tbuckley/cabot-search huggingface dataset:
P14.65 Survival in a consecutive series of 467 glioblastoma patients: impact of prognostic factors and recurrent treatment at two independent institutions
Authors: H Blakstad, J Brekke, M A Rahman, V S Arnesen, P Brandal, S A Lie, M Chekenya, D Goplen
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Glioblastoma (GBM) is an aggressive primary brain tumor with median overall survival (OS) of less than one year in unselected adult patients. There is no standard therapy at recurrence. We aimed to evaluate OS in a consecutive series of GBM patients from Norway’s two largest regional health authorities, compare the effect of physicians’ choice of antineoplastic treatment upon recurrence and identify prognostic and predictive factors. MATERIAL AND METHODS Clinicopathological data from n=467 patients with histologically confirmed GBM diagnosed and treated at Haukeland and Oslo university hospitals from January 2015 to December 2017 was retrospectively collected. Data included tumor location, methylation status of the methylguanine-DNA methyltransferase (MGMT) promoter and mutation of the isocitrate dehydrogenase (IDH) genes, patient age and sex, extent of tumor resection at primary diagnosis, and treatment at first, second and third tumor recurrences. Cox-proportional hazards regression with pairwise analyses adjusted for multiple testing with Scheffé’s post-hoc test were used to adjust effect of multiple risk factors on mortality. RESULTS Median OS was 12.1 months and 21.4 % and 6.8 % of patients were alive at 2 and 5 years, respectively. Treatment at recurrence varied between institutions but did not impact OS (p=0.201). Median time to progression was 8.2 months. Age, MGMT promoter methylation, tumor location and extent of tumor resection were all independent prognostic factors for OS. Patients receiving radiotherapy to 60 Gray with concomitant and adjuvant temozolomide at primary diagnosis had best outcome with median OS of 16.1 months and 9.3% were alive at 5 years. At first recurrence patients eligible for gammaknife/stereotactic radiosurgery (GK/SRS) or surgery, alone or combined with chemotherapy, had superior survival compared to chemotherapy alone (p&amp;lt;0.0001 and p=0.014, respectively). On Scheffé’s post-hoc analyses only GK/SRS was superior to chemotherapy (p=0.01). At second and third recurrence none of the antineoplastic strategies came across as superior or inferior to each other using Cox. On Scheffé’s post-hoc analyses chemotherapy alone and combined with bevacizumab were superior at second recurrence (p=0.008 and p=0.042, respectively) and chemotherapy combined with bevacizumab was superior at third recurrence (p=0.043), compared to no antineoplastic treatment. Our retrospective study is limited by small sample sizes and heterogeneous treatment groups, especially at second and third recurrences, as well as patient selection. CONCLUSION Recurrence treatment differed between the two institutions but there was no difference in OS. Our findings underline the lack of standard therapy upon GBM recurrence and the urgent need for novel therapeutic strategies.
Alternative splicing of viral transcripts: the dark side of HBV
Authors: Dina Kremsdorf, Bouchra Lekbaby, Pierre Bablon, Jules Sotty, Jérémy Augustin, Aurélie Schnuriger, Jonathan Pol, Patrick Soussan
Journal: Gut (2021)

Regulation of alternative splicing is one of the most efficient mechanisms to enlarge the proteomic diversity in eukaryotic organisms. Many viruses hijack the splicing machinery following infection to accomplish their replication cycle. Regarding the HBV, numerous reports have described alternative splicing events of the long viral transcript (pregenomic RNA), which also acts as a template for viral genome replication. Alternative splicing of HBV pregenomic RNAs allows the synthesis of at least 20 spliced variants. In addition, almost all these spliced forms give rise to defective particles, detected in the blood of infected patients. HBV-spliced RNAs have long been unconsidered, probably due to their uneasy detection in comparison to unspliced forms as well as for their dispensable role during viral replication. However, recent data highlighted the relevance of these HBV-spliced variants through (1) the trans-regulation of the alternative splicing of viral transcripts along the course of liver disease; (2) the ability to generate defective particle formation, putative biomarker of the liver disease progression; (3) modulation of viral replication; and (4) their intrinsic propensity to encode for novel viral proteins involved in liver pathogenesis and immune response. Altogether, tricky regulation of HBV alternative splicing may contribute to modulate multiple viral and cellular processes all along the course of HBV-related liver disease.
3D collagen matrices modulate the transcriptional trajectory of bone marrow hematopoietic progenitors into macrophage lineage commitment
Authors: Pan Zhang, Linmu Xu, Jingsong Gao, Guangkui Xu, Yanping Song, Guang Li, Jingjing Ren, Yunjie Zhang, Cheng Yang, Yu Zhang, Ruiheng Xie, Nu Zhang, Hui Yang
Journal: Bioactive Materials (2021)

