BMPs in P. sinensis are lacking.

Methods: Herein, we identified BMP gene family members, analyzed the phylogeny, collinear relationship, scaffold localization, gene structures, protein structures, transcription factors and dimorphic expression by using bioinformatic methods based on genomic and transcriptomic data of P. sinensis. Meanwhile, qRT-PCR was used to verify the RNA-Seq results and initially explore the function of the BMPs in the sex differentiation of P. sinensis.

Results: A total of 11 BMP genes were identified, 10 of which were localized to their respective genomic scaffolds. Phylogenetic analysis revealed that BMP genes were divided into eight subfamilies and shared similar motifs (“WII”, “FPL”, “TNHA”, “CCVP”, and “CGC”) and domain (TGF-β superfamily). The results of the sexually dimorphic expression profile and qRT-PCR showed that Bmp2, Bmp3, Bmp15l, Bmp5, Bmp6 and Bmp8a were significantly upregulated in ovaries, while Bmp2lb, Bmp7, Bmp2bl and Bmp10 were remarkable upregulated in testes, suggesting that these genes may play a role in sex differentiation of P. sinensis.

Discussion: Collectively, our comprehensive results enrich the basic date for studying the evolution and functions of BMP genes in P. sinensis.
Improved efficacy of mesenchymal stromal cells stably expressing CXCR4 and IL-10 in a xenogeneic graft versus host disease mouse model
Authors: Hervás-Salcedo Rosario , Fernández-García María , Hernando-Rodríguez Miriam , Suárez-Cabrera Cristian , Bueren Juan A. , Yáñez Rosa M.
Published: February 2023

Previous clinical trials have shown that mesenchymal stromal cells (MSCs) can modulate graft versus host disease (GvHD) after allogeneic hematopoietic transplantation, although with variable efficacy. To improve the anti-GvHD effect of these cells, adipose tissue derived-human MSCs (Ad-MSCs) were transduced with a lentiviral vector conferring stable expression of CXCR4, a molecule involved in cell migration to inflamed sites, and IL-10, a cytokine with potent anti-inflammatory properties. In vitro experiments showed that the expression of these molecules in Ad-MSCs (named CXCR4-IL10-MSCs) efficiently enhanced their migration towards SDF-1α and also improved their immunomodulatory properties compared to unmodified Ad-MSCs (WT-MSCs). Moreover, using a humanized GvHD mouse model, CXCR4-IL10-MSCs showed improved therapeutic effects, which were confirmed by histopathologic analysis in the target organs. Additionally, compared to WT-MSCs, CXCR4-IL10-MSCs induced a more marked reduction in the number of pro-inflammatory Th1 and Th17 cells, a higher polarization towards an anti-inflammatory T cell profile (CD3+-IL10+ cells), and increased the number of regulatory T and B cells. Our in vitro and in vivo studies strongly suggest that CXCR4-IL10-MSCs should constitute an important new generation of MSCs for the treatment of GvHD in patients transplanted with allogeneic hematopoietic grafts.
Genome-wide association study of the age of onset of type 1 diabetes reveals HTATIP2 as a novel T cell regulator
Authors: Cardinale Christopher J. , Chang Xiao , Wei Zhi , Qu Hui-Qi , Bradfield Jonathan P. , Polychronakos Constantin , Hakonarson Hakon
Published: February 2023

Introduction

Type 1 diabetes, a disorder caused by autoimmune destruction of pancreatic insulin-producing cells, is more difficult to manage when it presents at a younger age. We sought to identify genetic correlates of the age of onset by conducting the first genome-wide association study (GWAS) treating the age of first diagnosis as a quantitative trait.

Methods

We performed GWAS with a discovery cohort of 4,014 cases and a replication cohort of 493 independent cases. Genome-wide significant SNPs were mapped to a causal variant by Bayesian conditional analysis and gel shift assay. The causal protein-coding gene was identified and characterized by RNA interference treatment of primary human pan-CD4+ T cells with RNA-seq of the transcriptome. The candidate gene was evaluated functionally in primary cells by CD69 staining and proliferation assays.

Results

Our GWAS replicated the known association of the age of diagnosis with the human leukocyte antigen complex (HLA-DQB1). The second signal identified was in an intron of the NELL1 gene on chromosome 11 and fine-mapped to variant rs10833518 (P < 1.54 × 10−9). Homozygosity for the risk allele leads to average age of onset one year earlier. Knock-down of HIV TAT-interacting protein 2 (HTATIP2), but not other genes in the locus, resulted in alterations to gene expression in signal transduction pathways including MAP kinases and PI3-kinase. Higher levels of HTATIP2 expression are associated with increased viability, proliferation, and activation of T cells in the presence of signals from antigen and cytokine receptors.

