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Large-scale optical neutrino and dark-matter detectors rely on large-area photomultiplier tubes (PMTs) for cost-effective light detection. The new R14688-100 8-inch PMT developed by Hamamatsu provides state-of-the-art timing resolution of around 1 ns (FWHM), which can help improve vertex reconstruction and enable Cherenkov and scintillation light separation in scintillation-based detectors. This PMT also provides excellent charge resolution, allowing for precision photoelectron counting and improved energy reconstruction. The Eos experiment is the first large-scale optical detector to utilize these PMTs. In this manuscript we present a characterization of the R14688-100 single photoelectron response, such as the transit-time spreads, the dark-rates, and the afterpulsing. The single photoelectron response measurements are performed for the 206 PMTs that will be used in Eos.

Somatostatin analogues have recently been used as therapeutic targets for metastatic or surgically unresectable gastroenteropancreatic (GEP) neuroendocrine tumors (NETs), and associated somatostatin receptor (SSTR) expression has been well demonstrated in most GEP NETs, with the exception of rectal NETs. SSTR2 immunohistochemical expressions were evaluated in 350 surgically or endoscopically resected rectal NETs and compared to clinicopathologic factors. SSTR2 expression was observed in 234 (66.9%) rectal NET cases and associated tumors with smaller size (p = 0.001), low pT classification (p = 0.030), low AJCC tumor stage (p = 0.012), and absence of chromogranin expression (p = 0.009). Patients with rectal NET and SSTR2 expression had significantly better overall survival than those without SSTR2 expression both by univariable (p = 0.006) and multivariable (p = 0.014) analyses. In summary, approximately two-thirds of rectal NETs expressed SSTR2. SSTR2 expression was significantly associated with favorable behavior and good overall survival in patients with rectal NETs. Furthermore, SSTR2 expression can be used as prognostic factors. When metastatic disease occurs, SSTR2 expression can be used a possible target for somatostatin analogues.

Background In this randomized phase II study, we evaluated the efficacy and safety of sorafenib in combination with capecitabine and cisplatin (XP) as first‐line chemotherapy in advanced gastric cancer. Patients and Methods Patients with metastatic gastric or gastroesophageal junction adenocarcinoma were randomized (1:1) to receive either sorafenib plus XP (S + XP) or XP alone. In cases of disease progression in the XP arm, crossover to sorafenib alone was allowed. The primary endpoint was progression‐free survival (PFS). The secondary endpoints included overall survival (OS), response rates, safety profiles, and biomarkers, and the response rates and PFS with secondline sorafenib alone after progression in the XP arm. Results Between Jan 2011 and Feb 2013, a total of 195 patients were accrued (97 in the S + XP arm and 98 in the XP alone arm). The overall response rate was 54% with S + XP, and 52% with XP alone (p = 0.83). With a median follow‐up of 12.6 months (range, 0.1–29.2), the median PFS assessed by independent review was 5.6 months in the S + XP arm and 5.3 months in the XP arm (hazard ratio [HR] 0.92, 95% confidence interval [CI] 0.67–1.27, p = 0.61). Overall survival was not different between the two arms (median 11.7 vs. 10.8 months; HR 0.93, 95% CI 0.65–1.31, p = 0.66). Frequencies of grade 3/4 toxicities were similar between the S + XP and XP alone arms, except for neutropenia (21% vs. 37%), anorexia (0% vs. 5%), and hand‐foot skin reaction (7% vs. 1%). Among 51 patients who crossed over to sorafenib alone after disease progression in the XP arm, there was no objective response and their median PFS was 1.3 months (95% CI, 1.2–1.7). Conclusion The addition of sorafenib to XP chemotherapy was safe but not more effective than XP alone for first‐line treatment of metastatic gastric cancer. In this randomized phase II study, we evaluated the efficacy and safety of sorafenib in combination with capecitabine and cisplatin (XP) as first‐line chemotherapy in advanced gastric cancer. The combination of sorafenib and XP was feasible and well tolerated, but it did not show any differences in efficacy outcomes compared with standard XP. Further investigation of this combination regimen is not warranted in GC, at least in the first‐line setting, if patients are not selected by definite biomarkers.

Peucedanum japonicum (Umbelliferae) is widely distributed throughout Southeast Asian countries. The root of this plant is used in traditional medicine to treat colds and pain, whereas the young leaves are considered an edible vegetable. In this study, the differences in coumarin profiles for different parts of P. japonicum including the flowers, roots, leaves, and stems were compared using ultra-performance liquid chromatography time-of-flight mass spectrometry. Twenty-eight compounds were tentatively identified, including three compounds found in the genus Peucedanum for the first time. Principal component analysis using the data set of the measured mass values and intensities of the compounds exhibited distinct clustering of the flower, leaf, stem, and root samples. In addition, their anticancer activities were screened using an Aldo–keto reductase (AKR)1C1 assay on A549 human non-small-cell lung cancer cells and the flower extract inhibited AKR1C1 activity. Based on these results, seven compounds were selected as potential markers to distinguish between the flower part versus the root, stem, and leaf parts using an orthogonal partial least-squares discriminant analysis. This study is the first to provide information on the comparison of coumarin profiles from different parts of P. japonicum as well as their AKR1C1 inhibitory activities. Taken together, the flowers of P. japonicum offer a new use related to the efficacy of overcoming anticancer drug resistance, and may be a promising source for the isolation of active lead compounds.

