Intralesional injection of CpG ODNs complexed with glatiramer acetate mitigates systemic cytokine toxicities and synergistically advances checkpoint blockade efficacy.

PD-L1/PD-1 checkpoint inhibitors (CPIs) are mainstream agents for cancer immunotherapy, but the prognosis is unsatisfactory in solid tumor patients lacking preexisting T-cell reactivity. Adjunct therapy strategies including the intratumoral administration of immunostimulants aim to address this limitation. CpG oligodeoxynucleotides (ODNs), TLR9 agonists that can potentiate adaptive immunity, have been widely investigated to tackle PD-L1/PD-1 resistance, but clinical success has been hindered by inconsistent efficacy and immune-related toxicities caused by systemic exposure.

Greater residential greenness is associated with reduced epigenetic aging in adults.

Potential pathways linking urban green spaces to improved health include relaxation, stress alleviation, and improved immune system functioning. Epigenetic age acceleration (EAA) is a composite biomarker of biological aging based on DNA methylation measurements; it is predictive of morbidity and mortality. This cross-sectional study of 116 adult residents of a metropolitan area in central North Carolina investigated associations between exposure to residential green spaces and EAA using four previously developed epigenetic age formulas.

Assessing Family Caregiver Readiness for Hospital Discharge of Patients With Serious or Life-Limiting Illness Using Electronic Health Record (EHR) and Self-Reported Data.

Objective: To assess how patient and caregiver factors influence caregiver readiness for hospital discharge in palliative care patients.

Study Setting And Design: This transitional care study uses cross-sectional data from a randomized controlled trial conducted from 2018 to 2023 testing an intervention for caregivers of hospitalized adult patients with a serious or life-limiting illness who received a palliative care consult prior to transitioning out of the hospital.

Data Sources And Analytical Sample: Caregiver readiness was measured with the Family Readiness for Hospital Discharge Scale (n = 231).

Comparing the effects of verbenone, methyl salicylate, and permethrin on attacks of ambrosia beetles (Coleoptera: Curculionidae Scolytinae) in ornamental nurseries.

The granulate ambrosia beetle, Xylosandrus crassiusculus (Motschulsky), and the black stem borer, Xylosandrus germanus (Blandford) are important pests in ornamental nurseries in the eastern USA. These beetles are managed mainly using preventative trunk applications of pyrethroids, such as permethrin or bifenthrin when females typically fly out of woodlots and attack young trees in the spring. Verbenone and methyl salicylate are potential phytochemicals reported as repellants but not completely validated in ornamental nurseries for ambrosia beetle management as an alternative option.

Dual Biologic Therapy Induces Remission in Refractory Crohn's Disease With Vedolizumab and Ustekinumab.

Background: Despite advancements in the therapeutic armamentarium for Crohn's disease (CD), biologic and small molecule monotherapies are associated with sub-optimal response and remission rates. Utilizing dual biologic therapy (DBT) holds the potential to increase efficacy in the treatment of refractory or partially responsive CD. Evidence pertaining to this strategy remains limited.

Not all who meander are lost: migrating sea lamprey follow river thalwegs to facilitate safe and efficient passage upstream.

Efficient navigation is crucial for the reproductive success of many migratory species, often driven by competing pressures to conserve energy and reduce predation risk. Little is known about how non-homing species achieve this balance. We show that sea lamprey (Petromyzon marinus), an ancient extant vertebrate, uses persistent patterns in hydro-geomorphology to quickly and efficiently navigate through complex ecosystems.

Kalamari: a representative set of genomes of public health concern.

Kalamari is a resource that supports genomic epidemiology and pathogen surveillance. It consists of representative genomes and common contaminants. Kalamari also contains a custom taxonomy and software for downloading and formatting the data.

Stakeholders' Roles in Evolutionizing Education: An Evolutionary-Based Toolkit Surrounding Elementary Education.

There is a rapidly growing body of research in the field of evolutionary educational psychology that examines children's evolved motivational and educational inclinations as they relate to modern learning and schooling. It is generally agreed that schools are inherently mismatched with how children of our species evolved to learn, thereby contributing to difficulty learning and associated adverse schooling outcomes. Many researchers argue that, by making small changes to schools that help to better align instructional methods and childhood as a whole with our species' evolved learning mechanisms, we can lessen the negative impacts from evolutionary mismatch and create better outcomes for modern students.