Discussion

This study implicates HTATIP2 as a new type 1 diabetes gene acting via T cell regulation. Larger population sample sizes are expected to reveal additional loci.
Interpreting experience and working memory effects on L1 and L2 morphological prediction
Authors: Lozano-Argüelles Cristina , Sagarra Nuria , Casillas Joseph V.
Published: February 2023

The human brain tries to process information as efficiently as possible through mechanisms like prediction. Native speakers predict linguistic information extensively, but L2 learners show variability. Interpreters use prediction while working and research shows that interpreting experience mediates L2 prediction. However, it is unclear whether advantages related to interpreting are due to higher working memory (WM) capacity, a typical characteristic of professional interpreters. To better understand the role of WM during L1 and L2 prediction, English L2 learners of Spanish with and without interpreting experience and Spanish monolinguals completed a visual-world paradigm eye-tracking task and a number-letter sequencing working memory task. The eye-tracking task measured prediction of verbal morphology (present, past) based on suprasegmental information (lexical stress: paroxytone, oxytone) and segmental information (syllabic structure: CV, CVC). Results revealed that WM mediates L1 prediction, such that higher WM facilitates prediction of morphology in monolinguals. However, higher WM hinders prediction in L2 processing for non-interpreters. Interestingly, interpreters behaved similarly to monolinguals, with higher WM facilitating L2 prediction. This study provides further understanding of the variability in L2 prediction.
Impacts of morphological change and sea-level rise on stratification in the Pearl River Estuary
Authors: Ma Mengyao , Zhang Wenyan , Chen Wei , Deng Junjie , Schrum Corinna
Published: February 2023

The Pearl River Delta (PRD), where several megacities are located, has undergone drastic morphological changes caused by anthropogenic impact during the past few decades. In its main estuary, the water area has been reduced by 21% whilst the average water depth has increased by 2.24 m from 1970s to 2010s. The mainly human-induced morphological change together with sea level rise has jointly led to a remarkable change in the water stratification. However, the spatial and temporal variability of stratification in the estuary and associated driving mechanisms remain less understood. In this study, stratification in the Pearl River Estuary (PRE) in response to morphological change and external forcing is investigated by 3-dimensional numerical modeling. Simulation results indicate that stratification in the PRE exhibits distinct spatial and temporal variabilities. At a tidal-to-monthly time scale, variation of stratification is mainly driven by advection and straining through tidal forcing. At a monthly-to-seasonal scale, monsoon-driven river runoff and associated plume and fronts dominate the variation of stratification. Human-induced morphological change leads to an enhancement of stratification by up to four times in the PRE. Compared to an overwhelming human impact in the past few decades, future sea level rise would further enhance stratification, but to a much lesser extent than past human impacts. In addition, stratification in different areas of the estuary also responds differently to the driving factors. The western shoal of the estuary is most sensitive to changes in morphology and sea level due to its shallowness, followed by the channels and other parts of the estuary, which are less sensitive.
Comparative metagenomics at Solfatara and Pisciarelli hydrothermal systems in Italy reveal that ecological differences across substrates are not ubiquitous
Authors: Ugwuanyi Ifeoma R. , Fogel Marilyn L. , Bowden Roxane , Steele Andrew , De Natale Giuseppe , Troise Claudia , Somma Renato , Piochi Monica , Mormone Angela , Glamoclija Mihaela
Published: February 2023

Introduction

Continental hydrothermal systems (CHSs) are geochemically complex, and they support microbial communities that vary across substrates. However, our understanding of these variations across the complete range of substrates in CHS is limited because many previous studies have focused predominantly on aqueous settings.

Methods

Here we used metagenomes in the context of their environmental geochemistry to investigate the ecology of different substrates (i.e., water, mud and fumarolic deposits) from Solfatara and Pisciarelli.

Results and Discussion

Results indicate that both locations are lithologically similar with distinct fluid geochemistry. In particular, all substrates from Solfatara have similar chemistry whereas Pisciarelli substrates have varying chemistry; with water and mud from bubbling pools exhibiting high SO42− and NH4+ concentrations. Species alpha diversity was found to be different between locations but not across substrates, and pH was shown to be the most important driver of both diversity and microbial community composition. Based on cluster analysis, microbial community structure differed significantly between Pisciarelli substrates but not between Solfatara substrates. Pisciarelli mud pools, were dominated by (hyper)thermophilic archaea, and on average, bacteria dominated Pisciarelli fumarolic deposits and all investigated Solfatara environments. Carbon fixation and sulfur oxidation were the most important metabolic pathways fueled by volcanic outgassing at both locations. Together, results demonstrate that ecological differences across substrates are not a widespread phenomenon but specific to the system. Therefore, this study demonstrates the importance of analyzing different substrates of a CHS to understand the full range of microbial ecology to avoid biased ecological assessments.
Isolation, culture and characterization of Arsenophonus symbionts from two insect species reveal loss of infectious transmission and extended host range
Authors: Nadal-Jimenez Pol , Parratt Steven R. , Siozios Stefanos , Hurst Gregory D. D.
Published: February 2023

