bluuebunny/crossref_metadata_2025_split huggingface dataset:
Eight-gene metabolic signature related with tumor-associated macrophages predicting overall survival for hepatocellular carcinoma
Authors: Huo Junyu , Wu Liqun , Zang Yunjin , Dong Hongjing , Liu Xiaoqiang , He Fu , Zhang Xiao 
Published: January 2021

AbstractBackgroundIn recent years, the relationship between tumor-associated macrophages (TAMs) and solid tumors has become a research hotspot. This study aims to explore the close relationship of TAMs with metabolic reprogramming genes in hepatocellular carcinoma (HCC) to provide new methods of treatment for HCC.MethodsThe study selected 343 HCC patients with complete survival information (survival time > = 1 month) in the Cancer Genome Atlas (TCGA) as study subjects. Kaplan-Meier survival analysis assisted in determining the relationship between macrophage infiltration and overall survival (OS), and Pearson correlation tests were used to identify metabolic reprogramming genes (MRGs) associated with tumor macrophage abundance. Lasso regression algorithms were used on prognosis-related MRGs identified by Kaplan-Meier survival analysis and univariate Cox regression analysis to construct a risk score; another independent cohort (including 228 HCC patients) from the International Cancer Genome Consortium (ICGC) was used to verify prognostic signature externally.ResultsA risk score composed of 8 metabolic genes could accurately predict the OS of a training cohort (TCGA) and a testing cohort (ICGC). The risk score could be widely used for people with different clinical characteristics, and it is a predictor that is independent of other clinical factors that affect prognosis. As expected, compared with the low-risk group, the high-risk group exhibited an obviously higher macrophage abundance, together with a positive correlation between the risk score and the expression levels of three commonly used immune checkpoints (PD1, PDL1, and CTLA4).ConclusionOur study constructed and validated a novel eight-gene signature for predicting HCC patient OS, which may contribute to clinical treatment decisions.
Mucinous, endometrioid, and serous ovarian cancers with peritoneal dissemination are potent candidates for P-cadherin targeted therapy: a retrospective cohort study
Authors: Kayahashi Kayo , Mizumoto Yasunari , Matsuoka Ayumi , Obata Takeshi , Iwadare Junpei , Nakamura Mitsuhiro , Daikoku Takiko , Fujiwara Hiroshi 
Published: January 2021

Abstract
Background
Aberrant expression of P-cadherin has been reported in various cancers, and has been attracting attention as a target for cancer treatment. Ovarian cancer, the leading cause of death among gynecologic malignancies, is classified into four histological subtypes: serous, mucinous, endometrioid, and clear cell, and each has distinct biological behavior. Although a negative survival impact in serous ovarian cancer patients and some functional role in peritoneal dissemination have been reported, differences of P-cadherin expression in histological subtypes and the proportion and distribution of positive cells remain to be investigated. The aims of this study were to clarify the histological and distributional profiles of P-cadherin expression in ovarian cancer for development of target-therapy in near future.

Methods
A total of 162 primary, 60 metastatic, and 8 recurrent tumors (all cases from 162 ovarian cancer patients) were enrolled in the study. Immunohistochemistry was performed for P-cadherin expression. Associations with clinicopathological characteristics and survival were analyzed.

Results
P-cadherin expression showed a strong correlation with the FIGO stage, histological subtypes, positive peritoneal dissemination (P < 0.01), positive distant metastasis (P < 0.05), and trend toward negative overall survival probability (P = 0.050). P-cadherin was intensely and broadly expressed in mucinous, endometrioid, and serous subtypes (P < 0.01). Disseminated tumors demonstrated similar P-cadherin expression to primary tumors whereas metastatic lymph nodes demonstrated significantly decreased expression (P < 0.01).

Conclusions
Mucinous, endometrioid, and serous ovarian cancer patients accompanied with peritoneal disseminations are the most potent candidates for P-cadherin targeted drug delivery strategies. P-cadherin-targeted therapy may benefit and improve survival of poor-prognosis populations.
Neutral polysaccharide from Panax notoginseng enhanced cyclophosphamide antitumor efficacy in hepatoma H22-bearing mice
Authors: Liu Yan-Hong , Qin Hua-Yan , Zhong Yuan-Yuan , Li Shuang , Wang Hua-Jing , Wang Hong , Chen Li-Ling , Tang Xiang , Li Ya-Lin , Qian Zhong-Yi , Li Huai-Yu , Zhang Lei , Chen Tong 
Published: January 2021

