bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluating the use of synthetic T1-w images in new T2 lesion detection in multiple sclerosis
Authors: Valencia Liliana , Clèrigues Albert , Valverde Sergi , Salem Mostafa , Oliver Arnau , Rovira Àlex , Lladó Xavier
Published: September 2022

The assessment of disease activity using serial brain MRI scans is one of the most valuable strategies for monitoring treatment response in patients with multiple sclerosis (MS) receiving disease-modifying treatments. Recently, several deep learning approaches have been proposed to improve this analysis, obtaining a good trade-off between sensitivity and specificity, especially when using T1-w and T2-FLAIR images as inputs. However, the need to acquire two different types of images is time-consuming, costly and not always available in clinical practice. In this paper, we investigate an approach to generate synthetic T1-w images from T2-FLAIR images and subsequently analyse the impact of using original and synthetic T1-w images on the performance of a state-of-the-art approach for longitudinal MS lesion detection. We evaluate our approach on a dataset containing 136 images from MS patients, and 73 images with lesion activity (the appearance of new T2 lesions in follow-up scans). To evaluate the synthesis of the images, we analyse the structural similarity index metric and the median absolute error and obtain consistent results. To study the impact of synthetic T1-w images, we evaluate the performance of the new lesion detection approach when using (1) both T2-FLAIR and T1-w original images, (2) only T2-FLAIR images, and (3) both T2-FLAIR and synthetic T1-w images. Sensitivities of 0.75, 0.63, and 0.81, respectively, were obtained at the same false-positive rate (0.14) for all experiments. In addition, we also present the results obtained when using the data from the international MSSEG-2 challenge, showing also an improvement when including synthetic T1-w images. In conclusion, we show that the use of synthetic images can support the lack of data or even be used instead of the original image to homogenize the contrast of the different acquisitions in new T2 lesions detection algorithms.
Frequency-specific alterations in intrinsic low-frequency oscillations in newly diagnosed male patients with obstructive sleep apnea
Authors: Zeng Yaping , Shu Yongqiang , Liu Xiang , Li Panmei , Kong Linghong , Li Kunyao , Xie Wei , Zeng Li , Long Ting , Huang Ling , Li Haijun , Peng Dechang
Published: September 2022

Purpose

Previous studies found abnormal low-frequency spontaneous brain activity related to cognitive impairment in patients with obstructive sleep apnea (OSA). However, it is unclear if low-frequency spontaneous brain activity is related to specific frequency bands in OSA patients. In this study, we used the amplitude of low-frequency fluctuation (ALFF) method in patients with OSA to explore characteristics of spontaneous brain activity in the classical (0.01–0.1 Hz) and five sub-frequency bands (slow-2 to slow-6) and analyzed the relationship between spontaneous brain activity and clinical evaluation was analyzed.

Patients and methods

Resting-state magnetic resonance imaging data and clinical assessments were collected from 52 newly-diagnosed OSA patients and 62 healthy controls (HCs). We calculated the individual group ALFF values in the classical and five different sub-frequency bands. A two-sample t-test compared ALFF differences, and one-way analysis of variance explored interactions in frequency bands between the two groups.

Results

ALFF values in the OSA group were lower than those in the HC group in the bilateral precuneus/posterior cingulate cortex, bilateral angular gyrus, left inferior parietal lobule, brainstem, and right fusiform gyrus. In contrast, ALFF values in the OSA group were higher than those in the HC group in the bilateral cerebellum posterior lobe, bilateral superior frontal gyrus, bilateral middle frontal gyrus, left inferior frontal gyrus, left inferior temporal gyrus, and left fusiform gyrus. Some ALFF values in altered brain regions were associated with body mass index, apnea-hypopnea index, neck circumference, snoring history, minimum SaO2, average SaO2, arousal index, oxygen reduction index, deep sleep period naming, abstraction, and delayed recall in specific frequency bands.

Conclusion

Our results indicated the existence of frequency-specific differences in spontaneous brain activity in OSA patients, which were related to cognitive and other clinical symptoms. This study identified frequency-band characteristics related to brain damage, expanded the cognitive neuroimaging mechanism, and provided additional OSA neuroimaging markers.
Repeated inhibition of sigma-1 receptor suppresses GABAA receptor expression and long-term depression in the nucleus accumbens leading to depressive-like behaviors
Authors: Qin Yaoyao , Xu Weixing , Li Kunpeng , Luo Qi , Chen Xi , Wang Yue , Chen Lei , Sha Sha
Published: September 2022

