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Detection of tumor marker location in the breast and axilla using a less commonly utilized color Doppler ultrasound (CDUS) artifact. This prospective study was conducted between August and December 2023 and included consecutive patients with markers placed in the breast and axilla, both before and after neoadjuvant chemotherapy (NACT). Examinations were conducted using a 14 to 5 MHz linear array transducer with B-mode and Doppler capability. By reducing the velocity scale and increasing the color gain values, adjustments were made to create a bloom-like artifact. CDUS was performed with the ultrasound transmit frequency set between 14–5 MHz, color frequency between 6 and 7, color gain ranging from 58 to 80, and velocity scale within the range of 4.6–6.1 cm/s. Twenty patients, with a mean age of 55.50 years ± 12.04 SD (range, 31–72), were included in the study. 14 (70%) were pre-NACT, and six (30%) were post-NACT patients. A total of 20 breast lesions and six axillary lymph nodes were marked. The breast lesions and axillary lymph nodes where the biopsy marker was placed (14 breast lesions and five axillary lymph nodes before NACT, six breast lesions and one axillary lymph node after NACT) were localized with blooming-like artifact. The average size of breast lesions was 20.95 mm ± 6.56 SD (range, 15–40). For axillary lymph nodes, the average size was 20.63 mm ± 5.01 SD (range: 31–14). The blooming-like CDUS artifact is a novel and easily applicable method determining the location of metallic markers in the breast and axilla on diagnostic examinations. [ABSTRACT FROM AUTHOR]

Mining exploration programmes are being expensive and risky due to the limitations of conventional prospecting methods in identifying desired mineralisation. Worldwide, mining exploration programmes have a success rate of approximately 0.7%. Bio-geochemical methods, a sub-branch of geochemical prospecting, are used to identify potential mineralisation areas by studying the distribution of plants containing certain metals. Turkey's leading position in the world in terms of boron reserves increases the strategic importance of boron. On the other hand, metagenome analysis is an important tool in scientific research for detecting microorganisms. Our study aims to develop a cost-effective and efficient biological alternative method for detecting boron mines. Metagenome analysis output showed correlation with the presence of Calothrix sp. NIES-3974, Snodgrassella alvi , Xanthomonas citri , X. citri pv. Fuscans, Pseudomonas viciae , and Aphanothecaceae bacteria and detecting of the potential boron traces in soil. Modelling studies were also conducted on aquaporin z protein, related to the boron uptake, that can be used for utilising from boron detection. [ABSTRACT FROM AUTHOR]

The color Doppler twinkling artifact has been attributed to existing microbubbles or cavitation occurring on rough objects such as kidney stones, some breast biopsy clips, catheter guidewires and sandpaper. The objective was to investigate the correlation between the surface characteristics of helical constructs with different groove geometries and the occurrence of twinkling, as well as to identify locations conducive to bubble retention and/or cavitation. Six half-cylinders were created with a microscale 3-D printer with 5 µm resolution to replicate the geometry of twinkling helical constructs resembling catheter guidewires. Four copies of each marker including a non-twinkling control were printed. The half-cylinders had pitch (peak-to-peak distance) values ranging from 87.5 to 343 µm and amplitude (groove depth) values ranging from 41.5 to 209 µm. The half-cylinders were submerged in degassed water and optically imaged before and after ultrasound insonification to visualize bubbles on the cylinders. The cylinders remained submerged while scanning with the color Doppler mode at frequencies from 3.1 to 6.3 MHz using a GE Logiq E9 scanner and 9L linear array transducer. Two markers exhibited twinkling: one with pitch-to-amplitude ratio of 174/210 µm/µm (0.8) that twinkled only with pre-existing bubbles on the marker; the other had a ratio of 87/87 µm/µm (1.00) that twinkled without pre-existing bubbles on the marker. This work provides strong evidence that both existing bubbles and either cavitation or ultrasound wave interactions with patterned or rough surfaces are significant factors in producing the twinkling signature. [ABSTRACT FROM AUTHOR]

To better understand the pathogenesis of knee osteoarthritis (OA) through identification of serum diagnostics. We conducted multiple reaction monitoring mass spectrometry analysis of 107 peptides in baseline sera of two cohorts: the Foundation for National Institutes of Health (NIH) (n = 596 Kellgren-Lawrence (KL) grade 1–3 knee OA participants); and the Johnston County Osteoarthritis Project (n = 127 multi-joint controls free of radiographic OA of the hands, hips, knees (bilateral KL=0), and spine). Data were split into (70%) training and (30%) testing sets. Diagnostic peptide and clinical data predictors were selected by random forest (RF); selection was based on association (p < 0.05) with OA status in multivariable logistic regression models. Model performance was based on area under the curve (AUC) of receiver operating characteristic (ROC) and precision-recall (PR) curves. RF selected 23 peptides (19 proteins) and body mass index (BMI) as diagnostic of OA. BMI weakly diagnosed OA (ROC-AUC 0.57, PR-AUC 0.812) and only symptomatic OA cases. ACTG was the strongest univariable predictor (ROC-AUC 0.705, PR-AUC 0.897). The final model (8 serum peptides) was highly diagnostic (ROC-AUC 0.833, 95% confidence interval [CI] 0.751, 0.905; PR-AUC 0.929, 95% CI 0.876, 0.973) in the testing set and equally diagnostic of non-symptomatic and symptomatic cases (AUCs 0.830–0.835), and not significantly improved with addition of BMI. The STRING database predicted multiple high confidence interactions of the 19 diagnostic OA proteins. No more than 8 serum protein biomarkers were required to discriminate knee OA from non-OA. These biomarkers lend strong support to the involvement and cross-talk of complement and coagulation pathways in the development of OA. [ABSTRACT FROM AUTHOR]

