Loss of hepatocyte Usp53 protects mice from a form of xenobiotic-induced liver injury.

Background: Ubiquitin-specific protease 53 (USP53) deficiency is associated with familial intrahepatic cholestasis in which serum gamma-glutamyl transferase (GGT) activity is relatively low. However, how USP53 deficiency contributes to cholestasis is obscure. No animal model has been reported.

Development and Usability of an Advance Care Planning Website (My Voice) to Empower Patients With Heart Failure and Their Caregivers: Mixed Methods Study.

Background: Web-based advance care planning (ACP) interventions offer a promising solution to improve ACP engagement, but none are specifically designed to meet the needs of patients with heart failure and their caregivers.

Objective: We aimed to develop and assess the usability and acceptability of a web-based ACP decision aid called "My Voice," which is tailored for patients with heart failure and their caregivers.

Methods: This study's team and advisory board codeveloped the content for both patient and caregiver modules in "My Voice.

Frequency of supervised consumption service use and acute care utilization in people who inject drugs.

Background: Supervised consumption service (SCS) use among people who inject drugs may reduce acute care utilization; however, prior studies have been limited by self-reported outcomes and dichotomous exposures.

Methods: We conducted a prospective cohort study using linked questionnaire and health administrative data among people who inject drugs in Toronto, Canada (2018-2020). Baseline SCS use frequency was defined by a participant's self-reported proportion of injections performed at an SCS over the past six months: "all/most" (≥75 %), "some" (26-74 %), "few" (1-25 %), or "none" (0 %).

ZFYVE19 deficiency: a ciliopathy involving failure of cell division, with cell death.

Background And Aims: Variants in underlie a disorder characterised by progressive portal fibrosis, portal hypertension and eventual liver decompensation. We aim to create an animal model to elucidate the pathogenic mechanism.

Methods: knockout ( ) mice were generated and exposed to different liver toxins.

Understanding the Influence of Single Payer Health Insurance on Socioeconomic Disparities in Total Hip Arthroplasty (THA) Utilization: A Transnational Analysis.

Objective: Access to care varies between countries. It is theorized that income-based disparities in access may be reduced in countries with universal health insurance relative to the United States, but data are currently limited. We hypothesized that income-based differences in total hip arthroplasty (THA) utilization and outcomes would be larger in the United States than in Canada.

Comprehensive Bile Acid Profiling of ABCB4-mutated Patients and the Prognostic Role of Taurine-conjugated 3α,6α,7α,12α-Tetrahydroxylated Bile Acid in Cholestasis.

Background And Aims: We asked if comprehensive bile acid profiling could provide insights into the physiopathology of -mutated patients and evaluated the prognostic value of taurine-conjugated tetrahydroxylated bile acid (tauro-THBA) in cholestasis.

Methods: Serum bile acid profiles were evaluated in 13 -mutated patients with 65 healthy controls by ultra-high-performance liquid chromatography/multiple-reaction monitoring-mass spectrometry (UPLC/MRM-MS). The concentration of tauro-THBA was compared between -mutated patients with different prognoses.

Development and validation of a parsimonious prediction model for positive urine cultures in outpatient visits.

Urine culture is often considered the gold standard for detecting the presence of bacteria in the urine. Since culture is expensive and often requires 24-48 hours, clinicians often rely on urine dipstick test, which is considerably cheaper than culture and provides instant results. Despite its ease of use, urine dipstick test may lack sensitivity and specificity.

Polymeric micelles for cutaneous delivery of the hedgehog pathway inhibitor TAK-441: Formulation development and cutaneous biodistribution in porcine and human skin.

TAK-441 is a potent inhibitor of the hedgehog pathway (IC 4.4 nM) developed for the treatment of basal cell carcinoma that is active against the vismodegib-resistant Smoothened receptor D473H mutant. The objective of this study was to develop a micelle-based formulation of TAK-441 using D-α-Tocopherol polyethylene glycol 1000 succinate (TPGS) and to investigate its cutaneous delivery and biodistribution.

