A Canadian real-world, multi-center, prospective, observational study assessing the treatment duration, the treatment sequence, and the overall survival for patients treated with endocrine therapy ± targeted therapy in HR + HER2-negative advanced breast cancer.

Purpose: Understanding real-world treatment patterns and their effectiveness in HR + HER2- advanced breast cancer (aBC) in Canadian patients.

Patient And Methods: This was a multi-center, observational, prospective cohort study including men and pre-/peri-/postmenopausal women with HR + HER2- aBC receiving endocrine therapy (ET) or ET + targeted therapy (ET + TT). The primary objective was duration of treatment (DOT) with ET and ET + TT.

Molecular signatures associated with venous thromboembolism in children with acute lymphoblastic leukemia.

Background: Venous thromboembolism (VTE) is a frequent complication of childhood acute lymphoblastic leukemia (ALL).

Objectives: We aimed to identify molecular markers and signatures of leukemia microenvironment associated with VTE in childhood ALL, by dual-omics approach of gene expression (GEP) and DNA-methylation profiling.

Patients/methods: Eligible children were aged 1-21 years old with newly diagnosed ALL enrolled on the Dana Farber Cancer Institute 16-001 trial with available RNA sequencing data from bone marrow at diagnosis.

Proteomic characterization of regenerated cartilage following knee joint distraction; a human case-study.

Purpose: Knee joint distraction is a surgical procedure with cartilage-regenerating properties. The composition of joint distraction-regenerated cartilage in human patients is poorly documented. In this case-study, provided a unique opportunity to biomolecularly characterize the regenerated tissue from a patient who underwent bilateral distraction and later knee replacements.

PNKP safeguards stalled replication forks from nuclease-dependent degradation during replication stress.

Uncontrolled degradation and collapse of stalled replication forks (RFs) are primary sources of genomic instability, yet the molecular mechanisms for protecting forks from degradation/collapse remain to be fully elaborated. Here, we show that polynucleotide kinase-phosphatase (PNKP) localizes at stalled forks and protects stalled forks from excessive degradation. The loss of PNKP results in nucleolytic degradation of nascent DNA at stalled RFs.

Combination of Haloperidol With UNC9994, β-arrestin-Biased Analog of Aripiprazole, Ameliorates Schizophrenia-Related Phenotypes Induced by NMDAR Deficit in Mice.

Background: Glutamatergic system dysfunction contributes to a full spectrum of schizophrenia-like symptoms, including the cognitive and negative symptoms that are resistant to treatment with antipsychotic drugs (APDs). Aripiprazole, an atypical APD, acts as a dopamine partial agonist, and its combination with haloperidol (a typical APD) has been suggested as a potential strategy to improve schizophrenia. Recently, an analog of aripiprazole, UNC9994, was developed.