bluuebunny/crossref_metadata_2025 huggingface dataset:
Single-cell RNA sequencing reveals a novel inhibitory effect of ApoA4 on NAFL mediated by liver-specific subsets of myeloid cells
Authors: Liu Xiao-Huan , Zhou Jin-Ting , Yan Chun-xia , Cheng Cheng , Fan Jing-Na , Xu Jing , Zheng Qiangsun , Bai Qiang , Li Zongfang , Li Shengbin , Li Xiaoming
Published: November 2022

The liver immune microenvironment is a key element in the development of hepatic inflammation in NAFLD. ApoA4 deficiency increases the hepatic lipid burden, insulin resistance, and metabolic inflammation. However, the effect of ApoA4 on liver immune cells and the precise immune cell subsets that exacerbate fatty liver remain elusive. The aim of this study was to profile the hepatic immune cells affected by ApoA4 in NAFL. We performed scRNA-seq on liver immune cells from WT and ApoA4-deficient mice administered a high-fat diet. Immunostaining and qRT–PCR analysis were used to validate the results of scRNA-seq. We identified 10 discrete immune cell populations comprising macrophages, DCs, granulocytes, B, T and NK&NKT cells and characterized their subsets, gene expression profiles, and functional modules. ApoA4 deficiency led to significant increases in the abundance of specific subsets, including inflammatory macrophages (2-Mφ-Cxcl9 and 4-Mφ-Cxcl2) and activated granulocytes (0-Gran-Wfdc17). Moreover, ApoA4 deficiency resulted in higher Lgals3, Ctss, Fcgr2b, Spp1, Cxcl2, and Elane levels and lower Nr4a1 levels in hepatic immune cells. These genes were consistent with human NAFLD-associated marker genes linked to disease severity. The expression of NE and IL-1β in granulocytes and macrophages as key ApoA4 targets were validate in the presence or absence of ApoA4 by immunostaining. The scRNA-seq data analyses revealed reprogramming of liver immune cells resulted from ApoA4 deficiency. We uncovered that the emergence of ApoA4-associated immune subsets (namely Cxcl9+ macrophage, Cxcl2+ macrophage and Wfdc17+ granulocyte), pathways, and NAFLD-related marker genes may promote the development of NAFL. These findings may provide novel therapeutic targets for NAFL and the foundations for further studying the effects of ApoA4 on immune cells in various diseases.
Influence of PRRSV-1 vaccination and infection on mononuclear immune cells at the maternal-fetal interface
Authors: Stas Melissa R. , Kreutzmann Heinrich , Stadler Julia , Sassu Elena L. , Mair Kerstin H. , Koch Michaela , Knecht Christian , Stadler Maria , Dolezal Marlies , Balka Gyula , Zaruba Marianne , Mötz Marlene , Saalmüller Armin , Rümenapf Till , Gerner Wilhelm , Ladinig Andrea
Published: November 2022

Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most devastating viruses for the global swine industry. Infection during late gestation causes reproductive failure but the local immune responsein uteroremains poorly understood. In this study, an experimental PRRSV-infection model with two different PRRSV-1 field isolates was used to investigate the immune cell phenotypes at the maternal-fetal interface during late gestation. In addition, phenotypic changes induced by a modified live virus (MLV, ReproCyc®PRRS EU) vaccine were studied. Vaccinated (n = 12) and non-vaccinated pregnant gilts (n = 12) were challenged with either one of the PRRSV-1 field isolates (low vs. high virulent, LV or HV) or sham-inoculated at day 84 of gestation. Twenty-one days post infection all gilts were euthanized and the fetal preservation status for all fetuses per litter was assessed. Leukocytes from the maternal-fetal interface were isolated and PRRSV-induced changes were investigated usingex vivophenotyping by flow cytometry. PRRSV load in tissue from the maternal endometrium (ME) and fetal placenta (FP) was determined by RT-qPCR. In the ME, a vast increase in CD8β T cells with CD8αposCD27dimearly effector phenotype was found for fetuses from the non-vaccinated LV and HV-challenged gilts, compared to non-treated and vaccinated-only controls. HV-challenged fetuses also showed significant increases of lymphocytes with effector phenotypes in the FP, including NKp46posNK cells, CD8αhighγδ T cells, as well as CD8αposCD27pos/dimCD4 and CD8 T cells. In vaccinated animals, this common activation of effector phenotypes was more confined and the fetal preservation status significantly improved. Furthermore, a negative correlation between the viral load and CD163highCD169posmononuclear phagocytic cells was observed in the FP of HV-infected animals. These results suggest that the strong expansion of effector lymphocytes in gilts that were only infected causes immune-pathogenesis rather than protection. In contrast, the attenuated MLV seems to dampen this effect, yet presumably induces memory cells that limit reproductive failure. This work provides valuable insights into changes of local immune cell phenotypes following PRRSV vaccination and infection.
Ex vivo cytokine production in psoriatic disease: Towards specific signatures in cutaneous psoriasis and peripheral psoriatic arthritis
Authors: Larid Guillaume , Delwail Adriana , Dalle Thomas , Vasseur Philippe , Silvain Christine , Jégou Jean-François , Morel Franck , Lecron Jean-Claude , Gervais Elisabeth
Published: November 2022

Objectives

Psoriatic arthritis (PsA) and cutaneous psoriasis (PsO) are different phenotypes of psoriatic disease (PsD), whose underlying specific mechanisms remain incompletely understood. As cytokines are key elements to induce and tune up immune responses to drive inflammatory diseases, our objective was to assess whether clinical features, disease phenotype and PsA and PsO activity were associated with a particular ex vivo cytokine production profile.