Sigma-1 receptor (σ1R) downregulation in male mice is known to cause a depressive-like phenotype. The nucleus accumbens (NAc), a region associated with affective regulation, has high levels of σ1R. Here, we investigated the effect of repeated inhibition of σ1R in the NAc on depressive-like behaviors and synaptic plasticity by microinjecting σ1R antagonist NE-100 into NAc nuclei in mice (NE-100 mice); this was followed by behavioral tests and field potentials recordings. We first examined the effect of NE-100 administration on σ1R expression and found that cell surface levels of σ1R were significantly reduced in the NAc of NE-100 mice. Compared to control mice, NE-100 mice exhibited significantly prolonged immobility in forced swim test (FST) and tail suspension test (TST), impaired long-term depression (LTD) as well as multi-spike waveform field excitatory postsynaptic potential (fEPSP) with an extended duration and an increased paired-pulse ratio (PPR). Reduced levels of GABAA receptor (GABAAR)-α1, -α2, -β2, and -β3 subunits, membrane D2R, and PKC phosphorylation in the NAc were observed in NE-100 mice. Activation of GABAAR by muscimol corrected the extended fEPSP duration and increased PPR, restored LTD maintenance as well as alleviated depressive-like behaviors in NE-100 mice. The decline of PKC phosphorylation in the NAc of NE-100 mice was corrected by injecting NAc with quinpirole, a D2R agonist. Injections of quinpirole or PMA (a PKC activator) into NAc of NE-100 mice rescued the expression levels of GABAAR, and alleviated the increase in PPR and impairment in LTD; these effects were sensitive to GF109203X, a PKC inhibitor. Furthermore, injecting NAc with quinpirole or PMA relieved depressive-like behaviors in NE-100 mice. Collectively, these results indicate that repeated inhibition of σ1R in the NAc reduces D2R-mediated PKC phosphorylation and suppresses GABAAR expression, thus impairing LTD maintenance and leading to depressive-like behaviors.
A subpopulation of agouti-related peptide neurons exciting corticotropin-releasing hormone axon terminals in median eminence led to hypothalamic-pituitary-adrenal axis activation in response to food restriction
Authors: Yesmin Ruksana , Watanabe Miho , Sinha Adya Saran , Ishibashi Masaru , Wang Tianying , Fukuda Atsuo
Published: September 2022

The excitatory action of gamma-aminobutyric-acid (GABA) in the median-eminence (ME) led to the steady-state release of corticotropin-releasing hormone (CRH) from CRH axon terminals, which modulates the hypothalamic-pituitary-adrenal (HPA) axis. However, in ME, the source of excitatory GABAergic input is unknown. We examined agouti-related peptide (AgRP) expressing neurons in the arcuate nucleus as a possible source for excitatory GABAergic input. Here, we show that a subpopulation of activated AgRP neurons directly project to the CRH axon terminals in ME elevates serum corticosterone levels in 60% food-restricted mice. This increase in serum corticosterone is not dependent on activation of CRH neuronal soma in the paraventricular nucleus. Furthermore, conditional deletion of Na+-K+-2Cl– cotransporter-1 (NKCC1), which promotes depolarizing GABA action, from the CRH axon terminals results in significantly lower corticosterone levels in response to food restriction. These findings highlight the important role of a subset of AgRP neurons in HPA axis modulation via NKCC1-dependent GABAergic excitation in ME.
A longitudinal investigation of dietary diversity during the COVID-19 pandemic in Mandinka households in Kanifing, Brikama, and the West Kiang region in The Gambia
Authors: Sidebottom Richard , Wassie Solomon Bizuayehu , Cerami Carla , Jallow Momodou W. , Fennell Shailaja , Dalzell Sarah
Published: September 2022

The Covid pandemic has exposed fissures of inequality through heightened food insecurity and nutritional deficiency for vulnerable social cohorts with limited coping mechanisms. Given the multi-dimensional pathways through which its effects have been felt, several researchers have highlighted the need to analyse the pandemic in specific contexts. Using random and fixed effect regression models, this study analyzed longitudinal survey data collected from 103 Mandinka households in rural and urban Gambia. The study employed convenience and snowball sampling and involved the monthly collection of detailed income, food consumption, expenditure, sourcing, migration, health, and coping mechanism data through mobile phone interviews which yielded 676 observations. Food insecurity was manifest in terms of quality, not quantity, and spread unevenly across food types and households. Dietary outcomes and sourcing strategies were associated with location, improved sanitation, household size, changes in monthly income, Covid policy stringency, and Covid cases but these associations varied by food group. Staples were the most frequently consumed food group, and dark green vegetables were the least. Rural communities were more likely to eat more healthy millets but much less likely to consume dairy products or roots and tubers. Access to own production was also important for Vitamin A-rich foods but higher incomes and markets were key for protein and heme-iron-rich foods. Tighter Covid policy stringency was negatively associated with dietary diversity and, along with fear of market hoarding, was positively associated with reliance on a range of consumption and production coping mechanisms. Resilience was higher in larger households and those with improved water and sanitation. The number of Covid cases was associated with higher consumption of protein-rich foods and greater reliance on own produced iron-rich foods. Very few households received Government aid and those that did already had access to other income sources. Our findings suggest that the nature of food insecurity may have evolved over time during the pandemic. They also reiterate not only the importance of access to markets and employment but also that the capacity to absorb affordability shocks and maintain food choices through switching between sources for specific nutritious food groups varied by household and location.
A negative association between total cholesterol and bone mineral density in US adult women
Authors: Fang Weihua , Peng Peng , Xiao Fangjun , He Wei , Wei Qiushi , He Mincong
Published: September 2022

Background

The association between serum total cholesterol (TC) and bone mineral density (BMD) is still controversial. We aimed to evaluate the association of serum TC with BMD in general US adult women.

Methods

A cross-sectional study consisting of 7,092 (age range 20–85) participants from the National Health and Nutrition Examination Survey (NHANES) database was conducted. Weighted multivariate linear regression analyses were performed to evaluate association between serum TC and lumbar spine BMD. In addition, subgroup and interaction analysis were used in this study.

Results

The serum TC was negatively correlated with lumbar spine BMD after adjusting for confounders. Subgroup analysis found that the strongest negative association mainly exists in women aged over 45 years with body mass index (BMI) < 24.9 kg/m2, and this association is not significant in other groups.

