bluuebunny/crossref_metadata_2025 huggingface dataset:
A transient receptor potential channel-related model based on machine learning for evaluating tumor microenvironment and immunotherapeutic strategies in acute myeloid leukemia
Authors: Hua Jingsheng , Ding Tianling , Shao Yanping
Published: December 2022

Background

Acute myeloid leukemia (AML) is an aggressive hematopoietic malignancy. Transient receptor potential (TRP) channels in AML still need to be further explored. A TRP channel-related model based on machine learning was established in this study.

Methods

The data were downloaded from TCGA-LAML and Genome-Tissue Expression (GTEx). TRP-related genes (TRGs) were extracted from previous literature. With the use of Single-Sample Gene Set Enrichment Analysis (ssGSEA), TRP enrichment scores (TESs) were calculated. The limma package was used to identify differentially expressed genes (DEGs), and univariate Cox regression analysis was performed to identify prognostic DEGs. The above prognostic DEGs were analyzed by Random Survival Forest and least absolute shrinkage and selection operator (Lasso) analysis to create the TRP signature. The Kaplan–Meier and receiver operating characteristic (ROC) curves were plotted to investigate the efficiency and accuracy of prognostic prediction. Moreover, genomic mutation analysis was based on GISTIC analysis. Based on ESTIMATE, TIMER, MCPcounter, and ssGSEA, the tumor microenvironment and immunological characteristics were expressly evaluated to explore immunotherapeutic strategies. Enrichment analysis for TRP signature was based on the Kyoto Encyclopedia of Genes Genomes (KEGG), Gene Ontology (GO), over-representation analysis (ORA), and Gene Set Enrichment Analysis (GSEA). Genomics of Drug Sensitivity in Cancer (GDSC) and pRRophetic were used to carry out drug sensitivity analysis. Conclusively, SCHIP1 was randomly selected to perform in vitro cyto-functional experiments.

Results

The worse clinical outcomes of patients with higher TESs were observed. There were 107 differentially expressed TRGs identified. Our data revealed 57 prognostic TRGs. Eight TRGs were obtained to establish the prognostic TRP signature, and the worse clinical outcomes of patients with higher TRP scores were found. The efficiency and accuracy of TRP signature in predicting prognosis were confirmed by ROC curves and five external validation datasets. Our data revealed that the mutation rates of DNMT3A, IDH2, MUC16, and TTN were relatively high. The level of infiltrating immune cell populations, stromal, immune, and ESTIMATE scores increased as the TRP scores increased. Nevertheless, AML patients with lower TRP scores exhibited more tumor purity. The TRP scores were found to be correlated with immunomodulators and immune checkpoints, thus revealing immune characteristics and immunotherapeutic strategies. The IC50 values of six chemotherapeutics were lower in the high TRP score (HTS) group. Finally, it was found that SCHIP1 may be the oncogenic gene.

Conclusion

The results of this study will help in understanding the role of TRP and SCHIP1 in the prognosis and development of AML.
Efficacy and safety of neoadjuvant immunotherapy in resectable esophageal or gastroesophageal junction carcinoma: A pooled analysis of prospective clinical trials
Authors: Zhu Jie , Leng Xuefeng , Gao Binyang , Wang Bo , Zhang Hanlin , Wu Lei , Ma Jiabao , Tan Yan , Peng Lin , Han Yongtao , Wang Qifeng
Published: December 2022

Neoadjuvant chemoradiotherapy (NCRT) plus radical esophagectomy is currently the standard treatment for resectable esophageal or gastroesophageal junction (GEJ) carcinoma. The aim of this study is to evaluate the efficacy and safety of neoadjuvant immunotherapy in resectable esophageal or GEJ carcinoma. Prospective clinical trials investigating efficacy and/or safety of neoadjuvant immunotherapy with immune checkpoint inhibitors (ICIs) followed by radical esophagectomy in patients with newly diagnosed resectable esophageal or GEJ carcinoma were identified through literature search. Quality assessment was performed by using the Newcastle–Ottawa scale. Preliminary treatment outcomes of pathologically complete response (pCR, ypT0N0) and grade 3-4 adverse effects (AEs) were pooled together and then compared with standard NCRT of the historical control CROSS study by Chi-square (χ2) test. A two-sided P value < 0.05 was considered statistically significant. A total of 17 eligible non-randomized trials with 455 participants were included into analysis. The most common primary endpoint was pCR (n = 7, 41%), and the median sample size and follow-up period was 23 patients and 7.9 months, respectively. For patients receiving neoadjuvant immunotherapy, the overall pCR, R0 resection, and grade 3-4 AE rates were 33.2%, 95.5%, and 35.1%, respectively. For esophageal squamous cell carcinoma (ESCC) and adenocarcinoma (EAC), neoadjuvant immunochemoradiotherapy showed no significant improvement in pCR rate than NCRT (ESCC, 50% vs 48.7%, P = 0.9; EAC, 32.6% vs 23.1%, P = 0.22). Grade 3-4 AEs were the most common in patients with neoadjuvant immunochemoradiotherapy, significantly higher than immunochemotherapy (46.7% vs 32.8%, P = 0.04) and NCRT (46.7% vs 18.1%, P < 0.0001). In conclusion, for patients with resectable esophageal or GEJ carcinoma, the addition of ICIs to standard NCRT could not improve pCR rate in both ESCC and EAC, but significantly increased the risk of severe AEs. Large-scale phase 3 randomized trials were urgently needed to further confirm the survival benefit and safety profile of neoadjuvant immunotherapy.
How artificial potential field algorithms can help to simulate trade-offs in movement behaviour of reef fishes
Authors: Kruse Maren , Meyer Christian , Schneekloth Fabian , Reuter Hauke
Published: December 2022

Introduction

Space use patterns in fish result from the interactions between individual movement behaviour and characteristics of the environment. Herbivorous parrotfishes, for instance, are constrained by the availability of resources and different predation risks. The resulting spatial distribution of the fish population can strongly influence community composition and ecosystem resilience.