Physical signals provided by the extracellular matrix (ECM) are key microenvironmental parameters for the fate decision of hematopoietic stem and progenitor cells (HSPC) in bone marrow. Insights into cell-ECM interactions are critical for advancing HSC-based tissue engineering. Herein, we employed collagen hydrogels and collagen-alginate hydrogels of defined stiffness to study the behaviors of hematopoietic progenitor cells (HPCs). Three-dimensional (3D) collagen hydrogels with a stiffness of 45 Pa were found to promote HPC maintenance and colony formation of monocyte/macrophage progenitors. Using single-cell RNA sequencing (scRNA-seq), we also characterized the comprehensive transcriptional profiles of cells randomly selected from two-dimensional (2D) and 3D hydrogels. A distinct maturation trajectory from HPCs into macrophages within the 3D microenvironment was revealed by these results. 3D-derived macrophages expressed high levels of various cytokines and chemokines, such as Saa3, Cxcl2, Socs3 and Tnf. Furthermore, enhanced communication between 3D-macrophages and other hematopoietic clusters based on ligand-repair interactions was demonstrated through bioinformatic analyses. Our research underlines the regulatory role of matrix-dimensionality in HPC differentiation and therefore probably be applied to the generation of specialized macrophages.
Illness perceptions, financial toxicity, symptom burden, and survival in cancer clinical trial (CCT) participants.
Authors: Subha Perni, Chukwuma Azoba, Emily Gorton, Elyse R. Park, Bruce Allan Chabner, Beverly Moy, Ryan David Nipp
Journal: Journal of Clinical Oncology (2021)

160 Background: Patients’ perceptions of their illness are important for treatment decision-making and quality of life. Limited data exist describing associations of illness perceptions with other patient-centered outcomes, particularly in CCT participants. We sought to examine associations among illness perceptions and CCT patients’ financial toxicity, physical and psychological symptoms, and survival. Methods: From 7/2015-7/2017, we prospectively enrolled CCT participants who expressed interest in financial assistance programs (n = 157) and a group of patients matched by age, sex, cancer type, specific trial, and trial phase (n = 103). We assessed baseline illness perceptions (Brief Illness Perceptions Questionnaire [BIPQ] with scores &gt; 50 indicating negative perceptions), financial toxicity (degree costs of cancer care have been a burden, moderate to catastrophic indicating financial toxicity), physical (Edmonton Symptom Assessment Scale [ESAS]) and psychological (Patient Health Questionnaire-4 [PHQ-4]) symptoms. We used descriptive statistics to examine associations of BIPQ and sociodemographic/clinical factors, financial toxicity, ESAS, PHQ-4, and overall survival. We used the Kaplan-Meier method to estimate median survival times and Cox regression to assess the association of BIPQ and overall survival. Results: Among 260 patients, 189 (72.7%) completed BIPQ surveys (median age 69 [Range 26 to 83] years, 66.1% female). 68.8% had negative illness perceptions. We found no significant associations among negative illness perceptions and patients’ age, sex, race, education, marital status, performance status, insurance, cancer type, metastatic disease status, self-reported income, trial phase, trial year, or Charlson Comorbidity Index score. Patients with negative illness perceptions were more likely to report financial toxicity (69.8% vs 48.8%, p = 0.006), and had higher ESAS-total (Medians: 44 [Range 0-89] vs 21 [Range 0-78], p &lt; 0.001), PHQ-4 depression (Medians: 2 [Range 0-6] vs 0 [Range 0-6], p &lt; 0.001), and PHQ-4 anxiety (Medians: 3 [Range 0-6] vs 1 [Range 0-6], p &lt; 0.001) scores. Patients with negative illness perceptions had shorter overall survival (Medians: 22 [Range 10-29] vs 42 [Range 28-Not Reached] months, log-rank p = 0.004). Adjusting for receipt of financial assistance, patients with negative illness perceptions experienced higher risk of death (HR 1.65, 95% CI 1.10-2.48). Conclusions: In this prospective study of CCT participants, we found that patients with negative illness perceptions experienced greater financial toxicity, more symptom burden, and worse survival than those with more positive perceptions, despite comparable sociodemographic/clinical factors. These findings highlight the need to assess and address patients’ illness perceptions and financial burden when seeking to enhance patient-centered outcomes in oncology.
Common intestinal stoma complaints
Authors: Catherine Strong, Julia Hall, George Wilson, Kate Carney
Journal: BMJ (2021)

