The association of state policies and opioid analgesic amount dispensed from retail pharmacies.

Importance: States have implemented multiple policies likely to influence opioid prescribing; few national general population studies examine those policies' effects on per-capita opioid morphine milligram equivalents (MME) dispensed.

Objective: To examine state policies' effects on opioids per-capita MMEs dispensed at retail pharmacies.

Design: A longitudinal study of associations between MME per capita and implementation of policy interventions at different times across states.

Long-term safety and efficacy of Oleogel-S10 (birch bark extract) in epidermolysis bullosa: 24-month results from the Phase III EASE Study.

Background: Epidermolysis bullosa (EB) is a group of rare, severe, genetic disorders characterised by persistent skin fragility and open wounds. EB manifests as cutaneous and mucosal blistering, erosions and impaired wound healing.

Objectives: To determine the long-term efficacy, tolerability and safety of Oleogel-S10 (birch bark extract) in dystrophic (DEB) and junctional (JEB) EB in the 24-months open-label phase (OLP) of the EASE study.

The relationship of medical and recreational cannabis laws with opioid misuse and opioid use disorder in the USA: Does it depend on prior history of cannabis use?

Background: Wider availability of cannabis through medical and recreational legalization (MCL alone and RCL+MCL) has been hypothesized to contribute to reductions in opioid use, misuse, and related harms. We examined whether state adoption of cannabis laws was associated with changes in opioid outcomes overall and stratified by cannabis use.

Methods: Using National Survey on Drug Use and Health (NSDUH) data from 2015 to 2019, we estimated cannabis law associations with opioid (prescription opioid misuse and/or heroin use) misuse and use disorder.

Hydroxychloroquine prevents resistance and potentiates the antitumor effect of SHP2 inhibition in NF1-associated malignant peripheral nerve sheath tumors.

Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive sarcomas and the primary cause of mortality in patients with neurofibromatosis type 1 (NF1). These malignancies develop within preexisting benign lesions called plexiform neurofibromas (PNs). PNs are solely driven by biallelic loss eliciting RAS pathway activation, and they respond favorably to MEK inhibitor therapy.

A Tutorial on Indicating Responses and Their Importance in Mand Training.

Unlabelled: One of the most critical intervention strategies when working with individuals with significant language delays associated with autism spectrum disorder and related developmental delays is teaching mands. For mand training to be effective, an establishing operation (EO) must be in effect, yet EOs are often difficult to observe. Before learning to mand, an individual may point to or approach a reinforcer, which likely indicates an EO related to that reinforcer, and may be considered an indicating response (IR).

A Clinical Tutorial on Methods to Capture and Contrive Establishing Operations to Teach Mands.

Unlabelled: Mands are consistently described as critical learning targets for members of vulnerable populations in need of language intervention (Ala'i-Rosales et al., 2018; Michael, 1988; Sundberg, 2004). Reviews of the literature demonstrate a prevalence of the mand in the applied literature (e.

Utility of Candidate Genes From an Algorithm Designed to Predict Genetic Risk for Opioid Use Disorder.

Importance: Recently, the US Food and Drug Administration gave premarketing approval to an algorithm based on its purported ability to identify individuals at genetic risk for opioid use disorder (OUD). However, the clinical utility of the candidate genetic variants included in the algorithm has not been independently demonstrated.

Objective: To assess the utility of 15 genetic variants from an algorithm intended to predict OUD risk.

Mapping histological and functional maturation of human endocrine pancreas across early postnatal periods.

Human endocrine cell differentiation and islet morphogenesis play critical roles in determining islet cell mass and function, but the events and timeline of these processes are incompletely defined. To better understand early human islet cell development and maturation, we collected 115 pediatric pancreata and mapped morphological and spatiotemporal changes from birth through the first ten years of life. Using quantitative analyses and a combination of complementary tissue imaging approaches, including confocal microscopy and whole-slide imaging, we developed an integrated model for endocrine cell formation and islet architecture, including endocrine cell type heterogeneity and abundance, endocrine cell proliferation, and islet vascularization and innervation.

Selumetinib in adults with NF1 and inoperable plexiform neurofibroma: a phase 2 trial.

