bluuebunny/crossref_metadata_2025 huggingface dataset:
Chitotriosidase 1 in the cerebrospinal fluid as a putative biomarker for HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) progression
Authors: Gomes Yago Côrtes Pinheiro , Freitas Nicole Lardini , Souza Flávia Santos , Sandim Vanessa , Pereira Denise Abreu , Nogueira Fábio César Sousa , Echevarria-Lima Juliana , Leite Ana Claudia Celestino Bezerra , Lima Marco Antonio Sales Dantas , Silva Marcus Tulius Teixeira , Araújo Abelardo Queiroz Campos , Vicente Ana Carolina Paulo , Espíndola Otávio Melo
Published: August 2022

Human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is an inflammatory neurodegenerative disease that affects motor, urinary, intestinal, and sensory functions. Typically, HAM/TSP is slowly progressive, but it may vary from limited motor disability after decades (very slow progression) to loss of motor function in a few years from disease onset (rapid). In this study, we aimed to identify prognostic biomarkers for HAM/TSP to support patient management. Thus, proteomic analysis of the cerebrospinal fluid (CSF) was performed with samples from HTLV-1 asymptomatic carriers (AC) (n=13) and HAM/TSP patients (n=21) with rapid, typical, and very slow progression using quantitative label-free liquid chromatography/tandem mass spectrometry. Enrichment analyses were also carried out to identify key biological processes associated with distinct neurological conditions in HTLV-1 infection. Candidate biomarkers were validated by ELISA in paired CSF and serum samples, and samples from HTLV-1-seronegative individuals (n=9) were used as controls. CSF analysis identified 602 proteins. Leukocyte/cell activation, immune response processes and neurodegeneration pathways were enriched in rapid progressors. Conversely, HTLV-1 AC and HAM/TSP patients with typical and very slow progression had enriched processes for nervous system development. Differential expression analysis showed that soluble vascular cell adhesion molecule 1 (sVCAM-1), chitotriosidase 1 (CHIT1), and cathepsin C (CTSC) were upregulated in HAM/TSP. However, only CHIT1 was significantly elevated after validation, particularly in HAM/TSP rapid progressors. In contrast, none of these biomarkers were altered in serum. Additionally, CSF CHIT1 levels in HAM/TSP patients positively correlated with the speed of HAM/TSP progression, defined as points in the IPEC-2 HAM/TSP disability scale per year of disease, and with CSF levels of phosphorylated neurofilament heavy chain, neopterin, CXCL5, CXCL10, and CXCL11. In conclusion, higher CSF levels of CHIT1 were associated with HAM/TSP rapid progression and correlated with other biomarkers of neuroinflammation and neurodegeneration. Therefore, we propose CHIT1 as an additional or alternative CSF biomarker to identify HAM/TSP patients with a worse prognosis.
HDAC inhibitors Panobinostat and Romidepsin enhance tax transcription in HTLV-1-infected cell lines and freshly isolated patients’ T-cells
Authors: Schnell Annika P. , Kohrt Stephan , Aristodemou Aris , Taylor Graham P. , Bangham Charles R. M. , Thoma-Kress Andrea K.
Published: August 2022

The viral transactivator Tax plays a key role in HTLV-1 reactivation and de novo infection. Previous approaches focused on the histone deacetylase inhibitor (HDACi) Valproate as a latency-reversing agent to boost Tax expression and expose infected cells to the host’s immune response. However, following treatment with Valproate proviral load decreases in patients with HAM/TSP were only transient. Here, we hypothesize that other compounds, including more potent and selective HDACi, might prove superior to Valproate in manipulating Tax expression. Thus, a panel of HDACi (Vorinostat/SAHA/Zolinza, Panobinostat/LBH589/Farydak, Belinostat/PXD101/Beleodaq, Valproate, Entinostat/MS-275, Romidepsin/FK228/Istodax, and MC1568) was selected and tested for toxicity and potency in enhancing Tax expression. The impact of the compounds was evaluated in different model systems, including transiently transfected T-cells, chronically HTLV-1-infected T-cell lines, and freshly isolated PBMCs from HTLV-1 carriers ex vivo. We identified the pan-HDACi Panobinostat and class I HDACi Romidepsin as particularly potent agents at raising Tax expression. qRT-PCR analysis revealed that these inhibitors considerably boost tax and Tax-target gene transcription. However, despite this significant increase in tax transcription and histone acetylation, protein levels of Tax were only moderately enhanced. In conclusion, these data demonstrate the ability of Panobinostat and Romidepsin to manipulate Tax expression and provide a foundation for further research into eliminating latently infected cells. These findings also contribute to a better understanding of conditions limiting transcription and translation of viral gene products.
Establishment of three heterogeneous subtypes and a risk model of low-grade gliomas based on cell senescence-related genes
Authors: Chen Jing , Wu Lingjiao , Yang Hanjin , Zhang XiaoChen , Xv SuZhen , Qian Qiong
Published: August 2022

Background

Cellular senescence is a key element in the occurrence and progression of a variety of tumors. As a result, cellular senescence-related markers can be categorized based on the prognosis status of patients. Due to the heterogeneity and the complexity of the tumor microenvironment (TME), the long-term effectiveness of low-grade glioma (LGG) treatment remains a clinical challenge. Consequently, developing and refining effective treatment approaches to aid with LGG management is critical.

