Contaminated consignment simulation to support risk-based inspection design.

Invasive nonnative plant pests can cause extensive environmental and economic damage and are very difficult to eradicate once established. Phytosanitary inspections that aim to prevent biological invasions by limiting movement of nonnative plant pests across borders are a critical component of the biosecurity continuum. Inspections can also provide valuable information about when and where plant pests are crossing national boundaries. However, only a limited portion of the massive volume of goods imported daily can be inspected, necessitating a highly targeted, risk-based strategy. Furthermore, since inspections must prioritize detection and efficiency, their outcomes generally cannot be used to make inferences about risk for cargo pathways as a whole. Phytosanitary agencies need better tools for quantifying pests going undetected and designing risk-based inspection strategies appropriate for changing operational conditions. In this research, we present PoPS (Pest or Pathogen Spread) Border, an open-source consignment inspection simulator for measuring inspection outcomes under various cargo contamination scenarios to support recommendations for inspection protocols and estimate pest slippage rates. We used the tool to estimate contamination rates of historical interception data, quantify tradeoffs in effectiveness and workload for inspection strategies, and identify vulnerabilities in sampling protocols as changes in cargo configurations and contamination occur. These use cases demonstrate how this simulation approach permits testing inspection strategies and measuring quantities that would otherwise be impossible in a field-based setting. This work represents the first steps toward a decision support tool for creating dynamic inspection protocols that respond to changes in available resources, workload, and commerce trends.

Iteratively forecasting biological invasions with PoPS and a little help from our friends.

Ecological forecasting has vast potential to support environmental decision making with repeated, testable predictions across management-relevant timescales and locations. Yet resource managers rarely use co-designed forecasting systems or embed them in decision making. Although prediction of planned management outcomes is particularly important for biological invasions to optimize when and where resources should be allocated, spatial-temporal models of spread typically have not been openly shared, iteratively updated, or interactive to facilitate exploration of management actions. We describe a species-agnostic, open-source framework - called the Pest or Pathogen Spread (PoPS) Forecasting Platform - for co-designing near-term iterative forecasts of biological invasions. Two case studies are presented to demonstrate that iterative calibration yields higher forecast skill than using only the earliest-available data to predict future spread. The PoPS framework is a primary example of an ecological forecasting system that has been both scientifically improved and optimized for real-world decision making through sustained participation and use by management stakeholders.

A cross-sectional study on metabolic similarities and differences between inpatients with schizophrenia and those with mood disorders.

BACKGROUND: One of the main causes of death in psychiatric patients is cardiovascular diseases which are closely related with lifestyle-related diseases. Psychiatric disorders include schizophrenia and mood disorders, whose symptoms and treatment medicines are different, suggesting that they might have different metabolic disorders. Thus, we studied the differences of lifestyle-related diseases between schizophrenia and mood disorders in Japan. METHODS: This cross-sectional study was performed from 2015 to 2017. Study participants were 189 Japanese hospitalized patients (144 schizophrenia group, 45 mood disorders group) in the department of psychiatry at Kohnodai hospital. We examined physical disorders, metabolic status of glucose and lipid, estimated glomerular filtration rate (eGFR) and brain magnetic resonance imaging. We compared these data between schizophrenia and mood disorders groups using analysis of covariance or logistic regression analysis. In comparisons between inpatients with schizophrenia or mood disorders group and the standard, we quoted 'The National Health and Nutrition Survey in Japan 2015' by Ministry of Health, Labor and Welfare as the standard. RESULTS: eGFR and prevalence of smoking were significantly lower in patients with mood disorder group than those with schizophrenia group by adjustment for age. In comparisons between patients with schizophrenia group or mood disorders group and each standard, the ratio of silent brain infarction (SBI) and cerebral infarction were significantly high in both groups. Schizophrenia group showed significantly higher prevalence of diabetes, low high-density lipoprotein (HDL) cholesterolemia, metabolic syndrome and smoking than the standard. Mood disorders group had significantly high prevalence of low HDL-cholesterolemia compared with the standard. Fasting blood glucose and HbA1c were significantly higher in schizophrenia group and female mood disorders group than the standard. Female mood disorders group had significantly decreased eGFR with increased ratio of eGFR < 60 ml/min than the standard. CONCLUSIONS: Participants of both groups had increased ratio of SBI and cerebral infarction, accompanied with glucose and lipid disorders. Compared with schizophrenia group, mood disorders group showed significantly low eGFR and prevalence of smoking.