Conclusions

This study found that serum TC exhibit an inverse association with lumbar spine BMD in Us women aged over 45 years. The measurement of serum TC may provide information for predicting poor bone health outcomes in these women.
On the mechanism of the cholesterol lowering ability of soluble dietary fibers: Interaction of some bile salts with pectin, alginate, and chitosan studied by isothermal titration calorimetry
Authors: Massa Michele , Compari Carlotta , Fisicaro Emilia
Published: September 2022

Reducing high blood cholesterol is an important strategy to decrease the chances of a cardiovascular disease occurrence, the main cause of mortality in western developed countries. Therefore, the search for an alternative therapeutic or preventive approach being natural, biocompatible, and not toxic is still more relevant than ever. This need is particularly felt in Pediatrics for treating childhood hypercholesterolemia, due to statins interference in the production of steroid hormones in prepuberal children. Notwithstanding the general acceptance of the healthy role of the fibers in the diet, the mechanism underlying the cholesterol-lowering ability of soluble fibers is still under discussion. Therefore, we started a systematic study of the binding ability of some soluble dietary fibers (SDF) originated from different natural sources toward selected bile salts (BS) by isothermal titration calorimetry (ITC). Here we report the results of our ITC studies on the interaction of alginate, pectin and chitosan with sodium cholate (NaC), sodium deoxycholate (NaDC), sodium taurocholate (NaTC) and sodium taurodeoxycholate (NaTDC). Thermodynamic data on the micelle formation process of the above bile salts, as a premise to the study of their binding ability to the SDF, are also reported. Alginate does not show specific binding interaction with BS, while pectin shows a strong exothermic bond with NaDC in monomeric form. Chitosan, positively charged and soluble only at low pH, shows strong exothermic interactions with NaTC and NaTDC (soluble at pH = 3 in acetate buffer) with precipitate formation. For NaTC, the exothermic peak starts at about 5 mM. At this concentration NaTC bound on the fiber reaches locally the cmc value and micelles start forming on the fiber inducing its conformational change. For NaTDC the same process occurs at much lower concentrations, due to lower cmc, and with a greater quantity of heat involved. The first set of results here presented shows that for some SDF the binding of BS could be an important mechanism in cholesterol lowering but not the only one. The information here presented could be a starting point for the design of optimized functional foods with high cholesterol lowering ability.
Peking prognostic score is a useful prognostic factor in patients with gastric cancer liver metastases receiving hepatectomy
Authors: Xiong Jianping , Wu Yunzi , Hu Haitao , Kang Wenzhe , Li Yang , Jin Peng , Shao Xinxin , Li Weikun , Xie Yibin , Tian Yantao
Published: September 2022

Background

The present work evaluated how Peking prognostic score (PPS), the new prognostic index determined according to sarcopenia and lymphocyte-to-C-reactive protein ratio (LCR), was a prognostic factor for patients with gastric cancer liver metastases (GCLM) who received hepatectomy.

Methods

This work extracted information about patients with GCLM who underwent hepatectomy from June 2012 to May 2018. The PPS of the patients was calculated from sarcopenia status and LCR before surgery, and patients were then divided into three groups based on their PPS. This work also carried out univariate and multivariate analyses for identifying variables that were linked with overall survival (OS) together with recurrence-free survival (RFS) after hepatectomy among three groups according to PPS.

Results

This work included 108 GCLM cases who received hepatectomy. All cases were classified into 3 groups, i.e., 26 (24.1%), 48 (44.4%), and 34 (31.5%) in groups 0–2, separately. PPS exhibited positive relation with age (p < 0.001), body mass index (BMI; p = 0.012), and liver metastasis number. The relapse rate after hepatectomy in patients with GCLM was 69.4%. Additionally, the remnant liver relapse rates of groups 0–2 were 80.0, 68.7, and 53.5%. Patients in group 0 had significantly increased remnant liver relapse rates when compared with those in groups 0 and 1. PPS was significantly related to relapse patterns (p = 0.003). Relative to group 0, those of the other 2 groups showed dismal OS [hazard ratio (HR) = 3.98, 7.49 for groups 1 and 2; p < 0.001] along with RFS (HR = 3.65, 5.33 for groups 1 and 2; p < 0.001). As revealed by multivariate analysis, PPS independently predicted OS (p < 0.001) together with RFS (p < 0.001).

Conclusion

The PPS could be an easy nutrition-inflammation prognostic scoring system and an independent preoperative predictor of survival for GCLM cases after hepatectomy.
Oxidative stability and elemental analysis of sunflower (Helianthus annuus) edible oil produced in Brazil using a domestic extraction machine
Authors: Machate David Johane , Melo Elaine S. P. , Oliveira Lincoln Carlos Silva de , Bogo Danielle , Michels Flávio S. , Pott Arnildo , Cavalheiro Leandro F. , Guimarães Rita de Cássia Avellaneda , Freitas Karine de Cássia , Hiane Priscila Aiko , Caires Anderson R. L. , Vilela Marcelo Luiz Brandão , Oliveira Rodrigo Juliano , Nascimento Valter Aragão do
Published: September 2022

