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Rosen Kristiansen posted an update 2 weeks, 6 days ago
Reporting of clinical prediction models using machine learning in oncology is poor and needs urgent improvement, so readers and stakeholders can appraise the study methods, understand study findings, and reduce research waste.
Reporting of clinical prediction models using machine learning in oncology is poor and needs urgent improvement, so readers and stakeholders can appraise the study methods, understand study findings, and reduce research waste.Sarcopenia comprises a loss of muscle function and muscle mass. So far, the association between the later and mortality in older adults is inconsistent. A meta-analysis was performed to assess whether muscle mass measured by appendicular skeletal muscle mass index (ASMI) is associated with higher mortality in older adults. Articles of interest were searched for in two databases (PudMed® and Embase®). Cohort and case-control studies reporting ASMI and mortality and enrolling community-dwelling adults aged 65 years or more were included. Nine articles were eligible and included for analysis (n = 10,028). All but one study were considered of high quality by Newcastle-Ottawa Scale assessment. We calculated the standardized mean difference (SMD) for ASMI between dead and living individuals during follow-up across studies. A reduced pooled ASMI in individuals who died as compared to those who survived (ASMI SMD = -0.18, CI95% -0.23 to -0.12, REM) was found. A meta-regression was performed including ASMI SMD, grip strength SMD, body mass index (BMI), sex, study quality, method used to assess ASMI, site of study and age. BMI and ethnicity were found to significantly impact the difference in ASMI between dead and living individuals. These results reinforce the prognostic importance of assessing muscle mass in older adults.Poly-drug consumption contributes to fatal overdose in more than half of all poly-drug users. Analyzing decision-making networks may give insight into the motivations behind poly-drug use. We correlated average functional connectivity of the valuation system (VS), executive control system (ECS) and valuation-control complex (VCC) in a large population sample (n = 992) with drug use behaviour. VS connectivity is correlated with sedative use, ECS connectivity is separately correlated with hallucinogens and opiates. Network connectivity is also correlated with drug use via two-way interactions with other substances including alcohol and tobacco. These preliminary findings can contribute to our understanding of the common combinations of substance co-use and associated neural patterns.Zebrafish is broadly used as a model organism in gene loss-of-function studies in vivo, but its employment in vitro is greatly limited by the lack of efficient gene knockdown approaches in zebrafish cell lines such as ZF4. In this article, we attempted to induce silencing of telomere associated genes in ZF4 by applying the frequently-used siRNA transfection technology and a novel moiety-linked morpholino (vivo-MO). By proceeding with integrated optimization of siRNAs transfection and vivo-MOs treatment, we compared five transfection reagents and vivo-MOs simultaneously to evaluate the efficiency of terfa silencing in ZF4. 48 h after siRNAs transfection, Lipofectamine™ 3000 and X-tremeGENE™ HP leaded to knockdown in 35% and 43% of terfa transcription, respectively, while vivo-MO-terfa modulated 58% down-expression of zfTRF2 in contrast to vivo-MO-ctrl 72 h after treatment. Further siRNAs transfection targeting telomere associated genes by X-tremeGENE™ HP showed silencing in 40-68% of these genes without significant cytotoxicity and off-target effect. Our results confirmed the feasibility of gene loss-of-function studies in a zebrafish cell line, offered a systematic optimizing strategy to employ gene silencing experiments, and presented Lipofectamine™ 3000, X-tremeGENE™ HP and vivo-morpholinos as candidate gene silencing approaches for zebrafish in vitro gene loss-of-function studies. Successfully knockdown of shelterin genes further opened a new field for telomeric study in zebrafish.
The utility of post-mastectomy radiotherapy (PMRT) in women with a nodal complete response (CRn) to neoadjuvant chemotherapy (NAC) is unknown. The NSABP B-51 trial is evaluating this question, but has not reported results thus far. Therefore, we sought to answer this question with the National Cancer Database.
The National Cancer Database was queried for women with cT1-4N1-3M0 breast cancer who had undergone NAC and were ypN0 upon mastectomy. Statistics included multivariable logistic regression, Kaplan-Meier overall survival (OS) analysis, Cox proportional hazards modeling, and construction of forest plots.
Of 14,690 women, 10,092 (69%) underwent adjuvant PMRT and 4598 (31%) did not. selleck products The median follow-up was 55.6months. In all patients, the 10-year OS was 76.3% for PMRT and 78.6% without (p=0.412). There were no notable effects of PMRT on OS based on age or the axillary management (number of nodes removed). Specifically, in the NSABP B-51 population of cT1-3 cN1 patients, the 10-year OS was 82.6% for Pria.
In the absence of published results from NSABP B-51, this assessment of over 14,000 women from a contemporary US database revealed that PMRT may be most useful for a “moderately-high” risk group – women with more advanced primary and/or nodal disease at diagnosis, yet with tumor biology favorable enough that the disease does not progress or remain stable after NAC. The OS findings notwithstanding, this study cannot exclude potential differences between groups in recurrence-free survival, which is the primary endpoint of NSABP B-51, While the results of the NSABP B-51 will confirm optimal management for patients with limited nodal disease having a CRn following NAC, the present results suggest PMRT should remain the standard of care for more advanced disease than NSABP B-51 eligibility criteria.
The phase III FLAME trial (NCT01168479) showed an increase in five-year biochemical disease-free survival, with no significant increase in toxicity when adding a focal boost to external beam radiotherapy (EBRT) for localized prostate cancer [Kerkmeijer et al. JCO 2021]. The aim of this study was to investigate the association between delivered radiation dose to the anorectum and gastrointestinal (GI) toxicity (grade ≥2).
All patients in the FLAME trial were analyzed, irrespective of treatment arm. The dose-effect relation of the anorectal dose parameters (D2cm
and D50%) and GI toxicity grade ≥2 in four years of follow-up was assessed using a mixed model analysis for repeated measurements, adjusted for age, cardiovascular disease, diabetes mellitus, T-stage, baseline toxicity grade ≥1, hormonal therapy and institute.
A dose-effect relation for D2cm
and D50% was observed with adjusted odds ratios of 1.17 (95% CI 1.13-1.21, p<0.0001) and 1.20 (95% CI 1.14-1.25, p<0.0001) for GI toxicity, respectively.