Abstract
Background
Our previous studies demonstrated that the administration of crude Polysaccharide from Panax notoginseng (CPPN) can effectively prolong the lifespan of tumor-bearing mice via boosting the host immune system as well as weak cytotoxicity against hepatocellular carcinoma (HCC). In the present study, Neutral Polysaccharide (NPPN) were further purified from crude polysaccharide isolated from panax notoginseng. The effects of NPPN on the immune function and hematopoietic function of mice with low immunity and myelosuppression induced by cyclophosphamide (CTX) were investigated. The effect of NPPN combined with CTX on the tumor inhibition rate of the H22 tumor-bearing mice and the impact of NPPN on the proliferation of H22 liver cancer cells in vitro were investigated.

Methods
CPPN was obtained by water extraction and alcohol precipitation method, and further purified by DEAE Sepharose Fast Flow ion exchange resin column. NPPN was added to the immunosuppressed with myelosuppression mice induced by CTX. Thymus index, spleen index, lymphocyte proliferation stimulation index by adding of concanavalin A, determination of serum hemolysin, NK cell activity assay, mice carbon clearance experiment, blood count tests were detected. The tumor inhibition rate of the H22 tumor-bearing mice treated with NPPN combined with CTX was recorded.

Results
NPPN and 4 kinds of acid polysaccharide from Panax notoginseng (APPN) were successfully isolated from the CPPN by DEAE Sepharose Fast Flow ion exchange resin column. NPPN inhibited the growth of H22 cells and significantly increase the tumor inhibition rate of the H22 tumor-bearing mice combined with CTX. The elevation of the cellular and humoral immunity levels as well as a variety of blood count tests indicators of immunosuppressive with myelosuppression mice may contribute to the antitumor activity of NPPN.

Conclusion
NPPN has a potential antitumor activity for the treatment of liver cancer combined with cyclophosphamide.
The oncometabolite R-2-hydroxyglutarate dysregulates the differentiation of human mesenchymal stromal cells via inducing DNA hypermethylation
Authors: Liu Lizhen , Hu Kaimin , Feng Jingjing , Wang Huafang , Fu Shan , Wang Binsheng , Wang Limengmeng , Xu Yulin , Yu Xiaohong , Huang He 
Published: January 2021

Abstract
Background
Isocitrate dehydrogenase (IDH1/2) gene mutations are the most frequently observed mutations in cartilaginous tumors. The mutant IDH causes elevation in the levels of R-enantiomer of 2-hydroxylglutarate (R-2HG). Mesenchymal stromal cells (MSCs) are reasonable precursor cell candidates of cartilaginous tumors. This study aimed to investigate the effect of oncometabolite R-2HG on MSCs.

Methods
Human bone marrow MSCs treated with or without R-2HG at concentrations 0.1 to 1.5 mM were used for experiments. Cell Counting Kit-8 was used to detect the proliferation of MSCs. To determine the effects of R-2HG on MSC differentiation, cells were cultured in osteogenic, chondrogenic and adipogenic medium. Specific staining approaches were performed and differentiation-related genes were quantified. Furthermore, DNA methylation status was explored by Illumina array-based arrays. Real-time PCR was applied to examine the signaling component mRNAs involved in.

Results
R-2HG showed no influence on the proliferation of human MSCs. R-2HG blocked osteogenic differentiation, whereas promoted adipogenic differentiation of MSCs in a dose-dependent manner. R-2HG inhibited chondrogenic differentiation of MSCs, but increased the expression of genes related to chondrocyte hypertrophy in a lower concentration (1.0 mM). Moreover, R-2HG induced a pronounced DNA hypermethylation state of MSC. R-2HG also improved promotor methylation of lineage-specific genes during osteogenic and chondrogenic differentiation. In addition, R-2HG induced hypermethylation and decreased the mRNA levels of SHH, GLI1and GLI2, indicating Sonic Hedgehog (Shh) signaling inhibition.