The consumption of regular vegetable oils has been linked to energy acquisition, nutritional benefits, health improvement, and the regulation of metabolic diseases. This study evaluated fatty acids composition, physicochemical, thermal, oxidative, and optical properties, and quantified trace elements in the sunflower oil extracted by a domestic cold-press machine. The oil presented linoleic (54.00%) and oleic (37.29%) primary unsaturated fatty acids (91.67%), in which atherogenic (0.05), thrombogenic (0.16), hypocholesterolemic/hypercholesterolemic (21.97), peroxide (16.16), saponification (141.80), and relative density indices (0.92) demonstrated to be suitable for human consumption and possible health promotion. In addition, the concentrations of trace elements by ICP OES were ordered Zn > Fe > Al > Cu > Mn > Cr. Concentrations of Zn, Fe, Al, Cu, and Mn were lower than FAO/WHO and DRI/AI limits, while Cr concentrations exceeded the FAO/WHO limits, which can be used as an indicator of the polluted ambiance. Sunflower oil quantities daily consumption were calculated by taking into account non-carcinogenic risk (CR < 10−4), and total non-carcinogenic hazard index (HI < 1). Based on trace elements determined in this study, the suitable quantity of sunflower oil consumption varies according to individuals aged 8, 18, and 30 years and will be deemed 0.61, 1.46, and 1.65 g/kg, respectively, attending HI = 0.99 and CR < 10−4.
Probiotic effects of Lacticaseibacillus rhamnosus 1155 and Limosilactobacillus fermentum 2644 on hyperuricemic rats
Authors: Li Yanjun , Zhu Jun , Lin Guodong , Gao Kan , Yu Yunxia , Chen Su , Chen Lie , Chen Zuoguo , Li Li
Published: September 2022

Hyperuricemia is the main cause of gout and involved in the occurrence of multiple diseases, such as hypertension, metabolic disorders and chronic kidney disease. Emerging evidence suggests that lactic acid bacteria (LAB) have shown the beneficial effects on the prevention or treatment of hyperuricemia. In this study, the urate-lowering effect of two LAB strains, Lacticaseibacillus rhamnosus 1155 (LR1155) and Limosilactobacillus fermentum 2644 (LF2644) on hyperuricemic rats were investigated. A hyperuricemic rat model was induced by the intragastric treatment of potassium oxonate, combined with a high purine diet. The oral administration of LR1155, LF2644, or a combination of LR1155 and LF2644 for 4 weeks significantly prevented the rise of the serum uric acid (UA) induced by hyperuricemia. LR1155 and LF2644 significantly elevated the fecal UA levels, increased the UA content and up-regulated gene expression of UA transporter, ATP-binding cassette subfamily G-2 (ABCG2), in colon and jejunum tissues, suggesting the accelerated UA excretion from the intestine. Besides, LR1155 significantly inhibited the activity of xanthine oxidase (XOD) in liver and serum, benefited the reduce of UA production. In addition, LF2644 strengthened the gut barrier functions through an up-regulation of the gene expressions for occluding and mucin2, accompanied with the reduced inflammatory indicators of lipopolysaccharide (LPS) and interleukin-1β (IL-1β) in hyperuricemic rat. Moreover, using 16s rDNA high-throughput sequencing of feces, LR1155 was shown to improve the hyperuricemia induced gut microbial dysbiosis. The genera Roseburia, Butyricicoccus, Prevotella, Oscillibacter, and Bifidobacterium may associate with the effect of LR1155 on microbiota in hyperuricemic rats. Collectively, the results indicated that LR1155 and LF2644 exhibit urate-lowering effects and could be used alone or in combination as a new adjuvant treatment for hyperuricemia.
Functional role of cyanidin-3-O-glucoside in osteogenesis: A pilot study based on RNA-seq analysis
Authors: Chen Lin , Hu Bosen , Wang Xiaohong , Chen Yong , Zhou Bo
Published: September 2022

Cyanidin-3-O-glucoside (C3G) is the most widely distributed anthocyanin and it can reportedly reduce the risk of osteoporosis, but the molecular mechanism by which C3G promotes bone formation is poorly understood. In the current study, RNA sequencing (RNA-seq) was used to investigate the mechanism of action of C3G in osteogenesis. MC3T3-E1 mouse osteoblasts were divided into a C3G (100 μmol/L)-treated group and a vehicle-treated control group, and differentially expressed genes (DEGs) in groups were evaluated via RNA-seq analysis. The functions of the DEGs were evaluated by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, and the genes were validated by quantitative real-time PCR. The RNA-seq analysis identified 34 genes that were upregulated in C3G-treated cells compared to vehicle-treated cells, and 17 that were downregulated GO and KEGG pathway analyses indicated that these genes were highly enriched in functions related to lysosomes and glycolipid biosynthesis, among others. The differential expression of ATPase H+-transporting V0 subunit C (Atp6v0c), chemokine (C-X3-C motif) ligand 1 (Cx3cl1), and lymphocyte antigen 6 complex, locus A (Ly6a) genes was validated by quantitative real-time-PCR. Because these genes have been previously implicated in osteoporosis, they are potential target genes of C3G action in MC3T3-E1 cells. These results provide molecular level evidence for the therapeutic potential of C3G in the treatment of osteoporosis and other disorders of bone metabolism.
Prognostic significance of lncRNA AP004608.1 in prostate cancer
Authors: Li Wei , Zhou Runze , Sun Bo , Jin Xin , Chen Yuan , Xu Xuefen
Published: September 2022

This study aimed to screen and determine the value of AP004608.1 expression as a biomarker for Prostate cancer (PCa) survival. We investigated the expression and prognosis of AP004608.1 through bioinformatics analysis. Low AP004608.1 expression predicted favorable Overall survival (OS) and Progression-free survival (PFS) in PCa patients, according to the Cancer Genome Atlas (TCGA) database. Cox regression demonstrated that low AP004608.1 expression were in-dependent biomarkers for OS. Moreover, Gene Expression Omnibus (GEO) database was utilized to verify the prognostic role of AP004608.1 in PCa, and the similar results were reached. A meta-analysis revealed that low AP004608.1 expression was closely relevant to better OS. AP004608.1 could constitute a promising prognostic biomarker, and probably plays an important role in PCa.
APOBEC3B is overexpressed in cervical cancer and promotes the proliferation of cervical cancer cells through apoptosis, cell cycle, and p53 pathway
Authors: Wei Zhi , Gan Jianfeng , Feng Xuan , Zhang Mo , Chen Zhixian , Zhao Hongbo , Du Yan
Published: September 2022

Objective

APOBEC3B (A3B), a member of the APOBEC family of cytidine deaminases, has been gradually regarded as a key cancerous regulator. However, its expression and mechanism in cervical cancer (CC) have not been fully elucidated. This study was to investigate its expression pattern and potential mechanism on the cell cycle, as well as HPV oncogenes in CC.

