bluuebunny/crossref_metadata_2025 huggingface dataset:
Current and investigational drugs in early clinical development for portal hypertension
Authors: Sakiani Sasan , Heller Theo , Koh Christopher
Published: October 2022

Introduction

The development of portal hypertension leads to a majority of complications associated with chronic liver disease. Therefore, adequate treatment of portal hypertension is crucial in the management of such patients. Current treatment options are limited and consist mainly of medications that decrease the hyperdynamic circulation, such as non-selective beta blockers, and treatment of hypervolemia with diuretics. Despite these options, mortality rates have not improved over the last two decades. Newer, more effective treatment options are necessary to help improve survival and quality of life in these patients.

Areas covered

Multiple preclinical models and clinical studies have demonstrated potential efficacy of a variety of new treatment modalities. We introduce treatment options including the use of vasodilation promotors, vasoconstriction inhibitors, anticoagulants, antiangiogenics, and anti-inflammatory drugs. We examine the most recent studies for treatment options within these drug classes and offer insights as to which show the most promise in this field.

Methodology

Published studies that identified novel medical treatment options of portal hypertension were searched using PubMed (https://pubmed.ncbi.nlm.nih.gov/). Clinical trials listed in Clinicaltrials.gov were also searched with a focus on more recent and ongoing studies, including those with completed recruitment. Searching with key terms including “portal hypertension” as well as individually searching specific treatment medications that were listed in other publications was carried out. Finally, current societal guidelines and recent review articles relevant to the management of portal hypertension were evaluated, and listed references of interest were included.

Conclusion

Many ongoing early phase studies demonstrate promising results and may shape the field of portal hypertension management in future. As concrete results become available, larger RCTs will be required before making definitive conclusions regarding safety and efficacy and whether or not they can be incorporated into routine clinical practice. Statins, anticoagulants, and PDE inhibitors have been among the most studied and appear to be most promising.
Quantitative detection and genetic characterization of thermotolerant Campylobacter spp. in fresh chicken meats at retail in Japan
Authors: Asakura Hiroshi , Yamamoto Shiori , Yamada Kazuhiro , Kawase Jun , Nakamura Hiromi , Abe Kou-ichiro , Sasaki Yoshimasa , Ikeda Tetsuya , Nomoto Ryohei
Published: October 2022

Campylobacter jejuni and C. coli are one of the leading causes of gastrointestinal illnesses, and which are considered to be transmitted to humans mainly from chicken meats. Considering the less availability of quantitative contamination data in the retail chicken meats in Japan, 510 fresh chicken meats retailed at five distinct regions in Japan between June 2019 and March 2021 were examined. The quantitative testing resulted that 45.7% of the samples (254/510) were positive at mean ± standard deviation of 1.15 ± 1.03 logCFU/g, whereas 43 samples (8.4%) exceeded 3.0 logCFU/g. Seasonal comparison revealed increased bacterial counts in fall compared with spring and summer. As for the chicken slaughter age, those slaughtered at >75 days old were less contaminated than those at <75 days old. Genome sequencing analyses of 111 representative C. jejuni isolates resulted in the detection of three antimicrobial resistance genes (gyrA substitution T86I, tetO and blaOXA-61) at 25.2, 27.9 and 42.3%, respectively. In silico MLST analysis revealed the predominance of sequence types (ST)-21 clonal complex (CC), followed by ST-45CC and ST-464CC. The single nucleotide polymorphism (SNP)-based phylogenetic tree largely classified the sequenced C. jejuni isolates into two clusters (I and II), where all C. jejuni from highly contaminated samples (STs-21CC, -22CC and -45CC) belonged to cluster I, independent of both season and slaughter age. To our knowledge, this is the first example to study the current status of Campylobacter contamination levels in fresh chicken meats retailed in Japan. Our data would be contributable to future quantitative microbial risk assessment, to establish effective control measures for campylobacteriosis.
Jingmenviruses: Ubiquitous, understudied, segmented flavi-like viruses
Authors: Colmant Agathe M. G. , Charrel Rémi N. , Coutard Bruno
Published: October 2022

Jingmenviruses are a group of viruses identified recently, in 2014, and currently classified by the International Committee on Taxonomy of Viruses as unclassified Flaviviridae. These viruses closely related to flaviviruses are unique due to the segmented nature of their genome. The prototype jingmenvirus, Jingmen tick virus (JMTV), was discovered in Rhipicephalus microplus ticks collected from China in 2010. Jingmenviruses genomes are composed of four to five segments, encoding for up to seven structural proteins and two non-structural proteins, both of which display strong similarities with flaviviral non-structural proteins (NS2B/NS3 and NS5). Jingmenviruses are currently separated into two phylogenetic clades. One clade includes tick- and vertebrate-associated jingmenviruses, which have been detected in ticks and mosquitoes, as well as in humans, cattle, monkeys, bats, rodents, sheep, and tortoises. In addition to these molecular and serological detections, over a hundred human patients tested positive for jingmenviruses after developing febrile illness and flu-like symptoms in China and Serbia. The second phylogenetic clade includes insect-associated jingmenvirus sequences, which have been detected in a wide range of insect species, as well as in crustaceans, plants, and fungi. In addition to being found in various types of hosts, jingmenviruses are endemic, as they have been detected in a wide range of environments, all over the world. Taken together, all of these elements show that jingmenviruses correspond exactly to the definition of emerging viruses at risk of causing a pandemic, since they are already endemic, have a close association with arthropods, are found in animals in close contact with humans, and have caused sporadic cases of febrile illness in multiple patients. Despite these arguments, the vast majority of published data is from metagenomics studies and many aspects of jingmenvirus replication remain to be elucidated, such as their tropism, cycle of transmission, structure, and mechanisms of replication and restriction or epidemiology. It is therefore crucial to prioritize jingmenvirus research in the years to come, to be prepared for their emergence as human or veterinary pathogens.
Older adults with lower working memory capacity benefit from transcranial direct current stimulation when combined with working memory training: A preliminary study
Authors: Assecondi Sara , Hu Rong , Kroeker Jacob , Eskes Gail , Shapiro Kim
Published: October 2022

