Structure-Dependent Balance between Excited-State Deactivation Pathways in Cross-Conjugated Molecular Photoswitches.

Diaryl thieno-[3,4-]thiophenes (TT) are photoswitchable compounds that operate through reversible photoinduced cyclization/cycloreversion and have been designed specifically for integration within π-conjugated polymers to switchably manipulate polymer electronic properties. Here we report on how cross conjugating the central TT moiety impacts photocyclization dynamics as interrogated using transient absorption spectroscopy (TAS) for a series of switches built with electron-rich substituents that have various electronic interaction strengths with the TT core. For cross-conjugated structures exhibiting a propensity to switch in steady-state photoconversion experiments, ultrafast TAS reveals signatures of rapid dynamics (occurring within <1-10 ps) similar to those observed for unsubstituted switches and that are consistent with photocyclization.

Transcriptome-wide characterization of genetic perturbations.

Single cell CRISPR screens such as Perturb-seq enable transcriptomic profiling of genetic perturbations at scale. However, the data produced by these screens are often noisy due to cost and technical constraints, limiting power to detect true effects with conventional differential expression analyses. Here, we introduce TRanscriptome-wide Analysis of Differential Expression (TRADE), a statistical framework which estimates the transcriptome-wide distribution of true differential expression effects from noisy gene-level measurements.

Treatment of male stress urinary incontinence at time of inflatable penile prosthesis placement a review of contemporary literature.

Background And Objective: Male stress urinary incontinence (SUI) and erectile dysfunction (ED) are well established diagnoses within Men's Health, often more specifically within the prostate cancer survivorship cohort. Taken individually, well defined treatment algorithms exist with which many surgeons are comfortable; however, treatment of both in a single setting or staged fashion introduces complexity. Emerging treatment options also exist, and there is immature or minimal data when these are combined with inflatable penile prosthesis (IPP) insertion, radiation history, and/or variable degrees of incontinence.

Exciton Transfer Between Extended Electronic States in Conjugated Inter-Polyelectrolyte Complexes.

Artificial light harvesting, a process that involves converting sunlight into chemical potential energy, is considered to be a promising part of the overall solution to address urgent global energy challenges. Conjugated polyelectrolyte complexes (CPECs) are particularly attractive for this purpose due to their extended electronic states, tunable assembly thermodynamics, and sensitivity to their local environment. Importantly, ionically assembled complexes of conjugated polyelectrolytes can act as efficient donor-acceptor pairs for electronic energy transfer (EET).

High-dimensional phenotyping to define the genetic basis of cellular morphology.

The morphology of cells is dynamic and mediated by genetic and environmental factors. Characterizing how genetic variation impacts cell morphology can provide an important link between disease association and cellular function. Here, we combine genomic sequencing and high-content imaging approaches on iPSCs from 297 unique donors to investigate the relationship between genetic variants and cellular morphology to map what we term cell morphological quantitative trait loci (cmQTLs).

HAPNEST: efficient, large-scale generation and evaluation of synthetic datasets for genotypes and phenotypes.

Motivation: Existing methods for simulating synthetic genotype and phenotype datasets have limited scalability, constraining their usability for large-scale analyses. Moreover, a systematic approach for evaluating synthetic data quality and a benchmark synthetic dataset for developing and evaluating methods for polygenic risk scores are lacking.

Results: We present HAPNEST, a novel approach for efficiently generating diverse individual-level genotypic and phenotypic data.

Extremely sparse models of linkage disequilibrium in ancestrally diverse association studies.

Linkage disequilibrium (LD) is the correlation among nearby genetic variants. In genetic association studies, LD is often modeled using large correlation matrices, but this approach is inefficient, especially in ancestrally diverse studies. In the present study, we introduce LD graphical models (LDGMs), which are an extremely sparse and efficient representation of LD.

Pediatric renal trauma at a level 1 trauma center in a rural state: A 10-year institutional review and protocol implementation.

Introduction: Unintentional injury is a leading cause of mortality and morbidity in children. There is no consensus on the ideal, discrete management of pediatric renal trauma (PRT). Therefore, management protocols tend to be institution-specific.

Polygenic architecture of rare coding variation across 394,783 exomes.

Both common and rare genetic variants influence complex traits and common diseases. Genome-wide association studies have identified thousands of common-variant associations, and more recently, large-scale exome sequencing studies have identified rare-variant associations in hundreds of genes. However, rare-variant genetic architecture is not well characterized, and the relationship between common-variant and rare-variant architecture is unclear.

A RETROSPECTIVE ANALYSIS OF MORBIDITY AND MORTALITY IN CAPTIVE BLUE-CROWNED LAUGHING THRUSHES (): 1998-2018.

The blue-crowned laughingthrush (BCLT) () is a species of critically endangered passerine that is part of a Global Species Management Plan and experiences high mortality rates in some collections. Complete necropsy and medical records from 15 European institutions that housed BCLT between 1998 and 2018 were assessed to evaluate morbidity and mortality in the captive population. Medical records for 407 BCLT were received; a total of 191 morbidity events were recorded from 111 individual BCLT.

Shared components of heritability across genetically correlated traits.

Most disease-associated genetic variants are pleiotropic, affecting multiple genetically correlated traits. Their pleiotropic associations can be mechanistically informative: if many variants have similar patterns of association, they may act via similar pleiotropic mechanisms, forming a shared component of heritability. We developed pleiotropic decomposition regression (PDR) to identify shared components and their underlying genetic variants.

Partitioning gene-mediated disease heritability without eQTLs.