Methods

Based on the expressions of cell senescence-related genes (CSRGs) acquired from the cellAge database, consensus clustering was utilized to identify stable molecular subtypes. Clinical features, immune infiltration, route modifications, and genetic changes of various subtypes were also assessed. Following that, the least absolute shrinkage and selection operator (LASSO) regression and univariate Cox regression analysis were used for developing the cell senescence-related risk score (CSRS) model. Finally, a correlation study of the CSRS model with molecular, immunological, and immunotherapy parameters was performed.

Results

C1, C2, and C3, are the three senescence-related subtypes that were identified. Patients belonging to the C1 subtype had poor prognoses and a substantial proportion of them was in the grade G3. The differentially expressed genes (DEGs) among the three subtypes were used to develop the CSRS model. In both the training and independent validation cohort, the model had a high area under the receiver operating characteristic (ROC) curve in predicting the overall survival (OS) of patients. As a result, this model can predict clinical features and responses to immunotherapy in a variety of patients and it is a potential independent prognostic factor for LGG.

Conclusion

This research discovered three LGG subtypes related to cell senescence and created a CSRS model for six genes. Cell senescence was highly associated with unfavorable prognosis in LGG. The CSRS model can be used to predict the prognosis of patients and identify patients who would benefit from immunotherapy.
Modelling approaches for capturing plankton diversity (MODIV), their societal applications and data needs
Authors: Acevedo-Trejos Esteban , Cadier Mathilde , Chakraborty Subhendu , Chen Bingzhang , Cheung Shun Yan , Grigoratou Maria , Guill Christian , Hassenrück Christiane , Kerimoglu Onur , Klauschies Toni , Lindemann Christian , Palacz Artur , Ryabov Alexey , Scotti Marco , Smith S. Lan , Våge Selina , Prowe Friederike
Published: August 2022

Ecosystem models need to capture biodiversity, because it is a fundamental determinant of food web dynamics and consequently of the cycling of energy and matter in ecosystems. In oceanic food webs, the plankton compartment encompasses by far most of the biomass and diversity. Therefore, capturing plankton diversity is paramount for marine ecosystem modelling. In recent years, many models have been developed, each representing different aspects of plankton diversity, but a systematic comparison remains lacking. Here we present established modelling approaches to study plankton ecology and diversity, discussing the limitations and strengths of each approach. We emphasize their different spatial and temporal resolutions and consider the potential of these approaches as tools to address societal challenges. Finally, we make suggestions as to how better integration of field and experimental data with modelling could advance understanding of both plankton biodiversity specifically and more broadly the response of marine ecosystems to environmental change, including climate change.
De novo podocytopathy following moderna COVID-19 vaccine: A case report and racial disproportionality in adverse effect reports
Authors: Hong Li-Yu , Lee Chii-Hong , Chiu I-Jen
Published: August 2022

In this study, we report a case of de novo minimal change disease shortly after the second dose of the Moderna COVID-19 vaccine. A previously healthy 51-year-old Asian man presented with lower-limb edema and foamy urine 3 days after receiving the second dose of the vaccine. Laboratory data revealed the following: serum creatinine, 0.65 mg/dl; serum albumin, 1.3 g/dl; urine protein-to-creatinine ratio, 15.3 g. A renal biopsy was performed, and minimal change in the disease was confirmed. The patient achieved complete remission in the tenth week after starting treatment with prednisolone (1 mg/kg/day). Ethnic differences may influence the adverse effects of drugs and vaccines. However, there is very limited data to address the influence of ethnic diversity on disease prevalence, clinical presentation, and treatment outcomes in COVID-19 vaccine-associated glomerulonephritis.
Dynamic of bacterial and archaeal diversity in a tropical soil over 6 years of repeated organic and inorganic fertilization
Authors: Sadet-Bourgeteau Sophie , Djemiel Christophe , Chemidlin Prévost-Bouré Nicolas , Feder Frederic
Published: August 2022

The soil microbial community plays important roles in nutrient cycling, plant pathogen suppression, decomposition of residues and degradation of pollutants; as such, it is often regarded as a good indicator of soil quality. Repeated applications of mixed organic and inorganic materials in agriculture improve the soil microbial quality and in turn crop productivity. The soil microbial quality following several years of repeated fertilizer inputs has received considerable attention, but the dynamic of this community over time has never been assessed. We used high-throughput sequencing targeting 16S ribosomal RNA genes to investigate the evolution of the bacterial and archaeal community throughout 6 years of repeated organic and inorganic fertilizer applications. Soils were sampled from a field experiment in La Mare (Reunion Island, France), where different mixed organic-inorganic fertilizer inputs characterized by more or less stable organic matter were applied regularly for 6 years. Soil samples were taken each year, more than 6 months after the latest fertilizer application. The soil molecular biomass significantly increased in some organically fertilized plots (by 35–45% on average), 3–5 years after the first fertilizers application. The significant variations in soil molecular microbial biomass were explained by the fertilization practices (cumulated organic carbon inputs) and sometimes by the soil parameters (sand and soil carbon contents). The structure of the bacterial and archaeal community was more influenced by time than by the fertilization type. However, repeated fertilizer applications over time tended to modify the abundance of the bacterial phyla Acidobacteria, Actinobacteria, Bacteroidetes, Firmicutes, and Proteobacteria. To conclude, the present study highlights that the soil bacterial and archaeal community is lastingly modified after 6 years of repeated fertilizer inputs. These changes depend on the nature of the organic input and on the fertilization practice (frequency and applied quantity).
RNA-seq analysis reveals genes related to photosynthetic carbon partitioning and lipid production in Phaeodactylum tricornutum under alkaline conditions
Authors: Liu Jian , Yin Weihua , Zhang Xinya , Xie Xuan , Dong Guanghui , Lu Yao , Tao Baoxiang , Gong Qiangbin , Chen Xinyan , Shi Chao , Qin Yuan , Zeng Rensen , Li Dawei , Li Hongye , Zhao Chao , Zhang Huiying
Published: August 2022