Aging is a very diverse process: successful agers retain most cognitive functioning, while others experience mild to severe cognitive decline. This decline may eventually negatively impact one’s everyday activities. Therefore, scientists must develop approaches to counteract or, at least, slow down the negative change in cognitive performance of aging individuals. Combining cognitive training and transcranial direct current stimulation (tDCS) is a promising approach that capitalizes on the plasticity of brain networks. However, the efficacy of combined methods depends on individual characteristics, such as the cognitive and emotional state of the individual entering the training program. In this report, we explored the effectiveness of working memory training, combined with tDCS to the right dorsolateral prefrontal cortex (DLPFC), to manipulate working memory performance in older individuals. We hypothesized that individuals with lower working memory capacity would benefit the most from the combined regimen. Thirty older adults took part in a 5-day combined regimen. Before and after the training, we evaluated participants’ working memory performance with five working memory tasks. We found that individual characteristics influenced the outcome of combined cognitive training and tDCS regimens, with the intervention selectively benefiting old-old adults with lower working memory capacity. Future work should consider developing individualized treatments by considering individual differences in cognitive profiles.
Does cognitive aging follow an orchid and dandelion phenomenon?
Authors: Rodrigues Emma A. , Christie Gregory J. , Farzan Faranak , Moreno Sylvain
Published: October 2022

Cognitive reserve reflects the brain’s intrinsic adaptive capacity against the neurodegenerative effects of aging. The maintenance or enhancement of the brain’s cognitive reserve plays a crucial role in mitigating the severity of pathologies associated with aging. A new movement, social prescribing, which focuses on prescribing lifestyle activities as a treatment for patients, is growing in popularity as a solution against aging pathologies. However, few studies have demonstrated a clear impact of lifestyle activities on individual cognitive health, outside of floor and ceiling effects. Understanding who benefits from which lifestyle factors remains unclear. Here, we investigated the potential effects of lifestyle activities on individuals’ cognitive health from more than 3,530 older adults using a stratification method and advanced analysis technique. Our stratification methods allowed us to observe a new result: older adults who had relatively average cognitive scores were not impacted by lifestyle factors. By comparison, older adults with very high or very low cognitive scores were highly impacted by lifestyle factors. These findings expand the orchid and dandelion theory to the aging field, regarding the biological sensitivity of individuals to harmful and protective environmental effects. Our discoveries demonstrate the role of individual differences in the aging process and its importance for social prescribing programs.
Caenorhabditis elegans as a model system to evaluate neuroprotective potential of nano formulations
Authors: Chauhan Payal , Wadhwa Karan , Singh Govind
Published: October 2022

The impact of neurodegenerative illnesses on society is significant, but the mechanisms leading to neuronal malfunction and death in these conditions remain largely unknown despite identifying essential disease genes. To pinpoint the mechanisms behind the pathophysiology of neurodegenerative diseases, several researchers have turned to nematode C. elegans instead of using mammals. Since C. elegans is transparent, free-living, and amenable to culture, it has several benefits. As a result, all the neurons in C. elegans can be easily identified, and their connections are understood. Human proteins linked to Neurodegeneration can be made to express in them. It is also possible to analyze how C. elegans orthologs of the genes responsible for human neurodegenerative diseases function. In this article, we focused at some of the most important C. elegans neurodegeneration models that accurately represent many elements of human neurodegenerative illness. It has been observed that studies using the adaptable C. elegans have helped us in better understanding of human diseases. These studies have used it to replicate several aspects of human neurodegeneration. A nanotech approach involves engineering materials or equipments interacting with biological systems at the molecular level to trigger physiological responses by increasing stimulation, responding, and interacting with target sites while minimizing side effects, thus revolutionizing the treatment and diagnosis of neurodegenerative diseases. Nanotechnologies are being used to treat neurological disorders and deliver nanoscale drugs. This review explores the current and future uses of these nanotechnologies as innovative therapeutic modalities in treatment of neurodegenerative diseases using C elegans as an experimental model.
Research progress on neuromolecular imaging of REM sleep behavior disorder
Authors: Geng Chaofan , Zhang Hongju
Published: October 2022