Methods

Data from The Cancer Genome Atlas (TCGA) and Gene Expression (GEO) were used to indicate the mRNA expression pattern of A3B in cervical cancer. Western blot assay was used to detect A3B levels in SiHa and Hela cell lines. Immunohistochemistry (IHC) was used to explore A3B protein abundance and sublocation in cervical cancer as well as normal cervical tissues. Based on the Protein atlas (www.proteinatlas.org), A3B expression in the SiHa cell line is lower than in the HeLa cell line. Therefore, the SiHa cell line was used for A3B gene overexpression experiments while the HeLa cell line was used for knockdown experiments. Flow cytometry analysis was used to detect cell apoptosis. Biological function and cancer-related pathways of A3B were conducted using bioinformatics analysis.

Results

A3B mRNA was significantly overexpressed in cervical cancer in TCGA-cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), GSE67522, and GSE7803. A3B was more highly expressed in cervical cancers than in high-grade squamous intraepithelial lesions and normal controls. A3B expression was found to be progressively activated during cervical cancer development. IHC results showed that A3B was significantly higher in cervical cancer tissues than in normal cervical tissues. A3B plasmid-mediated overexpression experiments and A3B siRNA-mediated knockdown experiments showed that A3B significantly promotes cell proliferation, migration, cell cycle, and chemoresistance in cervical cancer cells by the p53 pathway. GO and KEGG analyses showed that A3B expression was strikingly associated with cell proliferation, apoptosis, and immune-associated pathways.

Conclusions

Taken together, our study implies that A3B promotes cell proliferation, migration, and cell cycle and inhibits cancer cell apoptosis through the p53-mediated signaling pathway. Moreover, A3B could also contribute to chemoresistance in cervical cancer cells. It may be a potential diagnostic biomarker and therapeutic target for chemoresistant cervical cancers.
Reliability of gradient-based segmentation for measuring metabolic parameters influenced by uptake time on 18F-PSMA-1007 PET/CT for prostate cancer
Authors: Lau Yu Ching , Chen Sirong , Ho Chi Lai , Cai Jing
Published: September 2022

Purpose

To determine an optimal setting for functional contouring and quantification of prostate cancer lesions with minimal variation by evaluating metabolic parameters on 18F-PSMA-1007 PET/CT measured by threshold-based and gradient-based methods under the influence of varying uptake time.

Methods and materials

Dual time point PET/CT was chosen to mimic varying uptake time in clinical setting. Positive lesions of patients who presented with newly diagnosed disease or biochemical recurrence after total prostatectomy were reviewed retrospectively. Gradient-based and threshold-based tools at 40%, 50% and 60% of lesion SUVmax (MIM 6.9) were used to create contours on PET. Contouring was considered completed if the target lesion, with its hottest voxel, was delineated from background tissues and nearby lesions under criteria specific to their operations. The changes in functional tumour volume (FTV) and metabolic tumour burden (MTB, defined as the product of SUVmean and FTV) were analysed. Lesion uptake patterns (increase/decrease/stable) were determined by the percentage change in tumour SUVmax at ±10% limit.

Results

A total of 275 lesions (135 intra-prostatic lesions, 65 lymph nodes, 45 bone lesions and 30 soft tissue lesions in pelvic region) in 68 patients were included. Mean uptake time of early and delayed imaging were 94 and 144 minutes respectively. Threshold-based method using 40% to 60% delineated only 85 (31%), 110 (40%) and 137 (50%) of lesions which all were contoured by gradient-based method. Although the overall percentage change using threshold at 50% was the smallest among other threshold levels in FTV measurement, it was still larger than gradient-based method (median: 50%=-7.6% vs gradient=0%). The overall percentage increase in MTB of gradient-based method (median: 6.3%) was compatible with the increase in tumour SUVmax. Only a small proportion of intra-prostatic lesions (<2%), LN (<4%), bone lesions (0%) and soft tissue lesions (<4%) demonstrated decrease uptake patterns.

Conclusions

With a high completion rate, gradient-based method is reliable for prostate cancer lesion contouring on 18F-PSMA-1007 PET/CT. Under the influence of varying uptake time, it has smaller variation than threshold-based method for measuring volumetric parameters. Therefore, gradient-based method is recommended for tumour delineation and quantification on 18F-PSMA-1007 PET/CT.
Global research trends and hotspots on glioma stem cells
Authors: Song Sirong , Wu Haiyang , Wang Fanchen , Jiao Jiji , Xu Lixia , Wang Hongguang , Tong Xiaoguang , Yan Hua
Published: September 2022

Background

Glioma stem cells (GSCs) are a sub-population of cancer stem cells with capacity of self-renewal and differentiation. Accumulated evidence has revealed that GSCs were shown to contribute to gliomagenesis, distant metastasis as well as the resistance to radiotherapy and chemotherapy. As a result, GSCs were regarded as a promising therapeutic target in human glioma. The purpose of our study is to identify current state and hotspots of GSCs research by analyzing scientific publications through bibliometric methods.

