CRISPR-Cas12a bends DNA to destabilize base pairs during target interrogation.

RNA-guided endonucleases are involved in processes ranging from adaptive immunity to site-specific transposition and have revolutionized genome editing. CRISPR-Cas9, -Cas12 and related proteins use guide RNAs to recognize ∼20-nucleotide target sites within genomic DNA by mechanisms that are not yet fully understood. We used structural and biochemical methods to assess early steps in DNA recognition by Cas12a protein-guide RNA complexes.

Variables Affecting 90-Day Overall Reimbursement After Anterior Cruciate Ligament Reconstruction: Analysis of Nearly 250,000 Patients in the United States.

Background: Anterior cruciate ligament reconstruction (ACLR) is a commonly performed orthopaedic procedure. As the number of ACLRs continues to increase in incidence, understanding the variability and drivers of cost to the health care system may help target cost-saving measures.

Purposes: To examine the variability in overall 90-day reimbursements (amount paid for health care services) for ACLR using a national, multi-insurance, administrative database and to assess factors associated with variability.

Frederick G Banting (1891-1941): A Pioneer in Diabetes Treatment.

The discovery of insulin by Frederick G Banting and his colleagues in 1921 marked a pivotal moment in medical history. Born in Ontario, Canada, in 1891, Banting's childhood was impacted by the death of his closest friend, Jane, who died of diabetes mellitus at a young age. This personal tragedy profoundly influenced him to choose a career in medicine and fueled his determination to find a cure for diabetes.

Deciphering the Phytochemical Potential of Hemp Hairy Roots: A Promising Source of Cannabisins and Triterpenes as Bioactive Compounds.

L., specifically hemp, is a traditional herbaceous plant with industrial and medicinal uses. While much research has focused on cannabinoids and terpenes, the potential of hemp roots is less explored due to bioproduction challenges.

The costs per live birth after uterus transplantation: results of the Swedish live donor trial.

Study Question: What is the cost per live birth after live donor uterus transplantation in a Swedish clinical trial setting?

Summary Answer: The total cost per child, from a health care perspective, was calculated to be €124 894 and if only surgically successful transplants are considered, the total cost per live birth was €107 120.

What Is Known Already: Uterus transplantation has proved to be a feasible treatment for uterine factor infertility by accomplished live births, both after live donor and deceased donor transplantation procedures. Our previous study, the only existing cost analysis of uterus transplantation, found that the initial (up to 2 months after surgeries) societal costs of preoperative interventions, live donor uterus transplantation surgeries, and postoperative care were between €50 000 and €100 000 (mean €74 000) in Year 2020 values per uterus transplantation.

Is COVID-19 infection during pregnancy a risk for congenital hearing loss?

Objective: Infections during pregnancy can increase the risk of congenital hearing loss. This population-based study investigated the effect of birthing parent COVID-19 infection during pregnancy on risk of congenital hearing loss in infants.

Methods: Records of infants born in 2022 were reviewed via a retrospective clinical audit of a universal state-wide newborn hearing screening program in Victoria, Australia.

Global Insights from Patients, Providers, and Staff on Challenges and Solutions in Managing Neovascular Age-Related Macular Degeneration.

Introduction: Neovascular age-related macular degeneration is a global public-health concern, associated with a considerable burden to individuals, healthcare systems, and society. The objective of this study was to understand different perspectives on the challenges associated with the clinical management of neovascular age-related macular degeneration, which could elucidate measures to comprehensively improve clinical care and outcomes.

Methods: A survey was carried out of patients with neovascular age-related macular degeneration, their providers, and clinic staff in 77 clinics across 24 countries on six continents, from a diverse range of healthcare systems, settings, and reimbursement models.

Improving Clinical Management of Diabetic Macular Edema: Insights from a Global Survey of Patients, Healthcare Providers, and Clinic Staff.

Introduction: In contrast with patients receiving therapy for retinal disease during clinical trials, those treated in routine clinical practice experience various challenges (including administrative, clinic, social, and patient-related factors) that can often result in high patient and clinic burden, and contribute to suboptimal visual outcomes. The objective of this study was to understand the challenges associated with clinical management of diabetic macular edema from the perspectives of patients, healthcare providers, and clinic staff, and identify opportunities to improve eye care for people with diabetes.

Methods: We conducted a survey of patients with diabetic macular edema, providers, and clinic staff in 78 clinics across 24 countries on six continents, representing a diverse range of individuals, healthcare systems, settings, and reimbursement models.

Bariatric surgeons' views on barriers and enablers to bariatric surgery in Australia and New Zealand: A qualitative content analysis.

Problem And Aims: Bariatric surgery can be an effective treatment for severe obesity, yet publicly-funded access is often limited. Bariatric surgeons contribute to decisions regarding consumer (non)progression to bariatric surgery. Still, little is known about their views on barriers and enablers to bariatric surgery in the Australian and New Zealand context.