### What you need to know

Approximately 100 000 people in the UK have an intestinal stoma,1 which are most commonly formed after surgery for cancer or inflammatory bowel disease (IBD). They can be described according to the part of the bowel (small or large) used to create the stoma and can be temporary (with potential for reversal at a later date) or permanent. Many different types of stoma exist (eg, nephrostomy, urostomy), but in this article we focus on common complaints associated with intestinal stomas that may lead patients to present to general practice.

Imagine a patient presenting to you in general practice with concerns about discomfort in their stoma. After a thorough history, you might examine them as follows:

Ask the patient whether the stoma has changed in appearance. Then, inspect the stoma looking specifically at whether it sits proud of the skin and if it is healthy, pink, and moist.

Consider digital examination of the stoma if you have concerns about function. This is an intimate examination, so good communication is essential. Ensure your patient has a replacement stoma bag and ask them to …
<i>KRAS</i> and <i>BRAF</i> Mutations in Stage II and III Colon Cancer: A Systematic Review and Meta-Analysis
Authors: Vincenzo Formica, Francesco Sera, Chiara Cremolini, Silvia Riondino, Cristina Morelli, Hendrik-Tobias Arkenau, Mario Roselli
Journal: JNCI Journal of the National Cancer Institute (2021)

KRAS and BRAF mutations are well-established predictive and prognostic factors in metastatic colorectal cancer; however, their impact in the adjuvant setting has not yet been established.We performed a meta-analysis of adjuvant phase III trials in patients with stage II and III colon cancer with available data on the impact of KRAS or BRAF mutations on both disease-free survival (DFS) and overall survival (OS). Trials were subgrouped based on whether adjustment for microsatellite instability (MSI) was performed and the subgroup effect was analyzed through a meta-regression. To increase the precision of the estimates, a joint DFS-OS (so-called "multivariate") meta-analysis was performed. All statistical tests were 2-sided.Nine trials were selected (QUASAR 2, PETACC-8, N0147, CALGB-89803, NSABP-C07, NSABP-C08, PETACC-3, QUASAR, MOSAIC) including a total of 10 893 patients. In the primary meta-analysis, KRAS mutation was associated with poor DFS (pooled hazard ratio [HR] = 1.36, 95% confidence interval [CI] = 1.15 to 1.61, P < .001) and OS (pooled HR = 1.27, 95% CI = 1.03 to 1.55, P = .03) and BRAF mutation was also associated with poor DFS (pooled HR = 1.33, 95% CI = 1.00 to 1.78, P = .05) and OS (pooled HR = 1.49, 95% CI = 1.31 to 1.70, P < .001). The effect of the mutations on outcome was enhanced in the MSI-adjusted subgroup for both the KRAS mutation (pooled HR for DFS = 1.43, 95% CI = 1.15 to 1.79, P = .001; and pooled HR for OS = 1.33, 95% CI = 1.03 to 1.71, P = .03) and the BRAF mutation (pooled HR for DFS = 1.59, 95% CI = 1.22 to 2.07, P = .001; and pooled HR for OS = 1.67, 95% CI = 1.37 to 2.04, P < .001). The interaction between BRAF and MSI adjustment was statistically significant for DFS (Pinteraction = .02). This interaction was even more pronounced in the DFS-OS multivariate meta-analysis.Both KRAS and BRAF mutations were statistically significantly associated with both DFS and OS, with the mutation effect being enhanced by MSI adjustment. Effective adjuvant treatment for microsatellite-stable BRAF or KRAS-mutated colon cancer represents an unmet clinical need, and exploring the use of recently available BRAF and KRAS inhibitors in this setting would be highly desirable.