Methods

All relevant publications on GSCs during 2003-2021 were extracted from the Science Citation Index Expanded of Web of Science Core Collection (WoSCC), and related information was collected and analyzed using Microsoft Excel 2016, GraphPad Prism 8 and VOSviewer software.

Results

A total of 4990 papers were included. The United States accounted for the largest number of publications (1852), the second average citations per item (ACI) value (67.54) as well as the highest H-index (157). Cancer Research was the most influential journal in this field. The most contributive institution was League of European Research Universities. RICH JN was the author with the most publications (109) and the highest H-index (59). All studies were clustered into 3 groups: “glioma stem cell properties”, “cell biological properties” and “oncology therapy”. The keywords “identification”, “CD133” and “side population” appeared earlier with the smaller average appearing years (AAY), and the keywords”radiotherapy” and “chemotherapy” had the latest AAY. The analysis of top cited articles showed that “temozolomide”, “epithelial-mesenchymal transition”, and “immunotherapy” emerged as new focused issues.

Conclusion

There has been a growing number of researches on GSCs. The United States has always been a leading player in this domain. In general, the research focus has gradually shifted from basic cellular biology to the solutions of clinical concerns. “Temozolomide resistance”, “epithelial-mesenchymal transition”, and “immunotherapy” should be given more attention in the future.
The association between outdoor air pollution and lung cancer risk in seven eastern metropolises of China: Trends in 2006-2014 and sex differences
Authors: Wang Wei , Meng Liu , Hu Zheyu , Yuan Xia , Zeng Weisi , Li Kunlun , Luo Hanjia , Tang Min , Zhou Xiao , Tian Xiaoqiong , Luo Chenhui , He Yi , Yang Shuo
Published: September 2022

There is a positive association between air pollution and lung cancer burden. This study aims to identify and examine lung cancer risks and mortality burdens associated with air pollutants, including PM10, NO2 and SO2, in seven eastern metropolises of China. The study population comprised a population from seven eastern metropolises of China. The yearly average values (YAV, μg/m3) of the PM10, NO2 and SO2 levels were extracted from China Statistical Yearbook (CSYB) for each selected city from 2006 to 2014. Data collected in the China Cancer Registry Annual Report (CCRAR) provide lung cancer incidence and mortality information. A two-level normal random intercept regression model was adopted to analyze the association between the lung cancer rates and individual air pollutant concentration within a five-year moving window of past exposure. The yearly average values of PM10, SO2 and NO2 significantly decreased from 2006 to 2014. Consistently, the male age-adjusted incidence rate (MAIR) and male age-adjusted mortality rate (MAMR) decreased significantly from 2006 to 2014.Air pollutants have a lag effect on lung cancer incidence and mortality for 2-3 years. NO2 has the significant association with MAIR (RR=1.57, 95% CI: 1.19-2.05, p=0.002), MAMR (RR=1.70, 95% CI: 1.32-2.18, p=0.0002) and female age-adjusted mortality rate (FAMR) (RR=1.27, 95% CI: 1.08-1.49, p=0.003). Our findings suggested that air pollutants may be related to the occurrence and mortality of lung cancer. NO2 was significantly associated with the risk of lung cancer, followed by SO2. Air pollutants have the strongest lag effect on the incidence and mortality of lung cancer within 2-3 years.
Clonal evolution characteristics and reduced dimension prognostic model for non-metastatic metachronous bilateral breast cancer
Authors: Li Lingyu , Li Jiaxuan , Jia Jiwei , He Hua , Li Mingyang , Yan Xu , Yu Qing , Guo Hanfei , Wang Hong , Lv Zheng , Sun Haishuang , Liao Guidong , Cui Jiuwei
Published: September 2022

Background

How to evaluate the prognosis and develop overall treatment strategies of metachronous bilateral breast cancer (MBBC) remains confused in clinical. Here, we investigated the correlation between clonal evolution and clinical characteristics of MBBC; we aim to establish a novel prognostic model in these patients.

Methods

The data from Surveillance, Epidemiology, and End Results (SEER) database and the First Hospital of Jilin University were analyzed for breast cancer–specific cumulative mortality (BCCM) by competing risk model. Meanwhile, whole-exome sequencing was applied for 10 lesions acquired at spatial–temporal distinct regions of five patients from our own hospital to reconstruct clonal evolutionary characteristics of MBBC. Then, dimensional-reduction (DR) cumulative incidence function (CIF) curves of MBBC features were established on different point in diagnostic interval time, to build a novel DR nomogram.

Results

Significant heterogeneity in genome and clinical features of MBBC was widespread. The mutational diversity of contralateral BC (CBC) was significantly higher than that in primary BC (PBC), and the most effective prognostic MATH ratio was significantly correlated with interval time (R2 = 0.85, p< 0.05). In SEER cohort study (n = 13,304), the interval time was not only significantly affected the BCCM by multivariate analysis (p< 0.000) but determined the weight of clinical features (T/N stage, grade and ER status) on PBC and CBC in prognostic evaluation. Thus, clinical parameters after DR based on interval time were incorporated into the nomogram for prognostic predicting BCCM. Concordance index was 0.773 (95% CI, 0.769–0.776) in training cohort (n = 8,869), and 0.819 (95% CI, 0.813–0.826) in validation cohort (n = 4,435).

