De novo expression of gastrokines in pancreatic precursor lesions impede the development of pancreatic cancer

Molecular events occurring in stepwise progression from pre-malignant lesions (pancreatic intraepithelial neoplasia; PanIN) to the development of pancreatic ductal adenocarcinoma (PDAC) are poorly understood. Thus, characterization of early PanIN lesions may reveal markers that can help in diagnosing PDAC at an early stage and allow understanding the pathology of the disease. We performed the molecular and histological assessment of patient-derived PanINs, tumor tissues and pancreas from mouse models with PDAC (KC mice that harbor K-RAS mutation in pancreatic tissue), where we noted marked upregulation of gastrokine (GKN) proteins. To further understand the role of gastrokine proteins in PDAC development, GKN-deficient KC mice were developed by intercrossing gastrokine-deficient mice with KC mice. Panc-02 (pancreatic cancer cells of mouse origin) were genetically modified to express GKN1 for further in vitro and in vivo analysis. Our results show that gastrokine proteins were absent in healthy pancreas and invasive cancer, while its expression was prominent in low-grade PanINs. We could detect these proteins in pancreatic juice and serum of KC mice. Furthermore, accelerated PanIN and tumor development were noted in gastrokine deficient KC mice. Loss of gastrokine 1 protein delayed apoptosis during carcinogenesis leading to the development of desmoplastic stroma while loss of gastrokine 2 increased the proliferation rate in precursor lesions. In summary, we identified gastrokine proteins in early pancreatic precursor lesions, where gastrokine proteins delay pancreatic carcinogenesis

Predictors of short-term anxiety outcome in subthalamic stimulation for Parkinson’s disease

\ua9 The Author(s) 2024.The effects of subthalamic nucleus deep brain stimulation (STN-DBS) on anxiety in Parkinson’s disease (PD) are understudied. We identified clinical predictors of STN-DBS effects on anxiety in this study. In this prospective, open-label, multicentre study, we assessed patients with anxiety undergoing STN-DBS for PD preoperatively and at 6-month follow-up postoperatively. We assessed the Hospital Anxiety and Depression Scale (HADS-anxiety and depression subscales), Unified PD Rating Scale-motor examination, Scales for Outcomes in PD-motor (SCOPA-M)-activities of daily living (ADL) and -motor complications, Non-Motor Symptom Scale (NMSS), PDQuestionnaire-8 (PDQ-8), and levodopa-equivalent daily dose. We tested changes at follow-up with Wilcoxon signed-rank test and corrected for multiple comparisons (Bonferroni method). We identified patients with a clinically relevant anxiety improvement of anxiety based on a designated threshold of \ubd standard deviation of baseline HADS-anxiety. Moreover, we investigated predictors of HADS-anxiety changes with correlations and linear regressions. We included 50 patients with clinically relevant baseline anxiety (i.e., HADS-anxiety ≥ 8) aged 63.1 years \ub1 8.3 with 10.4 years \ub1 4.5 PD duration. HADS-anxiety improved significantly at 6-month follow-up as 80% of our cohort experienced clinically relevant anxiety improvement. In predictor analyses, worse baseline SCOPA-ADL and NMSS-urinary domain were associated with greater HADS-anxiety improvements. HADS-anxiety and PDQ-8 changes correlated moderately. Worse preoperative ADL and urinary symptoms predicted favourable postoperative anxiety outcome, which in turn was directly proportionate to greater QoL improvement. This study highlights the importance of detailed anxiety assessments alongside other non-motor and motor symptoms when advising and monitoring patients undergoing STN-DBS for PD

A new 28Si single crystal: counting the atoms for the new kilogram definition

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Silver iodide sodalite for 129I immobilisation

Silver iodide sodalite was initially synthesised as a fine-grained major phase in a nominally stoichiometric composition following hot isostatic pressing at 850 °C with 100 MPa and its composition, Ag4Al3Si3O12I, was approximately verified by scanning electron microscopy. An alternative preparative method yielded a more dense and stoichiometric AgI sodalite on sintering and HIPing. As found for AgI, the I is released from AgI sodalite much more readily in reducing water than in ordinary water. Thus in normal PCT-B tests, the I release was <0.3 g/L in water, but it was ∼70 g/L under highly reducing conditions. This is an important point with regard to can material if HIPing is used for consolidation. © 2016 Elsevier B.V

Enhancement of excitonic and defect-related luminescence in neutron transmutation doped β-Ga2 O3

Neutron irradiation analysis, inductively coupled plasma mass spectrometry (ICPMS), and cathodoluminescence (CL) spectroscopy are used to investigate the influence of transmuted Ge incorporation on the luminescence properties of β-Ga2O3 single crystals. Calculations based on Ga2O3-neutron interaction reveal temporal variations of both Ge and Zn concentrations as a function of time during and after neutron irradiation. To produce a concentration of 5×1018Gedonors/cm3 from the neutron transmutation of Ga, the β-Ga2O3 crystal was irradiated for 27 h, which was accompanied by the incorporation of 1016Znacceptors/cm3. These calculated dopant concentrations are confirmed by ICPMS. The β-Ga2O3 crystals exhibit a UV band at 3.40 eV due to self-trapped holes (STHs) and two blue donor-acceptor pair (DAP) peaks at 3.14 eV (BL1) and 2.92 eV (BL2). In addition to the neutron-induced incorporation of substitutional Ge donors and Zn acceptors on Ga sites, Ga vacancies (VGa) were created by high-energy neutrons in the flux, which strongly enhanced the BL1 peak. The VGa acceptors compensate the neutron-induced Ge donors, making the Ga2O3 crystal highly resistive. Concurrent temperature-resolved CL measurements of the β-Ga2O3 before and after neutron irradiation reveal a twofold increase in both the STH and BL1 peaks. This result suggests that STHs are preferentially localized at an O site adjacent to VGa, as theoretically predicted by Kananen et al. [Appl. Phys. Lett. 110, 202104 (2017)10.1063/1.4983814.]. Analysis of the Ga2O3 CL temperature dependence reveals that the UV and BL1 bands after the neutron irradiation exhibit an equivalent activation energy of 100±10meV due to the presence of a neutron-induced defect that acts as an efficient competitive nonradiative recombination channel. The results also provide evidence that the BL1 and BL2 bands arise from different DAP pairs