Methods

Forty-eight patients (37 PsA and 11 PsO) and 11 healthy subjects (HS) were studied. Cytokine production by peripheral blood mononuclear cells (PBMC) that were either unstimulated, or stimulated with LPS or anti-CD3/CD28 antibodies, were analysed by multiplex assay in the culture supernatants.

Results

Cytokine signature of PsD includes a high level of TNFα in supernatants of LPS-stimulated PBMC, higher levels of IL-6 and lower levels of IFN-γ and IL-17A after CD3-CD28 stimulation, as well as higher spontaneous IL-1RA and TNFα production compared to HS. High body mass index (BMI) was associated with lower levels of IL-1β, and metabolic syndrome with lower levels of IFN-γ after LPS stimulation. In PsD, dermatological activity was related with higher IL-17A level, while rheumatic activity was linked with lower levels of IFN-γ and TNFα. Comparing each PsD subtype to HS, IL-1β and IL-6 productions are higher when using LPS stimulation in PsO patients with higher levels of IL-1β and IL-1α in peripheral PsA patients after CD3/CD28 stimulation. LPS stimulation induced high levels of IL-17A in peripheral PsA compared to axial PsA. PsA patients with axial PsA share some features with PsO but shows a distinct cytokine pattern compared to peripheral PsA.

Conclusion

PsO and the different PsA subtypes exhibit distinct ex vivo cytokine production profiles and common features of the so-called PsD. Analysis of IL-1 cytokine family and IL-6 seems to be of particular interest to distinguish PsO and peripheral PsA since it depends on monocytes in PsO and T-lymphocytes in peripheral PsA. Peripheral cytokine profiles are influenced by rheumatic and dermatological activity of the disease, and also by metabolic syndrome features. Our results highlight the crucial role of immune cell interactions with different patterns of interaction depending on clinical phenotype.
Using a risk assessment framework to spatially and temporally spread the fishery catch limit for Antarctic krill in the west Antarctic Peninsula: A template for krill fisheries elsewhere
Authors: Warwick-Evans V. , Constable A. , Dalla Rosa L. , Secchi E. R. , Seyboth E. , Trathan P. N.
Published: November 2022

The west Antarctic Peninsula is an important breeding and foraging location for marine predators that consume Antarctic Krill (Euphasia superba). It is also an important focus for the commercial fishery for Antarctic krill, managed by the Commission for the Conservation of Antarctic Marine Living Resources (CCAMLR). Aiming to minimise ecosystem risks from fishing, whilst enabling a sustainable fishery, CCAMLR has recently endorsed a new management framework that incorporates information about krill biomass estimates, sustainable harvest rates and a risk assessment to spatially and temporally distribute catch limits. We have applied a risk assessment framework to the west Antarctic Peninsula region (Subarea 48.1), with the aim of identifying the most appropriate management units by which to spatially and temporally distribute the local krill catch limit. We use the best data currently available for implementing the approach, recognising the framework is flexible and can accommodate new data, when available, to improve future estimates of risk. We evaluated 36 catch distribution scenarios for managing the fishery and provide advice about the scale at which the krill fishery can be managed. We show that the spatial distribution with which the fishery currently operates presents some of the highest risks of all scenarios evaluated. We highlight important issues that should be resolved, including data gaps, uncertainty and incorporating ecosystem dynamics. We emphasize that for the risk assessment to provide robust estimates of risk, it is important that the management units are at a similar scale to ecosystem function. Managing the fishery at small scales has the lowest risk but may necessitate a high level of management interaction. Our results offer advice to CCAMLR about near-term management and this approach could provide a template for the rest of the southwest Atlantic (Area 48), or fisheries elsewhere. As each data layer influences the outcome of the risk assessment, we recommend that updated estimates of the distribution, abundance and consumption of krill, and estimates of available krill biomass will be key as CCAMLR moves forward to develop a longer-term management strategy.
The polymerase δ-interacting protein family and their emerging roles in diseases
Authors: Huang Peiluo , Wu Lei , Zhu Ningxia , Zhao Hongtao , Du Juan
Published: November 2022

The polymerase δ-interacting protein (POLDIP) family is a new family that can interact with DNA polymerase δ (delta). The members of the POLDIP family include POLDIP1, POLDIP2, and POLDIP3. Screened by the two-hybrid method, POLDIP1, POLDIP2, and POLDIP3 were initially discovered and named for their ability to bind to the p50 subunit of DNA polymerase δ. Recent studies have confirmed that POLDIPs are involved in the regulation of signal transduction pathways in neurodevelopment, neuropsychiatric diseases, cardiovascular diseases, tumors, and other diseases. However, each protein participates in different signaling pathways. In this review, we elucidate upon the family in terms of their genes and protein structures, their biological functions, in addition to the pathways that they are involved in during the development of diverse diseases. Finally, to provide new insights to the scientific community, we used the TCGA database to analyze and summarize the gene expressions of POLDIP family members in various tumors, as well as the correlations between their expressions and the overall survival times of tumor patients. Our data summary will give researchers working on cancer new concepts.
Clinicopathologic features of renal cell carcinomas seen at the Aga Khan University Hospital in Kenya
Authors: Mutuiri Anderson , Gakinya Samuel
Published: November 2022

Introduction

Kidney cancer accounted for 1. 8% of global cancer deaths according to Globocan 2020 estimates, with most of these being renal cell carcinomas. Lower rates of renal cell carcinoma are reported for Africa and these are expected to change for a combination of reasons. The clinical and morphologic characteristics of renal cell carcinoma seen within Kenya have not been described before. This study aims to partially fill this gap.