OS10.5.A BrainWear: Longitudinal, objective assessment of physical activity in 42 HGG patients
Authors: S Dadhania, L Pakzad-Shahabi, S Mistry, K Le-Calvez, W Saleem, W Mohammed, M Williams
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND In patients with High Grade Glioma (HGG), QoL and physical function decline with progressive disease (PD). Objective assessment of physical functioning is challenging as patients spend most of their time away from the hospital. Wearable technology allows measurement of objective, continuous activity data in a non-obtrusive manner. BrainWear is a phase II feasibility study, collecting longitudinal physical activity (PA) data from patients with primary and secondary brain tumours. MATERIAL AND METHODS All agreed to wear an Axivity AX3 triaxial accelerometer and completed the EORTC QLQ C30 and BN20, the Montreal Cognitive Assessment (MoCA) and Multidimensional fatigue inventory (MFI) questionnaires. Accelerometers were changed at 14-day intervals, and PRO questionnaires completed at pre-specified study intervals. Age-sex matched controls were identified from the UK Biobank 7-day accelerometer study. Raw accelerometer data was processed using UK Biobank accelerometer software and inclusion of high-quality wear time selected as ≥72 hours of data in a 7-day data collection and data in each 1-hour period of a 24-hour cycle over multiple days. We analysed variation in activity by patient demographics and treatment days. The wilcoxin-signed rank test was used to compare participant activity between radiotherapy treatment days and non-treatment days, mixed effects models were used to evaluate longitudinal changes in activity and we used k-means clustering to characterise clusters of PA behaviours. RESULTS We have collected 3458 days of accelerometer data from 42 HGG patients with a median age of 59, 80% of which has been classified as high quality. Patients &amp;gt;60 years spend more time doing moderate activity compared to those &amp;lt;60 years (52 vs 33 minutes/day, p=0.012), and there are significant differences in mean vector magnitude (17.12 vs 16.85 mg, p=0.013) and walking (91 vs 72 minutes/day) between radiotherapy and non-radiotherapy days. In patients having a 6-week RT course, time spent in daily moderate activity falls 4-fold between week 1 and the second week after RT completion (70 minutes to 16 minutes/day). Comparing HGG patients to healthy controls shows a significant difference in time spent across all activities (p&amp;lt;0.05). K-means clustering analysis shows three distinct clusters, with 87% of HGG patients falling into the very inactive or moderately active groups. CONCLUSION Digital remote health monitoring is feasible and acceptable with 80% of data classified as high-quality wear-time suggesting good patient adherence. Triaxial accelerometer data collection captures objective evidence of a significant reduction in moderate daily activity at the time of expected peak RT side-effects and patients walk almost 30% less on non-RT treatment days. HGG patients show significantly lower levels of activity compared to matched healthy controls.
Environmental exposure as a risk-modifying factor in liver diseases: Knowns and unknowns
Authors: Juliane I. Beier, Gavin E. Arteel
Journal: Acta Pharmaceutica Sinica B (2021)

