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In-hospital cardiac arrest (IHCA) is associated with high mortality and poor neurological outcomes. Our objective was to assess whether the lactate-to-albumin ratio (LAR) can predict the outcomes in patients after IHCA. We retrospectively screened 75,987 hospitalised patients at a university hospital between 2015 and 2019. The primary endpoint was survival at 30-days. Neurological outcomes were assessed at 30 days using the cerebral performance category scale. 244 patients with IHCA and return of spontaneous circulation (ROSC) were included in this study and divided into quartiles of LAR. Overall, there were no differences in key baseline characteristics or rates of pre-existing comorbidities among the LAR quartiles. Patients with higher LAR had poorer survival after IHCA compared to patients with lower LAR: Q1, 70.4% of the patients; Q2, 50.8% of the patients; Q3, 26.2% of the patients; Q4, 6.6% of the patients (p = 0.001). Across increasing quartiles, the probability of a favourable neurological outcome in patients with ROSC after IHCA decreased: Q1: 49.2% of the patients; Q2: 32.8% of the patients; Q3: 14.7% of the patients; Q4: 3.2% of the patients (p = 0.001). The AUCs for predicting 30-days survival using the LAR were higher as compared to using a single measurement of lactate or albumin. The prognostic performance of LAR was superior to that of a single measurement of lactate or albumin for predicting survival after IHCA.

Heroin, a semisynthetic opioid drug synthesized from morphine, is the 3,6-diacetyl ester of morphine (diacetylmorphine). The post-mortem diagnosis of heroin-related death could be an issue and usually rely on a combination of investigations, including the autopsy, histological and toxicological analysis. We conducted the present study to evaluate the correlation between the heroin concentration in biological fluids (peripheral blood, bile and urine) and the post-mortem anti-6-MAM antibody expression in various tissues (brain, heart, lung, liver and kidney) using immunohistochemical staining. A quantitative analysis of the immunohistochemical reaction was carried out. 45 cases of heroin-related death investigated at the Forensic Pathology Institutes of the University of Rome, Foggia and Pisa were included. The control group was composed of 15 cases of death due to other causes, without brain lesions and negative toxicological analysis for drugs. We found a positive immunohistochemical reaction in different organs and it was related to the timing of heroin metabolization. No reaction was found in the control group. Our findings show that immunohistochemistry can be a valuable tool for the post-mortem diagnosis of acute heroin abuse. A better understanding of the timing of heroin's metabolism can be useful in the forensic field and for future therapeutic applications.

Purpose Multiple sclerosis (MS) is a disease characterized by inflammatory demyelinated lesions. New treatment strategies are being developed to stimulate myelin repair. Quantitative myelin imaging could facilitate these developments. This first-in-man study aimed to evaluate [11C]MeDAS as a PET tracer for myelin imaging in humans. Methods Six healthy controls and 11 MS patients underwent MRI and dynamic [11C]MeDAS PET scanning with arterial sampling. Lesion detection and classification were performed on MRI. [11C]MeDAS time-activity curves of brain regions and MS lesions were fitted with various compartment models for the identification of the best model to describe [11C]MeDAS kinetics. Several simplified methods were compared to the optimal compartment model. Results Visual analysis of the fits of [11C]MeDAS time-activity curves showed no preference for irreversible (2T3k) or reversible (2T4k) two-tissue compartment model. Both volume of distribution and binding potential estimates showed a high degree of variability. As this was not the case for 2T3k-derived net influx rate (Ki), the 2T3k model was selected as the model of choice. Simplified methods, such as SUV and MLAIR2 correlated well with 2T3k-derived Ki, but SUV showed subject-dependent bias when compared to 2T3k. Both the 2T3k model and the simplified methods were able to differentiate not only between gray and white matter, but also between lesions with different myelin densities. Conclusion [11C]MeDAS PET can be used for quantification of myelin density in MS patients and is able to distinguish differences in myelin density within MS lesions. The 2T3k model is the optimal compartment model and MLAIR2 is the best simplified method for quantification. Trial registration. NL7262. Registered 18 September 2018.

The morphology and functionality of the epithelial lining differ along the intestinal tract, but tissue renewal at all sites is driven by stem cells at the base of crypts(1-3). Whether stem cell numbers and behaviour vary at different sites is unknown. Here we show using intravital microscopy that, despite similarities in the number and distribution of proliferative cells with an Lgr5 signature in mice, small intestinal crypts contain twice as many effective stem cells as large intestinal crypts. We find that, although passively displaced by a conveyor-belt-like upward movement, small intestinal cells positioned away from the crypt base can function as long-term effective stem cells owing to Wnt-dependent retrograde cellular movement. By contrast, the near absence of retrograde movement in the large intestine restricts cell repositioning, leading to a reduction in effective stem cell number. Moreover, after suppression of the retrograde movement in the small intestine, the number of effective stem cells is reduced, and the rate of monoclonal conversion of crypts is accelerated. Together, these results show that the number of effective stem cells is determined by active retrograde movement, revealing a new channel of stem cell regulation that can be experimentally and pharmacologically manipulated.

Determination of plasma vitamin B12 (B12) is a frequently requested laboratory analysis, mainly employed to establish B12 deficiency. However, an increased level of B12 is a common unexpected finding that may be related to an increased concentration of one of the B12 binding proteins, haptocorrin or transcobalamin. This paper describes the extensive laboratory evaluation of a patient with an elevated level of plasma B12 with various well-established assays. Initial studies suggested the presence of a macromolecule consisting of haptocorrin bound B12. Specific determinations of the B12-binding proteins revealed normal amounts of haptocorrin but a markedly increase in both total and B12 saturated transcobalamin (holo-TC). The results are in accord with the presence of macro-transcobalamin. These experiments reveal that determination of the nature of the B12-macromolecules is troublesome due to differences in assays applied to measure these proteins. In addition, this publication creates awareness of macro-holo-TC as a cause of an unexplained increased B12 level.

Alveolar (AE) and cystic (CE) echinococcosis are two parasitic diseases caused by the tapeworms Echinococcus multilocularis and E. granulosus sensu lato (s. l.), respectively. Currently, AE and CE are mainly diagnosed by means of imaging techniques, serology, and clinical and epidemiological data. However, no viability markers that indicate parasite state during infection are available. Extracellular small RNAs (sRNAs) are short non-coding RNAs that can be secreted by cells through association with extracellular vesicles, proteins, or lipoproteins. Circulating sRNAs can show altered expression in pathological states; hence, they are intensively studied as biomarkers for several diseases. Here, we profiled the sRNA transcriptomes of AE and CE patients to identify novel biomarkers to aid in medical decisions when current diagnostic procedures are inconclusive. For this, endogenous and parasitic sRNAs were analyzed by sRNA sequencing in serum from disease negative, positive, and treated patients and patients harboring a non-parasitic lesion. Consequently, 20 differentially expressed sRNAs associated with AE, CE, and/or non-parasitic lesion were identified. Our results represent an in-depth characterization of the effect E. multilocularis and E. granulosus s. l. exert on the extracellular sRNA landscape in human infections and provide a set of novel candidate biomarkers for both AE and CE detection.

Delivery drones typically perform delivery by suspending the parcel vertically or landing the drone to drop off the package. However, because of the constrained landing area and the requirement for precise navigation, delivering items to customers who reside in multi-story apartment complexes poses a unique challenge. This research paper proposes a novel drone delivery system for multi-story apartment buildings with balconies that employ two methods for Vertical Grid Screening (VGS), i.e., Grid Screening (GS) and Square Screening (SS), to detect unique markers to identify the precise balcony that needs to receive the product. The developed drone has a frame size of 295 mm and is equipped with a stereo camera and a ranging sensor. The research paper also explores the scanning and trajectory methods required for autonomous flight to accurately approach the marker location. The proposed machine learning system is trained on a YOLOv5 model for image recognition of the marker, and four different models and batch sizes are compared. The 32-batch size with a 960 × 1280 resolution model provides an average of 0.97 confidence for an extended range. This system is tested outdoors and shows an accuracy of 95% for a planned trajectory with 398 ms detection time as a solution for last-mile delivery in urban areas.

(1) Background: Type 2 diabetes mellitus (T2DM) and metabolic syndrome are associated with decreased vitamin D. In contrast, high pro-neurotensin (pro-NT) levels are linked with an increased risk of T2DM and cardiovascular disease. We aimed to determine the validity of pro-NT and 25-dihydroxy vitamin D3 levels as predictors for T2DM complications; (2) Methods: One hundred T2DM, and one hundred healthy volunteers participated in this case-control study. Their Pro-NT and 25-hydroxyvitamin D3 levels were evaluated using the ELISA technique; (3) Results: Pro-NT and 25 (OH) vitamin D3 have significant validity and accuracy in T2DM prediction, 84.5%, and 90.5%, respectively (p = 0.001). At a value of 124 Pmol/L, Pro-NT showed 81% sensitivity and 88% specificity in predicting T2DM. At a value of 16.5, 25-Hydroxy vitamin D3 had 78.4% sensitivity and 68.3% specificity in predicting T2DM complications. At a value of >158 pmol/L, Pro-NT predicted T2DM complications with 67.6% sensitivity and 56.0% specificity; (4) Conclusions: 25 (OH) Vit D3 and Pro-NT could identify T2DM patients and predict T2DM complications. More extensive research is required to adequately validate this novel perspective with a large population study.

The kynurenine pathway (KP) plays a crucial role in the metabolism of tryptophan, an essential amino acid. Accumulating evidence suggests that the KP and its intermediates, as well as the kynurenine/tryptophan (K/T) ratio, are closely associated with inflammatory processes, including microinflammation. This study investigates the role of KP, its intermediates, and the K/T ratio as potential inflammatory markers capable of detecting microinflammation, which may not be revealed by conventional blood tests.

Objective: Acute hydrocephalus is a common complication in patients with aneurysmal subarachnoid hemorrhage (SAH). Several ventricular indices have been introduced to enable measurements of ventricular morphology. Previously, researchers have showed their diagnostic value for various neurological disorders. In this study, we evaluated the association between ventricular indices and the clinical course, occurrence of complications and outcome of SAH. Methods: A total of 745 SAH patients with available early admission computed tomography scans were included in the analyses. Six ventricular indices (bifrontal, bicaudate, ventricular and third ventricle ratios and Evans’ and Huckman’s indices) were measured. Primary endpoints included the occurrence of cerebral infarctions, in-hospital mortality and a poor outcome at 6 months. Secondary endpoints included different adverse events in the course of SAH. Clinically relevant cut-offs for the indices were determined using receiver operating curves. Univariate analyses were performed. Multivariate analyses were conducted on significant findings in a stepwise backward regression model. Results: The higher the values of the ventricular indices were and the older the patient was, the higher the WFNS and Fisher’s scores were, and the lower the SEBES score was at admission. Patients with larger ventricles showed a shorter duration of intracranial pressure increase > 20 mmHg and required decompressive craniectomy less frequently. Ventricular indices were independently associated with the parameters of inflammatory response after SAH (C-reactive protein in serum and interleukin-6 in cerebrospinal fluid and fever). Finally, there were independent correlations between larger ventricles and all the primary endpoints. Conclusions: The lower risk of intracranial pressure increase and absence of an association with vasospasm or systemic infections during SAH, and the poorer outcome in individuals with larger ventricles might be related to a more pronounced neuroinflammatory response after aneurysmal bleeding. These observations might be helpful in the development of specific medical and surgical treatment strategies for SAH patients depending on the initial ventricle measurements.

