bluuebunny/crossref_metadata_2025 huggingface dataset:
Image-Based Differentiation of Intracranial Metastasis From Glioblastoma Using Automated Machine Learning
Authors: Liu Yukun , Li Tianshi , Fan Ziwen , Li Yiming , Sun Zhiyan , Li Shaowu , Liang Yuchao , Zhou Chunyao , Zhu Qiang , Zhang Hong , Liu Xing , Wang Lei , Wang Yinyan
Published: May 2022

Purpose

The majority of solitary brain metastases appear similar to glioblastomas (GBMs) on magnetic resonance imaging (MRI). This study aimed to develop and validate an MRI-based model to differentiate intracranial metastases from GBMs using automated machine learning.

Materials and Methods

Radiomics features from 354 patients with brain metastases and 354 with GBMs were used to build prediction algorithms based on T2-weighted images, contrast-enhanced (CE) T1-weighted images, or both. The data of these subjects were subjected to a nested 10-fold split in the training and testing groups to build the best algorithms using the tree-based pipeline optimization tool (TPOT). The algorithms were independently validated using data from 124 institutional patients with solitary brain metastases and 103 patients with GBMs from the cancer genome atlas.

Results

Three groups of models were developed. The average areas under the receiver operating characteristic curve (AUCs) were 0.856 for CE T1-weighted images, 0.976 for T2-weighted images, and 0.988 for a combination in the testing groups, and the AUCs of the groups of models in the independent validation were 0.687, 0.831, and 0.867, respectively. A total of 149 radiomics features were considered as the most valuable features for the differential diagnosis of GBMs and metastases.

Conclusion

The models established by TPOT can distinguish glioblastoma from solitary brain metastases well, and its non-invasiveness, convenience, and robustness make it potentially useful for clinical applications.
Higher Cerebral Small Vessel Disease Burden in Patients With Small Intracerebral Hemorrhage
Authors: Wang Zi-Jie , Zhao Rui , Hu Xiao , Yang Wen-Song , Deng Lan , Lv Xin-Ni , Li Zuo-Qiao , Cheng Jing , Pu Ming-Jun , Tang Zhou-Ping , Wu Guo-Feng , Zhao Li-Bo , Xie Peng , Li Qi
Published: May 2022

Objective

To investigate the association between cerebral small vessel disease (SVD) and hematoma volume in primary intracerebral hemorrhage (ICH).

Methods

Patients from a prospective ICH cohort were enrolled. Admission and follow-up CT scan within 72 h after onset were reviewed to calculate the final hematoma volume. We evaluated cortical superficial siderosis and the global SVD score, including white matter hyperintensities, lacunes, enlarged perivascular space, and cerebral microbleeds on MRI. We conducted the multivariate logistic regression analyses to explore the association between SVD markers and small ICH, as well as hematoma volume. Hematoma location was stratified into lobar and non-lobar for subgroup analysis.

Results

A total of 187 patients with primary ICH (mean age 62.4 ± 13.4 years, 67.9% male) were enrolled. 94 (50.2%) patients had small ICH. The multivariate logistic regression analysis showed an association between global SVD score and small ICH [adjusted odds ratio (aOR) 1.27, 95% CI 1.03–1.57, p = 0.027] and a trend of higher global SVD score towards non-lobar small ICH (aOR 1.23, 95% CI 0.95–1.58, p = 0.122). In the multivariate linear regression analysis, global SVD score was inversely related to hematoma volume of all ICH (β = −0.084, 95% CI −0.142 to −0.025, p = 0.005) and non-lobar ICH (β = −0.112, 95% CI −0.186 to −0.037, p = 0.004). Lacune (β = −0.245, 95% CI −0.487 to −0.004, p = 0.046) was associated with lower non-lobar ICH volume.

Conclusion

Global SVD score is associated with small ICH and inversely correlated with hematoma volume. This finding predominantly exists in non-lobar ICH.
A Systematic Review of Insulin Management Recommendations to Improve Glycemic Control and Reduce Hypoglycemic Events During Ramadan Fasting in Patients With Insulin-Requiring Type 2 Diabetes
Authors: Kieu Alexander , Iles Ashley , Khan Moien AB , Östlundh Linda , Boyd Duston , Faris MoezAlIslam Ezzat
Published: May 2022

Background

Muslims with insulin-requiring type 2 diabetes are at high risk of hypo- and hyperglycemia while fasting during the month of Ramadan. Although a few reviews on diabetic management during Ramadan have been published, surveys reveal knowledge gaps remain among physicians.

Aim

This systematic review qualitatively analyzes what insulin dosing recommendations are likely to reduce hypoglycemic events and improve glycemic control during the Ramadan fasting for this high-risk group.

Methods

A comprehensive search in six databases and gray sources was performed from August 10, 2001, to August 10, 2021, for studies assessing which types of insulin and/or what dosing recommendations reduce hypoglycemic events and improve glycemic control during Ramadan. We excluded studies focusing mainly on oral antihyperglycemic medications, type 1 diabetes, persons with insulin pumps, and studies older than 20 years. Hypoglycemic event rates, pre-, and post-iftar blood glucose levels, overall average blood glucose, and hemoglobin A1c were analyzed, and a narrative synthesis was performed.

Results

Out of 1,101 collected articles, 14 eligible studies including 2,969 participants with an average age of 54.8 years, we found that insulin dose reduction may prevent hypoglycemia without causing subsequent hyperglycemia, and rapid-acting insulin analogs may improve post-iftar and overall blood glucose without incurring hypoglycemia.

