The purpose of this paper is to develop detailed insight into loyalty among football fans of Hibernian FC, moving beyond typologies to a more socially grounded approach. Issues explored include ...patterns of consumption, distinctions between fan groups, and antecedents of loyalty. The origins and development of the club are evaluated, and consumer fanaticism, football fan loyalty, consumption behaviour, and the sociological impact of fan communities are discussed. Data were collected using a variety of methods, including participant observation, in-depth interviews, and analysis of websites and fan forums. Key findings relate to the impact of family and community influences on loyalty, initial experiences of developing associations with the club, through to the impact of socialisation, and the lived experience of being a supporter. A supporter matrix is constructed as a portrayal of the loyalty found at the club. A range of theoretical implications is considered, and the matrix promoted as a tool for understanding loyalty in clubs with similar social structures and community connections.
Aim
Neoadjuvant treatment (NaT) for locally advanced rectal cancer prior to surgery has led to improved outcomes. However, the relationship between pathological response to NaT and survival is not ...entirely clear. The aim of this study was to assess the degree of pathological response to NaT on survival outcomes.
Methods
Clinical and pathological data were collected from a prospectively maintained pathology database between 2005 and 2017. The primary outcome was the overall survival based on pathological response categorized as complete, good partial, partial and minimal. Univariate and multivariate analyses were conducted to identify variables predictive of survival. Cox proportional hazard ratios were used for survival.
Results
A total of 596 patients had surgery following NaT for locally advanced rectal cancer. The median follow‐up was 4.57 years (interquartile range 2.21–8.15 years). The overall survival for complete pathological response was 75.6% vs. 37.3% for minimal response (P < 0.001). The overall survival at the end of the study in the good partial vs. partial response groups was 58.9% vs. 39% (P < 0.001). On multivariate analysis, the degree of pathological response remains an independent variable for overall and disease‐specific survival across all categories.
Discussion
In addition to other pathological variables, the degree of pathological response to NaT is an independent predictor for survival outcomes. Future verification of these findings elsewhere could support NaT response being used for adjuvant therapy decision making.
Ileus (delayed return of bowel function after surgery) is one of the highest priority research questions in modern day colorectal practice. Current Enhanced Recovery After Surgery (ERAS) guidance ...either does not include a specific recommendation for volume of postoperative oral fluids/foodstuffs or suggests ad-lib fluids. It is unclear if the volume of intake affects ileus rates. This systematic review aimed to determine the optimal fluid volume for patients to consume day one after elective colorectal surgery.
The literature was searched across seven databases, September 23, 2020. Randomised controlled trials of adults undergoing elective colorectal surgery, comparing oral intake postoperatively were eligible for inclusion. Two blinded reviewers assessed papers with disagreements resolved by a third independent reviewer. Main outcomes were ‘resolution of postoperative ileus’ and ‘length of hospital stay’. Secondary outcomes included vomiting, mortality and complications.
Of 2175 screened papers, eight were eligible for inclusion. All studies gave a clear liquid diet postoperatively. The comparison groups followed a traditional nil-by-mouth approach. All studies showed a minor reduction in postoperative ileus and hospital stay in the intervention group, but we are unable to determine the optimal postoperative oral fluid volume. The low number and poor quality of studies was a significant limitation. None of the trials were conducted within an ERAS protocol: only 883 patients were included in total.
From the current literature it is unclear how postoperative oral fluid volume intake affects gastrointestinal function and ileus in elective colorectal surgical patients. This remains an important area for further research.
•Only eight trials looked at post-operative oral fluid intake and ileus.•All trials had a graded introduction to diet, contrary to ERAS guidance.•The optimal volume of oral intake post-operatively remains unclear.•Oral fluid intake after elective colorectal surgery is an area for further research.
