bluuebunny/crossref_metadata_2025_split huggingface dataset:
O1 Elevated expression level of capillary morphogenesis gene 2 in pancreatic ductal adenocarcinoma cell is associated with distant metastasis and poor prognosis
Authors: Fang Ziqian , Griffiths Paul , Al-Sarireh Bilal , Jiang Wen G , Ye Lin 
Published: July 2021

Abstract

Introduction
Emerging evidence revealed the active role played by capillary morphogenesis gene 2 (CMG2) during the disease progression and metastasis of some cancers. It was shown that CMG2 was increased in pancreatic tumours in our previous research. The current study further validated this finding for the expression of CMG2 in pancreatic cancer and also dissected its clinical implication.

Method
Immunochemical staining of CMG2 was performed on a pancreatic cancer tissue microarray (PA2081, Biomax, n = 104). Clinical relevance of CMG2 was analysed in TCGA pancreatic cancer cohort and gene array data (GSE71729) using ANOVA and Kaplan-Meier analyses. Influence of CMG2 on adhesion to a mesothelial cell monolayer was determined using both Mia-PaCa-2 and PANC-1 cell lines with CMG2 knockdown.

Result
CMG2 is increased significantly in pancreatic ductal adenomas, P &lt; 0.001 compared with adjacent non-tumour tissues. Higher levels of CMG2 were also revealed in the distant metastases of pancreatic cancer, P &lt; 0.001 compared with both primary tumuors and distant metastasis. Elevated expression CMG2 protein in pancreatic cancers was also observed on the tissue microarray. Patients with higher CMG2 expression tumours had shorter overall survival (median = 15.8 months), P &lt; 0.001 compared with those patients with lower CMG2 expressing tumours (median = 30.4 months). Knockdown of the CMG2 significantly decreased the number of cells which adhere to the mesothelial cells (P &lt; 0.001).

Conclusion
Elevated CMG2 expression in pancreatic ductal adenocarcinomas is associated with distant metastasis and shorter survival which requires further investigation to shed light on its therapeutic potential.

Take-home Message
Elevated CMG2 expression in pancreatic ductal adenocarcinomas is associated with distant metastasis and shorter survival.
O4 Neural network image capture to predict response of oesophageal adenocarcinoma to neoadjuvant therapy
Authors: Rahman S , Early J , Sharpe B , Lloyd M , Grace B , De Vries M , Ramchurn S , Underwood T J 
Published: July 2021

Abstract

Introduction
Locally advanced oesophageal adenocarcinoma is typically treated with neoadjuvant chemotherapy (NACT) or chemoradiotherapy (NACRT) followed by surgery. Significant benefit to neoadjuvant treatment however is confined to a minority of patients (&lt;25%) and there are no reliable means of establishing prior to treatment in whom this benefit will occur. In this study, we assessed the utility of features extracted from high-resolution digital microscopy of pre-treatment biopsies in predicting response to neoadjuvant therapy in a machine-learning based modelling framework.

Method
A total of 102 cases were included in the study. Pre-treatment clinical information, including TNM staging, was obtained, along with diagnostic biopsies. Diagnostic biopsies were converted into high-resolution whole slide-images and features extracted using a pre-trained convolutional neural network (Xception). Elastic net regression models were then trained and validated with bootstrapping with 1000 resampled datasets. The response was considered according to Mandard tumour regression grade (TRG).

Result
There were 45 (44.1%) responders (TRG1-2) and 57 (57%) non-responders (TRG3-5) in the dataset. 34 patients (33.3%) received NACT and 68 (66.7%) received NACRT. A model trained with RNA-seq data achieved fair performance only in predicting response (AUC 0.598 95% CI 0.593–0.603), which was far exceeded by use of segmented diagnostic biopsy images (AUC 0.872 95% CI 0.869–0.875), which also produced well calibrated predictions of risk.

Conclusion
Despite using a small dataset, impressive performance in classifying response to neoadjuvant treatment can be achieved, particularly using automated image classification. Further study to refine the methodology is required before expansion to clinical settings.