Conclusions

Though initial findings are promising, more research is needed to confirm the benefits of insulin dose reduction, rapid-acting insulin analogs, and ultra-long-acting insulins.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/, identifier: CRD42021268943.
Changes in Functional Compounds, Volatiles, and Antioxidant Properties of Culinary Herb Coriander Leaves (Coriandrum sativum) Stored Under Red and Blue LED Light for Different Storage Times
Authors: Shoko Tinotenda , Manhivi Vimbainashe E. , Mtlhako Malebo , Sivakumar Dharini
Published: May 2022

This study evaluated the influence of red (630–640 nm) and blue (450 nm) light-emitting diodes (LED) lights on the changes in antioxidant constituents, activity, volatile compounds, and overall acceptability of Coriander leaves (Coriandrum sativum) during post-harvest storage. Coriander leaves are harvested at commercial maturity, packed in polyethylene terephthalate punnets, and exposed for 2 h to the red LED or blue LED lights separately during storage at 5°C and 85% RH up to 9 days. Coriander leaves exposed to the white light (2 h) and continuous darkness served as controls. Samples were removed from cold storage at 3, 6, and 9 days to determine the antioxidant constituents, their activity, retention of volatile compounds, and overall acceptance. Coriander leaves exposed to red and blue LED lights for 2 h showed a commercially allowable mass loss of up to 9 days compared to the other treatments. Compared to those exposed to red LED light (2 h) and the control, leaves exposed to blue LED light for 2 h and stored for 3–9 days showed a reduction in colour change (ΔE). The β-carotene content significantly peaked at 44.55% on day 6 in coriander leaves exposed to the red LED light. However, leaves exposed to blue and red LED light showed an increase in total phenolic content by 9.34 and 6.39% on day 9, respectively. Exposure to blue LED lights increased the antioxidant activities (DPPH, ABTS, and FRAP), quercetin content, and the concentration of typical coriander aroma, 2-tridecenal, 2-dodecenal, (E), and Z-9-19 hexadecenal on day 9. Coriander leaves exposed to blue LED light (2 h) and stored up to day 9 scored a higher acceptance level by the panellists. Thus, blue light LED treatment during post-harvest storage can be recommended to retain the antioxidant property of coriander leaves.
Association Between Wine Consumption and Cognitive Decline in Older People: A Systematic Review and Meta-Analysis of Longitudinal Studies
Authors: Lucerón-Lucas-Torres Maribel , Cavero-Redondo Iván , Martínez-Vizcaíno Vicente , Saz-Lara Alicia , Pascual-Morena Carlos , Álvarez-Bueno Celia
Published: May 2022

Background

Low-to-moderate alcohol consumption appears to have potential health benefits. Existing evidence concludes that wine may be associated with a lower incidence of certain diseases. This systematic review and meta-analysis aim to examine evidence on the association between wine consumption and cognitive decline and to analyze whether this association varies depending on the wine consumption level or is affected by individual and study characteristics, including mean age, percentage of women participants, and follow-up time.

Methods

In this systematic review and meta-analysis, we undertook a search in MEDLINE (via PubMed), Scopus, Cochrane, and Web of Science databases for longitudinal studies measuring the association between wine consumption and cognitive decline from their inception to May 2021. Effect sizes were calculated using the DerSimonian and Laird and Hartung-Knapp-Sidik-Jonkman methods.

Results

The search retrieved 6,055 articles, 16 of which were included in this systematic review. In total, 12 studies were included in the meta-analysis. The studies were published between 1997 and 2019. They were conducted in nine different countries. The sample size of the included studies ranged from 360 to 10,308 with a mean age of 70 years old. Using the DerSimoniand and Laird method, the pooled RR for the effect of wine consumption on cognitive decline was 0.72 (95% CI 0.63–0.80; I2 = 82.4%; τ2: 0.0154). Using the Hartung-Knapp-Sidik-Jonkman method, the RR was 0.65 (95% CI 0.52–0.79; I2 = 94,531%; τ2: 0.057).

Conclusions

This study may show a protective effect of wine consumption against cognitive decline. However, it would be important for future research to differentiate the types of wine within consumption.
Breast Milk and the Importance of Chrononutrition
Authors: Caba-Flores Mario Daniel , Ramos-Ligonio Angel , Camacho-Morales Alberto , Martínez-Valenzuela Carmen , Viveros-Contreras Rubí , Caba Mario
Published: May 2022

During pregnancy the human fetus receives timed cues from the circadian rhythms of temperature, metabolites, and hormones from the mother. This influence is interrupted after parturition, the infant does not secrete melatonin and their circadian rhythms are still immature. However, evolution provided the solution to this problem. The newborn can continue receiving the mother's timed cues through breastmilk. Colostrum, transitional, and mature human milk are extraordinary complex biofluids that besides nutrients, contain an array of other non-nutritive components. Upon birth the first milk, colostrum, is rich in bioactive, immunological factors, and in complex oligosaccharides which help the proper establishment of the microbiome in the gut, which is crucial for the infants' health. Hormones, such as glucocorticoids and melatonin, transfer from the mother's plasma to milk, and then the infant is exposed to circadian cues from their mother. Also, milk components of fat, proteins, amino acids, and endogenous cannabinoids, among others, have a markedly different concentration between day and night. In the present review, we give an overview of nutritive and non-nutritive components and their daily rhythms in human milk and explore their physiological importance for the infant. Finally, we highlight some interventions with a circadian approach that emphasize the importance of circadian rhythms in the newborn for their survival, proper growth, and development. It is estimated that ~600,000 deaths/year are due to suboptimal breastfeeding. It is advisable to increase the rate of exclusive breastfeeding, during the day and night, as was established by the evolution of our species.
Ginsenosides Rb1 Attenuates Chronic Social Defeat Stress-Induced Depressive Behavior via Regulation of SIRT1-NLRP3/Nrf2 Pathways
Authors: Jiang Ning , Zhang Yiwen , Yao Caihong , Huang Hong , Wang Qiong , Huang Shuangxue , He Qinghu , Liu Xinmin
Published: May 2022

