bluuebunny/crossref_metadata_2025_split huggingface dataset:
O22: CONJUGATED IRON NANOPARTICLES AS THERAPEUTIC CARRIERS FOR SPECIFIC TARGETING OF CANCER CELLS
Authors: Alfadli FF , Sarwary R , Correia J , Ramesh B , Welch H 
Published: April 2021

Abstract

Introduction
Precision medicine with minimal side effects remains the goal of cancer therapy. Iron oxide nanoparticles are non-toxic, successful carriers of substances, targeting tissues and delivering high payloads of conjugated agents. Interfering RNA (siRNA) disrupts protein expression, an effective treatment e.g. for hereditary amyloidosis. This study tested transferrin-conjugated dopamine-coated iron oxide nanoparticle (TF-dpFe3O4) delivery of siRNA to cells overexpressing transferrin receptor (TFR).

Method
Cells were cultured in FBS-DMEM/F12. Fe3O4 nanoparticles were prepared by co-precipitation, dopamine coated +/- transferrin conjugation. LDH/MTT assays assessed cell viability responses to [TF-dpFe3O4] or [dpFe3O4]. Protein expression was examined by PAGE, densitometry and immunofluorescence. Targeting efficacy was determined by MEK2 gene silencing using siRNA-conjugated TF-dpFe3O4 or dpFe3O4.

Result
T-47D cells expressed high levels of TFR and MEK2. No significant effect on cell viability was observed with ≤2.5mg/mL TF-dpFe3O4 or dpFe3O4. By conventional transfection, 10nM siRNA lowered MEK2 expression levels to 25% (48hr); levels rebounded to 50% by 72hr. 10nM siRNA-conjugated TF-dpFe3O4 (2.5mg/mL) reduced MEK2 expression by 50% (72hr) without rebound; expression of a-tubulin (control) was unaffected. In contrast, as MEK2 levels decreased, TFR levels increased 2.2-fold (72hrs).

Conclusion
TF-dpFe3O4 nanoparticles are safe/efficient vehicles for delivering siRNA to cancer cells over-expressing TFR. Over 72hrs, protein expression of MEK2 reduced by 50%, a target superior to conventional methods. Notably: as the MAPK pathway was inhibited, increases in TFR levels were observed, suggesting adaptations to damage or stress.

Take-home message
TF-dpFe3O4 nanoparticles are a safe and efficient vehicle for delivering siRNA to cancer cells over-expressing TFR, allowing for successful targeting and inhibition of MAPK pathway proteins, such as MEK2, that drive tumour growth.
O24: THE PANCREATIC EPSILON-CELLS RECOVER THE EMBRYONIC GHRELIN SECRETION IN RESPONSE TO BARIATRIC SURGERY
Authors: Camacho-Ramirez A , Almorza-Gomar D , Falckenheiner J , Pérez-Arana G , Prada-Oliveira JA 
Published: April 2021

Abstract

Introduction
Many surgical techniques are employed in the treatment of obesity. A main consequence of these techniques is the severe improvement of Type 2 Diabetes mellitus. Many hypotheses had been exposed to know the intrinsic mechanism developed in this relationship. The enterohormones seems to be a definitive effector. The ghrelin is an enterohormone released for the gastric fundus and it has been related to the mentioned improvement. We hypothesized about the role of pancreatic epsilon cells, which have the capacity to release ghrelin during the embryonic stages. We studied the changes in the ghrelin immunostaining in endocrine pancreas of rats which underwent bariatric surgery. MATERIAL AND

Method
We employed 16 non obese euglycemic male Wistar rats, randomised in the surgical groups. These groups were the surgical techniques (Sleeve gastric –SG- and Roux en Y Gastric Bypass –RYGB-), and two controls (fasting and surgical). After three months, rats were sacrificed; the pancreas were obtained and processed for the immuno-cytochemical technique.

Result
We reported a significant increase of epsilon cells (ghrelin positive/mm2 pancreatic area) in the pancreas of SG versus the control groups (vs FC, P&lt;0.01 and vs sham, P&lt;0.05). CONCLUSION. SG and RYGB are surgical techniques broadly employed in humans and both reduce severely the fundus. Paradoxically, the serum level of ghrelin in patients are preserved. We reported that the total suppression of the fundus gastric produced the recovery of an embryonic pancreatic function. This mechanism could be related with the complex physiologic mechanism that improve T2DM after bariatric surgery.