Vertically transmitted “Heritable” microbial symbionts represent an important component of the biology and ecology of invertebrates. These symbioses evolved originally from ones where infection/acquisition processes occurred within the environment (horizontal transmission). However, the pattern of evolution that follows transition from horizontal to vertical transmission is commonly obscured by the distant relationship between microbes with differing transmission modes. In contrast, the genus Arsenophonus provides an opportunity to investigate these processes with clarity, as it includes members that are obligate vertically transmitted symbionts, facultative vertically transmitted symbionts, strains with mixed modes of transmission and ones that are purely horizontally transmitted. Significantly, some of the strains are culturable and amenable to genetic analysis. We first report the isolation of Arsenophonus nasoniae strain aPv into culture from the ectoparasitic wasp Pachycrepoideus vindemmiae and characterize the symbiosis. We demonstrate maternal vertical transmission and find no evidence for paternal inheritance, horizontal transmission or reproductive parasitism phenotypes. This leads us to conclude this strain, in contrast to related strains, is a facultative heritable symbiont which is likely to be beneficial. We then report the serendipitous discovery and onward culture of a strain of Arsenophonus (strain aPb) from the blue butterfly, Polyommatus bellargus. This association extends the range of host species carrying Arsenophonus nasoniae/Arsenophonus apicola symbionts beyond the Hymenoptera for the first time. We perform basic metabolic analysis of the isolated strains using Biolog plates. This analysis indicates all strains utilize a restricted range of carbon sources, but these restrictions are particularly pronounced in the A. nasoniae aPv strain that is solely vertically transmitted. Finally, we demonstrate the Arsenophonus sp. strain aPb from the blue butterfly can infect Galleria waxworms, providing a model system for investigating the functional genetics of Arsenophonus-insect interactions. These results are consistent with a model of reduced metabolic competence in strains evolving under vertical transmission only. The data also broadens the range of host species infected with nasoniae/apicola clade strains beyond the Hymenoptera, and indicate the potential utility of the Galleria model for investigation of symbiosis mechanism.
Mechanisms of immune evasion of monkeypox virus
Authors: Zandi Milad , Shafaati Maryam , Hosseini Fatemeh
Published: February 2023

The mpox (disease caused by the monkeypox virus) epidemic in 2022 provides a good opportunity to study the immune response to mpox. Vaccinia virus-infected monocytes could be recognized by monkeypox virus-specific CD4+ and CD8+ T cells, which produce inflammatory cytokines including IFNγ and TNFα. However, these cells are mostly unable to react to monkeypox virus-infected cells. The monkeypox virus also has no effect on the expression of MHC classes. Cells infected with monkeypox virus can prevent T cells from being activated via their T cell receptors. Insensitivity is an MHC-independent strategy for controlling antiviral T cells activation and inflammatory cytokines production. It is likely a critical aspect of virus spread in the infected host. The ability of monkeypox virus to spread efficiently as cell-associated viremia may be explained by the evasion strategies employed by the virus to subvert immunological surveillance by virus-specific T cells.
Association of the risk factor UNC13A with survival and upper motor neuron involvement in amyotrophic lateral sclerosis
Authors: Manini Arianna , Casiraghi Valeria , Brusati Alberto , Maranzano Alessio , Gentile Francesco , Colombo Eleonora , Bonetti Ruggero , Peverelli Silvia , Invernizzi Sabrina , Gentilini Davide , Messina Stefano , Verde Federico , Poletti Barbara , Fogh Isabella , Morelli Claudia , Silani Vincenzo , Ratti Antonia , Ticozzi Nicola
Published: February 2023

Background

The UNC13A gene is an established susceptibility locus for amyotrophic lateral sclerosis (ALS) and a determinant of shorter survival after disease onset, with up to 33.0 months difference in life expectancy for carriers of the rs12608932 risk genotype. However, its overall effect on other clinical features and ALS phenotypic variability is controversial.

Methods

Genotype data of the UNC13A rs12608932 SNP (A–major allele; C–minor allele) was obtained from a cohort of 972 ALS patients. Demographic and clinical variables were collected, including cognitive and behavioral profiles, evaluated through the Edinburgh Cognitive and Behavioral ALS Screen (ECAS) – Italian version and the Frontal Behavioral Inventory (FBI); upper and lower motor neuron involvement, assessed by the Penn Upper Motor Neuron Score (PUMNS) and the Lower Motor Neuron Score (LMNS)/Medical Research Council (MRC) scores, respectively; the ALS Functional Rating Scale Revised (ALSFRS-R) score at evaluation and progression rate; age and site of onset; survival. The comparison between the three rs12608932 genotypes (AA, AC, and CC) was performed using the additive, dominant, and recessive genetic models.