Ginsenoside Rb1, a diol-type ginseng saponin, has various positive effects on the central nervous system. This study aimed to evaluate the antidepressant effects of Rb1 on chronic social defeat stress (CSDS) induced behavioral deficits and the exact neural cascades linked with inflammatory processes. The results of behavioral tests such as social interaction, tail suspension, and forced swimming revealed that oral treatment of Rb1 (35 and 70 mg/kg) alleviates depression-like behavior. Rb1 treatment increased antioxidant enzyme activity (SOD and CAT) and reduced lipid peroxidation (LPO) content in the hippocampus. Rb1 also suppressed the production of inflammatory cytokines (TNF-α, IL-18, and IL-1β) as well as microglial activation (Iba1) in response to CSDS. Moreover, Rb1 administration considerably reduced the protein expression of NLRP3 (inflammasome) and promoted the protein expressions of Nrf2, HO-1 and Sirtuin1(SIRT1) activation in the hippocampus. Our findings showed that Rb1 effectively restores the depressive-like behavior in CSDS-induced model mice, mediated in part by the normalization of oxidative stress levels. The suppression of neuroinflammation is mediated by the regulation of SIRT1-NLRP3/Nrf2 pathways. Our results asserted that the Rb1 is a novel therapeutic candidate for treating depression.
Illumina-Based Analysis Yields New Insights Into the Fungal Contamination Associated With the Processed Products of Crataegi Fructus
Authors: Yu Jingsheng , Guo Mengyue , Jiang Wenjun , Dao Yujie , Pang Xiaohui
Published: May 2022

Crataegi Fructus, a medicinal and edible herb in China, has been considered a popular dietary supplement globally. It is used for the treatment of dyspepsia and chronic heart failure according to the Chinese Pharmacopoeia (2020). However, fungal contamination in Crataegi Fructus affects its quality and safety, thus preventing its global promotion. In this study, we comprehensively studied the fungal community in processed products of Crataegi Fructus by high-throughput sequencing. A total of 21 Crataegi Fructus samples were collected from five provinces in China, and the samples were divided into five groups based on collection areas, as well as into three groups based on processing methods. We then targeted the internal transcribed spacer 2 sequence through the Illumina Miseq PE300 platform to investigate fungal composition and diversity. Results showed that all 21 samples were detected with fungal contamination, and Ascomycota was dominant at the phylum level. In the groups based on collection areas, Dothideomycetes, Pleosporaceae, andAlternariawere dominant at the class, family, and genus levels, respectively. In the groups based on processing methods, Dothideomycetes, Aspergillaceae, andAlternariawere the most abundant at the class, family, and genus levels, respectively. Differences in fungal communities between various groups were also observed. Furthermore, a total of 115 species were identified, among which seven were potential toxigenic, namely,Trichothecium roseum,Alternaria tenuissima,Aspergillus carbonarius,Penicillium brevicompactum,Aspergillus fumigatus,Rhizopus microspores, andPichia fermentans. In conclusion, this study reveals great fungal richness and diversity of Crataegi Fructus, providing references for the prevention and control of fungal contamination of Crataegi Fructus in practical production.
Inhibition of Dipeptidyl Peptidase-4 by Flavonoids: Structure–Activity Relationship, Kinetics and Interaction Mechanism
Authors: Pan Junkun , Zhang Qiang , Zhang Chunling , Yang Wenbo , Liu Hui , Lv Zhenzhen , Liu Jiechao , Jiao Zhonggao
Published: May 2022

With the aim to establish a structure-inhibitory activity relationship of flavonoids against dipeptidyl peptidase-4 (DPP-4) and elucidate the interaction mechanisms between them, a pannel of 70 structurally diverse flavonoids was used to evaluate their inhibitory activities against DPP-4, among which myricetin, hyperoside, narcissoside, cyanidin 3-O-glucoside, and isoliquiritigenin showed higher inhibitory activities in a concentration-dependent manner. Structure-activity relationship analysis revealed that introducing hydroxyl groups to C3', C4', and C6 of the flavonoid structure was beneficial to improving the inhibitory efficacy against DPP-4, whereas the hydroxylation at position 3 of ring C in the flavonoid structure was unfavorable for the inhibition. Besides, the methylation of the hydroxyl groups at C3', C4', and C7 of the flavonoid structure tended to lower the inhibitory activity against DPP-4, and the 2,3-double bond and 4-carbonyl group on ring C of the flavonoid structure was essential for the inhibition. Glycosylation affected the inhibitory activity diversely, depending on the structure of flavonoid aglycone, type of glycoside, as well as the position of substitution. Inhibition kinetic analysis suggested that myricetin reversibly inhibited DPP-4 in a non-competitive mode, whereas hyperoside, narcissoside, cyanidin 3-O-glucoside, and isoliquiritigenin all reversibly inhibited DPP-4 in a mixed type. Moreover, the fluorescence quenching analysis indicated that all the five flavonoid compounds could effectively quench the intrinsic fluorescence of DPP-4 by spontaneously binding with it to form an unstable complex. Hydrogen bonds and van der Waals were the predominant forces to maintain the complex of myricetin with DPP-4, and electrostatic forces might play an important role in stabilizing the complexes of the remaining four flavonoids with DPP-4. The binding of the tested flavonoids to DPP-4 could also induce the conformation change of DPP-4 and thus led to inhibition on the enzyme. Molecular docking simulation further ascertained the binding interactions between DPP-4 and the selected five flavonoids, among which hyperoside, narcissoside, cyaniding 3-O-glucoside, and isoliquiritigenin inserted into the active site cavity of DPP-4 and interacted with the key amino acid residues of the active site, whereas the binding site of myricetin was located in a minor cavity close to the active pockets of DPP-4.
The Methanol Extract of Polygonatum odoratum Ameliorates Colitis by Improving Intestinal Short-Chain Fatty Acids and Gas Production to Regulate Microbiota Dysbiosis in Mice
Authors: Ye Xuewei , Pi Xionge , Zheng Wenxin , Cen Yingxin , Ni Jiahui , Xu Langyu , Wu Kefei , Liu Wei , Li Lanjuan
Published: May 2022

