ZIC1 is a context-dependent medulloblastoma driver in the rhombic lip.

Transcription factors are frequent cancer driver genes, exhibiting noted specificity based on the precise cell of origin. We demonstrate that ZIC1 exhibits loss-of-function (LOF) somatic events in group 4 (G4) medulloblastoma through recurrent point mutations, subchromosomal deletions and mono-allelic epigenetic repression (60% of G4 medulloblastoma). In contrast, highly similar SHH medulloblastoma exhibits distinct and diametrically opposed gain-of-function mutations and copy number gains (20% of SHH medulloblastoma).

Renal Tubule-Specific Angiotensinogen Deletion Attenuates SGLT2 Expression and Ameliorates Diabetic Kidney Disease in Murine Models of Type 1 Diabetes.

The role of the intrarenal renin-angiotensin system (iRAS) in diabetic kidney disease (DKD) progression remains unclear. In this study, we generated mice with renal tubule-specific deletion of angiotensinogen (Agt; RT-Agt-/-) in both Akita and streptozotocin (STZ)-induced mouse model of diabetes. Both Akita RT-Agt-/- and STZ-RT-Agt-/- mice exhibited significant attenuation of glomerular hyperfiltration, urinary albumin/creatinine ratio, glomerulomegaly and tubular injury.

Building global collaborative research networks in paediatric critical care: a roadmap.

Paediatric critical care units are designed for children at a vulnerable stage of development, yet the evidence base for practice and policy in paediatric critical care remains scarce. In this Health Policy, we present a roadmap providing strategic guidance for international paediatric critical care trials. We convened a multidisciplinary group of 32 paediatric critical care experts from six continents representing paediatric critical care research networks and groups.

The IL-2 SYNTHORIN molecule promotes functionally adapted Tregs in a preclinical model of type 1 diabetes.

Deficits in IL-2 signaling can precipitate autoimmunity by altering the function and survival of FoxP3+ regulatory T cells (Tregs) while high concentrations of IL-2 fuel inflammatory responses. Recently, we showed that the non-beta IL-2 SYNTHORIN molecule SAR444336 (SAR'336) can bypass the induction of autoimmune and inflammatory responses by increasing its reliance on IL-2 receptor α chain subunit (CD25) to provide a bona fide IL-2 signal selectively to Tregs, making it an attractive approach for the control of autoimmunity. In this report, we further demonstrate that SAR'336 can support non-beta IL-2 signaling in murine Tregs and limit NK and CD8+ T cells' proliferation and function.

Severe hypophosphataemia and hypocalcaemia following intravenous ferric derisomaltose and denosumab administration.

Serum calcium and phosphorus levels are tightly regulated by the calciotropic hormone parathyroid hormone, fibroblast growth factor 23 and 1,25(OH) vitamin D. Commonly prescribed therapies for iron-deficiency anaemia (IDA) such as ferric carboxymaltose and ferric derisomaltose (FDM) have been shown to disrupt phosphorus homeostasis, resulting in hypophosphataemia. Similarly, denosumab use can result in hypocalcaemia due to the inhibition of osteoclastic maturation, activity and survival.

Factors Influencing Nerinetide Effect on Infarct Volume in Patients Without Alteplase in the Randomized ESCAPE-NA1 Trial.

Background: In the ESCAPE-NA1 trial (Efficacy and Safety of Nerinetide for the Treatment of Acute Ischemic Stroke), treatment with nerinetide was associated with a smaller infarct volume among patients who did not receive intravenous alteplase. We assessed the effect of nerinetide on the surrogate imaging outcome of final infarct volume in patients who did not receive intravenous alteplase and explored predictors of outcome and modifiers of nerinetide's effect on infarct volume.

Methods: ESCAPE-NA1 was a multicenter, randomized trial in which patients with acute stroke with a baseline Alberta Stroke Program Early CT Score >4, undergoing endovascular thrombectomy, were randomized to receive intravenous nerinetide or placebo.

Hypoxia is linked to acquired resistance to immune checkpoint inhibitors in lung cancer.

Despite the established use of immune checkpoint inhibitors (ICIs) to treat non-small cell lung cancer (NSCLC), only a subset of patients benefit from treatment and ∼50% of patients whose tumors respond eventually develop acquired resistance (AR). To identify novel drivers of AR, we generated murine Msh2 knock-out (KO) lung tumors that initially responded but eventually developed AR to anti-PD-1, alone or in combination with anti-CTLA-4. Resistant tumors harbored decreased infiltrating T cells and reduced cancer cell-intrinsic MHC-I and MHC-II levels, yet remained responsive to IFNγ.

Catheter Ablation or Antiarrhythmic Drugs for Ventricular Tachycardia.

Background: Patients with ventricular tachycardia and ischemic cardiomyopathy are at high risk for adverse outcomes. Catheter ablation is commonly used when antiarrhythmic drugs do not suppress ventricular tachycardia. Whether catheter ablation is more effective than antiarrhythmic drugs as a first-line therapy in patients with ventricular tachycardia is uncertain.

