A DNA unwinding equilibrium serves as a checkpoint for CRISPR-Cas12a target discrimination.

CRISPR-associated proteins such as Cas9 and Cas12a are programable RNA-guided nucleases that have emerged as powerful tools for genome manipulation and molecular diagnostics. However, these enzymes are prone to cleaving off-target sequences that contain mismatches between the RNA guide and DNA protospacer. In comparison to Cas9, Cas12a has demonstrated distinct sensitivity to protospacer-adjacent-motif (PAM) distal mismatches, and the molecular basis of Cas12a's enhanced target discrimination is of great interest.

Alcohol-Induced Mucociliary Dysfunction: Role of Defective CFTR Channel Function.

Unlabelled: Excessive alcohol use is thought to increase the risk of respiratory infections by impairing mucociliary clearance (MCC). In this study, we investigate the hypothesis that alcohol reduces the function of CFTR, the protein that is defective in individuals with cystic fibrosis, thus altering mucus properties to impair MCC and the airway's defense against inhaled pathogens.

Methods: Sprague Dawley rats with wild type CFTR (+/+), matched for age and sex, were administered either a Lieber-DeCarli alcohol diet or a control diet with the same number of calories for eight weeks.

Inpatient Pediatric Care and Clinician Workforce in Wisconsin: The State of the State.

Introduction: Availability of inpatient pediatric services declined across the United States from 2008 through 2018, with rural areas experiencing steepest declines. Despite the movement of pediatric care to children's centers, most children are still cared for in community hospitals nationally. Assessing the availability and providers of inpatient pediatric care in Wisconsin is an important step in ensuring the health care needs of children in the state continue to be met.

Mother-Child Relationship Quality from Preschool to Adolescence: Variation by Maternal Education.

Using longitudinal data from the National Institute of Child Health and Human Development Study of Early Child Care and Youth Development ( = 1,088), we examine changes in maternal perception of closeness and conflict in the mother-child relationship from the child's preschool to adolescent years, with attention to variation by maternal education. Analyses using individual growth models show that mother-child closeness increases, while mother-child conflict decreases from preschool to first grade. From first grade to age 15, mother-child closeness decreases, while mother-child conflict increases, both gradually.

The genomic basis of temporal niche evolution in a diurnal rodent.

Patterns of diel activity-how animals allocate their activity throughout the 24-h daily cycle-play key roles in shaping the internal physiology of an animal and its relationship with the external environment. Although shifts in diel activity patterns have occurred numerous times over the course of vertebrate evolution, the genomic correlates of such transitions remain unknown. Here, we use the African striped mouse (Rhabdomys pumilio), a species that transitioned from the ancestrally nocturnal diel niche of its close relatives to a diurnal one, to define patterns of naturally occurring molecular variation in diel niche traits.

Acute Recurrent Pancreatitis in a Pediatric Patient in the Setting of Viral Infection and COVID-19 Vaccination.

Acute pancreatitis within pediatric populations is predominately caused by mechanical obstruction, trauma, medications, and infections. We present a case of an adolescent female without any known anatomic or metabolic pre-disposition, developing recurrent acute pancreatitis that is seemingly related to acute viral infection and COVID-19 vaccination.

Vascular endothelial profilin-1 drives a protumorigenic tumor microenvironment and tumor progression in renal cancer.

Overexpression of actin-binding protein profilin-1 (Pfn1) correlates with advanced disease features and adverse clinical outcome of patients with clear cell renal carcinoma, the most prevalent form of renal cancer. We previously reported that Pfn1 is predominantly overexpressed in tumor-associated vascular endothelial cells in human clear cell renal carcinoma. In this study, we combined in vivo strategies involving endothelial cell-specific depletion and overexpression of Pfn1 to demonstrate a role of vascular endothelial Pfn1 in promoting tumorigenicity and enabling progressive growth and metastasis of renal carcinoma cells in a syngeneic orthotopic mouse model of kidney cancer.

Subjective and Performance-Based Cognition and Their Associations with Head Injury History in Older Former National Football League Players.

