Systematic review and meta-analysis: Prognostic impact of time from diagnosis to treatment in patients with acute myeloid leukemia.

Background: Acute myeloid leukemia (AML) has been considered an oncologic emergency that requires initiation of chemotherapy immediately after diagnosis. With the introduction of novel targeted therapies, there is a potential benefit associated with delaying definitive treatment for identification of actionable therapeutic targets. Unfortunately, cytogenetic/molecular testing can take >7 days to return, and there is not a consensus regarding the prognostic impact of time from diagnosis to treatment (TDT) in AML.

Efficiency of a randomized confirmatory basket trial design constrained to control the family wise error rate by indication.

Basket trials pool histologic indications sharing molecular pathophysiology, improving development efficiency. Currently, basket trials have been confirmatory only for exceptional therapies. Our previous randomized basket design may be generally suitable in the resource-intensive confirmatory phase, maintains high power even with modest effect sizes, and provides nearly -fold increased efficiency for indications, but controls false positives for the pooled result only.

Social Media, Digital Scholarship, and Academic Promotion in US Medical Schools.

Background And Objectives: Academic promotion is critical in academic medicine. Traditionally, peer-reviewed journal articles have been at the core of advancement deliberations. With the increasing prominence digital content and social media, an increasing number of academics have begun linking their scholarly value with their online activities.

Efficient two-stage sequential arrays of proof of concept studies for pharmaceutical portfolios.

Previous work has shown that individual randomized "proof-of-concept" (PoC) studies may be designed to maximize cost-effectiveness, subject to an overall PoC budget constraint. Maximizing cost-effectiveness has also been considered for arrays of simultaneously executed PoC studies. Defining Type III error as the opportunity cost of not performing a PoC study, we evaluate the common pharmaceutical practice of allocating PoC study funds in two stages.

Female Genital Mutilation/Cutting as Grounds for Asylum Requests in the US: An Analysis of More than 100 Cases.

Female Genital Mutilation or Cutting (FGM/C) is a human rights violation used to claim asylum in the US. We sought to understand the nature of these asylum requests. Analysis of 121 FGM/C-focused medical affidavits, and 132 legal case reports.

Medical students' individual and social empathy: A follow-up study.

The Social Empathy Index (SEI) measures self-reported empathy for individuals and for vulnerable groups. In a previous study, we published first-year medical students' SEI scores before and after completing a course on the social determinants of health. We re-administered the SEI to the original student cohort entering their 4th year.

Comorbid Insomnia With Obstructive Sleep Apnea: Clinical Characteristics and Risk Factors.

Study Objectives: Obstructive sleep apnea (OSA) and chronic insomnia are two common sleep disorders and both are considered independent risk factors for heart disease. The aim of this study was to investigate the prevalence of comorbid insomnia with OSA and to compare its clinical characteristics with those of OSA without insomnia.

Methods: Patients who visited two tertiary university hospital sleep centers were screened.

Pharmacological relevance of endoxifen in a laboratory simulation of breast cancer in postmenopausal patients.

Background: Tamoxifen is metabolically activated via a CYP2D6 enzyme system to the more potent hydroxylated derivatives 4-hydroxytamoxifen and endoxifen. This study addresses the pharmacological importance of endoxifen by simulating clinical scenarios in vitro.

Methods: Clinical levels of tamoxifen metabolites in postmenopausal breast cancer patients previously genotyped for CYP2D6 were used in vitro along with clinical estrogen levels (estrone and estradiol) in postmenopausal patients determined in previous studies.

Simulation with cells in vitro of tamoxifen treatment in premenopausal breast cancer patients with different CYP2D6 genotypes.

Background And Purpose: Tamoxifen is a prodrug that is metabolically activated by 4-hydroxylation to the potent primary metabolite 4-hydroxytamoxifen (4OHT) or via another primary metabolite N-desmethyltamoxifen (NDMTAM) to a biologically active secondary metabolite endoxifen through a cytochrome P450 2D6 variant system (CYP2D6). To elucidate the mechanism of action of tamoxifen and the importance of endoxifen for its effect, we determined the anti-oestrogenic efficacy of tamoxifen and its metabolites, including endoxifen, at concentrations corresponding to serum levels measured in breast cancer patients with various CYP2D6 genotypes (simulating tamoxifen treatment).

Experimental Approach: The biological effects of tamoxifen and its metabolites on cell growth and oestrogen-responsive gene modulation were evaluated in a panel of oestrogen receptor-positive breast cancer cell lines.

The association of intimate partner violence, recreational drug use with HIV seroprevalence among MSM.

Intimate partner violence (IPV) has been significantly associated with HIV among heterosexual individuals. Yet a similar relationship has not been so clearly described among men who have sex with men (MSM). The aim of this study was to investigate the association of IPV with HIV seroprevalence among MSM.

Region-based Statistical Analysis of 2D PAGE Images.

A new comprehensive procedure for statistical analysis of two-dimensional polyacrylamide gel electrophoresis (2D PAGE) images is proposed, including protein region quantification, normalization and statistical analysis. Protein regions are defined by the master watershed map that is obtained from the mean gel. By working with these protein regions, the approach bypasses the current bottleneck in the analysis of 2D PAGE images: it does not require spot matching.

Independent component analysis of 2-D electrophoresis gels.

We present a novel application of independent component analysis (ICA), an exploratory data analysis technique, to two-dimensional electrophoresis (2-DE) gels, which have been used to analyze differentially expressed proteins across groups. Unlike currently used pixel-wise statistical tests, ICA is a data-driven approach that utilizes the information contained in the entire gel data. We also apply ICA on wavelet-transformed 2-DE gels to address the high dimensionality and noise problems typically found in 2-DE gels.