Precision Medicine for High-Risk Gene Fusions in Pediatric AML: a focus on KMT2A, NUP98, and GLIS2 Rearrangements.

Robust genetic characterization of paediatric AML has demonstrated that fusion oncogenes are highly prevalent drivers of AML leukemogenesis in young children. Identification of fusion oncogenes associated with adverse outcomes has facilitated risk stratification of patients, although successful development of precision medicine approaches for most fusion-driven AML subtypes have been historically challenging. This knowledge gap has been in part due to difficulties in targeting structural alterations involving transcription factors and in identification of a therapeutic window for selective inhibition of the oncofusion without deleterious effects upon essential wild-type proteins.

Acceptance, Safety, and Effect Sizes in Online Dialectical Behavior Therapy for Borderline Personality Disorder: Interventional Pilot Study.

Background: The potential of telehealth psychotherapy (ie, the online delivery of treatment via a video web-based platform) is gaining increased attention. However, there is skepticism about its acceptance, safety, and efficacy for patients with high emotional and behavioral dysregulation.

Objective: This study aims to provide initial effect size estimates of symptom change from pre- to post treatment, and the acceptance and safety of telehealth dialectical behavior therapy (DBT) for individuals diagnosed with borderline personality disorder (BPD).

Characterization of Individuals Achieving Type 2 Diabetes Remission in Real-World Settings: Bridging Clinical Evidence and Patient Experiences.

The objectives of the study were to: 1) Describe characteristics and lifestyle factors of individuals who have achieved type 2 diabetes (T2D) remission (sub-diabetes glucose levels without glucose-lowering medications for ≥3 months) through changes to diet and exercise behaviour in real-world settings; 2) Investigate continuous glucose monitoring (CGM) profiles of these individuals and explore how dietary pattern may influence glucose regulation metrics. This cross-sectional study recruited individuals living with T2D who achieved remission via changes to diet or exercise behaviours. Various questionnaires were used to assess overall health and participants wore a blinded CGM for 14 days to assess glucose profiles and filled out three-day food records.

Antiseizure Medications in Poststroke Seizures: A Systematic Review and Network Meta-Analysis.

Background And Objectives: The most effective antiseizure medications (ASMs) for poststroke seizures (PSSs) remain unclear. We aimed to determine outcomes associated with ASMs in people with PSS.

Methods: We systematically searched electronic databases for studies on patients with PSS on ASMs.

Accelerating the Future of Oncology Drug Development: The Role of Consortia in the Delivery of Precision Oncology Early Phase Clinical Trials.

Purpose: Over the past 15 years, the landscape of early phase clinical trials (EPCTs) has undergone a remarkable expansion in both quantity and intricacy. The proliferation of sites, trials, sponsors, and contract research organizations has surged exponentially, marking a significant shift in research conduct. However, EPCT operations suffer from numerous inefficiencies, such as cumbersome start-up processes, which are particularly critical when drug safety and the recommended phase II dose need to be established in a timely manner.

Photomediated One-Pot Multicomponent Cascade Reaction for the Synthesis of N-Acyl/Sulfonyl-α-Phosphonated-1,2,3,4-Tetrahydroisoquinoline via Twice Acyl/Sulfonyl Iminium Formation.

N-acyl/sulfonyl-α-phosphonated 1,2,3,4-tetrahydroiso-quinolines (THIQs) are highly important structural motifs in organic synthesis and drug discovery. However, the one-pot approach enabling direct difunctionalization of THIQs remains challenging. Herein we report a photomediated one-pot multicomponent cascade reaction to access N-acyl/sulfonyl-α-phosphonated THIQs via twice acyl/sulfonyl iminium.

Who becomes an entrepreneur after university? Evidence from Canada.

In recent decades there has been significant interest among policy makers in supporting entrepreneurship among university students, with the goal to improve labor market outcomes and contribute to the economy through venture creation. Drawing from the 2018 National Graduate Survey in Canada, our study examines who engages in entrepreneurial activity after graduation, investigating differences among demographic groups and between those who participated in entrepreneurship education on campus and those who did not participate. We find that those graduates who participated in entrepreneurship education are more likely to be self-employed and own their own business three years after graduating than the general population of university graduates.

Naturally occurring variation in a cytochrome P450 modifies thiabendazole responses independently of beta-tubulin.

Widespread anthelmintic resistance has complicated the management of parasitic nematodes. Resistance to the benzimidazole (BZ) drug class is nearly ubiquitous in many species and is associated with mutations in beta-tubulin genes. However, mutations in beta-tubulin alone do not fully explain all BZ resistance.

The chromatin remodeler ADNP regulates neurodevelopmental disorder risk genes and neocortical neurogenesis.

Although chromatin remodelers are among the most important risk genes associated with neurodevelopmental disorders (NDDs), the roles of these complexes during brain development are in many cases unclear. Here, we focused on the recently discovered ChAHP chromatin remodeling complex. The zinc finger and homeodomain transcription factor ADNP is a core subunit of this complex, and de novo mutations lead to intellectual disability and autism spectrum disorder.

Anti-inflammatory effects of moxifloxacin and levofloxacin on cadmium-activated human astrocytes: Inhibition of proinflammatory cytokine release, TLR4/STAT3, and ERK/NF-κB signaling pathway.

Cadmium is a non-essential element and neurotoxin that causes neuroinflammation, which leads to neurodegenerative diseases and brain cancer. To date, there are no specific or effective therapeutic agents to control inflammation and alleviate cadmium-induced progressive destruction of brain cells. Fluoroquinolones (FQs), widely used antimicrobials with effective blood-brain barrier penetration, show promise in being repurposed as anti-inflammatory drugs.

