Table_1_Psychoeducation, motivational interviewing, cognitive remediation training, and/or social skills training in combination for psychosocial functioning of patients with schizophrenia spectrum disorders: A systematic review and meta-analysis of randomized controlled trials.DOCX

ObjectivesPsychoeducation, motivational interviewing, cognitive remediation training, and social skills training have been found to be effective interventions for patients with schizophrenia spectrum disorders. However, their efficacy on psychosocial functioning when provided in combination remains unclear, compared with all types of control conditions. It would also be meaningful to explore the differences of efficacy in patients with first-episode psychosis (FEP) and those with longer term of illness.MethodologyThe present review followed the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Full-text English journal articles of randomized controlled trials published in the past decade in the databases of PubMed, CINAHL Complete, Embase, and PsycINFO were searched. Included studies were all randomized controlled trials (RCTs) with participants diagnosed with schizophrenia spectrum disorders. The included studies should test combined interventions with at least two components from: psychoeducation, motivational interviewing, cognitive remediation training, and social skills training and incorporate assessment of psychosocial functioning at least at baseline and post-intervention.ResultsSeven studies were included for systematic review, and six of them were eligible for meta-analysis. Five out of the seven studies reported effects on psychosocial functioning that favored combined interventions over any type of control condition. A significant pooled effect was derived from the six studies, SMD = 1.03, 95% CI [0.06, 2.00], Z = 2.09, p = 0.04, I2 = 96%. However, the pool effect became insignificant when synthesizing five of the studies with non-FEP patients as participants and four of the studies testing relative effects of combined interventions compared with stand-alone interventions/interventions with one less component. None of the included studies adopted motivational interviewing and only one of the studies worked with FEP patients.ConclusionPsychoeducation, cognitive remediation training, and social skills training in combination can effectively enhance psychosocial functioning of patients with schizophrenia spectrum disorders. It is warranted to conduct more RCTs to test the effects of different specific combinations of the above interventions on psychosocial functioning, especially in FEP patients.</p

Intrinsic subtypes and benefit from postmastectomy radiotherapy in node-positive premenopausal breast cancer patients who received adjuvant chemotherapy – results from two independent randomized trials

<p><b>Background:</b> The study of the intrinsic molecular subtypes of breast cancer has revealed differences among them in terms of prognosis and response to chemotherapy and endocrine therapy. However, the ability of intrinsic subtypes to predict benefit from adjuvant radiotherapy has only been examined in few studies.</p> <p><b>Methods:</b> Gene expression-based intrinsic subtyping was performed in 228 breast tumors collected from two independent post-mastectomy clinical trials (British Columbia and the Danish Breast Cancer Cooperative Group 82b trials), where pre-menopausal patients with node-positive disease were randomized to adjuvant radiotherapy or not. All patients received adjuvant chemotherapy and a subgroup of patients underwent ovarian ablation. Tumors were classified into intrinsic subtypes: Luminal A, Luminal B, HER2-enriched, Basal-like and Normal-like using the research-based PAM50 classifier.</p> <p><b>Results:</b> In the British Columbia study, patients treated with radiation had an overall significant lower incidence of locoregional recurrence compared to the controls. For Luminal A tumors the risk of loco-regional recurrence was low and was further lowered by adjuvant radiation. These findings were validated in the DBCG 82b study. The individual data from the two cohorts were merged, the hazard ratio (HR) for loco-regional recurrence associated with giving radiation was 0.34 (0.19 to 0.61) overall and 0.12 (0.03 to 0.52) for Luminal A tumors.</p> <p><b>Conclusions:</b> In both postmastectomy trials, patients with Luminal A tumors turned out to have a significant lower incidence of loco-regional recurrence when randomized to adjuvant radiotherapy, leaving no indication to omit postmastectomy adjuvant radiation in pre-menopausal high-risk patients with Luminal A tumors. It was not possible to evaluate the effect of radiotherapy among the other subtypes because of limited sample sizes.</p

Single-Patient Molecular Testing with NanoString nCounter Data Using a Reference-Based Strategy for Batch Effect Correction

<div><p>A major weakness in many high-throughput genomic studies is the lack of consideration of a clinical environment where one patient at a time must be evaluated. We examined generalizable and platform-specific sources of variation from NanoString gene expression data on both ovarian cancer and Hodgkin lymphoma patients. A reference-based strategy, applicable to single-patient molecular testing is proposed for batch effect correction. The proposed protocol improved performance in an established Hodgkin lymphoma classifier, reducing batch-to-batch misclassification while retaining accuracy and precision. We suggest this strategy may facilitate development of NanoString and similar molecular assays by accelerating prospective validation and clinical uptake of relevant diagnostics.</p></div

PVCA and PCA plots of the Hodgkin Lymphoma clinical samples.

<p>We considered the PVCA plot (A) of the HL clinical samples run in different batches. The percentages represent the variability explained by each factor and first order interaction between factors. The PCA plot (B) provides a two-dimensional summary of the pairwise plot of the first three principal components, which represent 49% of the variability in the data. HL1, HL2, and HL3 label each of unique CodeSets corresponding to the HL gene list.</p

Percentage of genes detected above the limit of detection (LOD) by cohort.

<p>Each point on the boxplot represents a NanoString nCounter unique run (duplicates and triplicates included where available). The colored boxes represent the distribution of the percentage of genes detected in a particular cohort. The white line indicates the median. A cutoff of 50% was used for Cell Lines and clinical samples, and 95% was used for oligonucleotide samples. HL: Hodgkin lymphoma clinical samples, OC: ovarian cancer clinical samples, OVCL: ovarian cancer cell lines, HLO: oligonucleotides corresponding to the HL CodeSet, OVO: oligonucleotides corresponding to the OC CodeSet.</p

PVCA and PCA plots of the ovarian cancer clinical samples.

<p>We considered the PVCA plot (A) of the OC clinical samples run in different batches. The percentages represent the variability explained by each factor and first order interaction between factors. The PCA plot (B) provides a two-dimensional summary of the pairwise plot of the first three principal components, which represent 40% of the variability in the data. CS1, CS2, and CS3 label each of unique CodeSets corresponding to the OC gene list.</p

PVCA of the HL clinical samples after adjusting batch effect using different methods.

<p>We consider the PVCA plot of the HL clinical samples run in different batches after adjusting BE with different methods. In each plot, percentages represent the variability explained by each factor and first order interaction between factors.</p

Cohort Description.

<p>Cohort Description.</p

PVCA of the OC clinical samples after adjusting batch effect using different methods.

<p>We consider the PVCA plot of the OC clinical samples run in different batches after adjusting BE with different methods. In each plot, percentages represent the variability explained by each factor and first order interaction between factors.</p

Impact of BE on downstream analysis, illustrated using a HL prognostic model.

<p>The x and y axes correspond to risk scores obtained in HL1 and HL2 respectively. The dashed line represents the identity line, and the solid line represents the best linear fit. The horizontal line indicates the threshold used for prediction. The results in (A) correspond to scores not corrected for BE, and in (B) scores are corrected using 3 reference samples that were run in both CodeSets.</p