Alkaline pH can induce triacylglyceride accumulation in microalgae, however its molecular mechanism remains elusive. Here, we investigated the effect of 2-[N-cyclohexylamino]-ethane-sulfonic acid (CHES) -induced intracellular alkalization on the lipid production in Phaeodactylum tricornutum. Intracellular pH was increased upon CHES treatment, displaying a high BCECF fluorescence ratio. CHES treatment significantly induced lipid accumulation but had no change in cell density and biomass. The expression of genes involved in photoreaction, carbon fixation, glycolysis, pentose phosphate pathway, amino acid catabolism, GS/GOGAT cycle, TCA cycle, triacylglyceride assembly, de novo fatty acid synthesis were up-regulated, while that in amino acid biosynthesis were down-regulated under CHES conditions. Correspondingly, the activity of phosphoribulokinase, carbonic anhydrase, pyruvate dehydrogenase and acetaldehyde dehydrogenase were enhanced by CHES treatment. Chloroplast-specific biological processes were activated by CHES treatment in P. tricornutum, which redirects the flux of carbon into lipid biosynthesis, meanwhile stimulates de novo fatty acid biosynthesis, leading to lipid accumulation under CHES conditions. These indicate an enhancement of intermediate metabolism, resulting in lipid accumulation by CHES.
Molecular mechanism of Epimedium in the treatment of vascular dementia based on network pharmacology and molecular docking
Authors: Xie Chenchen , Tang Hao , Liu Gang , Li Changqing
Published: August 2022

Backgroud: Vascular dementia is the second most common cause of dementia after Alzheimer’s disease, accounting for an estimated 15% of cases. Recently, Epimedium has attracted great attention for its potential neuroprotective benefit. However, the direct role and mechanism of Epimedium on vascular dementia still lack systematic research. To systematically explore the possible pharmacological mechanism of Epimedium for the treatment of vascular dementia, network pharmacology, molecular docking, combined with experiment validation were conducted.

Methods: The bioactive compounds and targets of Epimedium were obtained from the TCMSP database. The potential targets of vascular dementia were identified from the DrugBank, OMIM, Genecards, Therapeutic Target Database, and DisGeNET databases. GO and KEGG pathway analyses were performed. Molecular docking was applied to validate the interaction between active components and hub targets. The bilateral common carotid artery occlusion (BCCAO) method was used for construction of a vascular dementia model in mice. The effects of Epimedium on learning and memory ability were examined by behavioral tests. The mechanisms of the cerebral protective effects of Epimedium were evaluated by WB, RT-PCR, and immunofluorescence.

Results: A total of 23 Epimedium active ingredients, and 71 intersecting targets of Epimedium against vascular dementia were obtained. The top five hub targets AKT1, TNF, IL1β, IL6, and MMP9 were identified, and molecular docking showed good binding. GO enrichment showed a total of 602 enrichment results, with 458 (80.56%) key targets mainly focused on biological processes (BP). The response to hypoxia, positive regulation of nitric oxide biosynthetic process, aging, inflammatory response, cellular response to lipopolysaccharide, negative regulation of apoptotic process were well ranked. KEGG pathway enrichment analysis identified the TNF signaling pathway as an important pathway, with the MAPK/extracellular signal-regulated kinase (ERK) and NF-κB signaling pathways as the key pathways involved. Consistently, in vivo experiments showed that Epimedium treatment improved learning and memory functions in mice with vascular dementia. In addition, Epimedium attenuated the activation of microglia and astrocytes in the hippocampal region after BCCAO. RT-qPCR and Western blot analysis showed that Epimedium not only affected the expression of AKT, TNF, IL1β, IL6, and MMP9, but also suppressed the TNF signaling pathway.

Conclusion: Epimedium may exert a protective effect against vascular dementia through the alleviation of oxidative stress, neuroinflammation, BBB dysfunction, apoptosis through TNF signaling pathway. This study explored the mechanism of Epimedium on vascular dementia systematically through network pharmacological and in vivo experiment approach, which provides insight into the treatment of vascular dementia.
High ratio of monocytes to high-density lipoprotein is associated with hemorrhagic transformation in acute ischemic stroke patients on intravenous thrombolysis
Authors: Xia Lingfan , Xu Tong , Zhan Zhenxiang , Wu Yucong , Xu Ye , Cao Yungang , Han Zhao
Published: August 2022

Background

Hemorrhagic transformation (HT) is a frequent, serious complication in acute ischemic stroke patients on intravenous thrombolysis. Here we investigated whether risk of HT is associated with the ratio of monocyte count to high-density lipoprotein level (MHR).

Materials and methods

Medical records were retrospectively examined for consecutive patients with acute ischemic stroke who received thrombolytic therapy. HT was diagnosed by computed tomography at 24–36 h after therapy. Potential association between MHR and HT was examined using logistic regression.

