bluuebunny/crossref_metadata_2025_split huggingface dataset:
Putative alternative translation start site-encoding nucleotides of CPR5 regulate growth and resistance
Authors: Faisal Muhammad B. , Gechev Tsanko S. , Mueller-Roeber Bernd , Dijkwel Paul P. 
Published: June 2020

Abstract
Background
The Arabidopsis CONSTITUTIVE EXPRESSER of PATHOGENESIS-RELATED GENES 5 (CPR5) has recently been shown to play a role in gating as part of the nuclear pore complex (NPC). Mutations in CPR5 cause multiple defects, including aberrant trichomes, reduced ploidy levels, reduced growth and enhanced resistance to bacterial and fungal pathogens. The pleiotropic nature of cpr5 mutations implicates that the CPR5 protein affects multiple pathways. However, little is known about the structural features that allow CPR5 to affect the different pathways.

Results
Our in silico studies suggest that in addition to three clusters of putative nuclear localization signals and four or five transmembrane domains, CPR5 contains two putative alternative translation start sites. To test the role of the methionine-encoding nucleotides implicated in those sites, metCPR5 cDNAs, in which the relevant nucleotides were changed to encode glutamine, were fused to the CPR5 native promoter and the constructs transformed to cpr5–2 plants to complement cpr5-compromised phenotypes. The control and metCPR5 constructs were able to complement all cpr5 phenotypes, although the extent of complementation depended on the specific complementing plant lines. Remarkably, plants transformed with metCPR5 constructs showed larger leaves and displayed reduced resistance when challenged to Pseudomonas syringae pv Pst DC3000, as compared to control plants. Thus, the methionine-encoding nucleotides regulate growth and resistance. We propose that structural features of the CPR5 N-terminus are implicated in selective gating of proteins involved in regulating the balance between growth and resistance.

Conclusion
Plants need to carefully balance the amount of resources used for growth and resistance. The Arabidopsis CPR5 protein regulates plant growth and immunity. Here we show that N-terminal features of CPR5 are involved in the regulation of the balance between growth and resistance. These findings may benefit efforts to improve plant yield, while maintaining optimal levels of disease resistance.
Intraoperative hypotension is associated with shortened overall survival after lung cancer surgery
Authors: Huang Wen-Wen , Zhu Wen-Zhi , Mu Dong-Liang , Ji Xin-Qiang , Li Xue-Ying , Ma Daqing , Wang Dong-Xin 
Published: June 2020

Abstract
Background
Intraoperative hypotension is associated with increased morbidity and mortality after surgery. We hypothesized that intraoperative hypotension might also be associated with worse long-term survival after cancer surgery. Herein, we analyzed the correlation between intraoperative hyper−/hypotension and overall survival after lung cancer surgery.

Methods
In this retrospective cohort study, 676 patients who received lung cancer surgery between January 1, 2006 and December 31, 2009 were reviewed. Intraoperative hyper- and hypotension were defined according to their correlation with long-term survival. The primary endpoint was overall survival. The association between episodes of intraoperative hyper−/hypotension and overall survival was analyzed with multivariable Cox proportional hazard models.

Results
Long-term follow-ups were completed in 515 patients with a median duration of 5.2 years. The estimated 5-year survival rates were 66.5, 61.3, 56.5, and 41.2% in patients with only hypertension (systolic blood pressure > 140 mmHg for ≥5 min), with both hyper- and hypotension (systolic blood pressure < 100 mmHg for ≥5 min), with neither hyper- nor hypotension, and with only hypotension during surgery, respectively. After adjusting confounding factors, intraoperative hypotension was significantly associated with shortened overall survival (compared with patients with only intraoperative hypertension, those with both hyper- and hypotension: hazard ratio [HR]1.033, 95% confidence interval [CI] 0.709 to 1.507, p = 0.864; those with neither hyper- nor hypotension: HR 0.952, 95% CI 0.608 to 1.489, p = 0.829; those with only hypotension: HR 1.736, 95% CI 1.218 to 2.475, p = 0.002).