Patients' attitudes toward artificial intelligence (AI) in cancer care: A scoping review protocol.

Background: Artificial intelligence broadly refers to computer systems that simulate intelligent behaviour with minimal human intervention. Emphasizing patient-centered care, research has explored patients' perspectives on artificial intelligence in medical care, indicating general acceptance of the technology but also concerns about supervision. However, these views have not been systematically examined from the perspective of patients with cancer, whose opinions may differ given the distinct psychosocial toll of the disease.

A scoping review protocol on brain PaCO2 levels at altitude.

Background: Aeromedical transfer of patients with ischemic stroke to access hyperacute stroke treatment is becoming increasingly common. Little is known about how rapid changes of altitude and atmospheric pressure can impact cerebral perfusion and ischemic burden. In patients with ischemic stroke, there is a theoretical possibility that this physiologic response of hypoxia-driven hyperventilation at higher altitude can lead to a relative drop in PaCO2.

Epidemiological trends and healthcare disparities in onychomycosis: An analysis of the All of Us research program.

Onychomycosis is a common, difficult to treat nail disorder. Our objective was to explore disparities in current clinical management practices for onychomycosis in patients from underrepresented groups and with specific comorbidities. We conducted a cross-sectional study using the All of Us (AoU) research program.

Safety of hyperbaric oxygen therapy in non-emergent patients with a history of seizures: A retrospective cohort study.

Background: Hyperbaric oxygen therapy (HBOT) is well established as a treatment for various medical conditions. However, it poses a risk of oxygen toxicity, which can cause seizures particularly in individuals with pre-existing seizure disorders. Consequently, seizure disorders are considered a relative contraindication to HBOT.

Rhodium-mediated Assembly of New Heterocycles: From Borylenes to Oxaboroles.

Base-stabilized rhodium borylene complex κ2-L(CO)Rh(BMes), 2; κ2-L = κ2-NN'-Rh,κ1-N-B-(2,5-[iPr2P=N(4-iPrC6H4)]2-N'(C4H2)-); Mes = mesityl, reacts with a series of alkynes (PhC≡C-R; R = Ph, Me, CO2Et, H) to yield unique structures whereby the alkyne has regioselectively added across boron and the carbon atom of a CO ligand. The resulting complexes, LRh[C(O)C(Ph)C(R)B(Mes)], 3R, react with additional CO to afford cycle-containing products, L(CO)Rh([[EQUATION]]), 5R, that ultimately release highly functionalized organic heterocycles of the form [[EQUATION]]=NPipp (Pipp = 4-iPrC6H4), 6. These oxaboroles, which were assembled from a primary hydroborane, CO, an alkyne, and an azide-generated NPipp, are structurally analogous to two of the five boron-containing therapeutics approved by the FDA.

Digital tools and technologies used in food fortification: A scoping review.

Food fortification (i.e., industrial fortification and biofortification) increases the micronutrient content of foods to improve population nutrition.

Stereotactic Radiosurgery for World Health Organization Grade 2 and 3 Oligodendroglioma: An International Multicenter Study.

Background And Objectives: Oligodendrogliomas are primary brain tumors classified as isocitrate deshydrogenase-mutant and 1p19q codeleted in the 2021 World Health Organization Classification of central nervous system tumors. Surgical resection, radiotherapy, and chemotherapy are well-established management options for these tumors. Few studies have evaluated the efficacy of stereotactic radiosurgery (SRS) for oligodendroglioma.

The Role of Artificial Intelligence in Predicting Optic Neuritis Subtypes From Ocular Fundus Photographs.

Background: Optic neuritis (ON) is a complex clinical syndrome that has diverse etiologies and treatments based on its subtypes. Notably, ON associated with multiple sclerosis (MS ON) has a good prognosis for recovery irrespective of treatment, whereas ON associated with other conditions including neuromyelitis optica spectrum disorders or myelin oligodendrocyte glycoprotein antibody-associated disease is often associated with less favorable outcomes. Delay in treatment of these non-MS ON subtypes can lead to irreversible vision loss.

Neurodevelopmental Outcomes after Multiple General Anesthetic Exposures before 5 Years of Age: A Cohort Study.

Background: The general anaesthesia or awake-regional anaesthesia in infancy (GAS) trial demonstrated evidence that most neurodevelopmental outcomes at 2 and 5 yr of age in infants who received a single general anesthetic for elective inguinal herniorrhaphy were clinically equivalent when compared to infants who did not receive general anesthesia. More than 20% of the children in the trial had at least one subsequent anesthetic exposure after their initial surgery. Using the GAS database, this study aimed to address whether multiple (two or more) general anesthetic exposures compared to one or no general anesthetic exposure in early childhood were associated with worse neurodevelopmental outcomes at 5 yr.

Use of the Ostial Flash balloon in aorto-ostial chronic total occlusion percutaneous coronary intervention.

Background: The use of the Ostial Flash balloon (Ostial Corporation) has received limited study in aorto-ostial chronic total occlusion (CTO) percutaneous coronary artery intervention (PCI).

Methods: The authors evaluated the outcomes of Ostial Flash balloon use in a large CTO-PCI registry (PROGRESS-CTO, NCT02061436).

Results: The Ostial Flash balloon was used in 54 of 907 aorto-ostial CTO PCIs in 905 patients (6.

Cisplatin exposure dysregulates insulin secretion in male and female mice.

Cancer survivors have an increased risk of developing Type 2 diabetes compared to the general population. Patients treated with cisplatin, a common chemotherapeutic agent, are more likely to develop metabolic syndrome and Type 2 diabetes than age- and sex-matched controls. Surprisingly, the impact of cisplatin on pancreatic islets has not been reported.