Glypican 2 (GPC2) is a member of the glypican gene family and is expressed in multiple kinds of cancer. However, the function and mechanism of GPC2 in colorectal cancer remains unclear. In this study, we aimed to identify the role of GPC2 on tumor cell proliferation and survival in colorectal cancer. Ten pairs of colon cancer and matched normal colon tissues were collected in this research. GEPIA was used to analysis the GPC2 gene expression profile in TGCA data base. RT-qPCR and western blot assay were performed to determine the mRNA and protein expressions. CCK-8, Flow cytometry and colon formation assay were applied to evaluate cell viability. IHC staining was performed to evaluate the protein expression in tissues. The function of GPC2 in vivo was verified by an animal model of colon cancer. Through the bioinformatics analysis and qRT-PCR validation, we found that GPC2 was upregulated in the colon cancer tissues and cells. GPC2 knockdown suppressed cell proliferation in vitro and in vivo was confirmed by the results of CCK-8, colony formation assays, and tumor xenograft models. Moreover, by the analysis of flow cytometry assay and gain-or-loss function experiments, we discovered that CEP164 was highly associated with the expression state of GPC2, and mediated G2/M-phase arrest in GPC2-downregulated tumor cells. GPC2 might be a novel oncogenic gene in colorectal cancer, suggesting that it could be a considerable marker for the diagnosis and prognosis of colorectal cancer. [ABSTRACT FROM AUTHOR]

The single-step genomic model has become the golden standard for routine evaluation in livestock species, such as Holstein dairy cattle. The single-step genomic model with direct estimation of marker effects has been proven to be efficient in accurately accounting for millions of genotype records. For diverse applications including frequent genomic evaluation updates on a weekly basis, estimates of the marker effects from the single-step evaluations play a central role in genomic prediction. In this study we focused on exploring the marker effect estimates from the single-step evaluation. Phenotypic, genotypic, and pedigree data were taken from the official evaluation for German dairy breeds in April 2021. A multilactation random regression test-day model was applied to more than 242 million test-day records separately for 4 traits: milk, fat, and protein yields, and somatic cell scores (SCS). Approximately one million genotyped Holstein animals were considered in the single-step genomic evaluations including ∼21 million animals in pedigree. Deregressed multiple across-country breeding values of Holstein bulls having daughters outside Germany were integrated into the national test-day data to increase the reliability of genomic breeding values. To assess the stability and bias of the marker effects of the single-step model, test-day records of the last 4 yr were deleted, and the integrated bulls born in the last 4 yr were truncated from the complete phenotypic dataset. Estimates of the marker effects were shown to be highly correlated, with correlations ∼0.9, between the full and truncated evaluations. Regression slope values of the marker-effect estimates from the full on the truncated evaluations were all close to their expected value, being ∼1.03. Calculated using random regression coefficients of the marker effect estimates, drastically different shapes of the genetic lactation curve were seen for 2 markers on chromosome 14 for the 4 test-day traits. The contribution of individual chromosomes to the total additive genetic variances seemed to follow the polygenic inheritance mode for protein yield and SCS. However, chromosome 14 was found to make an exceptionally large contribution to the total additive genetic variance for milk and fat yields because of markers near the major gene DGAT1. For the first lactation test-day traits, we obtained ∼0 correlations of chromosomal direct genomic values between any pair of the chromosomes; no spurious correlations were found in our analysis, thanks to the large reference population. For trait milk yield, chromosomal direct genomic values appeared to have a large variation in the between-lactation correlations among the chromosomes, especially between first and second or third lactations. The optimal features of the random regression test-day model and the single-step marker model allowed us to track the differences in the shapes of genetic lactation curves down to the individual markers. Furthermore, the single-step random regression test-day model enabled us to better understand the inheritance mode of the yield traits and SCS (e.g., variable chromosomal contributions to the total additive genetic variance and to the genetic correlations between lactations). [ABSTRACT FROM AUTHOR]

DBS has been shown to be an effective intervention for neurological disorders. However, the intervention is complex and many aspects have not been understood. Various clinical situations have no solution and follow trial and error approaches. Dystonia is a movement disorder characterized by involuntary muscle contractions, which gives rise to abnormal movements and postures. Status dystonicus (SD) represents a life-threatening condition that requires urgent assessment and management. Electrophysiological markers for risk of symptom worsening and SD related patterns of evolution in patients treated with long-term deep brain stimulation (DBS), and specially under the effect of withdrawal and renewals of simulation are needed. To this end, we study the variability of neural synchronization as a mechanism for symptom generation under successive perturbations to a system, i.e. withdrawals and renewals of neuromodulation, through computational simulation of clinical profiles under different plasticity conditions. The simulation shows that the neuroplasticity makeup influences the variability of oscillation synchronization patterns in virtual "patients". The difference between the effect of different electrophysiological signatures is remarkable and under a certain condition (equal medium long term potentiation and long term depression) the situation resembles that of a stable equilibrium, putatively making the sudden worsening or change less likely. Stability of variability can only be observed in this condition and is clearly distinct from other scenarios. Our results demonstrate that the neuroplasticity makeup affects the variability of the oscillatory synchrony. This i) informs the shaping of the electrophysiological makeup and ii) might serve as a marker for clinical behavior. • Variability of electrophysiological data is useful information for DBS patient management. • Modelling variability data sheds light on physiological signatures usually not accessible with in vivo data. • Risks associated with changes to neuromodulation can be elucidated via variability analysis. [ABSTRACT FROM AUTHOR]

Error in emergency medicine remains common and difficult to identify. To evaluate if questioning emergency physician reviewers as to whether or not they would have done something differently (Would you have done something differently? [WYHDSD]) can be a useful marker to identify error. Prospective data were collected on all patients presenting to an academic emergency department (ED) between 2017 and 2021. All cases who met the following criteria were identified: 1) returned to ED within 72 h and admitted; 2) transferred to intensive care unit from floor within 24 h of admission; 3) expired within 24 h of arrival; or 4) patient or provider complaint. Cases were randomly assigned to emergency physicians and reviewed using an electronic tool to assess for error and adverse events. Reviewers were then mandated to answer WYHDSD in the management of the case. During the study period, 6672 cases were reviewed. Of the 5857 cases where reviewers would not have done something differently, 5847 cases were found to have no error. The question WYHDSD had a sensitivity of 97.4% in predicting error and a negative predictive value of 99.8%. There was a significantly higher rate of near misses, adverse events, and errors attributable to an adverse event in cases where the reviewer would have done something differently (WHDSD) compared with cases where they would not. Therefore, asking reviewers if they WHDSD could potentially be used as a marker to identify error and improve patient care in the ED. [ABSTRACT FROM AUTHOR]