Idiopathic rapid eye movement sleep behavior disorder (iRBD) is an important non-motor complication of Parkinson's disease. At the same time, iRBD is considered to be the prodromal stage of α-synucleinopathy. This high risk of conversion suggests that iRBD becomes a nerve It is a window for early research on degenerative diseases and is the best candidate for neuroprotection trials. A wide range of neuroimaging techniques has improved our understanding of iRBD as a prodromal stage of the disease. In addition, neuroimaging of abnormal iRBD is expected to be a potential biomarker for predicting clinical phenotypic transformation. This article reviews the research progress of neuromolecular imaging in patients with iRBD from the perspective of iRBD transforming synucleinopathies.
Use of connectotyping on task functional MRI data reveals dynamic network level cross talking during task performance
Authors: Vazquez-Trejo Valeria , Nardos Binyam , Schlaggar Bradley L. , Fair Damien A. , Miranda-Dominguez Oscar
Published: October 2022

Task-based functional MRI (fMRI) has greatly improved understanding of brain functioning, enabling the identification of brain areas associated with specific cognitive operations. Traditional analyses are limited to associating activation patterns in particular regions with specific cognitive operation, largely ignoring regional cross-talk or dynamic connectivity, which we propose is crucial for characterization of brain function in the context of task fMRI. We use connectotyping, which efficiently models functional brain connectivity to reveal the progression of temporal brain connectivity patterns in task fMRI. Connectotyping was employed on data from twenty-four participants (12 male, mean age 24.8 years, 2.57 std. dev) who performed a widely spaced event-related fMRI word vs. pseudoword decision task, where stimuli were presented every 20 s. After filtering for movement, we ended up with 15 participants that completed each trial and had enough usable data for our analyses. Connectivity matrices were calculated per participant across time for each stimuli type. A Repeated Measures ANOVA applied on the connectotypes was used to characterize differences across time for words and pseudowords. Our group level analyses found significantly different dynamic connectivity patterns during word vs. pseudoword processing between the Fronto-Parietal and Cingulo-Parietal Systems, areas involved in cognitive task control, memory retrieval, and semantic processing. Our findings support the presence of dynamic changes in functional connectivity during task execution and that such changes can be characterized using connectotyping but not with traditional Pearson’s correlations.
Tryptophan-5-HT pathway disorder was uncovered in the olfactory bulb of a depression mice model by metabolomic analysis
Authors: Chen Guanghui , Zhou Siqi , Chen Qiang , Liu Mengmeng , Dong Meixue , Hou Jiabao , Zhou Benhong
Published: October 2022

Major depression (MD) is a severe mental illness that creates a heavy social burden, and the potential molecular mechanisms remain largely unknown. Lots of research demonstrate that the olfactory bulb is associated with MD. Recently, gas chromatography-mass spectrometry-based metabolomic studies on depressive rats indicated that metabolisms of purine and lipids were disordered in the olfactory bulb. With various physicochemical properties and extensive concentration ranges, a single analytical technique could not completely cover all metabolites, hence it is necessary to adopt another metabolomic technique to seek new biomarkers or molecular mechanisms for depression. Therefore, we adopted a liquid chromatography-mass spectrometry metabonomic technique in the chronic mild stress (CMS) model to investigate significant metabolic changes in the olfactory bulb of the mice. We discovered and identified 16 differential metabolites in the olfactory bulb of the CMS treatments. Metabolic pathway analysis by MetaboAnalyst 5.0 was generated according to the differential metabolites, which indicated that the tryptophan metabolism pathway was the core pathogenesis in the olfactory bulb of the CMS depression model. Further, the expressions of tryptophan hydroxylase (TpH) and aromatic amino acid decarboxylase (AAAD) were detected by western blotting and immunofluorescence staining. The expression of TpH was increased after CMS treatment, and the level of AAAD was unaltered. These results revealed that abnormal metabolism of the tryptophan pathway in the olfactory bulb mediated the occurrence of MD.
Potential biomarkers of Alzheimer’s disease and cerebral small vessel disease
Authors: Zou Chun , Huang Xiaohua , Zhang Yilong , Pan Mika , Xie Jieqiong , Chen Liechun , Meng Youshi , Zou Donghua , Luo Jiefeng
Published: October 2022

Background

Cerebral small vessel disease (CSVD) is associated with the pathogenesis of Alzheimer’s disease (AD). Effective treatments to alleviate AD are still not currently available. Hence, we explored markers and underlying molecular mechanisms associated with AD by utilizing gene expression profiles of AD and CSVD patients from public databases, providing more options for early diagnosis and its treatment.

Methods

Gene expression profiles were collected from GSE63060 (for AD) and GSE162790 (for CSVD). Differential analysis was performed between AD and mild cognitive impairment (MCI) or CSVD progression and CSVD no-progression. In both datasets, differentially expressed genes (DEGs) with the same expression direction were identified as common DEGs. Then protein-protein interaction (PPI) network was constructed for common DEGs. Differential immune cells and checkpoints were calculated between AD and MCI.

Results

A total of 146 common DEGs were identified. Common DEGs were mainly enriched in endocytosis and oxytocin signaling pathways. Interestingly, endocytosis and metabolic pathways were shown both from MCI to AD and from CSVD no-progression to CSVD progression. Moreover, SIRT1 was identified as a key gene by ranking degree of connectivity in the PPI network. SIRT1 was associated with obesity-related genes and metabolic disorders. Additionally, SIRT1 showed correlations with CD8 T cells, NK CD56 bright cells, and checkpoints in AD.