Results

The rs12608932 minor allele frequency was 0.31 in our ALS cohort, in comparison to 0.33–0.41 reported in other Caucasian ALS populations. Carriers of at least one minor C allele (AC + CC genotypes) had a shorter median survival than patients with the wild-type AA genotype (−11.7 months, p = 0.013), even after adjusting for age and site of onset, C9orf72 mutational status and gender. Patients harboring at least one major A allele (AA + AC genotypes) and particularly those with the wild-type AA genotype showed a significantly higher PUMNS compared to CC carriers (p = 0.015 and padj = 0.037, respectively), thus indicating a more severe upper motor neuron involvement. Our analysis did not detect significant associations with all the other clinical parameters considered.

Conclusion

Overall, our findings confirm the role of UNC13A as a determinant of survival in ALS patients and show the association of this locus also with upper motor neuron involvement.
Noninvasive intracranial pressure assessment by optic nerve sheath diameter: Automated measurements as an alternative to clinician-performed measurements
Authors: Netteland Dag Ferner , Aarhus Mads , Smistad Erik , Sandset Else Charlotte , Padayachy Llewellyn , Helseth Eirik , Brekken Reidar
Published: February 2023

Introduction

Optic nerve sheath diameter (ONSD) has shown promise as a noninvasive parameter for estimating intracranial pressure (ICP). In this study, we evaluated a novel automated method of measuring the ONSD in transorbital ultrasound imaging.

Methods

From adult traumatic brain injury (TBI) patients with invasive ICP monitoring, bedside manual ONSD measurements and ultrasound videos of the optic nerve sheath complex were simultaneously acquired. Automatic ONSD measurements were obtained by the processing of the ultrasound videos by a novel software based on a machine learning approach for segmentation of the optic nerve sheath. Agreement between manual and automated measurements, as well as their correlation to invasive ICP, was evaluated. Furthermore, the ability to distinguish dichotomized ICP for manual and automatic measurements of ONSD was compared, both for ICP dichotomized at ≥20 mmHg and at the 50th percentile (≥14 mmHg). Finally, we performed an exploratory subgroup analysis based on the software's judgment of optic nerve axis alignment to elucidate the reasons for variation in the agreement between automatic and manual measurements.

Results

A total of 43 ultrasound examinations were performed on 25 adult patients with TBI, resulting in 86 image sequences covering the right and left eyes. The median pairwise difference between automatically and manually measured ONSD was 0.06 mm (IQR −0.44 to 0.38 mm; p = 0.80). The manually measured ONSD showed a positive correlation with ICP, while automatically measured ONSD showed a trend toward, but not a statistically significant correlation with ICP. When examining the ability to distinguish dichotomized ICP, manual and automatic measurements performed with similar accuracy both for an ICP cutoff at 20 mmHg (manual: AUC 0.74, 95% CI 0.58–0.88; automatic: AUC 0.83, 95% CI 0.66–0.93) and for an ICP cutoff at 14 mmHg (manual: AUC 0.70, 95% CI 0.52–0.85; automatic: AUC 0.68, 95% CI 0.48–0.83). In the exploratory subgroup analysis, we found that the agreement between measurements was higher in the subgroup where the automatic software evaluated the optic nerve axis alignment as good as compared to intermediate/poor.

Conclusion

The novel automated method of measuring the ONSD on the ultrasound videos using segmentation of the optic nerve sheath showed a reasonable agreement with manual measurements and performed equally well in distinguishing high and low ICP.
Posterior white matter integrity and self-reported posterior cortical symptoms using the Colorado Posterior Cortical Questionnaire
Authors: Holden Samantha K. , Bettcher Brianne M. , Filley Christopher M. , Lopez-Paniagua Dan , Pelak Victoria S.
Published: February 2023

Background

The Colorado Posterior Cortical Questionnaire (CPC-Q) is a self-report, 15-item screening questionnaire for posterior cortical symptoms, including visuospatial and visuoperceptual difficulties. Changes in white matter connectivity may precede obvious gray matter atrophy in neurodegenerative conditions, especially posterior cortical atrophy. Integration of CPC-Q scores and measures of white matter integrity could contribute to earlier detection of posterior cortical syndromes.

Methods

We investigated the relationships between posterior cortical symptoms as captured by the CPC-Q and diffusion tensor imaging fractional anisotropy (DTI FA) of white matter regions of interest localized to posterior brain regions (posterior thalamic radiations, splenium of corpus callosum, tapetum). Comparisons were also made by diagnostic group [healthy older adult (n = 31), amnestic Alzheimer's disease (AD, n = 18), and posterior cortical atrophy (PCA, n = 9)] and by SENAS battery visuospatial composite score quartile. Exploratory comparisons of all available individual white matter region DTI FA to CPC-Q, as well as comparisons of DTI FA between diagnostic groups and visuospatial quartiles, were also made.

Results

CPC-Q score was correlated with the average DTI FA for the averaged posterior white matter regions of interest (r = −0.31, p = 0.02). Posterior thalamic radiation DTI FA was most strongly associated with CPC-Q (r = −0.34, p = 0.01) and visuospatial composite (r = 0.58, p < 0.01) scores and differed between the PCA and AD groups and the lower and higher visuospatial quartiles. The DTI FA of body and splenium of the corpus callosum also demonstrated this pattern but not the DTI FA of the tapetum.

