bluuebunny/crossref_metadata_2025 huggingface dataset:
Biochemical and Structural Insights on the Poplar Tau Glutathione Transferase GSTU19 and 20 Paralogs Binding Flavonoids
Authors: Sylvestre-Gonon Elodie , Morette Laura , Viloria Morgane , Mathiot Sandrine , Boutilliat Alexis , Favier Frédérique , Rouhier Nicolas , Didierjean Claude , Hecker Arnaud
Published: August 2022

Glutathione transferases (GSTs) constitute a widespread superfamily of enzymes notably involved in xenobiotic detoxification and/or in specialized metabolism. Populus trichocarpa genome (V4.1 assembly, Phytozome 13) consists of 74 genes coding for full-length GSTs and ten likely pseudogenes. These GSTs are divided into 11 classes, in which the tau class (GSTU) is the most abundant with 54 isoforms. PtGSTU19 and 20, two paralogs sharing more than 91% sequence identity (95% of sequence similarity), would have diverged from a common ancestor of P. trichocarpa and P. yatungensis species. These enzymes display the distinctive glutathione (GSH)-conjugation and peroxidase activities against model substrates. The resolution of the crystal structures of these proteins revealed significant structural differences despite their high sequence identity. PtGSTU20 has a well-defined deep pocket in the active site whereas the bottom of this pocket is disordered in PtGSTU19. In a screen of potential ligands, we were able to identify an interaction with flavonoids. Some of them, previously identified in poplar (chrysin, galangin, and pinocembrin), inhibited GSH-conjugation activity of both enzymes with a more pronounced effect on PtGSTU20. The crystal structures of PtGSTU20 complexed with these molecules provide evidence for their potential involvement in flavonoid transport in P. trichocarpa.
Stereotaxic atlas of the infant rat brain at postnatal days 7–13
Authors: Chen Yu-Nong , Zheng Xin , Chen Hai-Lin , Gao Jin-Xian , Li Xin-Xuan , Xie Jun-Fan , Xie Yu-Ping , Spruyt Karen , Shao Yu-Feng , Hou Yi-Ping
Published: August 2022

Recently, researchers have paid progressively more attention to the study of neural development in infant rats. However, due to the lack of complete intracerebral localization information, such as clear nuclear cluster boundaries, identified main brain structures, and reliable stereotaxic coordinates, it is difficult and restricted to apply technical neuroscience to infant rat’s brain. The present study was undertaken to refine the atlas of infant rats. As such, we established a stereotaxic atlas of the infant rat’s brain at postnatal days 7–13. Furthermore, dye calibration surgery was performed in P7–P13 infant rats by injecting Methylene blue, and sections were incubated in Nissl solutions. From the panoramic images of the brain sections, atlases were made. Our article has provided the appearance and measurements of P7–P13 Sprague–Dawley rat pups. Whereas the atlas contains a series of about 530 coronal brain section images from olfactory bulbs to the brainstem, a list of abbreviations of the main brain structures, and reliable stereotaxic coordinates, which were demonstrated by vertical and oblique injections with fluorescent dye DiI. The present findings demonstrated that our study of P7–P13 atlases has reasonable nucleus boundaries and accurate and good repeatability of stereotaxic coordinates, which can make up for the shortage of postnatal rat brain atlas currently in the field.
Children with strabismus and amblyopia presented abnormal spontaneous brain activities measured through fractional amplitude of low-frequency fluctuation (fALFF)
Authors: Hu Xiao-Qin , Shi Yi-Dan , Chen Jun , You Zhipeng , Pan Yi-Cong , Ling Qian , Wei Hong , Zou Jie , Ying Ping , Liao Xu-Lin , Su Ting , Wang Yi-Xin , Shao Yi
Published: August 2022

Purpose

Based on fMRI technology, we explored whether children with strabismus and amblyopia (SA) showed significant change in fractional amplitude of low-frequency fluctuation (fALFF) values in specific brain regions compared with healthy controls and whether this change could point to the clinical manifestations and pathogenesis of children with strabismus to a certain extent.

Methods

We enrolled 23 children with SA and the same number matched healthy controls in the ophthalmology department of the First Affiliated Hospital of Nanchang University, and the whole brain was scanned by rs-fMRI. The fALFF value of each brain area was derived to examine whether there is a statistical difference between the two groups. Meanwhile, the ROC curve was made in a view to evaluate whether this difference proves useful as a diagnostic index. Finally, we analyzed whether changes in the fALFF value of some specific brain regions are related to clinical manifestations.

Results

Compared with HCs, children with SA presented decreased fALFF values in the left temporal pole: the superior temporal gyrus, right middle temporal gyrus, right superior frontal gyrus, and right supplementary motor area. Meanwhile, they also showed higher fALFF values in specific brain areas, which included the left precentral gyrus, left inferior parietal, and left precuneus.