Supporting the Advancement of a National Agenda for Pediatric Healthcare Reform: A multi-year Evaluation of a Leadership Education in Neurodevelopmental and Related Disabilities Program.

Objectives: To evaluate the implementation and sustainability of the effect of a 1-year Leadership in Education for Neurodevelopmental and related Disabilities (LEND) program in a southeastern state, and to examine its impact on advancing the Maternal Child Health Bureau's (MCHB) Blueprint for Change-a national agenda for pediatric healthcare reform.

Methods: This study applies the Exploration, Preparation, Implementation, and Sustainment (EPIS) framework to rigorously evaluate LEND implementation and impact between 2018 and 2022. In-depth interviews (N = 24) were conducted among long-term (1-year) LEND trainees, via Zoom, in a southeastern state.

Cohort profile: the BangladEsh Longitudinal Investigation of Emerging Vascular and nonvascular Events (BELIEVE) cohort study.

Purpose: Bangladesh has experienced a rapid epidemiological transition from communicable to non-communicable diseases (NCDs) in recent decades. There is, however, limited evidence about multidimensional determinants of NCDs in this population. The BangladEsh Longitudinal Investigation of Emerging Vascular and nonvascular Events (BELIEVE) study is a household-based prospective cohort study established to investigate biological, behavioural, environmental and broader determinants of NCDs.

Exploring risk factors and antimicrobial susceptibility patterns associated with bacteriuria among Syrian refugees in makeshift camps.

Background: The health and well-being of refugees are critically compromised by harsh living conditions, which foster the emergence of infectious diseases and the misuse of antimicrobial agents. This multicentre cross-sectional community-based study investigated the prevalence of urine carriage of bacteria and the associated antimicrobial resistance patterns among Syrian refugees living in makeshift camps in Lebanon, an East Mediterranean country.

Methods: We used multivariable logistic regression models to identify the risk factors associated with bacteriuria in this vulnerable population.

Ravulizumab demonstrates long-term efficacy, safety and favorable patient survival in patients with paroxysmal nocturnal hemoglobinuria.

Ravulizumab is a second-generation complement component 5 (C5) inhibitor (C5i) approved for the treatment of paroxysmal nocturnal hemoglobinuria (PNH) following positive results from two pivotal trials in patients with PNH originally naive to C5i treatment and eculizumab-experienced patients with PNH. In both trials, after the 26week primary evaluation period, all patients received ravulizumab for up to 6 years. To report ravulizumab treatment outcomes in patients with PNH originally naive to C5i treatment and eculizumab-experienced patients with PNH treated for up to 6 years.

Severe Ethylene Glycol Toxicity: Multidisciplinary Management and Long-Term Renal Implications.

Ethylene glycol (C₂H₆O₂), a toxic alcohol commonly found in automotive antifreeze, de-icing solutions, and industrial coolants, can cause severe toxicity when ingested. Due to its sweet taste, it is often consumed accidentally or intentionally, leading to life-threatening consequences such as metabolic acidosis, acute kidney injury (AKI), and mortality. Prompt diagnosis and early treatment with antidotes such as fomepizole or ethanol, combined with hemodialysis, are essential in preventing severe outcomes.

Long-term Outcomes of Heineke-Mikulicz Anoplasty for Treatment of Skin-level Strictures.

Background: The Heineke-Mikulicz anoplasty (HMA) is a technique for addressing skin-level postoperative strictures following posterior sagittal anorectoplasty (PSARP) and posterior sagittal anorectovaginourethroplasty (PSARVUP). We aimed to evaluate the long-term outcomes with HMA as a treatment for postoperative anal strictures.

Methods: A retrospective review was conducted for patients with a history of ARM who underwent HMA for skin-level anal strictures.

Vagus nerve stimulation rescues impaired fear extinction and social interaction in a rat model of autism spectrum disorder.

Clinical diagnosis of anxiety disorders is highly prevalent in autism spectrum disorders (ASD). Available treatments for anxiety offer limited efficacy in the ASD population. Vagus nerve stimulation (VNS) has an anxiolytic effect in rats and, when coupled with fear extinction training, VNS enhances extinction of fear in healthy rats.

Safety and immunogenicity of an mRNA-1273 vaccine booster in adolescents.