The Panax L. genus is well-known for many positive physiological effects on humans, with major species including P. ginseng, P. quinquefolius, P. notoginseng, P. japonicus, and P. japonicus var. major, the first three of which are globally popular. The combination of UPLC-QTOF-MS and chemometrics were developed to profile “identification markers” enabling their differentiation. The establishment of reliable biomarkers that embody the intrinsic metabolites differentiating species within the same genus is a key in the modernization of traditional Chinese medicine. In this work, the metabolomic differences among these five species were shown, which is critical to ensure their appropriate use. Consequently, 49 compounds were characterized, including 38 identified robust biomarkers, which were mainly composed of saponins and contained small amounts of amino acids and fatty acids. VIP (projection variable importance) was used to identify these five kinds of ginseng. In conclusion, by illustrating the similarities and differences between the five species of ginseng with the use of an integrated strategy of combining UPLC-QTOF-MS and multivariate analysis, we provided a more efficient and more intelligent manner for explaining how the species differ and how their secondary metabolites affect this difference. The most important biomarkers that distinguished the five species included Notoginsenoside-R1, Majonoside R1, Vinaginsenoside R14, Ginsenoside-Rf, and Ginsenoside-Rd.

Pre-harvest sprouting (PHS) of rice (Oryza sativa L.) causes severe economic problems due to reduced grain quality and yield. Fine mapping was carried out to identify genes associated with PHS; the detected quantitative trait locus (QTL) was narrowed down to 50 Kbp using F3:4 populations, four polymorphic insertion and deletion (InDel) markers, and two cleaved amplified polymorphic sequence (CAPS) markers. In one region, five candidate genes were detected, and the SNP and InDel in each gene (Os01g0111400 and Os01g0111600) were confirmed to show the differences and resulting amino acid changes between parent plants. Based on haplotype, expression, and co-segregation analysis, the InDel in Os01g0111600 was confirmed to be associated with the PHS trait. The results of this study could be applied to improve the PHS tolerance of Japonica rice varieties, and they also improved our understanding of the genetic basis underlying PHS tolerance.

BACKGROUND: In patients with acute heart failure (AHF), the development of worsening renal function with appropriate decongestion is thought to be a benign functional change and not associated with poor prognosis. We investigated whether the benefit of decongestion outweighs the risk of concurrent kidney tubular damage and leads to better outcomes.; METHODS: We retrospectively analyzed data from the AKINESIS study, which enrolled AHF patients requiring intravenous diuretic therapy. Urine neutrophil gelatinase-associated lipocalin (uNGAL) and B-type natriuretic peptide (BNP) were serially measured during the hospitalization. Decongestion was defined as =30% BNP decrease at discharge compared to admission. Univariable and multivariable Cox models were assessed for one-year mortality.; RESULTS: Among 736 patients, 53% had =30% BNP decrease at discharge. Levels of uNGAL and BNP at each collection time point had positive but weak correlations (r=0.133). Patients without decongestion and with higher discharge uNGAL values had worse one-year mortality, while those with decongestion had better outcomes regardless of uNGAL values (p for interaction 0.018). This interaction was also significant when the change in BNP was analyzed as a continuous variable (p

Background Biliary atresia (BA) is a rare disorder characterized by obstructive jaundice in infants, shortly after birth. Postoperatively, some patients exhibit portal hypertension and progressive liver fibrosis. Splenomegaly is a symptom of portal hypertension. We aimed to investigate splenomegaly as a marker for complications of portal hypertension and the relationship between splenomegaly and liver fibrosis in the long-term native liver (NL). Methods Between 1977 and 2018, 71 patients underwent hepaticojejunostomy. We included 54 patients (34 NL group, 20 liver transplant (LT) group) who fulfilled the eligibility criteria. Spleen volume (SV), total bile acids, hyaluronic acid, type IV collagen, and aspartate aminotransferase-to-platelet ratio index (APRi) were measured. Data were analyzed using Student's t-test, regression analysis, and receiver operating characteristic (ROC) curve analysis (P Results Total bile acids, hyaluronic acid, type IV collagen, and APRi increased in NL patients with a large SV at >25 years. SV and type IV collagen were correlated with NL for >25 years (r = 0.79 [P = 0.006], y = 1.1 - [0.03 × type IV collagen] [P = 0.008]). In the ROC curve analysis, the cutoff value for type IV collagen was 165 ng/mL (P = 0.07). Conclusions We suggest that SV as a prognostic index for End-Stage Liver Disease may be useful in biliary atresia. Long-term follow-up is necessary because the clinical course may be favorable in childhood but worsen during adulthood.

Background: Physical activity (PA) has substantial health benefits and is important in combatting chronic diseases, which have been associated with elevated levels of advanced glycation endproducts (AGEs). AGEs play a role in the aging process, and an association between PA and AGEs has been reported. We aimed to investigate the relationship between PA and AGE accumulation in a general population and in a population with chronic diseases.Methods: This large cross-sectional population study used data from adult participants in the LifeLines project, with participant information drawn from the LifeLines database as well data from patients with diabetes mellitus or renal and/or cardiovascular diseases. Tissue AGE accumulation was assessed non-invasively by skin-autofluorescence (SAF) using an AGE reader (DiagnOptics Technologies BV, Groningen, the Netherlands). PA was assessed using the short questionnaire to assess health-enhancing physical activity (SQUASH). Multivariate linear regression analyses were adjusted for age, body mass index, sex, and smoking status.Results: Data from 63,452 participants (general population n = 59,177, chronic disease n = 4275) were analyzed. The general population was significantly younger (43.58 +/- 11.77 years, mean +/- SD) and had significantly lower SAF (1.90 +/- 0.42 arbitrary units (AU)) compared to the population with chronic disease (age: 55.51 +/- 12.07 years; SAF: 2.27 +/- 0.51 AU). In the group with chronic disease, more hours of moderate to vigorous physical activities per week were associated with lower SAF (beta= -0.002, 95% confidence interval (95%CI): -0.002 to -0.001). For the general population, there was no association between hours of moderate to vigorous activity and SAF (beta= 3.2 x 10(-5), 95%CI: 0.000-0.001, p = 0.742). However, there was an association in the general population between total hours of PA per week and SAF (beta= 4.2 x 10(-4), 95%CI: 0.000-0.001, p < 0.001), but this association was not found in the chronic disease population (beta = -3.2 x 10(-4), 95%CI: -0.001 to 0.000, p = 0.347).Conclusion: Our study demonstrates that an inverse relationship exists between PA and AGE accumulation in the population with chronic disease. More hours of moderate to vigorous activity is associated with a significantly decreased SAF. More PA is associated with a lower SAF, even after adjusting for the established predictors (age, body mass index, smoking status, and sex). Our findings could help to promote health and prolong longevity.

Background Plasma neutrophil gelatinase-associated lipocalin (pNGAL) has been investigated extensively in acute kidney injury. This study investigated its pathophysiological significance and utility as marker for graft failure and mortality in stable kidney transplant recipients (KTR). Methods Baseline pNGAL was measured in 698 KTR (58% male, age 53 ± 13 years, estimated glomerular filtration rate 52.4 ± 20.4 mL/min/1.73 m2) at median 5.4 (interquartile range 1.8–12.0) years after transplantation, enrolled in the prospective TransplantLines Food and Nutrition Biobank and Cohort Study. Results pNGAL concentrations were higher in males, younger patients, patients with a deceased-donor kidney and higher serum creatinine. Independent of these, pNGAL was positively associated with urinary protein excretion, systemic inflammation parameters and calcineurin inhibitor use. During median follow-up of 5.3 (4.5–6.0) years, death-censored graft failure rates were 3.9%, 7.3% and 25.0% across increasing tertiles of pNGAL (Plog-rank Conclusions pNGAL is associated with parameters of kidney graft damage and with graft failure. The latter association is particularly present in KTR with pre-existent poor kidney function and proteinuria. Trial Registration: ClinicalTrials.gov NCT02811835.

Background: Alzheimer's disease (AD) remains to date an incurable disease with a long asymptomatic phase. Early diagnosis in peripheral biofluids has emerged as key for identifying subjects at risk and developing therapeutics and preventative approaches., Objective: We apply proteomics discovery to identify salivary diagnostic biomarkers for AD, which are suitable for self-sampling and longitudinal biomonitoring during aging., Methods: 57 participants were recruited for the study and were categorized into Cognitively normal (CNh) (n = 19), mild cognitive impaired (MCI) (n = 21), and Alzheimer's disease (AD) (n = 17). On a subset of subjects, 3 CNh and 3 mild AD, shot-gun filter aided sample preparation (FASP) proteomics and liquid chromatography mass spectroscopy (LC-MS/MS) was employed in saliva and cerebrospinal fluid (CSF) to identify neural-derived proteins. The protein level of salivary Transthyretin (TTR) was validated using western blot analysis across groups., Results: We found that 19.8% of the proteins in saliva are shared with CSF. When we compared the saliva and CSF proteome, 24 hits were decreased with only one protein expressed more. Among the differentially expressed proteins, TTR with reported function in amyloid misfolding, shows a significant drop in AD samples, confirmed by western blot showing a 0.5-fold reduction in MCI and AD compared to CNh., Conclusion: A reduction in salivary TTR appears with the onset of cognitive symptoms. More in general, the proteomic profiling of saliva shows a plethora of biomarkers worth pursuing as non-invasive hallmarks of dementia in the preclinical stage.

Some companies make product offers or promotions that aim to improve the quality and attractiveness of their products and increase consumer attractiveness. Daihatsu Duri car dealership is one of them. Augmented reality (AR) is one of the media used for product marketing. This research is how to use Augmented Reality to promote Daihatsu dealers and display 3D objects of Rocky Daihatsu cars on mobile markers as promotional media. The results of this study indicate that in the menu display experiment, one menu that was not displayed successfully was to select zoom. Testing on markers can be tested properly. For remote experiments, at a distance of 60 cm it can be detected, but not consistently. Meanwhile, light testing shows that the ambient light type of ARCamera Light is a bit dark, and markers are not detected properly. A stable internet connection is required to use this app, and lighting is also very important as AR cameras cannot detect markers in low light, so they cannot display 3D objects automatically.%MCEPASTEBIN%

Gal-3 plays an important role in cell survival, mRNA splicing, and cell–cell and cell–matrix interactions. Depending on its cellular localization and cancer type, Gal-3 may have tumour-suppressive or tumour-promoting activities. Given the promising diagnostic role of Gal-3 in the urine of PCa patients found in our previous study, its concordant gene and protein expression levels, and its involvement in PCa-related biological processes (e.g., morphogenesis of the prostate gland epithelium), we aimed to investigate this protein immunohistochemically in tumour and normal prostate tissues. Gal-3 protein expression was evaluated in 48 tumour prostate tissues, eight normal prostate tissues and 14 adjacent-normal prostate tissues. Decreased Gal-3 staining was detected in tumour tissues compared with normal tissues. Although Gal-3 staining was decreased in tumour tissues with GS 5-8 and pT2 and pT3 stages compared with normal prostate tissue, no correlation was found between Gal-3 expression and PCa progression. In the present study, the pattern of cellular localization differed between groups, as Gal-3 was predominantly excluded from the nucleus in tumour tissues. Furthermore, Gal-3 had no significant effect on survival and relapse in these PCa patients. This work confirms Gal-3 as a promising marker for PCa diagnosis.