Take-home message
After bariatric surgery, the pancreas release of ghrelin increased as the response to gastric reduction.
O32: TRANSPARENCY IN SURGICAL RANDOMISED CONTROLLED TRIALS: CROSS-SECTIONAL, OBSERVATIONAL STUDY
Authors: Helliwell JA , Shelton B , Mahmood H , Blanco-Colino R , Fitzgerald JE , Harrison EM , Bhangu A , Chapman SJ 
Published: April 2021

Abstract

Introduction
Randomised controlled trials (RCT) often provide the scientific basis on which commissioning and treatment decisions are made. It is essential that their results and methods are reported transparently. The aim of this study was to explore transparency with respect to trial registration, disclosure of funding sources, conflicts of interest (COI), and data sharing.

Method
This was a cross-sectional review of surgical RCTs. Data were extracted from RCTs in ten high-impact journals published in the years 2009, 2012, 2015, and 2018. Outcomes of interest were the incidence of reported trial registration, disclosure of funding sources, disclosure of investigator COI, and presence of a statement of data sharing plans.

Result
A total of 475 were eligible for analysis. Trial registration was present in 73 (67%) studies in 2009, 137 (84%) in 2012, 111 (89%) in 2015 and 110 (93%) in 2018. Funding statements were provided in 55%, 65%, 69.4%, and 75.4% of manuscripts, respectively. Conflicts of interest statements were provided in 49.5%, 89.1%, 94.6%, and 98.3% of manuscripts, respectively. Data sharing statements were present in only 15 (3.2%) RCTs. Eleven of these were in studies published most recently in 2018.

Conclusion
Trial registration, presence of funding statements, and disclosure of personal conflicts of interest in surgical RCTs have improved rapidly over the last 10 years. In contrast, disclosure of data sharing plans is exceptionally low. This may contribute to research waste and represents an essential target for improvement.

Take-home message
Trial registration, presence of funding statements, and disclosure of personal conflicts of interest in surgical RCTs have improved rapidly over the last 10 years. In contrast, disclosure of data sharing plans is exceptionally low. This may contribute to research waste and represents an essential target for improvement.
O40: PRE-OPERATIVE MANAGEMENT AND SENSITISATION IN VASCULARIZED COMPOSITE ALLOTRANSPLANTATION: A SYSTEMATIC REVIEW
Authors: Geoghegan L , Al-Khalil M , Scarborough A , Murray A , Issa F 
Published: April 2021

Abstract

Introduction
Vascularised composite allotransplantation (VCA) permits like-for-like reconstruction following extensive soft tissue injuries. The initial management of extensive soft tissue injury can lead to the development of anti-HLA antibodies through injury, transfusion and cadaveric grafting. The role of antibody-mediated rejection, donor-specific antibodies and graft rejection in the context of VCA remains unclear. This systematic review aimed to determine whether pre-operative management strategies influence immunological outcome following VCA.

Method
A systematic review of MEDLINE, EMBASE and CINAHL using a PRISMA-compliant methodology up to February 2019 was conducted. Pre-operative, procedural and long-term outcome data were collected and recorded for all VCA recipients on an individual patient basis.

Result
The search revealed 3,847 records of which 114 met inclusion criteria and reported clinical data related to 100 patients who underwent 129 VCA transplants. Trauma (50%) and burns (15%) were the most frequent indications for VCA. Of all 114 studies, only one reported acute resuscitative management. Fifteen patients (14.7%) were sensitized prior to reconstructive transplantation with an 80% incidence of acute rejection in the first post-operative year. Seven patients demonstrated graft vasculopathy, only one of whom had demonstrated panel reactive antibodies.

Conclusion
Currently employed acute management strategies predispose to the development of anti-HLA antibodies, adding to the already complex immunological challenge of VCA. Early appropriate care is warranted in patients with extensive soft tissue loss where the resuscitative needs should be balanced against strategies to mitigate the immunological burden, particularly as reconstructive transplantation becomes a feasible option for future soft tissue coverage.

Take-home message
Acute resuscitative management may sensitise potential transplant recipients following major soft tissue injury. Early appropriate care is warranted.
O43: CLINICAL IMPACT OF GENE FUSIONS IN BREAST CANCER BRAIN METASTASES
Authors: Cosgrove N , Vareslija D , Furney SJ , Oesterreich S , Lee AV , Couch FJ , Young LS 
Published: April 2021

Abstract

Introduction
The incidence of brain metastases is increasing despite longer survival rates for patients with advanced breast cancer. The identification of novel therapeutic targets for these patients is an urgent unmet clinical need. Sequencing of metastatic tumours have largely focused on mutations however gene fusions have an important, yet underappreciated role in tumorigenesis and disease progression. In this study, we investigate the role of gene fusions in brain metastatic disease and their impact on altered therapeutic responses.

