Notes

AKIRIN2 handles the particular nuclear significance of proteasomes within vertebrates.
A handful of studies have investigated sexually antagonistic constraints on achieving sex-specific fitness optima, although exclusively through male-genome-limited evolution experiments. In this article, we established a female-limited X chromosome evolution experiment, where we used an X chromosome balancer to enforce the inheritance of the X through the matriline, thus removing exposure to male selective constraints. This approach eliminates the effects of sexually antagonistic selection on the X chromosome, permitting evolution toward a single sex-specific optimum. After multiple generations of selection, we found strong evidence that body size and development time had moved toward a female-specific optimum, whereas reproductive fitness and locomotion activity remained unchanged. The changes in body size and development time are consistent with previous results, and suggest that the X chromosome is enriched for sexually antagonistic genetic variation controlling these particular traits. The lack of change in reproductive fitness and locomotion activity could be due to a number of mutually nonexclusive explanations, including a lack of sexually antagonistic variance on the X chromosome for those traits or confounding effects of the use of the balancer chromosome. This study is the first to employ female-genome-limited selection and adds to the understanding of the complexity of sexually antagonistic genetic variation.Nonadherence to oral anticancer medications (OAMs) in the United States is as low as 33% for some cancers. The reasons for nonadherence to these lifesaving medications are multifactorial, yet the majority of studies focus on patient-level factors influencing uptake and adherence. Individually based interventions to increase patient adherence have not been effective, and this warrants attention to factors at the payor, pharmaceutical, and clinical systems levels. FL118 Based on the authors' research and clinical experiences, this commentary brings fresh attention to the long-standing issue of OAM nonadherence, a growing quality-of-care issue, from a systems perspective. In this commentary, the key driving factors in pharmaceutical and payor systems (state and federal laws, payor/insurance companies, and pharmaceutical companies), clinical systems (hospitals and providers), and patient contexts that have trickle-down effects on patient adherence to OAMs are outlined. In the end, the authors' recommendations include examining the influence of laws governing OAM drug pricing, OAM supply, and provider reimbursement; reducing the need for prior authorization of long-approved OAMs; identifying cost-effective ways for providers to monitor nonadherence; examining issues of provider bias in OAM prescriptions; and further elucidating in which contexts patients are likely to be able to adhere. These recommendations offer a starting point for an examination of the chain of systems influencing patient adherence and may help to finally resolve persistently high levels of OAM nonadherence.Objectives/hypothesis To investigate the profile of patients with laryngopharyngeal reflux (LPR) at hypopharyngeal-esophageal multichannel intraluminal impedance-pH (HEMII-pH) monitoring and the relationship between hypopharyngeal-proximal reflux episodes (HREs) and saliva pepsin concentration. Study design Prospective non-controlled. Methods Patients were recruited from three European hospitals from January 2018 to October 2019. Patients benefited from HEMII-pH monitoring and saliva collections to measure saliva pepsin concentration in the same time. Saliva pepsin concentration was measured in the morning (fasting), after lunch, and after dinner. The LPR profile of patients was studied through a breakdown of the HEMII-pH findings over the 24 hours of testing. The relationship between the concentrations of saliva pepsin and 24-hour HREs was studied through linear multiple regression. Results One hundred twenty-six patients completed the study. The HEMII-pH analyses revealed that 73.99% of HREs occurred outside 1-hour postmeal times, whereas 20.49% and 5.52% of HREs occurred during the 1-hour postmeal and nighttime, respectively. Seventy-four patients (58.73%) did not have nighttime HREs. Patients with both daytime and nighttime HREs had more severe HEMII-pH parameters and reflux symptom score compared with patients with only daytime HREs. There were no significant associations between HREs and saliva pepsin concentration. Conclusions Unlike gastroesophageal reflux disease, HREs occur less frequently after meals and nighttime. The analysis of the HEMII-pH profile of the LPR patients has to be considered to develop future personalized therapeutic strategies. Level of evidence 4 Laryngoscope, 2020.Objectives To compare the detection rates of prostate cancer between systematic biopsy and targeted biopsy using a stereotactic robot-assisted transperineal prostate platform. Materials and methods We identified consecutive men with suspicious lesion(s) on multi-parametric magnetic resonance imaging (mpMRI) who underwent both systematic and MRI-transrectal ultrasound (US) fusion targeted biopsy using our proprietary transperineal robot-assisted prostate biopsy platform between January 2015 to January 2019 at our institution for retrospectively analysis. Comparative analysis between systematic and targeted biopsy using McNemar's test and further stratified by prior biopsy status and PI-RADS v2.0 score. ISUP grade group ≥2 cancers (previously known as gleason grade ≥7) were considered to be clinically-significant. Results Five hundred patients were included in our final analysis, out of which 67 (13%) were low-risk cancer patients on AS. Of the 433 men without prior diagnosis of cancer, 288 (67%) were biopsy na and PI-RADS score. Targeted biopsy has greater sampling efficiency compared to systematic biopsy for both overall and clinically-significant prostate cancer (23.2% vs 9.8%, p less then 0.001 and 14.8% vs 5.6%, p less then 0.001) CONCLUSIONS Using our robot-assisted transperineal prostate platform, combined MRI-US targeted biopsy with concurrent systematic prostate systematic biopsy likely represents the optimal method for the detection of clinically-significant prostate cancer.
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