Cancer is considered as one of the main causes of human deaths and a global health challenge. Despite the therapeutic and diagnostic progresses, there is a high rate of mortality among cancer patients. Late diagnosis is one of the most important reasons of high mortality rate, which is mainly due to the lack of efficient and non-invasive diagnostic methods to monitor cancer patients. Therefore, the introduction of non-invasive markers can play an effective role in the early diagnosis and better therapeutic management in these patients. MicroRNAs (miRNAs) have critical functions in regulation of various physiological and pathophysiological cellular processes. Deregulation of miRNAs has been frequently reported in different tumor types. On the other hand, due to the high stability of these factors in body fluids, these factors can be used as the non-invasive tumor markers. In this study, for the first time, we discussed the role of miR-185 during tumor progression. It has been reported that miR-185 mainly functions as a tumor suppressor through the regulation of PI3K/AKT, JAK/STAT, TGF-β, Hippo, and WNT signaling pathways as well as the transcription factors and cell cycle components. PI3K/AKT was reported as the main oncogenic signaling pathway that can be inhibited by miR-185 during tumor progression. Therefore, miR-185/PI3K/AKT axis can be suggested as a probable target in tumor therapy that requires further animal studies. The present review can be an effective step towards introducing the miR-185 as a non-invasive diagnostic marker and a therapeutic target in cancer patients. • Late diagnosis is one of the most important reasons of high cancer mortality rate. • MiRNAs can be used as non-invasive markers for the early tumor detection. • MiR-185 can be suggested as a novel non-invasive diagnostic tumor marker. [ABSTRACT FROM AUTHOR]

Cancer is one of the leading causes of human deaths globally. Late diagnosis is one the main reasons of treatment failure and high mortality among cancer patients. Therefore, investigating the molecular mechanisms involved in tumor progression is required to identify the novel therapeutic targets and early detection markers. MicroRNAs (miRNAs) have important roles in regulation of the cellular and molecular mechanisms during tumor progression. Here, we discussed the role of miR-370 in regulation of cellular mechanisms during tumor progression. MiR-370 has mainly a tumor suppressor function by regulation of transcription factors and signaling pathways including WNT, phosphatidylinositol 3-kinase (PI3K)/AKT, Transforming growth factor beta (TGF-β), Janus kinase (JAK)-signal transducer and activator of transcription (STAT), and Nuclear factor-κB (NF-κB). The present review paves the way to introduce the miR-370 as a non-invasive marker for the early tumor detection in cancer patients. [Display omitted] • MiRNAs are always used as non-invasive diagnostic markers in various diseases. • We discussed the role of miR-370 in cellular processes during tumor progression. • MiR-370 can be used as a non-invasive early detection and therapeutic tumor marker. [ABSTRACT FROM AUTHOR]

[Display omitted] • Due to the high stability of miRNAs in body fluids, these factors can be considered as the non-invasive tumor markers. • We investigated the role of miR-382 during tumor development. • MiR-382 mainly functions as a tumor suppressor. • MiR-382 can be suggested as a diagnostic and therapeutic marker in cancer patients. Despite the recent progresses in therapeutic and diagnostic methods, there is still a significantly high rate of mortality among cancer patients. One of the main reasons for the high mortality rate in cancer patients is late diagnosis, which leads to the failure of therapeutic strategies. Therefore, investigation of cancer biology can lead to the introduction of early diagnostic markers in these patients. MicroRNAs (miRNAs) play an important role in regulation of cellular processes associated with tumor progression. Due to the high stability of miRNAs in body fluids, these factors can be considered as the non-invasive tumor markers. Deregulation of miR-382 has been widely reported in different cancers. Therefore, in this review, we investigated the role of miR-382 during tumor development. It has shown that miR-382 has mainly a tumor suppressive, which inhibits the growth of tumor cells through the regulation of signaling pathways, RNA-binding proteins, and transcription factors. Therefore, miR-382 can be suggested as a diagnostic and therapeutic marker in cancer patients. [ABSTRACT FROM AUTHOR]

In the recent years, Digital Image Correlation (DIC) was applied with very promising results to monitor cracks in reinforced concrete structures. However, current DIC measurements present some limitations to characterize the existing crack (already present in the reference image) and for long-term monitoring due to the principles of the correlation algorithm. This paper presents two techniques to complement DIC in these two cases. The first one is based on direct detection using existing algorithms. The second one is based on the detection of markers fixed around the crack. Their relative position in different images is used to compute the crack displacement that occurred between the inspections. A conventional DIC set-up can be used for this technique. Simplified and refined methods are proposed to quantify the measurement uncertainty and to determine the number and position of markers. Both techniques are validated in laboratory conditions and in-situ in an existing concrete bridge. The combination of the two presented techniques with conventional DIC is promising and could be of interest for applications with complicated crack patterns where a detailed understanding of the crack kinematics is required. • A direct detection technique is validated to characterize existing cracks in reinforced concrete structures. • A marker-based technique is proposed for long term monitoring of cracks in existing concrete structures. • The techniques are validated in laboratory conditions and in an existing prestressed concrete bridge. • Limits of applicability and recommendations are provided for both techniques based on the performed validation tests. [ABSTRACT FROM AUTHOR]

• Two kinds of semantic markers are proposed to support NER and RE, which has the ability to incorporate lexical semantic information of the targeted tokens from the pre-trained language models. • A marker-oriented directional attention is proposed to model the interaction and learn semantic dependencies between multiple tokens. • Our model achieves SOTA performance on three standard benchmarks (ACE05, ACE04 and SciERC). Recognizing entities and extracting their relations are significant tasks for information extraction. Many recent works focus on leveraging entity markers for better span (pair) representations, which have achieved promising performance. Nevertheless, existing works have two shortcomings: (1) previous markers are randomly embedded into distributed representations, which ignores semantic information relevant to the targeted tokens that we want to highlight. (2) most works simply implant markers into a sentence, which is weak to encode the interrelation between multiple tokens. In this work, we propose a marker collaborating model for entity and relation extraction, which is composed of two modules. The first module is semantic marker module, where two kinds of semantic markers are proposed to leverage semantic features from the PLMs. The second module is collaborative marker attention module, where a marker-oriented directional attention is proposed to model the interaction between multiple tokens. Our model yields SOTA performance on three standard benchmarks (ACE04, ACE05 and SciERC). [ABSTRACT FROM AUTHOR]