Results

A total of 340 patients were analyzed, and their median MHR was 0.44 (0.31–0.59). MHR was higher in the 51 patients (15.0%) with HT than in those who did not suffer HT (0.53 vs. 0.42, P = 0.001). Multivariate logistic regression showed that, after adjusting for potential confounders, MHR was an independent risk factor for HT (OR 7.50, 95% CI 1.64 to 34.35, P = 0.009). Risk of HT was significantly higher among patients whose MHR fell in the third quartile (0.42–0.53) and the fourth quartile (> 0.53) than among those with MHR in the first quartile (< 0.31; OR 3.53, 95% CI 1.11 to 11.20, P = 0.032; OR 4.79, 95% CI 1.49 to 15.42, P = 0.009).

Conclusion

High MHR may be independently associated with higher risk of HT in patients with acute ischemic stroke on intravenous thrombolysis.
The effect of general anesthesia on the test–retest reliability of resting-state fMRI metrics and optimization of scan length
Authors: Vedaei Faezeh , Alizadeh Mahdi , Romo Victor , Mohamed Feroze B. , Wu Chengyuan
Published: August 2022

Resting-state functional magnetic resonance imaging (rs-fMRI) has been known as a powerful tool in neuroscience. However, exploring the test–retest reliability of the metrics derived from the rs-fMRI BOLD signal is essential, particularly in the studies of patients with neurological disorders. Here, two factors, namely, the effect of anesthesia and scan length, have been estimated on the reliability of rs-fMRI measurements. A total of nine patients with drug-resistant epilepsy (DRE) requiring interstitial thermal therapy (LITT) were scanned in two states. The first scan was performed in an awake state before surgery on the same patient. The second scan was performed 2 weeks later under general anesthesia necessary for LITT surgery. At each state, two rs-fMRI sessions were obtained that each one lasted 15 min, and the effect of scan length was evaluated. Voxel-wise rs-fMRI metrics, including the amplitude of low-frequency fluctuation (ALFF), the fractional amplitude of low-frequency fluctuation (fALFF), functional connectivity (FC), and regional homogeneity (ReHo), were measured. Intraclass correlation coefficient (ICC) was calculated to estimate the reliability of the measurements in two states of awake and under anesthesia. Overall, it appeared that the reliability of rs-fMRI metrics improved under anesthesia. From the 15-min data, we found mean ICC values in awake state including 0.81, 0.51, 0.65, and 0.84 for ALFF, fALFF, FC, and ReHo, respectively, as well as 0.80, 0.59, 0.83, and 0.88 for ALFF, fALFF, FC, and ReHo, respectively, under anesthesia. Additionally, our findings revealed that reliability increases as the function of scan length. We showed that the optimized scan length to achieve less variability of rs-fMRI measurements was 3.1–7.5 min shorter in an anesthetized, compared to a wakeful state.
Rutin alleviated acrolein-induced cytotoxicity in Caco-2 and GES-1 cells by forming a cyclic hemiacetal product
Authors: Chen Peifang , Liu Shuang , Yin Zhao , Liang Pengjie , Wang Chunhua , Zhu Hanyue , Liu Yang , Ou Shiyi , Li Guoqiang
Published: August 2022

Acrolein (ACR), an α, β-unsaturated aldehyde, is a toxic compound formed during food processing, and the use of phenolics derived from dietary materials to scavenge ACR is a hot spot. In this study, rutin, a polyphenol widely present in various dietary materials, was used to investigate its capacity to scavenge ACR. It was shown that more than 98% of ACR was eliminated under the conditions of reaction time of 2 h, temperature of 80 °C, and molar ratio of rutin/ACR of 2/1. Further structural characterization of the formed adduct revealed that the adduct of rutin to ACR to form a cyclic hemiacetal compound (RAC) was the main scavenging mechanism. Besides, the stability of RAC during simulated in vitro digestion was evaluated, which showed that more than 83.61% of RAC was remained. Furthermore, the cytotoxicity of RAC against Caco-2 and GES-1 cells was significantly reduced compared with ACR, where the IC50 values of ACR were both below 20 μM while that of RAC were both above 140 μM. And the improvement of the loss of mitochondrial membrane potential (MMP) by RAC might be one of the detoxification pathways. The present study indicated that rutin was one of the potential ACR scavengers among natural polyphenols.
Clinical utility of a 1.5 T magnetic resonance imaging-guided linear accelerator during conventionally fractionated and hypofractionated prostate cancer radiotherapy
Authors: Turkkan Gorkem , Bilici Nazli , Sertel Huseyin , Keskus Yavuz , Alkaya Sercan , Tavli Busra , Ozkirim Muge , Fayda Merdan
Published: August 2022

Purpose

To report our initial experience with 1.5 T magnetic resonance imaging (MRI) linear accelerator (LINAC) in prostate cancer radiotherapy in terms of its use in a radiation oncology clinic.

Methods

The medical records of 14 prostate cancer patients treated with MRI-guided radiotherapy were retrospectively evaluated. The fraction time, adapt-to-position (ATP):adapt-to-shape (ATS) usage rate, machine-associated treatment interruption rate, median gamma pass rate, the percentage of planning target volume receiving at least 95% of the prescription dose coverage value of each ATS fraction, the effect of the learning curve on the fraction time and radiation-related acute gastrointestinal and genitourinary toxicities were evaluated.

Results

Fourteen patients have completed their treatment receiving a total of 375 fractions. Six patients (42%) were treated with the moderately hypofractionated regimen, five patients (36%) with conventionally fractionated, and three patients (22%) with the ultra-hypofractionated radiotherapy regimens. The ATP : ATS usage ratio was 3:372. The median fraction time was 46 min (range, 24-81 min). For the 3%/3 mm criterion, median gamma pass rate was 99.4% (range, 94.6–100%). Machine-related treatment interruptions were observed in 11 (2.9%) of 375 fractions, but this interruption rate decreased from 4.1% to 0.8%, after an upgrade. Three patients (22%) had gastrointestinal and five patients (36%) had genitourinary toxicity. No ≥grade 3 toxicity was observed.

