Targeted long-read sequencing to quantify methylation of the C9orf72 repeat expansion.

Background: The gene C9orf72 harbors a non-coding hexanucleotide repeat expansion known to cause amyotrophic lateral sclerosis and frontotemporal dementia. While previous studies have estimated the length of this repeat expansion in multiple tissues, technological limitations have impeded researchers from exploring additional features, such as methylation levels.

Methods: We aimed to characterize C9orf72 repeat expansions using a targeted, amplification-free long-read sequencing method.

MEGA12: Molecular Evolutionary Genetic Analysis version 12 for adaptive and green computing.

We introduce the 12th version of the Molecular Evolutionary Genetics Analysis (MEGA) software. This latest version brings many significant improvements by reducing the computational time needed for selecting optimal substitution models and conducting bootstrap tests on phylogenies using maximum likelihood (ML) methods. These improvements are achieved by implementing heuristics that minimize likely unnecessary computations.

Acceptance-based process variables on postpartum well-being and distress: The mediating role of psychological flexibility.

Objective: Although up to 20% of women experience postpartum depression and/or anxiety, current interventions are limited. Identifying the processes that impact outcomes can inform and enhance interventions. Our study aims to examine: (1) whether acceptance-based process variables (awareness, acceptance, cognitive defusion, psychological flexibility) were associated with postpartum outcomes; and (2) whether psychological flexibility mediated the relationship between treatment engagement and postpartum outcomes.

Developing a Strategy to Increase Lung Cancer Screening in Areas of Need.

Lung cancer screening (LCS) rates are low, and lung cancer mortality is high in the United States. This report describes a strategy that health systems can use to identify LCS areas of need and engage associated primary care providers and patients in screening. A research team from Jefferson Health (JH), a large, urban health system, used geocoded standardized lung cancer mortality rates (SMRs) to identify zip codes in Philadelphia where lung cancer mortality is high.

Painless Aortic Syndrome in a Patient with Syncope and Globus Sensation: A Case Report.

Introduction: Aortic dissection is a devastating clinical entity with a variety of presentations and requires prompt recognition and management. To our knowledge this is the first reported case of a patient who presented with a globus sensation and was diagnosed with an aortic dissection prior to clinical deterioration.

Case Report: The patient presented with an episode of near-syncope and globus sensation.

Relationship of Sex and Diagnosis With Symptoms and Illness Impact in Urologic Chronic Pelvic Pain; A Mapp Network Analysis.

Objective: To assess differences in clinical presentation and illness impact in men and women presenting with urologic chronic pelvic pain syndrome (UCPPS) and between men diagnosed with interstitial cystitis/bladder pain syndrome (IC/BPS) or chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS).

Methods: 356 men and 605 women from six sites across the United States were assessed using a comprehensive set of demographic, symptom, and illness impact measures. Multivariable regression analyses examined differences between men and women and between men previously diagnosed with CP/CPPS or IC/BPS.

Clinician Perspectives on Implementing HPV Vaccination Guidelines into Practice.

In the United States, HPV vaccination is available for unvaccinated 27 to 45 year olds based on a shared clinical decision with a health care provider. Since the implementation of the guideline, little has been known about provider perceptions of this recommendation. The purpose of this study was to elucidate health care provider perspectives on HPV vaccination for 27 to 45 year olds in the United States.

Mlh1-Pms1 ATPase activity is regulated distinctly by self-generated nicks and strand discrimination signals in mismatch repair.

In eukaryotic post-replicative mismatch repair, MutS homolog complexes detect mismatches and in the major eukaryotic pathway, recruit Mlh1-Pms1/MLH1-PMS2 (yeast/human) complexes, which nick the newly replicated DNA strand upon activation by the replication processivity clamp, PCNA. This incision enables mismatch removal and DNA repair. Beyond its endonuclease role, Mlh1-Pms1/MLH1-PMS2 also has ATPase activity, which genetic studies suggest is essential for mismatch repair, although its precise regulatory role on DNA remains unclear.