Abstract
The majority of compounds designed against cancer drug targets do not progress to become approved drugs, mainly due to lack of efficacy and/or unmanageable toxicity. Robust target evaluation ...is therefore required before progressing through the drug discovery process to reduce the high attrition rate. There are a wealth of publicly available databases that can be mined to generate data as part of a target evaluation. It can, however, be challenging to learn what databases are available, how and when they should be used, and to understand the associated limitations. Here, we have compiled and present key, freely accessible and easy-to-use databases that house informative datasets from in vitro, in vivo and clinical studies. We also highlight comprehensive target review databases that aim to bring together information from multiple sources into one-stop portals. In the post-genomics era, a key objective is to exploit the extensive cell, animal and patient characterization datasets in order to deliver precision medicine on a patient-specific basis. Effective utilization of the highlighted databases will go some way towards supporting the cancer research community achieve these aims.
Graphical Abstract
Graphical Abstract
HLTF is highly similar in domain organisation to yeast Rad5. We identify PTIP and RPA70, both involved in DNA replication and DNA repair, as HLTF-interacting proteins although cells depleted of HLTF ...did not show defects in cellular responses to DNA damage. In vitro, HLTF has ATPase activity and E3 ubiquitin ligase activity with a range of E2 ubiquitin conjugating enzymes. HLTF expression is severely reduced in a range of cancer cells, and we suggest that the HLTF antibodies generated in this study could be used for cancer diagnostic purposes.
Outcomes in locally advanced rectal cancer are improved by neoadjuvant therapy followed by surgical resection. Some patients respond completely to preoperative treatment. Therefore, predicting the ...pathological response to preoperative therapy is of clinical importance. Accurate prediction would allow for tailored approaches to neoadjuvant therapy.
All patients undergoing resection of rectal adenocarcinoma after neoadjuvant therapy between 2006 and 2015 were included in this cohort study. Patients were identified from a prospectively collected database and data were supplemented retrospectively with full blood count at diagnosis. Specimens resected following neoadjuvant therapy were graded according to pathological response. Follow-up data was obtained from the national registry. The primary outcome was complete pathological response.
Of 330 patients, 71 (21.5%) responded completely to preoperative therapy. Median age was 66 and 65% were male (n = 215). White cell count (WCC) was the most predictive marker, for predicting pCR; area under the curve (AUC) 0.666. This was higher than neutrophil/platelet ratio (AUC 0.652) or neutrophil/lymphocyte ratios (AUC = 0.437). Kaplan-Meier survival analysis showed those patients with WCC > 8 had poorer survival than those with WCC < 8 (p = 0.009).
Routinely collected haematology samples at the point of diagnosis can assist in predicting for complete response to neoadjuvant therapy. Although novel biomarkers will have a greater predictive value, this clinically available value test could help to assist in risk stratification of patients using routinely collected laboratory tests.
-mutant colorectal cancers are resistant to therapeutics, presenting a significant problem for ∼40% of cases. Rapalogs, which inhibit mTORC1 and thus protein synthesis, are significantly less potent ...in
-mutant colorectal cancer. Using
-mutant mouse models and mouse- and patient-derived organoids, we demonstrate that KRAS with G12D mutation fundamentally rewires translation to increase both bulk and mRNA-specific translation initiation. This occurs via the MNK/eIF4E pathway culminating in sustained expression of c-MYC. By genetic and small-molecule targeting of this pathway, we acutely sensitize KRAS
models to rapamycin via suppression of c-MYC. We show that 45% of colorectal cancers have high signaling through mTORC1 and the MNKs, with this signature correlating with a 3.5-year shorter cancer-specific survival in a subset of patients. This work provides a c-MYC-dependent cotargeting strategy with remarkable potency in multiple
-mutant mouse models and metastatic human organoids and identifies a patient population that may benefit from its clinical application. SIGNIFICANCE:
mutation and elevated c-MYC are widespread in many tumors but remain predominantly untargetable. We find that mutant
modulates translation, culminating in increased expression of c-MYC. We describe an effective strategy targeting mTORC1 and MNK in
-mutant mouse and human models, pathways that are also commonly co-upregulated in colorectal cancer.
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