Imaging Alzheimer's genetic risk using Diffusion MRI: a systematic review

Diffusion magnetic resonance imaging (dMRI) is an imaging technique which probes the random motion of water molecules in tissues and has been widely applied to investigate changes in white matter microstructure in Alzheimer’s Disease. This paper aims to systematically review studies that examined the effect of Alzheimer’s risk genes on white matter microstructure. We assimilated findings from 37 studies and reviewed their diffusion pre-processing and analysis methods. Most studies estimate the diffusion tensor (DT) and compare derived quantitative measures such as fractional anisotropy and mean diffusivity between groups. Those with increased AD genetic risk are associated with reduced anisotropy and increased diffusivity across the brain, most notably the temporal and frontal lobes, cingulum and corpus callosum. Structural abnormalities are most evident amongst those with established Alzheimer’s Disease. Recent studies employ signal representations and analysis frameworks beyond DT MRI but show that dMRI overall lacks specificity to disease pathology. However, as the field advances, these techniques may prove useful in pre-symptomatic diagnosis or staging of Alzheimer’s disease

Loss of p53 Attenuates the Contribution of IL-6 Deletion on Suppressed Tumor Progression and Extended Survival in Kras-Driven Murine Lung Cancer

Interleukin-6 (IL-6) is involved in lung cancer tumorigenesis, tumor progression, metastasis, and drug resistance. Previous studies show that blockade of IL-6 signaling can inhibit tumor growth and increase drug sensitivity in mouse models. Clinical trials in non-small cell lung cancer (NSCLC) reveal that IL-6 targeted therapy relieves NSCLC-related anemia and cachexia, although other clinical effects require further study. We crossed IL-6-/- mice with KrasG12D mutant mice, which develop lung tumors after activation of mutant KrasG12D, to investigate whether IL-6 inhibition contributes to tumor progression and survival time in vivo. KrasG12D; IL-6-/- mice exhibited increased tumorigenesis, but slower tumor growth and longer survival, than KrasG12D mice. Further, in order to investigate whether IL-6 deletion contributes to suppression of lung cancer metastasis, we generated KrasG12D; p53flox/flox; IL-6-/- mice, which developed lung cancer with a trend for reduced metastases and longer survival than KrasG12D; p53flox/flox mice. Tumors from KrasG12D; IL-6-/- mice showed increased expression of TNFα and decreased expression of CCL-19, CCL-20 and phosphorylated STAT3 (pSTAT3) than KrasG12D mice; however, these changes were not present between tumors from KrasG12D; p53flox/flox; IL-6-/- and KrasG12D; p53flox/flox mice. Upregulation of pSTAT3 and phosphorylated AKT (pAKT) were observed in KrasG12D tumors with p53 deletion. Taken together, these results indicate that IL-6 deletion accelerates tumorigenesis but delays tumor progression and prolongs survival time in a Kras-driven mouse model of lung cancer. However, these effects can be attenuated by p53 deletion

Emotions, COVID-19 related thoughts and satisfaction with life during the critical period from control to relaxation

IntroductionIn the context of declining mortality rates and increasing infectivity, it has become unavoidable for the majority of individuals to experience a COVID-19 infection at some point. This study aimed to investigate the psychological well-being of the general population during China’s transition period from strict control measures to relaxed policies in COVID-19 prevention and control, as well as the impact of COVID-19 related thoughts on emotion and life satisfaction during widespread infections.MethodsA cross-sectional study was conducted involving a sample size of 1578 participants. Participants completed self-report questionnaires assessing positive and negative emotions, thoughts about COVID-19, and satisfaction with life. Demographic characteristics such as sex, age, and education level were controlled for in the analysis.ResultsThe findings revealed that individuals who had been infected with COVID-19 (specifically the Omicron variant BA.5.2 or BF.7) reported lower levels of positive emotions compared to those who were uninfected or had recovered from the infection. There was a significant relationship between COVID-19-related thoughts, emotions, and life satisfaction. Positive COVID-19 related thoughts were found to mediate the relationship between negative emotions and satisfaction with life.DiscussionThis study represents a comprehensive examination conducted in China, focusing on assessing the impact of the COVID-19 pandemic on the general population during the critical transition period from control to relaxation. Throughout this period, the number of infections experienced fluctuations, initially rising but eventually declining over a one-month span. In such a momentous historical period, maintaining a positive perspective on COVID-19 and its management becomes paramount in enhancing the emotional well-being, life satisfaction and overall well-being of individuals

Research on the Implementation Path of Whole Grain Food Consumption from the Perspective of All-encompassing Approach to Food

The consumption of whole grain foods has positive significance for reducing grain loss and enhancing national health, which is a crucial direction for future developments in the food industry. However, current whole grain consumption in China falls far below recommended levels. This study analyzes the overall quantity, structure, and policy environment of whole grain food consumption in major countries across North America, Europe, Asia, and Africa. It analyzes key factors influencing whole grain food consumption from the aspects of products, consumers, market and policy. In conclusion, great efforts should be made to raise consumer awareness regarding whole grain consumption, advance the processing technology of whole grain foods, and foster nutrition-oriented agriculture through policy initiatives. In this way, the way toward increased whole grain food consumption can be paved and the growth of the whole grain food industry can be promoted

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types