Enhancing the Recovery Process for Undergraduate Women Survivors of Sexual Violence: Identifying Facilitators to Healing.

The psychosocial impact of sexual violence (SV) on college-aged women necessitates understanding positive influences of survivors' healing processes. The purpose of this study, therefore, was to investigate facilitators in the healing journey for undergraduate SV survivors. Seventeen women were interviewed using Photo-experiencing and Reflective Listening (PEARL).

Methods to Detect and Compare Cellular and Mitochondrial Changes in Senescent and Healthy Mesenchymal Stem Cells.

Cellular senescence is a multifaceted process marked by irreversible cell cycle arrest in response to stressors such as DNA damage, oxidative stress, and telomere shortening, leading to significant cellular and mitochondrial alterations. These changes impact mesenchymal stem cell (MSC) function, affecting their differentiation, self-renewal, and regenerative abilities. Senescent MSCs adopt the senescence-associated secretory phenotype (SASP), characterized by the secretion of pro-inflammatory factors that propagate senescence to neighboring cells.

Neuroinflammatory history results in overlapping transcriptional signatures with heroin exposure in the nucleus accumbens and alters responsiveness to heroin in male rats.

Recent progress in psychiatric research has highlighted neuroinflammation in the pathophysiology of opioid use disorder (OUD), suggesting that heightened immune responses in the brain may exacerbate opioid-related mechanisms. However, the molecular mechanisms resulting from neuroinflammation that impact opioid-induced behaviors and transcriptional pathways remain poorly understood. In this study, we have begun to address this critical knowledge gap by exploring the intersection between neuroinflammation and exposure to the opioid heroin, utilizing lipopolysaccharide (LPS)-induced neuroinflammation, to investigate transcriptional changes in the nucleus accumbens (NAc), an essential region in the mesolimbic dopamine system that mediates opioid reward.

Irritability and stress: Prospective, bidirectional relationships in adolescence.

Background: Irritability is a transdiagnostic risk factor for psychopathology and interpersonal problems in youth. However, there is little research on the role of life stress in irritability. The association between stress and irritability may be bidirectional, with irritability leading to stress exposure and stress aggravating irritability.

Effectiveness of ceftazidime-avibactam versus ceftolozane-tazobactam for multidrug-resistant Pseudomonas aeruginosa infections in the USA (CACTUS): a multicentre, retrospective, observational study.

Background: Ceftolozane-tazobactam and ceftazidime-avibactam are preferred treatment options for multidrug-resistant Pseudomonas aeruginosa infections; however, real-world comparative effectiveness studies are scarce. Pharmacokinetic and pharmacodynamic differences between the agents might affect clinical response rates. We aimed to compare the effectiveness of ceftolozane-tazobactam and ceftazidime-avibactam for treatment of invasive multidrug-resistant P aeruginosa infections.

Identification and Analysis of Small Nucleolar RNAs by Real-Time Quantitative PCR.

One of the greatest scientific achievements of the twenty-first century is the completion of The Human Genome Project (HGP). Thereafter, we came to know that the human genome codes nearly 2% for making proteins and thus named as coding genes, suggesting the rest of the genome as noncoding or junk. However, research in the past two decades has shown and established that noncoding RNAs are major contributors of regulating and modulating the various function of cells as well as tissues.

Quantitative Real-Time PCR for Circular RNA Detection and Analysis.

In eukaryotes, nearly 2% of the genome represented by the coding proteins. However, emerging evidence suggest more than 75% of the human genome referred to as noncoding part also plays a crucial role in governing major regulatory pathways. Noncoding RNAs can be categorized into several groups, such as microRNAs (miRNAs), small nuclear RNA (snRNAs), small nucleolar RNA (snoRNAs), transfer RNA (tRNA), and circular RNA (circRNAs), which contribute to this regulatory landscape.

Factors Influencing Patient Enrollment in a Community-based Physical Activity Program After Healthcare Provider Referral: A Mixed Methods Study.