Conclusion

Children with SA showed abnormal fALFF values in different brain regions. Most of these regions were allocated to the visual formation pathway, the eye movement-related pathway, or other visual-related pathways, suggesting the pathological mechanism of the patient.
Impaired feedforward control of movements in pianists with focal dystonia
Authors: Takiyama Ken , Mugikura Shuta , Furuya Shinichi
Published: August 2022

Learning accurate and fast movements typically accompanies the modulation of feedforward control. Nevertheless, it remains unclear how motor skill learning modulates feedforward control, such as through maladaptation of the sensorimotor system by extensive training (e.g., task-specific dystonia). Here, we examined the modulation of feedforward control through motor skill learning while focusing on the motion of piano playing at either a natural tempo or the fastest tempo. The current study compared the kinematics and keypress data among individuals in three groups: healthy and well-trained pianists (i.e., subjects with skill learning), non-musicians (i.e., subjects without skill learning), and patients with focal-hand dystonia (FHD) (i.e., subjects with maladaptation by skill learning). Compared to healthy pianists, patients with FHD showed impairment in some feedforward motion components that are relevant to classifying the two playing tempi. However, while focusing on motion components that are irrelevant to the tempo classification, patients with FHD showed movements comparable to those of healthy pianists. Furthermore, patients with FHD demonstrated significantly slower movement times than healthy pianists. Our results suggest that maladaptation by skill learning affects parts of feedforward control rather than its entirety. Nevertheless, the affected feedforward components are relevant to performing movements as fast as possible, which may underlie the speed dependence of dystonic symptoms.
Spontaneous brain activity, graph metrics, and head motion related to prospective post-traumatic stress disorder trauma-focused therapy response
Authors: van Lutterveld Remko , Varkevisser Tim , Kouwer Karlijn , van Rooij Sanne J. H. , Kennis Mitzy , Hueting Martine , van Montfort Simone , van Dellen Edwin , Geuze Elbert
Published: August 2022

Introduction

Trauma-focused psychotherapy for post-traumatic stress disorder (PTSD) is effective in about half of all patients. Investigating biological systems related to prospective treatment response is important to gain insight in mechanisms predisposing patients for successful intervention. We studied if spontaneous brain activity, brain network characteristics and head motion during the resting state are associated with future treatment success.

Methods

Functional magnetic resonance imaging scans were acquired from 46 veterans with PTSD around the start of treatment. Psychotherapy consisted of trauma-focused cognitive behavioral therapy (tf-CBT), eye movement desensitization and reprocessing (EMDR), or a combination thereof. After intervention, 24 patients were classified as treatment responders and 22 as treatment resistant. Differences between groups in spontaneous brain activity were evaluated using amplitude of low-frequency fluctuations (ALFF), while global and regional brain network characteristics were assessed using a minimum spanning tree (MST) approach. In addition, in-scanner head motion was assessed.

Results

No differences in spontaneous brain activity and global network characteristics were observed between the responder and non-responder group. The right inferior parietal lobule, right putamen and left superior parietal lobule had a more central position in the network in the responder group compared to the non-responder group, while the right dorsolateral prefrontal cortex (DLPFC), right inferior frontal gyrus and left inferior temporal gyrus had a less central position. In addition, responders showed less head motion.

Discussion

These results show that areas involved in executive functioning, attentional and action processes, learning, and visual-object processing, are related to prospective PTSD treatment response in veterans. In addition, these findings suggest that involuntary micromovements may be related to future treatment success.
Reliability of the triangle completion test in the real-world and in virtual reality
Authors: McLaren Ruth , Chaudhary Shikha , Rashid Usman , Ravindran Shobika , Taylor Denise
Published: August 2022

Background

The triangle completion test has been used to assess egocentric wayfinding for decades, yet there is little information on its reliability. We developed a virtual reality (VR) based test and investigated whether either test of spatial navigation was reliable.

Objective

To examine test-retest reliability of the real-world and VR triangle completion tests. A secondary objective was to examine the usability of the VR based test.

Materials and methods

Thirty healthy adults aged 18–45 years were recruited to this block randomized study. Participants completed two sessions of triangle completion tests in the real-world and VR on the same day with a break between sessions.

Results

In both test versions distance from the endpoint and angle of deviation showed poor test-retest reliability (r < 0.5). Distance traveled had moderate reliability in both the real-world and VR tests (r = 0.55 95% CI [0.23, 0.76]; r = 0.66 95% CI [0.4, 0.83, respectively]). The VR triangle test showed poor correlation with the real-world test.

Conclusion

The triangle completion test has poor test-retest reliability and demonstrates poor concurrent validity between the real-world and VR. Nevertheless, it was feasible to translate a real-world test of spatial navigation into VR. VR provides opportunities for development of clinically relevant spatial navigation tests in the future.
Associations of visual functions with attitudes about motor vehicle dashboards among older drivers
Authors: Swain Thomas A. , Snyder Scott W. , McGwin Jr Gerald , Owsley Cynthia
Published: August 2022

Purpose

Proper understanding and interaction with the dashboard is an essential aspect of safely operating a motor vehicle. A portion of this task is dependent on vision, yet no published information exists regarding dashboard ergonomics and visual function. This study sought to associate visual functions and person abilities of dashboard ergonomic dimensions relevant to older driver design preferences and attitudes.

Methods

In this population-based study of drivers, participants completed functional testing for habitual distance visual acuity, contrast sensitivity, visual field sensitivity, visual processing speed, and spatial ability. A questionnaire assessed attitudes and understanding of dashboard design, with questionnaire items generated from the content of focus groups of older drivers. Dashboard design domains identified in Rasch analysis of questionnaire responses were quantified using person ability measures for the cognitive processing, lighting, obstructions, and pattern recognition domains. Visual functions and person abilities were correlated using Spearman partial correlations, adjusting for age and sex.