Unknown SNP-to-gene regulatory architecture complicates efforts to link noncoding GWAS associations with genes implicated by sequencing or functional studies. eQTLs are often used to link SNPs to genes, but expression in bulk tissue explains a small fraction of disease heritability. A simple but successful approach has been to link SNPs with nearby genes via base pair windows, but genes may often be regulated by SNPs outside their window.

Magnetic Resonance Imaging-Guided Biopsy in Active Surveillance of Prostate Cancer.

Purpose: The underlying premise of prostate cancer active surveillance (AS) is that cancers likely to metastasize will be recognized and eliminated before cancer-related disease can ensue. Our study was designed to determine the prostate cancer upgrading rate when biopsy guided by magnetic resonance imaging (MRGBx) is used before entry and during AS.

Materials And Methods: The cohort included 519 men with low- or intermediate-risk prostate cancer who enrolled in prospective studies (NCT00949819 and NCT00102544) between February 2008 and February 2020.

Future perspective of focal therapy for localized prostate cancer.

Objective: To summarize the recent literature discussing focal therapy for localized prostate cancer.

Methods: A thorough literature review was performed using PubMed to identify recent studies involving focal therapy for the treatment of localized prostate cancer.

Results: In an effort to decrease the morbidity associated with prostate cancer treatment, many urologists are turning to focal therapy as an alternative treatment option.

The utilization of perfused cadaver simulation in urologic training: a pilot study.

Background: We sought to determine if participating in a surgical training session using perfused fresh human cadavers (PFHC) had a positive effect on urology residents' confidence in performing open and endoscopic procedures.

Methods: Urology residents at our institution participated in a surgical training session in the West Virginia University Fresh Tissue Training Program, which utilized fresh cadavers with vascular perfusion. The session consisted of performing different urologic procedures (open and endoscopic) on the perfused fresh human cadavers (PFHC).

The distribution of common-variant effect sizes.

The genetic effect-size distribution of a disease describes the number of risk variants, the range of their effect sizes and sample sizes that will be required to discover them. Accurate estimation has been a challenge. Here I propose Fourier Mixture Regression (FMR), validating that it accurately estimates real and simulated effect-size distributions.

Emerging role for local therapy in oligometastatic prostate cancer.

Oligometastatic prostate cancer is a subtype of metastatic disease that generally is defined by the presence of 5 or fewer metastatic lesions. Metastatic prostate cancer currently is treated with androgen deprivation therapy and additional systemic therapy, such as novel antiandrogen medications or chemotherapy. The management of metastatic prostate cancer is evolving, however, with the notion that some patients with low-burden metastatic disease may benefit from both local and systemic therapy.

The Risk of Prostate Cancer Progression in Active Surveillance Patients with Bilateral Disease Detected by Combined Magnetic Resonance Imaging-Fusion and Systematic Biopsy.

Purpose: We sought to evaluate whether bilateral prostate cancer detected at active surveillance (AS) enrollment is associated with progression to Grade Group (GG) ≥2 and to compare the efficacy of combined targeted biopsy plus systematic biopsy (Cbx) vs systematic biopsy (Sbx) or targeted biopsy alone to detect bilateral disease.

Materials And Methods: A prospectively maintained database of patients referred to our institution from 2007-2020 was queried. The study cohort included all AS patients with GG1 on confirmatory Cbx and followup of at least 1 year.

DETERMINATION OF VERTEBRAL HEART SCALE AND ECHOCARDIOGRAPHIC MEASUREMENTS IN HEALTHY ANESTHETIZED AFRICAN WILD DOGS () IN HUMAN CARE.

Cardiac disease is an important cause of mortality in African wild dogs in human care. Vertebral heart scale (VHS) is a well-documented objective measure of cardiac size and is commonly used in domestic dogs. The VHS of 63 clinically healthy African wild dogs housed in zoological institutions was retrospectively calculated.

Contemporary Clinical Isolates of Staphylococcus aureus from Pediatric Osteomyelitis Patients Display Unique Characteristics in a Mouse Model of Hematogenous Osteomyelitis.

Osteomyelitis can result from the direct inoculation of pathogens into bone during injury or surgery or from spread via the bloodstream, a condition called hematogenous osteomyelitis (HOM). HOM disproportionally affects children, and more than half of cases are caused by Staphylococcus aureus. Laboratory models of osteomyelitis mostly utilize direct injection of bacteria into the bone or implantation of foreign material and therefore do not directly interrogate the pathogenesis of pediatric hematogenous osteomyelitis.

Changes in Magnetic Resonance Imaging Using the Prostate Cancer Radiologic Estimation of Change in Sequential Evaluation Criteria to Detect Prostate Cancer Progression for Men on Active Surveillance.

Background: The ability of serial magnetic resonance imaging (MRI) to capture pathologic progression during active surveillance (AS) remains in question.

Objective: To determine whether changes in MRI are associated with pathologic progression for patients on AS.

Design, Setting, And Participants: From July 2007 through January 2020, we identified all patients evaluated for AS at our institution.

Using Prostate Imaging-Reporting and Data System (PI-RADS) Scores to Select an Optimal Prostate Biopsy Method: A Secondary Analysis of the Trio Study.

Background: While magnetic resonance imaging (MRI)-targeted biopsy (TBx) results in better prostate cancer (PCa) detection relative to systematic biopsy (SBx), the combination of both methods increases clinically significant PCa detection relative to either Bx method alone. However, combined Bx subjects patients to higher number of Bx cores and greater detection of clinically insignificant PCa.

Objective: To determine if prebiopsy prostate MRI can identify men who could forgo combined Bx without a substantial risk of missing clinically significant PCa (csPC).