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In the final analysis of a phase 1/phase 2 trial of autologous GD2-targeting CAR T cells in pediatric patients with high-risk metastatic, relapsed or refractory neuroblastoma, treatment was overall well tolerated, with an objective response rate of 66%. These findings were further supported by a case series involving the same therapy in a similar patient population.

B cell malignancies resistant to conventional treatments are potentially sensitive to CAR-T cell immune therapy, but its clinical applicability is limited by immune related adverse effects. Here authors show in a humanized mouse model that blocking IFNγ with the monoclonal antibody emapalumab mitigates the adverse effects of CAR.CD19-T cells without compromising their anti-lymphoma efficacy.

In a case series of five children with treatment-refractory neuroblastoma, it was feasible to manufacture and administer donor-derived GD2-specific CAR T cells and clinical responses were seen in four patients.

Loss-of-function variants in thyroid hormone transporter MCT8 cause a neurodevelopmental and metabolic disorder. Here the authors identify genotype-phenotype relationships, advance insights in MCT8 (dys)function and create a pathogenicity-severity variant classifier.

Leukaemia development has been reported as an associated risk of haematopoietic stem cell gene therapy (HSPC-GT) using retroviral vectors in different diseases. Here, the authors show a case of T-cell acute lymphoid leukaemia in a patient with Adenosine Deaminase-deficient Severe Combined Immunodeficiency (ADA-SCID) treated with retroviral gene therapy.

Marco Tartaglia and colleagues report the identification of mutations of SHOC2 in individuals with Noonan-like syndrome with loose anagen hair. The mutations cause aberrantly acquired N-myristoylation of SHOC2 resulting in aberrant targeting of SHOC2 to the plasma membrane. SHOC2 is believed to function as a scaffold linking RAS to downstream signal transducers.

IXPE has revealed how the spin of the accreting neutron star Hercules X-1 changes in three dimensions. The spin axis of the star moves both through the star and across the sky, hinting that the crust of the star is asymmetric by almost one part in a million.

The accretion geometry of X-ray binary Cygnus X-3 is determined here from IXPE observations. X-ray polarization reveals a narrow funnel with reflecting walls, which focuses emission, making Cyg X-3 appear as an ultraluminous X-ray source.

In June 2022, the IXPE satellite observed a shock passing through the jet of active galaxy Markarian 421. The rotation of the X-ray-polarized radiation over a 5-day period revealed that the jet contains a helical magnetic field.

A study reports the measurement of the polarization degree and angle of X-rays from Sagittarius A^* reflected off a nearby cloud, indicating an X-ray flare about 200 years ago.

X-ray polarimetry observations with the Imaging X-ray Polarimetry Explorer constrain the accretion geometry in an X-ray pulsar and provide evidence for a misalignment of the spin, magnetic and orbital axes in Her X-1.

X-ray polarization measurements of the Crab nebula and pulsar by the IXPE satellite reveal a global toroidal magnetic field with large variations in local polarization, suggesting a more complex turbulence distribution than anticipated.

Polarization can exceed 60% at the leading edge of the inner part of the Vela pulsar wind nebula; in contrast with the case of the supernova remnant, the electrons in the pulsar wind nebula are accelerated with little or no turbulence in a highly uniform magnetic field.

Polarization measurements are reported for the blazar Mk501, revealing a degree of X-ray polarization that is more than twice the optical value and supporting the shock-accelerated energy-stratified electron population scenario.

An investigation using various methods reports an association between adeno-associated virus 2 and paediatric hepatitis of unknown aetiology.

Type I interferons have been described to have protumor or antitumor functions depending on context. Here the authors show a protumor function for type I interferons in that they promote cancer stem cells by upregulating the chromatin remodeling factor KDM1B.

A case–control study investigating the causes of recent cases of acute hepatitis of unknown aetiology in 32 children identifies an association between adeno-associated virus infection and host genetics in disease susceptibility.

By integrating in-vivo tractography with ex-vivo dissection, this study maps the subcomponents of the Superior Longitudinal System and classifies them based on their anatomical plausibility, revealing the hierarchical and depth-dependent organization of association fibers of the brain.

A vesicle trafficking Rab11 effector switch is important for ciliogenesis. Here, the authors report a ciliopathy-related disorder caused by variants in WDR44, a Rab11 effector. WDR44 variants show higher affinity for Rab11 and can impair ciliogenesis.

Martin Zenker, Marco Tartaglia, Reza Ahmadian and colleagues report the identification of a restricted spectrum of NRAS mutations in individuals with Noonan syndrome. Functional testing revealed that the mutations confer enhanced stimulus-dependent MAPK activation.

Heterotopic ossification is a disorder characterized by the transformation of soft tissue to bone. In this study the authors report heterotopic ossification in a child caused by enhancer hijacking at the ARHGAP36 gene, the ectopic activation by an enhancer that it not its own.

Analysis of genomic and clinical features of acute erythroid leukemia in comparison to other myeloid disorders supports its distinct classification, defines subgroups and suggests therapeutic vulnerabilities.

AMBRA1-mediated degradation of cyclin D through CRL4–DDB1 regulates cell proliferation and prevents replication stress in neurodevelopment and cancer.

Genetic variants in ionotropic glutamate receptors have been implicated in neurodevelopmental disorders. Here, the authors report heterozygous de novo mutations in the GRIA2 gene in 28 individuals with intellectual disability and neurodevelopmental abnormalities associated with reduced Ca²⁺ transport and AMPAR currents.”

ERAP1 is an endoplasmic reticulum aminopeptidase that trims MHC Class-I peptides for antigen presentation. Here, the authors show that ERAP1 enhances Hedgehog signalling by sequestering USP47 from  βTrCP and promoting tumorigenesis through βTrCP degradation and increased Gli protein stability.

Biochemical and genetics studies identify CRL4^AMBRA1 as the ubiquitin ligase that has a key role in regulating the stability of D-type cyclins during cell-cycle progression.

Metabolic activity of specific human gut microorganisms contributes to liver steatosis in obese women.