© 2023 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by- nc-nd/4.0/), Objective: Sensitive cognitive markers are still needed for frontotemporal dementia (FTD). The Benson Complex Figure Test (BCFT) is an interesting candidate test, as it assesses visuospatial, visual memory, and executive abilities, allowing the detection of multiple mechanisms of cognitive impairment. To investigate differences in BCFT Copy, Recall and Recognition in presymptomatic and symptomatic FTD mutation carriers, and to explore its cognitive and neuroimaging correlates. Method: We included cross-sectional data from 332 presymptomatic and 136 symptomatic mutation carriers (GRN, MAPT or C9orf72 mutations), and 290 controls in the GENFI consortium. We examined gene-specific differences between mutation carriers (stratified by CDR® NACC-FTLD score) and controls using Quade's / Pearson Χ2 tests. We investigated associations with neuropsychological test scores and grey matter volume using partial correlations and multiple regression models respectively. Results: No significant differences were found between groups at CDR® NACC-FTLD 0-0.5. Symptomatic GRN and C9orf72 mutation carriers had lower Copy scores at CDR® NACC-FTLD ≥2. All three groups had lower Recall scores at CDR® NACC-FTLD ≥2, with MAPT mutation carriers starting at CDR® NACC-FTLD ≥1. All three groups had lower Recognition scores at CDR® NACC FTLD ≥2. Performance correlated with tests for visuoconstruction, memory, and executive function. Copy scores correlated with frontal-subcortical grey matter atrophy, while Recall scores correlated with temporal lobe atrophy. Conclusions: In the symptomatic stage, the BCFT identifies differential mechanisms of cognitive impairment depending on the genetic mutation, corroborated by gene-specific cognitive and neuroimaging correlates. Our findings suggest that impaired performance on the BCFT occurs relatively late in the genetic FTD disease process. Therefore its potential as cognitive biomarker for upcoming clinical trials in presymptomatic to early-stage FTD is most likely limited., The Dementia Research Centre is supported by Alzheimer's Research UK, Alzheimer's Society, Brain Research UK, and The Wolfson Foundation. This work was supported by the NIHR UCL/H Biomedical Research Centre, the Leonard Wolfson Experimental Neurology Centre (LWENC) Clinical Research Facility, and the UK Dementia Research Institute, which receives its funding from UK DRI Ltd., funded by the UK Medical Research Council, Alzheimer's Society and Alzheimer's Research UK. JDR is supported by the Miriam Marks Brain Research UK Senior Fellowship and has received funding from an MRC Clinician Scientist Fellowship (MR/M008525/1) and the NIHR Rare Disease Translational Research Collaboration (BRC149/NS/MH). This work was also supported by the MRC UK GENFI grant (MR/M023664/1), the Bluefield Project, the JPND GENFI-PROX grant (2019–02248), the Dioraphte Foundation [grant numbers 09–02-00], the Association for Frontotemporal Dementias Research Grant 2009, The Netherlands Organization for Scientific Research (NWO) (grant HCMI 056–13-018), ZonMw Memorabel (Deltaplan Dementie; project numbers 733050103 and 733050813), JPND PreFrontAls Consortium (project number 733051042) and Instituto de Salud Carlos III, Spain, and FEDER funds (grant number 20/00448). JBR is supported by the Wellcome Trust (103838), Medical Research Council (SUAG092 G116768) and the NIHR Cambridge Biomedical Research Centre (BRC-1215 − 20014: the views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care). This work was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany's Excellence Strategy within the framework of the Munich Cluster for Systems Neurology (EXC 2145 SyNergy – ID 390857198). JMP is supported by a fellowship award from Alzheimer Nederland (WE.15–2019.02). This work was conducted using the MRC Dementias Platform UK (MR/L023784/1 and MR/009076/1).

The paper deals with the issue of the mixed-reality usage in the design of production systems, its changes during expansion, or technological changes in the production, where it is necessary to flexibly and quickly verify the integration of a new machine into the existing layout and eliminate collision situations even before the installation of a physical machine in production. This is realized through Vumark’s design methodology, which was verified and applied in the conditions of the production environment of the Innovation and Prototyping Centre in the Faculty of Mechanical Engineering at the Technical University of Kosice. The individual parts of the paper describe the Vumark deployment procedure in the production area and the software and hardware resources that the user can apply. Three production machines and one robotic device selected from the Factory design software database were chosen for the experiment. The chosen method enables us to verify during the experiment several variants of deployment the machines in the layout and thus to find the optimal location in a very short time. The experiment showed that the chosen method is applicable in practice and brings savings of time, costs, and energy especially when changing the layout or replacing the machine in the production hall.

Insoluble particles in ice cores record signatures of past climate parameters like vegetation dynamics, volcanic activity, and aridity. For some of them, the analytical detection relies on intensive bench microscopy investigation and requires dedicated sample preparation steps. Both are laborious, require in-depth knowledge, and often restrict sampling strategies. To help overcome these limitations, we present a framework based on flow imaging microscopy coupled to a deep neural network for autonomous image classification of ice core particles. We train the network to classify seven commonly found classes, namely mineral dust, felsic and mafic (basaltic) volcanic ash grains (tephra), three species of pollen (Corylus avellana, Quercus robur, Quercus suber), and contamination particles that may be introduced onto the ice core surface during core handling operations. The trained network achieves 96.8 % classification accuracy at test time. We present the system's potential and its limitations with respect to the detection of mineral dust, pollen grains, and tephra shards, using both controlled materials and real ice core samples. The methodology requires little sample material, is non-destructive, fully reproducible, and does not require any sample preparation procedures. The presented framework can bolster research in the field by cutting down processing time, supporting human-operated microscopy, and further unlocking the paleoclimate potential of ice core records by providing the opportunity to identify an array of ice core particles. Suggestions for an improved system to be deployed within a continuous flow analysis workflow are also presented.

The most common cause in the etiology of sudden cardiac death (SCD) is ischemic heart disease due to atherosclerosis. Postmortem diagnosis can be made by histopathological examinations, but routine histopathological examinations are limited, especially in the early period of postmortem ischemia. For this reason, many methods are being investigated for the postmortem diagnosis of ischemia, and postmortem biochemical studies are promising. In our study, we evaluated the biochemical markers; hs-cTnT, NT-proBNP, H-FABP, pentraxin-3, copeptin, ischemic modified albumin (IMA), and PAPP-A in postmortem serums. In forensic pathology practice, it was investigated whether it would be useful to go to the diagnosis by measuring more than one marker in a single biological fluid in SCD cases. The study included 35 sudden cardiac death cases and 24 control cases and as a result of our study, hs-cTnT, NT-proBNP, and H-FABP values were found to be significantly higher in the SCD group than in the control group. Within the scope of the multi-marker strategy, models were tried to be developed in which the markers were used together, and it was concluded that the model consisting of the myocardial ischemia marker hs-cTnT, the myocardial stress marker NT-proBNP, and the inflammation marker pentraxin 3 was the most accurate combination by correctly classifying the cases at a rate of 94.9%. As a result, it was thought that it would be appropriate to use the multi-marker strategy which is widely used in clinical applications, also in forensic medicine applications.