To assess hippocampal function during stereoelectroencephalography (SEEG) investigations through the study of the medial temporal lobe event-related potential (ERP) MTL-P300. We recorded the MTL-P300 during a visual oddball task, using hippocampal electrodes implanted for SEEG in 71 patients, in a preoperative epilepsy investigation. The presence of an MTL-P300 and its amplitude were correlated with hippocampal involvement during seizures and memory function. Analysis using ROC curves revealed that an MTL-P300 amplitude below -46 µV, has a specificity of 93.3% in detecting the epileptogenic zone, and absence of the MTL-P300 in the left hippocampus of patients with typical language organization was associated with marked alteration of verbal memory scores. There was a significant correlation between performance in non-verbal memory tests and the amplitude of the MTL-P300 in the right hippocampus of patients with left hemispheric seizures (immediate visual recall: r = 0.67, p = 0.005; delayed visual recall: r = 0.56, p = 0.025). Using a linear regression, we confirmed that the absence of the MTL-P300 in the left hippocampus, the involvement of the left hippocampus during seizures, and the duration of epilepsy were predictors of verbal memory deficits. Analysis of the MTL-P300 during SEEG recording provides relevant information for the analysis of hippocampal functionality and can help to localize the epileptogenic zone. [ABSTRACT FROM AUTHOR]

One of the barriers to automating high-mix, variable-volume production is the process of installing the workpiece in the machine tool. In this paper, we propose a new principle for position and orientation measurements involving the use of 3-dimensional shape markers with shadows. We prototyped a marker system and demonstrated position and orientation measurements with a position precision of about 3 µm and an orientation precision of about 0.02 deg. We also proposed a method for transferring the position and orientation of workpieces between machine tools as an example of its application to a high-mix, variable-volume production system. [Display omitted] • The aim of the research was to apply position and orientation marker functions used in AR to manufacturing system. • New measurement principle was improved involving 3D shape markers and their projected shadows. • Precision of the developed marker was about 3 µm (position) and 0.02 deg (attitude). • A method of transferring workpiece for high-mix, variable-volume production was proposed. [ABSTRACT FROM AUTHOR]

Aberrant cell proliferation is one of the main characteristics of tumor cells that can be affected by many cellular processes and signaling pathways. Kinesin superfamily proteins (KIFs) are motor proteins that are involved in cytoplasmic transportations and chromosomal segregation during cell proliferation. Therefore, regulation of the KIF functions as vital factors in chromosomal stability is necessary to maintain normal cellular homeostasis and proliferation. KIF deregulations have been reported in various cancers. MicroRNAs (miRNAs) and signaling pathways are important regulators of KIF proteins. MiRNAs have key roles in regulation of the cell proliferation, migration, and apoptosis. In the present review, we discussed the role of miRNAs in tumor biology through the regulation of KIF proteins. It has been shown that miRNAs have mainly a tumor suppressor function via the KIF targeting. This review can be an effective step to introduce the miRNAs/KIFs axis as a probable therapeutic target in tumor cells. • Kinesin superfamily proteins (KIFs) are involved in cytoplasmic transportations and chromosomal segregation. • MicroRNAs (miRNAs) and signaling pathways are important regulators of KIF proteins. • This review can be an effective step to introduce the miRNAs/KIFs axis as a probable therapeutic target in tumor cells. [ABSTRACT FROM AUTHOR]

• As far as we know, the present study is the first to investigate the relationship between NAR and outcomes of aSAH. • This study will lead us to further explore the benefits of iatrogenic immunotherapy for patients with subarachnoid hemorrhage. Compelling evidence shows that inflammation contributes to the development of aneurysmal subarachnoid hemorrhage (aSAH). Several studies have conducted in the recent past have revealed that the neutrophil-to-albumin ratio (NAR) is a new marker of inflammation. However, whether NAR can predict the prognosis of patients with aSAH has not been fully elucidated. Therefore, the aim of this study was to investigate the relationship between NAR and prognosis of aSAH. A total of 555 consecutive patients diagnosed with aSAH were retrospectively enrolled. The NAR was assessed for each patient upon admission. At the same time, the demographic and clinical parameters of patients were collected. The Glasgow Outcome Scale (GOS, a score of 1–3) at 3 months was used to evaluate disease outcomes. Patients with unfavorable outcomes at 3 months were considerably older, had high levels of intraventricular and subarachnoidal hemorrhage, exhibited severe clinical conditions at admission, developed in-hospital complications, such as pneumonia and delayed cerebral ischemia. At admission, the NAR for GOS scores 4–5 was median [IQR] 0.231 [0.177–0.288] whereas that for GOS score 1–3 was 0.349 [0.264–4.449]; p < 0.001. The analysis revealed that the NAR was independently associated with unfavorable outcomes in patients with aSAH after adjusting for potential confounding factors (risk ratio [95% CI] 3.554 [2.601–4.857] per 0.1-point increment; p < 0.001). Moreover, a NAR of 0.274 was determined to be the best cutoff threshold for distinguishing between favorable and unfavorable outcomes in ROC analyses (AUC [95% CI] 0.782 [0.740–0.823]; p < 0.001; GOS 3–5: NAR ≥ 0.274 134/247 [54.3%] vs NAR < 0.274 47/308 [15.3%]; p < 0.001). This study demonstrates that NAR may be a novel prognostic marker in patients with aSAH. Elevated NAR is an independent factor predicting unfavorable outcome in patients with aSAH. [ABSTRACT FROM AUTHOR]