Fucosyltransferase 8 plays a crucial role in the invasion and metastasis of pancreatic ductal adenocarcinoma.

PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer. It is an aggressive malignancy associated with poor prognosis because of recurrence, metastasis, and treatment resistance. Aberrant glycosylation of cancer cells triggers their migration and invasion and is considered one of the most important prognostic cancer biomarkers. The current study aimed to identify glycan alterations and their relationship with the malignant potential of PDAC. METHODS: Using a lectin microarray, we evaluated glycan expression in 62 PDAC samples. Expression of fucosyltransferase 8 (FUT8), the only enzyme catalyzing core fucosylation, was investigated by immunohistochemistry. The role of FUT8 in PDAC invasion and metastasis was confirmed using an in vitro assay and a xenograft peritoneal metastasis mouse model. RESULTS: The microarray data demonstrated that core fucose-binding lectins were significantly higher in carcinoma than in normal pancreatic duct tissues. Similarly, FUT8 protein expression was significantly higher in carcinoma than in normal pancreatic duct tissues. High FUT8 protein expression was significantly associated with lymph-node metastases and relapse-free survival. FUT8 knockdown significantly reduced the invasion in PDAC cell lines and impaired peritoneal metastasis in the xenograft model. CONCLUSIONS: The findings of this study provide evidence that FUT8 plays a pivotal role in PDAC invasion and metastasis and might be a therapeutic target for this disease.

[Automated Classification of Calcification and Stent on Computed Tomography Coronary Angiography Using Deep Learning].

In computed tomography coronary angiography (CTCA), calcification and stent make it difficult to evaluate intravascular lumen. This is a cause of low positive-predictive value of coronary stenosis. Therefore, it is expected to develop a computer-aided diagnosis (CAD) system that can automatically detect stenosis in coronary arteries. The purpose of this study is to automatically recognize calcifications or stents in coronary arteries and classify them from the normal coronary artery in CTCA. We used 4960 coronary-cross-sectional images, which consisted of 1113 images with calcification, 1353 images with a stent, and 2494 normal artery images. These images were automatically classified using the deep convolutional neural network (LeNet, AlexNet, and GoogLeNet). The classification accuracy of LeNet, AlexNet, and GoogLeNet were 58.4%, 75.9%, and 81.3%, respectively. The proposed method would be a fundamental technique of CAD in CTCA.

Development of diabetes in a familial amyotrophic lateral sclerosis patient carrying the I113T SOD1 mutation. Case Report.

Familial amyotrophic lateral sclerosis (ALS) are caused by the mutations in the copper (Cu) / zinc (Zn) superoxide dismutase 1 (SOD1) gene. SOD1 has been reported to play a critical role in glucose metabolism in yeast and cell models, and mice. However, effects of SOD1 for glucose metabolism in humans remain unknown. A 72-year-old woman was admitted to our hospital due to hyperglycemia. She showed severe muscle atrophy and visceral fat accumulation due to ALS. Her serum free fatty acids levels elevated and serum Cu and Zn levels decreased. Her two younger brothers and aunt were also diagnosed as having ALS, and DNA sequence analysis revealed the presence of the I113T SOD1 mutation. She may have developed diabetes due to SOD1 dysfunction by the I113T SOD1 mutation, and severe insulin resistance induced by ALS. The I113T SOD1 mutation may be the causative factor for diabetes as well as familial ALS.

1 W single-frequency Tm-doped ZBLAN fiber MOPA around 810 nm.

We demonstrate a tunable narrow-linewidth fiber MOPA system around 810 nm for the light source of the Sr optical lattice clock. The coherent cw light source with a wavelength of 813.42 nm was generated by a combination of a narrow linewidth external-cavity laser diode and a Tm-doped ZBLAN fiber amplifier, which was upconversion-pumped by an Yb-doped fiber laser at 1064 nm. The maximum output power of 1.1 W was obtained with the launched power of 17 W, which is the highest power obtained from a Tm-doped fiber amplifier ever reported.

