Notes

Polyether ionophore kijimicin suppresses increase of Toxoplasma gondii and also regulates serious toxoplasmosis throughout rats.
Choosing actions that result in advantageous outcomes is a fundamental function of nervous systems. All computational decision-making models contain a mechanism that controls the variability of (or confidence in) action selection, but its neural implementation is unclear-especially in humans. We investigated this mechanism using two influential decision-making frameworks active inference (AI) and reinforcement learning (RL). In AI, the precision (inverse variance) of beliefs about policies controls action selection variability-similar to decision 'noise' parameters in RL-and is thought to be encoded by striatal dopamine signaling. We tested this hypothesis by administering a 'go/no-go' task to 75 healthy participants, and measuring striatal dopamine 2/3 receptor (D2/3R) availability in a subset (n = 25) using [11C]-(+)-PHNO positron emission tomography. In behavioral model comparison, RL performed best across the whole group but AI performed best in participants performing above chance levels. Limbic striatal D2/3R availability had linear relationships with AI policy precision (P = 0.029) as well as with RL irreducible decision 'noise' (P = 0.020), and this relationship with D2/3R availability was confirmed with a 'decision stochasticity' factor that aggregated across both models (P = 0.0006). These findings are consistent with occupancy of inhibitory striatal D2/3Rs decreasing the variability of action selection in humans. © The Author(s) 2020. Published by Oxford University Press.BACKGROUND Targeting the programmed death ligand 1 (PD-L1) pathway has become standard for many advanced malignancies. Whether PD-L1 expression predicts response is unclear. We assessed the association between PD-L1 expression and immunotherapy response using stratified meta-analysis. METHODS We performed a systematic review of randomized clinical trials published prior to October 2018 comparing overall survival (OS) in patients with advanced solid organ malignancies treated with immunotherapy or standard treatment. Pooled hazard ratios were calculated among patients with high and low PD-L1 levels independently. Differences between the two estimates were assessed using meta-analysis of study-level differences. Our primary analysis assessed a 1% threshold while secondary analyses utilized 5, 10 and 50%. RESULTS 14 eligible trials reporting on 8887 patients were included. While there was a significant OS benefit for immunotherapy compared with standard treatment for all patients, the magnitude of benefit was significantly larger among those with high PD-L1 expression (P = 0.006). This finding persisted regardless of threshold used and across subgroup analyses according to PD-L1 assay type, tumor histology, line of therapy, type of inhibitor and study methodology. CONCLUSIONS PD-L1 levels have important predictive value in determining the response to immunotherapy. However, patients with low PD-L1 levels also experience improved survival with immunotherapy compared with standard treatment. © The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail [email protected] is a common metabolic condition in neonatal period, but severe and persistent hypoglycemia can cause neurological damage and brain injury. The aim of the present study was to analyze the risk factors of neonatal hypoglycemia in clinic. A total of 135 neonatal hypoglycemia infants and 135 healthy infants were included in the present study. The differences in birth weight between neonatal hypoglycemia group and healthy control group were analyzed via t test. The associations between neonatal blood sugar level and relevant characteristic factors were explored using χ2 test. Binary logistic regression analysis was used to analyze risk factors related to the incidence of neonatal hypoglycemia. The results showed that the average birth weight was matched in neonatal hypoglycemia group and healthy control group. Neonatal blood sugar level of the infants was significantly associated with born term, birth weight, feed, gestational diabetes mellitus (GDM) and hypothermia (all P less then 0.05). Besides, logistic regression analysis showed that babies' born term (odds ratio (OR) = 2.715, 95% confidence interval (95% CI) 1.311-5.625), birth weight (OR = 1.910, 95% CI 1.234-2.955), improper feeding (OR = 3.165, 95% CI 1.295-7.736) and mother's GDM (OR = 2.184, 95% CI 1.153-4.134) were high risk factors for neonatal hypoglycemia. The incidence of hypoglycemia in infants was significantly associated with various clinical factors. And monitoring these risk factors is one of important measures to reduce long-term neurological damage caused by neonatal hypoglycemia. © 2020 The Author(s).Advances in understanding the pathophysiology of facioscapulohumeral dystrophy (FSHD) have led to the discovery of candidate therapeutics and it is important to identify markers of disease activity to inform clinical trial design. For drugs that inhibit DUX4 expression, measuring DUX4 or DUX4-target gene expression might be an interim measure of drug activity; however, only a subset of FHSD muscle biopsies show evidence of DUX4 expression. Our prior study showed that MRI T2-STIR-positive muscles had a higher probability of showing DUX4 expression than muscles with normal MRI characteristics. In the current study, we performed a one-year follow-up assessment of the same muscle with repeat MRI and muscle biopsy. There was little change in MRI characteristics over the one-year period and, similar to the initial evaluation, MRI T2-STIR-postive muscles had a higher expression of DUX4-regulated genes, as well as genes associated with inflammation, extracellular matrix, and cell cycle. Compared to the initial evaluation, overall the level of expression in these