The role of fatty acid ethyl esters (FAEEs) during human alcoholic pancreatitis is unknown. We compared FAEEs levels with their nonesterified fatty acids (NEFAs) precursors during alcohol intoxication and clinical alcoholic pancreatitis. The pathophysiology underlying FAEEs increase and their role as diagnostic biomarkers for alcoholic pancreatitis was investigated. A prospective blinded study compared FAEEs, NEFAs, and ethanol blood levels on hospitalization for alcoholic pancreatitis (n = 31), alcohol intoxication (n = 25), and in normal controls (n = 43). Serum FAEEs were measured at admission for nonalcoholic pancreatitis (n = 75). Mechanistic cell and animal studies were done. Median FAEEs were similarly elevated during alcohol intoxication (205 nmol/L; 95% confidence interval [CI], 71.8-515 nmol/L, P <.001) and alcoholic pancreatitis (103.1 nmol/L; 95% CI, 53-689 nmol/L, P <.001) vs controls (1.7 nmol/L; 95% CI, 0.02-4.3 nmol/L) or nonalcoholic pancreatitis (8 nmol/L; 95% CI, 1.1-11.5 nmol/L). Alcoholic pancreatitis increased serum NEFAs (1024 ± 710 μmol/L vs 307 ± 185 μmol/L in controls, P <.05). FAEEs comprised 0.1% to 2% of the parent NEFA concentrations. FAEES correlated strongly with NEFAs independent of ethanol levels in alcoholic pancreatitis but not during alcohol intoxication. On receiver operating characteristic curve analysis for diagnosing alcoholic pancreatitis, the area under the curve for serum FAEEs was 0.87 (95% CI, 0.78-0.95, P <.001). In mice and cells, alcohol administration transiently increased all FAEEs. Oleic acid ethyl ester was the only FAEE with a sustained increase up to 24 hours after intraperitoneal oleic acid plus ethanol administration. The sustained, alcohol-independent, large (20- to 50-fold) increase in circulating FAEEs during alcoholic pancreatitis results from their visceral release and mirrors the 2- to 4-fold increase in parent NEFA. The large areas under the curve of FAEEs on receiver operating characteristic curve analysis supports their role as alcoholic pancreatitis biomarkers. [Display omitted] Fatty acid ethyl esters are biomarkers that can help diagnose alcoholic pancreatitis. They are released by the breakdown of fat during pancreatitis and parallel the parent fatty acids released during fat breakdown. [ABSTRACT FROM AUTHOR]

Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has emerged in 2019 and caused a global pandemic in 2020, manifesting in the coronavirus disease 2019 (COVID-19). The majority of patients exhibit a mild form of the disease with no major complications; however, moderate to severe and fatal cases are of public health concerns. Predicting the potential prognosis of COVID-19 could assist healthcare workers in managing cases and controlling the pandemic in an effective way. Therefore, the objectives of the study were to search for biomarkers associated with COVID-19 mortality and predictors of the overall survival (OS). Here, clinical data of 6026 adult COVID-19 patients admitted to two large centers in Saudi Arabia (Riyadh and Hafar Al-Batin cities) between April and June 2020 were retrospectively analysed. More than 23% of the study subjects with available data have died, enabling the prediction of mortality in our cohort. Markers that were significantly associated with mortality in this study were older age, increased d -dimer in the blood, higher counts of WBCs, higher percentage of neutrophil, and a higher chest X-ray (CXR) score. The CXR scores were also positively associated with age, d -dimer, WBC count, and percentage of neutrophil. This supports the utility of CXR scores in the absence of blood testing. Predicting mortality based on Ct values of RT-PCR was not successful, necessitating a more quantitative RT-PCR to determine virus quantity in samples. Our work has also identified age, d -dimer concentration, leukocyte parameters and CXR score to be prognostic markers of the OS of COVID-19 patients. Overall, this retrospective study on hospitalised cohort of COVID-19 patients presents that age, haematological, and radiological data at the time of diagnosis are of value and could be used to guide better clinical management of COVID-19 patients. [ABSTRACT FROM AUTHOR]

Background: Hepatitis B e antigen (HBeAg) seroconversion is an important intermediate outcome in HBeAg-positive chronic hepatitis B patients. This study aimed to explore whether hepatitis B virus (HBV) RNA serum levels can predict HBeAg seroconversion treated with entecavir.Methods: Serum samples from HBeAg-positive children previously treated with entecavir were retrospectively analyzed. HBV RNA levels were measured at baseline, weeks 12, 24, 48, 72 of therapy. Ability of individual biomarkers to predict HBeAg seroconversion was evaluated using receiver operating characteristics (ROC) analyzes.Results: Serum HBV RNA was detectable in 51 children with a median of 6.05 (4.04-8.29) log10 IU/mL at baseline. Patients with subsequent HBeAg seroconversion showed a significantly larger decline in median HBV RNA levels during treatment from baseline to week 12 of 1.96 (0.30-3.38) and to week 24 of 2.27 (1.20-3.38) log10 IU/mL, respectively, in comparison to HBeAg-positive patients without HBeAg seroconversion (P < 0.001). Levels of HBV RNA at treatment weeks 12 and 24 showed good ability to predict HBeAg seroconversion (area under ROC scores > 0.85, P < 0.001).Conclusion: On-treatment HBV RNA dynamic predicts entecavir-induced HBeAg seroconversion in children with chronic hepatitis B living in China. [ABSTRACT FROM AUTHOR]

[Display omitted] • New biomarkers prognostic of proximal urea cycle disorders are strongly desirable. • Metabolic profiles of affected patients show high value of glutamine to glutamate ratio. • The ratio can be considered a more effective marker than citrulline and glutamine. • The ratio can be included in a newborn screening panel. 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. [ABSTRACT FROM AUTHOR]

Donor-derived cell-free DNA (dd-cfDNA) is considered a reliable marker of organ damage with potential applications in the follow-up of transplant recipients. In this work we present an assay based on the donor-recipient HLA-mismatch (human leukocyte antigen) at the HLA-DRB1 locus to monitor rejection by quantifying the percentage of dd-cfDNA using a droplet digital PCR (polymerase chain reaction) technique. A panel of probes targeting the HLA-DRB1 locus and covering >85% genetic variability was validated and used to assess dd-cfDNA levels in a prospective cohort of 19 adult heart transplant recipients (mean age 50.9±14.8 years). The assay was carried out on a total of 232 liquid biopsies collected at the same time as endomyocardial biopsy (EMB) during routine post-transplant follow-up. Results show a significant increase of dd-cfDNA related to ischemia-reperfusion injury (2.22±2.09%) and to acute cellular rejection (1.71±3.10%) compared to stable conditions (0.43±1.04%, p < 0.0001). On the contrary, no increase was observed during infections or vascular complications, underlining the potential role of this biomarker for rejection monitoring. With a cut-off of 0.11%, the test showed 70.8% specificity (95% CI, 58.17% - 81.40%) and 64.2% sensitivity (95% CI, 49.80% - 76.86%) in discriminating acute rejection from no rejection. These data demonstrate that this HLA mismatch-based droplet digital PCR method is effective for monitoring rejection in heart transplant recipients. Compared to next generation sequencing approaches, it is far more flexible, less expensive and provides faster results. [ABSTRACT FROM AUTHOR]