Take-home Message
Response to neoadjuvant treatment for oesophageal cancer can be predicted from diagnostic biopsies
O6 Analysis of angiogenic gene profiling after E-selectin + stem cell therapy in murine ischemic limb
Authors: Quiroz Hallie J , Shao Hongwei J , Li Yan , Ortiz Yulexi Y , Parikh Punam P , Lassance-Soares Roberta M , Liu Zhao-Jun J , Velazquez Omaida C 
Published: July 2021

Abstract

Introduction
There remains a paucity of novel therapeutics for limb salvage in patients with critical limb ischemia (CLI) for whom revascularization procedures have failed and amputation is imminent. We have shown that E-selectin+/Mesenchymal Stem Cell (MSC) injections into the ischemic limb tissue of a CLI mouse model improves revascularization and limb function. Thus, we sought to determine a mechanism of action for E-selectin+/MSC’s pro-angiogenic and tissue salvage properties.

Methods
MSC were extracted from donor mice bone marrow and subsequently engineered via viral transduction with E-selectin-ires-GFP/AAV and GFP/AAV (control) to create E-selectin-GFP+/MSC vs GFP+/MSC. Intramuscular injections of E-selectin-GFP+/MSC, GFP+/MSC, or PBS were performed in a mouse model of hindlimb ischemia. Laser doppler imaging (LDI), confocal laser microscopy, and treadmill exhaustion test were utilized to determine neovascularization and limb function. RNA extraction from engineered MSC (E-selectin-GFP+/MSC vs GFP+/MSC) and ischemic hindlimb tissues treated with E-selectin-GFP+/MSC vs GFP+/MSC was performed, followed by RT2 Profiler PCR Array analysis of 84 genes involved in angiogenesis. GFP+/MSC treated hindlimb tissue served as control. Student’s t-test or ANOVA was utilized to compare means and significance set at P &lt; 0.05.

Results
Compared with GFP+/MSC and PBS, treatment with E-selectin-GFP+/MSC increased ischemic leg LDI reperfusion (54% vs. 39% vs. 22%, P &lt; 0.001), treadmill distance traversed (162 m vs. 111 m vs. 110 m, P &lt; 0.01) and ischemic mouse footpad vessel density (23% vs. 14% vs. 14%, P &lt; 0.01). RT2 Profiler PCR Array demonstrated pro-angiogenic gene upregulation occurred in 7 genes (Csf3, Cxcl2, Cxcl5, Serpine1, F2, Lep, Tbx1, Table I.) in E-selectin-GFP+/MSC treated ischemic leg tissue while tumour necrosis factor (TNF) was found to be downregulated, when compared with GFP+/MSC treated tissues. Of these 7 upregulated genes, CXCl2, F2, Leptin and T-box1 (Table I.) are likely produced by E-selectin-GFP+/MSC, as analysis of cellular gene expression profiles of E-selectin-GFP+/MSC also revealed upregulation by 2-fold or more in these factors when compared to GFP+/MSC. Validation of gene functions in-vivo are under investigation.

Conclusion
Stem cell therapy using E-selectin-GFP+/MSC, in a murine model of CLI, confers both augmented postnatal neovascularization and increased limb function. The pro-angiogenic and pro-repair effects are likely mediated by upregulation of a panel of chemokines/cytokines and down-regulation of TNF in ischemic tissues treated with E-selectin-GFP+/MSC.
O11 Activated leukocyte cell adhesion molecule (ALCAM/CD166) is an important clinical and prognostic indicator in pancreatic cancer
Authors: Yang Y M , Sanders A J , Dong X , Cui Y , Hao C , Ji J , Jiang W G 
Published: July 2021

Abstract

Introduction
Activated leukocyte cell adhesion molecule (ALCAM/CD166) is a cell adhesion molecule and one of the potential metastasis ‘soil’ receptors that via homotypic and heterotypic interactions, mediates cell adhesion. The present study investigated the clinical, pathological and prognostic value of ALCAM in patients with pancreatic cancer.

Method
Pancreatic cancer tissues (n = 223), collected immediately after surgery, were analysed for levels of the ALCAM transcripts. The expression was analysed against clinical, pathological and clinical outcome of the patients. We validated our findings with an available TCGA database (n = 117), including correlations with the ALCAM interactive partners.