GIATAR: a Spatio-temporal Dataset of Global Invasive and Alien Species and their Traits.

Monitoring and managing the global spread of invasive and alien species requires accurate spatiotemporal records of species presence and information about the biological characteristics of species of interest including life cycle information, biotic and abiotic constraints and pathways of spread. The Global Invasive and Alien Traits And Records (GIATAR) dataset provides consolidated dated records of invasive and alien presence at the country-scale combined with a suite of biological information about pests of interest in a standardized, machine-readable format. We provide dated presence records for 46,666 alien taxa in 249 countries constituting 827,300 country-taxon pairs in locations where the taxon's invasive status is either alien, invasive, or unknown, joined with additional biological information for thousands of taxa. GIATAR is designed to be quickly updateable with future data and easy to integrate into ongoing research on global patterns of alien species movement using scripts provided to query and analyze data. GIATAR provides crucial data needed for researchers and policymakers to compare global invasion trends across a wide range of taxa.

Sperm-specific histone H1 in highly condensed sperm nucleus of Sargassum horneri.

Spermatogenesis is one of the most dramatic changes in cell differentiation. Remarkable chromatin condensation of the nucleus is observed in animal, plant, and algal sperm. Sperm nuclear basic proteins (SNBPs), such as protamine and sperm-specific histone, are involved in chromatin condensation of the sperm nucleus. Among brown algae, sperm of the oogamous Fucales algae have a condensed nucleus. However, the existence of sperm-specific SNBPs in Fucales algae was unclear. Here, we identified linker histone (histone H1) proteins in the sperm and analyzed changes in their gene expression pattern during spermatogenesis in Sargassum horneri. A search of transcriptomic data for histone H1 genes in showed six histone H1 genes, which we named ShH1.1a, ShH1b, ShH1.2, ShH1.3, ShH1.4, and ShH1.5. Analysis of SNBPs using SDS-PAGE and LC-MS/MS showed that sperm nuclei contain histone ShH1.2, ShH1.3, and ShH1.4 in addition to core histones. Both ShH1.2 and ShH1.3 genes were expressed in the vegetative thallus and the male and female receptacles (the organs producing antheridium or oogonium). Meanwhile, the ShH1.4 gene was expressed in the male receptacle but not in the vegetative thallus and female receptacles. From these results, ShH1.4 may be a sperm-specific histone H1 of S. horneri.

SAFARIS: a spatial analytic framework for pest forecast systems.

Non-native pests and diseases pose a risk of economic and environmental damage to managed and natural U.S. forests and agriculture. The U.S. Department of Agriculture (USDA) Animal and Plant Health Inspection Service (APHIS) Plant Protection and Quarantine (PPQ) protects the health of U.S. agriculture and natural resources against invasive pests and diseases through efforts to prevent the entry, establishment, and spread of non-native pests and diseases. Because each pest or disease has its own idiosyncratic characteristics, analyzing risk is highly complex. To help PPQ better respond to pest and disease threats, we developed the Spatial Analytic Framework for Advanced Risk Information Systems (SAFARIS), an integrated system designed to provide a seamless environment for producing predictive models. SAFARIS integrates pest biology information, climate and non-climate data drivers, and predictive models to provide users with readily accessible and easily customizable tools to analyze pest and disease risks. The phenology prediction models, spread forecasting models, and other climate-based analytical tools in SAFARIS help users understand which areas are suitable for establishment, when surveys would be most fruitful, and aid in other analyses that inform decision-making, operational efforts, and rapid response. Here we introduce the components of SAFARIS and provide two use cases demonstrating how pest-specific models developed with SAFARIS tools support PPQ in its mission. Although SAFARIS is designed to address the needs of PPQ, the flexible, web-based framework is publicly available, allowing any user to leverage the available data and tools to model pest and disease risks.

Colloid Carcinoma Arising in an Intestinal-Type Intraductal Papillary Mucinous Neoplasm with High-Grade Dysplasia Appearing as Signet-Ring Cells of the Pancreas by Serial Pancreatic Juice Aspiration Cytology: A Case Report.