Conclusion

1.5 T MRI-LINAC device could be used as a conventional LINAC device, when the conditions of the radiotherapy center are appropriate. MRI-guided prostate radiotherapy is safe and feasible, and high-quality studies with a larger number of patients and long-term results are needed to better evaluate this new technology.
Immune checkpoint inhibitor-related pneumonitis in non-small cell lung cancer: A review
Authors: Hao Yuxuan , Zhang Xiaoye , Yu Li
Published: August 2022

Immune checkpoint inhibitors (ICIs) have shown definite therapeutic effects in various types of cancers, especially non-small cell lung cancer (NSCLC). However, ICIs have unique side effects, called immune-related adverse events (irAEs), which can occur in various systems throughout the body. Among such irAEs, immune checkpoint inhibitor-related pneumonitis (ICI-P) is a fatal adverse reaction. In this review, we discussed the risk factors, pathogenesis, clinical characteristics, radiological manifestations, pathological features, diagnosis, grading, and management of ICI-P in NSCLC and the relationship between ICI-P and the efficacy of ICI therapy. In addition, we discussed the predictive factors for ICI-P. This review will play a crucial role in the prediction, evaluation, and management of ICI-P for widespread application of immunotherapy.
The prognostic value of immune-related genes AZGP1, SLCO5A1, and CTF1 in Uveal melanoma
Authors: Wang Wanpeng , Wang Sha
Published: August 2022

Objective

Uveal melanoma (UM) is an aggressive malignancy with a poor prognosis and no available effective treatment. Therefore, exploring a potential prognostic marker for UM could provide new possibilities for early detection, recurrence, and treatment.

Methods

In this study, we used “ConsensusClusterPlus” to classify patients with UM into subgroups, screened for significant differences in immune prognostic factors between subgroups, selected three genes using LASSO (Least absolute shrinkage and selection operator) regression to construct a risk model, and performed tumor immune cell infiltration analysis on the risk model. infiltration analysis, and then verified the heterogeneous role of the 3 core genes in other cancers by pan-cancer analysis and validate its expression by RT-qPCR in normal and tumor cells.

Results

We consistently categorized 80 UM patients into two subgroups after the immunogenetic set, where the UM1 subgroup had a better prognosis than the UM2 subgroup, and used 3 immune-related genes AZGP1, SLCO5A1, and CTF1 to derive risk scores as independent prognostic markers and predictors of UM clinicopathological features. We found significant differences in overall survival (OS) between low- and high-risk groups, and prognostic models were negatively correlated with B cell and myeloid dendritic cell and positively correlated with CD8+ T cell AZGP1 and CTF1 were significantly upregulated in UM cells compared with normal UM cells.

Conclusion

Immunogens are significantly associated with the prognosis of UM, and further classification based on genetic characteristics may help to develop immunotherapeutic strategies and provide new approaches to develop customized treatment strategies for patients.
The function and regulatory mechanism of RNA-binding proteins in breast cancer and their future clinical treatment prospects
Authors: Lu Xingjia , Zhong Jian , Liu Linlin , Zhang Wenzhu , Zhao Shengdi , Chen Liang , Wei Yuxian , Zhang Hong , Wu Jingxuan , Chen Wenlin , Ge Fei
Published: August 2022

Breast cancer is the most common female malignancy, but the mechanisms regulating gene expression leading to its development are complex. In recent years, as epigenetic research has intensified, RNA-binding proteins (RBPs) have been identified as a class of posttranscriptional regulators that can participate in regulating gene expression through the regulation of RNA stabilization and degradation, intracellular localization, alternative splicing and alternative polyadenylation, and translational control. RBPs play an important role in the development of normal mammary glands and breast cancer. Functional inactivation or abnormal expression of RBPs may be closely associated with breast cancer development. In this review, we focus on the function and regulatory mechanisms of RBPs in breast cancer, as well as the advantages and challenges of RBPs as potential diagnostic and therapeutic targets in breast cancer, and discuss the potential of RBPs in clinical treatment.
Minimal residual disease detection by next-generation sequencing in multiple myeloma: Promise and challenges for response-adapted therapy
Authors: Ferla Valeria , Antonini Elena , Perini Tommaso , Farina Francesca , Masottini Serena , Malato Simona , Marktel Sarah , Lupo Stanghellini Maria Teresa , Tresoldi Cristina , Ciceri Fabio , Marcatti Magda
Published: August 2022

