Early detection has the potential to reduce cancer mortality, but an effective screening test must demonstrate asymptomatic cancer detection years before conventional diagnosis in a longitudinal study. In the Taizhou Longitudinal Study (TZL), 123,115 healthy subjects provided plasma samples for long-term storage and were then monitored for cancer occurrence. Here we report the preliminary results of PanSeer, a noninvasive blood test based on circulating tumor DNA methylation, on TZL plasma samples from 605 asymptomatic individuals, 191 of whom were later diagnosed with stomach, esophageal, colorectal, lung or liver cancer within four years of blood draw. We also assay plasma samples from an additional 223 cancer patients, plus 200 primary tumor and normal tissues. We show that PanSeer detects five common types of cancer in 88% (95% CI: 80–93%) of post-diagnosis patients with a specificity of 96% (95% CI: 93–98%), We also demonstrate that PanSeer detects cancer in 95% (95% CI: 89–98%) of asymptomatic individuals who were later diagnosed, though future longitudinal studies are required to confirm this result. These results demonstrate that cancer can be non-invasively detected up to four years before current standard of care.

There is increasing evidence showing that the dynamic changes in the gut microbiota can alter brain physiology and behavior. Cognition was originally thought to be regulated only by the central nervous system. However, it is now becoming clear that many non-nervous system factors, including the gut-resident bacteria of the gastrointestinal tract, regulate and influence cognitive dysfunction as well as the process of neurodegeneration and cerebrovascular diseases. Extrinsic and intrinsic factors including dietary habits can regulate the composition of the microbiota. Microbes release metabolites and microbiota-derived molecules to further trigger host-derived cytokines and inflammation in the central nervous system, which contribute greatly to the pathogenesis of host brain disorders such as pain, depression, anxiety, autism, Alzheimer’s diseases, Parkinson’s disease, and stroke. Change of blood–brain barrier permeability, brain vascular physiology, and brain structure are among the most critical causes of the development of downstream neurological dysfunction. In this review, we will discuss the following parts: Overview of technical approaches used in gut microbiome studies Microbiota and immunity Gut microbiota and metabolites Microbiota-induced blood–brain barrier dysfunction Neuropsychiatric diseases ■ Stress and depression ■ Pain and migraine ■ Autism spectrum disorders Neurodegenerative diseases ■ Parkinson’s disease ■ Alzheimer’s disease ■ Amyotrophic lateral sclerosis ■ Multiple sclerosis Cerebrovascular disease ■ Atherosclerosis ■ Stroke ■ Arteriovenous malformation Conclusions and perspectives

Causative gene mutations have been identified in about 2% of those with amyotrophic lateral sclerosis (ALS), often, but not always, when there is a strong family history. There is an assumption that there is a genetic component to all ALS, but genome-wide association studies have yet to produce a robustly replicated result. A definitive estimate of ALS heritability is therefore required to determine whether ongoing efforts to find susceptibility genes are worth while. The authors performed two twin studies, one population- and one clinic-based. The authors used structural equation modelling to perform a meta-analysis of data from these studies and an existing twin study to estimate ALS heritability, and identified 171 twin pairs in which at least one twin had ALS. Five monozygotic twin pairs were concordant-affected, and 44 discordant-affected. No dizygotic twin pairs were concordant-affected, and 122 discordant-affected. The heritability of sporadic ALS was estimated as 0.61 (0.38 to 0.78) with the unshared environmental component 0.39 (0.22 to 0.62). ALS has a high heritability, and efforts to find causative genes should continue.

Objective To accurately measure the incidence of gastric cancer among patients with gastric precancerous lesions, and to quantify the excess incidence in comparison with people with normal mucosa on endoscopy and a general population. Design Population based cohort study. Setting Population of Sweden using data from its national disease registers. Participants 405 172 patients who had gastric biopsy samples taken for non-malignant indications between 1979 and 2011. Main outcome measures Incidence of gastric cancer, reported separately for patients with different mucosal changes in biopsy samples. Standardised incidence ratios provided estimation of the relative risk, using the general Swedish population as reference; and hazard ratios were derived from Cox regression modelling for internal comparisons with patients with normal gastric mucosa. Results After excluding the first two years of follow-up, 1599 cases of gastric cancer were identified. The annual crude incidence of gastric cancer was 20×10⁻⁵ for those in the normal mucosa group (standardised incidence ratio 1.0), 42×10⁻⁵ for those with minor changes (1.5), 59×10⁻⁵ for the gastritis group (1.8), 100×10⁻⁵ for the atrophic gastritis group (2.8), 129×10⁻⁵ for the intestinal metaplasia group (3.4), and 263×10⁻⁵ for the dysplasia group (6.5). Cox regression modelling confirmed that excess risks increased monotonically with progressive severity of gastric lesions, with the highest hazard ratio of 10.9 (dysplasia versus normal mucosa, 95% confidence interval 7.7 to 15.4). The increased incidence was stable throughout the follow-up period, and the gaps between cumulative incidence curves grew continuously. Conclusions Among patients who undergo gastroscopy with biopsy for clinical indications, approximately 1 in 256 with normal mucosa, 1 in 85 with gastritis, 1 in 50 with atrophic gastritis, 1 in 39 with intestinal metaplasia, and 1 in 19 with dysplasia will develop gastric cancer within 20 years. These numbers, along with cost-benefit analyses, should guide future surveillance policies for these particular patient groups.