Conclusion

The study revealed that the progression of AD is associated with abnormalities in gene expression and metabolism and that the SIRT1 gene may serve as a promising therapeutic target for the treatment of AD.
Association of low birthweight and small for gestational age with maternal ferritin levels: A retrospective cohort study in China
Authors: Tao Yun , Kang Jiawei , Liu Juan , Duan Jie , Wang Fang , Shi Yue , Li Yujuan , Wang Cheng , Xu Dan , Qu Xinlan , Guo Juanjuan , Ma Jianhong , Zhang Yuanzhen
Published: October 2022

Background

Birthweight have profound impacts on health status throughout lifetime, however, the relationship between maternal ferritin level in pregnancy and birthweight of the newborn remains controversial.

Objective

This retrospective cohort research was to analyze the association between maternal ferritin levels during pregnancy with birthweight outcomes, primarily for low birthweight (LBW) and small for gestational age (SGA).

Methods

Newborns weighing lower than 2,500 grams were defined as LBW. SGA is defined as birthweight lower than the 10th percentile of the distribution of newborns' birthweight of the same gestational age. Multivariable logistic regressions have been used to explore the association of maternal ferritin levels and birthweight related outcomes, in which the ferritin concentration was logarithm transformed in the model. We further used restricted cubic spline models to explore linear/non-linear dose–response manners of ferritin level and birthweight outcomes.

Results

A total of 3,566 pregnant women were included in the study. In the results of the present study, we observed that maternal ferritin levels were linearly associated with the risk of LBW (p-trend = 0.005) and SGA (p-trend = 0.04), with the adjusted odds ratios (ORs) of 1.78 (95% CI 1.37–2.32) for LBW and 1.87 (95% CI 1.38–2.54) for SGA with an increase in Ln-ferritin concentrations per unit. The adjusted ORs across quartiles of ferritin levels were 2.14 (95% CI 1.03–4.47) for Quartile 2, 3.13 (95% CI 1.47–6.69) for Quartile 3, and 3.63 (95% CI 1.52–8.68) for Quartile 4 for LBW. The adjusted ORs of LBW and SGA among women using supplemental iron were 0.56 (95% CI 0.38, 0.85) and 0.65 (95% CI 0.40, 1.05) compared with non-users, respectively.

Conclusions

Our findings found a linear dose–response relationship between ferritin levels and an increased risk of poor birthweight outcomes, suggesting that maternal ferritin level during pregnancy may provide an additional predictor for differentiating poor birthweight related outcomes. Further exploration should be conducted to ensure maternal ferritin thresholds and iron supplement doses.
The association between caffeine intake and risk of kidney stones: A population-based study
Authors: Geng Jiwen , Qiu Yuxuan , Kang Zhefeng , Li Yupei , Li Jiameng , Liao Ruoxi , Qin Zheng , Yang Qinbo , Su Baihai
Published: October 2022

Background

Although many studies have proven the beneficial effects of caffeine on human health, the association between caffeine intake and the risk of kidney stones is limited in large epidemiologic studies.

Objectives

We aimed to investigate the association between caffeine intake and the risk of kidney stones.

Methods

A total of 30,716 participants (with weight numbers of 204, 189, and 886) with a history of kidney stone were included in this analysis. All data were survey-weighted, and corresponding logistic regression models were performed to examine the associations between caffeine intake and the risk of kidney stones.

Results

In a fully adjusted model, a per-quartile increase in caffeine intake was associated with a 5.32% decreased risk of kidney stones. In the subgroup analysis, the multivariate-adjusted odds ratios (95% confidence intervals) of the risk of kidney stones for per-quartile increments in caffeine intake were 0.9650 (0.9643, 0.9656) for men, 0.9320 (0.9313, 0.9327) for women, 0.9384 (0.9378, 0.9389) for white race individuals, 1.0281 (1.0270, 1.0292) for nonwhite race individuals, 0.9460 (0.9455, 0.9465) for overweight/obese individuals, and 0.9314 (0.9303, 0.9324) for non-overweight individuals, 0.9100 (0.9094, 0.9105) for caffeine from coffee, and 1.0021 (1.0013, 1.0029) for caffeine from non-coffee sources.

Conclusion

Caffeine intake was negatively associated with the risk of kidney stones. In subgroup analyses, the negative association of caffeine with kidney stone risk was only found in white individuals. In addition, the decreased risk was found higher in women and non-overweight individuals. Especially for women, white individuals and non-overweight individuals. The protective effect of caffeine intake from coffee on stone formation was more significant than that of caffeine from non-coffee sources.
Addictive behavior and incident gallstone disease: A dose–response meta-analysis and Mendelian randomization study
Authors: Bai Ye , Zhang Min , Cui Huijie , Shan Xuefeng , Gu Dongqing , Wang Yutong , Tang Mingshuang , Wang Xin , Jiang Xia , Zhang Ben
Published: October 2022

Background

Previous studies have suggested associations between addictive behavior and gallstone disease (GSD) risk, yet conflicting results exist. It also remains unclear whether this association is causal or due to confounding or reverse associations. The present study aims to systematically analyze the epidemiological evidence for these associations, as well as estimate the potential causal relationships using Mendelian randomization (MR).

Methods

We analyzed four common addictive behaviors, including cigarette smoking, alcohol intake, coffee, and tea consumption (N = 126,906–4,584,729 participants) in this meta-analysis based on longitudinal studies. The two-sample MR was conducted using summary data from genome-wide associations with European ancestry (up to 1.2 million individuals).