Conclusion

The integrity of posterior white matter tracts is associated with scores on the CPC-Q, adding to the validation evidence for this new questionnaire. White matter regions that may be related to posterior cortical symptoms detected by the CPC-Q, and distinct from those affected in amnestic syndromes, include the posterior thalamic radiations and body and splenium of the corpus callosum. These findings are in line with previous neuroimaging studies of PCA and support continued research on white matter in posterior cortical dysfunction.
Detection of epileptic seizures through EEG signals using entropy features and ensemble learning
Authors: Dastgoshadeh Mahshid , Rabiei Zahra
Published: February 2023

Introduction

Epilepsy is a disorder of the central nervous system that is often accompanied by recurrent seizures. World health organization (WHO) estimated that more than 50 million people worldwide suffer from epilepsy. Although electroencephalogram (EEG) signals contain vital physiological and pathological information of brain and they are a prominent medical tool for detecting epileptic seizures, visual interpretation of such tools is time-consuming. Since early diagnosis of epilepsy is essential to control seizures, we present a new method using data mining and machine learning techniques to diagnose epileptic seizures automatically.

Methods

The proposed detection system consists of three main steps: In the first step, the input signals are pre-processed by discrete wavelet transform (DWT) and sub-bands containing useful information are extracted. In the second step, the features of each sub-band are extracted by approximate entropy (ApEn) and sample entropy (SampEn) and then these features are ranked by ANOVA test. Finally, feature selection is done by the FSFS technique. In the third step, three algorithms are used to classify seizures: Least squared support vector machine (LS-SVM), K nearest neighbors (KNN) and Naive Bayes model (NB).

Results and discussion

The average accuracy for both LS-SVM and NB was 98% and it was 94.5% for KNN, while the results show that the proposed method can detect epileptic seizures with an average accuracy of 99.5%, 99.01% of sensitivity and 100% of specificity which show an improvement over most similar methods and can be used as an effective tool in diagnosing this complication.
Neural correlates of disaster-related prenatal maternal stress in young adults from Project Ice Storm: Focus on amygdala, hippocampus, and prefrontal cortex
Authors: Li Xinyuan , Qureshi Muhammad Naveed Iqbal , Laplante David P. , Elgbeili Guillaume , Jones Sherri Lee , King Suzanne , Rosa-Neto Pedro
Published: February 2023

Background

Studies have shown that prenatal maternal stress alters volumes of the amygdala and hippocampus, and alters functional connectivity between the amygdala and prefrontal cortex. However, it remains unclear whether prenatal maternal stress (PNMS) affects volumes and functional connectivity of these structures at their subdivision levels.

Methods

T1-weighted MRI and resting-state functional MRI were obtained from 19-year-old young adult offspring with (n = 39, 18 male) and without (n = 65, 30 male) exposure to PNMS deriving from the 1998 ice storm. Volumes of amygdala nuclei, hippocampal subfields and prefrontal subregions were computed, and seed-to-seed functional connectivity analyses were conducted.

Results

Compared to controls, young adult offspring exposed to disaster-related PNMS had larger volumes of bilateral whole amygdala, driven by the lateral, basal, central, medial, cortical, accessory basal nuclei, and corticoamygdaloid transition; larger volumes of bilateral whole hippocampus, driven by the CA1, HATA, molecular layer, fissure, tail, CA3, CA4, and DG; and larger volume of the prefrontal cortex, driven by the left superior frontal. Inversely, young adult offspring exposed to disaster-related PNMS had lower functional connectivity between the whole amygdala and the prefrontal cortex (driven by bilateral frontal poles, the left superior frontal and left caudal middle frontal); and lower functional connectivity between the hippocampal tail and the prefrontal cortex (driven by the left lateral orbitofrontal).

Conclusion

These results suggest the possibility that effects of disaster-related PNMS on structure and function of subdivisions of offspring amygdala, hippocampus and prefrontal cortex could persist into young adulthood.
Acupoint catgut embedding for chronic non-specific low back pain: A protocol of randomized controlled trial
Authors: Li Xiaohui , Yin Xiuju , Feng Haiyan , Liao Wangbin , Zhao Jiayou , Su Wu , Fan Zhiyong , Wu Shan
Published: February 2023

Chronic non-specific low back pain (CNLBP) is one of the leading causes of disability worldwide. Acupoint embedding (ACE) is widely used in China for the treatment of chronic non-specific low back pain, but there are no rigorous randomized controlled trials (RCTs) to confirm the effectiveness and safety of ACE for chronic non-specific low back pain. In this study, we design a single-center, single-blind, prospective RCT, with the aim of evaluating the efficacy and safety of ACE for CNLBP. 82 participants with CNLBP will be randomized in a 1:1 ratio into an ACE group and a sham ACE group. Participants will receive either ACE treatment or sham ACE treatment at once every 2 weeks, for an 8-week period, and followed by 6 months of follow-up. The primary outcome will be the change in visual analog scale (VAS) scores before and after treatment. Secondary outcomes will include the Oswestry Disability Index (ODI), the Roland Morris Disability Questionnaire (RMDQ) and the Short Form 36-Health Survey (SF-36). Adverse events that occur during the course of the trial will be recorded. Data will be analyzed according to a predefined statistical analysis plan. This study was approved by the medical ethics committee of Guangzhou Panyu Hospital of Chinese Medicine (202230). Written informed consent from patients is required. This trial is registered in the Chinese Clinical Trial Registry (ChiCTR2200059245). Trial results will be published in a peer-reviewed academic journal.