Results

A total of 997 participants completed functional testing and the dashboard questionnaire. The mean age was 77.4 ± 4.6 years, and the majority were male (55%) and white (81%). The sample had a range of person abilities and visual functions. Contrast and visual field sensitivities were significantly associated with the cognitive processing, lighting, and pattern recognition dashboard design dimensions (p ≤ 0.0052). For all significant associations, increased visual function was indicative of better person ability. Visual processing speed, as measured by Trails B and UFOV2, was significantly associated with the lighting domain (p = 0.0008 and p = 0.0007, respectively). The UFOV2 measure was correlated with pattern recognition (p = 0.0165). Spatial ability was the only visual function associated with the visual obstruction dimension (p = 0.0347).

Conclusions

Person ability for dashboard design domains are related to visual function in older drivers. Results show person ability for domains increased with improved visual function. Future automotive engineering and design initiatives should consider these associations in improving dashboard designs to increase vehicle utility and accessibility.
Effect of a diet rich in galactose or fructose, with or without fructooligosaccharides, on gut microbiota composition in rats
Authors: Mhd Omar Nor Adila , Dicksved Johan , Kruger Johanita , Zamaratskaia Galia , Michaëlsson Karl , Wolk Alicja , Frank Jan , Landberg Rikard
Published: August 2022

Recent studies suggest that a diet rich in sugars significantly affects the gut microbiota. Adverse metabolic effects of sugars may partly be mediated by alterations of gut microbiota and gut health parameters, but experimental evidence is lacking. Therefore, we investigated the effects of high intake of fructose or galactose, with/without fructooligosaccharides (FOS), on gut microbiota composition in rats and explored the association between gut microbiota and low-grade systemic inflammation. Sprague–Dawley rats (n = 6/group) were fed the following isocaloric diets for 12 weeks (% of the dry weight of the sugars or FOS): (1) starch (control), (2) fructose (50%), (3) galactose (50%), (4) starch+FOS (15%) (FOS control), (5) fructose (50%)+FOS (15%), (6) galactose (50%)+FOS (15%), and (7) starch+olive (negative control). Microbiota composition in the large intestinal content was determined by sequencing amplicons from the 16S rRNA gene; 341F and 805R primers were used to generate amplicons from the V3 and V4 regions. Actinobacteria, Verrucomicrobia, Tenericutes, and Cyanobacteria composition differed between diets. Bifidobacterium was significantly higher in all diet groups where FOS was included. Modest associations between gut microbiota and metabolic factors as well as with gut permeability markers were observed, but no associations between gut microbiota and inflammation markers were observed. We found no coherent effect of galactose or fructose on gut microbiota composition. Added FOS increased Bifidobacterium but did not mitigate potential adverse metabolic effects induced by the sugars. However, gut microbiota composition was associated with several metabolic factors and gut permeability markers which warrant further investigations.
Phosphorylation of ovalbumin after pulsed electric fields pretreatment: Effects on conformation and immunoglobulin G/immunoglobulin E-binding ability
Authors: Yang Wenhua , Duan Wenjing , Li Qiuhong , Duan Dengle , Wang Qin
Published: August 2022

Ovalbumin (OVA) is one of major allergens of hen egg white with excellent nutritional and processing properties. Previous research exhibits that pulsed electric field (PEF) treatment could partially unfold OVA. This may contribute to the improvement of OVA phosphorylation. In this study, the effect of PEF pretreatment combined with phosphorylation on the structure and immunoglobulin (Ig) G/IgE-binding ability of OVA was investigated. The structural changes were measured by circular dichroism (CD), ultraviolet absorption, and fluorescence spectroscopy. The IgG- and IgE-binding abilities were determined by inhibition enzyme-linked immunosorbent assay (ELISA) using rabbit polyclonal antibodies and egg-allergy patients’ sera, respectively. The results showed that PEF pretreatment combined with phosphorylation markedly reduced the IgG- and IgE-binding abilities. It was attributed to the changes in secondary and tertiary structure, which was reflected in the increase of ultraviolet (UV) absorbance, α-helix content, and the increase the molecular weight. Moreover, it suggested PEF pretreatment improved the phosphorylation of OVA and enhanced the reduction of IgG/IgE-binding capacity of phosphorylated OVA. Therefore, PEF pretreatment combined with phosphorylation has the potential for developing a method for OVA desensitization.
Neural responsiveness to Chinese versus Western food images: An functional magnetic resonance imaging study of Chinese young adults
Authors: Xu Xi , Pu Jiajia , Shaw Amy , Jackson Todd
Published: August 2022