Rye (Seale cereale L.) is one of the few cross-pollinating small-grain cereals and is mainly used for bread baking, biogas production and as animal feed. In its largest cultivation area (Northern, Central and Eastern Europe, including the Russian Federation) two major rust diseases, stem rust (SR) caused by Puccinia graminis f. sp. secalis and leaf rust (LR) caused by Puccinia recondita, can cause severe yield losses. Whereas LR can be found in most rye growing areas every year, SR is occurring less regularly, but can become epidemic in some years. The general occurrence of stem rust in Germany is becoming more regular, especially when hot summers provide optimum conditions for the growth and the spread of this fungus. Resistant cultivars can be a successful way to control both diseases, but SR is not assessed in the (German) variety registration and still several cultivars can be found that are susceptible or medium resistant for LR. Before the studies of this thesis were conducted, no marker-associated SR resistance gene locus was known and only six LR resistance loci had been reported. Rust resistances can be classified into all-stage resistances (ASR), that are usually caused by single R-genes and adult-plant resistances (APR), that are characterized by smaller (quantitative) effects and can only be observed in the adult-plant stage and thus make field tests mandatory. This thesis aimed on identifying resistant genotypes and respective resistance loci for SR and LR resistances in the rye genome. Two different material groups were used: biparental populations composed of inbred lines and populations composed of self-incompatible single plants. In total ten biparental populations and two additional testcross populations were studied, each constituting 68-90 genotypes. Self-incompatible populations were genetic resources from the Russian Federation, Austria and the United States of America and had 68-74 single plants each. Inbred lines were assessed in multi-environmental field trials (4-6 environments per population) and to guarantee high disease pressure, SR was artificially inoculated in contrast to naturally occurring LR in all environments. In addition, two different kind of seedling tests, one based on inoculations of entire seedling plants and one based on inoculation of detached leaves, were used to assess SR resistance. Mixed linear models were used to analyze the phenotypic data from field experiments and (mixed) cumulative logit models were used to analyze ordinal data resulting from seedling tests. Due to small sample size of a single detached leaf per genotype and isolate in self-incompatible populations, the results based on cumulative modes were cross checked with a non-parametric test. Both, progenies from biparental populations and single plants from self-incompatible populations were genotyped with single nucleotide polymorphism (SNP) based markers (Illumina iSelect 10K SNP chip or DArTseqTM) and appropriate statistical tests for phenotype-marker association were applied. This was achieved by extending phenotypic models with additive and dominant marker effects and their respective interaction with the environment or the isolates. Two marker-associated SR ASR loci (Pgs1, Pgs3.1) could be identified in biparental populations that were responsible for (large) qualitative differences between resistant and susceptible plants in the field and/or seedling stage. Additionally, 14 quantitative trait loci (QTLs) were shown to be responsible for SR APR. For LR, except one QTL found at similar position compared to a previous study, two new genes (Pr7, Pr8) and three QTLs were identified. Self-incompatible rye populations were used for the first time for association mapping and three SR resistance loci (Pgs1 - Pgs3) could be identified. Two thereof were also found within biparental mapping populations by means of QTL mapping and this was considered as prove of this new method. Throughout all studies, the natural cross-pollinating character of rye had to be considered in choosing appropriate methods and for developing rust resistant rye hybrids. This thesis includes breeding material from the largest European rye breeding companies and experiments were conducted in close cooperation with them. The characterization of breeding material for SR and LR infection, development of (new) mapping approaches, detection of resistance loci and marker candidates in the rye genome and finally the discussion of selection strategies provides a solid basis for breeders to develop the most durable SR and LR resistant rye cultivars. For scientists, new research topics could be, for example, the cloning of rye genes or a more thorough understanding of pathogen dynamics to finally achieve durable resistance in future. Roggen (Secale cereale L.) ist einer der wenigen kleinkörnigen Fremdbefruchter bei den Getreiden und wird hauptsächlich zum Brotbacken, zur Biogasproduktion und als Tierfutter verwendet. Im größten Anbaugebiet (Nord-, Zentral- und Osteuropa inkl. Russland) können zwei Rost-Krankheiten, Schwarzrost (SR), verursacht durch Puccinia graminis f. sp. secalis und Braunrost (BR), verursacht durch Puccinia recondita, hohe Ertragsverluste verursachen. Resistente Sorten können eine erfolgreiche Möglichkeit zur Bekämpfung der Krankheiten sein, SR wird aber in Deutschland bei der Sortenzulassung nicht erfasst und man findet auch noch einige Sorten, die BR-anfällig oder nur mäßig resistent gegen BR sind. Vor der Durchführung dieser Studien, war kein Marker-assoziierter SR Resistenzgen-Locus bekannt und nur sechs BR Resistenzgen-Loci waren bereits beschrieben. Rostresistenzen können unterschieden werden in: All-Stadien-Resistenzen (ASR), welche üblicherweise durch einzelne R-Gene bedingt werden, und Adultpflanzen-Resistenzen (APR), welche durch kleinere (quantitative) Effekte charakterisiert sind. Letztere können nur im Adultpflanzen-Stadium beobachtet werden und deshalb sind Feldversuche notwendig. Diese Studie zielte darauf ab, resistente Genotypen und entsprechende Resistenz-Loci für SR und LR-Resistenzen im Roggen-Genom zu identifizieren. Dazu wurden zwei verschiedene Materialgruppen verwendet: Biparentale Populationen, die aus Inzucht-linien bestanden, und Populationen aus selbstinkompatiblen Einzelpflanzen. In Summe wurden zehn biparentale Populationen sowie zwei zusätzliche Testkreuzungs-Populationen mit jeweils 68-90 Genotypen untersucht. Selbstinkompatible Populationen waren genetische Ressourcen aus Russland, Österreich und den Vereinigten Staaten von Amerika und hatten jeweils 68-74 Pflanzen. Die Inzuchtlinien wurden in mehrortigen Feldversuchen (4-6 Umwelten pro Population) untersucht und um hohen Befall zu garantieren, wurde künstlich mit SR inokuliert, im Gegensatz zu BR, der an allen Orten natürlich auftrat. Zusätzlich wurden zwei verschiedene Sämlingstests, einer basierend auf kompletten Sämlingspflanzen, und einer basierend auf der Inokulation von abgeschnitten Blättern zur Bewertung der SR-Resistenz verwendet. Gemischte lineare Modelle wurden verwendet um die phänotypischen Daten aus den Feldversuchen zu analysieren und (gemischte) Grenzwertmodelle um die ordinalen Daten, die aus den Sämlingstests resultierten, zu analysieren. Aufgrund der kleinen Stichprobengröße in selbstinkompatiblen Populationen mit einem untersuchten Blatt pro Genotyp und Isolat, wurden die Ergebnisse basierend auf Grenzwertmodellen mit einem nicht-parametrischen Test gegengeprüft. Sowohl die Nachkommen der biparentalen Populationen als auch die Einzelpflanzen der selbstinkompatiblen Populationen wurden mit Einzelnukleotid-Polymorphismus (SNP)-basierten Markern (Illumina iSelect 10K SNP chip bzw. DArTseqTM) genotypisiert und passende statistische Test für die Phänotyp-Marker-Assoziation angewendet. Für diese wurden die phänotypischen Modelle mit additiven und dominanten Marker-Effekten und der entsprechenden Interaktion mit der Umwelt oder den Isolaten erweitert. Zwei Marker-assoziierte SR-ASR-Loci (Pgs1, Pgs3.1), welche für (große) qualitative Unterschiede im Adultpflanzen- und Sämlingsstadium verantwortlich waren, konnten in biparentalen Populationen identifiziert werden. Zusätzlich wurde gezeigt, dass 14 quantitative trait loci (QTL) für SR-ASR verantwortlich waren. Für BR, konnten, abgesehen von einem QTL, der an einer ähnlichen Position wie in einer anderen Studie gefunden wurde, zwei neue Gene (Pr7, Pr8) und drei weitere QTL identifiziert werden. Selbstinkompatible Populationen wurden hier zum ersten Mal für eine Assoziationskartierung verwendet und drei SR-Resistenzloci (Pgs1-Pgs3) gefunden. Zwei davon wurden auch mittels QTL-Kartierung in biparentalen Populationen gefunden was als Beweis für die Eignung dieser neuen Methode betrachtet wurde. Über alle Studien hinweg musste die natürliche Eigenschaft der Fremdbefruchtung bei Roggen bei der Wahl passender Methoden und der Entwicklung von rostresistenten Roggenhybriden beachtet werden. Diese Studie beinhaltet Zuchtmaterial von den größten europäischen Zuchtfirmen und die Experimente wurden in enger Zusammenarbeit mit diesen durchgeführt. Die Charakterisierung von Zuchtmaterial für SR- und BR-Befall, die Entwicklung von (neuen) Kartierungsmethoden, die Entdeckung von Resistenzloci und Markerkandidaten im Roggengenom und schließlich die Diskussion von Selektionsstrategien liefern eine solide Basis um dauerhafte SR- und BR-resistente Sorten zu entwickeln. Neue Forschungsthemen für Wissenschaftler könnten zum Beispiel die Klonierung von Resistenzgenen oder ein besseres Verständnis der Pathogen-Dynamik sein, um in Zukunft gezielt eine dauerhafte Resistenz zu erreichen.

Periprosthetic joint infection (PJI) is a rare yet devastating complication following total joint arthroplasty (TJA). Early and accurate diagnosis of PJI is paramount in order to maximize the chances of successful treatment. However, we are yet to identify a single "gold standard" test for the diagnosis of PJI. As a result, the diagnosis of PJI is often challenging. Currently, the 2018 ICM definition of PJI is the only validated diagnostic criteria available. This article will review the importance of serum and synovial biomarkers in the diagnosis of PJI. In addition, it will provide a brief overview of the emerging modalities for the identification of infections in this setting.

Simple Summary Colorectal cancer (CRC) patients with peritoneal metastases (PM) have a poor prognosis. Currently, research has been ongoing to develop new treatment options for CRC patients with PM. DNA/RNA alterations identification in the primary tumor might help identify patients who are at high risk for developing PM postoperatively. These patients could benefit from preventive or early treatment. The aim of this systematic review is to create an overview of studies which analyzed genomic DNA and RNA expression alteration correlated to PM with the goal of identifying potentially predictive biomarkers. We included 32 studies investigating primary colorectal tumors of 18,906 patients. Only BRAF mutations were reported as significantly associated with PM in 10 of 17 studies. As no specific biomarkers in the primary tumors of CRC patients could have been identified, further research with comprehensive genomic profiling is still desirable. Background: As colorectal cancer (CRC) patients with peritoneal metastases (PM) have a poor prognosis, new treatment options are currently being investigated for CRC patients. Specific biomarkers in the primary tumor could serve as a prediction tool to estimate the risk of distant metastatic spread. This would help identify patients eligible for early treatment. Aim: To give an overview of previously studied DNA and RNA alterations in the primary tumor correlated to colorectal PM and investigate which gene mutations should be further studied. Methods: A systematic review of all published studies reporting genomic analyses on the primary tissue of CRC tumors in relation to PM was undertaken according to PRISMA guidelines. Results: Overall, 32 studies with 18,906 patients were included. BRAF mutations were analyzed in 17 articles, of which 10 found a significant association with PM. For all other reported genes, no association with PM was found. Two analyses with broader cancer panels did not reveal any new biomarkers. Conclusion: An association of specific biomarkers in the primary tumors of CRC patients with metastatic spread into peritoneum could not be proven. The role of BRAF mutations should be further investigated. In addition, studies searching for potential novel biomarkers are still required.