Materials and methods

This was a cross-sectional descriptive study examining electronic histopathology reports from the Aga Khan University Hospital Nairobi Laboratory for the period January 2016 to May 2022.

Results

Sixty cases of renal cell carcinoma were identified. The mean age at diagnosis was 55.3 years. The most common histologic subtype diagnosed was clear cell renal cell carcinoma (41.7%), followed by papillary renal cell carcinoma and renal cell carcinoma not further specified (both 21.7%), and chromophobe renal cell carcinoma (11.7%). The most frequent specimen type was resection, followed by cores of renal masses. The mean tumor size was 8.5 cm. Sixty-seven percent of patients presented with Stage III and above.

Discussion

Renal masses were the commonest clinical indication for biopsy among the records reviewed. The male to female ratio, as well as the mean age at presentation were comparable to what is described in literature for other regions of the world. The proportions of the commonest histologic subtypes matched what is described in other parts of the world. Challenges in the identification of histologic subtypes included having a limited panel of antibodies for diagnosis and the lack of genetic molecular tests for histotyping.

Conclusion

The spectrum of histologic subtypes of renal cell carcinoma seen at a tertiary referral hospital in Nairobi, Kenya was similar to that described in other parts of Africa and the globe. The age at presentation with renal cell carcinoma was consistent with what has been described in literature. Challenges were identified in the accurate histotyping of renal cell carcinoma due to constrained resources. Majority of cases diagnosed presented at advanced stage.
Genetic variations and microbiome of the poultry red mite Dermanyssus gallinae
Authors: Nishide Yudai , Sugimoto Takafumi N. , Watanabe Kenji , Egami Hiroshi , Kageyama Daisuke
Published: November 2022

The poultry red mite Dermanyssus gallinae poses a significant threat to the health of hens and poultry production. A comprehensive understanding of D. gallinae is necessary to develop sustainable and efficacious control methods. Here we examined 144 D. gallinae collected from 18 poultry farms throughout the Japanese Archipelago for their genetic variations based on mitochondrial cytochrome c oxidase subunit I (COI) sequences, and microbiome variations based on amplicon sequencing of the 16S ribosomal RNA gene. According to COI sequencing, the Japanese samples were categorized into three haplogroups, which did not reflect the geographical distribution. Microbiome analyses found that the major bacteria associated with D. gallinae were Bartonella, Cardinium, Wolbachia, and Tsukamurella, with Bartonella being most predominant. Among 144 individual mites, all possessed one of the two major types of Bartonella (Bartonella sp. A), while 140 mites possessed the other type (Bartonella sp. B). The presence of the two strains of Bartonella was also confirmed by a single copy gene, rpoB. The presence of Bartonella in laid eggs suggested transovarial vertical transmission. Given that obligate blood-feeding arthropods generally require a supply of B vitamins from symbiotic bacteria, Bartonella may play an important role in mite survival. Rickettsiella, a major symbiont in European D. gallinae populations, and suggested to be an important symbiont by genomic data, was rarely found in Japanese populations. Cardinium detected from D. gallinae fell into a major clade found widely in arthropods, whereas Wolbachia detected in Japanese D. gallinae appear to be a new lineage, located at the base of Wolbachia phylogeny. Of the mitochondrial phylogeny, infection patterns of Cardinium and Wolbachia were strongly correlated, possibly suggesting one or both of the symbionts induce reproductive manipulations and increase spread in the host populations.
Decomposition rate and biochemical fate of carbon from natural polymers and microplastics in boreal lakes
Authors: Vesamäki Jussi S. , Nissinen Riitta , Kainz Martin J. , Pilecky Matthias , Tiirola Marja , Taipale Sami J.
Published: November 2022

Microbial mineralization of organic compounds is essential for carbon recycling in food webs. Microbes can decompose terrestrial recalcitrant and semi-recalcitrant polymers such as lignin and cellulose, which are precursors for humus formation. In addition to naturally occurring recalcitrant substrates, microplastics have been found in various aquatic environments. However, microbial utilization of lignin, hemicellulose, and microplastics as carbon sources in freshwaters and their biochemical fate and mineralization rate in freshwaters is poorly understood. To fill this knowledge gap, we investigated the biochemical fate and mineralization rates of several natural and synthetic polymer-derived carbon in clear and humic lake waters. We used stable isotope analysis to unravel the decomposition processes of different 13C-labeled substrates [polyethylene, polypropylene, polystyrene, lignin/hemicellulose, and leaves (Fagus sylvatica)]. We also used compound-specific isotope analysis and molecular biology to identify microbes associated with used substrates. Leaves and hemicellulose were rapidly decomposed compared to microplastics which were degraded slowly or below detection level. Furthermore, aromatic polystyrene was decomposed faster than aliphatic polyethylene and polypropylene. The major biochemical fate of decomposed substrate carbon was in microbial biomass. Bacteria were the main decomposers of all studied substrates, whereas fungal contribution was poor. Bacteria from the family Burkholderiaceae were identified as potential leaf and polystyrene decomposers, whereas polypropylene and polyethylene were not decomposed.
Adaptive changes of coral Galaxea fascicularis holobiont in response to nearshore stress
Authors: Zhu Wentao , Zhu Ming , Liu Xiangbo , Xia Jingquan , Wang Hao , Chen Rouwen , Li Xiubao
Published: November 2022