Results

An observational association of GSD risk was identified for smoking [RR: 1.17 (95% CI: 1.06–1.29)], drinking alcohol [0.84 (0.78–0.91)], consuming coffee [0.86 (0.79–0.93)], and tea [1.08 (1.04–1.12)]. Also, there was a linear relationship between smoking (pack-years), alcohol drinking (days per week), coffee consumption (cups per day), and GSD risk. Our MRs supported a causality of GSD incidence with lifetime smoking [1.008 (1.003–1.013), P = 0.001], current smoking [1.007 (1.002–1.011), P = 0.004], problematic alcohol use (PAU) [1.014 (1.001–1.026), P = 0.029], decaffeinated coffee intake (1.127 [1.043–1.217], P = 0.002), as well as caffeine-metabolism [0.997 (0.995–0.999), P = 0.013], and tea consumption [0.990 (0.982–0.997), P = 0.008], respectively.

Conclusion

Our study suggests cigarette smoking, alcohol abuse, and decaffeinated coffee are causal risk factors for GSD, whereas tea consumption can decrease the risk of gallstones due to the effect of caffeine metabolism or polyphenol intake.
Peptide Tat(48–60) YVEEL protects against necrotizing enterocolitis through inhibition of toll-like receptor 4-mediated signaling in a phosphatidylinositol 3-kinase/AKT dependent manner
Authors: Yan Xiangyun , Cao Yan , Chen Wenjuan , Yu Qinlei , Chen Yanjie , Yao Shuwen , Jiang Chengyao , Chen Xiaohui , Han Shuping
Published: October 2022

Necrotizing enterocolitis (NEC) is a catastrophic disease largely occurring in preterm infants, and toll-like receptor 4 (TLR4) has been implicated in its pathogenesis. The current therapeutic strategies for NEC are, however, far from optimal. In the present study, a whey-derived antioxidative peptide conjugated with a cell-penetrating TAT [Tat (48–60) YVEEL] was prepared to endow it with enhanced cell uptake capability and bioavailability. The protective effect of Tat (48–60) YVEEL on experimental NEC was evaluated both in vitro and in vivo. Inhibition of TLR4-mediated signaling by Tat (48–60) YVEEL was assessed in FHC and IEC-6 enterocytes, neonatal rat model of NEC, and the mechanism underlying this effect was determined. Tat (48–60) YVEEL significantly inhibited TLR4-mediated expression of pro-inflammatory cytokines, p65 nuclear translocation and restored the impaired enterocyte migration in cultured enterocytes. In addition, Tat (48–60) YVEEL administration strikingly increased the survival rate, and reduced the severity of NEC in rats through inhibition of TLR4-mediated signaling. These protective effects of Tat (48–60) YVEEL occurred in a PI3K/AKT dependent manner, as administration of PI3K activator Ys49 abrogated its protective effects. Combined with liposomes, Tat (48–60) YVEEL demonstrated longer retention in the intestines that better for potential clinical applications. These data demonstrate that Tat (48–60) YVEEL protects against NEC through inhibition of TLR4-mediated signaling in a PI3K/AKT dependent manner, and offer a potential therapeutic approach to this disease.
Prognostic value of lncRNAs related to fatty acid metabolism in lung adenocarcinoma and their correlation with tumor microenvironment based on bioinformatics analysis
Authors: Pan Ya-Qiang , Xiao Ying , Long Tao , Liu Chao , Gao Wen-Hui , Sun Yang-Yong , Liu Chang , Shi Yi-Jun , Li Shuang , Shao Ai-Zhong
Published: October 2022

Background

As a key regulator of metabolic pathways, long non-coding RNA (lncRNA) has received much attention for its relationship with reprogrammed fatty acid metabolism (FAM). This study aimed to investigate the role of the FAM-related lncRNAs in the prognostic management of patients with lung adenocarcinoma (LUAD) using bioinformatics analysis techniques.

Methods

We obtained LUAD-related transcriptomic data and clinical information from The Cancer Genome Atlas (TCGA) database. The lncRNA risk models associated with FMA were constructed by single-sample gene set enrichment analysis (ssGSEA), weighted gene co-expression network (WGCNA), differential expression analysis, overlap analysis, and Cox regression analysis. Kaplan-Meier (K-M) and receiver operating characteristic (ROC) curves were utilized to assess the predictive validity of the risk model. Gene set variation analysis (GSVA) revealed molecular mechanisms associated with the risk model. ssGSEA and microenvironment cell populations-counter (MCP-counter) demonstrated the immune landscape of LUAD patients. The relationships between lncRNAs, miRNAs, and mRNAs were predicted by using LncBase v.2 and miRTarBase. The lncRNA-miRNA-mRNA regulatory network was visualized with Cytoscape v3.4.0. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was performed using DAVID v6.8. Quantitative real-time fluorescence PCR (qRT-PCR) was performed to verify the expression levels of the prognostic lncRNAs.