Conclusions
The oncometabolite R-2HG dysregulated the chondrogenic and osteogenic differentiation of MSCs possibly via induction of DNA hypermethylation, improving the role of R-2HG in cartilaginous tumor development.
Secondary endpoints analysis in patients with estrogen receptor-positive metastatic breast cancer treated with everolimus and exemestane enrolled in Oral Care-BC
Authors: Nakatsukasa Katsuhiko , Niikura Naoki , Kashiwabara Kosuke , Amemiya Takeshi , Watanabe Ken-ichi , Hata Hironobu , Kikawa Yuichiro , Taniike Naoki , Yamanaka Takashi , Mitsunaga Sachiyo , Nakagami Kazuhiko , Adachi Moriyasu , Kondo Naoto , Shibuya Yasuyuki , Hayashi Naoki , Naito Mariko , Yamashita Toshinari , Umeda Masahiro , Mukai Hirofumi , Ota Yoshihide 
Published: January 2021

Abstract
Background
The Oral Care BC-trial reported that professional oral care (POC) reduces the incidence and severity of oral mucositis in patients receiving everolimus (EVE) and exemestane (EXE). However, the effect of POC on clinical response among patients receiving EVE and EXE was not established. We compared outcomes for estrogen receptor-positive metastatic breast cancer patients who received POC to those who had not, and evaluated clinical prognostic factors. All patients simultaneously received EVE and EXE.

Methods
Between May 2015 and Dec 2017, 174 eligible patients were enrolled in the Oral Care-BC trial. The primary endpoint was the comparative incidence of grade 1 or worse oral mucositis, as evaluated for both the groups over 8 weeks by an oncologist. The secondary endpoints were progression-free survival (PFS) and overall survival (OS). Data were collected after a follow-up period of 13.9 months.

Results
There were no significant differences in PFS between the POC and Control Groups (P = 0.801). A BMI <  25 mg/m2 and non-visceral metastasis were associated with longer PFS (P = 0.018 and P = 0.003, respectively) and the use of bone modifying agents (BMA) was associated with shorter PFS (P = 0.028). The PFS and OS between the POC and control groups were not significantly different in the Oral-Care BC trial.

Conclusions
POC did not influence the prognosis of estrogen receptor-positive metastatic breast cancer patients. Patients with non-visceral metastasis, a BMI <  25 mg/m2, and who did not receive BMA while receiving EVE and EXE may have better prognoses.

Trial registration
The study protocol was registered online at the University Hospital Medical Information Network (UMIN), Japan (protocol ID 000016109), on January 5, 2015 and at ClinicalTrials.gov (NCT02376985).
High-grade postoperative complications affect survival outcomes of patients with colorectal Cancer peritoneal metastases treated with Cytoreductive surgery and Hyperthermic Intraperitoneal chemotherapy
Authors: Zhou Sicheng , Feng Qiang , Zhang Jing , Zhou Haitao , Jiang Zheng , Liu Zheng , Zheng Zhaoxu , Chen Haipeng , Wang Zheng , Liang Jianwei , Pei Wei , Liu Qian , Zhou Zhixiang , Wang Xishan 
Published: January 2021

Abstract
Background
This study aimed to evaluate the impact of postoperative complications on long-term survival in patients with peritoneal metastasis (PM) arising from colorectal cancer (CRC) treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC).

Methods
Patients with PM arising from CRC treated with CRS and HIPEC were systematically reviewed at the China National Cancer Center and Huanxing Cancer Hospital from June 2017 to June 2019. High-grade complications that occurred within 30 days were defined as grade 3 to 4 events according to the Common Terminology Criteria for Adverse Events (CTCAE) classification. Univariate and multivariable Cox regression models for overall survival were created. Predictors of high-grade postoperative complications were evaluated with univariate and multivariate logistic regression analyses.

Results
In all, 86 consecutive cases were included in this study. Forty-one patients (47.7%) developed postoperative complications, while 22 patients (25.6%) experienced high-grade complications. No mortality occurred during the postoperative period. The median survival of all patients was 25 months, and the estimated 3-year overall survival (OS) rate was 35.0%. In the multivariable Cox regression analysis, a high peritoneal carcinomatosis index (PCI) score (HR, 1.07, 95% CI, 1.01–1.14; P=0.015) and grade 3–4 postoperative complications (HR, 1.86, 95% CI, 1.22–3.51; P=0.044) correlated with worse overall survival. High estimated blood loss (OR, 1.01, 95% CI, 1.01–1.02; P< 0.001) was identified as an independent risk factor for developing high-grade complications.

