Cyclin A/B RxL Macrocyclic Inhibitors to Treat Cancers with High E2F Activity.

Cancer cell proliferation requires precise control of E2F1 activity; excess activity promotes apoptosis. Here, we developed cell-permeable and bioavailable macrocycles that selectively kill small cell lung cancer (SCLC) cells with inherent high E2F1 activity by blocking RxL-mediated interactions of cyclin A and cyclin B with select substrates. Genome-wide CRISPR/Cas9 knockout and random mutagenesis screens found that cyclin A/B RxL macrocyclic inhibitors (cyclin A/Bi) induced apoptosis paradoxically by cyclin B- and Cdk2-dependent spindle assembly checkpoint activation (SAC).

Colonoscopy quality measures and adherence to follow-up guidelines among endoscopists participating in a U.S. endoscopy registry.

Background And Aims: Colonoscopy screening can substantially reduce colorectal cancer incidence and mortality. Colonoscopies may achieve maximum benefit when they are performed with high quality and accompanied by follow-up recommendations that adhere to clinical guidelines. This study aimed to determine to what extent endoscopists met targets for colonoscopy quality from 2016 through 2019 (the most recent years before the COVID-19 pandemic).

The Effect of the COVID Pandemic on the Rate of Same-Day Discharge in Primary Hip and Knee Arthroplasty.

Background: Same-day discharge (SDD) following primary total hip arthroplasty (THA) and total knee arthroplasty (TKA) started increasing prior to 2020. The purpose of this study was to evaluate the change in the rate of SDD after the pandemic and determine whether those changes became permanent.

Methods: The annual rate of SDD for 15,208 primary THA and TKA cases performed between January 1, 2015, and September 9, 2022, at a single institution was determined.

Identifying tumor type and cell type-specific gene expression alterations in pediatric central nervous system tumors.

Central nervous system (CNS) tumors are the leading cause of pediatric cancer death, and these patients have an increased risk for developing secondary neoplasms. Due to the low prevalence of pediatric CNS tumors, major advances in targeted therapies have been lagging compared to other adult tumors. We collect single nuclei RNA-seq data from 84,700 nuclei of 35 pediatric CNS tumors and three non-tumoral pediatric brain tissues and characterize tumor heterogeneity and transcriptomic alterations.

Total Synthesis of the Reported Structure of Cahuitamycin A: Insights into an Elusive Natural Product Scaffold.

In a 2016 screen of natural product extracts, a new family of natural products, the cahuitamycins, was discovered and found to inhibit biofilm formation in the human pathogen . The proposed molecular structures contained an unusual piperazic acid residue, which piqued interest related to their structure/function and biosynthesis. Herein we disclose the first total synthesis of the proposed structure of cahuitamycin A in a 12-step longest linear sequence and 18% overall yield.

Up-to-Date Breast, Cervical, and Colorectal Cancer Screening Test Use in the United States, 2021.

Introduction: We examined national estimates of breast, cervical, and colorectal cancer (CRC) screening test use and compared them with Healthy People 2030 national targets. Test use in 2021 was compared with prepandemic estimates.

Methods: In 2022, we used 2021 National Health Interview Survey (NHIS) data to estimate proportions of adults up to date with US Preventive Services Task Force recommendations for breast (women aged 50-74 y), cervical (women aged 21-65 y), and CRC screening (adults aged 50-75 y) across sociodemographic and health care access variables.

A very brief note on why bacterial evolution has physiology.

The majority of bacteria live and evolve in surface biofilms. Both growth in biofilms and horizontal transfer of DNA are regulated by quorum-sensing pheromone signals. The common regulation of bacterial surface growth and DNA transfers illustrates how physiology contributes to bacterial evolution.

OpenPBTA: The Open Pediatric Brain Tumor Atlas.

Pediatric brain and spinal cancers are collectively the leading disease-related cause of death in children; thus, we urgently need curative therapeutic strategies for these tumors. To accelerate such discoveries, the Children's Brain Tumor Network (CBTN) and Pacific Pediatric Neuro-Oncology Consortium (PNOC) created a systematic process for tumor biobanking, model generation, and sequencing with immediate access to harmonized data. We leverage these data to establish OpenPBTA, an open collaborative project with over 40 scalable analysis modules that genomically characterize 1,074 pediatric brain tumors.

Breast, cervical, and colorectal cancer screening test use in the US territories of Guam, Puerto Rico, and the US Virgin Islands.

Background: The United States Preventive Services Task Force (USPSTF) recommends breast, cervical, and colorectal cancer screening among eligible adults, but information on screening use in the US territories is limited.

Methods: To estimate the proportion of adults up-to-date with breast, cervical, and colorectal cancer screening based on USPSTF recommendations, we analyzed Behavioral Risk Factor Surveillance System data from 2016, 2018, and 2020 for the 50 US states and DC (US) and US territories of Guam and Puerto Rico and from 2016 for the US Virgin Islands. Age-standardized weighted proportions for up-to-date cancer screening were examined overall and by select characteristics for each jurisdiction.

Repetitive DNA is Functional and Encodes Parts of the Non-Coding RNA Repertoire.

This is a commentary on the article by Eviatar Nevo and Kexin Li entitled "Sympatric Speciation in Mole Rats and Wild Barley and Their Genome Repeatome Evolution: A Commentary", published recently in .

Tumor type and cell type-specific gene expression alterations in diverse pediatric central nervous system tumors identified using single nuclei RNA-seq.