Global change and local stressors are simultaneously affecting the nearshore corals, and microbiome flexibility may assist corals in thriving under such multiple stressors. Here, we investigated the effects of various environmental variables on Galaxea fascicularis holobiont from nearshore and offshore reefs. These nearshore reefs were more turbid, eutrophic, and warm than offshore reefs. However, coral physiological parameters did not differ significantly. Corals under stressful nearshore environments had low symbiont diversity and selected more tolerant Symbiodiniaceae. The bacterial diversity of offshore corals was significantly higher, and their community composition varied obviously. Diffusion limitations and environmental heterogeneity were essential in structuring microbial communities. Functional annotation analysis demonstrated significant differences between nearshore and offshore corals in bacterial functional groups. Environmental stress significantly reduced the complexity and connectivity of bacterial networks, and the abundances of keystone taxa altered considerably. These results indicated that corals could thrive nearshore through holobiont plasticity to cope with multiple environmental stresses.
Contemporary biophysical approaches for studying 14-3-3 protein-protein interactions
Authors: Thurairajah Bethany , Hudson Andrew J. , Doveston Richard G.
Published: November 2022

14-3-3 proteins are a family of regulatory hubs that function through a vast network of protein-protein interactions. Their dysfunction or dysregulation is implicated in a wide range of diseases, and thus they are attractive drug targets, especially for molecular glues that promote protein-protein interactions for therapeutic intervention. However, an incomplete understanding of the molecular mechanisms that underpin 14-3-3 function hampers progress in drug design and development. Biophysical methodologies are an essential element of the 14-3-3 analytical toolbox, but in many cases have not been fully exploited. Here, we present a contemporary review of the predominant biophysical techniques used to study 14-3-3 protein-protein interactions, with a focus on examples that address key questions and challenges in the 14-3-3 field.
Sensory organization of balance control in children with vestibular migraine and recurrent vertigo of childhood
Authors: Li Xiaofei , Liu Yalan , Lyu Yafeng , Li Yawei , Jian Huirong , Li Xiaoyi , Fan Zhaomin , Wang Haibo , Zhang Daogong
Published: November 2022

Background

Migraine plays an important role in some subgroups of children with recurrent vertigo. Moreover, the migraine component varies from definite to possibly absent as defined in this spectrum of three disorders—vestibular migraine of childhood (VMC), probable VMC (pVMC), and recurrent vertigo of childhood (RVC). However, studies on the sensory organization of balance control in these three disorders are rare.

Objective

To explore the balance control of children with RVC, VMC, and pVMC, when the three sensory systems are challenged.

Method

A retrospective analysis was performed on 125 children with VMC (18 female and 15 male; aged 11.64 ± 2.74), pVMC (10 female and eight male; aged 11.78 ± 2.51), and RVC (32 female and 42 male; aged 11.10 ± 2.60). All children in each subtype were divided into groups of children aged ≤ 12 years old and 13–17 years old. Vestibular examination screening and assessment for postural control using the six conditions of the sensory organization test (SOT) were performed. The three primary outcome measures were: equilibrium score (ES), strategy score (SS), and sensory analysis score of the SOT.

Results

Equilibrium score under six different conditions and composite score increased with age (all P-values < 0.05). The somatosensory and visual scores also improved with growing (P-values < 0.05). However, vestibular scores did not increase significantly with age as the other senses did (P > 0.05). In the children ≤ 12 year-old group, children with VMC had a significantly higher visual preference score than those with pVMC and RVC (P < 0.05). There was an effect of age on the horizontal HIT. Ocular vestibular evoked myogenic potential (oVEMP), cervical vestibular evoked myogenic potential (cVEMP), and unilateral weakness (UW) values showed no significant difference among three diseases.

Conclusion

Compared with patients at the age of 13–17 years old and with RVC and pVMC (both ≤ 12 years old), children with VMC had a higher degree of reliance on visual signals to maintain their balance and a poorer central integration of peripheral information before reaching 12 years of age. In addition, vision may predominate by weakening vestibular function based on visuo-vestibular interactions. It must be noted that peripheral vestibular examinations could not distinguish the three disease subtypes.
Radiomics features from perihematomal edema for prediction of prognosis in the patients with basal ganglia hemorrhage
Authors: Zhou Peng , Sun Quanye , Song Gesheng , Liu Zexiang , Qi Jianfeng , Yuan Xuhui , Wang Xu , Yan Shaofeng , Du Jianyang , Dai Zhengjun , Wang Jianjun , Hu Shaoshan
Published: November 2022

Objective

We developed and validated a clinical-radiomics nomogram to predict the prognosis of basal ganglia hemorrhage patients.

Methods

Retrospective analyses were conducted in 197 patients with basal ganglia hemorrhage (training cohort: n = 136, test cohort: n = 61) who were admitted to The First Affiliated Hospital of Shandong First Medical University (Shandong Provincial Qianfoshan Hospital) and underwent computed tomography (CT) scan. According to different prognoses, patients with basal ganglia hemorrhage were divided into two groups. Independent clinical risk factors were derived with univariate and multivariate regression analysis. Radiomics signatures were obtained using least absolute shrinkage and selection operator. A radiomics score (Rad-score) was generated by 12 radiomics signatures of perihematomal edema (PHE) from CT images that were correlated with the prognosis of basal ganglia hemorrhage patients. A clinical-radiomics nomogram was conducted by combing the Rad-score and clinical risk factors using logistic regression analysis. The prediction performance of the nomogram was tested in the training cohort and verified in the test cohort.