Assessment of minimal residual disease (MRD) is becoming a standard diagnostic tool for curable hematological malignancies such as chronic and acute myeloid leukemia. Multiple myeloma (MM) remains an incurable disease, as a major portion of patients even in complete response eventually relapse, suggesting that residual disease remains. Over the past decade, the treatment landscape of MM has radically changed with the introduction of new effective drugs and the availability of immunotherapy, including targeted antibodies and adoptive cell therapy. Therefore, conventional serological and morphological techniques have become suboptimal for the evaluation of depth of response. Recently, the International Myeloma Working Group (IMWG) introduced the definition of MRD negativity as the absence of clonal Plasma cells (PC) with a minimum sensitivity of <10−5 either by next-generation sequencing (NGS) using the LymphoSIGHT platform (Sequenta/Adaptative) or by next-generation flow cytometry (NGF) using EuroFlow approaches as the reference methods. While the definition of the LymphoSIGHT platform (Sequenta/Adaptive) as the standard method derives from its large use and validation in clinical studies on the prognostic value of NGS-based MRD, other commercially available options exist. Recently, the LymphoTrack assay has been evaluated in MM, demonstrating a sensitivity level of 10−5, hence qualifying as an alternative effective tool for MRD monitoring in MM. Here, we will review state-of-the-art methods for MRD assessment by NGS. We will summarize how MRD testing supports clinical trials as a useful tool in dynamic risk-adapted therapy. Finally, we will also discuss future promise and challenges of NGS-based MRD determination for clinical decision-making. In addition, we will present our real-life single-center experience with the commercially available NGS strategy LymphoTrack-MiSeq. Even with the limitation of a limited number of patients, our results confirm the LymphoTrack-MiSeq platform as a cost-effective, readily available, and standardized workflow with a sensitivity of 10−5. Our real-life data also confirm that achieving MRD negativity is an important prognostic factor in MM.
Computed tomography-based radiomics quantification predicts epidermal growth factor receptor mutation status and efficacy of first-line targeted therapy in lung adenocarcinoma
Authors: Jiang Meilin , Yang Pei , Li Jing , Peng Wenying , Pu Xingxiang , Chen Bolin , Li Jia , Wang Jingyi , Wu Lin
Published: August 2022

Background

Biomarkers that predict the efficacy of first-line tyrosine kinase inhibitors (TKIs) are pivotal in epidermal growth factor receptor (EGFR) mutant advanced lung adenocarcinoma. Imaging-based biomarkers have attracted much attention in anticancer therapy. This study aims to use the machine learning method to distinguish EGFR mutation status and further explores the predictive role of EGFR mutation-related radiomics features in response to first-line TKIs.

Methods

We retrospectively analyzed pretreatment CT images and clinical information from a cohort of lung adenocarcinomas. We entered the top-ranked features into a support vector machine (SVM) classifier to establish a radiomics signature that predicted EGFR mutation status. Furthermore, we identified the best response-related features based on EGFR mutant-related features in first-line TKI therapy patients. Then we test and validate the predictive effect of the best response-related features for progression-free survival (PFS).

Results

Six hundred ninety-two patients were enrolled in building radiomics signatures. The 13 top-ranked features were input into an SVM classifier to establish the radiomics signature of the training cohort (n = 514), and the predictive score of the radiomics signature was assessed on an independent validation group with 178 patients and obtained an area under the curve (AUC) of 74.13%, an F1 score of 68.29%, a specificity of 79.55%, an accuracy of 70.79%, and a sensitivity of 62.22%. More importantly, the skewness-Low (≤0.882) or 10th percentile-Low group (≤21.132) had a superior partial response (PR) rate than the skewness-High or 10th percentile-High group (p < 0.01). Higher skewness (hazard ratio (HR) = 1.722, p = 0.001) was also found to be significantly associated with worse PFS.

Conclusions

The radiomics signature can be used to predict EGFR mutation status. Skewness may contribute to the stratification of disease progression in lung cancer patients treated with first-line TKIs.
Quality assessment of clinical practice guidelines for neonatal sepsis using the Appraisal of Guidelines for Research and Evaluation (AGREE) II Instrument: A systematic review of neonatal guidelines
Authors: Amer Yasser S. , Shaiba Lana A. , Hadid Adnan , Anabrees Jasim , Almehery Abdulrahman , AAssiri Manal , Alnemri Abdulrahman , Darwish Amira R. Al , Baqawi Badi , Aboshaiqah Ahmad , Hneiny Layal , Almaghrabi Rana H. , El-Malky Ahmed M. , Al-Dajani Nawaf M.
Published: August 2022

Background and objective

Neonatal sepsis (NS) continues to be a critical healthcare priority for the coming decades worldwide. The aim of this study was to critically appraise the quality of recent clinical practice guidelines (CPGs) for neonatal sepsis and to summarize and compare their recommendations.

Methods

This study involves a systematic review of CPGs. We identified clinical questions and eligibility criteria and searched and screened for CPGs using bibliographic and CPG databases and professional societies. Each included CPG was assessed by four independent appraisers using the Appraisal of Guidelines for REsearch & Evaluation II (AGREE II) instrument. We summarized the recommendations in a comparison practical table. The systematic review was drafted according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement. Its protocol was registered in the PROSPERO International Prospective Register of Systematic Reviews (ID: CRD42021258732).

Results

Our search retrieved 4,432 citations; of which five CPGs were eligible and appraised: American Academy of Pediatrics (AAP 2018) (35 and 34 weeks); Canadian Pediatric Society (CPS 2017); National Institute for Health and Care Excellence (NICE 2021); and Queensland Maternity and Neonatal Services (QH 2020). Among these, the overall assessment of two evidence-based CPGs scored > 70% (NICE and QH), which was consistent with their higher scores in the six domains of the AGREE II instrument. In domain 3 (rigor of development), NICE and QH scored 99 and 60%, respectively. In domain 5 (applicability), they scored 96 and 74%, respectively, and in domain 6 (editorial independence), they scored 90 and 71%, respectively.

Conclusion

The methodological quality of the NICE CPG was superior followed by the QH CPG with relevant recommendations for use in practice.