Methods

In a novel approach, we combine individual-based modelling (IBM) with an artificial potential field algorithm to realistically represent fish movements and the decision-making process. Potential field algorithms, which are popular methods in mobile robot path planning, efficiently generate the best paths for an entity to navigate through vector fields of repellent and attracting forces. In our model the repellent and attracting forces are predation risk and food availability, both implemented as separate grid-based vector fields. The coupling of individual fish bioenergetics with a navigation capacity provides a mechanistic basis to analyse how the habitat structure influences population dynamics and space utilization.

Results

Model results indicate that movement patterns and the resulting spatial distributions strongly depend on habitat fragmentation with the bioenergetic capacity to spawn and reproduce being particularly susceptible processes at the individual level. The resulting spatial distributions of the population are more irregularly distributed among coral reef patches the more the coral reef habitat becomes fragmented and reduced.

Discussion

This heterogeneity can have strong implications for the delivered ecosystem functioning, e.g., by concentrating or diluting the grazing effort. Our results also highlight the importance of incorporating individual foraging-path patterns and the spatial exploitation of microhabitats into marine spatial planning by considering the effects of fragmentation. The integration of potential fields into IBMs represents a promising strategy to advance our understanding of complex decision-making in animals by implementing a more realistic and dynamic decision-making process, in which each fish weighs different rewards and risks of the environment. This information may help to identify core areas and essential habitat patches and assist in effective marine spatial management.
Synthetic aperture imagery for high-resolution imaging sonar
Authors: Huang Pan , Yang Peixuan
Published: December 2022

Synthetic aperture sonar (SAS) can provide high-resolution underwater images. Traditional fast imaging algorithms designed for multi-receiver synthetic aperture sonar (MSAS) are complex because the point target reference spectrum (PTRS) deduction and imaging algorithm development are complicated. This paper proposes an imaging algorithm for the MSAS system to solve this issue. The proposed method first approximates the two-round slant range based on the phase center approximation method. The PTRS, including the quasi-monostatic and bistatic deformation terms, can be easily deduced. After compensating for the bistatic deformation term based on the interpolation and complex multiplication with the preprocessing step, the MSAS imagery can be simplified to the focus of the traditional monostatic SAS. Therefore, the conventional imaging algorithms designed for traditional monostatic SAS can be used directly. The proposed method providing high-resolution imaging results is more efficient than the traditional methods.
Simulation of high-frequency dissolved oxygen dynamics in a shallow estuary, the Corsica River, Chesapeake Bay
Authors: Tian Richard , Cai Xun , Testa Jeremy M. , Brady Damian C. , Cerco Carl F. , Linker Lewis C.
Published: December 2022

Understanding shallow water biogeochemical dynamics is a challenge in coastal regions, due to the presence of highly variable land-water interface fluxes, tight coupling with sediment processes, tidal dynamics, and diurnal variability in biogeochemical processes. While the deployment of continuous monitoring devices has improved our understanding of high-frequency (12 - 24 hours) variability and spatial heterogeneity in shallow regions, mechanistic modeling of these dynamics has lagged behind conceptual and empirical models. The inherent complexity of shallow water systems is represented in the Corsica River estuary, a small basin within the Chesapeake Bay ecosystem, where abundant monitoring data have been collected from long-term monitoring stations, continuous monitoring sensors, synoptic sensor surveys, and measurements of sediment-water fluxes. A state-of-the-art modeling system, the Semi-implicit Cross-scale Hydroscience Integrated System Model (SCHISM), was applied to the Corsica domain with a high-resolution grid and nutrient loads from the most recent version of the Chesapeake Bay watershed model. The Corsica SCHISM model reproduced observed high-frequency variability in dissolved oxygen, as well as seasonal variability in chlorophyll-a and sediment-water fluxes. Time-series signal analyses using Empirical Model Decomposition and spectral analysis revealed that the diurnal and M2 tide frequencies are the dominant high-frequency modes and physical transport contributes a larger share to dissolved oxygen budgets than biogeochemical processes on an hourly time scale. Heterogeneity and patchiness in dissolved oxygen resulting from phytoplankton distributions and geometry-driven eddies amplify the physical transport effect, and on longer time scales oxygen is controlled more by photosynthesis and respiration. Our simulation demonstrates that interactions among physical and biological dynamics generate complex high-frequency variability in water quality and non-linear reposes to nutrient loading and environmental forcing in shallow water systems.
Seven-day sea surface temperature prediction using a 3DConv-LSTM model
Authors: Wei Li , Guan Lei
Published: December 2022