The MEK inhibitor selumetinib induces objective responses and provides clinical benefit in children with neurofibromatosis type 1 (NF1) and inoperable plexiform neurofibromas (PNs). To evaluate whether similar outcomes were possible in adult patients, in whom PN growth is generally slower than in pediatric patients, we conducted an open-label phase 2 study of selumetinib in adults with NF1 PNs. The study was designed to evaluate objective response rate (primary objective), tumor volumetric responses, patient-reported outcomes and pharmacodynamic effects in PN biopsies.

Science × art: spotlighting unconventional collaborations.

Science × art collaborations can effectively convey scientific insights to a wide audience. Throughout history, art has interpreted the natural world, offering vast, underexplored sources of biodiversity data. These artistic efforts also hold potential as valuable tools for understanding biodiversity.

Minimum 10-Year Clinical and Functional Outcomes, and Return to Sport After Sternoclavicular Joint Reconstruction for Sternoclavicular Joint Instability.

Background: Sternoclavicular joint (SCJ) instability can lead to pain, reduced function, and an inability to perform sports and activities of daily living. Reconstruction of the SCJ using hamstring autograft in a figure-of-8 configuration has demonstrated good outcomes at short- and midterm follow-ups, but there is a paucity of literature on long-term outcomes.

Purpose: To evaluate the long-term clinical and functional outcomes after SCJ reconstruction, with a focus on return to sport, instability recurrence, and revision surgery.

Highly Pathogenic Avian Influenza A(H5N1) Virus Infections in Humans.

Background: Highly pathogenic avian influenza A(H5N1) viruses have caused widespread infections in dairy cows and poultry in the United States, with sporadic human cases. We describe characteristics of human A(H5N1) cases identified from March through October 2024 in the United States.

Methods: We analyzed data from persons with laboratory-confirmed A(H5N1) virus infection using a standardized case-report form linked to laboratory results from the Centers for Disease Control and Prevention influenza A/H5 subtyping kit.

Mechanical Deformation Behavior of Polymer Blend Thin Films.

Examining the mechanical properties of polymer thin films is crucial for high-performance applications such as displays, coatings, sensors, and thermal management. It is important to design thin film microstructures that excel in high-demand situations without compromising mechanical integrity. Here, a polymer blend of polystyrene (PS) and polyisoprene (PI) is used as a model to explore microscale deformation behavior under uniaxial mechanical testing.

Venous thromboembolism in transfer trauma patients: A global problem.

Background: As air travel and immobility are risk factors for venous thromboembolism, we aimed to test the hypothesis that internationally transferred trauma patients have a high incidence of venous thromboembolism on arrival.

Methods: A prospectively maintained registry of all international transferred trauma patients who presented to our level I trauma center from January 2023 to June 2024 was retrospectively reviewed. Patients with either lower extremity venous duplex ultrasound or computed tomography scan of the chest with contrast on arrival were included.

Time to Therapy May Not Impact Diagnosis Upstaging in Patients Referred for Management of Luminal Gastrointestinal Neoplasia.

Background: The COVID-19 pandemic dramatically impacted endoscopy practice. Recommendations were to postpone elective cases, including procedures for removal of luminal neoplasia. This provided a natural experiment to evaluate outcomes related to these decisions and the impact of time to procedure on change in histology.

Bioreactor contamination monitoring using off-gassed volatile organic compounds (VOCs).

Metabolically active cells emit volatile organic compounds (VOCs) that can be used in real time to non-invasively monitor the health of cell cultures. We utilized these naturally occurring VOCs in an adapted culture method to detect differences in culturing Chinese hamster ovary (CHO) cells with and without Staphylococcus epidermidis and Aspergillus fumigatus contaminations. The VOC emissions from the cell cultures were extracted and measured from the culture flask headspace using polydimethylsiloxane (PDMS)-coated Twisters, which were subjected to thermal desorption-gas chromatography-mass spectrometry (TD-GC-MS) analysis.

Distinct virologic trajectories in chronic hepatitis B identify heterogeneity in response to nucleos(t)ide analogue therapy.

Background & Aims: The dynamics of HBV viral load (VL) in patients with chronic hepatitis B (CHB) on nucleos(t)ide analogue (NA) treatment and its relationship with liver disease are poorly understood. We aimed to study longitudinal VL patterns and their associations with CHB clinical outcomes.

Methods: Utilising large scale, routinely collected electronic health records from six centres in England, collated by the National Institute for Health and Care Research Health Informatics Collaborative (NIHR HIC), we applied latent class mixed models to investigate VL trajectory patterns in adults receiving NA treatment.

