Background. Incorporation of next-generation sequencing (NGS) technology into clinical utility in targeted and immunotherapies requires stringent validation, including the assessment of tumor mutational burden (TMB) and microsatellite instability (MSI) status by NGS as important biomarkers for response to immune checkpoint inhibitors. Materials and Methods. We designed an NGS assay, Cancer Sequencing YS panel (CSYS), and applied algorithms to detect five classes of genomic alterations and two genomic features of TMB and MSI. Results. By stringent validation, CSYS exhibited high sensitivity and predictive positive value of 99.7% and 99.9%, respectively, for single nucleotide variation; 100% and 99.9%, respectively, for short insertion and deletion (indel); and 95.5% and 100%, respectively, for copy number alteration (CNA). Moreover, CSYS achieved 100% specificity for both long indel (50-3,000 bp insertion and deletion) and gene rearrangement. Overall, we used 33 cell lines and

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The purpose of the study was to investigate the relationship between different exercise modes and visuospatial working memory in healthy older adults. A cross-sectional design was adopted. A total of 111 healthy older adults were enrolled in the study. They were classified by the exercise-related questionnaire to be in an open-skill group, closed-skill group or sedentary group. In experiment 1, the participants performed a visuospatial working memory task. The results indicated that both closed-skill (p < 0.05) and open-skill (p < 0.01) groups reached a higher accuracy than the sedentary group. Experiment 2 examined whether the exercise-induced benefit of working memory was manifested in passive maintenance or active manipulation of working memory which was assessed by visuospatial short-term memory task and visuospatial mental rotation task, respectively. The results showed that the open-skill (p < 0.01) group was more accurate than the sedentary group in the visuospatial short-term memory task, whereas the group difference in the visuospatial mental rotation task was not significant. These findings combined to suggest that physical exercise was associated with better visuospatial working memory in older adults. Furthermore, open-skill exercises that demand higher cognitive processing showed selective benefit for passive maintenance of working memory.

Background: Both physical exercise and cognitive training can effectively improve executive functions in older adults. However, whether physical activity combined with cognitive training is more effective than a single intervention remains controversial. The aim of this study was to perform a meta-analysis to evaluate the effect of combined physical and cognitive interventions on executive functions in older adults aged 65–80 years old. Methods: Randomized controlled trials of combined physical and cognitive interventions on executive functions in older adults were searched using the Web of Science, Elsevier Science, PubMed, EBSCO, Springer-Link, and NATURE databases. Data extraction and quality evaluation were done by Comprehensive Meta-Analysis, V3. Results: A total of 21 studies were included. The results showed that the combined physical and cognitive interventions produced significantly larger gains in executive functions, compared to the control group (standardized mean difference (SMD) = 0.26, 95% confidence interval (CI) [0.14, 0.39], p < 0.01). Furthermore, the effects of the combined physical and cognitive interventions were moderated by the study quality, intervention length, and intervention frequency. No significant differences were found between the combined interventions and the physical intervention alone (SMD = 0.13, 95% CI [−0.07, 0.33], p > 0.05) or the cognitive intervention alone (SMD = 0.13, 95% CI [−0.05, 0.30], p > 0.05). Conclusions: The combined physical and cognitive interventions effectively delayed the decrease of executive functions in older adults and this effect was influenced by the length and frequency of the intervention as well as the research quality. However, the effect of the combined physical and cognitive interventions was not significantly better than that of each intervention alone.

ObjectivesTo assess whether hypercapnia may predict the prognosis in chronic obstructive pulmonary disease (COPD).DesignProspective cohort study comparing the survival of patients with COPD and normocapnia to those with chronic hypercapnia.SettingPatients with consecutive COPD were enrolled between 1 May 1993 and 31 October 2006 at two medical centres. Follow-up was censored on 31 October 2011.ParticipantsA total of 275 patients with stable COPD and aged 40–85 years were enrolled. Diagnosis of hypercapnia was confirmed by blood gas analysis. Patients with near-terminal illness or comorbidities that affect PaCO2 (obstructive sleep apnoea, obesity-related hypoventilation, or neuromuscular disease) were excluded. The outcome of 98 patients with normocapnia and 177 with chronic hypercapnia was analysed.Outcome measuresOverall survival.ResultsMedian survival was longer in patients with normocapnia than in those with hypercapnia (6.5 vs 5.0 years, p=0.016). Multivariate COX regression analysis indicated that age (HR=1.043, 95% CI 1.012 to 1.076), Charlson Index, which is a measure of comorbidity (HR=1.172, 95% CI 1.067 to 1.288), use of medication (HR=0.565, 95% CI 0.379 to 0.842), body mass index (BMI) (HR=0.922, 95% CI 0.883 to 0.963), PaCO2 (HR=1.026, 95% CI 1.011 to 1.042), Cor pulmonale (HR=2.164, 95% CI 1.557 to 3.006), non-invasive positive-pressure ventilation (NPPV) (HR=0.615, 95% CI 0.429 to 0.881) and per cent of forced expiratory volume in 1 s (FEV1%) (HR=0.979, 95% CI 0.967 to 0.991), were independent risk factors for mortality.ConclusionsIncreased age, Charlson Index, chronic hypercapnia and Cor pulmonale, and decreased FEV1%, use of medication, BMI and NPPV, were associated with a poor prognosis in patients with COPD.