Method
RNA sequencing was performed on the largest reported cohort of patient matched primary and resected brain metastatic tumours (45 patients n=90 samples). Expressed gene fusions were detected computationally using STAR-Fusion and Arriba.

Result
We identified differential gene fusion burden in brain metastatic tumours (medium of 58) vs. primary breast tumours (medium of 38) (p &lt; 0.05). Enrichment for fusions in pathways associated with tumour cell plasticity and proliferation with recurrent fusions in known cancer driver genes related to MAPK, HER signaling identified. Of note, a fusion in CDK12 is of clinical importance. Increased genomic alterations and over expression of CDK12 is associated with brain metastases free survival in an independent cohort of primary breast tumours with a recorded history of brain metastases. It has been proposed that inhibition of CDK12 may induce BRCAness in tumours making them sensitive to PARP inhibition.

Conclusion
These results highlight the significant role of gene fusions in breast cancer brain metastases.

Abbreviations
MAPK Mitogen Activated Protein Kinase, HER Human Epidermal Receptor, CDK12 Cyclin Dependent Kinase 12

Take-home message
We highlight the significant role of gene fusions in breast cancer brain metastases and offer specific actionable genomic alterations to be exploited.
O44: WOUND HEALING INFLAMMATORY MARKERS PREDICT PROGNOSIS AND SURVIVAL IN EARLY BREAST CANCER
Authors: Singh U , Castle J , Greenhalgh S , Hussain U , Descamps T , Nash S , Wilson M , Hunt R , Kirwan CC 
Published: April 2021

Abstract

Introduction
Cancer is likened to a non-healing wound. There is limited evidence on the expression of wound healing tissue inflammatory markers, CD68(pan-macrophage marker), HO-1(tumour cell marker) and FAP(cancer-associated fibroblast marker) in human breast cancer.

Method
In 201 invasive breast cancer and 58 DCIS patients, CD68+TAM expression, tumour HO-1 and fibroblast FAP expression, quantified by immunohistochemistry(dichotomised: high/present vs low/absent), was correlated with tumour factors (grade, proliferation(Ki67), ER, HER2); demographic factors, behavioural factors (smoking, alcohol) and survival status(DFS, OS)

Result
High CD68+macrophage expression was increased in invasive breast cancer, compared to DCIS, and normal tissue distant from the tumour(59%,41%and 6% respectively; p&lt;0.001).In invasive cancer,CD68+TAM expression increased with increasing tumour grade(Grade 1:42%, Grade 2:58%, Grade 3:72%; p=0.006), high Ki67(71%vs.47%; p=0.004), ER negativity(79.4%vs.55.4%; p=0.01) and HER2(HER2 positive 81.8% vs. HER2 negative 56.3%; p=0.03). CD68+TAM expression was higher in high compared to low/intermediate grade DCIS(44% % vs. 31% p=0.52). CD68+TAM expression was increased in patients who self-reported alcohol intake(non-drinker 43% vs. drinker 62%; p=0.01). HO-1 was associated with shorter DFS(HR:3.22,p=0.027) and OS(HR:2.86,p=0.029).FAP fibroblast expression correlated with longer DFS (HR:0.296,p=0.029) and OS (HR:0.271,p=0.008).

Conclusion
Tumour inflammation as assessed by CD68+TAM expression shows utility in identifying aggressive breast cancer sub-types. The association reported between CD68+TAM density and alcohol intake suggests a possible mechanism for alcohol as a risk factor for breast cancer. The prognostic value of HO-1 and FAP expression demonstrated here suggests a functional role of these wound healing markers in breast cancer. HO-1:Heme-oxygenase-1; FAP:Fibroblast activation protein; TAM:Tumour associated macrophage; DCIS: Ductal carcinoma in situ

Take-home message
Wound healing pathways of inflammation may be implicated in early breast cancer development
O46: PERIOPERATIVE LIQUID BIOPSY MAY HELP PREDICT THE RISK OF RECURRENCE IN BREAST CANCER PATIENTS
Authors: Hassan F , O'Leary DP , Ita M , Corrigan M , Wang JH , Redmond HP 
Published: April 2021

Abstract

Introduction
Liquid biopsy analysis using cell-free DNA (cfDNA) and circulating tumour DNA (ctDNA) has emerged as a promising non-invasive technique to detect fragmented circulating tumour DNA. It has shown excellent diagnostic and prognostic potential in breast cancer. Here, we aimed to evaluate the peri-operative dynamics of cfDNA and ctDNA to determine their prognostic ability in breast cancer.