Result
Pancreatic cancer tissues had significantly higher levels of ALCAM transcript than normal tissues (P &lt; 0.00001). There were no significant differences with staging, differentiation and tumour locations. Tumours from patients who died of pancreatic cancer had significantly high levels of ALCAM compared with those who lived (P = 0.018), finding also supported by ROC analysis (P = 0.016). Multivariant analysis showed ALCAM as an independent prognosis factor for overall survival (hazardous ratio 5.485), with both nodal status and TNM staging contributing to the model (HR 2.578 and 3.02 respectively). A surprising finding was the relationship between ALCAM expression and microvessel embolism of tumour cells (P = 0.021, with vs without tumour embolism). ALCAM significantly correlated with its interactive protein partners including CD6 and ITGB1, but not L1CAM.

Conclusion
ALCAM/CD166 expression is aberrant in pancreatic cancer and the raised expression is an independent prognostic factor for the survival of the patients and the microvessel embolism by cancer cells.

Take-home Message
ALCAM is a prognostic indicator for survival and tumour embolism in pancreatic cancer
O13 Acid ceramidase: a potential biomarker for locally advanced rectal cancer?
Authors: Clifford Rachael Elizabeth , Govindarajah Naren , Bowden David , Sutton Paul , Parsons Jason , Vimalachandran Dale 
Published: July 2021

Abstract

Introduction
We have previously utilized proteomic and immuno-histochemical data to validate that high levels of acid ceramidase (AC) expression confers poorer neoadjuvant response in rectal cancer. Biological (siRNA, plasmid and CRISPR) AC manipulation altered radiosensitivity in-vitro. We aimed to assess the radiosensitising effect of pharmacological AC inhibitions and elucidate the potential underlying mechanism.

Methods
Optimal drug dosing was achieved using ELISA activity assays in multiple colorectal cancer cell lines (HCT116, HT29, LIM1215). Carmofur and a novel small molecular inhibitor (LCL521) were used as pharmacological inhibitors. Standard clonogenic assays assessed cell survival following increasing irradiation (2 D), volume change in 3 D spheroids and cell viability in patient derived organoids. Annexin V/PI staining was used to determine apoptosis.

Results
Carmofur clonogenic assays demonstrated reduced colony formation efficiency (CFE) and improved radiosensitivity across cell lines. HCT116 showed 0.438(CFE) control v 0.183(CFE) carmofur at 1 Gy, 0.140(CFE) control v 0.076(CFE) at 2 Gy (P = 0.000563). LCL521 dosing improved radiosensitivity in spheroid models. HCT116 volume day-15 2.36x10-5mm v control 4.15x10-5mm. siRNA-AC demonstrated increased apoptosis across time points compared to NT control (P = 0.035), and increased poly-ADP ribose polymerase-1 (PARP-1) cleavage in a p53-dependent process.

Conclusion
Initial work demonstrates that pharmacological inhibition of AC produces comparative radiosensitizing effects in these cell lines and cancer models. siRNA-AC increases apoptosis, suggestive of a potential underlying mechanism. This work further solidifies AC as a potential biomarker, however further recapitulation in more complex models and ultimately in-vivo is required to establish a translatable clinical role.
O14 Optimising the management of primary breast cancer in older women
Authors: Parks R M , Green A R , Cheung K L 
Published: July 2021

Abstract

Introduction
The risk of breast cancer increases with age and our global population is ageing. By 2040 the number of breast cancer cases diagnosed per year worldwide will double and over 40% of these will be in patients aged 70 or over. Despite this, there are few treatment guidelines specific to breast cancer in older women and none which consider the unique biological differences of this cohort.

Method
Surgical and core needle biopsy (CNB) specimens were obtained from an existing series of 1,785 women over the age of 70 with primary breast cancer, treated in a single institution with long-term (37+ years) follow-up. Of this cohort, 813 had primary surgical treatment. As part of previous work, it was possible to construct good quality tissue microarrays (TMAs) in 575 surgical specimens and 693 CNB specimens. Immunohistochemical staining for 32 biomarkers has been performed in all of the available TMAs. Association between histological score for each biomarker and tumour size, grade, recurrence rate, breast cancer specific and overall survival is currently being investigated in the whole cohort.