u araştırma, ülkemizde üretilen önemli yağ bitkilerinden biri olan aspirde (Carthamus tinctorius L.) pas hastalığına neden olan Puccinia carthami fungusunun teşhisi için PCR’a dayalı moleküler yöntemlerin geliştirilmesi amacıyla gerçekleştirilmiştir. Tez kapsamında fungusların moleküler tanısında yaygın olarak kullanılan ITS bölgesi ve β-tubulin geni hedef alınmıştır. Bunun için NCBI da bulunan Puccinia türlerinin ITS bölgesi ve β-tubulin gen dizileri kullanılmış, diziler bioedit programı aracılığı ile hizalanarak türe spesifik varyasyonun en fazla olduğu bölgeler tespit edilmiştir. Ardından varyasyon bölgesini çoğaltacak biçimde ortak dizilere özgü primerler tasarlanmıştır. Tez kapsamında 2 ITS (Pc.ITS-1 ve Pc.ITS-2) ve 1 β-tubulin (Pc.β-tub) primer çifti tasarlanıp kullanılmıştır. Bunlara ek olarak daha önce bölümümüzde yürütülen TÜBİTAK 2209A-Lisans projesi kapsamında P.tiriticina için tasarlanan ITS (Pt.ITS) ve β-tubulin (Pt.β-tub) primer çifti ile literatürde ayırıcı olduğu rapor edilen RA68 primeri de çalışmaya dahil edilmiştir. İncelenen primer çiftlerinin P.carthami’nin teşhisi için kullanılabilir olup olmadıkları bölgemizde gözlenen farklı fungal bitki patojenlerinde tarama yapılarak tespit edilmiştir. Tarama için Puccinia triticina, Ustilago, Phoma spp., Fusarium graminearum, Fusarium culmorum, Plasmaphora halstedi, Pyrenophora f. teres, Cochliobolus sativus, Macrophomina phaseolina fungusları kullanılmıştır. Sunulan tez çalışması kapsamında P.carthami’ye özgü tasarlanan primerlerden Pc.β-tub primeri P.carthami ve P.triticina’da aynı büyüklükte bantlar verirken çalışılan diğer patojenlerden ayrımı sağlanmıştır. Pt.β-tub primeri ise P.carthami’de herhangi bir DNA fragmenti çoğaltmamıştır. ITS bölgesine özgü tasarlanan primerlerden Pc.ITS-1 primer çiftinin birden fazla DNA fragmenti çoğaltımı ile hedef dışı genom bölgelerine de bağlanabildiği ancak P.carthami’ye özgü çoğalttığı 302 bç’lik DNA fragmenti ile de moleküler teşhis için kullanılabileceği görüşüne varılmıştır. Pc.ITS-2 primer çiftinde ise P.carthami’de çoğaltılan 364 bç ve 445 bç uzunluklarında 2 DNA fragmentinin teşhis için kullanılabileceği tespit edilmiştir. Bir diğer ITS bölgesi primeri olan Pt.ITS ise belirgin bir şekilde P.carthami ve P.triticina’yı kendi aralarında ve diğer patojenlerden ayırmıştır. Kullanılan tüm primerler arasında moleküler teşhis için en umut verici olan Pt.ITS primer çifti olmuştur. Ön bulgular bu primer çiftinin Puccina türlerine özgü ve türleri birbirinden ayırıcı nitelikte olabileceğini göstermektedir. Bunu doğrulamak için daha fazla Puccinia türü ile çalışmanın genişletilmesi gerekmektedir. Liretaürde P.triticina için rapor edilmiş RA68 primer çifti ile elde edilen sonuçlar ise RA68’in P.triticina için moleküler teşhiste kullanılabilirliği doğrulanmıştır. Bunun yanında P.carthami’de elde edilen 388 ve 452 bç uzunluğunda 2 DNA fragmentinin, P.carthami’de moleküler teşhis için alternatif olabileceği görüşüne varılmıştır. Sonuç olarak tez çalışmasında test edilen 6 primerden Pc.ITS-1 ve Pc.ITS-2, sadece P.carthami için ayırıcı iken Pt.ITS ve RA68 her iki Puccinia türü için de spesifik DNA fragmentleri üretmiştir. Böylece P.carthami’nin klasik yöntemlere göre hızlı ve tam teşhisini mümkün kılacak moleküler yöntem geliştirilmiştir. This research was carried out in order to develop PCR-based molecular methods for the diagnosis of Puccinia carthami fungus, which causes rust disease in safflower (Carthamus tinctorius L.), one of the important oil plants grown in our country. Within the scope of the thesis, the ITS region and β-tubulin gene, which are widely used in the molecular diagnosis of fungi, were targeted. For this, the ITS region and β-tubulin gene sequences of Puccinia species found in NCBI were used, and the regions with the highest species-specific variation were determined by aligning the sequences via the bioedit program. Then, primers specific to common sequences were designed to amplify the region of variation. Within the scope of the thesis, 2 ITS (Pc.ITS-1 and Pc.ITS-2) and 1 β-tubulin (Pc.β-tub) primer pairs were designed and used. In addition to these, ITS (Pt.ITS) and β-tubulin (Pt.β-tub) primer pair designed for P.tiriticina within the scope of the TÜBİTAK 2209A-License project previously carried out in our department, and the RA68 primer, which was reported to be distinctive in the literature, were also included in the study. Whether the examined primer pairs can be used for the diagnosis of P.carthami was determined by screening different fungal plant pathogens observed in our region. For screening, Puccinia triticina, Ustilago, Phoma spp., Fusarium graminearum, Fusarium culmorum, Plasmaphora halstedi, Pyrenophora f. teres, Cochliobolus sativus, Macrophomina phaseolina fungi were used. Within the scope of the presented thesis, Pc.β-tub primer, one of the primers designed specifically for P.carthami, gave bands of the same size in P.carthami and P.triticina, while distinguishing them from other pathogens studied. Pt.β-tub primer did not amplify any DNA fragments in P.carthami. It was concluded that Pc.ITS-1 primer pair, one of the primers designed specifically for ITS region, can bind to non-target genome regions by amplifying more than one DNA fragment, but it can also be used for molecular diagnosis with a 302 bp DNA fragment amplified specifically for P.carthami. In the Pc.ITS-2 primer pair, it was determined that 2 DNA fragments of 364 bp and 445 bp lengths amplified in P.carthami could be used for diagnosis. Another ITS region primer, Pt.ITS, distinctly separated P.carthami and P.triticina among themselves and from other pathogens. Of all the primers used, the Pt.ITS primer pair was the most promising for molecular diagnostics. Preliminary findings suggest that this primer pair may be specific to Puccina species and may be species discriminating. To confirm this, the study needs to be expanded with more Puccinia species. The results obtained with the RA68 primer pair reported for P. triticina in the literature confirmed the usability of RA68 in molecular diagnosis for P. triticina. In addition, it was concluded that 2 DNA fragments with a length of 388 and 452 bp obtained in P.carthami could be an alternative for molecular diagnosis in P.carthami. As a result, Pc.ITS-1 and Pc.ITS-2 of the 6 primers tested in the thesis study were distinctive only for P.carthami, while Pt.ITS and RA68 produced specific DNA fragments for both Puccinia species. Thus, a molecular method has been developed that will enable rapid and complete diagnosis of P.carthami according to classical methods.

Данная статья посвящена определению понятия когнитивного диссонанса и лингвистическим знакам англоязычного медиадискурса, репрезентирующим данный феномен. В статье приводятся определения когнитивного диссонанса, используемые в психологии, социологии, лингвистике, переводоведении, межкультурной коммуникации. Проведен обзор работ исследователей, занимавшихся изучением теории когнитивного диссонанса. Предпринята попытка вывести свое определение когнитивного диссонанса. В работе представлены определения медиадискурса. Рассматриваются ситуации возникновения когнитивного диссонанса, отражающиеся в медиадискурсе. Приводятся различные примеры проявления когнитивного диссонанса с анализом характерных языковых единиц (маркеров). В процессе исследования применялись следующие методы: метод дискурс-анализа, метод контекстуального анализа, концепт -анализ, метод функционально-стилистического анализа. Информация, полученная человеком посредством медиадискурса, может привести к возникновению психологического диссонанса, то есть ситуации, в которой новые сведения не вполне соответствуют (или даже совсем противоречат) его системе знаний. Для того, чтобы избавиться от неприятного состояния, человек либо меняет свое представление об этом явлении (или событии), либо меняет свое поведение. Он стремится к внутреннему балансу своей когнитивной системы. В данном случае малоприятное состояние все же побуждает человека вернуться к состоянию консонанса. Наша задача – объяснить этот феномен и на примерах из медиадискурса выделить языковые знаки, сигнализирующие о возникновении когнитивного диссонанса и/или свидетельствующие о попытке избавиться от него. Для этого нами были выработаны экстралингвистические и лингвистические критерии выявления когнитивного диссонанса. В этом заключается научная значимость исследования. Проведенное исследование может послужить основой для разработки методических рекомендаций по данному направлению, что является практической значимостью работы., Бұл мақала когнитивтік диссонанс анықтамасын және осы құбылысты көрсететін ағылшын тіліндегі медиадискурстың тілдік белгілерін бөліп шығаруға арналған. Мақалада психологияда, әлеуметтануда, лингвистикада, аударматануда, мәдениетаралық коммуникацияда қолданылатын когнитивті диссонанс құбылысына анықтамалар берілген. Когнитивті диссонанс теориясын зерттеумен айналысатын зерттеушілердің еңбектері қарастырылған. Сондай-ақ когнитивті диссонанстың анықтамасын шығарып алуға әрекет жасалынды. Жұмыста медиадискурстың анықтамасы берілген. Медиадискурс негізінде когнитивті диссонанстың пайда болу жағдайлары қарастырылған. Когнитивті диссонанс пайда болу жағдайларына әртүрлі мысалдар және де қолданылған тілдік бірліктерге (маркерлерге) талдау жасалынды. Адамның медиадискурс арқылы алған ақпараты психологиялық диссонанстың пайда болуына әкелуі мүмкін. Бұл жаңа ақпарат оның білім жүйесіне сәйкес келмейтін (немесе толығымен қайшы келетін) жағдай. Жағымсыз күйден құтылу үшін адам осы құбылыс (немесе оқиға) туралы өз идеясын немесе мінез-құлқын өзгертеді. Ол өзінің танымдық жүйесінің ішкі тепе-теңдігіне ұмтылады. Яғни, когнитивтік диссонанс жағдайы жағымсыз болғандықтан, адам үндестік күйіне оралуға ынталандырады. Зерттеу процесінде келесі әдістер қолданылды: дискурстық талдау әдісі, контекстік талдау әдісі, концепциялық талдау, функционалдық-стилистикалық талдау әдісі. Біздің міндетіміз - бұл құбылысты түсіндіру және когнитивті диссонанс пайда болуын ескертетін және/немесе одан құтылу әрекетін көрсететін медиадискурстағы тілдік белгілерін анықтау. Бұл мақсатты орындалу үшін біз экстралингвистикалық және лингвистикалық критерийлерді әзірледік. Медиадискурстағы мысалдарды қарастыру реципиенттер санасында туындаған диссонанстың бар екенін дәлелдейді. Жүргізілген зерттеулер осы бағыттағы әдістемелік ұсыныстарды әзірлеуге негіз бола алады., This article is dedicated to the definition of the concept of cognitive dissonance and linguistic signs of English media discourse, representing this phenomenon. The article deals with the definition of the phenomenon of cognitive dissonance, used in psychology, sociology, linguistics, translation studies, intercultural communication. A review of the work of researchers engaged in the study of the theory of cognitive dissonance is given. There is also an attempt to elaborate the definition of cognitive dissonance. The work presents the definition of media discourse as well. The situations of the emergence of cognitive dissonance based on media discourse are considered. Different examples of the manifestation of cognitive dissonance are given along with the analysis of characteristic linguistic units (markers). Information obtained by a person through media discourse can lead to the emergence of psychological dissonance, i.e. situations in which new information does not correspond (or completely contradicts) person’s system of knowledge. In order to get rid of an unpleasant situation, a person either changes one’s presentation of this phenomenon (event), or changes one’s behavior. He or she strives for internal balance. In this case, though situation is unpleasant, it still encourages an individual to return to the state of the consonance in one’s cognitive system. Our task is to explain this phenomenon and, using examples from media discourse, to highlight linguistic signs signalizing the occurrence of cognitive dissonance and/or indicating an attempt to remove the latter. In order to achieve the aim extra linguistic and linguistic criteria have been developed., Филологические науки, Выпуск 1 (68) 2023

On aborde le phénomène de l’enchaînement au moyen des unités lexicales servant de marqueurs prédicatifs. Partant de l’hypothèse que chaque type de discours a ses propres marqueurs, on montre comment ces prédicats participent à la structuration sémantique d’un article lexicographique. Au moyen de l’analyse prédicative, on étudie le rôle de ces marqueurs dépassant amplement l’organisation structurante d’un énoncé, mais participant à la construction de son unité prédicative englobante., This article discusses the phenomenon of chaining by means of lexical units which serve as predicative markers. Starting from the hypothesis that each type of discourse has its own markers, we will show how these predicates participate in the semantic structuring of a lexicographical article. Through predicative analysis, we will study the role of these markers which participate in but goes beyond the structuring organization of an utterance as an encompassing predicative unity.

