The role of brain somatic mutations in Alzheimer's disease (AD) is not well understood. Here, we perform deep whole-exome sequencing (average read depth 584×) in 111 postmortem hippocampal formation and matched blood samples from 52 patients with AD and 11 individuals not affected by AD. The number of somatic single nucleotide variations (SNVs) in AD brain specimens increases significantly with aging, and the rate of mutation accumulation in the brain is 4.8-fold slower than that in AD blood. The putatively pathogenic brain somatic mutations identified in 26.9% (14 of 52) of AD individuals are enriched in PI3K-AKT, MAPK, and AMPK pathway genes known to contribute to hyperphosphorylation of tau. We show that a pathogenic brain somatic mutation in PIN1 leads to a loss-of-function mutation. In vitro mimicking of haploinsufficiency of PIN1 aberrantly increases tau phosphorylation and aggregation. This study provides new insights into the genetic architecture underlying the pathogenesis of AD.

In 2019, the grading and staging system for neuroendocrine neoplasms (NENs) was significantly changed. In this study, we report the clinicopathological characteristics and surgical outcomes of patients with extrahepatic biliary NENs who underwent curative resection with or without adjuvant treatment.

The number of infrapopliteal runoff vessels seems to be one of the factors influencing arterial patency in patients who had undergone superficial femoral artery (SFA) angioplasty with stenting. However, the effectiveness of infrapopliteal runoff vessels in predicting patency during SFA angioplasty remains unclear. This study aimed to determine whether the number and quality of infrapopliteal runoff vessels affect the primary patency after SFA angioplasty with stenting in patients with claudication.

Advanced glycation end products (AGEs) have long been considered as potent molecules promoting neuronal cell death and contributing to neurodegenerative disorders such as Alzheimer's disease (AD). In this study, we demonstrate that AGE-albumin, the most abundant AGE product in human AD brains, is synthesized in activated microglial cells and secreted into the extracellular space. The rate of AGE-albumin synthesis in human microglial cells is markedly increased by amyloid-β exposure and oxidative stress. Exogenous AGE-albumin upregulates the receptor protein for AGE (RAGE) and augments calcium influx, leading to apoptosis of human primary neurons. In animal experiments, soluble RAGE (sRAGE), pyridoxamine or ALT-711 prevented Aβ-induced neuronal death in rat brains. Collectively, these results provide evidence for a new mechanism by which microglial cells promote death of neuronal cells through synthesis and secretion of AGE-albumin, thereby likely contributing to neurodegenerative diseases such as AD.

Postoperative delirium (POD) is a common complication that increases mortality and morbidity in older patients. This study aimed to evaluate the clinical significance of post-cholecystectomy delirium in older patients.

Emerging evidence has demonstrated that PIWI-interacting RNAs (piRNAs) play important roles in various physiological processes and contribute to cancer progression. Moreover, piRNAs and PIWI protein levels are associated with the prognosis and chemoresistance of various cancers. The limitations of biomarkers challenge early detection and monitoring of chemoresistance and cancer relapse.

Alzheimer's disease (AD) is the most common form of dementia; however, mechanisms and biomarkers remain unclear. Here, we examined hippocampal CA4 and dentate gyrus subfields, which are less studied in the context of AD pathology, in post-mortem AD and control tissue to identify possible biomarkers. We performed mass spectrometry-based proteomic analysis combined with label-free quantification for identification of differentially expressed proteins. We identified 4,328 proteins, of which 113 showed more than 2-fold higher or lower expression in AD hippocampi than in control tissues. Five proteins were identified as putative AD biomarkers (MDH2, PCLO, TRRAP, YWHAZ, and MUC19 isoform 5) and were cross-validated by immunoblotting, selected reaction monitoring, and MALDI imaging. We also used a bioinformatics approach to examine upstream signalling interactions of the 113 regulated proteins. Five upstream signalling (IGF1, BDNF, ZAP70, MYC, and cyclosporin A) factors showed novel interactions in AD hippocampi. Taken together, these results demonstrate a novel platform that may provide new strategies for the early detection of AD and thus its diagnosis.

Auditory fear conditioning is a well-characterized rodent learning model where a neutral auditory cue is paired with an aversive outcome to induce associative fear memory. The storage of long-term auditory fear memory requires long-term potentiation (LTP) in the lateral amygdala and de novo protein synthesis. Although many studies focused on individual proteins have shown their contribution to LTP and fear conditioning, non-biased genome-wide studies have only recently been possible with microarrays, which nevertheless fall short of measuring changes at the level of proteins. Here we employed quantitative proteomics to examine the expression of hundreds of proteins in the lateral amygdala in response to auditory fear conditioning. We found that various proteins previously implicated in LTP, learning and axon/dendrite growth were regulated by fear conditioning. A substantial number of proteins that were regulated by fear conditioning have not yet been studied specifically in learning or synaptic plasticity.

To identify meningioma-specific proteins, cerebrospinal fluid (CSF) from 4 patients with a meningioma and 4 patients with a non-brain tumorous lesion were analyzed.

Despite its limited benefits, operative site drainage after elective hepatectomy is routinely used. This study aimed to investigate the safety and effectiveness of left lateral sectionectomy without operative site drainage.

In ampullary adenocarcinoma cases, the clinical effects of 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) have not yet been well-studied, unlike other prognostic factors that have been reported till date. This study aimed to investigate the clinical impact of maximum standardized uptake value (SUVmax) in predicting the prognosis of ampullary adenocarcinoma.Thirty-eight patients who underwent pre-operative 18F-FDG PET/CT and curative-intent resection of ampullary adenocarcinoma at Pusan National University Hospital (Pusan, South Korea) between 2008 and 2017 were retrospectively analyzed in this study. We evaluated the clinicopathologic outcomes according to the SUVmax using univariate and multivariate Cox proportional hazard regression analyses and receiver operating characteristic analysis to arrive at a cutoff value.Lymph node metastasis was detected in 9 patients, and 15 patients experienced a recurrence during the follow-up period. Among 38 patients, 33 showed an increased FDG uptake by the main tumor. SUVmax of 4.55 was selected as a significant independent predictive factor for patient survival along with poor tumor differentiation and high neutrophil-to-lymphocyte ratio in multivariate analysis (P = .016, hazard ratio = 5.040). Patients with SUVmax under 4.55 exhibited significantly longer overall survival than the rest (<4.55 vs ≥4.55), and the 5-year overall survival was 82.8% versus 57.4% (P = .049).SUVmax of 4.55 on 18F-FDG PET/CT could be a predictive factor for tumor biology and long-term survival in patients with ampullary adenocarcinoma. Nevertheless, considering the cost aspect and its limited prognostic effect, this study seems to require more patient and multicenter studies.