Cross-cultural studies suggest that people typically prefer to eat familiar foods from their own culture rather than foreign foods from other cultures. On this basis, it is plausible that neural responsiveness elicited by palatable food images from one’s own culture differ from those elicited by food depictions from other cultures. Toward clarifying this issue, we examined neural activation and self-report responses to indigenous (Chinese) versus Western food images among young Chinese adults. Participants (33 women, 33 men) viewed Chinese food, Western food and furniture control images during a functional magnetic resonance imaging (fMRI) scan and then rated the images on “liking,” “wanting,” and “difficult resisting.” Analyses indicated there were no significant differences in self-report ratings of Chinese versus Western food images. However, Chinese food images elicited stronger activation in regions linked to cravings, taste perception, attention, reward, and visual processing (i.e., cerebellum crus, superior temporal gyrus, supramarginal gyrus, middle temporal gyrus, inferior parietal lobule, posterior insula, middle occipital gyrus; inferior occipital gyrus). Conversely, Western food images elicited stronger activation in areas involved in visual object recognition and visual processing (inferior temporal gyrus, middle occipital gyrus, calcarine). These findings underscored culture as a potentially important influence on neural responses to visual food cues and raised concerns about the ecological validity of using “standard” Western food images in neuroimaging studies of non-Western samples. Results also provide foundations for designing culturally informed research and intervention approaches in non-Westerns contexts guided by the use of external food cues that are most salient to the cultural group under study.
Identification and chemical profiling of anti-alcoholic liver disease biomarkers of ginseng Huang jiu using UPLC-Q-Orbitrap-HRMS and network pharmacology-based analyses
Authors: Wu Yongxi , Cai Yongyu , Ma Liting , Li Fangtong , Zhang Meiyu , Wang Yizhu , Zheng Fei , Pi Zifeng , Yue Hao
Published: August 2022

This study investigated the mechanism of characteristic non-volatile organic compounds (NVOCs) from ginseng Huang jiu (GH) in the treatment of alcoholic liver disease through UPLC-Q-Orbitrap-HRMS and network pharmacological analyses. Changes in NVOC contents in ginseng Huang jiu and ginseng-soaked wine fermented by different processing technologies were analyzed through liquid chromatography–mass spectrometry (LC-MS). A total of 96 ginsenosides were identified in ginseng Huang jiu throughout the fermentation process, which included 37 protopanaxadiol-type ginsenosides, 47 protopanaxatriol-type ginsenosides, and 4 oleanolic acid-type ginsenosides. Orthogonal partial least squares-discriminant analysis (OPLS-DA) revealed that 20(R)-Rg2, Gypenoside XVII, 20(S)-Rf3, CK, Rg5, Rh2, and other rare ginsenosides in ginseng Huang jiu could be the potential index for determining ginseng Huang jiu. In addition, ginseng Huang jiu could improve alcoholic liver disease by regulating the GSTP1, HRAS, AKR1B1, GSTA1, Androgen receptor (AR), GSR, and LDHB genes through bioinformatics analysis. This study provides new insights into improving the industrial production of ginseng Huang jiu and treating alcoholic liver disease with medicinal and food products.
Comparing the blood oxygen level–dependent fluctuation power of benign and malignant musculoskeletal tumors using functional magnetic resonance imaging
Authors: Duan Lisha , Huang Huiyuan , Sun Feng , Zhao Zhenjiang , Wang Mengjun , Xing Mei , Zang Yufeng , Xiu Xiaofei , Wang Meng , Yu Hong , Cui Jianling , Zhang Han
Published: August 2022

Purpose

The aim of this study is to compare the blood oxygen level–dependent (BOLD) fluctuation power in 96 frequency points ranging from 0 to 0.25 Hz between benign and malignant musculoskeletal (MSK) tumorsviapower spectrum analyses using functional magnetic resonance imaging (fMRI).

Materials and methods

BOLD-fMRI and T1-weighted imaging (T1WI) of 92 patients with benign or malignant MSK tumors were acquired by 1.5-T magnetic resonance scanner. For each patient, the tumor-related BOLD time series were extracted, and then, the power spectrum of BOLD time series was calculated and was then divided into 96 frequency points. A two-samplet-test was used to assess whether there was a significant difference in the powers (the “power” is the square of the BOLD fluctuation amplitude with arbitrary unit) of each frequency point between benign and malignant MSK tumors. The receiver operator characteristic (ROC) analysis was used to assess the diagnostic capability of distinguishing between benign and malignant MSK tumors.

Results

The result of the two-samplet-test showed that there was significant difference in the power between benign and malignant MSK tumor at frequency points of 58 (0.1508 Hz,P= 0.036), 59 (0.1534 Hz,P= 0.032), and 95 (0.247 Hz,P= 0.014), respectively. The ROC analysis of mean power of three frequency points showed that the area of under curve is 0.706 (P =0.009), and the cutoff value is 0.73130. If the power of the tumor greater than or equal to 0.73130 is considered the possibility of benign tumor, then the diagnostic sensitivity and specificity values are 83% and 59%, respectively. Thepost hocanalysis showed that the merged power of 0.1508 and 0.1534 Hz in benign MSK tumors was significantly higher than that in malignant ones (P= 0.014). The ROC analysis showed that, if the benign MSK tumor was diagnosed with the power greater than or equal to the cutoff value of 1.41241, then the sensitivity and specificity were 67% and 68%, respectively.

Conclusion

The mean power of three frequency points at 0.1508, 0.1534, and 0.247 Hz may potentially be a biomarker to differentiate benign from malignant MSK tumors. By combining the power of 0.1508 and 0.1534 Hz, we could better detect the difference between benign and malignant MSK tumors with higher specificity.
Identification of the novel prognostic biomarker, MLLT11, reveals its relationship with immune checkpoint markers in glioma
Authors: Chen Long , Xiong Zujian , Zhao Hongyu , Teng Chubei , Liu Hongwei , Huang Qi , Wanggou Siyi , Li Xuejun
Published: August 2022

Aim

This study aimed to explore the expression pattern of MLLT11 under different pathological features, evaluate its prognostic value for glioma patients, reveal the relationship between MLLT11 mRNA expression and immune cell infiltration in the tumor microenvironment (TME), and provide more evidence for the molecular diagnosis of glioma and immunotherapy.