Introduction And Objectives: Structured physical activity (PA) programs help to prevent and manage chronic diseases, yet systematic approaches to identify and enroll patients in these programs are lacking. Exercise is Medicine Greenville (EIMG) is a novel clinic-to-community model that identifies patients with chronic diseases in primary care settings and connects them to a structured, evidence-informed, community-based PA program. This study assessed influences on PA program enrollment using a mixed methods design.

Postcertification Wages Among Certified Peer Specialists Working in Peer Support and Other Occupations.

Objective: Although certification can raise the status of peer support work, certified peer specialists (CPSs) may continue to face financial hardship that affects their employment choices. This study aimed to explore how wages and financial well-being changed for CPSs over a 3-year postcertification period.

Methods: This study examined wages, job characteristics, and financial well-being for a cohort of 448 employed CPSs working in peer support (PS) or other, nonpeer (NP) jobs during the study period.

Computational deconvolution of cell type-specific gene expression in COPD and IPF lungs reveals disease severity associations.

Background: Chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) are debilitating diseases associated with divergent histopathological changes in the lungs. At present, due to cost and technical limitations, profiling cell types is not practical in large epidemiology cohorts (n > 1000). Here, we used computational deconvolution to identify cell types in COPD and IPF lungs whose abundances and cell type-specific gene expression are associated with disease diagnosis and severity.

Prescription Medication Use and Expenditure of Atrial Fibrillation in the United States.

Objectives: To study the national trends of anticoagulants, antiarrhythmic drugs (AAD), and expenditures in civilian non-institutionalized AF population.

Methods: The Medical Expenditure Panel Survey (MEPS) was queried from January 2016 to December 2021 to identify adults (age ≥ 18 years) with a diagnosis of AF utilizing ICD-10-CM code "I48". Prevalence of anticoagulants, AAD, and its expenditure and AF expenditure across clinical settings in the United States were estimated.

Defining harmful news reporting on community firearm violence: A modified Delphi consensus study.

Community firearm violence (CFV), including fatal and non-fatal shootings that result from interpersonal violence, disproportionately harms people from marginalized racial groups. News reporting on CFV can further exacerbate these harms. However, examining the effects of harmful news reporting on CFV on individuals, communities, and society is hindered by the lack of a consensus definition of harmful reporting on CFV.

Two Cases of Maggot-Associated Bacteremia in Xylazine-Induced Injection Wounds: An Emerging Threat.

The city of Philadelphia has seen an increase in homelessness and substance use disorders, often associated with xylazine-contaminated opiates. Here, we report the first two cases of wound infection and bacteremia associated with the Gram-negative rod species. Both cases were associated with maggot colonization in chronic lower extremity wounds from fentanyl/xylazine injections.

Momentary Associations Across Specific Affective States and Dysregulated Eating Experiences Among Children and Adolescents With Loss of Control Eating Symptoms.

Objective: Dysregulated eating is common among youth and is associated with trait-level negative affect and emotion regulation difficulties. Despite the transient nature of affect, momentary associations among affect and eating behavior are unclear, which limits development of more impactful treatment tools, such as "just-in-time" intervention approaches (JITAI). The current study (N = 62) drew from two ecological momentary assessment (EMA) studies involving children and adolescents who endorsed loss of control (LOC) eating symptoms during a two-week assessment period.

Underappreciated Effects of Delayed Graft Function in Pediatric Kidney Transplantation.

Purpose: In kidney transplantation (KT), delayed graft function (DGF) is associated with worse outcomes. However, it is unclear what effect DGF plays in long-term survival compared to the impact of the various transplant, donor, and recipient risk factors associated with DGF. This study aims to determine the effect of DGF alone on long-term survival in pediatric deceased donor kidney transplant recipients (DDKTRs).

Sleep, Screen Behaviors, and Adverse Childhood Experiences: A Cross-Sectional Study of U.S. Children and Adolescents.

To examine the associations between adverse childhood experiences (ACEs) and children's obesogenic behaviors (meeting recommendations for sleep duration and screen time) in a representative sample of U.S. children and adolescents.