Deep CRISPR mutagenesis characterizes the functional diversity of TP53 mutations.

The mutational landscape of TP53, a tumor suppressor mutated in about half of all cancers, includes over 2,000 known missense mutations. To fully leverage TP53 mutation status for personalized medicine, a thorough understanding of the functional diversity of these mutations is essential. We conducted a deep mutational scan using saturation genome editing with CRISPR-mediated homology-directed repair to engineer 9,225 TP53 variants in cancer cells.

The Molecular Bacterial Load Assay predicts treatment responses in patients with pre-XDR/XDR-tuberculosis more accurately than GeneXpert Ultra MTB/Rif.

Objectives: Early detection of treatment failure is essential to improve the management of drug-resistant tuberculosis (DR-TB). We evaluated the molecular bacterial load assay (MBLA) in comparison to standard diagnostic tests for monitoring therapy of patients affected by drug-resistant TB.

Methods: The performance of MBLA in tracking treatment response in a prospective cohort of patients with pulmonary MDR/RR- and pre-XDR/XDR-TB was compared with mycobacterial culture, mycobacterial DNA detection using GeneXpert (Xpert) and microscopy detection of sputum acid-fast-bacilli.

Vocal and Facial Behavior During Affect Production in Autism Spectrum Disorder.

Purpose: We investigate the extent to which automated audiovisual metrics extracted during an affect production task show statistically significant differences between a cohort of children diagnosed with autism spectrum disorder (ASD) and typically developing controls.

Method: Forty children with ASD and 21 neurotypical controls interacted with a multimodal conversational platform with a virtual agent, Tina, who guided them through tasks prompting facial and vocal communication of four emotions-happy, angry, sad, and afraid-under conditions of high and low verbal and social cognitive task demands.

Results: Individuals with ASD exhibited greater standard deviation of the fundamental frequency of the voice with the minima and maxima of the pitch contour occurring at an earlier time point as compared to controls.

Frequency and neuropathology of HTT repeat expansions in FTD/ALS: co-existence rather than causation.

Introduction: While ≥ 40 CAG repeat expansions in HTT present a well-established cause of Huntington's disease (HD), an enrichment of HTT repeat expansions was recently reported also in patients with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), including FTD/ALS patients with additional HD neuropathology. This raises the question whether the phenotypic spectrum of HTT expansions can be extended to ALS and FTD, and whether HTT should be considered as a new causative gene of FTD/ALS. If HTT repeat expansions were indeed systematically related to FTD/ALS, one would expect an increased frequency of HTT carriers in FTD/ALS, who can clinically/neuropathologically not be explained better than by the presence of the HTT repeat expansions.