We report a case of colloid carcinoma (CC) arising from an intestinal-type intraductal papillary mucinous neoplasm with high-grade dysplasia (IPMNHGD) of the pancreas, diagnosed with serial pancreatic juice aspiration cytological examination (SPACE). A rapidly growing intraductal papillary mucinous neoplasm (IPMN) in a 71-year-old Japanese man accelerated his hospitalization in our institute. Clinically, a large, ruptured pancreatic cyst was suspected. Cytologically, several mucin-positive signet-ring cells were scattered in the inflammatory, necrotic, or mucinous background. Signet-ring cells in cell block specimens were immunoreactive for MUC2, MUC5AC, maspin, S100P, and claudin-18. The final cytologic diagnosis was CC arising in an intestinal-type IPMNHGD with intraperitoneal penetration. The patient died two months after an explorative laparotomy. The cytologic diagnosis was achieved through SPACE, and the presence of signet-ring cells was characteristic. Anti-claudin-18.2-specific monoclonal antibody therapy will likely be used to treat patients with IPMNHGD in the future. This case highlights the diagnostic utility of SPACE, with particular emphasis on the characteristic presence of signet-ring cells. Furthermore, it anticipates the potential use of anti-claudin-18.2- specific monoclonal antibody therapy in the management of IPMNHGD patients.

Spotted lanternfly predicted to establish in California by 2033 without preventative management.

Models that are both spatially and temporally dynamic are needed to forecast where and when non-native pests and pathogens are likely to spread, to provide advance information for natural resource managers. The potential US range of the invasive spotted lanternfly (SLF, Lycorma delicatula) has been modeled, but until now, when it could reach the West Coast's multi-billion-dollar fruit industry has been unknown. We used process-based modeling to forecast the spread of SLF assuming no treatments to control populations occur. We found that SLF has a low probability of first reaching the grape-producing counties of California by 2027 and a high probability by 2033. Our study demonstrates the importance of spatio-temporal modeling for predicting the spread of invasive species to serve as an early alert for growers and other decision makers to prepare for impending risks of SLF invasion. It also provides a baseline for comparing future control options.

Neuromedin U-deficient rats do not lose body weight or food intake.

Studies in genetically modified mice establish that essential roles of endogenous neuromedin U (NMU) are anorexigenic function and metabolic regulation, indicating that NMU is expected to be a potential target for anti-obesity agents. However, in central administration experiments in rats, inconsistent results have been obtained, and the essential role of NMU energy metabolism in rats remain unclear. This study aims to elucidate the role of endogenous NMU in rats. We generated NMU knockout (KO) rats that unexpectedly showed no difference in body weight, adiposity, circulating metabolic markers, body temperature, locomotor activity, and food consumption in both normal and high fat chow feeding. Furthermore, unlike reported in mice, expressions of Nmu and NMU receptor type 2 (Nmur2) mRNA were hardly detectable in the rat hypothalamic nuclei regulating feeding and energy metabolism, including the arcuate nucleus and paraventricular nucleus, while Nmu was expressed in pars tuberalis and Nmur2 was expressed in the ependymal cell layer of the third ventricle. These results indicate that the species-specific expression pattern of Nmu and Nmur2 may allow NMU to have distinct functions across species, and that endogenous NMU does not function as an anorexigenic hormone in rats.

Surgical outcomes of totally extraperitoneal repair for inguinal hernia: A retrospective multicenter propensity score-matched study.

BACKGROUND: Laparoscopic surgical approaches, including total extraperitoneal repair (TEP), have been widely accepted for inguinal hernia repair in Japan. However, there are limited data regarding recurrence after TEP in Japan, given the limited versatility of this procedure. This study retrospectively evaluated the rates of hernia recurrence after TEP and open mesh repair at multiple Japanese centers. METHODS: This retrospective study evaluated 1917 patients who underwent inguinal hernia repair at 32 institutions in the Oita prefecture between January 2014 and December 2015. Eligible patients were grouped according to whether they underwent TEP (1011 patients) or open mesh repair (636 patients). Propensity score matching was performed 1:1 (total: 1076 patients, 538 patients from each group). The outcomes of interest were recurrence, morbidity, and postoperative recovery. RESULTS: The TEP and open mesh repair groups had similar baseline characteristics. After propensity score matching, there was no significant difference between the two groups in terms of recurrence rate (TEP: 0.5% vs open mesh repair: 1.0%, P = .375). However, the TEP group had significantly longer operating times (median: 70.2 min vs 65.0 min, P < .001), significantly less blood loss (0-5.1 mL vs 0-20.4 mL, P < .001), and significantly shorter postoperative hospital stays (median: 5.0 days vs 6.4 days, P < .001). The overall incidences of morbidity were 6.2% in the TEP group and 7.2% in the open mesh repair group (P = .535). CONCLUSION: This multicenter retrospective study with propensity score matching revealed that the recurrence rates were similarly low for TEP and open mesh repair of inguinal hernia. Thus, a well-trained surgical team could use TEP as a standard procedure.