Due to the application demand, users have higher expectations for the accuracy and resolution of sea surface temperature (SST) products. Recent advances in deep learning show great advantages in exploiting massive ocean datasets, and provides opportunities for investigating regional SST predictions in an efficiency approach. However, for deep learning-based SST prediction to be adopted by users, the output must be accurate. This paper investigates the 7-day SST prediction over the China seas and their adjacent waters at a 0.05° spatial resolution. To improve the prediction’s accuracy, we designed a deep learning model combining the three-dimensional convolution and long short-term memory under multi-input multi-output strategy. The Operational SST and Sea Ice Analysis (OSTIA) SST anomaly was used as training data. To test the model prediction ability, we verified the predicted results with the Sub-seasonal to Seasonal (S2S) prediction data from 2015 to 2019. Validation of the predicted SSTs using the OSTIA test datasets show that the root-mean-square error increases from 0.27°C to 0.53°C during the 1- to 7-day lead time, with predictability decreases from southeast to northwest in the study area. Furthermore, the comparison of predicted SST and S2S data with Argo shows that our model is slightly more accurate, which can achieve -0.08°C bias, with a standard deviation of 0.35°C for a 1-day lead time and -0.07°C bias, with a standard deviation of 0.59°C for a 7-day lead time. The results indicate that the proposed deep learning model is accurate and can be applied in regional daily SST prediction.
Analysis of the impact of social determinants and primary care morbidity on population health outcomes by combining big data: A research protocol
Authors: Couso-Viana Sabela , Bentué-Martínez Carmen , Delgado-Martín María Victoria , Cabeza-Irigoyen Elena , León-Latre Montserrat , Concheiro-Guisán Ana , Rodríguez-Álvarez María Xosé , Román-Rodríguez Miguel , Roca-Pardiñas Javier , Zúñiga-Antón María , García-Flaquer Ana , Pericàs-Pulido Pau , Sánchez-Recio Raquel , González-Álvarez Beatriz , Rodríguez-Pastoriza Sara , Gómez-Gómez Irene , Motrico Emma , Jiménez-Murillo José Luís , Rabanaque Isabel , Clavería Ana
Published: December 2022

Background

In recent years, different tools have been developed to facilitate analysis of social determinants of health (SDH) and apply this to health policy. The possibility of generating predictive models of health outcomes which combine a wide range of socioeconomic indicators with health problems is an approach that is receiving increasing attention. Our objectives are twofold: (1) to predict population health outcomes measured as hospital morbidity, taking primary care (PC) morbidity adjusted for SDH as predictors; and (2) to analyze the geographic variability of the impact of SDH-adjusted PC morbidity on hospital morbidity, by combining data sourced from electronic health records and selected operations of the National Statistics Institute (Instituto Nacional de Estadística/INE).

Methods

The following will be conducted: a qualitative study to select socio-health indicators using RAND methodology in accordance with SDH frameworks, based on indicators published by the INE in selected operations; and a quantitative study combining two large databases drawn from different Spain’s Autonomous Regions (ARs) to enable hospital morbidity to be ascertained, i.e., PC electronic health records and the minimum basic data set (MBDS) for hospital discharges. These will be linked to socioeconomic indicators, previously selected by geographic unit. The outcome variable will be hospital morbidity, and the independent variables will be age, sex, PC morbidity, geographic unit, and socioeconomic indicators.

Analysis

To achieve the first objective, predictive models will be used, with a test-and-training technique, fitting multiple logistic regression models. In the analysis of geographic variability, penalized mixed models will be used, with geographic units considered as random effects and independent predictors as fixed effects.

Discussion

This study seeks to show the relationship between SDH and population health, and the geographic differences determined by such determinants. The main limitations are posed by the collection of data for healthcare as opposed to research purposes, and the time lag between collection and publication of data, sampling errors and missing data in registries and surveys. The main strength lies in the project’s multidisciplinary nature (family medicine, pediatrics, public health, nursing, psychology, engineering, geography).
Case report: Biliobronchial fistula after biliary tract stenosis
Authors: Batalin Júnior Luís Maurício , Zandoná Mariana Conceição e Silva Seleme , Vargas Thomaz Almeida , Oliveira Julio Cesar de , Chiappetto Juliana Rocha Souza , Oliveira Cassio Vieira , Romeiro Fernando Gomes , Tanni Suzana Erico
Published: December 2022

Biliobronchial fistula (BBF) is a rare abnormality resulting from congenital or acquired communication between the bile ducts and the bronchial tree. Patients often suffer from chronic cough, dyspnea, and bilioptysis, a pathognomonic symptom of this condition. Conservative methods such as less-invasive procedures are gradually consolidating. Nonetheless, surgery remains the primary treatment, especially in more complex cases. We present the case of a 44-year-old woman with a chronic cough, no verified periods of fever, cyclic jaundice, and episodes of yellowish sputum. She had undergone cholecystectomy in 2018 and had been hospitalized several times since for pneumonia treatment. All consequent investigations for mycobacteriosis were negative. When referred to our hospital, she had cyclic jaundice and parenchymal consolidation in the right lower lobe. Suspected bilioptysis motivated the search for a biliobronchial fistula. Magnetic resonance cholangiography (MRC) confirmed stenosis of the biliary tract and fistulous path, and sputum analysis indicated high bilirubin levels. External biliary bypass was performed as an initial conservative and definitive therapy due to the presence of liver cirrhosis. Although BBF is a rare condition when bilioptysis is suspected, a diagnostic investigation should be initiated. Our case study proposes two criteria for diagnosis: an imaging exam demonstrating the fistulous path and confirmation of bilirubin in the sputum or bronchoalveolar lavage (BAL). When diagnosed, surgical correction should be performed.
Effects of oat (Avena sativa L.) hay diet supplementation on the intestinal microbiome and metabolome of Small-tail Han sheep
Authors: Su Shaofeng , Wang Liwei , Fu Shaoyin , Zhao Jie , He Xiaolong , Chen Qiuju , Belobrajdic Damien P. , Yu Chuanzong , Liu Hongkui , Wu Haiqing , Han Pingan , Yang Bin , Huang Yao , Liu Yongbin , He Jiangfeng
Published: December 2022