Conclusions

Bilateral heterogeneous characteristics and interval time were determinant prognostic factors of MBBC. The DR prognostic nomogram may help clinicians in prognostic evaluation and decision making.
Clinical applications of circulating tumor-derived DNA in the management of gastrointestinal cancers – current evidence and future directions
Authors: Lam Rachel C. T. , Johnson David , Lam Gigi , Li Michelle L. Y. , Wong Joyce W. L. , Lam W. K. Jacky , Chan K. C. Allen , Ma Brigette
Published: September 2022

Advances in Next Generation Sequencing (NGS) technologies have enabled the accurate detection and quantification of circulating tumor-derived (ct)DNA in most gastrointestinal (GI) cancers. The prognostic and predictive utility of ctDNA in patiets with different stages of colorectal (CRC), gastro-esophageal (GEC) and pancreaticobiliary cancers (PBC) are currently under active investigation. The most mature clinical data to date are derived from studies in the prognostic utility of personalized ctDNA-based NGS assays in the detection of minimal residual disease (MRD) and early recurrence after surgery in CRC and other GI cancers. These findings are being validated in several prospective studies which are designed to test if ctDNA could outperform conventional approaches in guiding adjuvant chemotherapy, and in post-operative surveillance in some GI cancers. Several adaptive studies using ctDNA as a screening platform are also being used to identify patients with actionable genomic alterations for clinical trials of targeted therapies. In the palliative setting, ctDNA monitoring during treatment has shown promise in the detection and tracking of clonal variants associated with acquired resistance to targeted therapies and immune-checkpoint inhibitors (ICI). Moreover, ctDNA may help to guide the therapeutic re-challenge of targeted therapies in patients who have prior exposure to such treatment. This review will examine the most updated research findings on ctDNA as a biomarker in CRC, GEC and PBCs. It aims to provide insights into how the unique strengths of this biomarker could be optimally leveraged in improving the management of these GI cancers.
Identification and validation of an immunological microenvironment signature and prediction model for epstein-barr virus positive lymphoma: Implications for immunotherapy
Authors: Yao Chenjiao , Xu Ruoyao , Li Qianyuan , Xiao Sheng , Hu Min , Xu Linyong , Zhuang Quan
Published: September 2022

Background

Epstein-Barr virus (EBV) is considered a carcinogenic virus, which is associated with high risk for poor prognosis in lymphoma patients, and there has been especially no satisfying and effective treatment for EBV+ lymphoma. We aimed to identify the immunological microenvironment molecular signatures which lead to the poor prognosis of EBV+ lymphoma patients.

Methods

Differential genes were screened with microarray data from the GEO database (GSE38885, GSE34143 and GSE13996). The data of lymphoid neoplasm diffuse large B-cell lymphoma (DLBC) from the TCGA database and GSE4475 were used to identify the prognostic genes. The data of GSE38885, GSE34143, GSE132929, GSE58445 and GSE13996 were used to eluate the immune cell infiltration. Formalin-fixed, paraffin-embedded tissue was collected for Real Time Quantitative PCR from 30 clinical samples, including 15 EBV+ and 15 EBV- lymphoma patients.

Results

Four differential genes between EBV+ and EBV- lymphoma patients were screened out with the significance of the survival and prognosis of lymphoma, including CHIT1, SIGLEC15, PLA2G2D and TMEM163. Using CIBERSORT to evaluate immune cell infiltration, we found the infiltration level of macrophages was significantly different between EBV+ and EBV- groups and was closely related to different genes. Preliminary clinical specimen verification identified that the expression levels of CHIT1 and TMEM163 were different between EBV+ and EBV- groups.

Conclusions

Our data suggest that differences in expression levels of CHIT1 and TMEM163 and macrophage infiltration levels may be important drivers of poor prognosis of EBV+ lymphoma patients. These hub genes may provide new insights into the prognosis and therapeutic target for EBV+ lymphoma.
Body composition as a predictor of chemotherapy-related toxicity in pancreatic cancer patients: A systematic review
Authors: Rizzo Stefania , Scala Isabel , Robayo Angela Rodriguez , Cefalì Marco , De Dosso Sara , Cappio Stefano , Xhepa Genti , Del Grande Filippo
Published: September 2022

Objectives

The objective of this systematic review was to assess associations between quantitative body composition measures extracted from imaging examinations and chemotherapy-related toxicity in pancreatic cancer patients. A secondary objective was to evaluate the different definitions of sarcopenia across included studies.

Methods

This systematic review was conducted according to the PRISMA statement. A comprehensive literature search of three electronic databases was performed by two authors. For each eligible article, information was collected concerning the clinical setting; basic study; population characteristics; technical; body composition features evaluated; CA 19.9 tumor marker levels; chemotherapy drugs administered; toxicities (hematologic, nausea/vomiting, diarrhea, neuropathy, reduction of number of cycles, overall toxicity); association of body composition values with toxicities. The overall quality of the included studies was critically evaluated.

Results

After the initial retrieval of 1137 articles, the systematic review included 12 articles (1/12 in the neo-adjuvant setting; 2/12 in the adjuvant setting; 3/12 in the metastatic setting; 2/12 in the unresectable setting; the other 4/12 included more than one clinical setting). The number of patients included ranged between 17 and 251; mean/median age ranged between 63 and 77 years; the percentage of sarcopenic patients ranged between 23 and 76%. The most frequent body composition parameter evaluated was skeletal muscle index (11/12). Chemotherapy regimens included gemcitabine (as monotherapy or in combination with other drugs); FOLFIRINOX and S-1. Among the trials including gemcitabine, 2/9 demonstrated an association with toxicity, whereas 7/9 did not; among those including FOLFIRINOX, one demonstrated associated toxicity whereas the others did not. Altogether, 4/12 papers demonstrated an association between the body composition values and the development of chemotherapy-related toxicities.