Results

We identified 249 differentially expressed FMA-related lncRNAs in TCGA-LUAD, six of which were used to construct a risk model with appreciable predictive power. GSVA results suggested that the risk model may be involved in regulating fatty acid synthesis/metabolism, gene repair, and immune/inflammatory responses in the LUAD process. Immune landscape analysis demonstrated a lower abundance of immune cells in the high-risk group of patients associated with poor prognosis. Moreover, we predicted 279 competing endogenous RNA (ceRNA) mechanisms for 6 prognostic lncRNAs with 39 miRNAs and 201 mRNAs. Functional enrichment analysis indicated that the ceRNA network may be involved in the process of LUAD by participating in genomic transcription, influencing the cell cycle, and regulating tissue and organogenesis. In vitro experiments showed that prognostic lncRNA CTA-384D8.35, lncRNA RP5-1059L7.1, and lncRNA Z83851.4 were significantly upregulated in LUAD primary tumor tissues, while lncRNA RP11-401P9.4, lncRNA CTA-384D8.35, and lncRNA RP11-259K15.2 were expressed at higher levels in paraneoplastic tissues.

Conclusion

In summary, the prognostic factors identified in this study can be used as potential biomarkers for clinical applications. ceRNA network construction provides a new vision for the study of LUAD pathogenesis.
Quality assurance for MRI-only radiation therapy: A voxel-wise population-based methodology for image and dose assessment of synthetic CT generation methods
Authors: Chourak Hilda , Barateau Anaïs , Tahri Safaa , Cadin Capucine , Lafond Caroline , Nunes Jean-Claude , Boue-Rafle Adrien , Perazzi Mathias , Greer Peter B. , Dowling Jason , de Crevoisier Renaud , Acosta Oscar
Published: October 2022

The quality assurance of synthetic CT (sCT) is crucial for safe clinical transfer to an MRI-only radiotherapy planning workflow. The aim of this work is to propose a population-based process assessing local errors in the generation of sCTs and their impact on dose distribution. For the analysis to be anatomically meaningful, a customized interpatient registration method brought the population data to the same coordinate system. Then, the voxel-based process was applied on two sCT generation methods: a bulk-density method and a generative adversarial network. The CT and MRI pairs of 39 patients treated by radiotherapy for prostate cancer were used for sCT generation, and 26 of them with delineated structures were selected for analysis. Voxel-wise errors in sCT compared to CT were assessed for image intensities and dose calculation, and a population-based statistical test was applied to identify the regions where discrepancies were significant. The cumulative histograms of the mean absolute dose error per volume of tissue were computed to give a quantitative indication of the error for each generation method. Accurate interpatient registration was achieved, with mean Dice scores higher than 0.91 for all organs. The proposed method produces three-dimensional maps that precisely show the location of the major discrepancies for both sCT generation methods, highlighting the heterogeneity of image and dose errors for sCT generation methods from MRI across the pelvic anatomy. Hence, this method provides additional information that will assist with both sCT development and quality control for MRI-based planning radiotherapy.
Case report: NAFLD and maple syrup urine disease: Is there an interplay between branched-chain amino acids and fructose consumption?
Authors: Moreira-Silva Helena , Ferreira Sandra , Almeida Manuela , Gonçalves Isabel , Cipriano Maria Augusta , Vizcaíno J. R. , Santos-Silva Ermelinda , Gomes-Martins Esmeralda
Published: October 2022

Background

The worldwide increase in pediatric overweight and obesity, in parallel with the global increase in the consumption of sucrose and fructose, is associated with non-alcoholic fatty liver disease (NAFLD). Elevated branched-chain amino acids (BCAAs) are a metabolic feature related to obesity and an early risk factor for insulin resistance and NAFLD. However, few studies have assessed metabolic risk factors and nutritional status in maple syrup urine disease (MSUD) patients under restricted BCAA and high carbohydrate diets.

Methods and results

Herein, we present a pilot report of a 17-year-old boy with classic MSUD with poor diet compliance and high fructose consumption, mainly during early adolescence. At that time, he was overweight and developed features of metabolic syndrome, including persistently elevated liver enzymes and hepatic steatosis. He underwent liver transplantation at the age of 13 years to prevent the risk of progressive cognitive impairment. Two months later, NAFLD relapsed in the graft, despite a better BCAA balance and weight loss. Nevertheless, 6 months after dietary restriction of fructose consumption, NAFLD had sustainably improved.

Conclusion

Childhood overweight and fructose overconsumption are wellestablished driving forces in the development of pediatric NAFLD. However, their role in the early onset and progression of NAFLD in the allograft remains to be established. Furthermore, it is not known whether the dysmetabolic state associated with elevated BCAAs may be contributory. Further studies are required with a cohort of MSUD subjects to validate our findings and to ascertain the possible interaction between a BCAA imbalance and dietary intake in the development of NAFLD.
Efficacy and safety of etanercept biosimilar rhTNFR-Fc in Chinese patients with juvenile idiopathic arthritis: An open-label multicenter observational study
Authors: Xu Xuefeng , Liu Xiaohui , Zheng Wenjie , Xiao Jihong , Li Xiaozhong , Wu Ling , Zou Lixia , Ouyang Qian , Shangguan Yaoyao , Lin Kezhao , Dai Xiaomei , Chen Yuanling , Xu Yiping , Wu Jianqiang , Lu Meiping
Published: October 2022

Background

Etanercept biosimilar recombinant human TNF-α receptor II: IgG Fc fusion protein (rhTNFR-Fc) has showed its efficacy and safety in Chinese patients with rheumatoid arthritis. However, data on rhTNFR-Fc's application in juvenile idiopathic arthritis (JIA) is limited.