Nagetiere werden häufig als Modelltiere in der biomedizinischen Forschung eingesetzt, zum Beispiel im Rahmen von präklinischen Studien. Daher ist die Analyse der Fortbewegung von Nagetieren wie Mäusen oder Ratten ein wichtiger Bestandteil von wissenschaftlichen Studien in diesem und ähnlichen Forschungsgebieten. Allerdings besteht für die Anwendung von externen Markern bei der Ganganalyse das Problem, dass lose Haut und Fell die verlässliche Quantifizierung des Ganges hochgradig erschweren, während markerlose Ansätze diverse andere Nachteile aufweisen.Das Ziel dieser Diplomarbeit, die hauptsächlich an der Brown University (RI, USA) durchgeführt wurde, ist die Entwicklung eines neuen markerbasierten Ganganalysesystems auf der Grundlage von biplanaren Hochgeschwindigkeits-Fluoroskopie-Aufnahmen.Anstatt Marker extern anzubringen, wurde ein optimiertes Set an Markern, bestehend aus zwölf röntgendichten Marker-Kugeln mit einem Durchmesser von 0.26 mm, entwickelt und in das Weichgewebe der hinteren Gliedmaße von Mäusen injiziert. Für diese Injektionen wurden die zugehörigen Methoden und Techniken entwickelt.Um die schnellen Bewegungen kleiner Tiere wie Mäuse visualisieren zu können, wurden Verbesserungen am aktuellen Röntgensystem vorgenommen, die eine fünffache Steigerung der Präzision bewirkten. Dadurch konnte der Animations-Workflow XROMM (X-ray Reconstruction of Moving Morphology) weiterentwickelt werden, sodass die Entstehung von microXROMM (micro X-ray Reconstruction of Moving Morphology) ermöglicht wurde.Die Eigenschaft des Weichgewebes, die Marker zu ummanteln, wurde validiert, in dem die Migration der Marker im Gewebe von zehn Mäusen wöchentlich im Zeitrahmen von vier Wochen gemessen wurde. Dies ergab eine Bewegung mit einem Median von bis zu 0.28±0.0178 mm pro Woche für den Kniemarker und bis zu 0.50±0.0299 mm pro Woche für den Hüftmarker. Als unterstützendes Ergebnis wurde eine Sezierung vorgenommen, die zeigte, dass die Ummantelung auf eine nicht-pathologische Weise zustande gekommen war.Die Leistung des neuen Ganglabors für Mäuse während der Bewegung wurde überprüft, in dem die entwickelte 3D Strichfigur mit der Skelettkinematik der Knochen während simulierter Bewegung einer toten Maus verglichen wurde. Diese Validierung zeigte eine durchschnittliche Abweichung von 2.1 deg für den 3D inkludierten Winkel zwischen Tibia und Femur, und 1.4 deg für den 3D inkludierten Winkel zwischen Femur und Pelvis.Die entwickelte Methode ist daher für die potenzielle zukünftige Anwendung für Hochdurchsatz-Studien geeignet, da sie einen reproduzierbaren und unkomplizierten Zugang zu röntgenbasierter Ganganalyse von Nagetieren bietet., Rodent models are extensively used in biomedical and comparative research, for example in the context of preclinical studies. Consequently, the analysis of rodent locomotion is an important measure for scientific studies in these research areas. However, loose skin and fur artifacts pose an issue for reliable gait quantification when using external markers, while markerless approaches are subject to other disadvantages.This thesis aims to develop a new marker-based rodent gait analysis system on the basis of high-speed biplanar X-ray fluoroscopy images. This project was mostly conducted at Brown University (RI, USA).Rather than attaching markers externally, an optimal marker set consisting of twelve radiopaque 0.26 mm marker beads was developed to be injected into the mouse hindlimb soft tissue. For this purpose, corresponding injection techniques were established.To enable the collection of fluoroscopy images of small animals such as mice and their high velocity movements, the current X-ray system settings were improved to yield a five-fold increase in precision. This facilitated advancements of the imaging workflow XROMM (X-ray Reconstruction of Moving Morphology) which enabled the establishment of microXROMM (micro X-ray Reconstruction of Moving Morphology). The soft tissue’s ability to encapsulate the markers was validated by measuring marker bead migration in ten mice weekly over the course of four weeks, yielding a median movement of up to 0.28±0.0178 mm per week for the knee marker and up to 0.50±0.0299 mm per week for the hip marker. A microdissection was conducted to complement the migration measurement results, showing the encapsulation takes place in a non-pathological manner.The performance of the novel mouse gait laboratory during movement was validated by comparing the generated 3D stick figure to bone motion during simulated movement of a dead mouse. This validation showed a mean deviation of 2.1 deg for the 3D included joint angle between tibia and femur, and 1.4 deg for the 3D included joint angle between femur and pelvis.The developed method is therefore suitable for potential future collaborators conducting high-throughput rodent studies, as it offers a reproducible and reasonably straight-forward approach to X-ray based rodent gait analysis.

Simple Summary Colorectal cancer (CRC) patients with peritoneal metastases (PM) have a poor prognosis. Currently, research has been ongoing to develop new treatment options for CRC patients with PM. DNA/RNA alterations identification in the primary tumor might help identify patients who are at high risk for developing PM postoperatively. These patients could benefit from preventive or early treatment. The aim of this systematic review is to create an overview of studies which analyzed genomic DNA and RNA expression alteration correlated to PM with the goal of identifying potentially predictive biomarkers. We included 32 studies investigating primary colorectal tumors of 18,906 patients. Only BRAF mutations were reported as significantly associated with PM in 10 of 17 studies. As no specific biomarkers in the primary tumors of CRC patients could have been identified, further research with comprehensive genomic profiling is still desirable. Background: As colorectal cancer (CRC) patients with peritoneal metastases (PM) have a poor prognosis, new treatment options are currently being investigated for CRC patients. Specific biomarkers in the primary tumor could serve as a prediction tool to estimate the risk of distant metastatic spread. This would help identify patients eligible for early treatment. Aim: To give an overview of previously studied DNA and RNA alterations in the primary tumor correlated to colorectal PM and investigate which gene mutations should be further studied. Methods: A systematic review of all published studies reporting genomic analyses on the primary tissue of CRC tumors in relation to PM was undertaken according to PRISMA guidelines. Results: Overall, 32 studies with 18,906 patients were included. BRAF mutations were analyzed in 17 articles, of which 10 found a significant association with PM. For all other reported genes, no association with PM was found. Two analyses with broader cancer panels did not reveal any new biomarkers. Conclusion: An association of specific biomarkers in the primary tumors of CRC patients with metastatic spread into peritoneum could not be proven. The role of BRAF mutations should be further investigated. In addition, studies searching for potential novel biomarkers are still required.

Background and Aim: Spermatogonial stem cells (SSCs) have previously been isolated from animals' testes, cultured in vitro, and successfully transplanted into compatible recipients. The SSC unique characteristic has potential for exploitation as a reproductive tool and this can be achieved through SSC intratesticular transplantation to surrogate sires. Here, we aimed at comprehensively analyzing published data on in vitro maintenance of SSC isolated from the testes of livestock animals and their applications. Materials and Methods: The literature search was performed in PubMed, Science Direct, and Google Scholar electronic databases. Data screening was conducted using Rayyan Intelligent Systematic Review software (https://www.rayyan.ai/). Duplicate papers were excluded from the study. Abstracts were read and relevant full papers were reviewed for data extraction. Results: From a total of 4786 full papers screened, data were extracted from 93 relevant papers. Of these, eight papers reported on long-term culture conditions (>1 month) for SSC in different livestock species, 22 papers on short-term cultures (5-15 days), 10 papers on transfection protocols, 18 papers on transplantation using different methods of preparation of livestock recipients, and five papers on donor-derived spermatogenesis. Conclusion: Optimization of SSC long-term culture systems has renewed the possibilities of utilization of these cells in gene-editing technologies to develop transgenic animals. Further, the development of genetically deficient recipients in the endogenous germline layer lends to a future possibility for the utilization of germ cell transplantation in livestock systems.

Cell-cell and cell-matrix adhesion proteins that have been implicated in colorectal epithelial integrity and epithelial-to-mesenchymal transition could be robust prognostic and potential predictive biomarkers for standard and novel therapies. We analyzed in situ protein expression of E-cadherin (ECAD), integrin beta 4 (ITGB4), zonula occludens 1 (ZO-1), and cytokeratins in a single-hospital series of Norwegian patients with colorectal cancer (CRC) stages I-IV (n = 922) using multiplex fluorescence-based immunohistochemistry (mfIHC) on tissue microarrays. Pharmacoproteomic associations were explored in 35 CRC cell lines annotated with drug sensitivity data on > 400 approved and investigational drugs. ECAD, ITGB4, and ZO-1 were positively associated with survival, while cytokeratins were negatively associated with survival. Only ECAD showed independent prognostic value in multivariable Cox models. Clinical and molecular associations for ECAD were technically validated on a different mfIHC platform, and the prognostic value was validated in another Norwegian series (n = 798). In preclinical models, low and high ECAD expression differentially associated with sensitivity to topoisomerase, aurora, and HSP90 inhibitors, and EGFR inhibitors. E-cadherin protein expression is a robust prognostic biomarker with potential clinical utility in CRC.

Background Spermatogenesis is the process by which male gametes are formed from spermatogonial stem cells and it is essential for the reliable transmission of genetic information between generations. To date, the dynamic transcriptional changes of defined populations of male germ cells in pigs have not been reported. Results To characterize the atlas of porcine spermatogenesis, we profiled the transcriptomes of ~ 16,966 testicular cells from a 150-day-old pig testis through single-cell RNA-sequencing (scRNA-seq). The scRNA-seq analysis identified spermatogonia, spermatocytes, spermatids and three somatic cell types in porcine testes. The functional enrichment analysis demonstrated that these cell types played diverse roles in porcine spermatogenesis. The accuracy of the defined porcine germ cell types was further validated by comparing the data from scRNA-seq with those from bulk RNA-seq. Since we delineated four distinct spermatogonial subsets, we further identified CD99 and PODXL2 as novel cell surface markers for undifferentiated and differentiating spermatogonia, respectively. Conclusions The present study has for the first time analyzed the transcriptome of male germ cells and somatic cells in porcine testes through scRNA-seq. Four subsets of spermatogonia were identified and two novel cell surface markers were discovered, which would be helpful for studies on spermatogonial differentiation in pigs. The datasets offer valuable information on porcine spermatogenesis, and pave the way for identification of key molecular markers involved in development of male germ cells.

Das Merkelzellkarzinom (MCC) ist ein hoch aggressiver Tumor, dessen Behandlung sich vor allem im fortgeschrittenen Stadium höchst problematisch gestaltet. Es konnte gezeigt werden, dass es signifikant häufiger linksseitig lokalisiert ist. Das Ziel war deshalb die Expression der TGF-\(\beta\) assoziierten Proteine Lefty und Nodal im MCC zu bestimmen und mit klinischen Parametern zu korrelieren. 29 Patienten wurden immunhistochemisch auf die Expression der Proteine Lefty und Nodal untersucht. Durch Anwendung des H-Scores wurde die Expression quantifiziert. Im Rahmen dieser Arbeit konnte gezeigt werden, dass niedrige Expressions-Level von Lefty im primären MCC einen starken Prädiktor für MCC-spezifische Todesfälle darstellen. Die Eignung von Lefty und Nodal als diagnostisch oder sogar therapeutisch bedeutsame Marker für die Behandlung des MCC sollte daher in weiterführenden Studien untersucht werden.