The potential impacts of methanol extract from Polygonatum odoratum on (YZM) colonic histopathology, gut gas production, short-chain fatty acids (SCFAs), and intestinal microbiota composition were evaluated with dextran sulfate sodium (DSS)-induced colitis mice in this study. These results indicated that YZM increased colon length and ameliorated colonic histopathology in DSS-induced colitis mice. Moreover, YZM administration reversed intestinal microbiota compositions leading to the inhibition of H2S-related bacteria (e.g., Desulfovibrionaceae) and the lower level of H2S and higher contents of SCFA-related bacteria (e.g., Muribaculaceae). Taken together, the effects of methanol extract from Polygonatum odoratum are studied to provide new enlightenment and clues for its application as a functional food and clinical drug. Our study first revealed the relationship between intestinal gas production and key bacteria in ulcerative colitis.
Obesity by High-Fat Diet Increases Pain Sensitivity by Reprogramming Branched-Chain Amino Acid Catabolism in Dorsal Root Ganglia
Authors: Lian Nan , Luo Kaiteng , Xie Huijing , Kang Yi , Tang Kuo , Lu Peilin , Li Tao
Published: May 2022

Obesity is a significant health concern as a result of poor-quality diet, for example, high-fat diet (HFD). Although multiple biological and molecular changes have been identified to contribute to HFD-induced pain susceptibility, the mechanisms are not fully understood. Here, we show that mice under 8 weeks of HFD were sensitive to mechanical and thermal stimuli, which was coupled with an accumulation of branched-chain amino acids (BCAAs) in lumbar dorsal root ganglia (DRG) due to local BCAA catabolism deficiency. This HFD-induced hyperalgesic phenotype could be exacerbated by supply of excessive BCAAs or mitigated by promotion of BCAA catabolism via BT2 treatment. In addition, our results suggested that HFD-related pain hypersensitivity was associated with a pro-inflammatory status in DRG, which could be regulated by BCAA abundance. Therefore, our study demonstrates that defective BCAA catabolism in DRG facilitates HFD-induced pain hypersensitivity by triggering inflammation. These findings not only reveal metabolic underpinnings for the pathogenesis of HFD-related hyperalgesia but also offer potential targets for developing diet-based therapy of chronic pain.
A Comprehensive Comparison of Different Selenium Supplements: Mitigation of Heat Stress and Exercise Fatigue-Induced Liver Injury
Authors: Chen Xinwei , Zhang Jian , Li He , Liu Wanlu , Xi Yu , Liu Xinqi
Published: May 2022

This study aimed to compare the protective effects of different selenium supplements against heat stress and exercise fatigue-induced liver injury and to investigate the potential mechanisms of action. Selenium-enriched soybean protein (SePro), selenium-enriched soybean peptides (SePPs), and selenomethionine (SeMet) are organic selenium supplements in which selenium replaces the sulfur in their sulfur-containing amino acids. Common peptides (PPs) are obtained by enzymatic hydrolysis of soybean protein which was extracted from common soybean. The SePPs with higher hydrolysis degree and selenium retention were isolated via alkaline solubilization and acid precipitation and the enzymatic hydrolysis of alkaline protease, neutral protease, and papain. The results showed that SePPs could significantly increase the antioxidant levels in rats, inhibit lipid peroxidation, and reduce liver enzyme levels in rat serum, while the histological findings indicated that the inflammatory cell infiltration in the liver tissue was reduced, and new cells appeared after treatment with SePPs. Moreover, SePPs could increase glutathione (GSH) and GSH peroxidase (GSH-Px) in the liver, as well as protect the liver by regulating the NF-κB/IκB pathway, prevent interleukin 1β (IL-1β), interleukin 6 (IL-6), and tumor necrosis factor α (TNF-α) release in the liver. The SePPs displayed higher antioxidant and anti-inflammatory activity in vivo than SePro, SeMet, Sodium selenite (Na2SeO3), and PPs. Therefore, SePPs could be used as a priority selenium resource to develop heatstroke prevention products or nutritional supplements.
Evaluation of a Dedicated Software “Elements™ Spine SRS, Brainlab®” for Target Volume Definition in the Treatment of Spinal Bone Metastases With Stereotactic Body Radiotherapy
Authors: Rogé Maximilien , Henni Ahmed Hadj , Neggaz Yasmine Adda , Mallet Romain , Hanzen Chantal , Dubray Bernard , Colard Elyse , Gensanne David , Thureau Sébastien
Published: May 2022

Introduction

Stereotactic body radiotherapy (SBRT) is a treatment option for spine metastases. The International Spine Radiosurgery Consortium (ISRC) has published consensus guidelines for target delineation in spine SBRT. A new software called Elements™ Spine SRS by Brainlab® that includes the module Elements SmartBrush Spine (v3.0, Munich, Germany) has been developed specifically for SBRT treatment of spine metastases, and the latter provides the ability to perform semiautomatic clinical target volume (CTV) generation based on gross tumor volume (GTV) localization and guidelines. The aims of our study were to evaluate this software by studying differences in volumes between semiautomatic CTV contours compared to manual contouring performed by an expert radiation oncologist and to determine the dosimetric impact of these differences on treatment plans.

