High platelet-to-lymphocyte ratio is associated with poor prognosis in patients with unresectable intrahepatic cholangiocarcinoma receiving gemcitabine plus cisplatin

Background Several systemic inflammatory response (SIR) markers, including platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and albumin-to-globulin ratio (AGR), have emerged as prognostic markers in various cancers. The aim of this study was to explore the impact of SIR markers on the survival outcomes of unresectable intrahepatic cholangiocarcinoma (IHC) patients. Methods Patients with histologically confirmed, unresectable IHC treated with gemcitabine plus cisplatin (GP) chemotherapy in a single tertiary hospital from 2012 to 2016 were retrospectively reviewed. Progression-free survival (PFS) and overall survival (OS) were determined using unadjusted Kaplan-Meier and adjusted Cox-proportional-hazards analysis. Time-dependent receiver operating characteristic (ROC) analysis was performed to compare the performance of the SIR markers in predicting OS. Results A total of 137 patients received a median of six cycles (interquartile range [IQR], 3–11) of GP chemotherapy with a median observation time of 9.9 months (range, 1.8–54.7 months). The median PFS and OS of all patients were 7.8 months and 9.9 months, respectively. Among the SIR markers, high PLR (> 148) and high NLR (> 5) were associated with a short PFS (Hazard ratio [HR] 1.828, P = 0.006; HR 1.738, P = 0.030, respectively) and short OS (HR 2.332, P < 0.001; HR 2.273, P < 0.001, respectively). Low LMR (< 3.5) and low AGR (< 1.2) were associated with a short OS (HR 2.423, P < 0.001; HR 1.768, P = 0.002, respectively). In multivariable cox-regression analysis, high PLR (HR 1.766, P = 0.009) and distant lymph node (LN) metastasis (HR 2.085, P = 0.001) were associated with a short PFS. High PLR (HR 1.856, P = 0.002) was an independent predictor of a short OS, along with distant LN metastasis (HR 1.929; P < 0.001), low LMR (HR 1.691; P = 0.041), and low level of serum albumin (< 3.5 g/dL) (HR 1.632; P = 0.043). Time-dependent ROC analysis revealed that the area under the curve of PLR for predicting overall survival was greater than that of NLR, LMR, and AGR at most time points. Conclusions High PLR was an independent prognostic factor of a short PFS and OS in patients with unresectable IHC receiving GP chemotherapy.This study was supported by the Seoul National University College of Medicine Research Fund (2018)

Optimal timing of endoscopic retrograde cholangiopancreatography for acute cholangitis associated with distal malignant biliary obstruction

Background There is a lack of studies regarding the optimal timing for endoscopic retrograde cholangiopancreatography (ERCP) in patients with cholangitis caused by distal malignant biliary obstruction (MBO). This study aims to investigate the optimal timing of ERCP in patients with acute cholangitis associated with distal MBO with a naïve papilla. Methods A total of 421 patients with acute cholangitis, associated with distal MBO, were enrolled for this study. An urgent ERCP was defined as being an ERCP performed within 24 h following emergency room (ER) arrival, and early ERCP was defined as an ERCP performed between 24 and 48 h following ER arrival. We evaluated both 30-day and 180-day mortality as primary outcomes, according to the timing of the ERCP. Results The urgent ERCP group showed the lowest 30-day mortality rate (2.2%), as compared to the early and delayed ERCP groups (4.3% and 13.5%) (P < 0.001). The 180-day mortality rate was lowest in the urgent ERCP group, followed by early ERCP and delayed ERCP groups (39.4%, 44.8%, 60.8%; P = 0.006). A subgroup analysis showed that in both the primary distal MBO group, as well as in the moderate-to-severe cholangitis group, the urgent ERCP had significantly improved in both 30-day and 180-day mortality rates. However, in the secondary MBO and mild cholangitis groups, the difference in mortality rate between urgent, early, and delayed ERCP groups was not significant. Conclusions In patients with acute cholangitis associated with distal MBO, urgent ERCP might be helpful in improving the prognosis, especially in patients with primary distal MBO or moderate-to-severe cholangitis

Association between glycemic status and the risk of acute pancreatitis: a nationwide population-based study

Background Although diabetes is reportedly associated with the occurrence of acute pancreatitis (AP), the risk of AP according to the duration and severity of diabetes is not yet clear. We aimed to investigate the risk of AP based on glycemic status and the presence of comorbidities using a nationwide population-based study. Methods We enrolled 3,912,496 adults who underwent health examinations under the National Health Insurance Service in 2009. All participants were categorized by glycemic status as normoglycemic, impaired fasting glucose (IFG), or diabetes. Baseline characteristics and the presence of comorbidities at the time of health check-up were investigated, and the occurrence of AP was followed up until 31 December 2018. We estimated the adjusted hazard ratios (aHRs) for AP occurrence according to the glycemic status, duration of diabetes (new-onset, duration < 5 years, or ≥ 5 years), type and number of anti-diabetic medications, and presence of comorbidities. Results During the observation period of 32,116,716.93 person-years, 8,933 cases of AP occurred. Compared with normoglycemia, the aHRs (95% confidence interval) were 1.153 (1.097–1.212) in IFG, 1.389 (1.260–1.531) in new-onset diabetes, 1.634 (1.496–1.785) in known diabetes < 5 years, and 1.656 (1.513–1.813) in patients with known diabetes aged ≥ 5 years. The presence of comorbidities associated with diabetes severity had a synergistic effect on the relationship between diabetes and AP occurrence. Conclusion As glycemic status worsens, the risk of AP increases, and there is a synergistic effect when comorbidities coexist. To reduce the risk of AP, active control of factors that can cause AP should be considered in patients with long-standing diabetes and comorbidities

