New Circulating Circular RNAs with Diagnostic and Prognostic Potential in Advanced Colorectal Cancer

Circular RNAs (circRNAs) are a group of special endogenous long non-coding RNAs which are highly stable in the circulation, and, thus, more suitable as new biomarkers of colorectal cancer (CRC). The aim of our study was to explore the plasma expression levels of four circRNAs: has_circ_0001445, hsa_circ_0003028, hsa_circ_0007915 and hsa_circ_0008717 in patients with CRC and to evaluate their associations with clinicopathological characteristics and the clinical outcome of the patients. CircRNAs were extracted from patients’ plasma obtained prior to chemotherapy. Their expression levels were measured by qPCR and calculated applying the 2^−ΔΔCt method. The levels of all four circRNAs were significantly increased in the plasma of CRC patients. At the optimal cut-off values hsa_circ_0001445 and hsa_circ_0007915 in plasma could significantly distinguish between patients with or without metastatic CRC with 92.56% sensitivity and 42.86% specificity, and with 86.07% sensitivity and 57.14% specificity, respectively. The mean overall survival (OS) of patients with high/intermediate expression of hsa_circ_0001445 was 30 months, significantly higher in comparison with the mean OS of the patients with low expression—20 months (log-rank test, p = 0.034). In multivariate Cox regression analysis, the low levels of hsa_circ_0001445 were also associated with shorter survival (HR = 1.59, 95% CI: 1.02–2.47, p = 0.040). A prognostic significance of hsa_circ_0001445 for patients with metastatic CRC was established.     

Stability of rigid blocks exposed to single-pulse excitation

This paper proposes a numerical procedure that can predict the minimum duration of a rectangular, half-cycle sine wave, linearly increasing and triangular single-pulse excitation required to overturn the rigid block resting on a moving base. Since the linearization assumption in the derivation of an analytical solution, which has already been used by Housner and other researchers, cannot be valid for a block with various slenderness ratios and dimensions, a derivation of numerical solutions which would be valid for all types of block is necessary. The proposed numerical procedure takes into account the possibility of sliding and uplifting of the block from the base. The numerical algorithm for the proposed numerical procedure in a commercial code C++ is given in the “Appendix.”     

Estimation of sedimentation rate in the Middle and South Adriatic Sea using 137Cs

(137)Cs activity concentrations were studied in the sediment profiles collected at five locations in the Middle and South Adriatic. In the sediment profiles collected from the South Adriatic Pit, the deepest part of the Adriatic Sea, two (137)Cs peaks were identified. The peak in the deeper layer was attributed to the period of intensive atmospheric nuclear weapon tests (early 1960s), and the other to the Chernobyl nuclear accident (1986). Those peaks could be used to estimate sedimentation rates by relating them to the respective time periods. Grain-size analysis showed no changes in vertical distribution through the depth of the sediment profile, and these results indicate uniform sedimentation, as is expected in deeper marine environments. It was not possible to identify respective peaks on more shallow locations due to disturbance of the seabed either by trawlers (locations Palagru?a and Jabuka) or by river sediment (location Albania). The highest sedimentation rates were found in Albania (～4 mm y(-1)) and Jabuka (3.1 mm y(-1)). For Palagru?a, the sedimentation rate was estimated to be 1.8 mm y(-1), similar to the South Adriatic Pit where the sedimentation rate was estimated to be 1.8±0.5 mm y(-1). Low sedimentation rates found for the Middle and South Adriatic Sea are consistent with previously reported results for the rest of the Mediterranean.     