Purpose: Investigate the association between self-reported subjective and performance-based cognition among older (50-70 years) former professional American football players, as well as the relationship of cognitive measures with concussion history and years of football participation, as a proxy for repetitive head impact exposure.

Methods: Among older former National Football League (NFL) players ( N = 172; mean age = 60.69 ± 5.

The Water Surrounding the Iceberg: Cultural Racism and Health Inequities.

Unlabelled: Policy Points Cultural racism-or the widespread values that privilege and protect Whiteness and White social and economic power-permeates all levels of society, uplifts other dimensions of racism, and contributes to health inequities. Overt forms of racism, such as racial hate crimes, represent only the "tip of the iceberg," whereas structural and institutional racism represent its base. This paper advances cultural racism as the "water surrounding the iceberg," allowing it to float while obscuring its base.

Digital Storytelling as a Tool to Increase Colorectal Cancer Screening Intention in a Latinx Church Community.

Although colorectal cancer screening (CRCS) rates have improved for all racial groups due to wider availability of screening, Latinx continue to have lower screening rates and are more likely to be diagnosed with later stages of colorectal cancer compared to non-Latinx whites. More culturally tailored educational interventions are needed to reach this population. This study introduced a digital storytelling (DST) intervention in a church community setting and explored its potential to influence CRCS intention and perception among Latinx and the acceptability of the DST intervention.

Type 2 diabetes, hepatic decompensation, and hepatocellular carcinoma in patients with non-alcoholic fatty liver disease: an individual participant-level data meta-analysis.

Background: Data are scarce regarding the development of hepatic decompensation in patients with non-alcoholic fatty liver disease (NAFLD) with and without type 2 diabetes. We aimed to assess the risk of hepatic decompensation in people with NAFLD with and without type 2 diabetes.

Methods: We did a meta-analysis of individual participant-level data from six cohorts in the USA, Japan, and Turkey.

Using smart phone technology to improve daily living skills for individuals with intellectual disabilities.

Background: Individuals with intellectual disabilities need continued supports in completing daily living tasks to increase the likelihood of achieving independence. Fortunately, research has shown that assistive technology, and particularly video prompting helps support independent living for individuals with intellectual disabilities.

Aims: This study investigated the efficacy of a highly customizable task analysis smartphone application in assisting three young adults with intellectual disabilities learn how to cook three different multistep recipes.

Newly Acquired Burnout During the Coronavirus Disease 2019 (COVID-19) Pandemic: A Retrospective Cohort Study on the Experiences of New York State Primary Care Clinicians.

The well-being of primary care clinicians represents an area of increasing interest amid concerns that the COVID-19 pandemic may have exacerbated already high prevalence rates of clinician burnout. This retrospective cohort study was designed to identify demographic, clinical, and work-specific factors that may have contributed to newly acquired burnout after the onset of the COVID-19 pandemic. An anonymous web-based questionnaire distributed in August 2020 to New York State (NYS) primary care clinicians, via email outreach and newsletters, produced 1,499 NYS primary care clinician survey respondents.

Characterizing the Protein Isoforms of (), the PKGI Ortholog in .

The () gene of encodes a cGMP-dependent protein kinase (PKG), which is a major effector of the cGMP signaling pathway involved in the regulation of behaviour and metabolic traits. Despite being well studied at the transcript level, little is known about the gene at the protein level. Here, we provide a detailed characterization of the gene protein (FOR) products and present new tools for their study, including five isoform-specific antibodies and a transgenic strain that carries an HA-labelled allele ().

Early Adaptive Schemas and Sexual Wellbeing in Women: Exploring Differences in Menopausal Status.

There is limited research concerning the relationship between early adaptive schema, from Young's Schema Theory, and women's sexual wellbeing. Schema Theory posits that early adaptive schema start forming in early childhood from core emotional needs being met, and positively influence individuals' concept of self, relationships with others, and their behaviours. Building on this theory, the current study explored the relationship of early adaptive schema and adult women's sexual wellbeing at pre-, peri-, and post-menopause.