Supplementation of the sheep diet with oats (Avena sativa L.) improves animal growth and meat quality, however effects on intestinal microbes and their metabolites was not clear. This study aimed to establish the effect of dietary oat supplementation on rumen and colonic microbial abundance and explore the relationship with subsequent changes in digesta metabolites. Twenty Small-tail Han sheep were randomly assigned to a diet containing 30 g/100 g of maize straw (Control) or oat hay (Oat). After 90-days on experimental diets, rumen and colon digesta were collected and microbial diversity was determined by 16S rRNA gene Illumina NovaSeq sequencing and metabolomics was conducted using Ultra-high performance liquid chromatography Q-Exactive mass spectrometry (UHPLC-QE-MS). Compared to Control group, oat hay increased the abundance of Bacteroidetes and Fibrobacteres as well as known short-chain fatty acid (SCFA) producers Prevotellaceae, Ruminococcaceae and Fibrobacteraceae in rumen (p < 0.05). In rumen digesta, the Oat group showed had higher levels of (3Z,6Z)-3,6-nonadienal, Limonene-1,2-epoxide, P-tolualdehyde, and Salicylaldehyde compared to Control (p < 0.05) and these metabolites were positively correlated with the abundance of cecal Prevotellaceae NK3B31. In conclusion, supplementation of the sheep diet with oat hay improved desirable microbes and metabolites in the rumen, providing insight into mechanisms whereby meat quality can be improved by oat hay supplementation.
Diversity and antibacterial potential of the Actinobacteria associated with Apis mellifera ligustica
Authors: Cui Pu , Wu Haoyang , Jiang Taoshan , Tao Jian , Zhu Zhiwei , Liu Peng , Yu Linsheng , Zhang Yinglao
Published: December 2022

Insect-associated Actinobacteria are a potentially rich source of novel natural products with antibacterial activity. Here, the community composition of Actinobacteria associated with Apis mellifera ligustica was investigated by integrated culture-dependent and independent methods. A total of 61 strains of Streptomyces genera were isolated from the honeycomb, larva, and different anatomical parts of the honeybee’s body using the culture-dependent method. Amplicon sequencing analyses revealed that the actinobacterial communities were dominated by the family of Bifidobacteriaceae and Microbacteriaceae in the honeybee gut, and Nocardiaceae and Pseudonocardiaceae in the honeycomb, whereas only Streptomyces genera were isolated by the culture-dependent method. Culture-independent analyses showed more diverse actinobacterial communities than those of culture-dependent methods. The antibacterial bioassay showed that most crude extracts of representative isolates exhibited antibacterial activities. Among them, the crude extract of Streptomyces sp. FCF01 showed the best antibacterial activities against Staphylococcus aureus, Micrococcus tetragenus, and Pseudomonas syringae pv. actinidiae (Psa) with the disc diameter of inhibition zone diameter (IZD) of 23.00, 15.00, and 13.33 mm, respectively. Chemical analysis of Streptomyces sp. FCF01 led to the isolation of three secondary metabolites, including mayamycin (1), mayamycin B (2), and N-(2-Hydroxyphenyl) acetamide (3). Among them, compound 1 displayed strong antibacterial activity against S. aureus, M. tetragenus, and Psa with minimum inhibitory concentrations (MIC) values of 6.25, 12.5, and 6.25 μg/ml, respectively. In addition, two novel derivative compounds 1a and 1b were synthesized by acetylation of compound 1. Both compounds 1a and 1b displayed similar antibacterial activities with those of metabolite 1. These results indicated that Streptomyces species associated with honeybees had great potential in finding antibiotics.
Causal associations between gut microbiota and adverse pregnancy outcomes: A two-sample Mendelian randomization study
Authors: Li Chuang , Liu Caixia , Li Na
Published: December 2022

Growing evidence indicates that gut microbiota could be closely associated with a variety of adverse pregnancy outcomes (APOs), but a causal link between gut microbiome and APOs has yet to be established. Therefore, in this study, we comprehensively investigated the relationship between gut microbiota and APOs to identify specific causal bacteria that may be associated with the development and occurrence of APOs by conducting a two-sample Mendelian randomization (MR) analysis. The microbiome genome-wide association study (GWAS) from the MiBioGen consortium was used as exposure data, and the GWAS for six common APOs was used as outcome data. Single-nucleotide polymorphisms (SNPs) that significantly correlated to exposure, data obtained from published GWAS, were selected as instrumental variables (IVs). We used the inverse variance-weighted (IVW) test as the main MR analysis to estimate the causal relationship. The Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) and MR-Egger regression were used to confirm the presence of horizontal pleiotropy and to exclude outlier SNPs. We performed Cochran's Q test to assess the heterogeneity among SNPs associated with each bacterium. The leave-one-out sensitivity analysis was used to evaluate whether the overall estimates were affected by a single SNP. Our analysis shows a causal association between specific gut microbiota and APOs. Our findings offer novel insights into the gut microbiota-mediated development mechanism of APOs.
Intracellular and intercellular transport of RNA organelles in CXG repeat disorders: The strength of weak ties
Authors: Nabariya Deepti Kailash , Heinz Annika , Derksen Sabrina , Krauß Sybille
Published: December 2022