Results

The clinical model conducted by four clinical risk factors and 12 radiomcis features were used to establish the Rad-score. The clinical-radiomics nomogram outperformed the clinical model in the training cohort [area under the curve (AUC), 0.92 vs. 0.85] and the test cohort (AUC, 0.91 vs 0.85). The clinical-radiomics nomogram showed good calibration and clinical benefit in both the training and test cohorts.

Conclusion

Radiomics features of PHE in patients with basal ganglia hemorrhage could contribute to the outcome prediction. The clinical-radiomics nomogram may help first-line clinicians to make individual clinical treatment decisions for patients with basal ganglia hemorrhage.
Associations between exercise capacity, p16INK4a expression and inflammation among adult survivors of childhood cancer
Authors: Goodenough Chelsea G. , Wogksch Matthew D. , Kundu Mondira , Lear Matthew , Thomas Paul G. , Srivastava Deo Kumar , Wang Zhaoming , Armstrong Gregory T. , Hudson Melissa M. , Robison Leslie L. , Ness Kirsten K.
Published: November 2022

Background

Over 50% of childhood cancer survivors are exercise intolerant, with maximal aerobic capacities comparable to individuals decades older, suggesting early physiologic ageing. In addition, 36% of survivors are obese. Optimal exercise capacity provides a foundation to support daily function and healthy body habitus and is associated with benefits to cognition, cardiovascular health, and longevity. Cellular senescence and inflammation are key mechanisms that drive age-related disease, quantifiable as biomarkers in peripheral blood.

Aims

This study aimed to evaluate associations between p16INKa, a biomarker of cellular senescence, and inflammation and exercise capacity among adult survivors of childhood cancer.

Materials and methods

Eligible survivors were recruited from the St. Jude Lifetime (SJLIFE) Cohort Study. Exercise capacity was assessed by maximal oxygen uptake (VO2, ml/kg/min) obtained via cardiopulmonary exercise testing using a modified Bruce protocol. Body fat (%) was determined from dual energy x-ray absorptiometry (DEXA). Peripheral blood samples were used to evaluate log2 p16INK4a mRNA expression, a biomarker of cellular senescence, and inflammation with high sensitivity C-reactive protein (hs-CRP) levels. Multivariable regression evaluated associations between p16INK4a, hs-CRP, body fat, and exercise capacity.

Results

Participants included 185 five-year childhood cancer survivors (mean age 36.6 [range 20.1 - 55.7] years, 44% male, 77% non-Hispanic white, 53% leukemia/lymphoma). Compared to males, females had lower peak VO2 (mean ± SD, 22.5 ± 8.2 vs. 28.8 ± 7.7 ml/kg/min, p<0.01), higher p16INK4a expression (9.6 ± 1.2 vs. 9.2 ± 1.2 fold, p=0.02), and hs-CRP concentration (5.9 ± 8.4 vs. 3.3 ± 3.9 mg/L, p=0.01). Among females (n=103), hs-CRP concentration (β -0.2, 95% CI -0.34 to -0.05, p=0.01) and p16INK4a expression (β-5.32, 95% CI 10.42 to -0.22, p=0.04) were inversely associated and statistically significant with peak exercise capacity, with a significant interaction between p16INK4a expression and body fat (β 0.15, 95% CI 0.02 to 0.28, p=0.03). Among males (n=82), p16INK4a expression (β -1.01, 95% CI -2.14 to 0.12, p=0.08), and body fat (β -0.54, 95% CI -0.70 to -0.38, p<0.01) were inversely associated with peak exercise capacity.

Conclusion

Inflammation and p16INK4a expression, a biomarker of cellular senescence, are associated with lower exercise capacity in childhood cancer survivors, suggesting potential targets or outcome measures for interventions designed to prevent or remediate accelerated physiologic ageing in this population.
Predictive machine learning model for microvascular invasion identification in hepatocellular carcinoma based on the LI-RADS system
Authors: Yang Xue , Shao Guoqing , Liu Jiaojiao , Liu Bin , Cai Chao , Zeng Daobing , Li Hongjun
Published: November 2022

Purposes

This study aimed to establish a predictive model of microvascular invasion (MVI) in hepatocellular carcinoma (HCC) by contrast-enhanced computed tomography (CT), which relied on a combination of machine learning approach and imaging features covering Liver Imaging and Reporting and Data System (LI-RADS) features.

Methods

The retrospective study included 279 patients with surgery who underwent preoperative enhanced CT. They were randomly allocated to training set, validation set, and test set (167 patients vs. 56 patients vs. 56 patients, respectively). Significant imaging findings for predicting MVI were identified through the Least Absolute Shrinkage and Selection Operator (LASSO) logistic regression method. Predictive models were performed by machine learning algorithm, support vector machine (SVM), in the training set and validation set, and evaluated in the test set. Further, a combined model adding clinical findings to the radiologic model was developed. Based on the LI-RADS category, subgroup analyses were conducted.