Central nervous system (CNS) tumors are the leading cause of pediatric cancer death, and these patients have an increased risk for developing secondary neoplasms. Due to the low prevalence of pediatric CNS tumors, major advances in targeted therapies have been lagging compared to other adult tumors. We collected single nuclei RNA-seq data from 35 pediatric CNS tumors and three non-tumoral pediatric brain tissues (84,700 nuclei) and characterized tumor heterogeneity and transcriptomic alterations.

Serology and Comorbidities in Patients With Fracture Nonunion: A Multicenter Evaluation of 640 Patients.

Introduction: This multicenter cohort study investigated the association of serology and comorbid conditions with septic and aseptic nonunion.

Methods: From January 1, 2011, to December 31, 2017, consecutive individuals surgically treated for nonunion were identified from seven centers. Nonunion-type, comorbid conditions and serology were assessed.

Cancer Screening Test Use-U.S., 2019.

Introduction: The U.S. Preventive Services Task Force recommends breast, cervical, and colorectal cancer screening to reduce mortality from these cancers, but screening use has been below national targets.

What we have learned about evolutionary genome change in the past 7 decades.

Cytogenetics and genomics have completely transformed our understanding of evolutionary genome change since the early 1950s. The point of this paper is to outline some of the empirical findings responsible for that transformation. The discovery of transposable elements (TEs) in maize by McClintock, and their subsequent rediscovery in all forms of life, tell us that organisms have the inherent capacity to evolve dispersed genomic networks encoding complex cellular and multicellular adaptations.

Health plan-based mailed fecal testing for colorectal cancer screening among dual-eligible Medicaid/Medicare enrollees: Outcomes of 2 program models.

Background: Health insurance plans are increasingly offering mailed fecal immunochemical test (FIT) programs for colorectal cancer (CRC) screening, but few studies have compared the outcomes of different program models (eg, invitation strategies).

Methods: This study compares the outcomes of 2 health plan-based mailed FIT program models. In the first program (2016), FIT kits were mailed to all eligible enrollees; in the second program (2018), FIT kits were mailed only to enrollees who opted in after an outreach phone call.

Structural and Biochemical Characterization of the Flavin-Dependent Siderophore-Interacting Protein from .

is an opportunistic pathogen with a high mortality rate due to multi-drug-resistant strains. The synthesis and uptake of the iron-chelating siderophores acinetobactin (Acb) and preacinetobactin (pre-Acb) have been shown to be essential for virulence. Here, we report the kinetic and structural characterization of BauF, a flavin-dependent siderophore-interacting protein (SIP) required for the reduction of Fe(III) bound to Acb/pre-Acb and release of Fe(II).

Why the third way of evolution is necessary.

The Third Way of Evolution was founded in 2014 to make the public aware that contemporary evolution science is not limited to the neo-Darwinian Modern Synthesis of the past century. This was important to do because evolution was challenged as incapable of explaining biological complexity by the Intelligent Design movement. Expounding biological theories like the Modern Synthesis is always subject to limited empirical evidence, fundamental concepts that inevitably change over time, and conceptual preferences that often prove to be misleading.

Screening for Colorectal Cancer in the United States: Correlates and Time Trends by Type of Test.

Background: It is strongly recommended that adults aged 50-75 years be screened for colorectal cancer. Recommended screening options include colonoscopy, sigmoidoscopy, CT colonography, guaiac fecal occult blood testing (FOBT), fecal immunochemical testing (FIT), or the more recently introduced FIT-DNA (FIT in combination with a stool DNA test). Colorectal cancer screening programs can benefit from knowledge of patterns of use by test type and within population subgroups.

What can evolutionary biology learn from cancer biology?

Detecting and treating cancer effectively involves understanding the disease as one of somatic cell and tumor macroevolution. That understanding is key to avoid triggering an adverse reaction to therapy that generates an untreatable and deadly tumor population. Macroevolution differs from microevolution by karyotype changes rather than isolated localized mutations being the major source of hereditary variation.

How Chaotic Is Genome Chaos?

Cancer genomes evolve in a punctuated manner during tumor evolution. Abrupt genome restructuring at key steps in this evolution has been called "genome chaos." To answer whether widespread genome change is truly chaotic, this review (i) summarizes the limited number of cell and molecular systems that execute genome restructuring, (ii) describes the characteristic signatures of DNA changes that result from activity of those systems, and (iii) examines two cases where genome restructuring is determined to a significant degree by cell type or viral infection.

Broad Spectrum Antibiotic Xanthocillin X Effectively Kills Dysregulation of Heme Biosynthesis.

Isonitrile natural products exhibit promising antibacterial activities. However, their mechanism of action (MoA) remains largely unknown. Based on the nanomolar potency of xanthocillin X () against diverse difficult-to-treat Gram-negative bacteria, including the critical priority pathogen , we performed in-depth studies to decipher its MoA.

Macrophages in SHH subgroup medulloblastoma display dynamic heterogeneity that varies with treatment modality.

Tumor-associated macrophages (TAMs) play an important role in tumor immunity and comprise of subsets that have distinct phenotype, function, and ontology. Transcriptomic analyses of human medulloblastoma, the most common malignant pediatric brain cancer, showed that medulloblastomas (MBs) with activated sonic hedgehog signaling (SHH-MB) have significantly more TAMs than other MB subtypes. Therefore, we examined MB-associated TAMs by single-cell RNA sequencing of autochthonous murine SHH-MB at steady state and under two distinct treatment modalities: molecular-targeted inhibitor and radiation.