Inducible auto-phosphorylation regulates a widespread family of nucleotidyltransferase toxins.

Nucleotidyltransferases (NTases) control diverse physiological processes, including RNA modification, DNA replication and repair, and antibiotic resistance. The Mycobacterium tuberculosis NTase toxin family, MenT, modifies tRNAs to block translation. MenT toxin activity can be stringently regulated by diverse MenA antitoxins.

Reigniting Intensive Care Unit Liberation.

Background: The Society of Critical Care Medicine has established guidelines to manage pain, sedation, delirium, immobility, family participation, and sleep disruption in the intensive care unit, a set of interventions known as the intensive care unit liberation (ABCDEF) bundle. Adherence to these guidelines has shown positive results.

Local Problem: In the intensive care units of a level I trauma academic teaching hospital in central Texas, the rate of bedside nursing staff adherence to the ABCDEF bundle was only 67.

Predictors of residual disease after breast conservation surgery for ductal carcinoma in situ: A retrospective study.

Background: Breast-conserving therapy is the standard of care for ductal carcinoma in situ (DCIS). Debate on what constitutes a satisfactory margin persists. This study aimed to identify predictors of residual disease at re-excision.

Synthesis and insecticidal activity of N-(5-phenylpyrazin-2-yl)-benzamide derivatives: Elucidation of mode of action on chitin biosynthesis through symptomology and genetic studies.

Among the six-membered heterocycles, the pyrazine ring is poorly explored in crop protection and does not feature in any product listed in the current IRAC MoA classification. In an effort to identify new leads for internal research, we synthesized a series of N-(5-phenylpyrazin-2-yl)-benzamide derivatives and evaluated them for their insecticidal activity. N-(5-phenylpyrazin-2-yl)-benzamide derivatives 3 were prepared using an automated two-step synthesis protocol.

Generation of murine tumor models refractory to αPD-1/-L1 therapies due to defects in antigen processing/presentation or IFNγ signaling using CRISPR/Cas9.

Immune checkpoint blockade (ICB) targeting the programmed cell death protein 1 (PD-1) and its ligand 1 (PD-L1) fails to provide clinical benefit for most cancer patients due to primary or acquired resistance. Drivers of ICB resistance include tumor antigen processing/presentation machinery (APM) and IFNγ signaling mutations. Thus, there is an unmet clinical need to develop alternative therapies for these patients.

Peptide Binder to Glypican-3 as a Theranostic Agent for Hepatocellular Carcinoma.

Glypican-3 (GPC3) is a membrane-associated glycoprotein that is significantly upregulated in hepatocellular carcinomas (HCC) with minimal to no expression in normal tissues. The differential expression of GPC3 between tumor and normal tissues provides an opportunity for targeted radiopharmaceutical therapy to treat HCC, a leading cause of cancer-related deaths worldwide. : DOTA-RYZ-GPC3 (RAYZ-8009) comprises a novel macrocyclic peptide binder to GPC3, a linker, and a chelator that can be complexed with different radioisotopes.

Uncovering receptor-ligand interactions using a high-avidity CRISPR activation screening platform.

The majority of clinically approved drugs target proteins that are secreted or cell surface bound. However, further advances in this area have been hindered by the challenging nature of receptor deorphanization, as there are still many secreted and cell-bound proteins with unknown binding partners. Here, we developed an advanced screening platform that combines CRISPR-CAS9 guide-mediated gene activation (CRISPRa) and high-avidity bead-based selection.

Why Gerontology Needs Anthropology: Toward an Applied Anthropological Gerontology.

In this essay, we argue that gerontologists should increase their engagement with anthropologists to increase transdisciplinary collaboration, fulfill the interdisciplinary promise of gerontology as a field, and to ensure the work of anthropologists is formed by, and employed in, situations where meaningful engagement with practitioners and policymakers can lead to social change. Anthropology is the study of human societies in historical, biological, and sociocultural context, comprising a holistic field of study that can contribute unique methods, approaches, and theories to the field of gerontology. Although increasing amounts of anthropological scholarship have focused on older adulthood, this critical work of anthropologists still needs to be utilized by those in positions of power to enact change.

SERPINB3-MYC axis induces the basal-like/squamous subtype and enhances disease progression in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) exhibits distinct molecular subtypes: classical/progenitor and basal-like/squamous. Our study aimed to identify genes contributing to the development of the basal-like/squamous subtype, known for its aggressiveness. Transcriptome analyses revealed consistent upregulation of SERPINB3 in basal-like/squamous PDAC, correlating with reduced patient survival.

The increasing complexity of femoral fragility fractures: incidence, fracture patterns and management over a 10-year period.

Introduction: The purpose of this study was to determine whether there have been changes in the numbers and complexity of femoral fragility fractures presenting to our department over a period of 10 years.

Methods: Patients >60 years presenting with femoral fragility fractures to our institution in 2018-2019 (397 fractures) were compared with respect to demographic data, incidence rates, fracture classification and surgical management with a historical cohort from 2009-2010 (335 fractures). Pathological and high velocity fractures were excluded.

Making Home: The Role of Social Networks on Identity, Health, and Quality of Life Among Rural Lesbian and Gay Older Adults.

Background And Objectives: Gay and lesbian older persons face a host of health inequalities related to their identity as they age. Challenges to health access and appropriate social support may be even more exacerbated for those living in rural environments; this may be due to the lack of supportive and affirming social connections. This project aimed to explore and describe the social networks and the relationship of these social networks to identity, health, and quality of life of gay and lesbian individuals in rural communities.