Methods

A total of 35 volumes (“Expert GTV” and “Expert CTV”) from 30 patients were defined by a single expert. A semiautomatic definition of these 35 CTVs based on the location of “Expert GTV” and following ISRC guidelines was also performed in Elements SmartBrush Spine (“Brainlab CTV”). The spatial overlap between “Brainlab” and “Expert” CTVs was calculated using the Dice similarity coefficient (DSC). We considered a threshold of 0.80 or above to indicate that Elements SmartBrush Spine performed very well with adequate contours for clinical use. Two dosimetric treatment plans, each corresponding to a specific planning target volume (PTV; Expert PTV, Brainlab PTV), were created for 11 patients.

Results

We showed that “Brainlab CTV” and “Expert CTV” mean volumes were 29.8 ± 16.1 and 28.7 ± 15.7 cm3, respectively (p = 0.23). We also showed that the mean DSC for semiautomatic contouring relative to expert manual contouring was 0.85 ± 0.08 and less than 0.80 in five cases. For metastases involving the vertebral body only (n = 13,37%), the mean DSC was 0.90 ± 0.03, and for ones involving other or several vertebral regions (n = 22.63%), the mean DSC was 0.81 ± 0.08 (p < 0.001). The comparison of dosimetric treatment plans was performed for equivalent PTV coverage. There were no differences between doses received by organs at risk (spinal cord and esophagus) for Expert and Brainlab PTVs, respectively.

Conclusion

The results showed that the semiautomatic method had quite good accuracy and can be used in clinical routine even for complex lesions.
TET1 Isoforms Have Distinct Expression Pattern, Localization and Regulation in Breast Cancer
Authors: Alzahayqa Mahmoud , Jamous Abrar , Khatib Areej A. H. , Salah Zaidoun
Published: May 2022

TET1 regulates gene expression by demethylating their regulatory sequences through the conversion of 5-methylcytosine to 5-hyroxymethylcytosine. TET1 plays important roles in tissue homeostasis. In breast cancer, TET1 was shown to play controversial roles. Moreover, TET1 has at least two isoforms (long and short) that have distinct expression pattern and apparently different functions in tissue development and disease including breast cancer. We hypothesized that TET1 isoforms have different expression patterns, localization and regulation in different types of breast cancer. To prove our hypothesis, we studied the expression of TET1 isoforms in basal and luminal breast cancer cell lines, as well as in basal and luminal breast cancer animal models. We also studied the effect of different hormones on the expression of the two isoforms. Moreover, we assessed the distribution of the isoforms between the cytoplasm and nucleus. Finally, we overexpressed the full length in a breast cancer cell line and tested its effect on cancer cell behavior. In this study, we demonstrate that while Estrogen and GnRH downregulate the expression of long TET1, they lead to upregulation of short TET1 expression. In addition, we uncovered that luminal cells show higher expression level of the long isoform. We also show that while all TET1 isoforms are almost depleted in a basal breast cancer animal model, the expression of the short isoform is induced in luminal breast cancer model. The short form is expressed mainly in the cytoplasm while the long isoform is expressed mainly in the nucleus. Finally, we show that long TET1 overexpression suppresses cell oncogenic phenotypes. In conclusion, our data suggest that TET1 isoforms have distinct expression pattern, localization and regulation in breast cancer and that long TET1 suppresses oncogenic phenotypes, and that further studies are necessary to elucidate the functional roles of different TET1 isoforms in breast cancer.
A Novel and Robust Prognostic Model for Hepatocellular Carcinoma Based on Enhancer RNAs-Regulated Genes
Authors: Zhang Wei , Chen Kegong , Tian Wei , Zhang Qi , Sun Lin , Wang Yupeng , Liu Meina , Zhang Qiuju
Published: May 2022

Evidence has demonstrated that enhancer RNAs (eRNAs) play a vital role in the progression and prognosis of cancers, but few studies have focused on the prognostic ability of eRNA-regulated genes (eRGs) for hepatocellular carcinoma (HCC). Using gene expression profiles of HCC patients from the TCGA-LIHC and eRNA expression profiles from the enhancer RNA in cancers (eRic) data portal, we developed a novel and robust prognostic signature composed of 10 eRGs based on Lasso-penalized Cox regression analysis. According to the signature, HCC patients were stratified into high- and low-risk groups, which have been shown to have significant differences in tumor immune microenvironment, immune checkpoints, HLA-related genes, DNA damage repair-related genes, Gene-set variation analysis (GSVA), and the lower half-maximal inhibitory concentration (IC50) of Sorafenib. The prognostic nomogram combining the signature, age, and TNM stage had good predictive ability in the training set (TCGA-LIHC) with the concordance index (C-index) of 0.73 and the AUCs for 1-, 3-, and 5-year OS of 0.82, 0.77, 0.74, respectively. In external validation set (GSE14520), the nomogram also performed well with the C-index of 0.71 and the AUCs for 1-, 3-, and 5-year OS of 0.74, 0.77, 0.74, respectively. In addition, an important eRG (AKR1C3) was validated using two HCC cell lines (Huh7 and MHCC-LM3) in vitro, and the results demonstrated the overexpression of AKR1C3 is related to cell proliferation, migration, and invasion in HCC. Altogether, our eRGs signature and nomogram can predict prognosis accurately and conveniently, facilitate individualized treatment, and improve prognosis for HCC patients.
Wnt/β-Catenin Inhibition by CWP232291 as a Novel Therapeutic Strategy in Ovarian Cancer
Authors: Wang Wenyu , Cho Untack , Yoo Anna , Jung Chae-Lim , Kim Boyun , Kim Heeyeon , Lee Juwon , Jo HyunA , Han Youngjin , Song Myoung-Hyun , Lee Ja-Oh , Kim Se Ik , Lee Maria , Ku Ja-Lok , Lee Cheol , Song Yong Sang
Published: May 2022