Systematic review registration

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021258732, PROSPERO (CRD42021258732).
Validity of Broselow tape for estimating the weight of children in pediatric emergency: A cross-sectional study
Authors: Zhu Shuzhen , Zhu Jihua , Zhou Hongqin , Chen Xiuping , Liang Jianfeng , Liu Lijun , Zhang Caidi , Zhao Yingying , Chen Yanyan , Wu Xiao , Ye Sheng , Jiang Kewen
Published: August 2022

Objective

To assess the validity of the Broselow tape in estimating the weight of Chinese children in pediatric emergency.

Methods

A cross-sectional study was conducted in the emergency department of the Children's Hospital of Zhejiang University School of Medicine (Hangzhou, Zhejiang Province, China) in March 2022. Broselow tape was used to estimate weight and its validity was compared with the advanced child life support (APLS) method.

Results

The study included 442 children (mean age: 48 months; male-to-female ratio: 1.13:1). The < 10, 10–19 and > 19-kg groups included 44, 257, and 141 children, respectively. The color concordance rates of the Broselow tape-estimated weight in the three groups were 56.8, 57.2, and 68.1%, respectively. The percentage of weight estimations within 10% of actual weight were 65.8% (59.1, 65.8, and 68.1% for the <10, 10–19 and > 19-kg groups, respectively) and 44.8% (40.9, 50.6, and 35.5% for the < 10, 10–19 and > 19-kg groups, respectively) using the Broselow tape and the APLS method, respectively. The correlation between the Broselow tape estimated weight and actual weight was r = 0.931 (P < 0.0001, 95% CI: 0.918–0.943), while the correlation between actual weight and the APLS method calculated weight was r = 0.883 (P < 0.0001, 95% CI: 0.861–0.902). The mean percentage error using the Broselow tape was 1.0 ± 12.0% (P < 0.001 vs. −7.2 ± 17.2% of the APLS method).

Conclusion

The Broselow tape may be an available method for predicting the weights of Chinese children in pediatric emergency.
Transjugular intrahepatic portosystemic shunt for the prevention of rebleeding in patients with cirrhosis and portal vein thrombosis: Systematic review and meta-analysis
Authors: Guo Ding-Fan , Fan Lin-Wei , Le Qi , Huang Cai-Bin
Published: August 2022

Background: Transjugular intrahepatic portosystemic shunt (TIPS) has been performed on patients with cirrhosis and portal vein thrombosis (PVT) to prevent rebleeding; however, the associated evidence is scarce. Hence, the study aimed to evaluate the feasibility and efficacy of TIPS in patients with cirrhosis and PVT and promote personalized treatment in such patients.

Methods: Literature was systematically obtained from PubMed, EMBASE, Cochrane Library, and Web of Science. Data from the included studies were extracted, and meta-analyses by the random effects model were used to pool data across studies. Heterogeneity was assessed using Cochran’s Q and I2 statistics. The source of heterogeneity was explored using subgroup analyses and meta-regressions.

Results: A total of 11 studies comprising 703 patients with cirrhosis and portal vein thrombosis (PVT: complete, 32.2%; chronic, 90.2%; superior mesenteric vein or splenic vein involvement, 55.2%; cavernous transformation, 26.8%) were included. TIPS showed feasibility in 95% of the cases (95% confidence interval [CI]: 89%–99%) with heterogeneity (I2 = 84%, p < 0.01) due to cavernous transformation. The pooled rebleeding rate was 13% (95% CI: 7%–20%) with heterogeneity (I2 = 75%, p < 0.01) explained by chronic PVT and anticoagulation (AC) therapy. Hepatic encephalopathy occurred in 32% of patients. The survival rate, portal vein recanalization rate, and shunt patency rate were 80%, 82%, and 77%, respectively.

Conclusion: TIPS is feasible and effectively prevents rebleeding in patients with cirrhosis and PVT, regardless of cavernous transformation of the portal vein. Due to a potentially high risk of rebleeding and no apparent benefits of AC, post-TIPS AC must be employed cautiously.

Systematic Review Registration: [https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=258765], identifier [CRD42021258765].
Effects of 3,4-diaminopyridine on myasthenia gravis: Preliminary results of an open-label study
Authors: Ceccanti Marco , Libonati Laura , Ruffolo Gabriele , Cifelli Pierangelo , Moret Federica , Frasca Vittorio , Palma Eleonora , Inghilleri Maurizio , Cambieri Chiara
Published: August 2022

Background: 3,4-diaminopyridine (3,4-DAP) can lead to clinical and electrophysiological improvement in myasthenic syndrome; it may thus represent a valuable therapeutic option for patients intolerant to pyridostigmine.

Objective: to assess 3,4-diaminopyridine (3,4-DAP) effects and tolerability in patients with anti-AChR myasthenia gravis.

Method: Effects were monitored electrophysiologically by repetitive nerve stimulation (RNS) and by standardized clinical testing (QMG score) before and after a single dose administration of 3,4-DAP 10 mg per os in 15 patients. Patients were divided according to their Myasthenia Gravis Foundation of America (MGFA) class into mild and severe.

Results: No significant side effects were found, apart from transient paresthesia. 3,4-DAP had a significant effect on the QMG score (p = 0.0251), on repetitive nerve stimulation (p = 0.0251), and on the forced vital capacity (p = 0.03), thus indicating that it may reduce the level of disability and the decremental muscle response. When the patients were divided according to the MGFA classification, 3,4-DAP showed a positive effect in the severe group, either for the QMG score (p = 0.031) or for the RNS decrement (p = 0.031). No significant difference was observed in any of the outcome measures within the mild group (p > 0.05). A direct effect of 3,4-DAP on nicotinic ACh receptors (nAChRs) was excluded since human nAChRs reconstituted in an expression system, which were not affected by 3,4-DAP application.

