INTRODUCTION This study aimed to perform a more precise estimation of the association between tumor necrosis factor-alpha (TNF-α) - 308 G/A single nucleotide polymorphism (SNP) and the risk of development of AP and its phenotypes based on all available published studies. METHODS The study was carried out according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and is registered in PROSPERO (CRD42020176190). The literature search was conducted via: Clarivate Analytics' Scopus, PubMed, Cochrane Central Register of Controlled Trials and China National Knowledge Infrastructure databases, from inception to December 2020 with no language restrictions. Two reviewers were involved independently in study selection, data extraction and appraising the studies that were included. The quality of included studies was evaluated using the Strengthening the Reporting of Genetic Association (STREGA) and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. Frequencies of genotypes and alleles of TNF-alpha (G>A 308, rs1800629) gene, with 95% Odds ratio was used. RESULTS Four studies met the inclusion criteria with moderate risk of bias. This study revealed no significant association between TNF-α - 308 G/A SNP and AP, and the risk of AP development. Moreover, there was no significant association between genotype or allele frequency distribution and clinical manifestations (acute versus chronic) of AP. The certainty of evidence per GRADE was very low. CONCLUSIONS Due to very low certainty of evidence, whether there is an association between TNF-α - 308 G/A SNP and AP, warrants further well-designed multi-centric studies to adjudicate a better understanding of the role of genetic factors in the etiopathogenesis of AP.

The aim of this work was to evaluate the influence of cheese milk standardization on chemical composition, fat and protein recovery, yield and sensory properties of Croatian soft Protected Geographical Indication (PGI) Lički škripavac cheese. Standardization of milk to the casein/fat ratio of 0.7 was carried out by adding skimmed milk powder (SMP) to cheese milk and by skimming part of the milk fat. Results showed that losses of fat by whey were significantly (p < 0.05) lower after Lički škripavac cheese produced from standardized milk by skimming part of the milk fat. Standardization of cheese milk by addition of SMP caused higher losses of protein (p < 0.05) and total solids (p < 0.0001) by whey. Both methods of cheese milk standardization caused a significant (p < 0.01) decrease in milk fat and fat in dry matter content in cheese. In contrast, standardization of cheese milk caused a significant (p < 0.01) increase in protein content in cheese milk. Moisture in non-fat substance (MNFS) significantly (p < 0.05) decreased. Optimization of the casein/fat ratio did not cause a significant increase in fat recovery, but protein recovery significantly increased (p < 0.01). Addition of SMP to cheese milk significantly (p < 0.01) increased actual and adjusted cheese yield. The addition of SMP led to a noticeably higher (p = 0.10) sensory score of Lički škripavac cheese.

Background: Self-reported information may not accurately capture smoking exposure. We aimed to evaluate whether smoking-associated DNA methylation markers improve urothelial cell carcinoma (UCC) risk prediction. Methods: Conditional logistic regression was used to assess associations between blood-based methylation and UCC risk using two matched case–control samples: 404 pairs from the Melbourne Collaborative Cohort Study (MCCS) and 440 pairs from the Women's Health Initiative (WHI) cohort. Results were pooled using fixed-effects meta-analysis. We developed methylation-based predictors of UCC and evaluated their prediction accuracy on two replication data sets using the area under the curve (AUC). Results: The meta-analysis identified associations (P < 4.7 × 10−5) for 29 of 1,061 smoking-associated methylation sites, but these were substantially attenuated after adjustment for self-reported smoking. Nominally significant associations (P < 0.05) were found for 387 (36%) and 86 (8%) of smoking-associated markers without/with adjustment for self-reported smoking, respectively, with same direction of association as with smoking for 387 (100%) and 79 (92%) markers. A Lasso-based predictor was associated with UCC risk in one replication data set in MCCS [N = 134; odds ratio per SD (OR) = 1.37; 95% CI, 1.00–1.90] after confounder adjustment; AUC = 0.66, compared with AUC = 0.64 without methylation information. Limited evidence of replication was found in the second testing data set in WHI (N = 440; OR = 1.09; 95% CI, 0.91–1.30). Conclusions: Combination of smoking-associated methylation marks may provide some improvement to UCC risk prediction. Our findings need further evaluation using larger data sets. Impact: DNA methylation may be associated with UCC risk beyond traditional smoking assessment and could contribute to some improvements in stratification of UCC risk in the general population.