The determination of the authenticity of extra virgin olive oils (EVOOs) has become more interesting in recent years. Italy is the first country in Europe in terms of number of Protected Designation of Origin (PDO) oils, which connects consumers to a feeling of tradition and thus to higher quality standards. This work focused on the consideration of the inorganic content as a possible marker of EVOOs. Ten vegetable oils (VOs), eight Italian EVOOs and seven not Italian EVOOs were analyzed. After pretreatment by acid mineralization, Al, Ba, Ca, Cu, Fe, K, Li, Mg, Mn, Na, P, Sb, Se and Zn were determined by ICP-OES. The electrochemical properties of a selected group of EVOOs and other vegetal oils of different botanical origin were investigated by voltammetry. Carbon paste electrodes (CPEs) were prepared. The features observed in the voltammograms reflect the reactions of electroactive compounds, which are present in the oils. A chemometric treatment of the results was performed to assess the possibility to distinguish (i) the region of provenience considering the inorganic profile; and (ii) the plant species from which each oil was obtained on the basis of the current profile registered during voltammetric analysis. Inorganic composition seems to be a useful marker for the assessment of the geographical origin of an EVOO. The EVOO-CPEs voltammetry seems to have a good ability to distinguish the plant species of origin. This method could be useful to monitor the conservation status of the oils, as the redox profile is linked to the oxidative degradation state.

PURPOSE: Triggering of inflammatory responses and disruption of blood-spinal cord barrier (BSCB) integrity are considered pivotal events in the pathophysiology of traumatic spinal cord injury (TSCI). Yet, these events are poorly understood and described in humans. This study aims to describe inflammatory responses and BSCB integrity in human TSCI.METHODS: Fifteen TSCI patients and fifteen non-TSCI patients were prospectively recruited from Aarhus University Hospital, Denmark. Peripheral blood (PB) and cerebrospinal fluid (CSF) were collected at median day 0 [IQR: 1], median day 9 [IQR: 2], and median day 148 [IQR: 49] after injury. PB and CSF were analyzed for immune cells by flow cytometry, cytokines by multiplex immunoassay, and BSCB integrity by IgG Index.RESULTS: Eleven TSCI patients completed follow-up. Results showed alterations in innate and adaptive immune cell counts over time. TSCI patients had significantly increased cytokine concentrations in CSF at the first and second follow-up, while only concentrations of interleukin (IL)-4, IL-8, and tumor necrosis factor-α remained significantly increased at the third follow-up. In PB, TSCI patients had significantly increased IL-6, IL-8, and IL-10 concentrations and significantly decreased interferon-γ concentrations at the first follow-up. Results further showed increased IgG Index indicative of BSCB disruption in seven TSCI patients at the first follow-up, five TSCI patients at the second follow-up, and two patients at the third follow-up.CONCLUSIONS: Our results suggest that TSCI mainly triggers innate inflammatory responses that resolves over time, although with some degree of non-resolving inflammation, particularly in CSF. Our results cannot confirm BSCB disruption in all TSCI patients.

Introduction: It is unclear whether polyomavirus BK (BKPyV) microribonucleic acid (miRNA) measurement has additional diagnostic and predictive value in kidney transplant recipients (KTR) as compared to current methods of monitoring BKPyV DNA loads. Patients and methods: A retrospective, longitudinal study was performed in 30 KTR with BKPyV viruria (n = 10), BKPyV viremia (n = 10), or BKPyV-associated neuropathy (BKPyVAN) (n = 10). Bkv-miR-B1-3p and 5p and BKPyV DNA load were measured in urine and plasma and compared using receiver operating characteristic (ROC) curves. Results: Levels of Bkv-miR-B1-3p and 5p and BKPyV DNA correlated strongly. Overall, mostly analog courses of urinary and plasma miRNA and DNA loads were observed. Areas under the ROC curves were not significantly different between miRNAs and DNA. Only, in contrast to BKPyV DNA load, BKPyV miRNA levels increased from 6 to 12 months in the viremia group, while in the BKPyVAN group, a decline was seen in both DNA and miRNA. Conclusions: In this study, we could not demonstrate an additional value of BKPyV miRNA detection compared to BKPyV DNA monitoring in the early phase after kidney transplantation. We did observe significant differences between the viremia and the BKPyVAN groups during follow-up. This study was performed with a small number of patients and therefore results should be verified in a larger patient cohort. Furthermore, future studies with larger patient groups are necessary to elucidate final clinical value of these data. (Figure presented.).

Ruoran Wang,1 Min He,2 Jing Zhang,1 Shaobo Wang,3 Jianguo Xu1 1Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China; 2Department of Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China; 3Department of Infectious Diseases, Xi’an Hospital of Traditional Chinese Medicine, Xi’an, Shannxi Province, People’s Republic of ChinaCorrespondence: Jianguo XuDepartment of Neurosurgery, West China Hospital, Sichuan University, No. 37, Guoxue Alley, Chengdu, 610041, People’s Republic of ChinaEmail xujg@scu.edu.cnShaobo WangDepartment of Infectious Diseases, Xi’an Hospital of Traditional Chinese Medicine, No. 69, Fengcheng 8th Road, Xi’an, 710016, People’s Republic of ChinaEmail 1307799083@qq.comBackground: As an inflammation-based marker, red cell distribution width to platelet ratio (RPR) has been verified to be associated with disease severity and outcome in many clinical settings. We designed this study to evaluate the prognostic value of RPR in patients with traumatic brain injury (TBI).Methods: A total of 420 patients admitted with TBI were included in this study. Laboratory and clinical data were collected from an electronic medical record system. Univariate and multivariate logistic regression analyses were sequentially performed to discover risk factors of in-hospital mortality. Receiver operating characteristic (ROC) curves were drawn to confirm the predictive value of different markers including RPR in training set and testing set.Results: Non-survivors had higher level of RPR than survivors (P< 0.001). Logistic regression analysis showed that RPR was significantly associated with mortality even after adjusting for confounding factors (P< 0.001). The area under the ROC curve (AUC) value of Glasgow Coma Scale (GCS) for predicting mortality was 0.761 and 0775 in training set and testing set, respectively. And the constructed predictive model incorporating RPR had the highest AUC value of 0.858 and 0.884 in training set and testing set.Conclusion: RPR is significantly associated with mortality in TBI patients. Utilizing RPR to construct a predictive model is valuable to evaluate prognosis of TBI patients.Keywords: red cell distribution to platelet ratio, traumatic brain injury, prognosis, marker

Ruoran Wang,1 Min He,2 Jing Zhang,1 Shaobo Wang,3 Jianguo Xu1 1Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China; 2Department of Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China; 3Department of Infectious Diseases, Xi’an Hospital of Traditional Chinese Medicine, Xi’an, Shannxi Province, People’s Republic of ChinaCorrespondence: Jianguo XuDepartment of Neurosurgery, West China Hospital, Sichuan University, No. 37, Guoxue Alley, Chengdu, 610041, People’s Republic of ChinaEmail xujg@scu.edu.cnShaobo WangDepartment of Infectious Diseases, Xi’an Hospital of Traditional Chinese Medicine, No. 69, Fengcheng 8th Road, Xi’an, 710016, People’s Republic of ChinaEmail 1307799083@qq.comBackground: As an inflammation-based marker, red cell distribution width to platelet ratio (RPR) has been verified to be associated with disease severity and outcome in many clinical settings. We designed this study to evaluate the prognostic value of RPR in patients with traumatic brain injury (TBI).Methods: A total of 420 patients admitted with TBI were included in this study. Laboratory and clinical data were collected from an electronic medical record system. Univariate and multivariate logistic regression analyses were sequentially performed to discover risk factors of in-hospital mortality. Receiver operating characteristic (ROC) curves were drawn to confirm the predictive value of different markers including RPR in training set and testing set.Results: Non-survivors had higher level of RPR than survivors (P< 0.001). Logistic regression analysis showed that RPR was significantly associated with mortality even after adjusting for confounding factors (P< 0.001). The area under the ROC curve (AUC) value of Glasgow Coma Scale (GCS) for predicting mortality was 0.761 and 0775 in training set and testing set, respectively. And the constructed predictive model incorporating RPR had the highest AUC value of 0.858 and 0.884 in training set and testing set.Conclusion: RPR is significantly associated with mortality in TBI patients. Utilizing RPR to construct a predictive model is valuable to evaluate prognosis of TBI patients.Keywords: red cell distribution to platelet ratio, traumatic brain injury, prognosis, marker

The burial of a cadaver results in reduced arthropod activity and disruptions in colonisation patterns. Here, the distribution and diversity of mite taxa was studied across decomposition stages of shallowly buried pig carcasses (Sus scrofa domesticus). In total 300 mites (88 species) were collected from three pig shallow graves compared to 129 mites (46 species) from control (bare) soil samples at the same depth. A successional pattern of Acari higher taxa and families was observed, and species richness and biodiversity fluctuated throughout decomposition, whereas active decay showed the greatest biodiversity. Mesostigmata mites were the most abundant in ‘cadaver soils’ with a significant difference in the abundance of Parasitidae mites, whereas Oribatida mites (true soil mites) were the most abundant in control soils. Certain mite species were significantly associated with decay stages: Cornigamasus lunaris with ‘bloated’, Gamasodes spiniger with ‘active’, Eugamasus sp. and Lorryia reticulata with ‘advanced’, and Macrocheles matrius and Ramusella clavipectinata in ‘dry’. Scheloribates laevigatus was a marker of bare soil at a shallow depth and Vulgoramasus remberti of buried decomposition, not specific to any decay stage. Analysis of mite assemblages associated with head, torso and posterior body showed that Parasitus evertsi and M. matrius are attracted to beneath the thighs, whereas L. reticulata to beneath the head. This study highlights the value of mites as indicator species of decomposition and its stages, confirming (1) a succession of Acari on buried remains and (2) species specificity to body regions.

Purpose Physical work exposures are associated with sickness absence among older employees. We aimed to examine if they similarly contribute to all-cause sickness absence during early and mid-careers. Methods We used questionnaire data on physical work exposures linked to register data on sickness absence from 3542 municipal employees aged 19–39 years. Follow-up for the number of sickness absence days was 12 months. Exposures to physical workload, occupational environmental hazards, and sedentary work were divided into quartiles. In addition, duration of daily exposure to heavy work was included. Negative binomial regression models were used. Results Higher exposure to physical workload or hazardous exposures was associated with a higher number of sickness absence days. The age and gender adjusted rate ratios for sickness absence days among the participants whose exposure to physical workload was in the highest exposure quartile were 2.1 (95% CI 1.8‒2.5) compared with those whose exposure was in the lowest quartile. In addition, rate ratios for sickness absence days among participants who reported that they do heavy physical work 1.1‒2.0 h, 2.1‒4.0 h or over 4 h daily were 1.6 (1.3‒1.9), 1.5 (1.3‒1.8) and 1.7 (1.5‒2.1), respectively, compared with those who reported not doing physical work. Further adjustment for lifestyle factors or health characteristics attenuated the associations only slightly. Conclusion Exposure to physically demanding work is associated with a higher number of sickness absence days among municipal employees below 40 years of age. Physical working conditions should be considered when aiming to support later work ability.

