Lateral prefrontal and posterior parietal cortical areas exhibit task-dependent activation during working memory tasks in humans and monkeys. Neurons in these regions become synchronized during ...attention-demanding tasks, but the contribution of these interactions to working memory is largely unknown. Using simultaneous recordings of neural activity from multiple areas in both regions, we find widespread, task-dependent, and content-specific synchronization of activity across the fronto-parietal network during visual working memory. The patterns of synchronization are prevalent among stimulus-selective neurons and are governed by influences arising in parietal cortex. These results indicate that short-term memories are represented by large-scale patterns of synchronized activity across the fronto-parietal network.
•This ESMO Clinical Practice Guideline provides key recommendations on the management of localised colon cancer.•Authorship includes a multidisciplinary group of experts from different institutions ...and countries in Europe and abroad.•Diagnostic work-up is reviewed.•Key treatment recommendations are included in each section.•Follow-up indications are provided.
The Colorectal Cancer Subtyping Consortium identified four gene expression consensus molecular subtypes, CMS1 (immune), CMS2 (canonical), CMS3 (metabolic), and CMS4 (mesenchymal), using multiple ...microarray or RNA-sequencing datasets of primary tumor samples mainly from early stage colon cancer patients. Consequently, rectal tumors and stage IV tumors (possibly reflective of more aggressive disease) were underrepresented, and no chemo- and/or radiotherapy pretreated samples or metastatic lesions were included. In view of their possible effect on gene expression and consequently subtype classification, sample source and treatments received by the patients before collection must be carefully considered when applying the classifier to new datasets. Recently, several correlative analyses of clinical trials demonstrated the applicability of this classification to the metastatic setting, confirmed the prognostic value of CMS subtypes after relapse and hinted at differential sensitivity to treatments. Here, we discuss why contexts and equivocal factors need to be taken into account when analyzing clinical trial data, including potential selection biases, type of platform, and type of algorithm used for subtype prediction. This perspective article facilitates both our clinical and research understanding of the application of this classifier to expedite subtype-based clinical trials.
Environmental noise exposure has been considered one of the most common hazards worldwide, especially in the workplace environment, and could produce a variety of health issues. Some epidemiological ...evidence supports the association between occupational noise exposition and a high risk for hypertension and cardiovascular diseases. Wang et al. has conducted an observational cross‐sectional study using occupational data of 4746 workers, 32.4% were exposed to high occupational noise. These exposed individuals had a moderate increase in the risk for hypertension (adjusted odds ratio OR, 1.30; 95% confidence interval CI, 1.05–1.62). The subgroup analyses showed that the relationship between noise and hypertension prevalence was stronger in young participants (OR, 1.70; 95% CI, 1.21–2.40). Noise exposure activates the sympathetic and endocrine systems producing an increase in blood pressure and the changes in other biological risk factors. Moreover, a recently published study showed that oxidative stress and DNA damage were significantly higher in subjects exposed to noise. Emotional stress reactions and unconscious physiological stress could also be potential mechanisms for hypertension. Finally, physiological stress caused by noise exposure may also increase indulgence in unhealthy behaviors, such as smoking and alcohol consumption, and indirectly result in an increased risk of hypertension and cardiovascular diseases. Previously published studies showed relationships between environmental noise exposure (including road traffic, railway, and aircraft noises) and the development of hypertension and cardiovascular diseases. Thus, the study by Wang et al. emphasizes the importance of environmental control in the prevention of cardiovascular diseases, not only in the workplace but also outside it.
Dinoflagellates are main primary producers in the oceans, the cause of algal blooms and endosymbionts of marine invertebrates. Much remains to be understood about their biology, including their ...peculiar crystalline chromosomes. We assembled 94 chromosome-scale scaffolds of the genome of the coral endosymbiont Symbiodinium microadriaticum and analyzed their organization. Genes are enriched towards the ends of chromosomes and are arranged in alternating unidirectional blocks. Some chromosomes are enriched for genes involved in specific biological processes. The chromosomes fold as linear rods and each is composed of a series of structural domains separated by boundaries. Domain boundaries are positioned at sites where transcription of two gene blocks converges and disappear when cells are treated with chemicals that block transcription, indicating correlations between gene orientation, transcription and chromosome folding. The description of the genetic and spatial organization of the S. microadriaticum genome provides a foundation for deeper exploration of the extraordinary biology of dinoflagellates and their chromosomes.
Circulating tumor DNA (ctDNA) is a potential source for tumor genome analysis. We explored the concordance between the mutational status of RAS in tumor tissue and ctDNA in metastatic colorectal ...cancer (mCRC) patients to establish eligibility for anti-epidermal growth factor receptor (EGFR) therapy.
A prospective-retrospective cohort study was carried out. Tumor tissue from 146 mCRC patients was tested for RAS status with standard of care (SoC) PCR techniques, and Digital PCR (BEAMing) was used both in plasma and tumor tissue.
ctDNA BEAMing RAS testing showed 89.7% agreement with SoC (Kappa index 0.80; 95% CI 0.71 − 0.90) and BEAMing in tissue showed 90.9% agreement with SoC (Kappa index 0.83; 95% CI 0.74 − 0.92). Fifteen cases (10.3%) showed discordant tissue-plasma results. ctDNA analysis identified nine cases of low frequency RAS mutations that were not detected in tissue, possibly due to technical sensitivity or heterogeneity. In six cases,RAS mutations were not detected in plasma, potentially explained by low tumor burden or ctDNA shedding. Prediction of treatment benefit in patients receiving anti-EGFR plus irinotecan in second- or third-line was equivalent if tested with SoC PCR and ctDNA. Forty-eight percent of the patients showed mutant allele fractions in plasma below 1%.
Plasma RAS determination showed high overall agreement and captured a mCRC population responsive to anti-EGFR therapy with the same predictive level as SoC tissue testing. The feasibility and practicality of ctDNA analysis may translate into an alternative tool for anti-EGFR treatment selection.
...early high adherence levels decrease long-term cardiovascular mortality, supporting the importance of early blood pressure control. ...patients who developed complications of hypertension during ...the follow-up period need a more intensive level of adherence to antihypertensive medication than those without complications. CR is based on electronic pharmacy records and does not use patient data. ...since only medication dispensing records were used, the patient's actual adherence to antihypertensive drugs can be different.
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