RNA is a vital biomolecule, the function of which is tightly spatiotemporally regulated. RNA organelles are biological structures that either membrane-less or surrounded by membrane. They are produced by the all the cells and indulge in vital cellular mechanisms. They include the intracellular RNA granules and the extracellular exosomes. RNA granules play an essential role in intracellular regulation of RNA localization, stability and translation. Aberrant regulation of RNA is connected to disease development. For example, in microsatellite diseases such as CXG repeat expansion disorders, the mutant CXG repeat RNA’s localization and function are affected. RNA is not only transported intracellularly but can also be transported between cells via exosomes. The loading of the exosomes is regulated by RNA-protein complexes, and recent studies show that cytosolic RNA granules and exosomes share common content. Intracellular RNA granules and exosome loading may therefore be related. Exosomes can also transfer pathogenic molecules of CXG diseases from cell to cell, thereby driving disease progression. Both intracellular RNA granules and extracellular RNA vesicles may serve as a source for diagnostic and treatment strategies. In therapeutic approaches, pharmaceutical agents may be loaded into exosomes which then transport them to the desired cells/tissues. This is a promising target specific treatment strategy with few side effects. With respect to diagnostics, disease-specific content of exosomes, e.g., RNA-signatures, can serve as attractive biomarker of central nervous system diseases detecting early physiological disturbances, even before symptoms of neurodegeneration appear and irreparable damage to the nervous system occurs. In this review, we summarize the known function of cytoplasmic RNA granules and extracellular vesicles, as well as their role and dysfunction in CXG repeat expansion disorders. We also provide a summary of established protocols for the isolation and characterization of both cytoplasmic and extracellular RNA organelles.
Stromal protein CCN family contributes to the poor prognosis in lower-grade gioma by modulating immunity, matrix, stemness, and metabolism
Authors: Liu Zhihui , Wu Jiasheng , Ji Hang , Zhao Hongtao , Wang Fang , Dong Jiawei , Zhang Jiheng , Wang Nan , Yan Xiuwei , Wang Kaikai , Hu Shaoshan
Published: December 2022

Background: The CCN family of stromal proteins is involved in the regulation of many important biological functions. However, the role of dysregulated CCN proteins in lower-grade glioma (LGG) remain less understand.

Methods: The clinical significance of the CCN proteins was explored based on RNA-seq profiles from multiple cohorts. A CCNScore was constructed using LASSO regression analysis. The PanCanAtlas data and MEXPRESS database were employed to elucidate molecular underpinnings.

Results: The expression of CCN4 was associated with poor prognosis in LGG. The CCNScore (CCN1 = 0.06, CCN4 = 0.86) showed implication in prognosis prediction, subtype assessment and therapy selection. The gene mutation pattern of the high-CCNScore group was similar with glioblastoma, including EGFR, PTEN, and NF1 mutation frequently. Besides, the high-CCNScore group was comprised of samples mainly classic-like and mesenchymal-like, had lower methylation levels, higher stemness, higher inflammation, higher levels of extracellular matrix remodel and dysfunction of metabolic pathways. On the other hand, the low-CCNScore group consisted mainly of IDH-mutation LGG, and was characterized by TP53, CIC, and ATRX gene mutations, hyper-methylation status, lower stemness, lower proliferation, immune quietness and low extracellular matrix stiffness.

Conclusion: In summary, these results outlined the role of CCN family in LGG and provided a potential and promising therapeutic target.
Plasmid parB contributes to uropathogenic Escherichia coli colonization in vivo by acting on biofilm formation and global gene regulation
Authors: Song Ningning , De Greve Henri , Wang Quanjun , Hernalsteens Jean-Pierre , Li Zhaoli
Published: December 2022

The endogenous plasmid pUTI89 harbored by the uropathogenic Escherichia coli (UPEC) strain UTI89 plays an important role in the acute stage of infection. The partitioning gene parB is important for stable inheritance of pUTI89. However, the function of partitioning genes located on the plasmid in pathogenesis of UPEC still needs to be further investigated. In the present study, we observed that disruption of the parB gene leads to a deficiency in biofilm formation in vitro. Moreover, in a mixed infection with the wild type strain and the parB mutant, in an ascending UTI mouse model, the mutant displayed a lower bacterial burden in the bladder and kidneys, not only at the acute infection stage but also extending to 72 hours post infection. However, in the single infection test, the reduced colonization ability of the parB mutant was only observed at six hpi in the bladder, but not in the kidneys. The colonization capacity in vivo of the parB-complemented strain was recovered. qRT-PCR assay suggested that ParB could be a global regulator, influencing the expression of genes located on both the endogenous plasmid and chromosome, while the gene parA or the operon parAB could not. Our study demonstrates that parB contributes to the virulence of UPEC by influencing biofilm formation and proposes that the parB gene of the endogenous plasmid could regulate gene expression globally.
Identification and mechanistic basis of non-ACE2 blocking neutralizing antibodies from COVID-19 patients with deep RNA sequencing and molecular dynamics simulations
Authors: Fredericks Alger M. , East Kyle W. , Shi Yuanjun , Liu Jinchan , Maschietto Federica , Ayala Alfred , Cioffi William G. , Cohen Maya , Fairbrother William G. , Lefort Craig T. , Nau Gerard J. , Levy Mitchell M. , Wang Jimin , Batista Victor S. , Lisi George P. , Monaghan Sean F.
Published: December 2022

