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).

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.

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.

Delivery of N-Cadherin Targeting Peptides to Vascular Tissues by Surface-Modified Polyurethane Nanoparticles via a Drug-Coated Balloon.

Restenosis remains a long-standing limitation to effectively maintain functional blood flow after percutaneous transluminal angioplasty (PTA). While the use of drug-coated balloons (DCBs) containing antiproliferative drugs has improved patient outcomes, limited tissue transfer and poor therapeutic targeting capabilities contribute to off-target cytotoxicity, precluding adequate endothelial repair. In this work, a DCB system was designed and tested to achieve defined arterial delivery of an antirestenosis therapeutic candidate, cadherin-2 (N-cadherin) mimetic peptides (NCad), shown to selectively inhibit smooth muscle cell migration and limit intimal thickening in early animal PTA models.

A novel COL3A1 gene variant associated with sudden death due to spontaneous pneumothorax.

Spontaneous pneumothorax (SP) is a condition defined by abnormal gas accumulation in the chest cavity. Mutations of the collagen type III alpha 1 chain, COL3A1 gene, are primarily linked to vascular Ehlers-Danlos syndrome (vEDS); however, they can also contribute to structural changes in the tissue, like bullae of the lungs. In this case report, we present a young, thinly built boy who died due to a spontaneous pneumothorax.

Parental experiences of caring for their preschool children after declining vaccines: a qualitative systematic review.

Objective: This review synthesizes qualitative research about the experiences of parental caregivers enhancing their children's health after making the decision to not vaccinate their preschool children. This review aims to help health care providers understand the parental work involved in caring for under-vaccinated or unvaccinated children.

Introduction: Much of the current qualitative research literature about parents who are vaccine-hesitant or who decide not to vaccinate their children focuses on parental perceptions about the safety and efficacy of vaccines and decision-making.

The aerial epidermis is a major site of quinolizidine alkaloid biosynthesis in narrow-leafed lupin.

Lupins are promising protein crops that accumulate toxic quinolizidine alkaloids (QAs) in the seeds, complicating their end-use. QAs are synthesized in green organs (leaves, stems, and pods) and a subset of them is transported to the seeds during fruit development. The exact sites of biosynthesis and accumulation remain unknown; however, mesophyll cells have been proposed as sources, and epidermal cells as sinks.

Immunogenicity of bivalent versus monovalent mRNA booster vaccination among adult paramedics in Canada who had received three prior mRNA wild-type doses.

Comparative immunogenicity from different mRNA booster vaccines (directed at WT, BA.1 or BA.4/5 antigens) remains unclear.

Outcomes following resective and disconnective strategies in the treatment of epileptic spasms: a systematic review of the literature and individual patient data meta-analysis.

Epileptic spasms (ES) are a unique seizure type typically presenting in the form of infantile epileptic spasms syndrome (IESS) with characteristic hypsarrhythmia on scalp EEG and a preponderance with developmental delay or regression. While pharmacotherapy is the mainstay of treatment, surgical options, including disconnective or resective procedures, are increasingly recognized as viable therapeutic options for recurrent or persistent ES. However, limited data on safety, effectiveness, and prognostic factors hinder informed decision-making regarding surgery indications, timing, and intervention type.

Real-time evaluation of an automated computer vision system to monitor pain behavior in older adults.

Regular use of standardized observational tools to assess nonverbal pain behaviors results in improved pain care for older adults with severe dementia. While frequent monitoring of pain behaviors in long-term care (LTC) is constrained by resource limitations, computer vision technology has the potential to mitigate these challenges. A computerized algorithm designed to assess pain behavior in older adults with and without dementia was recently developed and validated using video recordings.

Creating a national breastfeeding and lactation policy for Canadian surgical residents.

Background: Despite known benefits of breastfeeding and challenges medical trainees face lactating at work, research specific to Canadian surgical trainees is lacking. Our objectives were to examine existing breastfeeding and lactation policies, query experiences and opinions of surgical trainees and program directors, and propose a comprehensive policy for programs nation-wide.

Methods: A multi-disciplinary team developed this two-part study.

A case study: exploring the impact of 3D printed models on cognitive integration during clinical skills training.

Background: Cognitive integration occurs when trainees make conceptual connections between relevant knowledges and is known to improve learning. While several experimental studies have demonstrated how text and audio-visual instruction can be designed to enhance cognitive integration, clinical skills training in real-world contexts may require alternative educational strategies. Introducing three-dimensional (3D) printed models during clinical skills instruction may offer unique learning opportunities to support cognitive integration.

Evaluating the Podcast as an Equity, Diversity and Inclusion resource: a cross-sectional survey analysis.

Background: Equity-deserving groups are communities marginalized from institutional power by oppressive forces (e.g., racism, sexism, homophobia, ableism).

Resident perceptions of learning challenges in concussion care education.

Background: Resident-focused curricula that support competency acquisition in concussion care are currently lacking. We sought to fill this gap by developing and evaluating Spiral Integrated Curricula (SIC) using the cognitive constructivism paradigm and the Utilization-Focused Evaluation (UFE) framework. The evidence-based curricula consisted of academic half-days (AHDs) and clinics for first- and second-year family medicine residents.

Freeze-dried plasma: Hemostasis and biophysical analyses for damage control resuscitation.

Background: Effective hemorrhage protocols prioritize immediate hemostatic resuscitation to manage hemorrhagic shock. Prehospital resuscitation using blood products, such as whole blood or alternatively dried plasma in its absence, has the potential to improve outcomes in hemorrhagic shock patients. However, integrating blood products into prehospital care poses substantial logistical challenges due to issues with storage, transport, and administration in field environments.

Early Initiation of Bundle Sheath Cells During Leaf Development as Visualised by SCARECROW Expression in Dicotyledonous C Plants.

The C type of dicotyledonous plants exhibit a higher density of reticulate veins than the C type, with a nearly 1:1 ratio of mesophyll cells (MCs) to bundle sheath cells (BSCs). To understand how this C-type cell pattern is formed, we identified two SCARECROW (SCR) genes in C Flaveria bidentis, FbSCR1 and FbSCR2, that fully or partially complement the endodermal cell layer-defective phenotype of Arabidopsis scr mutant. We then created FbSCRs promoter β-glucuronidase reporter (GUS) lines of F.

Bibliometric study and visual analysis of postoperative diabetes mellitus in kidney transplant recipients based on WoSCC database.

Background: In recent years, the increase of the post-transplantation diabetes mellitus (PTDM) after renal transplantation encourages people to do a lot of research on the disease. This paper conducted a bibliometric study on PTDM related literature to explore the risk factors of diabetes after kidney transplantation, as well as the current status, hotspots and development trends of PTDM research, so as to provide reference for researchers in related fields.

Methods: We searched the Web of Science Core Collection (WoSCC) database for PTDM literature from January 1, 1990, to August 20, 2023, and used VOSviewer, CiteSpace, and the R package 'bibliometrix' to do bibliometric analysis.

Syphilis Point of Care Rapid Test and Immediate Treatment Evaluation (SPRITE) study: a mixed-methods implementation science research protocol of eight public health units in Ontario, Canada.

Introduction: Urgent, tailored and equitable action is needed to address the alarming rise in syphilis rates in Canada. In the last decade, the rates of infectious syphilis have increased by 345% in Ontario, Canada. Underserved populations-people who use drugs, un(der)housed individuals and those living in rural and remote areas-face unique social and healthcare challenges that increase their vulnerability to syphilis infections and hinder their access to timely diagnosis and treatment.