TTK (also known as Mps1) is the core component of the spindle assembly checkpoint, which ensures proper distribution of chromosomes to daughter cells to maintain genome integrity and to balance growth and division. However, the function of TTK in tumorigenesis has not been extensively studied, especially in relation to the development of gastric cancer. In this study, survival and tumor recurrence data related to TTK expression level in gastric cancer patients were collected and analyzed. We observed that TTK expression was negatively correlated with survival and tumor recurrence in vivo. TTK was also upregulated in gastric cancer cells and was observed to be essential for the proliferation and survival of gastric cancer cells. Knockdown of TTK inhibited proliferation and increased apoptosis. Furthermore, we report that TTK regulates the proliferation and apoptosis of tumor cells through the Akt-mTOR pathway. Knockdown of TTK inhibited activation of Akt-mTOR signaling. In summary, our data indicate that TTK is involved in the regulation of gastric cancer proliferation and apoptosis.Hydrophobic neo-antigens are more immunogenic because they are better presented by the major histocompatibility complex (MHC) and better recognized by T cells. Tumor cells can evade the immune response by expressing checkpoints such as PD-L1. Checkpoint blockade reactivates immune recognition and can be effective in diseases such as melanoma, which harbors a high tumor mutational burden (TMB). Cancers presenting low or intermediate TMB can also respond to checkpoint blockade, albeit less frequently, suggesting the need for biological markers predicting response. We calculated the hydrophobicity of neo-peptides produced by probabilistic in silico simulation of the genomic UV exposure mutational signature. We also computed the hydrophobicity of potential neo-peptides and extent of UV exposure based on the UV mutational signature enrichment (UVMSE) score in The Cancer Genome Atlas (TCGA) (N = 3543 tumors), and in our cohort of 151 immunotherapy-treated patients. In silico simulation showed that UV exposure significantly increased hydrophobicity of neo-peptides, especially over multiple mutagenic cycles. There was also a strong correlation (R2 = 0.953) between weighted UVMSE and hydrophobicity of neo-peptides in TCGA melanoma patients. Importantly, UVMSE was able to predict better response (p=0.0026), progression-free survival (p = 0.036) and overall survival (p = 0.052) after immunotherapy in patients with low/intermediate TMB, but not in patients with high TMB. We show that higher UVMSE scores could be a useful predictor of better immunotherapy outcome, especially in patients with low/intermediate TMB, likely due to increased hydrophobicity (and hence immunogenicity) of neo-peptides.Aims Depression is an important issue in heart failure (HF). The study investigated whole-brain and regional brain glucose metabolism in HF patients and its association with depression comorbidity. Methods and results Twenty-nine hospitalized patients with symptomatic systolic HF (left ventricular ejection fraction 13) exhibited different metabolic patterns that could be used to differentiate between 'epiphenomenal' and 'real' depression. Namely, presence of whole-brain hypometabolism suggested 'epiphenomenal' depression, whereas absence suggested 'real' depression. Presence of significant relative regional brain hypometabolism enhanced the likelihood of 'real' depression diagnosis.Background There is a need to better understand the experiences and support needs of paid and family carers of people with an intellectual disability and dementia, and the role of Intellectual Disability Dementia Care Pathways (IDDCPs). This study explored the experiences of carers, and IDDCPs and other support structures within those experiences. Methods A constructivist grounded theory methodology was implemented. Data were obtained through 23 semi-structured interviews with two family carers, eight paid carers and eight healthcare professionals. Findings The study's theory produced five interrelated categories Impact of Dementia, Challenging the Diagnosis Process, Continuum of Support, Continuity and Continuum of Understanding. Conclusions Findings have demonstrated the importance of planning and supporting carers' holistic needs; the role of an IDDCP in the post-diagnostic support (or lack of it) for carers; and the importance of a timely diagnosis of dementia. Recommendations for practice are offered.Objective Neurodevelopmental disorders (NDDs) often associate with epilepsy or craniofacial malformations. Recent large-scale DNA analyses identified hundreds of candidate genes for NDDs, but a large portion of the cases still remain unexplained. We aimed to identify novel candidate genes for NDDs. Methods We performed exome sequencing of 95 patients with NDDs including 51 with trigonocephaly and subsequent targeted sequencing of additional 463 NDD patients, functional analyses of variant in vitro, and evaluations of autism spectrum disorder (ASD)-like phenotypes and seizure-related phenotypes in vivo. Results We identified de novo truncation variants in nine novel genes; CYP1A1, C14orf119, FLI1, CYB5R4, SEL1L2, RAB11FIP2, ZMYND8, ZNF143, and MSX2. MSX2 variants have been described in patients with cranial malformations, and our present patient with the MSX2 de novo truncation variant showed cranial meningocele and partial epilepsy. MSX2 protein is known to be ubiquitinated by an E3 ubiquitin ligase PJA1, and interestingly we found a PJA1 hemizygous p.Arg376Cys variant recurrently in seven Japanese NDD patients; five with trigonocephaly and one with partial epilepsy, and the variant was absent in 886 Japanese control individuals. Imatinib molecular weight Pja1 knock-in mice carrying p.Arg365Cys, which is equivalent to p.Arg376Cys in human, showed a significant decrease in PJA1 protein amount, suggesting a loss-of-function effect of the variant. Pja1 knockout mice displayed moderate deficits in isolation-induced ultrasonic vocalizations and increased seizure susceptibility to pentylenetetrazole. Interpretation These findings propose novel candidate genes including PJA1 and MSX2 for NDDs associated with craniofacial abnormalities and/or epilepsy.