Clinical trial registration

https://www.chictr.org.cn, identifier ChiCTR2200059245.
Prognostic significance of sarcopenia diagnosed based on the anthropometric equation for progression-free survival and overall survival in patients with colorectal cancer
Authors: Xie Hailun , Wei Lishuang , Gao Shunhui , Liu Mingxiang , Liang Yanren , Yuan Guanghui , Wang Qiwen , Xu Yansong , Tang Shuangyi , Gan Jialiang
Published: February 2023

Background

The purpose of this study was to investigate the prognostic significance of sarcopenia diagnosed based on anthropometric equations for progression-free survival (PFS) and overall survival (OS) in patients with colorectal cancer (CRC).

Methods

A total of 1,441 CRC patients who underwent surgical treatment between January 2012 and December 2016 were enrolled in this study. Sarcopenia was diagnosed according to validated anthropometric equations. The Kaplan–Meier method with the log-rank test was used to estimate the survival curve. Cox proportional hazards regression models with forward selection were used to evaluate risk factors affecting the prognosis of CRC patients. R package “survival” was used to build the prognostic nomograms to predict 1–5 years of PFS and OS in CRC patients. The concordance index (C-index) and calibration curve were used to evaluate the prognostic accuracy of the prognostic nomogram.

Results

Two hundred and seventy-one patients (18.8%) were diagnosed with sarcopenia. Sarcopenia was significantly associated with advanced age, large tumor size, and high mortality. Compared with the non-sarcopenia patients, the PFS of sarcopenia patients was worse (5-year PFS, 48.34 vs. 58.80%, p = 0.003). Multivariate survival analysis showed that patients with sarcopenia had a higher risk (23.9%) of adverse PFS (HR, 1.239; 95%CI: 1.019–1.505, p = 0.031) than patients without sarcopenia. The OS of patients with sarcopenia was significantly worse than that of patients without sarcopenia (5-year OS: 50.92 vs. 61.62%, p = 0.001). In CRC patients, sarcopenia was independently associated with poor OS (HR: 1.273, 95%CI: 1.042–1.556, p < 0.001). Moreover, sarcopenia effectively differentiated the OS of CRC patients in the normal carcinoembryonic antigen (CEA) subgroup but not in the high CEA subgroup. Notably, sarcopenia can provide effective prognostic stratification in CRC patients at different pathological stages. Nomograms that integrated prognostic features were built to predict the risk of adverse outcomes in CRC patients. The C-index and calibration curves showed that these nomograms had good prediction accuracy. Internal validation confirmed that our nomogram has wide application potential.

Conclusion

Sarcopenia diagnosed based on anthropometric equations is an independent risk factor for PFS and OS in CRC patients.
Possible mechanism of metabolic and drug resistance with L-asparaginase therapy in childhood leukaemia
Authors: Zhou Ruizhi , Liang Tianqi , Li Tianwen , Huang Junbin , Chen Chun
Published: February 2023

L-asparaginase, which hydrolyzes asparagine into aspartic acid and ammonia, is frequently used to treat acute lymphoblastic leukaemia in children. When combined with other chemotherapy drugs, the event-free survival rate is 90%. Due to immunogenicity and drug resistance, however, not all patients benefit from it, restricting the use of L-asparaginase therapy in other haematological cancers. To solve the problem of immunogenicity, several L-ASNase variants have emerged, such as Erwinia-ASNase and PEG-ASNase. However, even when Erwinia-ASNase is used as a substitute for E. coli-ASNase or PEG-ASNase, allergic reactions occur in 3%-33% of patients. All of these factors contributed to the development of novel L-ASNases. Additionally, L-ASNase resistance mechanisms, such as the methylation status of ASNS promoters and activation of autophagy, have further emphasized the importance of personalized treatment for paediatric haematological neoplasms. In this review, we discussed the metabolic effects of L-ASNase, mechanisms of drug resistance, applications in non-ALL leukaemia, and the development of novel L-ASNase.
T cell receptor gene repertoire profiles in subgroups of patients with chronic lymphocytic leukemia bearing distinct genomic aberrations
Authors: Vlachonikola Elisavet , Pechlivanis Nikolaos , Karakatsoulis Georgios , Sofou Electra , Gkoliou Glykeria , Jeromin Sabine , Stavroyianni Niki , Ranghetti Pamela , Scarfo Lydia , Österholm Cecilia , Mansouri Larry , Notopoulou Sofia , Siorenta Alexandra , Anagnostopoulos Achilles , Ghia Paolo , Haferlach Claudia , Rosenquist Richard , Psomopoulos Fotis , Kouvatsi Anastasia , Baliakas Panagiotis , Stamatopoulos Kostas , Chatzidimitriou Anastasia
Published: February 2023