Sherman S Coleman: Beloved Surgeon, Educator, and Friend.

Dr. Sherman S. Coleman was a superior surgeon, a pioneer of multiple orthopedic organizations, and a remarkable educator of surgical principles.

The Reporting of Race and Ethnicity in the Conduct Disorder Literature: A Time-Sensitive Review.

Background: Among presenting conditions in pediatric acute care settings, conduct disorder (CD) is a potentially stigmatizing yet common diagnosis in the setting of behavioral dysregulation requiring psychiatric admission. Concerns exist about over-diagnosis of CD in non-Hispanic Black children relative to White peers and the potential for the CD diagnosis to obfuscate manifestations of co-occurring psychiatric conditions.

Methods: We evaluated the number of manuscripts on CD diagnoses that report race and ethnicity and co-occurring mental health characteristics (i.

Gender differences in the context of interventions for improving health literacy in migrants: a qualitative evidence synthesis.

Background: Health literacy can be defined as a person's knowledge, motivation and competence in four steps of health-related information processing - accessing, understanding, appraising and applying health-related information. Individuals with experience of migration may encounter difficulties with or barriers to these steps that may, in turn, lead to poorer health outcomes than those of the general population. Moreover, women and men have different health challenges and needs and may respond differently to interventions aimed at improving health literacy.

"Feeling Like You Matter:" LGBTQ + Young Adult Perspectives on Affirmative Mental Healthcare.

The purpose of this study was to explore the experiences of LGBTQ + young people in mental healthcare and to understand their perspectives on what affirmative mental healthcare practice should look like. Between June and September of 2023, interviews were conducted with LGBTQ + young people ages 18-26 years in Los Angeles and Seattle. Interviews lasted 30 to 60 min and were transcribed verbatim for thematic analysis (N = 28).

Nanobodies against the myelin enzyme CNPase as tools for structural and functional studies.

2',3'-Cyclic nucleotide 3'-phosphodiesterase (CNPase) is an abundant constituent of central nervous system non-compact myelin, and its loss in mice and humans causes neurodegeneration. Additionally, CNPase is frequently used as a marker antigen for myelinating cells. The catalytic activity of CNPase, the 3'-hydrolysis of 2',3'-cyclic nucleotides, is well characterised in vitro, but the in vivo function of CNPase remains unclear.

Factors Associated With Receipt of Tobacco Treatment Integrated With Nurse Navigation in a Centralized Lung Cancer Screening Program at an Urban Academic Medical Center.

Purpose: Optimal approaches for tobacco treatment counseling among individuals who currently smoke and are undergoing shared decision-making (SDM) and lung cancer screening (LCS) are unknown. The objective of this cross-sectional study was to determine the rate of reported interest in tobacco treatment counseling and pharmacotherapy among individuals who currently smoke and are receiving integrated nurse navigation for LCS and tobacco treatment in a centralized LCS Program.

Methods: We identified individuals undergoing SDM through our centralized LCS Program between March 2021 and March 2022.

Development of Prediction Models for Severe Pain and Urinary Symptoms After Ureteroscopy With Ureteral Stent Placement: Results From the STENTS Study and Initial Validation of Pain Interference.

Purpose: We developed prediction models for severe pain and urinary symptoms after ureteroscopy with ureteral stent placement.

Materials And Methods: The development cohort included 424 adults and adolescents enrolled in the multicenter STENTS prospective cohort study who underwent ureteroscopy with stent placement for urinary stones. The validation cohort was an independent prospective cohort of 115 adults.

Living Donation and Pregnancy-Related Complications: State of the Evidence and Call To Action for Improved Risk Assessment.

Living kidney donation and living liver donation significantly increases organ supply to make lifesaving transplants possible, offering survival benefits to the recipients and cost savings to society. Of all living donors, 40% are women of childbearing age. However, limited data exist regarding the effect of donation on future pregnancies and of pregnancy-related complications on postdonation outcomes.

Corticostriatal maldevelopment in the R6/2 mouse model of juvenile Huntington's disease.

There is a growing consensus that brain development in Huntington's disease (HD) is abnormal, leading to the idea that HD is not only a neurodegenerative but also a neurodevelopmental disorder. Indeed, structural and functional abnormalities have been observed during brain development in both humans and animal models of HD. However, a concurrent study of cortical and striatal development in a genetic model of HD is still lacking.

Outcome of Surgery for Hypothalamic Hamartoma-Related Epilepsy: A Systematic Review and Individual Participant Data Meta-Analysis.

Background And Objectives: There is a paucity of data directly comparing the outcome of surgical techniques available for the treatment of hypothalamic hamartomas (HHs). This study aims to evaluate the safety and efficacy of commonly used surgical approaches in the treatment of HH-related epilepsy.

Methods: A systematic review and individual participant data (IPD) meta-analysis was conducted.