Method
Breast cancer patients undergoing curative surgery were included. Blood samples were taken pre-operatively and 30 days post-operatively. cfDNA was extracted and measured using spectrophotometry. DNA integrity (long/short DNA fragments) was measured using ALU247 and ALU115 primers. PIK3CA mutation at exon 9 and 20 in ctDNA was detected using high resolution melting (HRM) real-time PCR combined with parallel internal controls. Ethical approval was granted.

Result
A total of 29 patients were studied, 14 disease-free group (DF) and 15 disease recurrence group (DR). The median follow-up was 36 months. cfDNA concentrations and DNA integrity were significantly higher in DR group compared to the DF group pre-operatively (cfDNA concentrations, p=0.0004; DNA integrity, p=0.039) and at 30 day post-operative time period (cfDNA concentrations, p=0.04; DNA integrity, p=0.03). Higher post–operative cfDNA concentrations were predictive of poor disease-free survival (HR: 3.8, p=0.02). Post-operative PIK3CA mutation detection in ctDNA was associated with a higher risk of recurrence (Odds ratio: 1.86, 95% CI: 0.36-12.9).

Conclusion
cfDNA and ctDNA assessment can provide valuable prognostic information at the time of surgery and have the potential to stratify the risk of recurrence and allow more personalised follow-up plan in breast cancer patients.

Take-home message
Liquid biopsy is a non- invasive and easily reproducible blood test that can provide important prognostic information at 30 days following surgery and may help clinicians to predict which breast cancer patients are at higher risk of recurrence following surgery.
O49: EFFECT OF AFIMOXIFENE (Z-4-HYDROXYTAMOXIFEN) ON ADIPOSE-DERIVED STEM CELLS
Authors: Challapalli RS , Dwyer RM , McInerney N , Kerin MJ , Lowery AJ 
Published: April 2021

Abstract

Background
Adipose-derived stem cells (ADSCs) are a promising cell source for adipose tissue engineering. Currently, novel breast reconstruction techniques using ADSCs are actively being explored. Systemic chemo- & hormonal therapy may impede tissue regeneration in breast cancer patients. However, the effect of hormonal therapy on ADSCs and their regenerative capabilities is poorly understood.

Aims
The current study aims to analyse the effect of Afimoxifene, an active metabolite of Tamoxifen, on proliferation and viability of ADSCs in vitro

Method
Lipoaspirates or adipose tissue were obtained with informed consent from breast cancer patients and healthy controls. The isolated ADSCs were subjected to single or multiple dose(s) of Z-4-Hydroxytamoxifen (12.5nM, 25nM, 50nM, 100nM and 1μM) and, analyzed on days 1, 3 and 5, using CellTitre 96 ® AQueous Cell proliferation assay. T47D and MDA-MB-231 cell lines were used as positive and negative controls, respectively.

Result
ADSCs were obtained from a total of 3 patients. ADSCs were isolated from a cancer patient with/without active disease at the time of sample procurement and healthy subjects opting for elective cosmetic procedures. Morphology, CFU assay and adipogenic differentiation assay were used to validate stem cell population. Afimoxifene demonstrated no statistically significant reduction in the viability or proliferation of the ADSCs, irrespective of the dose- or time-dependent exposure or cancer status (p &gt;0.05).

Conclusion
Afimoxifene has no deleterious effect on viability or proliferation of human ADSCs up to 1μM concentration.

Key words
Adipose-derived stem cells, Afimoxifene, Breast reconstruction, Hormone therapy, Tamoxifen.

Take-home message
Afimoxifene has no deleterious effect on viability or proliferation of human ADSCs up to 1μM concentration
O52: THE IMPACT OF STUDENT BACKGROUND ON PERFORMANCE AND STRESS DURING SURGICAL SIMULATION
Authors: Soualhi A , Amin MSA , Aydin A , Khan MS , Dasgupta P , Makanjuola J , Ahmed K 
Published: April 2021

Abstract

Introduction
Early exposure of medical students to surgical skills has been associated with an increased interest in pursuing a career in surgery. This study aimed to investigate the impact of student background on basic laparoscopic skills acquisition and perceived stress to workload during simulation.

Method
Students were recruited to a course modelled on the European Basic Laparoscopic Urological Skills (E-BLUS) programme. Students filled out a pre-course demographic survey, and a post-course survey that evaluated perceived stress to workload (SURG-TLX). Pre- and post-course confidence in laparoscopic skills, performance in the course, as well as SURG-TLX parameters were statistically compared for all demographic factors.