Azathioprine-induced severe myelosuppression accompanied by massive hair loss and painful oral ulcer in an autoimmune hepatitis patient with NUDT15 minor variant: A case report.

This report highlights azathioprine-induced severe myelosuppression in the patient with NUDT15 minor variant. This case report is particularly instructive because several typical symptoms are the clues to this critical adverse drug reaction.

Phase 2 trial of leuprorelin in patients with spinal and bulbar muscular atrophy.

OBJECTIVE: Spinal and bulbar muscular atrophy (SBMA) is a hereditary motor neuron disease caused by the expansion of a polyglutamine tract in the androgen receptor (AR). Animal studies have shown that the pathogenesis of SBMA is dependent on serum testosterone level. This study is aimed at evaluating the efficacy and safety of androgen deprivation by leuprorelin acetate in patients with SBMA. METHODS: Fifty SBMA patients underwent subcutaneous injections of leuprorelin acetate or placebo in a randomized, placebo-controlled trial for 48 weeks, followed by an open-label trial for an additional 96 weeks, in which 19 patients of the leuprorelin group and 15 of the placebo group received leuprorelin acetate. The patients who did not participate in the open-label trial were also followed up for the 96-week period (UMIN000000474). RESULTS: Leuprorelin acetate significantly extended the duration of cricopharyngeal opening in videofluorography and decreased mutant AR accumulation in scrotal skin biopsy. The patients treated with leuprorelin acetate for 144 weeks exhibited significantly greater functional scores and better swallowing parameters than those who received placebo. Autopsy of one patient who received leuprorelin acetate for 118 weeks suggested that androgen deprivation inhibits the nuclear accumulation or stabilization, or both, of mutant AR in the motor neurons of the spinal cord and brainstem. INTERPRETATION: These observations suggest that administration of leuprorelin acetate suppresses the deterioration of neuromuscular impairment in SBMA by inhibiting the toxic accumulation of mutant AR. The results of this phase 2 trial support the start of large-scale clinical trials of androgen deprivation for SBMA.

The profile of motor unit number estimation (MUNE) in spinal and bulbar muscular atrophy.

OBJECTIVE: Spinal and bulbar muscular atrophy (SBMA) is a lower motor neuron disease caused by the expansion of a trinucleotide CAG repeat in the androgen receptor (AR) gene. The fundamental histopathological finding of this disease is an extensive loss of lower motor neurons in the spinal cord and brainstem. It is, however, difficult to evaluate clinically the degree of motor neuron degeneration, which stresses the need for biomarkers to detect the remaining neuronal function. METHODS: The authors performed motor unit number estimation (MUNE) in 52 patients with SBMA, to investigate whether this method could be a potential biomarker of SBMA, and re-evaluated MUNE 1 year later in a subgroup of the patients. RESULTS: The number of functioning motor units was remarkably reduced in patients with SBMA compared with controls, and was correlated with both ipsilateral grip power and disease duration. A longitudinal analysis demonstrated a further reduction in motor units within 1 year. CONCLUSIONS: The results suggest that MUNE is an electrophysiological parameter that reflects the severity and progression of motor neuron degeneration in patients with SBMA.

Rare Neurologic Disease-Associated Mutations of AIMP1 are Related with Inhibitory Neuronal Differentiation Which is Reversed by Ibuprofen.