Background Activation of NADPH oxidase (PHOX) plays a critical role in mediating dopaminergic neuroinflammation. In the present study, we investigated the role of PHOX in methamphetamine (MA)-induced neurotoxic and inflammatory changes in mice. Methods We examined changes in mitogen-activated protein kinases (MAPKs), mitochondrial function [i.e., mitochondrial membrane potential, intramitochondrial Ca 2+ accumulation, mitochondrial oxidative burdens, mitochondrial superoxide dismutase expression, and mitochondrial translocation of the cleaved form of protein kinase C delta type (cleaved PKCδ)], microglial activity, and pro-apoptotic changes [i.e., cytosolic cytochrome c release, cleaved caspase 3, and terminal deoxynucleotidyl transferase dUDP nick-end labeling (TUNEL) positive populations] after a neurotoxic dose of MA in the striatum of mice to achieve a better understanding of the effects of apocynin, a non-specific PHOX inhibitor, or genetic inhibition of p47phox (by using p47phox knockout mice or p47phox antisense oligonucleotide) against MA-induced dopaminergic neurotoxicity. Results Phosphorylation of extracellular signal-regulated kinases (ERK1/2) was most pronounced out of MAPKs after MA. We observed MA-induced phosphorylation and membrane translocation of p47phox in the striatum of mice. The activation of p47phox promoted mitochondrial stresses followed by microglial activation into the M1 phenotype, and pro-apoptotic changes, and led to dopaminergic impairments. ERK activated these signaling pathways. Apocynin or genetic inhibition of p47phox significantly protected these signaling processes induced by MA. ERK inhibitor U0126 did not exhibit any additional positive effects against protective activity mediated by apocynin or p47phox genetic inhibition, suggesting that ERK regulates p47phox activation, and ERK constitutes the crucial target for apocynin-mediated inhibition of PHOX activation. Conclusions Our results indicate that the neuroprotective mechanism of apocynin against MA insult is via preventing mitochondrial burdens, microglial activation, and pro-apoptotic signaling process by the ERK-dependent activation of p47phox.

BackgroundElevation of serum ferritin levels is frequently observed in non-alcoholic fatty liver disease (NAFLD) patients. Our study aims to examine the association between serum ferritin levels and NAFLD in Korean population.Methods and resultsA total of 25,597 participants were selected from Korean National Health and Nutritional Examination Surveys 2007–2012. The NAFLD liver fat score (NLFS) was used to define NAFLD. Elevation of ALT levels was defined as ALT level > 40 IU/L for male and ALT level > 31 IU/L for female. Multiple logistic regression was used to examine the association of serum ferritin levels and NAFLD by sex. After adjusting for multiple covariates, the ORs (95% CI) of the elevated ALT levels were 1.56 (95% CI: 1.17–2.07), 1.84 (95% CI: 1.39–2.45), and 4.08 (95% CI: 3.08–5.40) for the second, third and fourth serum ferritin quartiles in male (p for trend < 0.01), 1.67 (95% CI: 1.24–2.23), 2.23 (95% CI: 1.68–2.96), and 5.72 (95% CI: 4.32–7.60) for the second, third and fourth serum ferritin quartiles in female (p for trend < 0.01). Serum ferritin levels were also significantly associated with NAFLD and liver fibrosis both in male and female.ConclusionsElevation of serum ferritin level is significantly associated with NAFLD and blood ALT elevation in Korean general population.

BackgroundSystemic inflammation is associated with survival outcomes in colon cancer. However, it is not well-known which systemic inflammatory marker is a powerful prognostic marker in patients with colon cancer.MethodsA total of 4535 colon cancer patients were included in this study. We developed a novel prognostic index using a robust combination of seven systemic inflammation-associated blood features of the discovery set. The predictability and generality of the novel prognostic index were evaluated in the discovery, validation and replication sets.ResultsAmong all combinations, the combination of albumin and monocyte count was the best candidate expression. The final formula of the proposed novel index is named the Prognostic Immune and Nutritional Index (PINI). The concordance index of PINI for overall and progression-free survival was the highest in the discovery, validation and replication sets compared to existing prognostic inflammatory markers. PINI was found to be a significant independent prognostic factor for both overall and progression-free survival.ConclusionsPINI is a novel prognostic index that has improved discriminatory power in colon cancer patients and appears to be superior to existing prognostic inflammatory markers. PINI can be utilised for decision-making regarding personalised treatment as the complement of the TNM staging system.