Purpose Colorectal cancer (CRC) can be classified according to the chromosomal-instability pathway (a microsatellite-stable (MSS) pathway) and the microsatellite-instability (MSI) pathway. Adjuvant therapy after surgery in advanced CRC is usually based on fluoropyrimidine 5-fluorouracil (5-FU) alone or combined with other agents. Controversy however remains on the use of 5-FU-based regimens in treating MSI-related tumours. Aims To systematically investigate the relationship between tumour microsatellite profile and 5-year overall survival in patients with CRC treated with 5-FU. Methods A systematic literature review of PubMed and Embase databases was conducted. Pre-specified criteria determined study inclusion/exclusion. The PRISMA and QUADAS-2 criteria were used to assess study suitability and quality respectively. Patients were categorised as having either MSI or MSS CRC. Overall 5-year survival was estimated from Kaplan–Meier curves. Publication bias was assessed using funnel-plots and Egger’s test. Results 1807 studies were identified, with meta-analysis performed using nine studies. 5-FU treated individuals with CRC who died at 5 years were found to be 0.31 times less likely to have MSI than those who were alive, although this was not statistically significant. There was an insufficient number of studies to enable subgroup analysis by stage. Conclusions In this meta-analysis, MSI status does not alter 5-year survival of patients with CRC patients treated with adjuvant 5-FU, however there is significant heterogeneity in the design of individual studies in the data synthesis. More studies are necessary to clarify whether CRC patients with MSI CRC, in particular early stage, should be offered 5-FU based adjuvant chemotherapy.

Upland rice grown by rice farmers is having the lowest productivity in the rice production system. Drought stress is the most severe abiotic constraint for upland rice. The improvement of rice productivity in such ecosystems is essential to meet the food security needs of the population. Therefore, the cultivation of drought tolerant rice is becoming an increasingly important task. Numerous minor traits have been proposed to assist plant breeders in their selection, but most of these traits are not used in breeding because they are not practical for breeding purposes, have low heritability, or are not very correlated with grain productivity. There has been shown, that standardization of drought screening improves heritability under stress to the values similar to those obtained for the yields under well-watered conditions. Nowadays there has now been proven that drought-resistant varieties can be developed by direct selection for productivity under stressful conditions. Currently, there have been identified many quantitative trait loci (QTL) of drought tolerance in rice, but only a few of them are suitable for use in marker breeding. However, the identified genes of great drought tolerance can be effectively used in breeding for drought tolerance. The use of molecular markers will improve the efficiency of breeding work. The current review has briefly considered the importance of rice, its various production systems, and the impact of drought stress on rice production. There have been discussed the physiological mechanisms contributing to the maintenance of grain productivity under drought conditions, and there have been analyzed the breeding methods for improvement of drought resistance.

Context Tangwang Mingmu granule (TWMM), a traditional Chinese medicine, has been widely used in the treatment of diabetic retinopathy (DR), the most common microvascular complication in diabetes mellitus. Objective To establish a method to select target compounds from herbs for a pharmacokinetic study using network pharmacology, which could be applied in clinical settings. Materials and methods First, UPLC/Q Exactive Q-Orbitrap and GCMS 2010 were used to determine the non-volatile and volatile ingredients of TWMM. Based on the identified compounds, network pharmacology was used to screen the key compounds and targets of TWMM in the treatment of DR. Based on the compound-target-pathway network and identification of components emigrant into blood, the potential compound markers in vivo were chosen. Then, Sprague-Dawley (SD) rats were administrated of TWMM at a 9.6 g/kg dose to investigating pharmacokinetic parameters using the UPLC-QQQ-MS. Results Ninety and forty-five compounds were identified by UPLC-MS and GC-MS, respectively. Based on the network pharmacology, nine compounds with a degree value above 15 were screened and implied that these compounds are the most active in DR treatment. Moreover, criteria of degree value greater than 7 were applied, and PTGS2, NOS2, AKT1, ESR1, TNF, and MAPK14 were inferred as the core targets in treating DR. After identification of components absorbed into blood, luteolin and formononetin were selected and used to investigate the pharmacokinetic parameters of TWMM after its oral administration. Conclusions The reported strategy provides a method that combines ingredient profiling, network pharmacology, and pharmacokinetics to determine luteolin and formononetin as the pharmacokinetic markers of TWMM. This strategy provides a clinically relevant methodology that allows for the screening of pharmacokinetic markers in Chinese medicines.

Background To date, there is no reliable non-invasive marker for the early detection and diagnosis of endometriosis available possibly resulting in a delayed diagnosis and consequently an unnecessary long ordeal for the individual woman. Therefore, the primary objective of the current study was to evaluate whether the combination of a thyroid-stimulating hormone (TSH) level > 2.5 µlU/ml and premenstrual spotting could serve as non-invasive markers of endometriosis. A secondary objective was to determine whether typical symptoms of endometriosis like dysmenorrhea and/or dyspareunia could increase the diagnostic reliability. Methods We conducted a retrospective, case–control study with 167 female patients at the Department of OB/GYN and REI (UniKiD) of the medical center of the University of Düsseldorf, between January 2015 and December 2016. 107 women with surgically confirmed endometriosis were compared to 60 without endometriosis (controls). To evaluate the diagnostic accuracy, we considered sensitivity, specificity and predictive values. In order to assess the association between the non-invasive markers and endometriosis an odds ratio (OR) with a 95% confidence interval was calculated. Results In our cohort, diagnosis of endometriosis with non-invasive markers according to their sensitivity yielded the following ranking: increased TSH level, premenstrual spotting, combination of both previous parameters, addition of dysmenorrhea, addition of dyspareunia and combination of all parameters. Conclusion The existence of endometriosis should be taken into consideration when a patient suffers from thyroid dysfunction and premenstrual spotting. Apart from an increased TSH level, the presence of premenstrual spotting underlines the possible diagnosis of endometriosis with non-invasive markers and therefore, the patient´s history needs to be taken into account carefully. Trial registration The retrospective study was approved by the Ethics Committee of the medical faculty of the Heinrich-Heine University, Düsseldorf, Germany, Registration number Düsseldorf: 5371R (approved: April 04th, 2016). Since the design of the study was retrospective no written informed consent was necessary.

Proximal urea cycle disorders (PUCDs) are not included in most newborn screening programs due to the lack of adequate markers to monitor. Failure to alter citrulline and glutamine levels, the prognostic markers commonly used, can results in high false negative. Therefore, new biomarkers, prognostic of PUCDs, are strongly desirable.We used tandem mass spectrometry to analyze blood spot from PUCDs patients during their follow up in our referral center focusing on glutamine to glutamate (Gln/Glu) ratio. We reanalyzed the same specimens of three patients after two months and the specimen of a new patient with suspicious of PUCD disorder.Specimens of our patients shown a significant elevation of the ratio Gln/Glu compared to that of a healthy population (p 0.05) as well as the specimens analyzed after two months, while the glutamine concentration dropped. New patient, showing high value of the ratio, was molecularly confirmed as PUCD patient. We further analyzed the blood spots from a neonatal population in order to fix a cut-off value and include it in a newborn screening panel.Our preliminary results suggest that the Gln/Glu ratio could be a very useful diagnostic marker, more stable over time than glutamine, which could improve the performance in early PUCDs identification.

Background: The high-temperature requirement A 1 (HtrA1) is a multidomain secretory protein with serine-protease activity, expressed in many tissues, including placenta, where its expression is higher in the first trimester, suggesting an association of this serine protease in early phases of human placenta development. In this study, we evaluated maternal serum HtrA1 levels in the first and third trimester of gestation. In particular, we evaluated a possible role of HtrA1 as an early marker of gestational diabetes mellitus (GDM) in the first trimester of gestation. Methods: We evaluated HtrA1 serum levels in the third trimester (36–40 weeks) in normal pregnancies (n = 20) and GDM pregnancies (n = 20) by using ELISA analysis. Secondly, we performed the same analysis by using the first trimester sera (10–12 weeks) of healthy pregnant women that will develop a normal pregnancy (n = 210) or GDM (n = 28) during pregnancy. Results: We found that HtrA1 serum levels in the third trimester were higher in pregnancies complicated by GDM. Interestingly, higher HtrA1 serum levels were also found in the first trimester in women developing GDM later during the second–third trimester. No significant differences in terms of maternal age and gestational age were found between cases and controls. Women with GDM shown significantly higher pre-pregnancy BMI values compared to controls. Moreover, the probability of GDM occurrence significantly increased with increasing HtrA1 levels and BMI values. The ROC curve showed a good accuracy in predicting GDM, with an AUC of 0.74 (95%CI: 0.64–0.92). Conclusions: These results suggest an important role of HtrA1 as an early predictive marker of GDM in the first trimester of gestation, showing a significative clinical relevance for prevention of this disease.

Glioblastoma is a highly lethal grade of astrocytoma with very low median survival. Despite extensive efforts, there is still a lack of alternatives that might improve these prospects. We uncovered that the chemotherapeutic agent temozolomide impinges on fatty acid synthesis and desaturation in newly diagnosed glioblastoma. This response is, however, blunted in recurring glioblastoma from the same patient. Further, we describe that disrupting cellular fatty acid homeostasis in favor of accumulation of saturated fatty acids such as palmitate synergizes with temozolomide treatment. Pharmacological inhibition of SCD and/or FADS2 allows palmitate accumulation and thus greatly augments temozolomide efficacy. This effect was independent of common GBM prognostic factors and was effective against cancer cells from recurring glioblastoma. In summary, we provide evidence that intracellular accumulation of saturated fatty acids in conjunction with temozolomide based chemotherapy induces death in glioblastoma cells derived from patients. ispartof: FRONTIERS IN ONCOLOGY vol:12 ispartof: location:Switzerland status: published

Objective: MicroRNAs have been explored as potential biomarkers for many pathological processes including coronary artery disease. In this study, we aimed to compare the circulating levels of selected atherosclerosis-associated miRNAs in patients with a history of early-onset coronary artery disease with that of age- and sex-matched healthy controls and older patients with late-onset coronary artery disease. Methods: Study population consisted of 30 patients with early onset coronary artery disease, 31 age- and sex-matched healthy controls, and 30 patients with late-onset coronary artery disease. Plasma levels of 13 microRNAs (endothelial cell-related miR-126, -92a/b; vascular smooth muscle cell-related miR-145; inflammation-related miR-16, -21, -125b, -146a/b, -147b, -150, -155; lipometabolism-related miR-27b, -122, -370) were evaluated by using real-time polymerase chain reaction. Results: In patients with early onset coronary artery disease, plasma expressions of the -lipometabolism-related miR-27b, miR-122; inflammation-related miR-125b, miR-146a/b, miR-147b, miR-150, miR-155; and VSMC-related miR-145 were significantly downregulated and endothelial cell-related miR-126 was significantly upregulated compared to age- and sex-matched healthy controls. Circulating microRNA profile of patients with early onset coronary artery disease was also different from that of older patients with late-onset coronary artery disease. Plasma levels of miR-21, miR-27b, miR-122, miR-125b, miR-146b, miR-147b, and miR-155 were lower and plasma levels of miR-16 and miR-92a were higher in patients with early onset coronary artery disease compared to older patients with late-onset coronary artery disease. Conclusion: MicroRNAs are promising biomarkers for early onset coronary artery disease.