Thrombosis of the great cerebral vein in a hemodialysis patient

Cerebral venous thrombosis is a rare condition with various clinical presentations which may delay diagnosis. It is frequently associated with severe consequences. We present the first documented case of thrombosis of the great cerebral vein in a hemodialysis patient. A 29‐year‐old female patient with end‐stage renal disease of unknown etiology was admitted to a hospital with altered consciousness and nausea. Severe headache in the right parietal area had started 2 days before. On examination, she was in the poor overall condition, dysartric, with a severe nystagmus. Urgent brain multislice computerized tomography and magnetic resonance imaging revealed thrombosis of the great cerebral vein with hypodense zones in hypothalamus, thalamus and basal ganglia. She was treated with heparin bolus of 25000 IU with a favorable outcome. Detailed examination demonstrated increased lupus anticoagulant (LA) 1 and LA2 and increased LA1/LA2. Control magnetic resonance imaging performed 1 year later revealed multiple vascular lesions within the brain. Acetylsalicylate was introduced in therapy. Thrombosis of the cerebral veins should be suspected in patients with end‐stage renal disease, altered neurological status and signs of increased intracranial pressure.     

Combined effects of inulin,pectin and guar gum on the quality and stability of partially baked frozen bread

Many attempts have been made to increase the nutritional value of bread by adding dietary fibre. However, fibre enrichment is usually associated with various technological problems. The aim of this study was to optimise the composition of a blend of inulin, pectin and guar gum to enrich the fibre content of partially baked frozen bread without impairing its technological quality. We prepared 20 formulations following a central composite design, together with 4 control breads. Bread enriched with inulin had higher crumb hardness, lower specific volume, shape, moisture content, and crumb cohesiveness than control bread, but improved flavour. Pectin and guar improved moisture content and crumb cohesiveness. There was no interaction between inulin and pectin for any of the bread attributes investigated, while interactions between inulin and guar were small. In contrast, guar and pectin significantly interacted to decrease volume and increase crumb hardness and chewiness. A desirability function method identified the optimised blend as containing 3% inulin, 0.9–1% pectin and 0.3–0.4% guar. Bread enriched with such blend had the following characteristics: specific volume, 4.06 cm³/g; shape, 0.63; crumb hardness, 189 g; resilience, 0.36; cohesiveness, 0.84; chewiness, 169 g; and flavour score, 4.6. Experimental values were close to the predicted ones, with prediction errors below 10% for all attributes tested. The specific volume, crumb hardness and chewiness of the enriched bread were superior to those of unenriched bread. However, undesirable textural changes occurred in the enriched bread during 12 weeks of frozen storage, and these changes strongly depended on the fibre blend composition.     

Changes in the composition and sensory properties of Croatian cheese in a lamb skin sack (Sir iz mišine) during ripening

Croatian traditional cheese, which ripens in a lamb skin sack, was studied to determine compositional, biochemical and sensory changes over 60 days of ripening. The ripening time had a significant effect on the chemical, biochemical and sensory parameters, particularly on the medium‐ and long‐chain free fatty acids (P < 0.05) and total FFAs (P < 0.001). At the end of ripening palmitic, oleic and stearic acids were the predominant FFAs. Cheese ripened for more than 45 days was less acceptable to consumers as a consequence of extensive proteolysis and lipolysis. Therefore, ripening for more than 45 days, which is commonly practised by cheesemakers, is not recommended.     

An efficient visual tracking method for multiple moving targets

An efficient algorithm of the edge detection according to integrating the edge gradient with the average filter is proposed, which can significantly reduce sensitivity of the background subtraction method to noise and illumination. Taking into account the features of the target such as color, size, etc., a new modified Nearest Neighbor （NN） algorithm for data association using the target features is designed. A designed Interacting Multiple Model （IMM） filter is utilized to track the maneuvering target motion, i.e. the feature point （called the centroid of the target） motion of the target. The algorithms are validated via an example with natural video sequences. The results show the algorithms are performances and validity for visual tracking. In complex environment, the algorithm can still work well.     

