Activation of executioner caspases is a predictor of progression-free survival in glioblastoma patients: a systems medicine approach.

Glioblastoma (GBM) is the most common and aggressive primary brain tumor in adults. GBM cells are highly resistant to apoptosis induced by antitumor drugs and radiotherapy resulting in cancer progression. We assessed whether a systems medicine approach, analysing the ability of tumor cells to execute apoptosis could be utilized to predict the response of GBM patients to treatment. Concentrations of the key proapoptotic proteins procaspase-3, procaspase-9, Smac and Apaf-1 and the antiapopotic protein XIAP were determined in a panel of GBM cell lines and GBM patient tumor resections. These values were used as input for APOPTO-CELL, a systems biological based mathematical model built to predict cellular susceptibility to undergo caspase activation. The modeling was capable of accurately distinguishing between GBM cells that die or survive in response to treatment with temozolomide in 10 of the 11 lines analysed. Importantly the results obtained using GBM patient samples show that APOPTO-CELL was capable of stratifying patients according to their progression-free survival times and predicted the ability of tumor cells to support caspase activation in 16 of the 21 GBM patients analysed. Calculating the susceptibility to apoptosis execution may be a potent tool in predicting GBM patient therapy responsiveness and may allow for the use of APOPTO-CELL in a clinical setting

Calnexin, an ER-induced protein, is a prognostic marker and potential therapeutic target in colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is a leading cause of cancer mortality in the Western world and commonly treated with genotoxic chemotherapy. Stress in the endoplasmic reticulum (ER) was implicated to contribute to chemotherapeutic resistance. Hence, ER stress related protein may be of prognostic or therapeutic significance. METHODS: The expression levels of ER stress proteins calnexin, calreticulin, GRP78 and GRP94 were determined in n = 23 Stage II and III colon cancer fresh frozen tumour and matched normal tissue samples. Data were validated in a cohort of n = 11 rectal cancer patients treated with radiochemotherapy in the neoadjuvant setting. The calnexin gene was silenced using siRNA in HCT116 cells. RESULTS: There were no increased levels of ER stress proteins in tumour compared to matched normal tissue samples in Stage II or III CRC. However, increased calnexin protein levels were predictive of poor clinical outcome in the patient cohort. Data were validated in the rectal cancer cohort treated in the neoadjuvant setting. Calnexin gene-silencing significantly reduced cell survival and increased cancer cell susceptibility to 5FU chemotherapy. CONCLUSION: Increased tumour protein levels of calnexin may be of prognostic significance in CRC, and calnexin may represent a potential target for future therapies

Erratum to: Calnexin, an ER stress-induced protein, is a prognostic marker and potential therapeutic target in colorectal cancer

Erratum to: Calnexin, an ER stress-induced protein, is a prognostic marker and potential therapeutic target in colorectal cancer

Genomic epidemiology of SARS-CoV-2 in a UK university identifies dynamics of transmission

AbstractUnderstanding SARS-CoV-2 transmission in higher education settings is important to limit spread between students, and into at-risk populations. In this study, we sequenced 482 SARS-CoV-2 isolates from the University of Cambridge from 5 October to 6 December 2020. We perform a detailed phylogenetic comparison with 972 isolates from the surrounding community, complemented with epidemiological and contact tracing data, to determine transmission dynamics. We observe limited viral introductions into the university; the majority of student cases were linked to a single genetic cluster, likely following social gatherings at a venue outside the university. We identify considerable onward transmission associated with student accommodation and courses; this was effectively contained using local infection control measures and following a national lockdown. Transmission clusters were largely segregated within the university or the community. Our study highlights key determinants of SARS-CoV-2 transmission and effective interventions in a higher education setting that will inform public health policy during pandemics.</jats:p

The role of anxiety in golf putting performance

INTRODUCTION: Anxiety’s influence on performance continues to be one of the main research interests for sport psychologists (Hanin, 2000). It is apparent, though, that there is a lack of empirical research characterising the multi-disciplinary effect of anxiety on sports performance. The current study aimed to ascertain biomechanical (accuracy, movement variability) and psychological (anxiety) markers to determine how anxiety affects golf putting. METHOD: 22 healthy subjects (12 male, 10 female, 21.7±2.0 yrs, 175.3±8.1 cm, 76.4±10.0 kg, all data mean±SD) who had played golf recreationally previously but with no recorded handicap were recruited. Subjects performed thirty 3.05 m putts using their own putter under a control and anxiety condition. Anxiety was elevated using environmental cues (e.g. presence of spectators) and a competition scenario. Three-dimensional motion was tracked using a six camera Motion AnalysisTM system operating at 240 Hz. Final ball position from the hole was ascertained using overhead digital photogrammetry. Self reported anxiety was measured pre, during and post putting using standardised self-report anxiety questionnaires. The Competitive State Anxiety Inventory (CSAI) was used to measure state anxiety intensity and direction across three sub scales (i.e. cognitive anxiety, somatic anxiety and selfconfidence). The shorter Mental Readiness Form (MRF) was used to obtain anxiety measures during performance. RESULTS: Significant changes in self-reported anxiety were reported between the control and anxiety conditions. Student’s t-test revealed that performance, as measured by distance from hole was not different in control (0.68±0.52 m) and anxiety conditions (0.56±0.33 m). Females, n=10, significantly worsened their performance under anxiety condition (1.02±0.45 m) compared to control (0.73±0.37 m). Movement analysis showed that swing tempo, represented as a ratio of backswing to downswing time increased significantly (p<0.05), from 0.57 to 0.65 from control to anxious conditions respectively. Total swing time increased by an average 0.16 s for anxious putts and left wrist angle was also more open at impact by 0.97 degrees. CONCLUSION: Results show anxiety did not cause significant change in putting performance overall

Development of Indicators to Assess Quality of Care for Prostate Cancer

Background:The development, monitoring, and reporting of indicator measures that describe standard of care provide the gold standard for assessing quality of care and patient outcomes. Although indicator measures have been reported, little evidence of their use in measuring and benchmarking performance is available. A standard set, defining numerator, denominator, and risk adjustments, will enable global benchmarking of quality of care.Objective:To develop a set of indicators to enable assessment and reporting of quality of care for men with localised prostate cancer (PCa).Design, setting, and participants:Candidate indicators were identified from the literature. An international panel was invited to participate in a modified Delphi process. Teleconferences were held before and after each voting round to provide instruction and to review results.Outcome measurements and statistical analysis:Panellists were asked to rate each proposed indicator on a Likert scale of 1–9 in a two-round iterative process. Calculations required to report on the endorsed indicators were evaluated and modified to reflect the data capture of the Prostate Cancer Outcomes Registry–Australia and New Zealand (PCOR-ANZ).Results and limitations:A total of 97 candidate indicators were identified, of which 12 were endorsed. The set includes indicators covering pre-, intra-, and post-treatment of PCa care, within the limits of the data captured by PCOR-ANZ.Conclusions:The 12 endorsed quality measures enable international benchmarking on the quality of care of men with localised PCa. Reporting on these indicators enhances safety and efficacy of treatment, reduces variation in care, and can improve patient outcomes.Patient summary:PCa has the highest incidence of all cancers in men. Early diagnosis and relatively high survival rates mean issues of quality of care and best possible health outcomes for patients are important. This paper identifies 12 important measurable quality indicators in PCa care