Methods

Using large-scale bioinformatic approach and RNA sequencing (RNA-seq) data from public databases The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), and The Gene Expression Omnibus (GEO)), we investigated the relationship between MLLT11 mRNA levels and pathologic characteristics. The distribution in the different subtypes was observed based on Verhaak bulk and Neftel single-cell classification. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were used for bioinformatic analysis. Kaplan–Meier survival analysis and Cox regression analysis were used for survival analysis. Correlation analyses were performed between MLLT11 expression and 22 immune cells and immune checkpoints in the TME.

Results

We found that MLLT11 expression is decreased in high-grade glioma tissues; we further verified this result by RT­PCR, Western blotting, and immunohistochemistry using our clinical samples. According to the Verhaak classification, high MLLT11 expression is mostly clustered in pro-neutral (PN) and neutral (NE) subtypes, while in the Neftel classification, MLLT11 mainly clustered in neural progenitor-like (NPC-like) neoplastic cells. Survival analysis revealed that low levels of MLLT11 expression are associated with a poorer prognosis; MLLT11 was identified as an independent prognostic factor in multivariate Cox regression analyses. Functional enrichment analyses of MLLT11 with correlated expression indicated that low MLLT11 expression is associated with the biological process related to the extracellular matrix, and the high expression group is related to the synaptic structure. Correlation analyses suggest that declined MLLT11 expression is associated with increased macrophage infiltration in glioma, especially M2 macrophage, and verified by RT­PCR, Western blotting, and immunohistochemistry using our clinical glioma samples. MLLT11 had a highly negative correlation with immune checkpoint inhibitor (ICI) genes including PDCD1, PD-L1, TIM3(HAVCR2), and PD‐L2 (PDCD1LG2).

Conclusion

MLLT11 plays a crucial role in the progression of glioma and has the potential to be a new prognostic marker for glioma.
Case report: Giant unilocular prostate cystadenoma: A rarer condition with a single cystic mass
Authors: Wang Wenda , Xiao Yu , Fang Shiyuan , Qiao Yi , Rong Shi , Wang Fengdan , Sun Hao , Jin Zhengyu
Published: August 2022

Prostate cystadenoma is a rare benign prostatic neoplasm, which grows outside prostate and locates midline between the urinary bladder and rectum. It usually presents as multilocular cysts, thus, named giant multilocular prostate cystadenoma. The definite diagnosis is difficult to be made before surgery, and it depends on histopathology. Here, we report a rarer condition of prostate cystadenoma, which manifests as a giant unilocular cyst with a solid nodule inside. The 55-year-old Chinese male patient presented with dysuria and constipation. MRI revealed a 10.5 × 8.2 cm mono-cystic lesion displacing the rectum to the posterior, prostate, and bladder to the anterior, with a 2.8 × 2.1 cm solid nodule at the anterior wall. 18F-FDG PET/CT demonstrated an elevated SUVmax (3.5) of the solid nodule. Laparoscopic pelvic mass resection was performed and prostate cystadenoma was diagnosed. In conclusion, when a mass of single locular cyst sits in the male pelvis, the diagnosis of prostate cystadenoma could not be excluded.
Development and external validation of a dynamic nomogram to predict the survival for adenosquamous carcinoma of the pancreas
Authors: Ren Chao , Ma Yifei , Jin Jiabin , Ding Jiachun , Jiang Yina , Wu Yinying , Li Wei , Yang Xue , Han Liang , Ma Qingyong , Wu Zheng , Shi Yusheng , Wang Zheng
Published: August 2022

Objective

We aimed to develop a nomogram to predict the survival and prognosis of adenosquamous carcinoma of the pancreas (ASCP).

Background

Adenosquamous carcinoma of the pancreas (ASCP) is a relatively rare histological subtype of pancreatic exocrine neoplasms. It was reported a worse survival in ASCP than in pancreatic adenocarcinoma (PDAC). Prediction of ASCP prognosis is of great importance.

Methods

Histologically confirmed ASCP patients from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) Program database were finally enrolled and divided into development and internal validation cohorts. Moreover, a multi-center cohort of 70 patients from China was registered as the external validation. A nomogram was developed based on independent predictors of ASCP determined in multivariable analysis.

Results

A total of 233 patients from SEER were finally included. Univariate and Multivariate analysis showed that tumor size, radiotherapy, chemotherapy, and lymph node ratio (LNR) were considered the independent prognostic indicators. We developed a nomogram according to these four parameters. The C index of the nomogram in the development cohort was 0.696. Through analysis of the area under the curve (AUC) of the different cohorts, we observed that the predictive efficacy of the nomogram for 1-, and 2-year overall survival (OS) were better than those of the American Joint Committee on Cancer (AJCC) TNM (8th) staging system both in the development and validation cohort. External validation confirmed that 1-year survival is 67.2% vs. 29.7%, similar to the internal cohort analysis.