gene categories remained stable over the one-year period; however, there was some variability for each individual muscle biopsied. The pooled data from both the initial and one-year follow-up evaluations identified several FSHD subgroups based on gene expression, as well as a set of genes-composed of DUX4-target genes, inflammatory and immune genes, and cell cycle control genes-that distinguished all of the FSHD samples from the controls. These candidate markers of disease activity need to be replicated in independent datasets, and, if validated, may provide useful measures of disease progression and response to therapy. © The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email [email protected] virus (BTV) and epizootic hemorrhagic disease virus (EHDV) cause hemorrhagic disease (HD) in wild ruminants and bluetongue disease (BT) and epizootic hemorrhagic disease (EHD) in livestock. These viruses are transmitted by biting midges in the genus Culicoides (family Ceratopogonidae). Mortality from this disease can reach 90% in certain breeds of sheep and in white-tailed deer (Odocoileus virginianus). From January until December of 2012, we conducted a prospective study to determine the origin and routes of transmission of BTV and EHDV in captive deer and cattle. The objective was to determine the abundance of Culicoides spp. and BTV/EHDV infection prevalence in midges, cattle, and deer in an area experiencing an outbreak of BT and EHD. Agar gel immunodiffusion (AGID) tests to detect for EHDV and BTV antibodies were conducted on serum collected from cattle and deer, quantitative reverse transcriptase polymerase chain reaction (RT-qPCR) was utilized for BTV/EHDV RNA detection in tissues from dead CR assays. BTV viral nucleic acid was detected in three pools from three different species of midges C. crepuscularis, C. debilipalpis, and C. stellifer. © The Author(s) 2020. Published by Oxford University Press on behalf of Entomological Society of America.All rights reserved. For permissions, please e-mail [email protected] No data on the recently introduced infliximab (IFX) biosimilar SB2 in inflammatory bowel disease (IBD) are available. METHODS The Sicilian Prospective Observational Study of Patients With IBD Treated With Infliximab Biosimilar SB2 is a multicenter, observational, prospective study performed among the cohort of the Sicilian Network for Inflammatory Bowel Disease. All consecutive IBD patients starting the IFX biosimilar SB2 from its introduction in Sicily (March 2018) to September 2019 (18 months) were enrolled. RESULTS Two hundred seventy-six patients (Crohn disease 49.3%, ulcerative colitis 50.7%) were included 127 (46.0%) were naïve to IFX and naïve to anti-tumor necrosis factor medications (anti-TNFs), 65 (23.5%) were naïve to IFX and previously exposed to anti-TNFs, 17 (6.2%) were switched from an IFX originator to SB2, 43 (15.6%) were switched from the biosimilar CT-P13 to SB2, and 24 (8.7%) were multiply switched (from IFX originator to CT-P13 to SB2). The cumulative number of infusions of SB2 was 1798, and the total follow-up time was 182.7 patient-years. Sixty-seven serious adverse events occurred in 57 patients (20.7%; incidence rate 36.7 per 100 patient-year), and 31 of these events caused the withdrawal of the drug. The effectiveness after 8 weeks of treatment was evaluated in patients naïve to IFX (n = 192) 110 patients (57.3%) had steroid-free remission, while 56 patients had no response (29.2%). Adavosertib in vitro At the end of follow-up, 72 patients (26.1%) interrupted the treatment, without significant differences in treatment persistency estimations between the five groups (log-rank P = 0.15). CONCLUSIONS The safety and effectiveness of SB2 seem to be overall similar to those reported for the IFX originator and CT-P13. © 2020 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail [email protected] prognosis of pancreatic adenocarcinoma is dismal. Hence, advances in multidisciplinary treatment strategies, including surgery, are urgently needed. Early recurrence of distant organ metastases suggests that there are occult metastases even in cases with resectable disease. Several randomized controlled trials on adjuvant chemotherapy have been conducted to prolong survival after resection. CONKO-001 study was the first to demonstrate significant improvement in disease-free survival after surgery with gemcitabine administration. The JASPAC-01 study showed the superiority of adjuvant S1 over gemcitabine in survival after resection. Based on the results, adjuvant S1 therapy is the prescribed standard of care in Japan. Recently, the PRODIGE 24/CCTG PA.6 study showed that survival of patients treated with a modified FOLFIRINOX regimen as adjuvant therapy was significantly longer than those treated with adjuvant gemcitabine therapy. Although the evidence from these trials on adjuvant chemotherapy have been the gold-standard treatment for curatively resected and fully recovered patients, resectable disease at diagnosis is not the status, resected disease after curative resection. Currently, neoadjuvant therapy is considered to be a promising alternative to surgery for pancreatic cancer. Although there are many reports regarding neoadjuvant chemoradiotherapy, so far there has been no solid evidence proving the advantage of this strategy versus standard up-front surgery. Newly obtained results from the Prep-02/JSAP05 randomized phase II/III study, comparing neoadjuvant therapy with up-front surgery, revealed significant improvement in overall survival with neoadjuvant chemotherapy by intention-to-treat analysis. Thus, neoadjuvant intervention might become a new standard strategy in cases undergoing planned resection for pancreatic cancer. © The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail [email protected].
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