Barriers to blood donation on social media:An analysis of Facebook and Twitter posts

Background: To better understand donor behavior and ensure a safe and sufficient blood supply, various observational studies have examined barriers to blood donation. This study used Facebook and Twitter data to enhance existing research on donation barriers and associated emotions communicated on social media by both donors and non-donors. Study design and methods: We conducted a semantic network analysis (SNA) with 168 232 public Dutch language social media messages from Facebook and Twitter during 2012-2018. SNA uses concepts as nodes in a network and the relationship (ie, co-occurrence) as links between them. We identified the relationship between donation barriers, non-donation (voluntary and involuntary), and dissatisfaction (anger and disappointment) within social media messages. This computational method was combined with an analysis examining significant relationships in-depth. Results: Twelve donation barriers were identified: lifestyle, donation location, medical reasons, no invitation, opening times, physical reactions, pregnancy, remuneration, sexual risk behavior, time constraints, travels, and waiting times. More messages related to involuntary non-donation compared to voluntary non-donation. Involuntary non-donation was associated most strongly with medical reasons and sexual risk behavior, while voluntary non-donation was associated most strongly with resentment regarding remuneration of the blood bankʼs top management. Anger associated most strongly with sexual risk behavior and disappointment most strongly with medical reasons. Conclusion: Discussions around blood donation are increasingly taking place online. Donation barriers found in this study differ from those in survey research. Insights into how donation barriers are communicated in an ever-growing online environment can be utilized to enhance recruitment and retention strategies

Transcriptome analysis reveals tumor microenvironment changes in glioblastoma

A better understanding of transcriptional evolution of IDH-wild-type glioblastoma may be crucial for treatment optimization. Here, we perform RNA sequencing (RNA-seq) (n = 322 test, n = 245 validation) on paired primary-recurrent glioblastoma resections of patients treated with the current standard of care. Transcriptional subtypes form an interconnected continuum in a two-dimensional space. Recurrent tumors show preferential mesenchymal progression. Over time, hallmark glioblastoma genes are not significantly altered. Instead, tumor purity decreases over time and is accompanied by co-increases in neuron and oligodendrocyte marker genes and, independently, tumor-associated macrophages. A decrease is observed in endothelial marker genes. These composition changes are confirmed by single-cell RNA-seq and immunohistochemistry. An extracellular matrix-associated gene set increases at recurrence and bulk, single-cell RNA, and immunohistochemistry indicate it is expressed mainly by pericytes. This signature is associated with significantly worse survival at recurrence. Our data demonstrate that glioblastomas evolve mainly by microenvironment (re-)organization rather than molecular evolution of tumor cells

The EGFRvIII transcriptome in glioblastoma, a meta-omics analysis.

BACKGROUND: EGFR is among the genes most frequently altered in glioblastoma, with exons 2-7 deletions (EGFRvIII) being amongst its most common genomic mutations. There are conflicting reports about its prognostic role and it remains unclear whether and how it differs in signalling compared with wildtype EGFR. METHODS: To better understand the oncogenic role of EGFRvIII, we leveraged four large datasets into one large glioblastoma transcriptome dataset (n=741) alongside 81 whole-genome samples from two datasets. RESULTS: The EGFRvIII/EGFR expression ratios differ strongly between tumours and ranges from 1% to 95%. Interestingly, the slope of relative EGFRvIII expression is near-linear, which argues against a more positive selection pressure than EGFR wildtype. An absence of selection pressure is also suggested by the similar survival between EGFRvIII positive and negative glioblastoma patients. EGFRvIII levels are inversely correlated with pan-EGFR (all wildtype and mutant variants) expression, which indicates that EGFRvIII has a higher potency in downstream pathway activation. EGFRvIII-positive glioblastomas have a lower CDK4 or MDM2 amplification incidence than EGFRvIII-negative (p=0.007), which may point towards crosstalk between these pathways. EGFRvIII-expressing tumours have an upregulation of 'classical' subtype genes compared to those with EGFR-amplification only (p=3.873e-6). Genomic breakpoints of the EGFRvIII deletions have a preference towards the 3' end of the large intron-1. These preferred breakpoints preserve a cryptic exon resulting in a novel EGFRvIII variant and preserve an intronic enhancer. CONCLUSIONS: These data provide deeper insights into the complex EGFRvIII biology and provide new insights for targeting EGFRvIII mutated tumours

Delineating the molecular and phenotypic spectrum of the SETD1B-related syndrome

Purpose: Pathogenic variants in SETD1B have been associated with a syndromic neurodevelopmental disorder including intellectual disability, language delay, and seizures. To date, clinical features have been described for 11 patients with (likely) pathogenic SETD1B sequence variants. This study aims to further delineate the spectrum of the SETD1B-related syndrome based on characterizing an expanded patient cohort. Methods: We perform an in-depth clinical characterization of a cohort of 36 unpublished individuals with SETD1B sequence variants, describing their molecular and phenotypic spectrum. Selected variants were functionally tested using in vitro and genome-wide methylation assays. Results: Our data present evidence for a loss-of-function mechanism of SETD1B variants, resulting in a core clinical phenotype of global developmental delay, language delay including regression, intellectual disability, autism and other behavioral issues, and variable epilepsy phenotypes. Developmental delay appeared to precede seizure onset, suggesting SETD1B dysfunction impacts physiological neurodevelopment even in the absence of epileptic activity. Males are significantly overrepresented and more severely affected, and we speculate that sex-linked traits could affect susceptibility to penetrance and the clinical spectrum of SETD1B variants. Conclusion: Insights from this extensive cohort will facilitate the counseling regarding the molecular and phenotypic landscape of newly diagnosed patients with the SETD1B-related syndrome