Antigen recognition and T-cell mediated cytotoxicity in clear-cell renal cell carcinoma (ccRCC) remains incompletely understood. To address this knowledge gap, we analysed 115 multiregion tumour samples collected from 15 treatment-naive patients pre- and post-nivolumab therapy, and at autopsy in three patients. We performed whole-exome sequencing, RNAseq, TCRseq, multiplex immunofluorescence and flow cytometry analyses and correlated with clinical response. We observed pre-treatment intratumoural TCR clonal expansions suggesting pre-existing immunity. Nivolumab maintained pre-treatment expanded, clustered TCR clones in responders, suggesting ongoing antigen-driven stimulation of T-cells. T-cells in responders were enriched for expanded TCF7+CD8+ T-cells and upregulated GZMK/B upon nivolumab-binding. By contrast, nivolumab promoted accumulation of new TCR clones in non-responders, replacing pre-treatment expanded clonotypes. In this dataset, mutational features did not correlate with response to nivolumab and human endogenous retrovirus expression correlated indirectly. Our data suggests that nivolumab potentiates clinical responses in ccRCC by binding pre-existing expanded CD8+ T-cells to enhance cytotoxicity.

By a closer inspection of the Friedman-Jorgenson-Kramer algorithm related to the prime geodesic theorem on cofinite Fuchsian groups of the first kind, we refine the constants therein. The newly obtained effective upper bound for Huber’s constant is in the modular surface case approximately 74000 74000 -times smaller than the previously claimed one. The degree of reduction in the case of an upper bound for Faltings’s delta function ranges from 10 8 10^{8} to 10 16 10^{16} .

Abstract Tearful crying is a ubiquitous and likely uniquely human phenomenon. Scholars have argued that emotional tears serve an attachment function: Tears are thought to act as a social glue by evoking social support intentions. Initial experimental studies supported this proposition across several methodologies, but these were conducted almost exclusively on participants from North America and Europe, resulting in limited generalizability. This project examined the tears-social support intentions effect and possible mediating and moderating variables in a fully pre-registered study across 7007 participants (24,886 ratings) and 41 countries spanning all populated continents. Participants were presented with four pictures out of 100 possible targets with or without digitally-added tears. We confirmed the main prediction that seeing a tearful individual elicits the intention to support, d = 0.49 [0.43, 0.55]. Our data suggest that this effect could be mediated by perceiving the crying target as warmer and more helpless, feeling more connected, as well as feeling more empathic concern for the crier, but not by an increase in personal distress of the observer. The effect was moderated by the situational valence, identifying the target as part of one's group, and trait empathic concern. A neutral situation, high trait empathic concern, and low identification increased the effect. We observed high heterogeneity across countries that was, via split-half validation, best explained by country-level GDP per capita and subjective well-being with stronger effects for higher-scoring countries. These findings suggest that tears can function as social glue, providing one possible explanation why emotional crying persists into adulthood.

INTRODUCTION:Obstructive Sleep Apnea (OSA)represents the complete or partial obstruction of the airway.Clinically OSA manifests as sleepness during the day,heavy snoring as well as waking up during the night dues the lack of air.Obesity,gender and orthodontic malocclusion are mentioned in the literature as the etiologic factor for Obstructive Sleep Apnea. AIM: The aim of this study was to find the relationship in the analyzed studies between the Obstructive Sleep Apnea and orthodontic malocclusion at non-obese adults. MATERIAL AND METHODS:The electornic search of the database was performed,using PubMed and Googlescholar,with the aim to find the relevante articles which correlate the OSA and orthodontic malocclusion.Keyword included:obstrucitve sleep apnea,orthodontic malocclusion,cephalometric analysis,impact,association,body mass index,obesity,adults,non obesity. Inclusion criteria were:nonobesity,orthodontic malocclusion,adults,articles published from 1999 to 2019,articles in English,full articles avaiable. RESULTS:Two hundred papers included keywords.The number of articles that included the fully set criteria was nine.These nine articles were analyzed in detail. CONCLUSION:Analyzed articles showed that there is relationship between the Obstructive Sleep Apnea and orthodontic malocclusion in non-obese adults.It was also showed that orthodontic malocclusion is etiological factor for OSA in non-obese adults.