Quantifying the effect of human interindividual kinetic differences on the relative potency value for riddelliine N-oxide at low dose levels by a new approach methodology.

Pyrrolizidine alkaloid N-oxides (PA-N-oxides) are predominant in plants and herbal foods, and are converted to pyrrolizidine alkaloids (PAs) upon consumption, leading to toxicity. The effect of interindividual kinetic differences on the relative potency values of PA-N-oxides compared to their PAs (REP) was studied, with riddelliine N-oxide (RIDO) and riddelliine (RID) as model compounds. In vitro kinetic data measured in incubations with 30 fecal and 25 liver S9 donor samples showed high variation across individuals, where the interindividual variability was captured with Bayesian multilevel regression.

Development of a new Peyronie's disease self-assessment screening app.

Peyronie's disease (PD) is an underdiagnosed and undertreated fibroproliferative disorder associated with the formation of plaques that results in penile curvature and discourages some men from seeking medical consultation. The PD self-assessment app, a digital application (app), was developed to increase PD awareness, provide men with a self-screening and educational tool for PD, and help eliminate barriers to seeking consultation with a physician. Prior to deployment, 4 board-certified urologists provided qualitative reviews on the app's usability and utility as a screening tool.

An influenza mRNA vaccine protects ferrets from lethal infection with highly pathogenic avian influenza A(H5N1) virus.

The global spread of the highly pathogenic avian influenza (HPAI) A(H5N1) virus poses a serious pandemic threat, necessitating the swift development of effective vaccines. The success of messenger RNA (mRNA) vaccine technology in the COVID-19 pandemic, marked by its rapid development and scalability, demonstrates its potential for addressing other infectious threats, such as HPAI A(H5N1). We therefore evaluated mRNA vaccine candidates targeting panzootic influenza A(H5) clade 2.

Harm Reduction: The Neglected Pillar of US Drug Policy.

Harm reduction programs provide tools that enable people who use drugs to do so more safely in a nonstigmatizing environment without the goal of them necessarily seeking treatment or abstinence. Most harm reduction programs in the United States distribute sterile syringes and naloxone and safely dispose of used syringes and other drug use supplies. Many also provide drug checking services, and other safer use supplies.

A Prehospital Quality Improvement Framework to Reduce Mortality and Other Harms Associated with Opioid Use Disorder.

Objectives: In response to the escalating overdose crisis there is an urgent need for innovative strategies to reduce overdose death. Emergency Medical Services (EMS) is uniquely poised to reduce mortality and other harms associated with opioid use through prevention, harm reduction, and treatment, yet there is a paucity of nationally recognized best practices or quality measures to guide prehospital quality improvement (QI) efforts related to opioid use disorder (OUD).

Methods: A multidisciplinary team of subject matter experts in addiction medicine, EMS, public health, and QI was convened to develop recommendations for a model QI framework for prehospital OUD prevention, harm reduction, and treatment based on the Model for Improvement framework.

Physicochemical and Microbiological Stability of Ursodiol Oral Compounded Suspensions.

Objective: In the United States, ursodiol is commercially available as solid dosage forms, which represents a problem for children who cannot swallow capsules or tablets. There is a lack of an age-appropriate formulation for ursodiol, and the extemporaneous preparation of an oral suspension with an extended beyond-use-date (BUD) may represent a good therapeutic alternative for the pediatric population. However, all pharmacists need validated stability studies to prepare oral liquids with high quality and safety.

Discovery of PF-07265028, A Selective Small Molecule Inhibitor of Hematopoietic Progenitor Kinase 1 (HPK1) for the Treatment of Cancer.

Hematopoietic progenitor kinase 1 (HPK1/MAP4K1) represents a high interest target for the treatment of cancer through an immune-mediated mechanism. Herein we present highlights of the drug discovery campaign within the lactam/azalactam series of inhibitors that yielded a small molecule (, PF-07265028), which was advanced to a phase 1 clinical trial (NCT05233436). Key components of the discovery effort included optimization of potency through mitigation of ligand strain as guided by the use of cocrystal structures, mitigation of ADME liabilities (plasma instability and fraction metabolism by CYP2D6), and optimization of kinase selectivity, particularly over immune-modulating kinases with high homology to HPK1.