Conclusion
Careful patient selection, high levels of technical skill and improved perioperative management are crucial to ensure patient survival benefits after CRS+HIPEC.
Postoperative complicated peripheral cortical cataract after ultrasound cycloplasty: a case report
Authors: Luo Jihan , Liu Zhen , Zhao Lin , Zhou Yi , Kong Li , Sun Yang 
Published: January 2021

Abstract
Background
Ultrasound cycloplasty (UCP) is a non-invasive procedure for glaucoma treatment. Using high-intensity focused ultrasound to work on the ciliary body, the generation of aqueous humor can be reduced and the drainage of aqueous humor through the uveoscleral pathway can be enhanced. Recently, this therapy is gradually gaining clinical recognition. We report a case of a patient with glaucoma who accepted UCP in another hospital, but because of a worsening of a preexistent cataract and an insufficient IOP lowering effect, finally underwent cataract surgery in both eyes in our hospital, during the surgery we observed the unusual opacities probably due to UCP mistreatment.

Case presentation
Patient was diagnosed as chronic angle closure glaucoma and catacract, accepted UCP on both eyes in another hospital 4 months ago. After the UCP therapy, the pupil was vertical ellipse, the UCP didn’t have a sufficient effect on IOP and forced us to do cataract surgery to lower IOP. During the cataract surgery, some unusual white opacities in the peripheral cortex with clear boundary were found. Inaccurate WtW measurement was the most likely cause of the injury, which resulted in the use of the small-size UCP probe and the downward movement of the UCP probe.

Conclusion
UCP should not be a first line treatment in a patient with cataract and angle closure glaucoma, cataract extraction is a better choice. The appropriate case selection needs to be more strict and the preoperative indexes measurements need to be more accurate.
Optic nerve pit maculopathy worsened during pregnancy: a case report
Authors: Torrado-Cobian Laura A. , Fivgas George D. 
Published: January 2021

Abstract
Background
To report a case of Optic Disc Pit (ODP) maculopathy exacerbated during pregnancy.

Case presentation
A 30-year-old female developed unilateral blurry vision at 10-weeks gestation. Ophthalmic examination revealed left eye reduced visual acuity (VA) with the presence of subretinal fluid temporal to the disc extending to the fovea. On Spectral Domain Optical Coherence Tomography (SD-OCT) subretinal, and intraretinal fluid was confirmed. Laser photocoagulation was tried in an attempt to prevent surgical intervention without success; subsequently, pars plana vitrectomy, internal limiting membrane peel and gas tamponade was performed. Three-weeks later, a full thickness macular hole developed, and repeat surgery was performed. Nine-months after the second surgery the macular hole was closed with near complete resorption of edema.

Conclusions
No trigger factors for ODP maculopathy have been reported before. We report a case of worsening ODP maculopathy during pregnancy with good visual outcome after surgical intervention.
Infantile onset Sandhoff disease: clinical manifestation and a novel common mutation in Thai patients
Authors: Tim-Aroon Thipwimol , Wichajarn Khunton , Katanyuwong Kamornwan , Tanpaiboon Pranoot , Vatanavicharn Nithiwat , Sakpichaisakul Kullasate , Kongkrapan Arthaporn , Eu-ahsunthornwattana Jakris , Thongpradit Supranee , Moolsuwan Kanya , Satproedprai Nusara , Mahasirimongkol Surakameth , Lerksuthirat Tassanee , Suktitipat Bhoom , Jinawath Natini , Wattanasirichaigoon Duangrurdee 
Published: January 2021

Abstract
Background
Sandhoff disease (SD) is an autosomal recessive lysosomal storage disorder, resulting in accumulation of GM2 ganglioside, particular in neuronal cells. The disorder is caused by deficiency of β-hexosaminidase B (HEX-B), due to pathogenic variant of human HEXB gene.

Method
This study describes clinical features, biochemical, and genetic defects among Thai patients with infantile SD during 2008–2019.

Results
Five unrelated Thai patients presenting with developmental regression, axial hypotonia, seizures, exaggerated startle response to noise, and macular cherry red spot were confirmed to have infantile SD based on deficient HEX enzyme activities and biallelic variants of the HEXB gene. In addition, an uncommon presenting feature, cardiac defect, was observed in one patient. All the patients died in their early childhood. Plasma total HEX and HEX-B activities were severely deficient. Sequencing analysis of HEXB gene identified two variants including c.1652G>A (p.Cys551Tyr) and a novel variant of c.761T>C (p.Leu254Ser), in 90 and 10% of the mutant alleles found, respectively. The results from in silico analysis using multiple bioinformatics tools were in agreement that the p.Cys551Tyr and the p.Leu254Ser are likely pathogenic variants. Molecular modelling suggested that the Cys551Tyr disrupt disulfide bond, leading to protein destabilization while the Leu254Ser resulted in change of secondary structure from helix to coil and disturbing conformation of the active site of the enzyme. Genome-wide SNP array analysis showed no significant relatedness between the five affected individuals. These two variants were not present in control individuals. The prevalence of infantile SD in Thai population is estimated 1 in 1,458,521 and carrier frequency at 1 in 604.