Variants of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) continue to cause disease and impair the effectiveness of treatments. The therapeutic potential of convergent neutralizing antibodies (NAbs) from fully recovered patients has been explored in several early stages of novel drugs. Here, we identified initially elicited NAbs (Ig Heavy, Ig lambda, Ig kappa) in response to COVID-19 infection in patients admitted to the intensive care unit at a single center with deep RNA sequencing (>100 million reads) of peripheral blood as a diagnostic tool for predicting the severity of the disease and as a means to pinpoint specific compensatory NAb treatments. Clinical data were prospectively collected at multiple time points during ICU admission, and amino acid sequences for the NAb CDR3 segments were identified. Patients who survived severe COVID-19 had significantly more of a Class 3 antibody (C135) to SARS-CoV-2 compared to non-survivors (15059.4 vs. 1412.7, p = 0.016). In addition to highlighting the utility of RNA sequencing in revealing unique NAb profiles in COVID-19 patients with different outcomes, we provided a physical basis for our findings via atomistic modeling combined with molecular dynamics simulations. We established the interactions of the Class 3 NAb C135 with the SARS-CoV-2 spike protein, proposing a mechanistic basis for inhibition via multiple conformations that can effectively prevent ACE2 from binding to the spike protein, despite C135 not directly blocking the ACE2 binding motif. Overall, we demonstrate that deep RNA sequencing combined with structural modeling offers the new potential to identify and understand novel therapeutic(s) NAbs in individuals lacking certain immune responses due to their poor endogenous production. Our results suggest a possible window of opportunity for administration of such NAbs when their full sequence becomes available. A method involving rapid deep RNA sequencing of patients infected with SARS-CoV-2 or its variants at the earliest infection time could help to develop personalized treatments using the identified specific NAbs.
Targeting GSTP1-dependent ferroptosis in lung cancer radiotherapy: Existing evidence and future directions
Authors: Tan Xin , Huang Xiang , Niu Baolong , Guo Xingdong , Lei Xiao , Qu Baolin
Published: December 2022

Radiotherapy is applied in about 70% patients with tumors, yet radioresistance of tumor cells remains a challenge that limits the efficacy of radiotherapy. Ferroptosis, an iron-dependent lipid peroxidation regulated cell death, is involved in the development of a variety of tumors. Interestingly, there is evidence that ferroptosis inducers in tumor treatment can significantly improve radiotherapy sensitivity. In addition, related studies show that Glutathione S-transferase P1 (GSTP1) is closely related to the development of ferroptosis. The potential mechanism of targeting GSTP1 to inhibit tumor cells from evading ferroptosis leading to radioresistance has been proposed in this review, which implies that GSTP1 may play a key role in radiosensitization of lung cancer via ferroptosis pathway.
A three-week in-hospital multidisciplinary body weight reduction program exerts beneficial effects on physical and mental health and fatiguability of elderly patients with obesity
Authors: Guerrini Usubini Anna , Bottacchi Michela , Bondesan Adele , Caroli Diana , Castelnuovo Gianluca , Sartorio Alessandro
Published: December 2022

Introduction

Obesity represents one of the most serious problems of public health affecting elderly populations in an increasingly relevant way. The aim of the current study was to assess the effects of a 3-week in-hospital multidisciplinary body weight reduction program (BWRP) in a sample of elderly patients with obesity on reducing body mass index (BMI), improving fatigue, muscle performance, and psychological well-being.

Methods

Two hundred and thirty-seven consecutive elderly in-patients with obesity (males = 84; females = 153; age range = 65–86 yrs.; mean BMI = 43.7) undergoing a three-week multidisciplinary BWRP participated in the study. Data on BMI, fatiguability (measured with the Fatigue Severity Scale, FSS), muscle performance (evaluated with the Stair Climbing Test, SCT), and psychological well-being (assessed with the Psychological General Well- Being Index, PGWBI) were collected before and after the intervention.

Results

Results showed that BWRP was capable to reduce BMI [F(1.00, 235.00) = 1226.8; p < 0.001; ƞ2 = 0.024], improve perceived fatigue [F(1,234) = 296.80125; p < 0.001; ƞ2 = 0.129], physical performance [F(1.00,158.00) = 119.26; p < 0.001; ƞ2 = 0.026], and enhance psychological well-being [F(1,235) = 169.0; p < 0.001; ƞ2 = 0.103] in both males and females.

Discussion

Although it will be necessary to demonstrate with further longitudinal studies whether the reported beneficial effects will be maintained over time, the effectiveness of a 3-week BWRP on different aspects involved in determining a level of autonomy and good quality of life of elderly obese patients appears to represent a valid attempt to counteract – at least in part – the unavoidable and progressive disability of these patients.
Efficacy and safety of antivirals in treating hearing loss: A systematic review and network meta-analysis
Authors: Liu Li-Mei , Xia Li-Li
Published: December 2022

Objectives

This study aimed to compare and rank the therapeutic effects of antivirals in treating hearing loss using a network meta-analysis approach.

Methods

We searched the PubMed, Embase, and Cochrane Library databases to identify eligible randomized controlled trials (RCTs) through April 2022. Placebo-controlled or head-to-head RCTs of three categories of antivirals for hearing loss were included, and pooled relative risks (RRs) with 95% confidence interval (CI) were calculated using pairwise and network meta-analyses.