Conclusions
For patients undergoing lung cancer surgery, intraoperative hypotension, but not hypertension, was associated with shortened overall survival.
Cardiac-specific methylation patterns of circulating DNA for identification of cardiomyocyte death
Authors: Liu Qin , Ma Jian , Deng Hua , Huang Shu-Jun , Rao Jiao , Xu Wei-Bin , Huang Jing-Si , Sun Shan-Quan , Zhang Liang 
Published: June 2020

Abstract
Background
Correct detection of human cardiomyocyte death is essential for definitive diagnosis and appropriate management of cardiovascular diseases. Although current strategies have proven utility in clinical cardiology, they have some limitations. Our aim was to develop a new approach to monitor myocardial death using methylation patterns of circulating cell-free DNA (cf-DNA).

Methods
We first examined the methylation status of FAM101A in heart tissue and blood of individual donors using quantitative methylation-sensitive PCR (qMS-PCR). The concentrations and kinetics of cardiac cf-DNA in plasma from five congenital heart disease (CHD) children before and after they underwent cardiac surgery at serial time points were then investigated.

Results
We identified demethylated FAM101A specifically present in heart tissue. Importantly, our time course experiments demonstrated that the plasma cardiac cf-DNA level increased quickly during the early post-cardiac surgery phase, peaking at 4–6 h, decreased progressively (24 h) and returned to baseline (72 h). Moreover, cardiac cf-DNA concentrations pre- and post-operation were closely correlated with plasma troponin levels.

Conclusions
We proposed a novel strategy for the correct detection of cardiomyocyte death, based on analysis of plasma cf-DNA carrying the cardiac-specific methylation signature. Our pilot study may lead to new tests for human cardiac pathologies.
Delay in treatment initiation and its association with clinical severity and infectiousness among new adult pulmonary tuberculosis patients in Tigray, northern Ethiopia
Authors: Tedla Kiros , Medhin Girmay , Berhe Gebretsadik , Mulugeta Afework , Berhe Nega 
Published: June 2020

Abstract
Background
Delayed treatment initiation of tuberculosis (TB) increases disease progression and development of complications which may lead to a higher level of infectiousness, clinical severity and increased mortality. But published evidences that investigated the effect of delayed initiation of treatment on clinical severity and level of infectiousness of pulmonary tuberculosis patients is scarce in Tigray, Northern Ethiopia.

Objective
To investigate the association of delayed treatment initiation of new adult Pulmonary Tuberculosis patients with clinical severity and level of infectiousness.

Methods
In this cross-sectional study design, a total of 875 newly diagnosed adult pulmonary tuberculosis patients were recruited from 21 health facilities from October 2018 to October 2019. Health facilities and study participants were selected by a simple random sampling method. Data were collected using questionnaires through face-to-face interviews of patients within the first 2 weeks of treatment initiation. Clinical severity was assessed by Bandim tuberculosis score and level of infectiousness was assessed by smear positivity or lung cavitations. Data were analyzed using SPSS version 21 software program. Logistic regression analysis was used to ascertain the association of delay with clinical severity and level of infectiousness. P-BMC Public Health of less than 0.05 was reported as being statistically significant.

Results
Those who had initiated treatment without delay and those who have initiated treatment after a medium delay of 31 to 60 days were significantly associated with decreased clinical score compared to those who initiated treatment after a delay of more than two months. Compared with patients who have initiated treatment within one month, the level of infectiousness was greater for delay of 30–60 days and above 60 days. Patients having more than 3 family members have higher level of infectiousness as compared to those who have a maximum of 3 family members. Whereas, patients having at least two rooms and being HIV negative had lower levels of infectiousness compared to their counter patients.

Conclusion
Narrowing the gap between their initial occurrence of TB symptoms and treatment initiation is the way forward to improve clinical courses of TB patients and to reduce the level of infectiousness of TB to other people from these patients.
Radiogenomics correlation between MR imaging features and mRNA-based subtypes in lower-grade glioma
Authors: Liu Zhenyin , Zhang Jing 
Published: June 2020

Abstract
Background
To investigate associations between lower-grade glioma (LGG) mRNA-based subtypes (R1-R4) and MR features.

Methods
mRNA-based subtyping was obtained from the LGG dataset in The Cancer Genome Atlas (TCGA). We identified matching patients (n = 145) in The Cancer Imaging Archive (TCIA) who underwent MR imaging. The associations between mRNA-based subtypes and MR features were assessed.