Background: Liposomal irinotecan (nal-IRI) plus 5-fluorouracil and leucovorin (5-FU/LV) was effective and well-tolerated in patients with metastatic pancreatic adenocarcinoma (mPAC) that progressed on gemcitabine-based therapy in the global NAPOLI-1 trial. Real-world data may further clarify the outcomes and safety profile of nal-IRI + 5-FU/LV in clinical practice. Methods: This retrospective analysis included patients with mPAC who received nal-IRI + 5-FU/LV following gemcitabine-based therapy under a Managed Access Program in Korea. Results: From January 2017 to April 2018, 86 patients across 10 institutions received nal-IRI + 5-FU/LV (median age, 61 years; 60% male; ECOG performance status, 0–1). A total of 35 (41%) and 51 (59%) patients had received less than two and two or more lines of chemotherapy before inclusion, respectively. At a median follow up of 6.4 months, median overall survival (OS) was 9.4 months (95% confidence interval [CI] 7.4–11.4) and median progression-free survival (PFS) was 3.5 months (95% CI 1.3–5.7). Six-month OS and PFS rates were 65.1% and 37.5%, respectively. Objective response and disease control rates were 10% and 55%, respectively. Most common grade 3–4 toxicities were neutropenia (37.2%), nausea (10.5%), vomiting (9.3%), anorexia (8.1%) and diarrhoea (4.7%). Conclusion: Real-life data for Korean patients indicate that, consistent with NAPOLI-1, nal-IRI + 5-FU/LV is effective and well-tolerated in patients with mPAC that progressed on gemcitabine-based therapy.

BackgroundSelf-expanding metallic stenting (SEMS) is usual for the temporary resolution of obstructive left-sided colorectal cancer (CRC) as a bridge to elective surgery. However, there is no consensus regarding adequate time intervals from stenting to radical surgery. The aim of this study was to identify the optimal time interval that results in favorable short- and long-term outcomes.MethodsData on patients with obstructive left-sided CRC who underwent elective radical surgery after clinically successful SEMS deployment in five tertiary referral hospitals from 2004 to 2016 were analyzed, retrospectively. An inverse probability treatment-weighted propensity score analysis was used to minimize bias. Postoperative short- and long-term outcomes were compared between two groups: an early surgery (within 8 days) group and delayed surgery (after 8 days) group.ResultsOf 311 patients, 148 (47.6%) underwent early and 163 (52.4%) underwent delayed surgery. The median surgery interval was 9.0 days. After adjustment, the groups had similar patient and tumor characteristics. In terms of short-term outcomes, there was no difference in hospitalization length or postoperative complications. No deaths were observed. With a median follow-up of 71.0 months, no significant difference was observed between the groups in 5-year overall survival (early vs. delayed surgery: 79.6% vs. 71.3%, P = 0.370) and 5-year disease-free survival (early vs. delayed surgery: 59.1% vs. 60.4%, P = 0.970).ConclusionsIn obstructive left-sided CRC, the time interval between SEMS and radical surgery did not significantly influence short- and long-term outcomes. Therefore, early surgery after SEMS could be suggested if there is no reason to postpone surgery for preoperative medical optimization.

Background: FOLFIRINOX (fluorouracil, folinic acid, irinotecan plus oxaliplatin) is an effective standard first-line treatment option for advanced pancreatic ductal adenocarcinoma (PDAC). There is no clear consensus on the second-line treatment following progression on FOLFIRINOX. In this multicenter retrospective analysis, we evaluated the efficacy and tolerability of second-line nab-P/Gem (nab-paclitaxel and gemcitabine) after progression on FOLFIRNOX in PDAC. Methods: Patients with unresectable or metastatic PDAC who received nab-P/Gem after progression on FOLFIRINOX between February 2016 and February 2019 were identified from five referral cancer centers in South Korea. Baseline characteristics, treatment history, survival outcomes, and toxicity profile were obtained retrospectively from medical records. Results: A total of 102 patients treated with second-line nab-P/Gem for advanced PDAC after progression on FOLFIRINOX were included. At the time of nab-P/Gem, the median age was 60 years, with males comprising 49.0%, and most (75.5%) had metastatic disease. Patients received a median of three cycles (range 1–12) of nab-P/Gem. The median overall survival (OS) and progression-free survival (PFS) from the start of second-line nab-P/Gem therapy were 9.8 (95% CI, 8.9–10.6) and 4.6 months (3.7–5.5), respectively. A partial response was achieved in 8.5%, and the disease control rate was 73.6%. From the start of first-line FOLFIRIOX, the OS1+2 and PFS1+2 were 20.9 (15.7–26.1) and 13.9 (10.8–17.0) months, respectively, with a 2-year survival rate of 45.1%. There was no treatment-related mortality and grade ⩾3 toxicity was observed in 60.2%. Conclusion: Our results showed that nab-P/Gem was an effective and tolerable second-line treatment option in medically fit patients with advanced PDAC who progressed on first-line FOLFIRNOX. ClinicalTrials.gov identifier: NCT04133155