Results

Six RCTs with 405 patients were included in the final analysis. The results showed that ganciclovir had relatively better effects on the incidence of hearing recovery (surface under the cumulative ranking: 88.8%) compared with other antivirals. However, pairwise comparison analyses found that the use of antivirals significantly increased the incidence of hearing recovery compared with the use of a placebo (RR: 1.27; 95% CI: 1.04–1.54; P = 0.017), while no significant difference was observed between any two categories of antivirals. Finally, the use of antivirals did not increase the risk of adverse events compared with the use of a placebo (RR: 1.27; 95% CI: 0.82–1.98; P = 0.285).

Conclusion

Antivirals are more efficacious than placebos for hearing recovery in patients with hearing loss, and ganciclovir is the most likely to increase the incidence of hearing recovery.
SARS-CoV-2 (COVID-19) as a possible risk factor for neurodevelopmental disorders
Authors: Dubey Harikesh , Sharma Ravindra K. , Krishnan Suraj , Knickmeyer Rebecca
Published: December 2022

Pregnant women constitute one of the most vulnerable populations to be affected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the cause of coronavirus disease 2019. SARS-CoV-2 infection during pregnancy could negatively impact fetal brain development via multiple mechanisms. Accumulating evidence indicates that mother to fetus transmission of SARS-CoV-2 does occur, albeit rarely. When it does occur, there is a potential for neuroinvasion via immune cells, retrograde axonal transport, and olfactory bulb and lymphatic pathways. In the absence of maternal to fetal transmission, there is still the potential for negative neurodevelopmental outcomes as a consequence of disrupted placental development and function leading to preeclampsia, preterm birth, and intrauterine growth restriction. In addition, maternal immune activation may lead to hypomyelination, microglial activation, white matter damage, and reduced neurogenesis in the developing fetus. Moreover, maternal immune activation can disrupt the maternal or fetal hypothalamic-pituitary-adrenal (HPA) axis leading to altered neurodevelopment. Finally, pro-inflammatory cytokines can potentially alter epigenetic processes within the developing brain. In this review, we address each of these potential mechanisms. We propose that SARS-CoV-2 could lead to neurodevelopmental disorders in a subset of pregnant women and that long-term studies are warranted.
Cerebral perfusion alterations in patients with trigeminal neuralgia as measured by pseudo-continuous arterial spin labeling
Authors: Zhou Qianling , Li Meng , Fan Qisen , Chen Feng , Jiang Guihua , Wang Tianyue , He Qinmeng , Fu Shishun , Yin Yi , Lin Jinzhi , Yan Jianhao
Published: December 2022

Background

Accumulating evidence suggests that trigeminal neuralgia (TN) causes structural and functional alterations in the brain. However, only a few studies have focused on cerebral blood flow (CBF) changes in patients with TN. This study aimed to explore whether altered cerebral perfusion patterns exist in patients with TN and investigate the relationship between abnormal regional CBF (rCBF) and clinical characteristics of TN.

Materials and methods

This study included 28 patients with TN and 30 age- and sex-matched healthy controls (HCs) who underwent perfusion functional MRI (fMRI) of the brain using pseudo-continuous arterial spin labeling (pCASL) in the resting state. The regions of significantly altered CBF in patients with TN were detected using group comparison analyses. Then, the relationships between the clinical characteristics and abnormal rCBF were further investigated.

Results

Compared to the control group, patients with TN exhibited increased rCBF, primarily in the thalamus, middle frontal gyrus (MFG), and left insula. Furthermore, the CBF values of the thalamus were negatively correlated with the pain intensity of TN and positively correlated with pain duration in patients with TN.

Conclusion

Primary alterations in rCBF in patients with TN occurred in different brain regions related to pain, which are involved in cognitive-affective interaction, pain perception, and pain modulation. These results indicate that non-invasive resting cerebral perfusion imaging may contribute complementary information to further understanding the neuropathological mechanism underlying TN.
The yeast molecular chaperone, Hsp104, influences transthyretin aggregate formation
Authors: Knier Adam S. , Davis Emily E. , Buchholz Hannah E. , Dorweiler Jane E. , Flannagan Lauryn E. , Manogaran Anita L.
Published: December 2022

Patients with the fatal disorder Transthyretin Amyloidosis (ATTR) experience polyneuropathy through the progressive destruction of peripheral nervous tissue. In these patients, the transthyretin (TTR) protein dissociates from its functional tetrameric structure, misfolds, and aggregates into extracellular amyloid deposits that are associated with disease progression. These aggregates form large fibrillar structures as well as shorter oligomeric aggregates that are suspected to be cytotoxic. Several studies have shown that these extracellular TTR aggregates enter the cell and accumulate intracellularly, which is associated with increased proteostasis response. However, there are limited experimental models to study how proteostasis influences internalized TTR aggregates. Here, we use a humanized yeast system to recapitulate intracellular TTR aggregating protein in vivo. The yeast molecular chaperone Hsp104 is a disaggregase that has been shown to fragment amyloidogenic aggregates associated with certain yeast prions and reduce protein aggregation associated with human neurogenerative diseases. In yeast, we found that TTR forms both SDS-resistant oligomers and SDS-sensitive large molecular weight complexes. In actively dividing cultures, Hsp104 has no impact on oligomeric or large aggregate populations, yet overexpression of Hsp104 is loosely associated with an increase in overall aggregate size. Interestingly, a potentiating mutation in the middle domain of Hsp104 consistently results in an increase in overall TTR aggregate size. These data suggest a novel approach to aggregate management, where the Hsp104 variant shifts aggregate populations away from toxic oligomeric species to more inert larger aggregates. In aged cultures Hsp104 overexpression has no impact on TTR aggregation profiles suggesting that these chaperone approaches to shift aggregate populations are not effective with age, possibly due to proteostasis decline.
Apigenin remodels the gut microbiota to ameliorate ulcerative colitis
Authors: Fu Rongrong , Wang Lechen , Meng Ying , Xue Wenqing , Liang Jingjie , Peng Zimu , Meng Jing , Zhang Min
Published: December 2022