Results
In the TCGA-LGG dataset, patients with the R2 subtype had the shortest median OS months (P < 0.05). The time-dependent ROC for the R2 subtype was 0.78 for survival at 12 months, 0.76 for survival at 24 months, and 0.76 for survival at 36 months. In the TCIA-LGG dataset, 41 (23.7%) R1 subtype, 40 (23.1%) R2 subtype, 19 (11.0%) R3 subtype and 45 (26.0%) R4 subtype cases were identified. Multivariate analysis revealed that enhancing margin (ill-defined, OR: 9.985; P = 0.003) and T1 + C/T2 mismatch (yes, OR: 0.091; P = 0.023) were associated with the R1 subtype (AUC: 0.708). The average accuracy of the ten-fold cross validation was 71%. Proportion of contrast-enhanced (CE) tumour (> 5%, OR: 14.733; P < 0.001) and necrosis/cystic changes (yes, OR: 0.252; P = 0.009) were associated with the R2 subtype (AUC: 0.832). The average accuracy of the ten-fold cross validation was 82%. Haemorrhage (yes, OR: 8.55; P < 0.001) was positively associated with the R3 subtype (AUC: 0.689). The average accuracy of the ten-fold cross validation was 87%. Proportion of CE tumour (> 5%, OR: 0.14; P < 0.001) was negatively associated with the R4 subtype (AUC: 0.672). The average accuracy of the ten-fold cross validation was 71%. For the prediction of the R2 subtype, the nomogram showed good discrimination and calibration. Decision curve analysis demonstrated that prediction with the R2 model was clinically useful.

Conclusions
Patients with the R2 subtype had the worst prognosis. We demonstrated that MRI features can identify distinct LGG mRNA-based molecular subtypes.
Potential enhancement of host immunity and anti-tumor efficacy of nanoscale curcumin and resveratrol in colorectal cancers by modulated electro- hyperthermia
Authors: Kuo I-Ming , Lee Jih-Jong , Wang Yu-Shan , Chiang Hsin-Chien , Huang Cheng-Chung , Hsieh Pei-Jong , Han Winston , Ke Chiao-Hsu , Liao Albert T. C. , Lin Chen-Si 
Published: June 2020

Abstract
Background
Modulated electro-hyperthermia (mEHT) is a form of hyperthermia used in cancer treatment. mEHT has demonstrated the ability to activate host immunity by inducing the release of heat shock proteins, triggering apoptosis, and destroying the integrity of cell membranes to enhance cellular uptake of chemo-drugs in tumor cells. Both curcumin and resveratrol are phytochemicals that function as effective antioxidants, immune activators, and potential inhibitors of tumor development. However, poor bioavailability is a major obstacle for use in clinical cancer treatment.

Methods
This purpose of this study was to investigate whether mEHT can increase anti-cancer efficacy of nanosized curcumin and resveratrol in in vitro and in vivo models. The in vitro study included cell proliferation assay, cell cycle, and apoptosis analysis. Serum concentration was analyzed for the absorption of curcumin and resveratrol in SD rat model. The in vivo CT26/BALB/c animal tumor model was used for validating the safety, tumor growth curve, and immune cell infiltration within tumor tissues after combined mEHT/curcumin/resveratrol treatment.

Results
The results indicate co-treatment of mEHT with nano-curcumin and resveratrol significantly induced cell cycle arrest and apoptosis of CT26 cells. The serum concentrations of curcumin and resveratrol were significantly elevated when mEHT was applied. The combination also inhibited the growth of CT26 colon cancer by inducing apoptosis and HSP70 expression of tumor cells while recruiting CD3+ T-cells and F4/80+ macrophages.