Results

We included 116 patients with MVI which were diagnosed through pathological confirmation. Six imaging features were selected about MVI prediction: four LI-RADS features (corona enhancement, enhancing capsule, non-rim aterial phase hyperehancement, tumor size) and two non-LI-RADS features (internal arteries, non-smooth tumor margin). The radiological feature with the best accuracy was corona enhancement followed by internal arteries and tumor size. The accuracies of the radiological model and combined model were 0.725–0.714 and 0.802–0.732 in the training set, validation set, and test set, respectively. In the LR-4/5 subgroup, a sensitivity of 100% and an NPV of 100% were obtained by the high-sensitivity threshold. A specificity of 100% and a PPV of 100% were acquired through the high specificity threshold in the LR-M subgroup.

Conclusion

A combination of LI-RADS features and non-LI-RADS features and serum alpha-fetoprotein value could be applied as a preoperative biomarker for predicting MVI by the machine learning approach. Furthermore, its good performance in the subgroup by LI-RADS category may help optimize the management of HCC patients.
Post COVID-19 vaccination headache: A clinical and epidemiological evaluation
Authors: Ceccardi Giulia , Schiano di Cola Francesca , Di Cesare Marco , Liberini Paolo , Magoni Mauro , Perani Cristiano , Gasparotti Roberto , Rao Renata , Padovani Alessandro
Published: November 2022

Introduction

This study aimed to assess the prevalence and clinical characteristics of headaches, in particular secondary headaches.

Materials and Methods

This observational study was performed at the ASST Spedali Civili of Brescia, Italy. Visits to the Emergency Department (ED) and subsequent hospitalizations regarding a new or worsening headache in the 16 days following the administration of the COVID-19 vaccine between January 2021 and January 2022 were recorded and compared with those of January 2019–January 2020.

Results

The ratio between ED admissions due to headaches and total ED admissions was significantly higher in 2021 compared with 2019 (4.84% vs. 4.27%; p < 0.0001). Two-hundred and eighty-nine ED headache admissions (10.8% of all ED headache admissions) were time-correlated to the COVID-19 vaccination, of which 40 were hospitalized in order to exclude a symptomatic etiology. At discharge, 32 patients had a diagnosis of benign headache not attributed to any cranial/extracranial disorder and eight patients of secondary headache, whose diagnoses were the following: Headache attributed to cranial and/or cervical vascular disorder (n = 4); headache attributed to nonvascular intracranial disorder (n = 2); headache or facial pain attributed to disorder of the cranium, neck, eyes, ears, nose, sinuses, teeth, mouth, or other facial or cervical structure (n = 1); and painful lesions of the cranial nerves (n = 1). The headache most frequently reported by patients had migraine-like characteristics: the localization was predominantly frontal or temporal, the pain was described as throbbing and severe in intensity and it was frequently accompanied by nausea/vomit, and photo-phonophobia. Over half—regardless of the final diagnosis—of hospitalized patients had a history of primary headaches.

Conclusions

Following the spread of COVID-19 vaccination, the number of ED admissions due to headaches significantly increased. However, less than 14% of all the ED visits due to a headache time-correlated to the COVID-19 vaccination were actually hospitalized, with most patients documenting a benign headache, possibly related to the generic side effects of the vaccination. Only 8/40 hospitalized patients were diagnosed with a secondary headache. These benign headaches would actually fulfill diagnostic criteria for 8.1 Headaches attributed to the use of or exposure to a substance (ICHD-3), although, at the time being, it does not include vaccines as possible substances.

The headache migraine-like characteristics’ reported by most patients could suggest activation of the trigeminovascular pathway by all the cytokines and other pro-inflammatory molecules released following the vaccination.
The serum acylcarnitines profile in epileptic children treated with valproic acid and the protective roles of peroxisome proliferator-activated receptor a activation in valproic acid-induced liver injury
Authors: Ma Yiyi , Wang Minglu , Guo Shuaishuai , Li Tong , Liu Xiaodong , Zhao Limei
Published: November 2022

Valproic acid (VPA) is widely used as a major drug in the treatment of epilepsy. Despite the undisputed pharmacological importance and effectiveness of VPA, its potential hepatotoxicity is still a major concern. Being a simple fatty acid, the hepatotoxicity induced by VPA has long been considered to be due primarily to its interference with fatty acid β-oxidation (β-FAO). The aim of this study was to investigate the biomarkers for VPA-induced abnormal liver function in epileptic children and to determine potential mechanisms of its liver injury. Targeted metabolomics analysis of acylcarnitines (ACs) was performed in children’s serum. Metabolomic analysis revealed that VPA -induced abnormal liver function resulted in the accumulation of serum long-chain acylcarnitines (LCACs), and the reduced expression of β-FAO relevant genes (Carnitine palmitoyltrans-ferase (CPT)1, CPT2 and Long-chain acyl-CoA dehydrogenase (LCAD)), indicating the disruption of β-FAO. As direct peroxisome proliferator-activated receptor a (PPARα)- regulated genes, CPT1A, CPT2 and LCAD were up-regulated after treatment with PPARα agonist, fenofibrate (Feno), indicating the improvement of β-FAO. Feno significantly ameliorated the accumulation of various lipids in the plasma of VPA-induced hepatotoxic mice by activating PPARα, significantly reduced the plasma ACs concentration, and attenuated VPA-induced hepatic steatosis. Enhanced oxidative stress and induced by VPA exposure were significantly recovered using Feno treatment. In conclusion, this study indicates VPA-induced β-FAO disruption might lead to liver injury, and a significant Feno protective effect against VPA -induced hepatotoxicity through reversing fatty acid metabolism.
EGFR exon 20 insertion variants A763_Y764insFQEA and D770delinsGY confer favorable sensitivity to currently approved EGFR-specific tyrosine kinase inhibitors
Authors: Yang Guangjian , Yang Yaning , Hu Jiaqi , Xu Haiyan , Zhang Shuyang , Wang Yan
Published: November 2022