Conclusion

The nomogram showed good performance in predicting the survival of ASCP. It could help surgeons to make clinical decisions and develop further plans.
Small but strong: Pivotal roles and potential applications of snoRNAs in hematopoietic malignancies
Authors: Dong Jian , Wang Hui , Zhang Zhaoru , Yang Lin , Qian Xinyue , Qian Wenchang , Han Yingli , Huang He , Qian Pengxu
Published: August 2022

Small nucleolar RNAs (snoRNAs) belong to a family of noncoding RNAs that are 60-300 nucleotides in length, and they are classified into two classes according to their structure and function: C/D box snoRNAs, playing an essential role in 2’-O-methylation modification on ribosomal RNA; H/ACA box snoRNAs, involved in the pseudouridylation of rRNA. SnoRNAs with unclear functions, no predictable targets, and unusual subcellular locations are called orphan snoRNAs. Recent studies have revealed abnormal expression and demonstrated the pivotal roles of snoRNAs and their host genes in various types of hematological malignancies. This review discusses recent discoveries concerning snoRNAs in a variety of hematological malignancies, including multiple myeloma, lymphoma and leukemia, and sheds light on the application of snoRNAs as diagnostic and prognostic markers as well as therapeutic targets of hematological malignancies in the future.
An automated approach for predicting glioma grade and survival of LGG patients using CNN and radiomics
Authors: Xu Chenan , Peng Yuanyuan , Zhu Weifang , Chen Zhongyue , Li Jianrui , Tan Wenhao , Zhang Zhiqiang , Chen Xinjian
Published: August 2022

Objectives

To develop and validate an efficient and automatically computational approach for stratifying glioma grades and predicting survival of lower-grade glioma (LGG) patients using an integration of state-of-the-art convolutional neural network (CNN) and radiomics.

Method

This retrospective study reviewed 470 preoperative MR images of glioma from BraTs public dataset (n=269) and Jinling hospital (n=201). A fully automated pipeline incorporating tumor segmentation and grading was developed, which can avoid variability and subjectivity of manual segmentations. First, an integrated approach by fusing CNN features and radiomics features was employed to stratify glioma grades. Then, a deep-radiomics signature based on the integrated approach for predicting survival of LGG patients was developed and subsequently validated in an independent cohort.

Results

The performance of tumor segmentation achieved a Dice coefficient of 0.81. The intraclass correlation coefficients (ICCs) of the radiomics features between the segmentation network and physicians were all over 0.75. The performance of glioma grading based on integrated approach achieved the area under the curve (AUC) of 0.958, showing the effectiveness of the integrated approach. The multivariable Cox regression results demonstrated that the deep-radiomics signature remained an independent prognostic factor and the integrated nomogram showed significantly better performance than the clinical nomogram in predicting overall survival of LGG patients (C-index: 0.865 vs. 0.796, P=0.005).

Conclusion

The proposed integrated approach can be noninvasively and efficiently applied in prediction of gliomas grade and survival. Moreover, our fully automated pipeline successfully achieved computerized segmentation instead of manual segmentation, which shows the potential to be a reproducible approach in clinical practice.
Osteoporosis, fracture and survival: Application of machine learning in breast cancer prediction models
Authors: Ji Lichen , Zhang Wei , Zhong Xugang , Zhao Tingxiao , Sun Xixi , Zhu Senbo , Tong Yu , Luo Junchao , Xu Youjia , Yang Di , Kang Yao , Wang Jin , Bi Qing
Published: August 2022

The risk of osteoporosis in breast cancer patients is higher than that in healthy populations. The fracture and death rates increase after patients are diagnosed with osteoporosis. We aimed to develop machine learning-based models to predict the risk of osteoporosis as well as the relative fracture occurrence and prognosis. We selected 749 breast cancer patients from two independent Chinese centers and applied six different methods of machine learning to develop osteoporosis, fracture and survival risk assessment models. The performance of the models was compared with that of current models, such as FRAX, OSTA and TNM, by applying ROC, DCA curve analysis, and the calculation of accuracy and sensitivity in both internal and independent external cohorts. Three models were developed. The XGB model demonstrated the best discriminatory performance among the models. Internal and external validation revealed that the AUCs of the osteoporosis model were 0.86 and 0.87, compared with the FRAX model (0.84 and 0.72)/OSTA model (0.77 and 0.66), respectively. The fracture model had high AUCs in the internal and external cohorts of 0.93 and 0.92, which were higher than those of the FRAX model (0.89 and 0.86). The survival model was also assessed and showed high reliability via internal and external validation (AUC of 0.96 and 0.95), which was better than that of the TNM model (AUCs of 0.87 and 0.87). Our models offer a solid approach to help improve decision making.
Development and validation of cuproptosis-related gene signature in the prognostic prediction of liver cancer
Authors: Liu Yanqing , Liu Yang , Ye Shujun , Feng Huijin , Ma Lianjun
Published: August 2022

Liver cancer is a generic term referring to several cancer types arising from the liver. Every year, liver cancer causes lots of deaths and other burdens to the people all over the world. Though the techniques in the diagnosis and therapy of liver cancer have undergone significant advances, the current status of treating liver cancer is not satisfactory enough. The improvement of techniques for the prognosis of liver cancer patients will be a great supplement for the treatment of liver cancer. Cuproptosis is a newly identified regulatory cell death type, which may have a close connection to liver cancer pathology. Here, we developed a prognostic model for liver cancer based on the cuproptosis-related mRNAs and lncRNAs. This model can not only effectively predict the potential survival of liver cancer patients, but also be applied to evaluate the infiltration of immune cell, tumor mutation burden, and sensitivity to anti-tumor drugs in liver cancer. In addition, this model has been successfully validated in lots of liver cancer patients’ data. In summary, we wish this model can become a helpful tool for clinical use in the therapy of liver cancer.
Multisystem inflammatory syndrome in children related to COVID-19: Data from a Mexican national referral children's hospital
Authors: Menchaca-Aguayo Héctor , Alpizar-Rodriguez Deshire , Ramos-Tiñini Pamela , Faugier-Fuentes Enrique
Published: August 2022