Introduction

Ulcerative colitis (UC), a chronic non-specific colorectal inflammatory disease with unclear etiology, has long plagued human health. Gut microbiota dysbiosis destroy homeostasis of the colon, which is closely related to ulcerative colitis progress. Apigenin, a flavonoid widely present in celery, has been found to improve ulcerative colitis. However, the potential molecular mechanism of apigenin ameliorating ulcerative colitis through protecting intestinal barrier and regulating gut microbiota remains undefined.

Methods

Dextran sodium sulfate (DSS)-induced colitis mouse model was conducted to evaluate the effect of apigenin on UC. Disease activity index score of mice, colon tissue pathological, cytokines analysis, intestinal tight junction proteins expression, and colonic content short-chain fatty acids (SCFAs) and 16S rRNA gene sequencing were conducted to reflect the protection of apigenin on UC.

Results

The results indicated that apigenin significantly relieved the intestinal pathological injury, increased goblet cells quantity and mucin secretion, promoted anti-inflammatory cytokines IL-10 expression, and inhibited the expression of proinflammatory cytokines, TNF-α, IL-1β, IL-6 and MPO activity of colon tissue. Apigenin increased ZO-1, claudin-1 and occludin expressions to restore the integrity of the intestinal barrier. Moreover, apigenin remodeled the disordered gut microbiota by regulating the abundance of Akkermansia, Turicibacter, Klebsiella, Romboutsia, etc., and its metabolites (SCFAs), attenuating DSS-induced colon injury. We also investigated the effect of apigenin supplementation on potential metabolic pathways of gut microbiota.

Conclusion

Apigenin effectively ameliorated DSS-induced UC via balancing gut microbiome to inhibit inflammation and protect gut barrier. With low toxicity and high efficiency, apigenin might serve as a potential therapeutic strategy for the treatment of UC via regulating the interaction and mechanism between host and microorganism.
Trend of adherence to iron supplementation during pregnancy among Ethiopian women based on Ethiopian demographic and health surveys: A Multivariable decomposition analysis
Authors: Delie Amare Mebrat , Gezie Lemma Derseh , Gebeyehu Asaye Alamneh , Tarekegn Gebrekidan Ewnetu , Muche Achenef Asmamaw
Published: December 2022

Background

Iron deficiency is one of the significant factors of anemia during pregnancy. Iron supplementation is the main method of prevention and control of iron deficiency anemia, and its effectiveness depends on adherence to the iron supplementation.

Methods

This study was based on a secondary analysis of 2005, 2011, and 2016 EDHS data. After the data was weighted using sampling weight, 696, 1,282, and 3,096 in 2005, 2011, and 2016 EDHS data, respectively, were used for the final analysis. The data were edited, cleaned, coded, managed, and analyzed using StataCorp version 16 software. A logit-based multivariable decomposition analysis was used to identify variables significantly associated with the change in the adherence level during pregnancy.

Results

Adherence levels increased from 1.1% (95% CI; 0.4, 2.7) in 2005 EDHS to 12.4% (95% CI; 10.9, 14.1) in 2016 EDHS. About 30.9% of the overall change in the adherence level to iron supplement use during pregnancy was due to the difference in women's sociodemographic-related variables. After adjusting for these compositional changes, ~69.1% of the change in the adherence level was because of the difference in the coefficients (behavior-related variables). Among the behavioral characteristics, women's age-group, rich wealth index, and secondary and above-secondary educational status of their husbands had a statistically significant effect on the positive change in the adherence level of pregnant mothers.

Conclusion

The adherence level to iron supplement use during pregnancy has increased significantly over the last decade in Ethiopia. Both the compositional and behavioral characteristics of women play a major role in the increasing trend of adherence levels.
Prolonged survival in patients with local chronic infection after high-grade glioma treatment: Two case reports
Authors: Solár Peter , Mackerle Zdenek , Hendrych Michal , Pospisil Petr , Lakomy Radek , Valekova Hana , Hermanova Marketa , Jancalek Radim
Published: December 2022

High-grade gliomas are primary brain tumors with poor prognosis, despite surgical treatment followed by radiotherapy and concomitant chemotherapy. We present two cases of long-term survival in patients treated for high-grade glioma and concomitant prolonged bacterial wound infection. The first patient treated for glioblastoma IDH-wildtype had been without disease progression for 61 months from the first resected recurrence. Despite incomplete chemotherapy-induced myelosuppression in the second patient with anaplastic astrocytoma IDH-mutant, she died without disease relapse after 14 years from the diagnosis due to other comorbidities. We assume that the documented prolonged survival could be related to the bacterial infection.