Background: The EGFR exon 20 insertions (ex20ins) D770_N771insSVD and V769_D770insASV are most frequent in non-small-cell lung cancer (NSCLC) and are associated with intrinsic resistance to currently approved EGFR tyrosine kinase inhibitors (TKIs). A763_Y764insFQEA and D770delinsGY, respectively, account for 3%–8% and 2.0%–4.8% of EGFR ex20ins in NSCLC and are associated with a more favorable response to EGFR-specific TKIs as per case reports. The aim of this study was to elucidate the molecular structures of these mutants and their binding affinities to diverse EGFR TKIs and compare the clinical outcomes in NSCLC patients harboring these mutations.

Methods: A real-world cohort study was conducted to evaluate and compare the clinical outcomes of EGFR TKIs among NSCLC patients with different EGFR ex20ins mutants in response to EGFR TKIs. The structures of A763_Y764insFQEA and D770delinsGY were also analyzed and drug binding simulations were performed.

Results: With a median follow-up of 24.0 months, the first-line objective response rate (ORR), disease control rate (DCR), and median progression-free survival (PFS) were, respectively, 0 (0/16), 50.0% (8/16), and 2.07 months (95%CI, 0–6.25) in patients harboring D770_N771insSVD and V769_D770insASV variants and 33.3% (4/12), 83.3% (10/12), and 9.97 months (95%CI, 4.75–15.19) in patients with A763_Y764insFQEA and D770delinsGY variants. There was a significant difference between the PFS of these two subgroups (median, 9.97 vs.2.07 months, HR = 0.33, 95%CI, 0.13–0.85, p = 0.02). Similarly, the PFS was significantly longer after second-line treatment with EGFR TKIs in patients harboring A763_Y764insFQEA and D770delinsGY compared to those with other insertions (median, 6.77 vs.2.23 months, HR = 0.14, p < 0.001). Computational simulations indicated that A763_Y764insFQEA and D770delinsGY mutants were structurally similar to wild-type EGFR. In contrast, the C-helix and phosphate-binding loop of D770_N771insSVD and V769_D770insASV had shifted into the drug-binding pocket, resulting in significant steric hindrance and a lack of affinity for the currently approved EGFR inhibitors.

Conclusion: NSCLC patients harboring A763_Y764insFQEA and D770delinsGY insertions of EGFR are responsive to the currently approved EGFR TKIs as opposed to patients with the D770_N771insSVD and V769_D770insASV variants. Therefore, A763_Y764insFQEA and D770delinsGY should be classified as active mutations among heterogeneous EGFR ex20ins subtypes and the carriers can be treated with the suitable EGFR TKIs.
Underwater hyperspectral imaging system for deep-sea exploration
Authors: Xue Qingsheng , Li Hui , Lu Fengqin , Bai Haoxuan
Published: November 2022

As a technology that combines spectral technology and imaging technology, hyperspectral imaging technology can obtain the spectral and spatial information about the targets effectively. Hence, the underwater hyperspectral imaging technology has a fast development since it was first used underwater. Many kinds of hyperspectral imagers used for underwater detection at different depths were developed. However, the underwater hyperspectral imagers used at deep sea were rarely reported while the required detection depth increased. To satisfy the deep-sea exploration requirements, an underwater hyperspectral imaging system was designed. An optical system with a low F-number and a compact structure was first designed. The F-number of the system is 2.5. The focal length of the objective lens is 25 mm, and the field of view of the objective lens is 35.2°.The wavelength range of the system is from 400 to 1000 nm, and the spectral resolution of the spectrometer is better than 3 nm. The instrument cabin and other structures for waterproofing were designed. A minicomputer used for control communication, data acquisition, and processing was equipped in the actual system. The isolation performance and imaging quality were tested in the laboratory environment. According to the test result, the system has a good imaging quality and spectral detection capability. Also, the system can be used at 6000 m underwater, which may provide a new feasible technical scheme for deep-sea exploration.
Predicting mortality in acute kidney injury patients undergoing continuous renal replacement therapy using a visualization model: A retrospective study
Authors: Zeng Zhenguo , Zou Kang , Qing Chen , Wang Jiao , Tang Yunliang
Published: November 2022

Background: Patients with severe acute kidney injury (AKI) require continuous renal replacement therapy (CRRT) when hemodynamically unstable. We aimed to identify prognostic factors and develop a nomogram that could predict mortality in patients with AKI undergoing CRRT.

Methods: Data were extracted from the Dryad Digital Repository. We enrolled 1,002 participants and grouped them randomly into training (n = 670) and verification (n = 332) datasets based on a 2:1 proportion. Based on Cox proportional modeling of the training set, we created a web-based dynamic nomogram to estimate all-cause mortality.