An oxidative metal ions-free lignin-catalyzed multifunctional hydrogel bioelectronics for codable eye communication.

To meet the stringent requirements of wearable and flexible electronics for functionality and comfort, it is urgent to develop green conductive, self-adhesive, and stretchable functional hydrogels. The chelates of transition metal ions and lignosulfonate sodium (LS) can impart multi-functionality to the hydrogel and significantly improve the hydrogel's gelation speed. However, the presence of metal ions may weaken the adhesiveness of hydrogels by shielding the functional adhesive groups.

Consent-Related Outcomes in the Alteplase Compared to Tenecteplase Trial.

Background And Objectives: In recent years, researchers have sought to address the challenges of obtaining informed consent for participation in acute stroke trials. We studied outcomes related to the use of deferral of consent in the phase 3 Alteplase Compared to Tenecteplase (AcT) trial.

Methods: As part of our protocol, we captured methods of consent, participant withdrawals, door-to-randomization times, and door-to-needle times.

A new subtype of serovar 6, K6b:O3, of Actinobacillus pleuropneumoniae based on genotypic analysis.

We have analyzed the capsule (CPS) and the lipopolysaccharide O-Antigen (O-Ag) biosynthesis loci of fifteen field isolates of Actinobacillus pleuropneumoniae, including eleven North American and four Japanese ones, reactive to antisera against serovars 3, 6, 8 and/or 15. Ten North American isolates amplified a serovar 6-indicative fragment derived from the capsular loci, whereas one North American isolate and all four Japanese isolates amplified the serovar 6-indicative fragment as well as the serovar 3-indicative fragment. The five isolates producing a 3/6 banding pattern contain a type I CPS locus, named K6b, similar to serovar 6, but with differences in the cpxABCD and cpsABC gene sequences and the length of intergenic regions (modF-cpxA, and cpsC-cpsD).

Xanthan gum modulation of octenyl succinic anhydrate starch-based high internal phase emulsions: Characterization, rheological behavior, and 3D printing applications.

The growing popularity of three-dimensional (3D) food printing has highlighted the need for suitable printable materials. This study explores the impact of xanthan gum on octenyl succinic anhydride (OSA) starch-stabilized High Internal Phase Emulsions (HIPEs) for 3D food printing applications. Xanthan gum was added to increase the viscosity of the continuous phase, which helps to slow down the movement and reduce the collision of emulsion droplets.

Side effect management algorithms for niraparib/abiraterone acetate in prostate cancer.

Introduction: Niraparib, a PARP1/2 inhibitor, is newly approved in combination with abiraterone acetate (AA) plus prednisone or prednisolone (niraparib/AA+P) for the treatment of adult patients with BRCA-mutated, treatment-naïve metastatic castration resistant prostate cancer (mCRPC). Detailed guidance beyond the prescribing information may be helpful in managing the side effect profile and dosing practicalities of this combination therapy.

Materials And Methods: A panel of specialists convened to design management algorithms for four common niraparib/AA+P treatment-related adverse events (AEs) in mCRPC; anemia, thrombocytopenia, hypertension, and nausea.

Disease Activity in Pregnant and Postpartum Women With Multiple Sclerosis Receiving Ocrelizumab or Other Disease-Modifying Therapies.

Background And Objectives: Women with multiple sclerosis (MS) are at risk of disease reactivation in the early postpartum period. Ocrelizumab (OCR) is an anti-CD20 therapy highly effective at reducing MS disease activity. Data remain limited regarding use of disease-modifying therapies (DMTs), including OCR, and disease activity during peripregnancy periods.

The effect of concurrent clopidogrel and omeprazole administration on clopidogrel metabolism and platelet function in healthy cats.

Background: Some studies in humans show that the concurrent use of clopidogrel and omeprazole decreases plasma clopidogrel active metabolite (CAM) concentrations and clopidogrel antiplatelet effects. Whether this drug interaction occurs in cats is unknown.

Hypothesis: We hypothesized that administration of clopidogrel with omeprazole would decrease plasma CAM concentrations and decrease clopidogrel antiplatelet effects in healthy cats.

Efficacy of weekly versus daily cholecalciferol for repleting serum vitamin D (25(OH)D) deficiency: A systematic review and meta-analysis of randomized controlled trials.

Background/rationale: Weekly cholecalciferol can replace daily supplementation to reduce pill burden in patients with complex medication regimens and hypovitaminosis D, but evidence supporting this switch is unclear.

Objective: We aimed to determine whether weekly cholecalciferol was superior to daily cholecalciferol to replete patients with hypovitaminosis D.

Methods: We conducted a systematic review of randomized controlled trials involving participants with baseline hypovitaminosis D (<30 ng/ml) comparing weekly versus daily cholecalciferol dosing and where serum cholecalciferol was measured within 120 days of starting treatment.