The poor prognosis of ovarian cancer patients mainly results from a lack of early diagnosis approaches and a high rate of relapse. Only a very modest improvement has been made in ovarian cancer patient survival with traditional treatments. More targeted therapies precisely matching each patient are strongly needed. The aberrant activation of Wnt/β-catenin signaling pathway plays a fundamental role in cancer development and progression in various types of cancer including ovarian cancer. Recent insight into this pathway has revealed the potential of targeting Wnt/β-catenin in ovarian cancer treatment. This study aims to investigate the effect of CWP232291, a small molecular Wnt/β-catenin inhibitor on ovarian cancer progression. Various in vitro, in vivo and ex vivo models are established for CWP232291 testing. Results show that CWP232291 could significantly attenuate ovarian cancer growth through inhibition of β-catenin. Noticeably, CWP232291 could also s suppress the growth of cisplatin-resistant cell lines and ovarian cancer patient-derived organoids. Overall, this study has firstly demonstrated the anti-tumor effect of CWP232291 in ovarian cancer and proposed Wnt/β-catenin pathway inhibition as a novel therapeutic strategy against ovarian cancer.
The LINC01929/miR-6875-5p/ADAMTS12 Axis in the ceRNA Network Regulates the Development of Advanced Bladder Cancer
Authors: Xiong YuFeng , Pang MingRui , Du Yang , Yu Xi , Yuan JingPing , Liu Wen , Wang Lei , Liu XiuHeng
Published: May 2022

Considering its speedy development and extremely low 5-year overall survival rate worldwide, bladder cancer (BCa) is one of the most common and highly malignant tumors. Increasing evidence suggests that protein-coding mRNAs and non-coding RNAs, including long non-coding RNAs (lncRNAs) and micro RNAs (miRNAs), play an essential role in regulating the biological processes of cancer. To investigate the molecular regulation associated with poor prognosis during advanced BCa development, we constructed a competitive endogenous RNA (ceRNA) network. Using transcriptome profiles from The Cancer Genome Atlas and Gene Expression Omnibus databases, we performed differential expression (DE) analysis, weighted gene co-expression network analysis, functional enrichment analysis, survival analysis, prediction of miRNA targeting, and Pearson correlation analysis. Through layers of selection, 8 lncRNAs-28 mRNAs and 8 miRNAs-28 mRNAs pairs shared similar expression patterns, constituting a core ceRNA regulatory network related to the invasion, progression, and metastasis of advanced clinical stage (ACS) BCa. Subsequently, we conducted real time qPCR, western blotting, and immunohistochemistry to validate expression trend bioinformatics analysis on 3, 2, and 3 differentially expressed mRNAs, lncRNAs, and miRNAs, respectively. The most significantly differentially expressed LINC01929, miR-6875-5p and ADAMTS12 were selected for in vitro experiments to assess the functional role of the LINC01929/miR-6875-5p/ADAMTS12 axis. RNA pull-down, luciferase assays, and rescue assays were performed to examine the binding of LINC01929 and miR-6875-5p. Increasing trends in COL6A1, CDH11, ADAMTS12, LINC01705, and LINC01929 expression variation were verified as consistent with previous DE analysis results in ACS-BCa, compared with low clinical stage (LCS) BCa. Expression trends in parts of these RNAs, such as hsa-miR-6875-5p, hsa-miR-6784-5p, COL6A1, and CDH11, were measured in accordance with DE analysis in LCS-BCa, compared with normal bladder urothelium. Through experimental validation, the cancer-promoting molecule ADAMST12 was found to play a key role in the development of advanced BCa. Functionally, ADAMTS12 knockdown inhibited the progression of bladder cancer. Overexpression of LINC01929 promoted bladder cancer development, while overexpression of miR-6785-5p inhibited bladder cancer development. Mechanistically, LINC01929 acted as a sponge for miR-6785-5p and partially reversed the role of miR-6785-5p. Our findings provide an elucidation of the molecular mechanism by which advanced bladder cancer highly expressed LINC01929 upregulates ADAMTS12 expression through competitive adsorption of miR-6875-5p. It provides a new target for the prognosis and diagnosis of advanced bladder cancer.
Identification of LSM Family Members as Novel Unfavorable Biomarkers in Hepatocellular Carcinoma
Authors: Zhuang Hongkai , Chen Bo , Tang Chenwei , Chen Xinming , Tan Wenliang , Yang Lei , Xie Zhiqin , Ma Xiaowu , Wang Qingbin , Zhang Chuanzhao , Shang Changzhen , Chen Yajin
Published: May 2022

Background

Smith-like (LSM) family members play critical roles in multiple oncologic processes in several types of malignancies. The study on LSM family members of HCC might provide new insights into the tumorigenesis and therapeutic strategies of HCC.