The precise diagnostics of different diseases is very important for its treatment. It is particularly important to differentiate the disease on the early stages when the pathological alterations have not yet caused great harm to the whole organism, since this allows using greater number of therapies and increase the recovery probability. One of the methods of early diagnostics is based on examination of human biological liquids (blood, tears, cervical mucus, urine, etc,). A small drop of liquid is drawn on an object-plate and dried out slowly, thus a thin dry film (facies) remains. In the process of fluid crystallization there appear characteristic patterns (markers) in the facies. Each marker is a highly definite sign of some pathology even at an early stage of a disease development. When mass population health examination is carried out, it is necessary to analyze a large number of images This is the reason the problem of algorithm and software development for automated processing of images is rather urgent nowadays. Mathematical models of facies images are needed to formalize the tasks of image processing and synthesis of algorithms. The facies has a round shape, as it is obtained from a drop of liquid. Facies images have a radial-ring structure due to the peculiarities of the drying and crystallization of the contained fractions. These facies features should be taken into account in their imaging models. In this paper, autoregressive models of circular images are used to represent facies images. These models use grids defined on concentric circles or Archimedes' spirals. The radial-ring structure of facies image correlations is naturally taken into account in these models. The paper contains examples of model identification, that is, estimation of the values ​​of its parameters at which the correlation properties of the model are closest to the characteristics of a given facies. It is shown that the classification of the facies type (corresponding to the general condition of the patient) is possible according to these estimates. [ABSTRACT FROM AUTHOR]

This paper is described on the improvement of the Active Textbook System (A-txt) and the consideration for Copyright Law when the A-txt is used. The A-txt is a next-generation electronic educational material system proposed by the authors that can digitally expand the general paper books with general-purpose terminals. This system is the original system that allows you to easily attach additional digital content to any location by using figures and sentences on paper as augmented reality (AR) markers. Initially, A-txt, which was developed for each type of mobile OS, is provided on a unified platform by using Unity, and it has become possible to concentrate budgets and human resources. This time, we have added new functions to make usability better and improved the screen display by modifying the source code. In addition, as a measure to use figures in books as AR markers without infringing copyright, we experimentally have found the minimum necessary range in which A-txt can be used without inconvenience. In the process, we also have found a method to increase the recognition rate of markers. [ABSTRACT FROM AUTHOR]

Few studies have specifically evaluated the development of cuff-tear arthropathy (CTA) after a rotator cuff repair in the postoperative early to mid-term. This study aimed to identify the factors associated with the development of CTA, to evaluate the effect of arthropathy on functional outcomes, and to evaluate the incidence of CTA 3-10 years after an arthroscopic rotator cuff repair. A total of 312 patients who underwent an arthroscopic repair of a large or massive full-thickness rotator cuff tear with a minimum follow-up of 3 years were retrospectively divided into 2 groups for analysis: those with postrepair CTA (arthritic glenohumeral changes due to rotator cuff insufficiency) and those without. CTA was assessed using the Seebauer and modified Hamada-Fukuda classification systems. Pre-, intra-, and postoperative patient characteristics; characteristics of the rotator cuff tear; clinical and radiological parameters; and pre- and postoperative functional scores were compared. The rate of development of CTA was 11.5% (36 of 312 patients, 13 centric and 23 eccentric arthropathy). CTA was more frequently associated with the poor integrity of the supraspinatus tendon after repair (P <.001) and massive tears (P =.006). Postoperative pseudoparalysis (P <.001), symptomatic retear (P <.001), tear size (P =.026), critical shoulder angle (P =.001), preoperative acromiohumeral interval (P =.046), and the humeral head superior migration (P =.001) were found to be associated with the development of CTA. However, only postoperative pseudoparalysis was found to be an independent risk factor (P <.001, odds ratio: 2.965). Patients with postrepair CTA had significantly worse functional outcome scores. The postoperative development of pseudoparalysis may be a marker of CTA in the future and that closer follow-up may be necessary. [ABSTRACT FROM AUTHOR]

Stroke embolic source have an unknown origin in 30-40% of cases. Mechanical thrombectomy for acute large vessel occlusion stroke has provided us with a method to directly retrieve the thrombi from patients for analysis. By collecting stroke-causing thrombi from known sources, we can then use high-throughput RNA sequencing (RNAseq) technology to directly measure the gene expression signatures of these clots. This may allow us to identify genetic markers to predict the cause of cryptogenic embolism. This is a prospective study in which RNAseq was used to analyze cerebral thrombi retrieved by mechanical thrombectomy devices in acute ischemic stroke patients. Samples were separated into two groups based on known stroke thrombus etiology, including Carotid group (patients with ipsilateral >70% carotid stenosis) and Atrial fibrillation (AF) group (patients with atrial fibrillation). Gene expression was compared by RNAseq analysis between the groups. From October 2016 to September 2017, 8 thrombi (4 in Carotid group, 4 in Afib group) were included in this study. There were 131 genes that were significantly up- or down-regulated between the two groups defined as a false discovery rate ≤ 0.05 and a fold change ≥ 2. Twenty-six genes were selected as candidate gene biomarkers based on the criteria in the methods section. Candidate genes HSPA1B , which encodes a heatshock protein, and GPRC5B , which encodes a G-protein, showed the greatest fold differences in expression between the two groups. This study has shown that RNA sequencing of acute ischemic stroke thrombi is feasible and indentified potential novel biomarkers for identifying stroke-causing thrombi origin, especially in cryptogenic stroke. [ABSTRACT FROM AUTHOR]

Pollution by microplastics (MPs) has caused potential threats to the environment. Understanding the sources of MPs in the environment can help control their emissions and reduce environmental risks. Source apportionment of MPs has been conducted according to the characteristics of MPs themselves (such as types of polymers and morphological characteristics). However, the specificity and resolution of the appointments of sources need to be improved. Organic pollutants adsorbed on MPs can be used as a novel and reliable indicator to identify the source of MPs in the environment. In the present work, the analytical methods of MPs and organic pollutants adsorbed on MPs were critically reviewed, and the occurrence of organic pollutants and factors influencing their adsorption on MPs were discussed. Furthermore, the potential applications of organic pollutants adsorbed on MPs as indicators for determining the sources of MPs were highlighted. The study would help recognize the sources of MPs, which will support efforts aimed at reducing their emissions and further pollution of the ecosystem. [Display omitted] • Obtaining undamaged microplastics is crucial for identifying adsorbed pollutants. • It is essential to prevent pollutant loss during the pretreatment of microplastics. • Research on organic pollutants adsorbed on microplastics is limited. • Tracking source of microplastics by analyzing adsorbed pollutants is promising. [ABSTRACT FROM AUTHOR]