BACKGROUND: Hypomyelinating leukodystrophy 3 (HLD3), previously characterized as a congenital diseases associated with oligodendrocyte myelination, is increasingly regarded as primarily affecting neuronal cells. METHODS: We used N1E-115 cells as the neuronal cell model to investigate whether HLD3-associated mutant proteins of cytoplasmic aminoacyl-tRNA synthase complex-interacting multifunctional protein 1 (AIMP1) aggregate in organelles and affect neuronal differentiation. RESULTS: 292CA frame-shift type mutant proteins harboring a two-base (CA) deletion at the 292th nucleotide are mainly localized in the lysosome where they form aggregates. Similar results are observed in mutant proteins harboring the Gln39-to-Ter (Q39X) mutation. Interestingly, the frame-shift mutant-specific peptide specifically interacts with actin to block actin fiber formation. The presence of actin with 292CA mutant proteins, but not with wild type or Q39X ones, in the lysosome is detectable by immunoprecipitation of the lysosome. Furthermore, expression of 292CA or Q39X mutants in cells inhibits neuronal differentiation. Treatment with ibuprofen reverses mutant-mediated inhibitory differentiation as well as the localization in the lysosome. CONCLUSIONS: These results not only explain the cell pathological mechanisms inhibiting phenotype differentiation in cells expressing HLD3-associated mutants but also identify the first chemical that restores such cells in vitro.

Pharmacokinetic and toxicodynamic evaluation of 5-fluorouracil administration after major hepatectomy in a rat model.

BACKGROUND: Chemotherapy after hepatectomy for colorectal liver metastasis has not been established, due to the toxic side effects, which are likely related to impaired drug clearance during liver regeneration. We investigated the pharmacokinetic and toxicodynamic evaluation of 5-fluorouracil (5-FU) during liver regeneration after major hepatectomy in a rat model. METHODS: Thirty-six male Wistar rats were divided into control (C), control with chemotherapy (CC), hepatectomy (H), and hepatectomy with chemotherapy (HC) groups. The CC and HC groups were administered 5-FU for 4 days. Plasma 5-FU, liver weight, and liver dihydropyrimidine dehydrogenase (DPD) were measured. The ileal villous height was measured to determine adverse effects. RESULTS: The area under the curve and maximum plasma concentration of 5-FU increased by up to 51% and 32%, respectively, in the HC group compared to the CC group. The liver regeneration rate was significantly lower in the HC group than in the H group (67.3 ± 7.4 vs 33.0 ± 5.7%, p < 0.001). The HC group had a significantly lower liver DPD than the CC group (4.4 ± 1.1 mg vs 6.9 ± 1.1 mg, p < 0.01). The HC group had a significantly lower ileal villous height than the CC group (253 ± 40 µm vs. 318 ± 36 µm, p < 0.05). CONCLUSIONS: Reduction of the total liver DPD following major hepatectomy caused increased plasma 5-FU levels and 5-FU-associated toxicity.

Metabolic changes of Japanese schizophrenic patients transferred from hospitalization to outpatients.

It is well known that schizophrenic patients have high incidence of metabolic syndrome and life-style related diseases. There are reports that the rates of these diseases are increased more in outpatients than inpatients, but are also reports that the rates are not different between both patient groups. These differences might be related to the length of hospitalization. Hospitalization of Japanese psychiatric patients is about 300 days, much longer than western countries (below 50 days). Therefore, we investigated lipid and glucose metabolism of schizophrenic patients transferred from hospitalization to outpatients at Kohnodai hospital with a mean of 80 days hospitalization period to clarify metabolic characteristics in Japanese patients. Study participants were 144 schizophrenia inpatients and 109 outpatients at Kohnodai Hospital. These 109 outpatients were followed for approximately 2 years, without changes of administrated drugs, and from 144 inpatients. Data from outpatients were obtained at 6 months, 1 year and 2 years after their discharge. Outpatients 2 years after discharge had significantly higher levels of total cholesterol, triglyceride and non-high density lipoprotein (non-HDL) cholesterol than inpatients, accompanied with an increase of body weight. Serum HDL-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) levels had no significant difference between both groups. These lipids and glucose levels also showed the same tendency in outpatients 0.5 year and 1 year after discharge as those after 2 years. We found that schizophrenic patients in our study appeared to have changes of lipid metabolism 2 years after their discharge, but no significant changes of glucose metabolism, such as FPG and HbA1c.