Impact of timing of antiseizure medication withdrawal on seizure recurrence in glioma patients:a retrospective observational study

Background: Withdrawal of antiseizure medication treatment (ASM) can be considered after completion of antitumour treatment in glioma patients who no longer suffer from seizures. We compared the risk for recurrent seizures after ASM withdrawal between patients with short-term, medium-term versus long-term seizure freedom after antitumour treatment. Methods: In this retrospective observational study, the primary outcome was time to recurrent seizure, from the starting date of no ASM treatment up to 36 months follow-up. Cox proportional hazards models were used to study the effect of risk factors on time to recurrent seizure. Stratification was done with information known at baseline. Short-term seizure freedom was defined as ≥ 3 months, but &lt; 12 months; medium-term as 12–24 months; and long-term as ≥ 24 months seizure freedom from the date of last antitumour treatment. Results: This study comprised of 109 patients; 31% (34/109) were in the short-term, 29% (32/109) in the medium-term, and 39% (43/109) in the long-term group. A recurrent seizure was experienced by 47% (16/34) of the patients in the short-term, 31% (10/32) in the medium-term, and 44% (19/43) in the long-term group. Seizure recurrence risk was similar between patients in the short-term group as compared to the medium-term (cause-specific adjusted hazard ratio [aHR] = 0.65 [95%CI = 0.29–1.46]) and long-term group (cause-specific aHR = 1.04 [95%CI = 0.52–2.09]). Conclusions: Seizure recurrence risk is relatively similar between patients with short-term, medium-term, and long-term seizure freedom after completion of antitumour treatment.</p

Barriers to blood donation on social media: An analysis of Facebook and Twitter posts

Background: To better understand donor behavior and ensure a safe and sufficient blood supply, various observational studies have examined barriers to blood donation. This study used Facebook and Twitter data to enhance existing research on donation barriers and associated emotions communicated on social media by both donors and non-donors. Study design and methods: We conducted a semantic network analysis (SNA) with 168 232 public Dutch language social media messages from Facebook and Twitter during 2012-2018. SNA uses concepts as nodes in a network and the relationship (ie, co-occurrence) as links between them. We identified the relationship between donation barriers, non-donation (voluntary and involuntary), and dissatisfaction (anger and disappointment) within social media messages. This computational method was combined with an analysis examining significant relationships in-depth. Results: Twelve donation barriers were identified: lifestyle, donation location, medical reasons, no invitation, opening times, physical reactions, pregnancy, remuneration, sexual risk behavior, time constraints, travels, and waiting times. More messages related to involuntary non-donation compared to voluntary non-donation. Involuntary non-donation was associated most strongly with medical reasons and sexual risk behavior, while voluntary non-donation was associated most strongly with resentment regarding remuneration of the blood bankʼs top management. Anger associated most strongly with sexual risk behavior and disappointment most strongly with medical reasons. Conclusion: Discussions around blood donation are increasingly taking place online. Donation barriers found in this study differ from those in survey research. Insights into how donation barriers are communicated in an ever-growing online environment can be utilized to enhance recruitment and retention strategies

STABILITY OF ACTIONABLE MUTATIONS IN PRIMARY AND RECURRENT GLIOBLASTOMAS

Neurolog

Molecular Evolution of IDH Wild-Type Glioblastomas Treated With Standard of Care Affects Survival and Design of Precision Medicine Trials: A Report From the EORTC 1542 Study

peer reviewedPURPOSE: Precision medicine trials in glioblastoma (GBM) are often conducted at tumor recurrence. However, second surgeries for recurrent GBM are not routinely performed, and therefore, molecular data for trial inclusion are predominantly derived from the primary sample. This study aims to establish whether molecular targets change during tumor progression and, if so, whether this affects precision medicine trial design. MATERIALS AND METHODS: We collected 186 pairs of primary-recurrent GBM samples from patients receiving chemoradiotherapy with temozolomide and sequenced approximately 300 cancer genes. MGMT, TERT, and EGFRvIII status was individually determined. RESULTS: The molecular profile of our cohort was identical to that of other GBM cohorts (IDH wild-type [WT], 95%; EGFR amplified, approximately 50%), indicating that patients amenable to second surgery do not represent a specific molecular subtype. Molecular events in IDH WT GBMs were stable in approximately 80% of events, but changes in mutation status were observed for all examined genes (range, approximately 90% and 60% for TERT and EGFR mutations, respectively), and such changes strongly affected targeted trial size and design. A similar pattern of GBM driver instability was observed within MGMT promoter-methylated tumors. MGMT promoter methylation status remained prognostic at tumor recurrence. The observation that hypermutation at GBM recurrence was rare (8%) and not correlated with outcome was relevant for immunotherapy-based treatments. CONCLUSION: This large cohort of matched primary and recurrent IDH WT tumors establishes the frequency of GBM driver instability after chemoradiotherapy with temozolomide. This allows per gene or pathway calculation of trial size at tumor recurrence, using molecular data of the primary tumor only. We also identify genes for which repeat surgery is necessary because of low mutation retention rate