Conclusions
The results of this study have suggested that this natural, non-toxic compound can be an effective anti-tumor strategy for clinical cancer therapy. mEHT can enable cellular uptake of potential anti-tumor materials and create a favorable tumor microenvironment for an immunological chain reaction that improves the success of combined treatments of curcumin and resveratrol.
Prevalence and incidence of cancer related lymphedema in low and middle-income countries: a systematic review and meta-analysis
Authors: Torgbenu Eric , Luckett Tim , Buhagiar Mark A. , Chang Sungwon , Phillips Jane L. 
Published: June 2020

AbstractBackgroundLittle is known about the prevalence and incidence in low and middle-income countries (LMICs) of secondary lymphedema due to cancer. The purpose of the study is to estimate the prevalence and incidence in LMICs of secondary lymphedema related to cancer and/or its treatment(s) and identify risk factors.MethodA systematic review and meta-analysis was conducted. Medline, EMBASE and CINAHL were searched in June 2019 for peer-reviewed articles that assessed prevalence and/or incidence of cancer-related lymphedema in LMICs. Risk of bias was assessed using the Joanna Briggs Institute Critical Appraisal Checklist for Prevalence Studies. Estimates of pooled prevalence and incidence estimates were calculated with 95% confidence intervals (CI), with sub-group analyses grouping studies according to: country of origin, study design, risk of bias, setting, treatment, and lymphedema site and measurement. Heterogeneity was measured usingX2and I2, with interpretation guided by the Cochrane Handbook for Systematic Reviews.ResultsOf 8766 articles, 36 were included. Most reported on arm lymphedema secondary to breast cancer treatment (n = 31), with the remainder reporting on leg lymphedema following gynecological cancer treatment (n = 5). Arm lymphedema was mostly measured by arm circumference (n = 16/31 studies), and leg lymphedema through self-report (n = 3/5 studies). Eight studies used more than one lymphedema measurement. Only two studies that measured prevalence of leg lymphedema could be included in a meta-analysis (pooled prevalence =10.0, 95% CI 7.0–13.0,I2 = 0%). The pooled prevalence of arm lymphedema was 27%, with considerable heterogeneity (95% CI 20.0–34.0,I2 = 94.69%,n = 13 studies). The pooled incidence for arm lymphedema was 21%, also with considerable heterogeneity (95% CI 15.0–26.0,I2 = 95.29%,n = 11 studies). There was evidence that higher body mass index (> 25) was associated with increased risk of arm lymphedema (OR: 1.98, 95% CI 1.45–2.70,I2 = 84.0%,P < 0.0001,n = 4 studies).ConclusionBetter understanding the factors that contribute to variability in cancer-related arm lymphedema in LMICs is an important first step to developing targeted interventions to improve quality of life. Standardising measurement of lymphedema globally and better reporting would enable comparison within the context of information about cancer treatments and lymphedema care.
An agent-based model of prostate Cancer bone metastasis progression and response to Radium223
Authors: Casarin Stefano , Dondossola Eleonora 
Published: June 2020

Abstract
Background
Bone metastasis is the most frequent complication in prostate cancer patients and associated outcome remains fatal. Radium223 (Rad223), a bone targeting radioisotope improves overall survival in patients (3.6 months vs. placebo). However, clinical response is often followed by relapse and disease progression, and associated mechanisms of efficacy and resistance are poorly understood.
Research efforts to overcome this gap require a substantial investment of time and resources. Computational models, integrated with experimental data, can overcome this limitation and drive research in a more effective fashion.

Methods
Accordingly, we developed a predictive agent-based model of prostate cancer bone metastasis progression and response to Rad223 as an agile platform to maximize its efficacy. The driving coefficients were calibrated on ad hoc experimental observations retrieved from intravital microscopy and the outcome further validated, in vivo.

Results
In this work we offered a detailed description of our data-integrated computational infrastructure, tested its accuracy and robustness, quantified the uncertainty of its driving coefficients, and showed the role of tumor size and distance from bone on Rad223 efficacy. In silico tumor growth, which is strongly driven by its mitotic character as identified by sensitivity analysis, matched in vivo trend with 98.3% confidence. Tumor size determined efficacy of Rad223, with larger lesions insensitive to therapy, while medium- and micro-sized tumors displayed up to 5.02 and 152.28-fold size decrease compared to control-treated tumors, respectively. Eradication events occurred in 65 ± 2% of cases in micro-tumors only. In addition, Rad223 lost any therapeutic effect, also on micro-tumors, for distances bigger than 400 μm from the bone interface.