Molecular and polymeric films formed on silicon by solution-phase reactions

Thesis (Ph.D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2000.Includes bibliographical references.This thesis details studies of the chemical reactivity of silicon surfaces and the development of new reactions for manipulating its surface properties by the formation of covalently attached molecular and polymeric films. Silicon is the central material in modern electronic devices, and the ability to tailor its surface, particularly in a hydrogen-terminated form, at a molecular level has been desired. In this research, porous and crystalline silicon were examined as substrates, where the latter material can offer notable interesting luminescent properties. Chapters 2 and 3 discuss the formation of molecular films on hydrogen-terminated silicon surfaces by reactions using alcohols and Grignard and organolithium reagents. In the first reaction, alcohols formed alkoxy films to silicon surfaces via Si-0 bonds after reaction for 1-2 h at 40-90 °C. Alcohols were suggested to react with surface Si-Si bonds to cleave these bonds and produce Si-OR and Si-H species. In the second reaction, molecular films were obtained on silicon by exposing silicon substrates to Grignard and organolithium reagents at room temperature for 1-6 h and a quench with an anhydrous acid. A mechanism is proposed whereby the reagent alkyl anions cleaved surface Si-Si bonds and produced Si-R attachments anchored by Si-C bonds and an equivalent of silyl anions that were later quenched using an acid or an acyl halide. Both reactions caused little surface oxidation, and modified porous silicon samples retained their luminescent properties. Molecular films formed on crystalline silicon supports by these reactions exhibited a surfoce coverage of 50-90 % and moderate packing density. Chapters 4 and 5 describe the use of these thin molecular films for forming polymer films on crystalline silicon supports. In Chapter 4, a pyrrole-terminated molecular film was formed on a hydrogen-terminated silicon substrate using a pyrrole-terminated organolithium reagent. The electrochemical polymerization of pyrrole on the support produced polypyrrole films that were covalently attached to the substrate. The resulting polymer films demonstrated improved physical properties such as smooth and uniform surface morphology and strong adhesion to the substrate over those formed to native hydrogen-terminated silicon surfaces. Similarly, the junctions containing a modified silicon substrate exhibited enhanced electrical characteristics due to efficient charge transfer at the interface over those of an unmodified substrate. In Chapter 5, a norbomene-terminated molecular film was prepared on silicon bearing thin native oxide and used for a surface-initiated ring-opening metathesis polymerization (ROMP) process. In this strategy, a Ru-based ROMP catalyst was immobilized onto the modified silicon surface by reaction with a norbornenyl monolayer. Upon exposure to solutions of various norbornene-based monomers, the attached catalyst produced a series of grafted polymer films with control over thickness and chemical composition of the films. By combining this method with microcontact printing ([mu]CP), the procedure was used to generate patterned polymer films on silicon by simple solution-phase reactions.by Namyoung Kim.Ph.D

Advances in higher-order chromatin architecture: the move towards 4D genome

In eukaryotes, the genome is hierarchically packed inside the nucleus, which facilitates physical contact between cis-regulatory elements (CREs), such as enhancers and promoters. Accumulating evidence highlights the critical role of higher-order chromatin structure in precise regulation of spatiotemporal gene expression under diverse biological contexts including lineage commitment and cell activation by external stimulus. Genomics and imaging-based technologies, such as Hi-C and DNA fluorescence in situ hybridization (FISH), have revealed the key principles of genome folding, while newly developed tools focus on improvement in resolution, throughput and modality at single-cell and population levels, and challenge the knowledge obtained through conventional approaches. In this review, we discuss recent advances in our understanding of principles of higher-order chromosome conformation and technologies to investigate 4D chromatin interactions.11Nsciescopuskciothe

Spatial transcriptomics in neuroscience

Abstract The brain is one of the most complex living tissue types and is composed of an exceptional diversity of cell types displaying unique functional connectivity. Single-cell RNA sequencing (scRNA-seq) can be used to efficiently map the molecular identities of the various cell types in the brain by providing the transcriptomic profiles of individual cells isolated from the tissue. However, the lack of spatial context in scRNA-seq prevents a comprehensive understanding of how different configurations of cell types give rise to specific functions in individual brain regions and how each distinct cell is connected to form a functional unit. To understand how the various cell types contribute to specific brain functions, it is crucial to correlate the identities of individual cells obtained through scRNA-seq with their spatial information in intact tissue. Spatial transcriptomics (ST) can resolve the complex spatial organization of cell types in the brain and their connectivity. Various ST tools developed during the past decade based on imaging and sequencing technology have permitted the creation of functional atlases of the brain and have pulled the properties of neural circuits into ever-sharper focus. In this review, we present a summary of several ST tools and their applications in neuroscience and discuss the unprecedented insights these tools have made possible