A homozygous variant in INTS11 links mitosis and neurogenesis defects to a severe neurodevelopmental disorder.

The INTS11 endonuclease is crucial in modulating gene expression and has only recently been linked to human neurodevelopmental disorders (NDDs). However, how INTS11 participates in human development and disease remains unclear. Here, we identify a homozygous INTS11 variant in two siblings with a severe NDD. The variant impairs INTS11 catalytic activity, supported by its substrate's accumulation, and causes G2/M arrest in patient cells with length-dependent dysregulation of genes involved in mitosis and neural development, including the NDD gene CDKL5. The mutant knockin (KI) in induced pluripotent stem cells (iPSCs) disturbs their mitotic spindle organization and thus leads to slow proliferation and increased apoptosis, possibly through the decreased neurally functional CDKL5-induced extracellular signal-regulated kinase (ERK) pathway inhibition. The generation of neural progenitor cells (NPCs) from the mutant iPSCs is also delayed, with long transcript loss concerning neurogenesis. Our work reveals a mechanism underlying INTS11 dysfunction-caused human NDD and provides an iPSC model for this disease.

Treatment planning computed tomography radiomics for predicting treatment outcomes and haematological toxicities in locally advanced cervical cancer treated with radiotherapy: A retrospective cohort study.

OBJECTIVE: We evaluated whether radiomic features extracted from planning computed tomography (CT) scans predict clinical end points in patients with locally advanced cervical cancer (LACC) undergoing intensity-modulated radiation therapy and brachytherapy. DESIGN: A retrospective cohort study. SETTING: Xiangya Hospital of Central South University, Changsha, Hunan, China. POPULATION: Two hundred and fifty-seven LACC patients who were treated with intensity-modulated radiotherapy from 2014 to 2017. METHODS: Patients were allocated into the training/validation sets (3:1 ratio) using proportional random sampling, resulting in the same proportion of groups in the two sets. We extracted 254 radiomic features from each of the gross target volume, pelvis and sacral vertebrae. The sequentially backward elimination support vector machine algorithm was used for feature selection and end point prediction. MAIN OUTCOMES AND MEASURES: Clinical end points include tumour complete response (CR), 5-year overall survival (OS), anaemia, and leucopenia. RESULTS: A combination of ten clinicopathological parameters and 34 radiomic features performed best for predicting CR (validation balanced accuracy: 80.8%). The validation balanced accuracy of 54 radiomic features was 85.8% for OS, and their scores can stratify patients into the low-risk and high-risk groups (5-year OS: 95.5% versus 36.4%, p < 0.001). The clinical and radiomic models were also predictive of anaemia and leucopenia (validation balanced accuracies: 71.0% and 69.9%). CONCLUSION: This study demonstrated that combining clinicopathological parameters with CT-based radiomics may have value for predicting clinical end points in LACC. If validated, this model may guide therapeutic strategy to optimise the effectiveness and minimise toxicity or treatment for LACC.

Surface polaritons of small coated cylinders illuminated by normal incident TM and TE plane waves.

The surface polariton properties of TM or TE plane wave scattered by a coated cylinder are investigated in this paper. The coated cylinder (whose outer radius is much smaller than the wavelength) is assumed to be electrically small and low dissipative. Analytical formulas of the plasmonic resonances are derived and found to agree well with those obtained from exact expressions in the classical scattering theory. The behaviors of the scattering coefficients at resonances are also discussed and compared for different cases. While a single cylinder has the resonance at the relative permittivity of epsilon(r) = -1 (or relative permeability of mu(r) = -1) for the TE (or TM) polarization, the resonances of the coated cylinders change with different n values (where n denotes the series term or mode of the field), and also the inner and outer radii. It is shown that the scattered field in the near zone can be enhanced significantly compared to the incident wave. For the TE incident case, we take a silver coated nano-cylinder as an example to illuminate the near-field optical effect. Also, we have studied the peak values of the nth order scattered field for different n values and electrical parameter k0b (where k0 is the wavenumber of the free space and b denotes the outer radius of the cylinder) around the cylinder. The derived new formulas for total cross sections are given and they may provide us with some potential photonic applications such as surface cleaning and etching.