RYZ101 (Ac-225 DOTATATE) Opportunity beyond Gastroenteropancreatic Neuroendocrine Tumors: Preclinical Efficacy in Small-Cell Lung Cancer.

Overexpression of somatostatin receptors (SSTR), particularly SSTR2, is found in gastroenteropancreatic neuroendocrine tumors (GEP-NET), and subsets of other solid tumors such as small-cell lung cancer (SCLC). SCLC accounts for approximately 13% to 15% of lung cancer and lacks effective therapeutic options. IHC analysis indicates that up to 50% of SCLC tumors are SSTR2-positive, with a substantial subset showing high and homogenous expression.

The Use of Amplified ATP Bioluminescence for Rapid Sterility Testing of Drug Product Formulations.

The use of amplified adenosine trisphosphate (ATP) bioluminescence has been established within AstraZeneca as a technique for assessing the sterility of drug product formulations. A platform validation was generated that challenged the technology with a range of organisms and inoculum levels, and the approach to onboarding additional drug products has been designed to maximize the understanding of the drug product behavior when samples may be limited during the development phases of the life cycle of a drug product. Many activities to support sterility assurance take place during product development.

Global rural health disparities in Alzheimer's disease and related dementias: State of the science.

Introduction: Individuals living in rural communities are at heightened risk for Alzheimer's disease and related dementias (ADRD), which parallels other persistent place-based health disparities. Identifying multiple potentially modifiable risk factors specific to rural areas that contribute to ADRD is an essential first step in understanding the complex interplay between various barriers and facilitators.

Methods: An interdisciplinary, international group of ADRD researchers convened to address the overarching question of: "What can be done to begin minimizing the rural health disparities that contribute uniquely to ADRD?" In this state of the science appraisal, we explore what is known about the biological, behavioral, sociocultural, and environmental influences on ADRD disparities in rural settings.

Relationship Functioning and Gut Microbiota Composition among Older Adult Couples.

An emerging area of research extends work on couple functioning and physical health to gut health, a critical marker of general health and known to diminish with age. As a foray into this area, we conducted a pilot study to (1) determine the feasibility of remote data collection, including a fecal sample, from older adult couples, (2) examine within-couple concordance in gut microbiota composition, and (3) examine associations between relationship functioning and gut microbiota composition. Couples (N = 30) were recruited from the community.

The complete genome assemblies of 19 insect pests of worldwide importance to agriculture.

There are many insect pests worldwide that damage agricultural crop and reduce yield either by direct feeding or by the transmission of plant diseases. To date, control of pest insects has been achieved largely by applying synthetic insecticides. However, insecticide use can be seriously impacted by legislation that limits their use or by the evolution of resistance in the target pest.

What the Solitaire illusion tells us about perception of numerosity.

In four experiments we investigated the Solitaire illusion. In this illusion, most observers see as more numerous a set of dots that forms a single central group, compared to dots on the outside of that group. We confirmed and extended the effect to configurations with much higher numerosity than the original and of various colours.

Engagement and Advocacy of Community-Based Organizations Serving Older Adults in Native American, Rural, and Homeless Communities During the COVID-19 Pandemic.

Older adults in Native American, rural, and homeless communities have been disproportionately affected by the Coronavirus Disease 2019 (COVID-19) pandemic due to structural and systemic inequities. However, community-based organizations (CBOs) serving these older adults are well positioned as frontline responders and trusted messengers to support their needs and provide vital services that enable them to stay safe. This commentary argues that CBOs are essential for engaging with and responding to community needs during a pandemic.

An environmental scan of aging-related micro-credentials: Implications for gerontology and gerontologists.

The purpose and rise of formal academic programs in gerontology at colleges and universities has been well documented over the last fifty years. What has been less well-documented is the rise of alternative pathways to gerontology training and gerontological competence, including micro-credentialing. Micro-credentials (MCs) are intended to provide quick-to-complete, competency-based education around specific topics to demonstrate relevant skills to employers.

Recovering individual haplotypes and a contiguous genome assembly from pooled long-read sequencing of the diamondback moth (Lepidoptera: Plutellidae).

The assembly of divergent haplotypes using noisy long-read data presents a challenge to the reconstruction of haploid genome assemblies, due to overlapping distributions of technical sequencing error, intralocus genetic variation, and interlocus similarity within these data. Here, we present a comparative analysis of assembly algorithms representing overlap-layout-consensus, repeat graph, and de Bruijn graph methods. We examine how postprocessing strategies attempting to reduce redundant heterozygosity interact with the choice of initial assembly algorithm and ultimately produce a series of chromosome-level assemblies for an agricultural pest, the diamondback moth, Plutella xylostella (L.

Evaluation of the ITV-margin and variables affecting bladder and mesorectal deformation during long course neoadjuvant radiotherapy for rectal cancer.

Internal target volume (ITV) margins were estimated by evaluating the movement of mesorectum and bladder during neoadjuvant long-course radiation therapy (RT) for rectal cancer. In this prospective study, 23 patients with rectal cancer had planning CT (pCT) and weekly cone beam CT (CBCT) in supine position during preoperative long-course RT. Mesorectal wall motion was analyzed based on the coordinates of the most anterior, posterior, left and right points on the pCT and CBCT.