Environmental Factors That Affect Parathyroid Hormone and Calcitonin Levels

Calciotropic hormones, parathyroid hormone (PTH) and calcitonin are involved in the regulation of bone mineral metabolism and maintenance of calcium and phosphate homeostasis in the body. Therefore, an understanding of environmental and genetic factors influencing PTH and calcitonin levels is crucial. Genetic factors are estimated to account for 60% of variations in PTH levels, while the genetic background of interindividual calcitonin variations has not yet been studied. In this review, we analyzed the literature discussing the influence of environmental factors (lifestyle factors and pollutants) on PTH and calcitonin levels. Among lifestyle factors, smoking, body mass index (BMI), diet, alcohol, and exercise were analyzed; among pollutants, heavy metals and chemicals were analyzed. Lifestyle factors that showed the clearest association with PTH levels were smoking, BMI, exercise, and micronutrients taken from the diet (vitamin D and calcium). Smoking, vitamin D, and calcium intake led to a decrease in PTH levels, while higher BMI and exercise led to an increase in PTH levels. In terms of pollutants, exposure to cadmium led to a decrease in PTH levels, while exposure to lead increased PTH levels. Several studies have investigated the effect of chemicals on PTH levels in humans. Compared to PTH studies, a smaller number of studies analyzed the influence of environmental factors on calcitonin levels, which gives great variability in results. Only a few studies have analyzed the influence of pollutants on calcitonin levels in humans. The lifestyle factor with the clearest relationship with calcitonin was smoking (smokers had increased calcitonin levels). Given the importance of PTH and calcitonin in maintaining calcium and phosphate homeostasis and bone mineral metabolism, additional studies on the influence of environmental factors that could affect PTH and calcitonin levels are crucial.     

Electronic speckle pattern shearing interferometer with a photopolymer holographic grating

A photopolymer holographic grating is used to produce the two sheared images in an electronic speckle pattern shearing interferometer. A ground glass screen following the grating eliminates unwanted diffraction orders and removes the requirement for the CCD camera to resolve the diffraction grating's pitch. The sheared images on the ground glass are further imaged onto the CCD camera. The fringe pattern contrast was estimated to be above 90%. A validation of the system was done by comparing the theoretical phase difference distribution with the experimental data from the three-point bending test.     

Optineurin Deficiency and Insufficiency Lead to Higher Microglial TDP-43 Protein Levels

Mutations in optineurin, a ubiquitin-binding adaptor protein, cause amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease of motor neurons linked to chronic inflammation and protein aggregation. The majority of ALS patients, including those carrying the optineurin mutations, exhibit cytoplasmic mislocalization, ubiquitination, and aggregation of nuclear TAR DNA-binding protein 43 kDa (TDP-43). To address the crosstalk between optineurin and TDP-43, we generated optineurin knockout (KO) neuronal and microglial cell lines using the CRISPR/Cas9 approach. Interestingly, we observed that loss of optineurin resulted in elevated TDP-43 protein expression in microglial BV2 but not neuronal Neuro 2a and NSC-34 cell lines. No changes were observed at the mRNA level, suggesting that this increase was post-translationally regulated. To confirm this observation in primary cells, we then used microglia and macrophages from an optineurin loss-of-function mouse model that lacks the C-terminal ubiquitin-binding region (Optn^470T), mimicking optineurin truncations in ALS patients. As observed in the BV2 cells, we also found elevated basal levels of TDP-43 protein in Optn^470T microglia and bone marrow-derived macrophages. To test if inflammation could further enhance TDP-43 accumulation in cells lacking functional optineurin, we stimulated them with lipopolysaccharide (LPS), and we observed a significant increase in TDP-43 expression following LPS treatment of WT cells. However, this was absent in both BV2 Optn KO and primary Optn^470T microglia, which exhibited the same elevated TDP-43 levels as in basal conditions. Furthermore, we did not observe nuclear TDP-43 depletion or cytoplasmic aggregate formation in either Optn^470T microglia or LPS-treated WT or Optn^470T microglia. Taken together, our results show that optineurin deficiency and insufficiency post-translationally upregulate microglial TDP-43 protein levels and that elevated TDP-43 levels in cells lacking functional optineurin could not be further increased by an inflammatory stimulus, suggesting the presence of a plateau.