Conclusion: Our results suggest that 3,4-DAP may be a useful add-on therapy, especially in most severe patients or when immunosuppressive treatment has not yet reached its full effect or when significant side-effects are associated with anticholinesterase.
Airway immune response in the mouse models of obesity-related asthma
Authors: Kong Jingwei , Yang Fan , Bai Minghua , Zong Yuhan , Li Zhuqing , Meng Xianghe , Zhao Xiaoshan , Wang Ji
Published: August 2022

The prevalence rates of obesity and its complications have increased dramatically worldwide. Obesity can lead to low-grade chronic systemic inflammation, which predisposes individuals to an increased risk of morbidity and mortality. Although obesity has received considerable interest in recent years, the essential role of obesity in asthma development has not been explored. Asthma is a common chronic inflammatory airway disease caused by various environmental allergens. Obesity is a critical risk factor for asthma exacerbation due to systemic inflammation, and obesity-related asthma is listed as an asthma phenotype. A suitable model can contribute to the understanding of the in-depth mechanisms of obese asthma. However, stable models for simulating clinical phenotypes and the impact of modeling on immune response vary across studies. Given that inflammation is one of the central mechanisms in asthma pathogenesis, this review will discuss immune responses in the airways of obese asthmatic mice on the basis of diverse modeling protocols.
One of the isoamylase isoforms, CMI294C, is required for semi-amylopectin synthesis in the rhodophyte Cyanidioschyzon merolae
Authors: Maeno Toshiki , Yamakawa Yuki , Takiyasu Yohei , Miyauchi Hiroki , Nakamura Yasunori , Ono Masami , Ozaki Noriaki , Utsumi Yoshinori , Cenci Ugo , Colleoni Christophe , Ball Steven , Tsuzuki Mikio , Fujiwara Shoko
Published: August 2022

Most rhodophytes synthesize semi-amylopectin as a storage polysaccharide, whereas some species in the most primitive class (Cyanidiophyceae) make glycogen. To know the roles of isoamylases in semi-amylopectin synthesis, we investigated the effects of isoamylase gene (CMI294C and CMS197C)-deficiencies on semi-amylopectin molecular structure and starch granule morphology in Cyanidioschyzon merolae (Cyanidiophyceae). Semi-amylopectin content in a CMS197C-disruption mutant (ΔCMS197C) was not significantly different from that in the control strain, while that in a CMI294C-disruption mutant (ΔCMI294C) was much lower than those in the control strain, suggesting that CMI294C is essential for semi-amylopectin synthesis. Scanning electron microscopy showed that the ΔCMI294C strain contained smaller starch granules, while the ΔCMS197C strain had normal size, but donut-shaped granules, unlike those of the control strain. Although the chain length distribution of starch from the control strain displayed a semi-amylopectin pattern with a peak around degree of polymerization (DP) 11–13, differences in chain length profiles revealed that the ΔCMS197C strain has more short chains (DP of 3 and 4) than the control strain, while the ΔCMI294C strain has more long chains (DP ≥12). These findings suggest that CMI294C-type isoamylase, which can debranch a wide range of chains, probably plays an important role in semi-amylopectin synthesis unique in the Rhodophyta.
Stable Sparse Classifiers predict cognitive impairment from gait patterns
Authors: Aznielle-Rodríguez Tania , Ontivero-Ortega Marlis , Galán-García Lídice , Sahli Hichem , Valdés-Sosa Mitchell
Published: August 2022

Background

Although gait patterns disturbances are known to be related to cognitive decline, there is no consensus on the possibility of predicting one from the other. It is necessary to find the optimal gait features, experimental protocols, and computational algorithms to achieve this purpose.

Purposes

To assess the efficacy of the Stable Sparse Classifiers procedure (SSC) for discriminating young and healthy older adults (YA vs. HE), as well as healthy and cognitively impaired elderly groups (HE vs. MCI-E) from their gait patterns. To identify the walking tasks or combinations of tasks and specific spatio-temporal gait features (STGF) that allow the best prediction with SSC.

Methods

A sample of 125 participants (40 young- and 85 older-adults) was studied. They underwent assessment with five neuropsychological tests that explore different cognitive domains. A summarized cognitive index (MDCog), based on the Mahalanobis distance from normative data, was calculated. The sample was divided into three groups (young adults, healthy and cognitively impaired elderly adults) using k-means clustering of MDCog in addition to Age. The participants executed four walking tasks (normal, fast, easy- and hard-dual tasks) and their gait patterns, measured with a body-fixed Inertial Measurement Unit, were used to calculate 16 STGF and dual-task costs. SSC was then employed to predict which group the participants belonged to. The classification's performance was assessed using the area under the receiver operating curves (AUC) and the stable biomarkers were identified.

Results

The discrimination HE vs. MCI-E revealed that the combination of the easy dual-task and the fast walking task had the best prediction performance (AUC = 0.86, sensitivity: 90.1%, specificity: 96.9%, accuracy: 95.8%). The features related to gait variability and to the amplitude of vertical acceleration had the largest predictive power. SSC prediction accuracy was better than the accuracies obtained with linear discriminant analysis and support vector machine classifiers.

Conclusions

The study corroborated that the changes in gait patterns can be used to discriminate between young and healthy older adults and more importantly between healthy and cognitively impaired adults. A subset of gait tasks and STGF optimal for achieving this goal with SSC were identified, with the latter method superior to other classification techniques.