Methods

The clinical significance and oncologic biological functions of LSM family members were assessed through multiple bioinformatics methods and in vitro studies. The potential correlation between LSM family members and tumor immunity was also investigated using single sample gene set enrichment analysis (ssGSEA) and the ESTIMATE algorithm.

Results

LSM family member overexpression in HCC was significantly correlated with poor clinical outcomes such as higher TNM stage, advanced histologic grade, and worse prognosis. A risk score system based on LSM5, LSM10, LSM12, and LSM14B showed a reliable predictive ability for OS of HCC patients. Functional enrichment analysis demonstrated that LSM family members overexpressed were all involved in cell cycle related biological processes. Besides, LSM12, LSM14A, and LSM14B were found to be significantly associated with PI3K-Akt-mTOR and T cell receptor signaling pathways. Tumors with LSM12, LSM14A, and LSM14B overexpression exhibited lower infiltration of activated CD8+ T cells with declined cytolytic activity and immune score, but increased infiltration of Th2 cells and Th2/Th1. LSM12, LSM14A, and LSM14B overexpression is also associated with higher tumor-related immune checkpoints (e.g., PD-L1, B7-H3, and PVR) expression and increased therapeutic insensitivity to immune checkpoint blockade (ICB). Moreover, the knockdown of LSM12, LSM14A, and LSM14B significantly inhibited the proliferation and invasion of HCC cells.

Conclusion

This study systematically investigated the expression pattern and biological values of LSM family members in HCC and identified LSM family members as novel therapeutic targets in HCC.
Development and Validation of a Prediction Model for Positive Margins in Breast-Conserving Surgery
Authors: Zhao Rong , Xing Jun , Gao Jinnan
Published: May 2022

Background

The chances of second surgery due to positive margins in patients receiving breast-conversing surgery (BCS) were about 20-40%. This study aims to develop and validate a nomogram to predict the status of breast-conserving margins.

Methods

The database identified patients with core needle biopsy-proven ductal carcinoma in situ (DCIS) or invasive breast carcinoma who underwent BCS in Shanxi Bethune Hospital between January 1, 2015 and December 31, 2021 (n = 573). The patients were divided into two models: (1) The first model consists of 398 patients who underwent BCS between 2015 and 2019; (2) The validation model consists of 175 patients who underwent BCS between 2020 and 2021. The development of the nomogram was based on the findings of multivariate logistic regression analysis. Discrimination was assessed by computing the C-index. The Hosmer-Lemeshow goodness-of-fit test was used to validate the calibration performance.

Results

The final multivariate regression model was developed as a nomogram, including blood flow signals (OR = 2.88, p = 0.001), grade (OR = 2.46, p = 0.002), microcalcifications (OR = 2.39, p = 0.003), tumor size in ultrasound (OR = 2.12, p = 0.011) and cerbB-2 status (OR = 1.99, p = 0.042). C-indices were calculated of 0.71 (95% CI: 0.64-0.78) and 0.68 (95% CI: 0.59-0.78) for the modeling and the validation group, respectively. The calibration of the model was considered adequate in the validation group (p > 0.05).

Conclusion

We developed a nomogram that enables the estimation of the preoperative risk of positive BCS margins. Our nomogram provides a valuable tool for identifying high-risk patients who might have to undergo a wider excision.
Distinct Age-Related Clinical Features and Risk Assessment in Chinese With Chronic Lymphocytic Leukemia
Authors: Tian Zheng , Liu Ming , Fang Xiaosheng , Zhou Xiangxiang , Li Peipei , Li Ying , Zhang Lingyan , Liu Fang , Zhang Ya , Wang Xin
Published: May 2022

The biological and clinical features of chronic lymphocytic leukemia (CLL) exhibited profound heterogeneity across Chinese and patients of predominately European descent. However, the age-related peculiarities and risk assessment of Chinese CLL patients remained ill-defined. The present study demonstrated that CLL patients were characterized by the earlier age at onset in China (median age at diagnosis: 63 years old) than in the United States (median age at diagnosis: 69 years old). Young patients from Shandong Provincial Hospital CLL database displayed prolonged overall survival than the Surveillance, Epidemiology, and End Results cohort. Furthermore, among Chinese CLL patients, young patients showed an increased relapse rate compared with elderly patients. To optimize the risk assessment of CLL patients, novel risk score models named PR-Score and HBG-Score were developed for predicting the outcomes of young and elderly CLL patients respectively. The neonatal survival prediction systems were superior to international prognostic index for CLL (CLL-IPI) and Binet stage in assessing the overall survival and progression free survival of CLL patients. The analyses highlighted refinement of risk evaluation for CLL patients in different age groups, providing insights into individualized diagnosis and treatment of CLL.
Comprehensive Analysis of Sterol O-Acyltransferase 1 as a Prognostic Biomarker and Its Association With Immune Infiltration in Glioma
Authors: Guo Xuyang , Zhou Shaolong , Yang Zhuo , Li Zi-An , Hu Weihua , Dai Lirui , Liang Wulong , Wang Xinjun
Published: May 2022