A global research priority agenda to advance public health responses to fatty liver disease.

Background & Aims: An estimated 38% of adults worldwide have non-alcoholic fatty liver disease (NAFLD). From individual impacts to widespread public health and economic consequences, the implications of this disease are profound. This study aimed to develop an aligned, prioritised fatty liver disease research agenda for the global health community.

Opportunities to expand postpartum support for those in recovery from opioid use disorder: Results from a qualitative study.

Introduction: Over the past two decades the national prevalence of opioid use disorder (OUD) during pregnancy has increased more than 600%. Managing recovery from OUD during the postpartum period can be particularly challenging. Thus, we sought to identify ways to expand perinatal OUD treatment to ultimately reduce risk of postpartum return to opioid misuse.

A hypothetical intervention to reduce inequities in anxiety for Multiracial people: simulating an intervention on childhood adversity.

Multiracial people report higher mean Adverse Childhood Experiences (ACEs) scores and prevalence of anxiety than other racial groups. Studies using statistical interactions to estimate racial differences in ACEs-anxiety associations do not show stronger associations for Multiracial people. Using data from Waves 1 (1995-97) through 4 (2008-09) of the National Longitudinal Study of Adolescent to Adult Health (Add Health), we simulated a stochastic intervention over 1,000 resampled datasets to estimate the race-specific cases averted per 1,000 of anxiety if all racial groups had the same exposure distribution of ACEs as Whites.

Racial Differences in Associations Between Adverse Childhood Experiences and Physical, Mental, and Behavioral Health.

Introduction: Adverse childhood experiences (ACEs) are associated with poor adulthood health, with individuals experiencing multiple ACEs at greatest risk. Multiracial people have high mean ACEs scores and elevated risk of several outcomes, but are infrequently the focus of health equity research. This study aimed to determine whether this group should be targeted for prevention efforts.

Black Mothers' Concern for Their Children as a Measure of Vicarious Racism-Related Vigilance and Allostatic Load.

This study investigates the relationship between allostatic load and a novel form of altruistic racism-related fear, or concern for how racism might harm another, which we term Using a subsample of Black mothers from the African American Women's Heart & Health Study (N = 140), which includes detailed health and survey data on a community sample of Black women in the San Francisco Bay Area, this study investigates the relationship between Black mothers' experiences with racism-related vigilance as it relates to their children and allostatic load-a multisystem metric of underlying health across multiple biological systems. Findings indicate that vicarious racism-related vigilance was positively associated with allostatic load (i.e.

Host and Water Microbiota Are Differentially Linked to Potential Human Pathogen Accumulation in Oysters.

Oysters play an important role in coastal ecology and are a globally popular seafood source. However, their filter-feeding lifestyle enables coastal pathogens, toxins, and pollutants to accumulate in their tissues, potentially endangering human health. While pathogen concentrations in coastal waters are often linked to environmental conditions and runoff events, these do not always correlate with pathogen concentrations in oysters.

A DNA Unwinding Equilibrium Serves as a Checkpoint for CRISPR-Cas12a Target Discrimination.

CRISPR-associated proteins such as Cas9 and Cas12a are programable RNA-guided nucleases that have emerged as powerful tools for genome manipulation and molecular diagnostics. However, these enzymes are prone to cleaving off-target sequences that contain mismatches between the RNA guide and DNA protospacer. In comparison to Cas9, Cas12a has demonstrated distinct sensitivity to protospacer-adjacent-motif (PAM) distal mismatches, and the molecular basis of Cas12a's enhanced target discrimination is of great interest.

Ultra-Rare Genetic Variation in Relapsing Polychondritis: A Whole-Exome Sequencing Study.

Objective: Relapsing polychondritis (RP) is a systemic inflammatory disease of unknown etiology. The study objective was to examine the contribution of rare genetic variations in RP.

Methods: We performed a case-control exome-wide rare variant association analysis including 66 unrelated European American RP cases and 2923 healthy controls.