There are currently no validated biomarkers for anorexia nervosa (AN), though recent literature suggests an increased research interest in this area. Biomarkers are objective, measurable indicators of illness that can be used to assist with diagnosis, risk assessment, and tracking of illness state. Related to biomarkers are endophenotypes, which are quantifiable phenomena that are distinct from symptoms and which link genes to manifest illness. In this scoping review, we sought to provide a summary of recent research conducted in the pursuit of biomarkers and endophenotypes for AN. The findings indicate that a number of possible biomarkers which can assess the presence or severity of AN independently of weight status, including psychophysical (e.g., eye-tracking) and biological (e.g., immune, endocrine, metabolomic, neurobiological) markers, are currently under investigation. However, this research is still in early phases and lacking in replication studies. Endophenotype research has largely been confined to the study of several neurocognitive features, with mixed evidence to support their classification as possible endophenotypes for the disorder. The study of biomarkers and endophenotypes in AN involves significant challenges due to confounding factors of illness-related sequalae, such as starvation. Future research in these areas must prioritise direct evaluation of the sensitivity, specificity and test-retest reliability of proposed biomarkers and enhanced control of confounding physical consequences of AN in the study of biomarkers and endophenotypes. • There are no established biomarkers for the psychiatric symptoms of AN. • There is inconclusive support for proposed cognitive endophenotypes of AN. • Illness sequalae complicate the search for biomarkers and endophenotypes in AN. • Detailed evaluations of marker specificity, sensitivity and reliability are needed. [ABSTRACT FROM AUTHOR]

• The isolated anti-GPC3 Nbs specifically bind to the recombinant and endogenous GPC3. • Epitope mapping shows that these Nbs bind to the N-terminal subunit of GPC3. • Anti-GPC3 Nb G64 displays high protein stability in serum at 37℃. • Anti-GPC3 Nb G64 has no impact on the proliferation of HEK293T and HepG2 cells. Glypican-3 (GPC3) is a highly specific diagnostic marker for hepatocellular carcinoma (HCC) diagnosis and a potential target in HCC therapy. Nanobodies (Nbs) are promising targeting molecules due to their high specificity and strong affinities to antigens, high stability, deep tissue penetration, and low immunogenicity. In this study, we isolated Nbs against GPC3 marker protein from a synthetic Nb library by phage display. To characterize these Nbs, we performed enzyme-linked immunosorbent assay, immunoprecipitation assay, and immunofluorescent assay to demonstrate that four (G8, G10, G11, and G64) of them bound specifically to recombinant as well as endogenous GPC3, and epitope mapping showed they all bound to N-terminal subunit of GPC3. Furthermore, we found that G64 exhibited high protein stability and GPC3 binding activity in serum at 37℃ for at least 96 h, and G64 did not affect the proliferation of HEK293T cells and HCC cell line HepG2. Our study provides four anti-GPC3 Nbs as promising targeting molecules for HCC diagnostic and therapeutic drugs. [ABSTRACT FROM AUTHOR]

The clinical diagnosis of Parkinson's disease (PD) based on motor signs is often preceded by several non-motor symptoms that can indicate early prodromal neurodegenerative processes. Such prodromal symptoms can aid the early detection of PD, but their specificity for prodromal PD in comparison to prodromes of other movement disorders is still largely unclear. We here aim to give a first insight into the published evidence of prodromal non-motor symptoms in PD, dementia with Lewy bodies (DLB), multiple system atrophy (MSA), Huntington's disease (HD), progressive supranuclear palsy (PSP) and spinocerebellar ataxia (SCA). REM-sleep behavior disorder (RBD) and autonomic dysfunction have been observed in the prodromes of PD, MSA, DLB and SCA. Depression and cognitive decline have been reported for prodromal PD, DLB, HD, SCA, and PSP. Olfactory loss has only been described in prodromal PD/DLB. However, estimating the specificity of prodromal non-motor symptoms in PD is so far complicated by scarce prospective evidence and study limitations. Information on marker specificity is a prerequisite for an accurate early (differential) diagnosis of prodromal diseases, as well as specific recruitment for targeted neuroprotective interventions. We here would like to raise awareness of these issues and encourage further prospective research of prodromal non-motor symptoms in neurodegenerative movement disorders and other diseases. [ABSTRACT FROM AUTHOR]

Ideal digesta markers used for feeding studies are inert, unabsorbable, and move with the digesta they are intended to mark. Both chromium (III) and cobalt (III) salts of EDTA (CrEDTA and CoEDTA, respectively) are used as markers of liquid digesta in dairy cattle research. A small portion is absorbed and excreted in urine, but the markers are assumed to remain unreactive and as inert salts in the digesta and animal. The degree to which these colored salts remain bound in solution can be estimated through spectrophotometric measurement at their wavelength (λ) of peak absorbance. The objective of this in vitro study was to evaluate whether CrEDTA and CoEDTA dissociate under reducing conditions that could be experienced in the rumen. In a completely randomized design with 2 replicate analytical runs and samples in duplicate within run, approximately 26 mg/L Cr from CrEDTA or Co from CoEDTA was incubated in a 26-mL reaction volume containing 20 mL of Goering and Van Soest medium without tryptone, 3 mL of CoEDTA or CrEDTA solutions, or water (reagent blanks), and 3.0 mL of a combination of distilled water with 0, 0.25, 0.50, 0.75, or 1.00 mL of reducing solution (RedSol). After incubation for 0.5 h at 39°C, absorbance was read at λ = 535, 465, and 560 nm, the peak λ for EDTA salts of Co(III), Co(II), and Cr(III), respectively. Mean reagent blank values were subtracted from CoEDTA and CrEDTA data. The absorbance data at peak λ were analyzed by marker in models that included RedSol with analytical run as a random variable. Contrasts were used to detect linear through quartic effects of RedSol. Samples with RedSol had redox potentials of −250 to −328 mV, which are within the range of reported ruminal measures. As RedSol increased, CoEDTA showed a linear decline of 75% in ABS at 535 nm and a quadratic 4-fold increase followed by a 60% decline at 465 nm. These responses indicate a reduction of Co(III) to Co(II) and subsequent dissociation of Co(II)EDTA. The absorbance of CrEDTA at 560 nm showed a tendency for an 8% linear decrease as RedSol increased. Wavescans from λ = 330 to 700 nm showed CrEDTA retaining its characteristic 2-peak pattern as RedSol increased, whereas CoEDTA curves deformed entirely. We conclude that CoEDTA is not a stable, inert digesta marker under reducing conditions achievable in the rumen and is therefore unsuitable for use in studies with ruminants. Reexamination of the suitability of available liquid digesta markers is advised. [ABSTRACT FROM AUTHOR]