Safety, immunogenicity, and effectiveness of an mRNA-1273 50-μg booster were evaluated in adolescents (12-17 years), with and without pre-booster SARS-CoV-2 infection. Participants who had received the 2-dose mRNA-1273 100-µg primary series in the TeenCOVE trial (NCT04649151) were offered the mRNA-1273 50-μg booster. Primary objectives included safety and inference of effectiveness by establishing noninferiority of neutralizing antibody (nAb) responses after the booster compared with the nAb post-primary series of mRNA-1273 among young adults in COVE (NCT04470427).

Pan-tumor analysis to investigate the obesity paradox in immune checkpoint blockade.

Background: Obesity is a risk factor for developing cancer but is also associated with improved outcomes after treatment with immune checkpoint inhibitors (ICIs), a phenomenon called the obesity paradox. To interrogate mechanisms of divergent immune responses in obese and non-obese patients, we examined the relationship among obesity status, clinical responses, and immune profiles from a diverse, pan-tumor cohort of patients treated with ICI-based therapy.

Methods: From June 2021 to March 2023, we prospectively collected serial peripheral blood samples from patients with advanced or metastatic solid tumors who received ICI as standard of care at Johns Hopkins.

Prioritizing emergency department antibiotic stewardship interventions for skin and soft tissue infections using judgment analysis.

Objective: Skin and soft tissue infections (SSTIs) account for over 2.8 million annual emergency department (ED) visits and often result in suboptimal antibiotic therapy. The objective of this study was to evaluate a set of interventions in minimizing inappropriate prescription of antibiotics for presumed SSTIs in the ED.

Exercise induces dynamic changes in intra-articular metabolism and inflammation associated with remodeling of the infrapatellar fat pad in mice.

We hypothesized that daily exercise promotes joint health by upregulating anti-inflammatory mediators via adaptive molecular and metabolic changes in the infrapatellar fat pad (IFP). We tested this hypothesis by conducting time-resolved analyses between 1 and 14 days of voluntary wheel running exercise in C57BL/6J mice. IFP structure and cellularity were evaluated by histomorphology, picrosirius red collagen staining, and flow cytometry analysis of stromal vascular fraction cells.

Diabetes visits in paediatric versus adult clinics for young adults (YA) with T1D: Pre-pandemic and pandemic care.

Background: Young adults (YA) with type 1 diabetes mellitus (T1D) are at high risk of worsening glycated haemoglobin (HbA1c) with fewer follow-up visits. We examined the association of demographic and diabetes characteristics with care utilization, including in-person and telehealth visits, pre- (1 April 2019 to 15 March 2020) and during the COVID-19 pandemic (30 March 2020 to 15 March 2021) for YA (ages: 18-30) with T1D, comparing those seen in paediatric versus adult diabetes clinics at a single diabetes centre.

Methods: Data were obtained from the electronic health record for YA with a pre-pandemic HbA1c.

Virtual assessment of internal rotation in reverse shoulder arthroplasty based on statistical shape models of scapular size.

Background: The purpose of this study was to assess impingement-free internal rotation (IR) in a virtual reverse shoulder arthroplasty simulation using a Statistical Shape Model based on scapula size.

Methods: A database of over 10,000 scapulae utilized for preoperative planning for shoulder arthroplasty was analyzed with a Statistical Shape Model to obtain 5 scapula sizes including the mean and 2 standard deviations. For each scapula model, one glenosphere size (33-42 mm) was selected as the best fit based on consensus among 3 shoulder surgeons.

Comparisons of Risk Scores for Infective Endocarditis Surgery: A Meta-Analysis.

While multiple scoring systems exist to predict mortality in cardiac surgery, their utility in infective endocarditis (IE) remains uncertain, prompting this study to compare their prognostic accuracy. We conducted a comprehensive review using Ovid Medline, Embase, and Cochrane Central Register of Controlled Trials. Data were pooled using Open-Meta[Analyst] software, and calibration analysis was performed with Review Manager 5.

Malnutrition and risks of atrial fibrillation recurrence after catheter ablation.

Background: Recent data showed an association between malnutrition and increased all-cause mortality and thromboembolic risk in patients with atrial fibrillation (AF). However, the impact of malnutrition on the clinical outcomes for patients undergoing catheter ablation for AF is still debated. Our study aimed to examine this relationship using all existing available data.