Background

Microenvironmental interactions of the malignant clone with T cells are critical throughout the natural history of chronic lymphocytic leukemia (CLL). Indeed, clonal expansions of T cells and shared clonotypes exist between different CLL patients, strongly implying clonal selection by antigens. Moreover, immunogenic neoepitopes have been isolated from the clonotypic B cell receptor immunoglobulin sequences, offering a rationale for immunotherapeutic approaches. Here, we interrogated the T cell receptor (TR) gene repertoire of CLL patients with different genomic aberration profiles aiming to identify unique signatures that would point towards an additional source of immunogenic neoepitopes for T cells.

Experimental design

TR gene repertoire profiling using next generation sequencing in groups of patients with CLL carrying one of the following copy-number aberrations (CNAs): del(11q), del(17p), del(13q), trisomy 12, or gene mutations inTP53orNOTCH1.

Results

Oligoclonal expansions were found in all patients with distinct recurrent genomic aberrations; these were more pronounced in cases bearing CNAs, particularly trisomy 12, rather than gene mutations. Shared clonotypes were found both within and across groups, which appeared to be CLL-biased based on extensive comparisons against TR databases from various entities. Moreover,in silicoanalysis identified TR clonotypes with high binding affinity to neoepitopes predicted to arise fromTP53andNOTCH1mutations.

Conclusions

Distinct TR repertoire profiles were identified in groups of patients with CLL bearing different genomic aberrations, alluding to distinct selection processes. Abnormal protein expression and gene dosage effects associated with recurrent genomic aberrations likely represent a relevant source of CLL-specific selecting antigens.
Minimally invasive sleeve lobectomy for centrally located lung cancer: A real-world study with propensity-score matching
Authors: Chen Tangbing , Zhao Weigang , Ji Chunyu , Luo Jizhuang , Wang Yiyang , Liu Yuan , Weder Walter , Fang Wentao
Published: February 2023

Background

The safety, feasibility, and prognosis of sleeve lobectomy by minimally invasive surgery (MIS) remain to be validated. The purpose of this study was to investigate outcomes in real-world patients receiving minimally invasive sleeve lobectomy in a balanced large cohort.

Methods

Between January 2013 and December 2018, 578 consecutive patients undergoing sleeve resection at a high-volume center were retrospectively analyzed. Surgical and oncologic outcomes were compared between MIS and thoracotomy patients after propensity-score matching (PSM).

Results

MIS sleeve lobectomy was increasingly used as a time-trend in real-world. Before PSM, the MIS group had smaller tumor size, more T2-stage cases, and more right upper lobe sleeve lobectomies compared to the Open group. After 1:4 PSM by patient demographics and tumoral characteristics, 100 cases of MIS and 338 cases of Open sleeve lobectomy were further analyzed. Although median operation time was longer in the MIS group than in the Open group (170.5 minutes vs.149.5 minutes, P < 0.001), patients in MIS group had significantly less estimated intraoperative blood loss (100 ml vs. 200 ml, P = 0.003), shorter drainage duration (5 days vs. 6 days, P = 0.027) and less amount of drainage (1280 ml vs. 1640 ml, P < 0.001) after surgery. Complete resection rate, combined angioplasty, number of dissected lymph nodes, post-operative length of stay, postoperative morbidity and mortality rate, and application of adjuvant therapy were similar between the two matched groups. Conversion to open thoracotomy was necessary in 13.6% patients, but with similar perioperative outcomes compared to Open cases except for longer operation time. More lower lobe sleeve lobectomies were accomplished via robot-assisted thoracoscopic surgery than via video-assisted thoracoscopic surgery (40.0% vs. 12.0%, P = 0.017) in MIS patients. Five-year overall survivals (MIS vs. Open: 72.7% vs. 64.4%, P = 0.156) and five-year progression-free survivals (MIS vs. Open: 49.2% vs. 50.5%, P = 0.605) were similar between the two matched groups.

Conclusions

MIS sleeve lobectomy is associated with similar or even better perioperative results and oncologic outcomes to open thoracotomy. Conversion to thoracotomy does not compromise perioperative outcomes. Robot surgery may be preferable for more complex sleeve resections.
Clinical characteristics of pancreatic and biliary tract cancers in Lynch syndrome: A retrospective analysis from the Finnish National Lynch Syndrome Research Registry
Authors: Zalevskaja Kristina , Mecklin Jukka-Pekka , Seppälä Toni T.
Published: February 2023

Introduction

Patients with Lynch syndrome (LS) have an increased lifetime risk of pancreatic cancer (PC) and biliary tract cancer (BTC). These cancers have a notoriously pessimistic prognosis due to late diagnosis and limited therapeutic options. There are limited data based on small cohorts reviewing PC and BTC in LS patients.