Objectives

To describe characteristics of patients with the pediatric inflammatory multisystem syndrome, temporally associated with SARS-CoV-2 (PIMS-TS)/multisystem inflammatory syndrome in children (MIS-C) and to identify factors associated with admission to the pediatric intensive care unit (PICU) in the Mexican children without coronavirus disease 2019 (COVID-19) vaccination.

Methods

This was a cross-sectional study performed at Hospital Infantil de Mexico Federico Gomez, a referral children's hospital in Mexico. The study included all cases that met the criteria for PIMS-TS/MIS-C, unvaccinated, between March 2020 and January 2022. The primary outcome was the admission to PICU. Associations of PICU admission with demographic and clinical variables were estimated using logistic regression analyses.

Results

We identified a total of 90 cases, with a median age of 7.5 years old, 47 (52.2%) girls. A previously healthy status was recorded in 76 (85%) children. All patients had positive PCR, serology test, or COVID-19 exposure. PICU admission was reported in 41 (45.6%) children. No deaths were reported. Patients received as treatment only corticosteroids in 53.3% of the cases. In univariable analyses, baseline factors associated with PICU admission were older age, hypotension or shock, positive PCR test, hypoalbuminemia, elevated procalcitonin, ferritin, and lymphopenia. Age, shock at admission, and hypoalbuminemia remained independently associated in the multivariable analysis adjusted by gender and previously healthy status.

Conclusion

We found a high proportion of previously healthy children in patients with PIMS-TS/MIS-C in our center. Critical care attention was received by nearly half of the children. The main treatment used was steroids. Age, shock at admission, and hypoalbuminemia were factors associated with PICU admission.
Walking alone milestone combined reading-frame rule improves early prediction of Duchenne muscular dystrophy
Authors: Ma Yan-li , Zhang Wei-hua , Chen Guo-hong , Song Li-fang , Wang Yuan , Yuan Rui-li , Wang Ying , Cheng Xiu-yong
Published: August 2022

Objective

To explore the potential of walking alone milestone combined reading-frame rule to improve the early diagnosis of Duchenne muscular dystrophy (DMD).

Method

To retrospectively describe the genotype and phenotype of Duchenne and Becker muscular dystrophies (BMD) patients with deletions and duplicates in the dystrophin gene. The sensitivity and specificity of the reading frame rule were calculated and compared to that of the combined reading frame rule and walking alone milestone. The diagnostic coincidence rate of two different methods was analyzed.

Result

One hundred sixty-nine male DMD/BMD patients were enrolled, including 17 cases of BMD and 152 cases of DMD. The diagnostic coincidence rate, diagnostic sensitivity, and specificity of the reading-frame rule for DMD/BMD were 85.2, 86.8, and 70.59%, respectively. The sensitivity and specificity of the reading frame principle combined with the walking alone milestone for DMD/BMD were 96.05 and 70.59%, respectively. The diagnostic coincidence rate increased to 93.49%, significantly different from that predicted by reading- frame rule (P < 0.05).

Conclusion

The reading-frame rule combined with the walking alone milestone significantly improved the early diagnosis rate of DMD.
Self-Reported Overall Adherence and Correct Inhalation Technique Discordance in Chronic Obstructive Pulmonary Disease Population
Authors: Hendrychova Tereza , Svoboda Michal , Maly Josef , Vlcek Jiri , Zimcikova Eva , Dvorak Tomas , Zatloukal Jaromir , Volakova Eva , Plutinsky Marek , Brat Kristian , Popelkova Patrice , Kopecky Michal , Novotna Barbora , Koblizek Vladimir
Published: August 2022

Background: Adherence to inhaled medication constitutes a major problem in patients with chronic obstructive pulmonary disease (COPD) globally. However, large studies evaluating adherence in its entirety and capturing a large variety of potentially associated factors are still lacking.

Objective: To study both elementary types of adherence to chronic inhaled COPD medication in “real-life” COPD patients and to assess relationships with a wide-ranging spectrum of clinical parameters.

Methods: Data from the Czech Multicentre Research Database (CMRD) of COPD, an observational prospective study, were used. Overall adherence (OA) was evaluated with Morisky Medication Adherence Scale (©MMAS-4) and adherence to an application technique (A-ApplT) with the Five Steps Assessment. Mann–Whitney U test, Spearman’s correlation, and logistic regression were used to explore relationships between variables.

Results: Data of 546 participants (69.6% of all patients from the CMRD) were analyzed. Two-thirds self-reported optimal OA, but only less than one-third demonstrated A-ApplT without any error. OA did not correlate with A-ApplT. Next, better OA was associated with higher education, a higher number of inhalers, a lower rate of exacerbations, poorer lung function, higher degree of upper respiratory tract symptoms (SNOT-22), absence of depressive symptoms, ex-smoking status, regular mouthwash after inhaled corticosteroids (ICS), and flu vaccination. By contrast, better A-ApplT was associated with a lower number of inhalers, better lung function, and regular mouthwash after ICS. Independent predictors of nonoptimal OA included lower degree of education, absence of flu vaccination, anemia, depression, and peptic ulcer history, whereas independent predictors of lower A-ApplT were lower education, absence of regular mouthwash after ICS, and higher COPD Assessment Test score.