Metabolic reprogramming is a hallmark of glioma, and sterol O-acyltransferase 1 (SOAT1) is an essential target for metabolic therapy. However, the prognostic value of SOAT1 and its association with immune infiltration has not been fully elucidated. Using RNA-seq and clinical data of glioma patients from The Cancer Genome Atlas (TCGA), SOAT1 was found to be correlated with poor prognosis in glioma and the advanced malignancy of clinicopathological characteristics. Next, the correlation between SOAT1 expression and tumor-infiltrating immune cells was performed using the single-sample GSEA algorithm, gene expression profiling interactive analysis (GEPIA), and tumor immune estimation resource version 2 (TIMER2.0); it was found that SOAT1 expression was positively correlated with multiple tumor-infiltrating immune cells. To further verify these results, immunofluorescence was conducted on paraffin-embedded glioma specimens, and a positive trend of the correlation between SOAT1 expression and Treg infiltration was observed in this cohort. Finally, differentially expressed gene analysis, and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed to explore the biological processes and signaling pathways that SOAT1 may be involved in during glioma pathogenesis. A protein-protein interaction network was established, and co-expression analysis was conducted to investigate the regulatory mechanism of SOAT1 in glioma. To the best of our knowledge, this is the first comprehensive study reporting that SOAT1 may serve as a novel prognostic biomarker associated with immune infiltrates, providing a novel perspective for glioma metabolic therapy.
Vision-Related Quality of Life in Patients With Atypical Optic Neuritis
Authors: Jiang Zhaocai , Qian Haiyan , Wei Shihui
Published: May 2022

Aim

To evaluate the vision-related quality of life (QOL) in patients with atypical optic neuritis through the 39-item National Eye Institute Visual Function Questionnaire (NEI VFQ-39).

Methods

Fifty-seven patients with atypical optic neuritis were scheduled in the research unit from June 1 to December 31, 2019. Besides collecting the clinical data, NEI VFQ-39, the Chinese version, was applied to all subjects. The NEI VFQ-39 subscale item scores were compared among subgroups divided by different classifications, and a correlation analysis of the NEI VFQ-39 scores and best-corrected visual acuity (BCVA) for better-seeing and worse-seeing eyes was performed.

Results

The mean age of scheduled patients was 34.3 ± 12.4 years, with the majority being female (70.2%). The mean composite score was 58.62 ± 17.62. Twenty-nine (50.9%) patients were affected binocularly, and the most subscale scores and composite scores of binocular incidences were lower than those of monocular incidence significantly. However, there was no statistically significant difference in composite scores between patients with and without periocular pain. The patients with worse BCVA in the better-seeing eye have lower scores than those with better BCVA in the better-seeing eye. Most NEI VFQ-39 scores have strong correlations with the BCVA for better-seeing and worse-seeing eyes.

Conclusion

Atypical optic neuritis has a significant and comprehensive influence on patients' visual function outcomes and quality of life associated with vision. Improving their BCVA in the better-seeing eye can improve their vision-related QOL.
Stillbirth and Associated Factors Among Women Who Gave Birth at Hiwot Fana Specialized University Hospital, Harar, Eastern Ethiopia
Authors: Mengistu Seble , Debella Adera , Mulatu Teshale , Mesfin Firehiwot , Danusa Kababa Temesgen , Dheresa Merga
Published: May 2022

Background

Stillbirth, which accounts for half of all the perinatal mortality, is not counted on policy, program, and investment agendas around the globe. It has been underestimated public health burden, particularly in developing countries. Ethiopia is among the top countries with a large prevalence of stillbirth in the world. However, there is a dearth of study on the current magnitude of stillbirth in the study area. Therefore, this study intended to assess the prevalence of stillbirth and its associated factors to bridge the gap.

Methods

A hospital-based retrospective study was conducted from 1 to 28 February 2019 and data were collected by reviewing the chart records of all the women who gave birth in the past 2 years (January 2016 to December 2018) at Hiwot Fana Specialized University Hospital. Data were entered into EpiData version 4.2.0.0 software and transported to SPSS version 23 for analysis. Descriptive statistics such as frequency, mean, and SDs were generated. Determinants of stillbirth were analyzed using a binary logistic regression and presented by adjusted odds ratio (AOR) with a 95% CI.

Results

The prevalence of stillbirth was 14.5% (95% CI: 11.7%, 17.6%). Low birth weight (AOR = 2.42, 95% CI: 1.23–4.76), prematurity (AOR = 2.10, 95% CI: 1.10–4.01), premature rupture of membranes (AOR = 2.08, 95% CI: 1.14–3.77), antepartum hemorrhage (AOR = 3.33, 95% CI: 1.66–6.67), obstructed labor (AOR = 2.87, 95% CI: 1.48–5.56), and preeclampsia (AOR = 2.91, 95% CI: 1.28–6.62) were an independently associated with stillbirth.

Conclusion

The prevalence of stillbirth in this study was high. Low birth weight, preterm birth, premature rupture of membranes, antepartum hemorrhage, obstructed labor, and preeclampsia were independently associated with a stillbirth. Therefore, much study is needed involving different stakeholders to reduce stillbirths by improving the health status of women through the provision of quality maternal care including referral systems.
COVID-19 Pandemic-Related Restrictions: Factors That May Affect Perinatal Maternal Mental Health and Implications for Infant Development
Authors: Kokkinaki Theano , Hatzidaki Eleftheria
Published: May 2022

This review aims to discuss the factors that may affect maternal mental health and infant development in COVID-19 pandemic condition. Toward this direction, the two objectives of this review are the following: (a) to discuss possible factors that may have affected negatively perinatal mental health through the pandemic-related restrictions; and (b) to present the implications of adversely affected maternal emotional wellbeing on infant development. We conclude that the pandemic may has affected maternal mental health with possible detrimental effects for the infants of the COVID-19 generation. We highlight the need for evidence-based interventions to be integrated within the health system for prenatal and postpartum care in an effort to promote maternal mental health and infant development.