Comprehensive characterization of tumor microenvironment in colorectal cancer via molecular analysis.

Colorectal cancer (CRC) remains a challenging and deadly disease with high tumor microenvironment (TME) heterogeneity. Using an integrative multi-omics analysis and artificial intelligence-enabled spatial analysis of whole-slide images, we performed a comprehensive characterization of TME in colorectal cancer (CCCRC). CRC samples were classified into four CCCRC subtypes with distinct TME features, namely, C1 as the proliferative subtype with low immunogenicity; C2 as the immunosuppressed subtype with the terminally exhausted immune characteristics; C3 as the immune-excluded subtype with the distinct upregulation of stromal components and a lack of T cell infiltration in the tumor core; and C4 as the immunomodulatory subtype with the remarkable upregulation of anti-tumor immune components. The four CCCRC subtypes had distinct histopathologic and molecular characteristics, therapeutic efficacy, and prognosis. We found that the C1 subtype may be suitable for chemotherapy and cetuximab, the C2 subtype may benefit from a combination of chemotherapy and bevacizumab, the C3 subtype has increased sensitivity to the WNT pathway inhibitor WIKI4, and the C4 subtype is a potential candidate for immune checkpoint blockade treatment. Importantly, we established a simple gene classifier for accurate identification of each CCCRC subtype. Collectively our integrative analysis ultimately established a holistic framework to thoroughly dissect the TME of CRC, and the CCCRC classification system with high biological interpretability may contribute to biomarker discovery and future clinical trial design.

Correlation between nutrition, oral health, and different sarcopenia groups among elderly outpatients of community hospitals: a cross-sectional study of 1505 participants in China.

BACKGROUND: Studies have rarely explored the association between oral health status and different sarcopenia groups (possible sarcopenia, diagnosed sarcopenia, and severe sarcopenia). Moreover, these studies have not reported any definitive conclusions of their relationship. We aimed to characterize the oral health status, prevalence of sarcopenia, and risk factors in different sarcopenia groups of elderly outpatients of community hospitals. Furthermore, we determined the correlation among nutrition, oral health, and different sarcopenia groups. METHODS: Overall, 1505 elderly participants (aged ≥ 65 years) completed the survey. The Mini Nutritional Assessment short-form (MNA-SF) was used to assess the nutrition status of the elderly. Oral health was assessed using the instrument of the oral health assessment index of the elderly (General Oral Health Assessment Index [GOHAI]), and the number of remaining natural teeth (NRT) was counted. Data on muscle mass, muscle strength, and gait speed were collected, and sarcopenia was classified into three groups (possible sarcopenia, diagnosed sarcopenia, and severe sarcopenia) according to the Asian Working Group for Sarcopenia 2019. Multinomial logistic regression multivariate analysis was used to test their relationships. RESULTS: Eighty-eight (5.8%) participants were identified as having possible sarcopenia; 142 (9.5%), diagnosed sarcopenia; 136 (9.0%), severe sarcopenia; and 1139 (75.7%), no sarcopenia. Of the seven variables, advancing age was typically associated with an increasing prevalence of sarcopenia (odds ratio [OR] = 1.06-1.47, 95% confidence interval [CI] = 1.06-1.47). The results showed that household income (OR = 0.57, 95% CI = 0.33-0.98), education level (OR = 3.32, 95% CI = 1.09-10.07), and chronic diseases (OR = 0.34, 95% CI = 0.19-0.62) were significantly associated with the severe sarcopenia group. Physical activity scores were significantly associated with the diagnosed sarcopenia and severe sarcopenia groups. Participants with < 20 NRT were more likely to have diagnosed sarcopenia (OR = 5.55, 95% CI = 3.80-8.12) or severe sarcopenia (OR = 6.66, 95% CI = 4.13-10.76) than participants with > 20 NRT. The GOHAI score was associated with the diagnosed sarcopenia (OR = 5.55, 95% CI = 3.80-8.12) and severe sarcopenia (OR = 6.66, 95% CI = 4.13-10.78) groups. The MNA-SF score was associated with the different sarcopenia groups. CONCLUSIONS: Assessing early and improving lifestyle with respect to nutrition and oral health may be an effective way to reduce or delay the occurrence of sarcopenia.

Altered white matter microstructure in 22q11.2 deletion syndrome: a multisite diffusion tensor imaging study.