Results
Results to date have revealed a unique biological cluster in older women with primary breast cancer that is not seen in a comparative younger cohort. In the future, bioinformatics analysis will determine which biomarkers and in what combination, can predict chance of recurrence/overall survival in this cohort.

Conclusions
This information will be used to create a prognostic tool specific to assist older women with decision making regarding primary treatment of breast cancer.
O15 Venous Leg Ulceration: an assessment of associated lifestyle, sociodemographic and clinical factors using UK Biobank
Authors: Salim Safa , Vidal-Diez Alberto , Machin Matthew , Patterson Benjamin O , Onida Sarah , Davies Alun H 
Published: July 2021

Abstract

Introduction
A number of factors have reportedly been associated with venous leg ulceration (VLU) however many of these remain disputed. UK Biobank (UKB) is an electronic dataset that provides in-depth detail on the lives of its participants. The aim of this research is to utilise UKB to understand factors associated with VLU.

Methods
Participants in the UKB with historical or active venous ulceration were identified and an age, sex and comorbidity matched control group was formed. A multivariate logistic regression was used to explore factors associated with VLU with significant factors expressed through odds ratios (OR). Mortality was investigated using a Kaplan Meier plot and log-rank test. Data analysis was preformed using R Studio Version 1.2.5033 and Python 3.8.10.

Results
Factors associated with VLU included; male gender, older age, deprivation (OR 1.27), obesity (OR 1.40), current smoking (OR 1.21), immoderate alcohol intake (OR 1.32), previous deep vein thrombosis (OR 3.07), depression and loneliness (OR 1.21). Biochemical factors associated with VLU included low haemoglobin concentrations (OR 1.50), low circulating lymphocyte percentages (OR 1.57), raised glycated haemoglobin (HbA1c) (OR 2.92), raised c-reactive protein (OR 1.41), raised cystatin C (OR 1.11) and low Vitamin D levels (OR 1.52). At a median follow up of 11.5 years, the mortality in VLU participants was 28%; significantly higher than in controls (P &lt; 0.001).

Conclusion
Participants with VLU are comorbid with poorer physical, social and psychological wellbeing.
O23 Outcomes after non-operative management of perforated diverticular disease: a population based cohort study
Authors: Adiamah A , Ban L , Otete H , Crooks C J , West J , Humes D J 
Published: July 2021

Abstract

Introduction
The management of perforated diverticular disease has changed in the last 10 years with a move towards less surgical intervention. This population based cohort study aimed to define the risk of mortality and readmission following non-operative management of perforated diverticular disease (DD).

Method
Patients diagnosed with perforated DD and managed without surgery were identified from the linked Clinical Practice Research Datalink and Hospital Episode Statistics data from 2000 to 2013. The outcomes were 1-year case-fatality, re-admissions and surgery at re-admission.

Result
In total, 880 patients with perforated DD were managed without surgery, comprising of 523 females (59.4%). One year case-fatality was 33.2% (293/880). The majority of deaths occurred in the first 90 days following the index admission with a 90 day case-fatality of 28.8%. 90 day survival varied by age with 97.2% survival at 90 days in those under 65 years compared to 85.0% in those between 65–74 years and 51.5% in those over 75 years.
Of 767 patients discharged from hospital, 250 (32.6%, 250/767) were re-admitted (47 elective(6.1%) and 203 emergency(26.5%)) during a median of 1.6 years of follow-up (iqr 0.1–3.9 years) with similar proportions in each age category. In the first year of follow-up only 5.1% of patients required surgery of whom 16/767 (2.1%) required elective and 23/767 (3.0%) emergency surgery.

Conclusion
Conservative management of perforated diverticulitis in those under 65 years is feasible and safe. A third of patients are readmitted during follow-up, however, re-intervention rates following conservative management were low across all age categories.

Take-home Message
In younger patients (&lt;65yrs) conservative management of perforated diverticulitis is feasible and safe. A third of conservatively managed patients are readmitted during follow-up, however, need for surgery on readmission is rare.
O37 Carotid surgery during the COVID-19 pandemic
Authors: Busuttil A , Jacob L , Elanwar S , Lim C. S , Baker D. M 
Published: July 2021

Abstract

Introduction
The aim of this prospective study was to evaluate the efficacy and safety of carotid endarterectomy for symptomatic carotid stenosis during the COVID-19 pandemic.