Result
Twenty-three participants completed the course, fifteen (65%) of which were female. Ten students were junior (first and second year), and thirteen were senior (third year and above). Hobbies were grouped into either requiring hand-eye coordination (n=9), manual dexterity (n=9), or no relevance to surgery (n=5). No significant differences were found in demographic factors for course performance or pre- and post-course confidence. No significant differences were found between male and female students, and between different hobby groups, in all SURG-TLX parameters. Senior students reported a significantly higher Physical Demand of the SURG-TLX compared to juniors (p=0.042). No differences were found in other parameters.

Conclusion
Our study showed no correlation between student background (notably sex and stage of medical school) and basic laparoscopic skills acquisition or stress during simulation. We therefore suggest that medical students are provided with more exposure to acquire basic laparoscopic skills regardless of their background.

Take-home message
Medical student background is not a discriminator in surgical simulation performance and stress. All medical students, regardless of their sex or stage of medical school, should be given the opportunity to practice laparoscopic skills.
O53: SO YOU WANT TO BE A ROBOTIC SURGEON? THE EFFECT OF BASELINE PSYCHOMOTOR ABILITY AND VIDEO-GAME EXPERIENCE ON ROBOTIC SURGICAL SKILL: A RANDOMISED CONTROL TRIAL
Authors: Hay D , Ahmed K , Dasgupta P , Challacombe B 
Published: April 2021

Abstract

Introduction
We assessed whether expert mentoring improved the rate of uptake of robotic surgical skill and whether general advanced psychomotor ability (PMA), and specific video-game experience (VGE) had any impact on robotic surgical skill.

Method
Twenty robotically naive medical students were blinded and randomised to two cohorts; control (CC) and intervention (IC). Each student's initial performance on a variety of da Vinci Skills Simulator (dVSSim) exercises was measured and then reassessed following an independent practice (CC) or mentor guided practice session (IC). Outcome metrics were overall score, time to completion, economy of motion and master workspace range. Quantitative, questionnaire data was collected to evaluate the relationship between robotic surgical skill, PMA and VGE. Statistical analysis was performed with SPSS software utilising the independent t-test.

Result
On average, overall score for CC improved by 16.8% compared to 43.3% for the IC (p=0.04). Time to completion improved by 26.2% (CC) vs. 40% (IC), economy of motion by 16.5% vs. 25% and master workspace range by 8% vs. 11%. PMA correlated with better initial performances for all metrics, especially for overall score (p=0.003) and economy of motion (p=0.03). Students with more VGE had overall scores that were on average 20% better than those with little or no experience and this relationship was also seen for economy of motion and master workspace range.

Conclusion
Expert mentoring leads to a greater improvement in performance than independent practice alone. Advanced PMA correlates with greater innate robotic skill, as does VGE, but to a lesser extent.

Take-home message
1) Expert mentoring leads to a greater improvement in performance than independent practice alone. 2) Advanced PMA correlates with greater innate robotic skill, as does VGE, but to a lesser extent.
O55: FOSTERING A CULTURE OF INNOVATION IN MEDICAL STUDENTS AS FUTURE SURGEONS
Authors: Sawhney R , Kenner M , Bolton W 
Published: April 2021

Abstract

Introduction
In recent years, new technologies and rising costs in the NHS have created a thirst for innovation, particularly in surgical specialties. Centres for medical education are being encouraged to cultivate enterprise and innovative thinking among their students.
A one-day educational conference was organised by a student-led surgical society to introduce students to technological advancements in surgery and underline the scope for innovation within the NHS.

Method
The conference included: three keynote speeches, surgical skills workshops (basic and advanced suturing, plastics and general surgery-oriented skills), 3D-printing demonstration, minimally-invasive surgery simulation, virtual reality interaction and an innovation ‘hack-a-thon’ addressing an unmet need in surgery.
An online questionnaire comprising Likert-scale and free-text responses was circulated to all attendees.

Result
72 delegates attended and 63 completed feedback forms (87.5%). As a consequence of attending the conference, participants reported an increase in interest in surgical careers (4.40-4.68, p &lt;0.001), inspiration to innovate (3.77-4.21, p &lt;0.001), and ability to innovate (3.69-4.06, p &lt;0.001) before and after attending. Furthermore, 89% of delegates saw more scope for innovation in the NHS as a result of attending the conference. Finances and cultural attitudes resisting change were identified as major barriers to innovation; necessity for innovation (cost-cutting, improving patient outcomes and quality of life) was the primary driver.

Conclusion
This event had a significant impact on fostering innovative thinking among medical students. From the results, interventions listed above are meaningful in encouraging a culture of innovation among future surgeons.

Take-home message
This student-led conference had a positive impact on fostering innovative thinking among medical students. From the results, interventions such as inspiring talks, interactive skills workshops, and hack-a-thons can be meaningful tools for encouraging a culture of innovation among future surgeons.