22q11.2 deletion syndrome (22q11DS)-a neurodevelopmental condition caused by a hemizygous deletion on chromosome 22-is associated with an elevated risk of psychosis and other developmental brain disorders. Prior single-site diffusion magnetic resonance imaging (dMRI) studies have reported altered white matter (WM) microstructure in 22q11DS, but small samples and variable methods have led to contradictory results. Here we present the largest study ever conducted of dMRI-derived measures of WM microstructure in 22q11DS (334 22q11.2 deletion carriers and 260 healthy age- and sex-matched controls; age range 6-52 years). Using harmonization protocols developed by the ENIGMA-DTI working group, we identified widespread reductions in mean, axial and radial diffusivities in 22q11DS, most pronounced in regions with major cortico-cortical and cortico-thalamic fibers: the corona radiata, corpus callosum, superior longitudinal fasciculus, posterior thalamic radiations, and sagittal stratum (Cohen's d's ranging from -0.9 to -1.3). Only the posterior limb of the internal capsule (IC), comprised primarily of corticofugal fibers, showed higher axial diffusivity in 22q11DS. 22q11DS patients showed higher mean fractional anisotropy (FA) in callosal and projection fibers (IC and corona radiata) relative to controls, but lower FA than controls in regions with predominantly association fibers. Psychotic illness in 22q11DS was associated with more substantial diffusivity reductions in multiple regions. Overall, these findings indicate large effects of the 22q11.2 deletion on WM microstructure, especially in major cortico-cortical connections. Taken together with findings from animal models, this pattern of abnormalities may reflect disrupted neurogenesis of projection neurons in outer cortical layers.

Large-scale mapping of cortical alterations in 22q11.2 deletion syndrome: Convergence with idiopathic psychosis and effects of deletion size.

The 22q11.2 deletion (22q11DS) is a common chromosomal microdeletion and a potent risk factor for psychotic illness. Prior studies reported widespread cortical changes in 22q11DS, but were generally underpowered to characterize neuroanatomic abnormalities associated with psychosis in 22q11DS, and/or neuroanatomic effects of variability in deletion size. To address these issues, we developed the ENIGMA (Enhancing Neuro Imaging Genetics Through Meta-Analysis) 22q11.2 Working Group, representing the largest analysis of brain structural alterations in 22q11DS to date. The imaging data were collected from 10 centers worldwide, including 474 subjects with 22q11DS (age = 18.2 ± 8.6; 46.9% female) and 315 typically developing, matched controls (age = 18.0 ± 9.2; 45.9% female). Compared to controls, 22q11DS individuals showed thicker cortical gray matter overall (left/right hemispheres: Cohen's d = 0.61/0.65), but focal thickness reduction in temporal and cingulate cortex. Cortical surface area (SA), however, showed pervasive reductions in 22q11DS (left/right hemispheres: d = -1.01/-1.02). 22q11DS cases vs. controls were classified with 93.8% accuracy based on these neuroanatomic patterns. Comparison of 22q11DS-psychosis to idiopathic schizophrenia (ENIGMA-Schizophrenia Working Group) revealed significant convergence of affected brain regions, particularly in fronto-temporal cortex. Finally, cortical SA was significantly greater in 22q11DS cases with smaller 1.5 Mb deletions, relative to those with typical 3 Mb deletions. We found a robust neuroanatomic signature of 22q11DS, and the first evidence that deletion size impacts brain structure. Psychotic illness in this highly penetrant deletion was associated with similar neuroanatomic abnormalities to idiopathic schizophrenia. These consistent cross-site findings highlight the homogeneity of this single genetic etiology, and support the suitability of 22q11DS as a biological model of schizophrenia.

Tract specific analysis in patients with sickle cell disease.

Sickle cell disease (SCD) is a hereditary blood disorder in which the oxygen-carrying hemoglobin molecule in red blood cells is abnormal. It affects numerous people in the world and leads to a shorter life span, pain, anemia, serious infections and neurocognitive decline. Tract-Specific Analysis (TSA) is a statistical method to evaluate white matter alterations due to neurocognitive diseases, using diffusion tensor magnetic resonance images. Here, for the first time, TSA is used to compare 11 major brain white matter (WM) tracts between SCD patients and age-matched healthy subjects. Alterations are found in the corpus callosum (CC), the cortico-spinal tract (CST), inferior fronto-occipital fasciculus (IFO), inferior longitudinal fasciculus (ILF), superior longitudinal fasciculus (SLF), and uncinated fasciculus (UNC). Based on previous studies on the neurocognitive functions of these tracts, the significant areas found in this paper might be related to several cognitive impairments and depression, both of which are observed in SCD patients.