Conclusions

There is a wide variability of results about the association of body composition and chemotherapy-related toxicity in PC patients. Furthermore, cut-off values to define sarcopenia in PC patients are not yet uniformly defined.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022337753, identifier CRD42022337753.
Intermittent MEK inhibition for the treatment of metastatic uveal melanoma
Authors: Khan Shaheer , Patel Sapna P. , Shoushtari Alexander N. , Ambrosini Grazia , Cremers Serge , Lee Shing , Franks Lauren , Singh-Kandah Shahnaz , Hernandez Susana , Sender Naomi , Vuolo Kristina , Nesson Alexandra , Mundi Prabhjot , Izar Benjamin , Schwartz Gary K. , Carvajal Richard D.
Published: September 2022

Introduction

Uveal melanoma (UM) is associated with poor outcomes in the metastatic setting and harbors activating mutations resulting in upregulation of MAPK signaling in almost all cases. The efficacy of selumetinib, an oral allosteric inhibitor of MEK1/2, was limited when administered at a continual dosing schedule of 75 mg BID. Preclinical studies demonstrate that intermittent MEK inhibition reduces compensatory pathway activation and promotes T cell activation. We hypothesized that intermittent dosing of selumetinib would reduce toxicity, allow for the administration of increased doses, and achieve more complete pathway inhibition, thus resulting in improved antitumor activity.

Methods

We conducted a phase Ib trial of selumetinib using an intermittent dosing schedule in patients with metastatic UM. The primary objective was to estimate the maximum tolerated dose (MTD) and assess safety and tolerability. Secondary objectives included assessment of the overall response rate (RR), progression-free survival (PFS) and overall survival (OS). Tumor biopsies were collected at baseline, on day 3 (on treatment), and between days 11-14 (off treatment) from 9 patients for pharmacodynamic (PD) assessments.

Results

29 patients were enrolled and received at least one dose of selumetinib across 4 dose levels (DL; DL1: 100 mg BID; DL2: 125 mg BID; DL3: 150 mg BID; DL4: 175 mg BID). All patients experienced a treatment-related adverse event (TRAE), with 5/29 (17%) developing a grade 3 or higher TRAE. Five dose limiting toxicities (DLT) were observed: 2/20 in DL2, 2/5 in DL3, 1/1 in DL4. The estimated MTD was 150 mg BID (DL3), with an estimated probability of toxicity of 29% (90% probability interval 16%-44%). No responses were observed; 11/29 patients achieved a best response of stable disease (SD). The median PFS and OS were 1.8 months (95% CI 1.7, 4.5) and 7.1 months (95% CI 5.3, 11.5). PD analysis demonstrated at least partial pathway inhibition in all samples at day 3, with reactivation between days 11-14 in 7 of those cases.

Conclusions

We identified 150 mg BID as the MTD of intermittent selumetinib, representing a 100% increase over the continuous dose MTD (75 mg BID). However, no significant clinical efficacy was observed using this dosing schedule.
Case report: Different mechanisms of drug resistance in a synchronous multiple primary lung cancer patient after EGFR-TKI treatment
Authors: Xie Shaonan , Liu Qingyi
Published: September 2022

Non-small-cell lung cancer (NSCLC) is the most common cancer in the world. In recent years, the incidence of synchronous multiple primary lung cancer (SMPLC) has gradually increased. Surgery is the preferred method to treat these patients. The management of SMPLC patients who cannot tolerate surgical treatment is controversial. We report a rare case in which a 70-year-old Chinese woman with no history of smoking had three primary lung adenocarcinoma lesions. Two lesions had epidermal growth factor receptor (EGFR) exon 19 deletion mutations, and one lesion had the L858R mutation. After first-generation EGFR–tyrosine kinase inhibitor (TKI) treatment, the three lesions all showed a good response until disease progression. After the corresponding drug treatments were given based on the different drug resistance mechanisms, good responsiveness was shown in each lessions. This case suggests that in the treatment of SMPLC, it is necessary to learn the molecular-biological information of each lesion due to the differences thereof, and a targeted treatment regimen should be developed on this basis.
The prognostic value of fibrinogen to albumin ratio in malignant tumor patients: A meta-analysis
Authors: Li Baibei , Deng Huachu , Lei Biao , Chen Leijie , Zhang Xinyuan , Sha Dingran
Published: September 2022

Background

Recent studies have shown that the fibrinogen to albumin ratio (FAR) is closely related to the prognosis of various cancers. The aim of this systematic review and meta-analysis was to investigate the prognostic value of FAR in malignancies based on the available evidence.

Method

To systematically search the Cochrane Library, Embase, PubMed, Google Scholar, Baidu scholars, CNKI and VIP databases for relevant studies published before April 1, 2022, and to evaluate the fibrinogen-to-albumin ratio (FAR) and survival of patients with malignant tumors through a meta-analysis relationship between the results. Results. This meta-analysis included 19 eligible studies involving 5926 cancer patients. We found that high FAR was associated with poor overall survival (HR=2.25, 95%CI 1.86-2.74, p<0.001), recurrence-free survival (HR=2.29, 95%CI 1.91-2.76, P<0.001), progression-free survival (HR: 2.10, 95%CI 1.58-2.79, p<0.001), disease-free survival (HR=1.52, 95%CI 1.17-1.96, p=0.001), and time to recurrence (HR: 1.555, 95%CI 1.031-2.346, P=0.035) was significantly correlated.

Conclusions

High FAR is significantly associated with poor clinical outcomes in cancer, suggesting that it may be an important predictor of prognosis in patients with malignancies.