Results: The model incorporated phosphate, Charlson comorbidity index, body mass index, mean arterial pressure, levels of creatinine and albumin, and sequential organ failure assessment scores as independent predictive indicators. Model calibration and discrimination were satisfactory. In the training dataset, the area under the curves (AUCs) for estimating the 28-, 56-, and 84-day all-cause mortality were 0.779, 0.780, and 0.787, respectively. The model exhibited excellent calibration and discrimination in the validation dataset, with AUC values of 0.791, 0.778, and 0.806 for estimating 28-, 56-, and 84-day all-cause mortality, respectively. The calibration curves exhibited the consistency of the model between the two cohorts. To visualize the results, we created a web-based calculator.

Conclusion: We created a web-based calculator for assessing fatality risk in patients with AKI receiving CRRT, which may help rationalize clinical decision-making and personalized therapy.
4 days in dry immersion increases arterial wall response to ultrasound wave as measured using radio-frequency signal, comparison with spaceflight data
Authors: Arbeille Philippe , Greaves Danielle , Guillon Laurent , Hughson Richard L
Published: November 2022

Recent studies have reported a significant increase in common carotid artery (CCA) intima media thickness, wall stiffness and reflectivity to ultrasound, in astronauts, after six months of spaceflight. The hypothesis was that 4 days in dry immersion (subjects under bags of water) will be sufficient to change the CCA wall reflectivity to ultrasound similar to what observed after spaceflight. Such response would be quantified using the amplitude of the ultrasound signal returned to the probe by the target concerned. [coefficient of signal return (Rs)]. The Rs for anterior and posterior CCA wall, sternocleidomastoid muscle, intima layer and CCA lumen were calculated from the ultrasound radio frequency (RF) data displayed along each echographic line. After four days of DI, Rs increased in the CCA posterior wall (+15% +/- 10 from pre DI, p < 0.05), while no significant change was observed in the other targets. The observed increase in Rs with DI was approximately half compared to what was observed after six months of space flight (+34% +/- 14). This difference may be explained by dose response (dry immersion only four days in duration). As a marker of tissue-level physical changes, Rs provide complimentary information alongside previously observed CCA wall thickness and stiffness.
Versatile role of Pseudomonas fuscovaginae cyclic lipopeptides in plant and microbial interactions
Authors: Ferrarini Enrico , Špacapan Mihael , Lam Van Bach , McCann Andrea , Cesa-Luna Catherine , Marahatta Bishnu Prasad , De Pauw Edwin , De Mot René , Venturi Vittorio , Höfte Monica
Published: November 2022

Pseudomonas fuscovaginae is the most prominent bacterial sheath rot pathogen, causing sheath brown rot disease in rice. This disease occurs worldwide and it is characterized by typical necrotic lesions on the sheath, as well as a reduction in the number of emitted panicles and filled grains. P. fuscovaginae has been shown to produce syringotoxin and fuscopeptin cyclic lipopeptides (CLPs), which have been linked to pathogenicity. In this study, we investigated the role of P. fuscovaginae UPB0736 CLPs in plant pathogenicity, antifungal activity and swarming motility. To do so, we sequenced the strain to obtain a single-contig genome and we constructed deletion mutants in the biosynthetic gene clusters responsible for the synthesis of CLPs. We show that UPB0736 produces a third CLP of 13 amino acids, now named asplenin, and we link this CLP with the swarming activity of the strain. We could then show that syringotoxin is particularly active against Rhizoctonia solani in vitro. By testing the mutants in planta we investigated the role of both fuscopeptin and syringotoxin in causing sheath rot lesions. We proved that the presence of these two CLPs considerably affected the number of emitted panicles, although their number was still significantly affected in the mutants deficient in both fuscopeptin and syringotoxin. These results reveal the importance of CLPs in P. fuscovaginae pathogenicity, but also suggest that other pathogenicity factors may be involved.
The effect of circular soil biosolarization treatment on the physiology, metabolomics, and microbiome of tomato plants under certain abiotic stresses
Authors: Haber Zechariah , Wilhelmi María del Mar Rubio , Fernández-Bayo Jesus D. , Harrold Duff R. , Stapleton James J. , Toubiana David , VanderGheynst Jean S. , Blumwald Eduardo , Simmons Christopher W. , Sade Nir , Achmon Yigal
Published: November 2022

Soil biosolarization (SBS) is an alternative technique for soil pest control to standard techniques such as soil fumigation and soil solarization (SS). By using both solar heating and fermentation of organic amendments, faster and more effective control of soilborne pathogens can be achieved. A circular economy may be created by using the residues of a given crop as organic amendments to biosolarize fields that produce that crop, which is termed circular soil biosolarization (CSBS). In this study, CSBS was employed by biosolarizing soil with amended tomato pomace (TP) residues and examining its impact on tomato cropping under conditions of abiotic stresses, specifically high salinity and nitrogen deficiency. The results showed that in the absence of abiotic stress, CSBS can benefit plant physiological performance, growth and yield relative to SS. Moreover, CSBS significantly mitigated the impacts of abiotic stress conditions. The results also showed that CSBS impacted the soil microbiome and plant metabolome. Mycoplana and Kaistobacter genera were found to be positively correlated with benefits to tomato plants health under abiotic stress conditions. Conversely, the relative abundance of the orders RB41, MND1, and the family Ellin6075 and were negatively correlated with tomato plants health. Moreover, several metabolites were significantly affected in plants grown in SS- and CSBS-treated soils under abiotic stress conditions. The metabolite xylonic acid isomer was found to be significantly negatively correlated with tomato plants health performance across all treatments. These findings improve understanding of the interactions between CSBS, soil ecology, and crop physiology under abiotic stress conditions.