Conclusion
The study suggests that SD likely represents the most common subtype of rare infantile GM2 gangliosidosis identified among Thai patients. We firstly described a potential common variant in HEXB in Thai patients with infantile onset SD. The data can aid a rapid molecular confirmation of infantile SD starting with the hotspot variant and the use of expanded carrier testing.
Association of telomere length and telomerase methylation with n-3 fatty acids in preschool children with obesity
Authors: Liu Xuanyi , Liu Xiaozhou , Shi Qiaoyu , Fan Xiuqin , Qi Kemin 
Published: January 2021

Abstract
Background
Telomeres play a crucial role in cellular survival and its length is a predictor for onset of chronic non-communicable diseases. Studies on association between telomeres and obesity in children have brought discrepant results and the underlying mechanisms and influential factors are to be elucidated. This study aimed to investigate changes in telomere length and telomerase reverse transcriptase (TERT) DNA methylation, and further to determine their correlation with n-3 polyunsaturated fatty acids (PUFAs) in preschool children with obesity.

Methods
Forty-six preschool children with obesity aged 3 to 4 years were included in the study, with equal numbers of age- and gender-matched children with normal weight as control. Leukocyte telomere length was determined by the ratio of telomeric product and single copy gene obtained using real-time qPCR. DNA methylation of TERT promoter was analyzed by bisulfite sequencing. Fatty acids in erythrocytes were measured by gas chromatography with a total of 15 fatty acids analyzed. The total saturated fatty acids (SFAs), total n-6 PUFAs, total n-3 PUFAs, and the ratio of arachidonic acid (AA) to docosahexaenoic acid (DHA) were calculated. Then the correlation between leukocyte telomere length, TERT promoter methylation and fatty acids was determined.

Results
In preschool children with obesity, leukocyte telomeres were shortened and had a negative association with the body mass index. The methylated fractions in 13 of 25 CpG sites in the TERT promoter were increased by approximately 3 to 35% in the children with obesity compared to the normal weight children. Erythrocyte lauric acid and total SFAs, lenoleic acid and total n-6 PUFAs were higher, and DHA was lower in the children with obesity than those in the children with normal weight. Correlative analysis showed that leukocyte telomere length had a positive association with total SFAs and DHA, and a negative association with the AA/DHA ratio. However, no association between erythrocyte DHA and the TERT promoter methylation was found.

Conclusion
These data indicate that the reduced body DHA content and increased AA/DHA ratio may be associated with shortened leukocyte telomeres in child obesity, which is probably not involved in the TERT promoter methylation.
Stigma of mental illness and cultural factors in Pacific Rim region: a systematic review
Authors: Ran Mao-Sheng , Hall Brian J. , Su Tin Tin , Prawira Benny , Breth-Petersen Matilde , Li Xu-Hong , Zhang Tian-Ming 
Published: January 2021

AbstractBackgroundAlthough cultural factors play a crucial role in experience of stigma, there is scant review on the impact and importance of culture on stigma of mental illness across Pacific Rim Region. This study aims to investigate: 1) the cultural factors related to stigmatizing beliefs about mental illness in Pacific Rim region, and 2) culture-specific measures and interventions on stigma of mental illness.MethodsA systematic search of papers was conducted in the MEDLINE, Embase, CINAHL, Web of Science, PsycINFO, Scopus, Cochrane Library and Google scholar through January 2003 to April 2019.ResultsForty-one studies in Pacific Rim region which met the inclusion criteria were included in the study. The rate of stigma of mental illness (e.g., public stigma: from 25.4 to 85.2%) was relatively high in Pacific Rim region. Culture factors (e.g., Collectivism, Confucianism, face concern and familism, religion and supernatural beliefs) contributed to people’s stigmatizing behaviors and attitudes toward persons with mental illness, their relatives and mental health professionals. Certain measurements were developed and employed to assess different type of cultural factors related to stigma of mental illness.ConclusionsCultural factors play an important role in influencing the rate and performance of stigma of mental illness. Further research on stigma of mental illness and culture-specific interventions to reduce the stigma should be conducted in the Pacific Rim region.