Citations

Background: Tumor mutational burden (TMB) is an FDA-approved biomarker for immune checkpoint inhibitor (ICI) therapy. However, its predictive value varies among tumor types and molecular contexts. We investigated whether a very high TMB identifies a biologically distinct subset and whether a higher cutoff provides additional clinical insights beyond the conventional high TMB threshold. Methods: We analyzed 133 patients with advanced solid tumors and TMB ≥ 10 mutations/Mb (mut/Mb) who underwent tumor genomic profiling using a 523-gene DNA/RNA next-generation sequencing panel. Tumors were stratified into prespecified TMB categories: 10–20 mut/Mb (TMB-H) and >20 mut/Mb (TMB-VH). The clinical characteristics, ICI outcomes (in the treated subset), and pathway-level genomic features were compared between groups. Results: TMB-VH was observed in 42/133 (31.6%) patients and spanned more than 20 tumor types. MSI was markedly more prevalent in TMB-VH than in TMB-H tumors (38.1% vs. 2.2%; Fisher’s exact p = 8.9 × 10−8). Pathway-level comparisons did not identify statistically significant differences after false discovery rate correction (all q > 0.05), and the observed patterns were descriptive in nature. In the ICI-treated subset with complete follow-up, objective response did not differ according to the TMB group. Overall survival (OS) was also similar between groups, whether measured from metastatic diagnosis (log-rank p = 0.937) or from ICI initiation (log-rank p = 0.814), although OS was numerically longer in the TMB-VH group in both analyses without reaching statistical significance. Conclusions: In this cohort study, TMB-VH was strongly associated with MSI but not independently associated with improved ICI outcomes. Larger multicenter cohorts are needed to validate pathway-oriented patterns and clarify the clinical utility of extreme TMB thresholds across various histologies. Integrating the functional context (e.g., MSI status, gene-level context, and pathway-level features) with TMB magnitude may enable more robust, tumor-aware biomarker models for immunotherapy selection.

Objective To identify people with history of mental health disorders before the COVID-19 pandemic in the Brazilian population and estimate the prevalence of mood swings and the subjective distress of the pandemic among individuals with or without mental health disorders. Methods Through an online survey, participants were asked about presence or absence of mental health disorders. In addition, they answered the Brunel Mood Scale and the Impact of Event Scale. The mean percentile of mood swing indicators and psychological impact scores were estimated, and data were analyzed by logistic regression. Results 13,248 people participated (70.5% women, mean age 35.4 years, 31.2% with history of mental health disorder). Women and younger people were more likely to be diagnosed with mental health disorder. All participants had significant changes in mood due to the pandemic. Anger, depressed mood, mental confusion, and fatigue were higher among individuals with bipolar disorder or with combined disorders. Individuals with mental health disorders had a greater subjective distress, especially the group with bipolar disorder (OR = 4.89 [3.64–6.56]) and combined disorders (OR = 6.89 [5.21–9.10]). Conclusion Individuals previously diagnosed with mental health disorders at some point in life are more vulnerable to psychological impact from the pandemic.

Background: Isolation measures used to contain epidemics generate social interaction restrictions and impose changes in routines of the public that increase negative psychological outcomes. Anxiety and depression are the most common symptoms. Objective: To evaluate the mental health of the Brazilian population during the SARs-CoV-2 pandemic and its relationship with demographic and health characteristics. Methods: Adults from all Brazilian States participated (n = 12,196; women: 69.8%, mean age = 35.2 years). The Depression, Anxiety and Stress Scale, and the Impact of Event Scale–revised were used (online survey). Data validity and reliability were verified by confirmatory factor analysis and ordinal alpha coefficient. The probability of presenting psychological symptoms was calculated by multiple logistic regression and odds ratio (OR) (0 = without symptoms, 1 = with mild, moderate, and severe levels of symptoms). Results: High prevalence of depression (61.3%), anxiety (44.2%), stress (50.8%), and psychological impact (54.9%) due to the isolation experienced from the pandemic was found. Younger individuals (OR = 1.58–3.58), those that felt unsafe (OR = 1.75–2.92), with a previous diagnosis of mental health (OR = 1.72–2.64) and/or had general health problems before the pandemic (OR = 1.17–1.51), who noticed changes in their mental state due to the pandemic context (OR = 2.53–9.07), and excessively exposed to the news (OR = 1.19–2.18) were at increased risk of developing symptoms. Women (OR = 1.35–1.65) and those with lower economic status (OR = 1.38–2.69) were more likely to develop psychological symptoms. Lower educational levels increased the likelihood of depressive (OR = 1.03–1.34) and intrusive symptoms (OR = 1.09–1.51). Conclusions: The pandemic and related factors can have a high impact on the mental health of the population. Demographic characteristics can influence the occurrence of psychological symptoms.

Innovations on the field of smart hydrogels are now being held with loads of advantages. With recent progress, smart polymers can now be used on the market for specific target/objectives desired on medicine. However, the field of smart hydrogels has not been fully overviewed on the ground for drug delivery. In this study, a novel pH‐sensitive smart hydrogel for drug delivery was investigated. Polyvinyl‐alcohol (PVA) with polyacrylic acid (PAA) was blended adding synthetic hydroxyapatite (Hap) with freeze‐thawed cycles and its effects were studied in terms of mechanical strength, bioactivity, and drug release profile. Mechanical strength towards compression tests was decreased after addition of Hap and storage modulus (G') increased. Bioactivity was confirmed after 14 days on simulated body fluid (SBF). Improvement of swelling and gel fraction with the addition of Hap throughout the polymer matrix. Moreover, a study was performed with theophylline‐loaded samples for drug‐delivery studies. Copyright © 2015 John Wiley & Sons, Ltd.