Liver diseases are considered to predominantly possess an inherited or xenobiotic etiology. However, inheritance drives the ability to appropriately adapt to environmental stressors, and disease is the culmination of a maladaptive response. Thus "pure" genetic and "pure" xenobiotic liver diseases are modified by each other and other factors, identified or unknown. The purpose of this review is to highlight the knowledgebase of environmental exposure as a potential risk modifying agent for the development of liver disease by other causes. This exercise is not to argue that all liver diseases have an environmental component, but to challenge the assumption that the current state of our knowledge is sufficient in all cases to conclusively dismiss this as a possibility. This review also discusses key new tools and approaches that will likely be critical to address this question in the future. Taken together, identifying the key gaps in our understanding is critical for the field to move forward, or at the very least to "know what we don't know."
Author Correction: Pan-viral serology implicates enteroviruses in acute flaccid myelitis
Authors: Ryan D. Schubert, Isobel A. Hawes, Prashanth S. Ramachandran, Akshaya Ramesh, Emily D. Crawford, John E. Pak, Wesley Wu, Carly K. Cheung, Brian D. O’Donovan, Cristina M. Tato, Amy Lyden, Michelle Tan, Rene Sit, Gavin M. Sowa, Hannah A. Sample, Kelsey C. Zorn, Debarko Banerji, Lillian M. Khan, Riley Bove, Stephen L. Hauser, Amy A. Gelfand, Bethany L. Johnson-Kerner, Kendall Nash, Kalpathy S. Krishnamoorthy, Tanuja Chitnis, Joy Z. Ding, Hugh J. McMillan, Charles Y. Chiu, Benjamin Briggs, Carol A. Glaser, Cynthia Yen, Victoria Chu, Debra A. Wadford, Samuel R. Dominguez, Terry Fei Fan Ng, Rachel L. Marine, Adriana S. Lopez, W. Allan Nix, Ariane Soldatos, Mark P. Gorman, Leslie Benson, Kevin Messacar, Jennifer L. Konopka-Anstadt, M. Steven Oberste, Joseph L. DeRisi, Michael R. Wilson
Journal: Nature Medicine (2021)
Social and health factors associated with unfavourable treatment outcome in adolescents and young adults with tuberculosis in Brazil: a national retrospective cohort study
Authors: Louisa Chenciner, Kristi Sidney Annerstedt, Julia M Pescarini, Tom Wingfield
Journal: The Lancet Global Health (2021)

Tuberculosis elimination strategies in Brazil might neglect adolescents and young adults aged 10-24 years, hampering tuberculosis control. However, little is known about factors associated with tuberculosis treatment outcomes in this underserved group. In this study, we aimed to investigate social and health factors associated with unfavourable treatment outcomes in young people with tuberculosis in Brazil.A national retrospective cohort study was done using data from Sistema de Informação de Agravos de Notificação (SINAN), the national tuberculosis registry in Brazil. People aged 10-24 years (young people) with tuberculosis registered in SINAN between Jan 1, 2015, and Dec 31, 2018, were included. Unfavourable outcomes were defined as loss to follow-up, treatment failure, and death. Favourable outcome was defined as treatment success. Multiple logistic regression models estimated the association between social and health factors and tuberculosis treatment outcomes.67 360 young people with tuberculosis were notified to SINAN, and we included 41 870 young people in our study. 7024 (17%) of the 41 870 included individuals had unfavourable treatment outcomes. Young people who received government cash transfers were less likely to have an unfavourable outcome (adjusted odds ratio 0·83, 95% CI 0·70-0·99). Homelessness (3·03, 2·07-4·42), HIV (2·89, 2·45-3·40), and illicit drug use (2·22, 1·93-2·55) were the main factors associated with unfavourable treatment outcome.In this national cohort of young people with tuberculosis in Brazil, tuberculosis treatment success rates were lower than WHO End TB Strategy targets, with almost a fifth of participants experiencing unfavourable treatment outcomes. Homelessness, HIV, and illicit drug use were the main factors associated with unfavourable outcome. In Brazil, strategies are required to support this underserved group to ensure favourable tuberculosis treatment outcomes.Wellcome Trust, UK Medical Research Council, and UK Foreign Commonwealth and Development Office.
When Professional Meets Personal: How Should Research Staff Advertise on Social Media for Research Opportunities?
Authors: Liza-Marie Johnson, Devan M. Duenas, Benjamin S. Wilfond
Journal: The American Journal of Bioethics (2021)

"When Professional Meets Personal: How Should Research Staff Advertise on Social Media for Research Opportunities?." The American Journal of Bioethics, 21(10), pp. 38–39