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Excessive use of pesticides and fertilizers in agriculture in order to increase yields has proved unnecessary because a large part of them remain unused and have negative effects on the environment and human health. Therefore, it is a great challenge for farmers to replace the application of pesticides and fertilizers with nanopesticides and nanofertilizers, with the aim of reducing the use of mineral fertilizers and increasing yields, as well as supporting agricultural development. This review provides a detailed overview of the classification of pesticides, commonly used nanoparticles in agriculture and their function, as well as impact of nanopesticides and nanofertilizers on the environment. The application of nanopesticides and nanofertilizers and new delivery mechanisms to improve crop productivity are reviewed and described. Particularly, the advantage of the nanoencapsulation process is emphasized for both pesticides and fertilizers. For hydrophobic pesticides, it may be a tool to provide greater stability, dispersion in aqueous media, and allowing a controlled release of the active compound, which increases its effectiveness. In nanofertilizers, micro- or macronutrients can be encapsulated by nanomaterials which allow to release of nutrients into the soil gradually and in a controlled way maintaining soil fertility, thus preventing eutrophication and pollution of water resources. Risks assessment of application of nanopesticides and nanofertilizers in agriculture are required for their correct and safe application.

O hiperestrogenismo em cães tem várias etiologias, dentre elas, o resultado da excessiva produção de estrógeno por tumores testiculares ou ovarianos. É descrito também que pode ter origem devido a um desequilíbrio entre os hormônios andrógenos e estrógenos. Como resultado do hiperestrogenismo, manifestam-se dermatoses clínicas como, alopecia bilateral simétrica, pelagem rarefeita, facilmente destacáveis, hiperpigmentação variável. O diagnóstico é baseado no histórico, anamnese, sinais clínicos, ultrassonografia testicular, dosagem hormonal de estrógenos séricos e realização de exame histopatológico. O tratamento de eleição é a orquiectomia. O objetivo do presente estudo é relatar a ocorrência de uma dermatose secundária ao hiperestrogenismo em um cão jovem.

This paper describes the influence of deformation by equal-channel angular pressing (ECAP) on the solid particle erosion resistance of the AlSi7Mg0.3 alloy and AlSi7Mg0.3 based composite material reinforced with the addition of 4 % of fly ash (FA) particles. Both, alloy and composite samples were produced using the compo-casting method. The samples have been subjected to ECAP in multiple passes with the rotation of samples around the vertical axis for the angle of 90° after each pass. Particles of silicon carbide (SiC) have been used as erodent while their impact angle was varied (30° and 90°). Observed samples of AlSi7Mg0.3 alloy generally showed higher wear resistance at 90° angle where material fatigue predominates, than at a 30° angle where abrasion-related phenomena predominate. On the other hand, AlSi7Mg0.3 based composite material exhibited erosion wear at 30° angle less than at 90° angle after one ECAP pass. Evaluation of the erosion resistance has been made based on mass and volume loss. After two passes of ECAP, the matrix structure of the AlSi7Mg0.3 based composite material, as well as that of the AlSi7Mg0.3 alloy was improved from the aspect of erosion resistance.

This paper analyzes the impact of multimedia content on success in learning to write and read the letters of the alphabet. For the research purpose and according to the ADDIE model of instructional design, a multimedia application was created for learning to write and read the letters of the alphabet. This paper describes the application interface display, which presents the functions and the parts of the program code. In the focus of the research are the technical possibilities for the use of multimedia application, as well as the impact of its use on the awareness of pupils and teachers on the importance of the introduction of multimedia teaching content. The main research was focused on the effectiveness of learning to write and read the letters of the alphabet and was carried out by comparing the performance of pupils at the end of the school year in two primary schools.Keywords: application; e-learning; education; improving learning. --- U ovom radu ispituje se utjecaj multimedijskoga sadržaja na učenje čitanja i pisanja slova. U svrhu istraživanja izrađena je multimedijska aplikacija za učenje čitanja i pisanja slova, prema ADDIE modelu instrukcijskoga dizajna. U radu je opisana aplikacija prikazom aplikacijskoga sučelja, opisom funkcija i dijelova koda. Istražene su tehničke mogućnosti korištenja multimedijske aplikacije kao i utjecaj njezine uporabe na svijest učenika i nastavnika o važnosti uvođenja multimedijskih nastavnih sadržaja. Glavno se istraživanje odnosi na uspjeh učenja čitanja i pisanja slova, a provedeno je usporedbom postignuća učenika na kraju školske godine u dvije osnovne škole.Ključne riječi: aplikacija; e-učenje; obrazovanje; poboljšavanje nastave.