Method
Re-organisation of stroke services due to the COVID-19 pandemic resulted in carotid endarterectomy for symptomatic disease being performed in two hospitals; Covid-19 free and non-free sites. Patients were referred from multiple online regional neurovascular multi-disciplinary team meetings, and managed according to the pre-Covid-19 guidance. All patients referred for carotid endarterectomy between 23 March 2020 and 31 July 2020 were included. Demographic, medical history, imaging, peri-operative, complication and follow-up data were collected and analysed prospectively.

Result
28 patients were referred for carotid endarterectomy, of whom 21 patients underwent surgery. The mean time to surgery was 11 days (3–35). The technical success rate was 100%. Peri-operatively and within 30-days post-operatively, no patient suffered death or stroke. There were 2 minor complications; one non-ST elevation myocardial infarction, and another wound haematoma and infection requiring readmission for antibiotics. No patient developed new COVID-19 infection post-operatively. Of the 7 patients not operated on; 2 were medically unfit for surgery, three declined surgery, and two had free floating thrombus that was managed successfully with anti-coagulation.

Conclusion
During the pandemic, the provision of carotid endarterectomy for symptomatic carotid diseases was carried out safely and within the current recommendations, with several pre-cautionary measures being undertaken. Therefore, symptomatic carotid intervention should still be considered to reduce the risk of stroke provided similar pre-cautionary measures are undertaken.

Take-home Message
Carotid surgery should continue during successive waves of the COVID-19 pandemic
O39 Unidimensional and functional pain assessment tools in postoperative adult patients: a systematic review of their development and utility
Authors: Baamer R M , Iqbal A , Lobo D N , Knaggs R D , Levy N A , Toh L S 
Published: July 2021

Abstract

Introduction
The Visual Analogue Scale (VAS), Numeric Rating Scale (NRS), Verbal descriptor scale, and faces pain scale are used to measure postoperative pain in adults. However, their utility in this population has not been reviewed systematically. We aimed to summarise and appraise the evidence relating to the measurement properties of unidimensional tools when used for this population and to identify available tools assessing the impact of pain on the restoration of function.

Method
Four databases (MEDLINE, EMBASE, CINAHL, PsycINFO) were searched up to August 2020 for relevant studies. Two reviewers independently screened articles and assessed risk of bias using the COensus-based Standards for the selection of health Measurement Instruments (COSMIN) checklist.

Result
Thirty-one studies were included. Only one study included an objective pain score; a tool assessing pain interference with function and reported low-quality evidence for construct validity. Studies looked at unidimensional tools were underpinned by low or very low-quality evidence for reliability, and all displayed a low quality of evidence of indeterminate responsiveness. Measurement error was only reported for VAS in one study of moderate quality. Interpretability results were available only for VAS and NRS. Feasibility results varied based on the included population.

Conclusion
Despite the extensive use of unidimensional tools, there is no evidence to suggest that any of these tools has superior measurement properties for postoperative pain. Therefore, future studies should be prioritised to assess their validity, measurement error and responsiveness. Validation studies of pain assessment tools that promote function are needed.

Take-home Message
Take home message: Functional pain scores should be assessed and validated for postoperative pain.
Epidemiology and burden of chronic kidney disease-associated pruritus
Authors: Kim Dana , Pollock Carol 
Published: August 2021

ABSTRACT
Chronic kidney disease–associated pruritus (CKD-aP) is a common, yet underrecognized condition in patients with CKD and end-stage kidney disease (ESKD). Real-world observational studies indicate that CKD-aP affects up to 80% of ESKD patients undergoing haemodialysis (HD), with ∼40% experiencing moderate to severe itch. CKD-aP can negatively impact patients’ mental and physical health-related quality of life (HRQoL) and is also associated with sleep disturbance and depression. Several studies have found that CKD-aP is a predictor of adverse medical outcomes, including an increased risk of hospitalizations and mortality. In this article we review the literature relating to the epidemiology of CKD-aP to describe its prevalence across the treatment spectrum of CKD (non-dialysis, HD, peritoneal dialysis and transplant recipients) and to summarize potential risk factors associated with its development. We also review key data from studies that have evaluated the impact of CKD-aP on HRQoL and medical outcomes.