Methods

In this retrospective study of the Lynch Syndrome Registry of Finland (LSRFi), records of genetically verified LS patients diagnosed with PC or BTC between 1982 and 2020 were analyzed.

Results

Thirty-nine patients were included: tumor(s) were in the pancreas in 26 patients, in the biliary tract in 10, and in the ampulla of Vater in three. A pathogenic germline variant was found in MLH1 in 33 of 39 patients. Twenty-six patients with 28 tumors located in the pancreas were identified: 23 pancreatic ductal adenocarcinomas (PDACs) and five neuroendocrine tumors (NETs). The median age at diagnosis of PC was 64 years (range of 38–81). In PC, the 5-year overall survival (OS) rate was 20%, and in PDAC, it was 13.6%. Ten patients with BTC were diagnosed: two intrahepatic, five perihilar, two distal extrahepatic cholangiocarcinomas, and one gallbladder carcinoma. Eight patients were male, and the median age at diagnosis was 54 years (range of 34–82). The 5-year OS rate for BTC was 30%. Metachronous tumors were diagnosed in 28 patients (70%). Colorectal cancer was the most common metachronous tumor, diagnosed in 20 patients (51%), and diagnosed prior to PC or BTC in all cases. Curative surgery was attempted on 17 of 39 patients. For 30 patients (91%), the cause of death was PC or BTC; two patients died from another LS-associated cancer, and one died from a stroke.

Conclusion

Although the survival of LS patients with PC or BTC is better than in sporadic cancers, it is still poor and may be reflected by the relatively higher surgical resectability accounted for by the earlier age of onset. More studies on analyses of the molecular and immune profile, screening, and management of LS-associated pancreaticobiliary cancers are warranted.
Celastrol inhibits store operated calcium entry and suppresses psoriasis
Authors: Yuan Xiaoman , Tang Bin , Chen Yilan , Zhou Lijuan , Deng Jingwen , Han Lin , Zhai Yonggong , Zhou Yandong , Gill Donald L. , Lu Chuanjian , Wang Youjun
Published: February 2023

Introduction: Psoriasis is an inflammatory autoimmune skin disease that is hard to cure and prone to relapse. Currently available global immunosuppressive agents for psoriasis may cause severe side effects, thus it is crucial to identify new therapeutic reagents and druggable signaling pathways for psoriasis.

Methods: To check the effects of SOCE inhibitors on psoriasis, we used animal models, biochemical approaches, together with various imaging techniques, including calcium, confocal and FRET imaging.

Results and discussion: Store operated calcium (Ca2+) entry (SOCE), mediated by STIM1 and Orai1, is crucial for the function of keratinocytes and immune cells, the two major players in psoriasis. Here we showed that a natural compound celastrol is a novel SOCE inhibitor, and it ameliorated the skin lesion and reduced PASI scores in imiquimod-induced psoriasis-like mice. Celastrol dose- and time-dependently inhibited SOCE in HEK cells and HaCaT cells, a keratinocyte cell line. Mechanistically, celastrol inhibited SOCE via its actions both on STIM1 and Orai1. It inhibited Ca2+ entry through constitutively-active Orai1 mutants independent of STIM1. Rather than blocking the conformational switch and oligomerization of STIM1 during SOCE activation, celastrol diminished the transition from oligomerized STIM1 into aggregates, thus locking STIM1 in a partially active state. As a result, it abolished the functional coupling between STIM1 and Orai1, diminishing SOCE signals. Overall, our findings identified a new SOCE inhibitor celastrol that suppresses psoriasis, suggesting that SOCE pathway may serve as a new druggable target for treating psoriasis.
Zein-based nanoparticles: Preparation, characterization, and pharmaceutical application
Authors: Liu Guijin , An Dongyu , Li Junjian , Deng Shiming
Published: February 2023

Zein, as one of the natural and GRAS proteins in plant, is renewable, nontoxic, biocompatible and biodegradable. Over the past decade, many research efforts have been devoted to zein-based biomaterials for several industrial applications. Combining with research experiences in our research group, the preparation methods, characterizations and pharmaceutical applications of zein-based nanoparticles were summarized in this review. Zein NPs with different particle nanostructures have been prepared by chemical crosslinking, desolvating, dispersing and micromixing strategies. The pharmaceutical applications of zein NPs are mainly focus on the drug delivery. Zein NPs can improve the drug stability, increase the oral bioavailability, control the drug release and enhance the drug targeting, thereby improving the pharmaceutical effect effectively. More efforts are required to analyze the relationship among preparation methods, particle nanostructures and pharmaceutical properties in virtue of quality by design approach, and further promote the scale-up production and clinical application of zein NPs.