Methods

A prospective, observational, multicenter study was performed at 6 institutes in China from July 2020 to December 2021. In a 24-week follow-up, patients with JIA including polyarticular JIA and enthesitis related arthritis received rhTNFR-Fc plus methotrexate (MTX) treatment. The primary outcome parameters were improvements of cJADAS-10 (clinical Juvenile Arthritis Disease Activity Score), and the secondary outcome parameter was an inactive disease.

Results

60 patients completed at least 12-week follow-up, and 57 completed 24-week follow-up. They had high C reactive protein values (11.6 mg/L) and cJADAS-10 (14.6) at baseline. Thirteen patients had morning stiffness. 33 patients showed synovial thickening, and 34 showed bone marrow edemas on MRI. Ultrasonography demonstrated significant joint effusions in 43 patients. The cJADAS-10 sharply decreased from 14.66 at the baseline to 2.4 at 24 weeks of rhTNFR-Fc therapy, respectively (P < 0.01). About half of patients achieved inactive disease at 24 weeks of therapy. Compared with the baseline, the number of patients with morning stiffness, joint effusions, bone marrow edema and synovial thickening on MRI significantly decreased at 24 weeks. Adverse events were consistent with known side effects of biologic agents.

Conclusions

The present study indicated that the combination of rhTNFR-Fc and MTX significantly improve symptoms and disease activity of children with JIA. This study suggests etanercept biosimilar rhTNFR-Fc as an effective and safe therapy for children with JIA.
The effects of dexmedetomidine for patient-controlled analgesia on postoperative sleep quality and gastrointestinal motility function after surgery: A prospective, randomized, double-blind, and controlled trial
Authors: Sui Xin , Wang Yue , Jin Mingxin , Li Kun , Jiang Ge , Song Ailing , He Zhaoyi , Yin Chengke , Zhao Jingshun , Wang Liping , Han Fei
Published: October 2022

Background: Postoperative poor sleep quality and decreased gastrointestinal motility function are common clinical problems. This study investigated the effects of dexmedetomidine (DEX) combined with sufentanil for patient-controlled analgesia (PCA) on postoperative sleep quality and gastrointestinal motility function after surgery in patients with colorectal cancer.

Methods: Patients undergoing colorectal cancer surgery were randomly divided into three groups, DEX 0, 200, or 400 μg, each combined with sufentanil 150 μg for PCA immediately after surgery. The primary outcome was sleep quality in the first 7 days after surgery based on the Athens Insomnia Scale (AIS) score. The secondary outcome was postoperative gastrointestinal motility recovery evaluated by the time of first flatus, first feces and first diet. Postoperative pain intensity, side effects and the length of postoperative hospital stay were also compared among groups. The study was registered with the Chinese Clinical Trial Registry (https://www.chictr.org.cn/enIndex.aspx, ChiCTR2000032601).

Results: Ultimately, 210 cases were included. Sleep quality was better in the DEX 200 μg group and DEX 400 μg group than in the DEX 0 μg group. Overall, in the DEX 200 μg group and DEX 400 μg group, the AIS score (p < 0.05) and the incidence of sleep disturbance (7.3%, 4.5% vs. 19.6%, p < 0.001) were lower than those in the DEX 0 μg group in the first 7 days after surgery. There were no significant differences in postoperative gastrointestinal motility among the three groups in the total surgical categories (p > 0.05). In the laparoscopic surgery patients of each group, the time of postoperative first flatus (p = 0.02) and first feces (p = 0.01) was significantly longer in the DEX 400 μg group than in the DEX 0 μg group. There were no differences in postoperative pain intensity, side effects or length of postoperative hospital stay (p > 0.05).

Conclusion: The continuous infusion of DEX (200 or 400 μg) for PCA significantly improved postoperative sleep quality after colorectal cancer surgery. DEX (200 μg) was better at improving postoperative sleep quality without affecting gastrointestinal motility function than DEX (400 μg) in patients who underwent laparoscopic colorectal cancer surgery.
Quantitative rheo-microscopy of soft matter
Authors: Villa Stefano , Edera Paolo , Brizioli Matteo , Trappe Veronique , Giavazzi Fabio , Cerbino Roberto
Published: October 2022

Direct observation of the microscopic material structure and dynamics during rheological shear tests is the goal of rheo-microscopy experiments. Microscopically, they shed light on the many mechanisms and processes that determine the mechanical properties at the macroscopic scale. Moreover, they permit for the determination of the actual deformation field, which is particularly relevant to assess shear banding or wall slip. While microscopic observation of the sample during mechanical probing is achieved by a variety of custom and commercial instruments, the possibility of performing quantitative rheology is not commonly available. Here, we describe a flexible rheo-microscopy setup that is built around a parallel-sliding-plate, stress-controlled shear cell, optimized to be mounted horizontally on a commercial microscope. Mechanically, soft materials with moduli ranging from few tens of Pa up to tens of kPa can be subjected to a variety of waveforms, ranging from standard step stress and oscillatory stress to more peculiar signals, such as triangular waves or any other signal of interest. Optically, the shear cell is designed to be compatible with different imaging methods (e.g. bright field or confocal microscopy). Most of the components of the shear cell are commercially available, and those that are not can be reproduced by a standard machine shop, easing the implementation of the rheo-microscopy setup in interested laboratories.
Multi-arrays of 3D cylindrical microdetectors for beam characterization and microdosimetry in proton therapy
Authors: Bachiller-Perea Diana , Zhang Mingming , Fleta Celeste , Quirion David , Bassignana Daniela , Gómez Faustino , Guardiola Consuelo
Published: October 2022