Conclusions
This model has the potential to be further developed to test additional bone targeting agents such as other radiopharmaceuticals or bisphosphonates.
MAGE-A4, NY-ESO-1 and SAGE mRNA expression rates and co-expression relationships in solid tumours
Authors: Ishihara Mikiya , Kageyama Shinichi , Miyahara Yoshihiro , Ishikawa Takeshi , Ueda Shugo , Soga Norihito , Naota Hiroaki , Mukai Katsumi , Harada Naozumi , Ikeda Hiroaki , Shiku Hiroshi 
Published: June 2020

Abstract
Background
Cancer testis (CT) antigens are promising targets for cancer immunotherapies such as cancer vaccines and genetically modified adoptive T cell therapy. In this study, we evaluated the expression of three CT antigens, melanoma-associated antigen A4 (MAGE-A4), New York oesophageal squamous cell carcinoma 1 (NY-ESO-1) and sarcoma antigen gene (SAGE).

Methods
MAGE-A4, NY-ESO-1 and/or SAGE antigen expression in tumour samples was evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). Informed consent was obtained from individuals prior to study enrolment.

Results
In total, 585 samples in 21 tumour types were evaluated between June 2009 and March 2018. The positive expression rates of these CT antigens were as follows: MAGE-A4, 34.6% (range, 30.7–38.7); NY-ESO-1, 21.0% (range, 17.2–25.1); and SAGE, 21.8% (range, 18.5–25.4). The MAGE-A4 antigen was expressed in 54.9% of oesophageal cancers, 37.5% of head and neck cancers, 35.0% of gastric cancers and 34.2% of ovarian cancers; the NY-ESO-1 antigen was expressed in 28.6% of lung cancers, 25.3% of oesophageal cancers and 22.6% of ovarian cancers; and the SAGE antigen was expressed in 35.3% of prostate cancers, 32.9% of oesophageal cancers and 26.3% of ovarian cancers. The most common tumour type in this study was oesophageal cancer. MAGE-A4, NY-ESO-1 and SAGE antigen expression were assessed in 214 oesophageal cancer samples, among which 24 (11.2%) were triple-positive, 58 (27.1%) were positive for any two, 59 (27.6%) were positive for any one, and 73 (34.1%) were triple negative.

Conclusions
Oesophageal cancer exhibited a relatively high rate of CT antigen mRNA expression positivity.
Nomograms that predict the survival of patients with adenocarcinoma in villous adenoma of the colorectum: a SEER-based study
Authors: Tang Chao-Tao , Zeng Ling , Yang Jing , Zeng Chunyan , Chen Youxiang 
Published: June 2020

Abstract
Background
Considering that the knowledge of adenocarcinoma in villous adenoma of the colorectum is limited to several case reports, we designed a study to investigate independent prognostic factors and developed nomograms for predicting the survival of patients.

Methods
Univariate and multivariate Cox regression analyses were used to evaluate prognostic factors. A nomogram predicting cancer-specific survival (CSS) was performed; internally and externally validated; evaluated by receiver operating characteristic (ROC) curve, C-index, and decision curve analyses; and compared to the 7th TNM stage.

Results
Patients with adenocarcinoma in villous adenoma of the colorectum had a 1-year overall survival (OS) rate of 88.3% (95% CI: 87.1–89.5%), a 3-year OS rate of 75.1% (95% CI: 73.3–77%) and a 5-year OS rate of 64.5% (95% CI: 62–67.1%). Nomograms for 1-, 3- and 5-year CSS predictions were constructed and performed better with a higher C-index than the 7th TNM staging (internal: 0.716 vs 0.663; P < 0.001; external: 0.713 vs 0.647; P < 0.001). Additionally, the nomogram showed good agreement between internal and external validation. According to DCA analysis, compared to the 7th TNM stage, the nomogram showed a greater benefit across the period of follow-up regardless of the internal cohort or external cohort.

Conclusion
Age, race, T stage, pathologic grade, N stage, tumor size and M stage were prognostic factors for both OS and CSS. The constructed nomograms were more effective and accurate for predicting the 1-, 3- and 5-year CSS of patients with adenocarcinoma in villous adenoma than 7th TNM staging.