Emergency department utilization, admissions, and revisits in the United States (New York), Canada (Ontario), and New Zealand: A retrospective cross-sectional analysis.

Background: Emergency department (ED) utilization is a significant concern in many countries, but few population-based studies have compared ED use. Our objective was to compare ED utilization in New York (United States), Ontario (Canada), and New Zealand (NZ).

Methods: A retrospective cross-sectional analysis of all ED visits between January 1, 2016, and September 30, 2017, for adults ≥18 years using data from the State Emergency Department and Inpatient Databases (New York), the National Ambulatory Care Reporting System and Discharge Abstract Data (Ontario), and the National Non-Admitted Patient Collection and the National Minimum Data Set (New Zealand).

Cre recombinase expression cooperates with homozygous FLT3 internal tandem duplication knockin mouse model to induce acute myeloid leukemia.

Murine models offer a valuable tool to recapitulate genetically defined subtypes of AML, and to assess the potential of compound mutations and clonal evolution during disease progression. This is of particular importance for difficult to treat leukemias such as FLT3 internal tandem duplication (ITD) positive AML. While conditional gene targeting by Cre recombinase is a powerful technology that has revolutionized biomedical research, consequences of Cre expression such as lack of fidelity, toxicity or off-target effects need to be taken into consideration.

Poly-hydroxylated bile acids and their prognostic roles in Alagille syndrome.

Background: The liver manifestations of Alagille syndrome (ALGS) are highly variable, and factors affecting its prognosis are poorly understood. We asked whether the composition of bile acids in ALGS patients with good clinical outcomes differs from that in patients with poor outcomes and whether bile acids could be used as prognostic biomarkers.

Methods: Blood for bile acid profiling was collected from genetically confirmed JAG1-associated ALGS patients before one year of age.

Severe Thrombocytopenia, Thrombosis and Anti-PF4 Antibody after Pfizer-BioNTech COVID-19 mRNA Vaccine Booster-Is It Vaccine-Induced Immune Thrombotic Thrombocytopenia?

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a serious and life-threatening complication occurring after adenovirus-vector COVID-19 vaccines, and is rarely reported after other vaccine types. Herein, we report a case of possible VITT after the Pfizer-BioNTech mRNA vaccine booster, who presented with extensive lower limb deep vein thrombosis, severe thrombocytopenia, markedly elevated D-dimer and positive anti-PF4 antibody occurring 2 weeks post-vaccination, concurrent with a lupus anticoagulant. A complete recovery was made after intravenous immunoglobulin, prednisolone and anticoagulation with the oral direct Xa inhibitor rivaroxaban.

Neonatal Dubin-Johnson Syndrome and its Differentiation from Biliary Atresia.

Background And Aims: The aim was to determine if liver biochemistry indices can be used as biomarkers to help differentiate patients with neonatal Dubin-Johnson syndrome (nDJS) from those with biliary atresia (BA).

Methods: Patients with genetically-confirmed nDJS or cholangiographically confirmed BA were retrospectively enrolled and randomly assigned to discovery or verification cohorts. Their liver chemistries, measured during the neonatal period, were compared.

Targeting cell cycle and apoptosis to overcome chemotherapy resistance in acute myeloid leukemia.

Chemotherapy-resistant acute myeloid leukemia (AML), frequently driven by clonal evolution, has a dismal prognosis. A genome-wide CRISPR knockout screen investigating resistance to doxorubicin and cytarabine (Dox/AraC) in human AML cell lines identified gene knockouts involving AraC metabolism and genes that regulate cell cycle arrest (cyclin dependent kinase inhibitor 2A (CDKN2A), checkpoint kinase 2 (CHEK2) and TP53) as contributing to resistance. In human AML cohorts, reduced expression of CDKN2A conferred inferior overall survival and CDKN2A downregulation occurred at relapse in paired diagnosis-relapse samples, validating its clinical relevance.