The present work shows the performance of two new large microdosimetry multi-array systems having two different configurations, namely, pixel and strip configurations. They cover radiation sensitive areas of 1.9 cm × 0.1 cm and 5.1 cm × 0.1 cm, respectively. The microdosimetry systems are based on arrays of 3D cylindrical silicon microdetectors. The 3D electrodes are etched inside the silicon and have a 25 μm diameter and a 20 μm depth. Each of these unit cells is completely isolated from the others and has a well defined 3D micrometric radiation sensitive volume. The pixel-type device consists of 25 × 5 independent silicon-based detectors (500 in total), each one connected to a readout channel, collecting information in 2D in the transverse planes to the particle beam direction. The distance between the individual detectors (pitch) is 200 μm in the horizontal axis and 250 μm in the vertical one. In the case of the strip-type system, we have 512 “columns” (or strips) of 10 detectors per column. Each strip is connected to a readout channel, giving us information in one dimension, but with better statistics than a single pixel. In this system, both the horizontal and vertical pitches are 100 μm.

Both systems have been tested under proton beam irradiations at different energies between 6 and 24 MeV to obtain the corresponding microdosimetry quantities along the Bragg peak and distal edge. The measurements were performed at the Accélérateur Linéaire et Tandem à Orsay (ALTO, France). The microdosimetry quantities were successfully obtained with spatial resolutions of 100–250 μm. Experimental results were compared to Monte Carlo simulations and an overall good agreement was found. Both microdetector systems showed a good microdosimetry performance under clinical-equivalent fluence rates along distances of several centimeters. This work demonstrates that the two new systems having different configurations can be clinically used as microdosimeters for measuring the lineal energy distributions in the context of proton therapy treatments. Additionally, they could be also used for beam monitoring.
Analysis of intraoperative microscopy imaging techniques and their future applications
Authors: Zhan Huiling , Sun Caihong , Xu Mingyu , Luo Tianyi , Wang Guangxing , Xi Gangqin , Liu Zhiyi , Zhuo Shuangmu
Published: October 2022

During tumor resection, doctors use intraoperative biopsies to determine the tumor margin. However, the pathological procedures of traditional diagnostic methods, such as imprint cytology and frozen section analysis, are complicated and time-consuming. As this is not conducive to surgeries, their applications are limited to a large extent. Therefore, novel fast microscopy imaging technologies with resolutions comparable to those of pathological tissue sections are necessary. Stimulated Raman scattering (SRS), photoacoustic microscopy (PAM), multiphoton microscopy (MPM), and optical coherence microscopy (OCM) exhibit the advantages of high spatial resolution, large imaging depth, avoiding damage to biological tissues, label-free detection, and the availability of biochemical information of tissues. Additionally, they are superior to intraoperative biopsies owing to their fast imaging speeds. Therefore, they possess broad application prospects in tumor resection surgeries and the diagnosis of other diseases. This study briefly introduces the basic principles, structural characteristics, advantages and disadvantages, and the existing research status of SRS, PAM, MPM, and OCM in biomedicine. Furthermore, we propose a multi-mode hybrid detection technology that can be used for surgeries. The combination of the proposed technology with deep learning-based artificial intelligence can form the basis for intraoperative diagnosis in the future.
Hyperbilirubinemia after surgical repair for acute type a aortic dissection: A propensity score-matched analysis
Authors: Wang Zhigang , Xu Jingfang , Cheng Xiaofeng , Zhang Lifang , Wang Dongjin , Pan Jun
Published: October 2022

Background: Inflammation and oxidative stress are known to participate in the pathogenesis of hyperbilirubinemia. It has been known that acute type A aortic dissection (ATAAD) surgical repair often associates with complications which might affect the long-term prognosis. However, the clinical significance of postoperative hyperbilirubinemia (PH) has not been evaluated. Here in this study, we examined the incidence, risk factors, and prognosis of PH after ATAAD surgery.

Methods: This retrospective study enrolled a total of 970 patients who received ATAAD surgical repair from January 2014 to December 2019. PH was defined as serum total bilirubin >3.0 mg/dl within the first week after the surgery. Propensity score matching was used to reduce selection bias and eliminate potential confounding factors. Kaplan–Meier survival and Cox proportional hazards regression analyses were conducted to explore the association between PH and postoperative long-term survival.

Results: Development of PH (183 patients) was associated with a higher 30-Day mortality (20.8% vs. 9.0%, p < 0.001). Advanced age [odds ratio (OR) 1.538, p = 0.006], higher baseline total bilirubin level (OR 1.735, p = 0.026), preoperative pericardial tamponade (OR 3.192, p = 0.024), prolonged cardiopulmonary bypass (CPB) duration (OR 2.008, p = 0.005), and elevated postoperative central venous pressure (CVP) level (OR 2.183, p < 0.001) were associated with PH. The Kaplan-Meier analysis showed patients who developed PH were associated with poor long-term survival (p = 0.044). Cox analysis showed that the presence of PH (hazard ratio 2.006, p = 0.003) was an independent risk factor for increased mortality.

Conclusion: PH is a common complication in patients undergoing ATAAD surgical repair that associates with worse short- and long-term prognosis. Our data indicated that age, preoperative total bilirubin level, pericardial tamponade, CPB duration, and postoperative CVP level were risk factors for the development of PH.