Conclusions: Parameters associated with OA and A-ApplT differ, and those associated with both adherence domains are sometimes associated inversely. Based on this finding, we understand these as two separate constructs with an overlap.
Integrating network pharmacology analysis and pharmacodynamic evaluation for exploring the active components and molecular mechanism of moutan seed coat extract to improve cognitive impairment
Authors: Wang Yue , Wu Xinyan , Yang Kailin , Liu Qing , Jiang Baoping , Yang Runmei , Xiao Peigen , He Chunnian
Published: August 2022

Paeonia suffruticosa (Moutan) is a traditional medicinal plant in China. Its seed coat is rich in resveratrol oligomer, especially suffruticosol B (SB). Previous studies had shown that the seed coat extracts of Paeonia suffruticosa (PSCE) had good cholinesterase inhibitory activity and neuroprotective effect, but the effective dose range was unknown, and the pharmacodynamic components and molecular mechanism of PSCE had not been discussed. The current study aimed to screen the pharmacodynamic components in PSCE and investigate the improvement effect of PSCE and the selected SB on scopolamine-induced cognitive dysfunction in mice and its mechanism. The results of high-throughput sequencing and bioinformatics analysis showed that suffruticosol B (SB) and trans-gnetin H (GH) might be the main active components of PSCE; PSCE might improve cognitive dysfunction through p53, HIF-1, MAPK, and PI3K-Akt signaling pathways, while SB and GH might improve cognitive dysfunction through HIF-1 signaling pathway. SB and GH had good molecular docking activity with the target of HIF-1 signaling pathway. The pharmacodynamic activities of PSCE and SB were further verified by behavioral experiments. PSCE and SB could improve the recognition ability of familiar and new objects and shorten the escape latency in the Morris Water Maze test (PSCE 120 mg∙kg-1, p < 0.05; SB 60 mg∙kg-1, p < 0.01); PSCE and SB could increase Ach and GSH levels, enhance the activities of ChAT, SOD and CAT, decrease the levels of IL-1β, IL-6, and TNF-α, and decrease the activity of AChE. In conclusion, the results indicated that PSCE might exert pharmacodynamic activity through multiple components, targets, and pathways, and SB and GH might be the main active components of PSCE. PSCE and SB might improve cognitive dysfunction by regulating cholinergic, antioxidant, and anti-inflammatory effects. These results indicated that PSCE and SB might be potential anti-AD drug candidates, providing a scientific basis for the development and utilization of Moutan bark.
Research progress and applications of nanobody in human infectious diseases
Authors: Mei Yaxian , Chen Yuanzhi , Sivaccumar Jwala P. , An Zhiqiang , Xia Ningshao , Luo Wenxin
Published: August 2022

Infectious diseases, caused by pathogenic microorganisms, are capable of affecting crises. In addition to persistent infectious diseases such as malaria and dengue fever, the vicious outbreaks of infectious diseases such as Neocon, Ebola and SARS-CoV-2 in recent years have prompted the search for more efficient and convenient means for better diagnosis and treatment. Antibodies have attracted a lot of attention due to their good structural characteristics and applications. Nanobodies are the smallest functional single-domain antibodies known to be able to bind stably to antigens, with the advantages of high stability, high hydrophilicity, and easy expression and modification. They can directly target antigen epitopes or be constructed as multivalent nanobodies or nanobody fusion proteins to exert therapeutic effects. This paper focuses on the construction methods and potential functions of nanobodies, outlines the progress of their research, and highlights their various applications in human infectious diseases.
Better detoxifying effect of ripe forsythiae fructus over green forsythiae fructus and the potential mechanisms involving bile acids metabolism and gut microbiota
Authors: Wang Tao , Li Xu-Jiong , Qin Ling-Hao , Liang Xue , Xue Huan-Huan , Guo Jing , Li Shi-Fei , Zhang Li-Wei
Published: August 2022

Forsythiae Fructus (FF), the fruit of Forsythia suspensa (Thunb.) Vahl. (Lianqiao), is one of the most fundamental herbs in Traditional Chinese Medicines (TCM), mainly due to its heat-clearing and detoxifying effects. There are two types of FF, the greenish fruits that start to ripen (GF) and the yellow fruits that are fully ripe (RF), called “Qingqiao” and “Laoqiao” referred to the Chinese Pharmacopoeia, respectively. It undergoes a complex series of changes during the maturation of FF. However, the clinical uses and preparation of phytopharmaceuticals of FF have not been distinguished to date. Moreover, there is limited information on the study of the difference in pharmacological activity between RF and GF. In this study, a rat model of bile duct ligation (BDL)-induced cholestasis was used to compare the differences in their effects. RF was found to have better results than GF in addressing toxic bile acids (BAs) accumulation and related pathological conditions caused by BDL. The underlying mechanism may be related to the interventions of gut microbiota. The results of the present study suggest that the better detoxifying effect of RF than GF may be indirectly exerted through the regulation of gut microbiota and thus the improvement of BAs metabolism.