• Combination of CA19-9, CCA-CA, CA-S27 and WFA+-MUC1 as GB-score increases their power in diagnosis of CCA. • High GB-score indicates poor prognosis and short survival of CCA patients. • High GB-score is an independent poor prognostic indicator for CCA. Aberrant glycosylation has been reported to play important roles in progression of cholangiocarcinoma (CCA) and hence the aberrant expressed glycans are beneficial markers for diagnosis and prognostic prediction of CCA. Five CCA-associated glycobiomarkers—carbohydrate antigen 19–9 (CA19-9), carbohydrate antigen-S27 (CA-S27), CCA-associated carbohydrate antigen (CCA-CA), WFA-positive MUC1 (WFA+-MUC1), and WFA-positive M2BP (WFA+-M2BP), in the sera from CCA patients (N = 138) were determined in comparison with non-CCA control subjects (N = 246). Receiver operating characteristic analysis suggested the significance of each glycobiomarker in discriminating CCA from non-CCA with area under curve of 0.580–0.777. High levels of CA19-9, CCA-CA, CA-S27, or WFA+-MUC1 were associated with poor prognosis and poor survival of CCA patients. Combination of these glycobiomarkers and graded as a GlycoBiomarker (GB)-score could increase the power of the tests in diagnosis than an individual marker with 81% of sensitivity, specificity and accuracy. According to the GB-score, these glycobiomarkers not only increased diagnostic power but also discriminated survival of patients indicating the diagnostic and prognostic values of GB-score. [ABSTRACT FROM AUTHOR]

• Circulating EMMPRIN levels in patients with OSA were significantly elevated compared to controls in Chinese individuals. • Circulating EMMPRIN levels were positively associated with the severity of OSA. • EMMPRIN could be a potential biomarker for predicting the occurrence of OSA. Obstructive Sleep Apnea (OSA) is a sleep-related breathing disorder which is strongly associated with the development of cardiovascular diseases. The aim of the study was to investigate the association between circulating extracellular matrix metalloproteinase inducer (EMMPRIN) and OSA risk. This was a cross-sectional study in which a total of 144 patients were recruited. Demographic data, blood biochemical parameters and polysomnography parameters were collected. We used a powerful high-throughput Multiplex Immunobead Assay technique to simultaneously detect circulating levels of EMMPRIN and E-selectin. Circulating levels of EMMPRIN were significantly increased in patients with OSA compared to controls (7.58[6.21–8.80] vs 1.47[0.80–5.91] ng/ml, P < 0.001). After adjusting for confounding factors, we found that circulating EMMPRIN levels were independently associated with the presence of OSA (odds ratio[OR] = 2.240, 95% confidence interval [CI] = 1.391–3.607, P < 0.001). Furthermore, circulating EMMPRIN showed greater discriminatory accuracy in predicting the presence of OSA (AUC:0.904). Circulating EMMPRIN levels were significantly increased in patients with OSA, and may be a novel marker for predicting the risk of OSA. [ABSTRACT FROM AUTHOR]

The objectives of our study were to expand phenotypic characterization of digital cushion thickness (DCT) to the Jersey breed and include mature bulls and to identify breed-specific quantitative trait loci (QTL) for DCT within the Jersey or Holstein breeds and common QTL across breeds and sexes to better understand biological regulation and guide future use of marker-assisted selection. In a cohort of 698 cows and 85 bulls (Holstein and Jersey) from 8 farms in New York State, data were collected on DCT, body condition score (BCS), withers height, and sacral height. All animals underwent sonographic examination of the digital cushion evaluated at the sole ulcer site for the right front and hind feet. Linear mixed models were conducted on DCT separately for cows and bulls with fixed effects of time point, breed, age, digit, and BCS group. The models included random effects to control for the random subset of animals per farm, repeated measures, and multiple measurements from each animal. The phenotypic results indicated that DCT varied by time point, breed, age, digit, and BCS group for cows and by breed, age, digit, and BCS group for bulls. For the genotypic study, 616 cow DNA samples were genotyped on the Illumina BovineHD 777K BeadChip (Illumina Inc., San Diego, CA), whereas 76 bull DNA samples were genotyped on different platforms ranging from 5K to 150K. Multiple genome-wide association studies were conducted to highlight pertinent phenotyping parameters and genetic markers for genomic selection. Data were separated into 8 data sets based on different combinations of breed and sex. Each data set was assessed for quality of markers and samples before conducting genome-wide association studies for DCT, testing the inheritance models and genetic variation of digit, foot, and average thickness. Ten markers passed the Bonferroni correction threshold and 9 passed false discovery rate from 10 genome-wide association studies using a combination of the covariates breed, sex, genotyping batch plate, age, BCS, withers height, and sacral height. Of the 43 candidate genes, 8 novel biologically plausible genes were identified on Bos taurus autosomes 3, 4, 7, and 9: SFRS18 and LRRFIP1 function in fat deposition, whereas AHR , BZW2 , EFNA5 , USP45 , and VAV3 effect bone growth, and SOSTDC1 is related to epidermal keratinocyte function. The genetic markers associated with DCT in this study were explored for variation between cows and bulls within and across breeds for their potential use in marker-assisted selection. [ABSTRACT FROM AUTHOR]

Background: In cases of total hip arthroplasty (THA) dislocation, a synovial fluid aspiration is often performed to evaluate for periprosthetic joint infection (PJI). It is currently unclear how aseptic dislocation of a THA influences synovial fluid white blood cell (WBC) count and polymorphonuclear percentage (PMN%). The primary aim of this study is to investigate the influence of THA dislocation on synovial WBC count and PMN%.Methods: Twenty-eight patients who underwent a synovial aspiration of a THA between 2014 and 2019 were identified and enrolled in our case-control study. Patients with an aseptic THA dislocation and synovial hip aspiration were matched against patients without dislocation, patients undergoing hip aspiration before aseptic THA revision surgery, and patients undergoing hip aspiration before septic THA revision surgery.Results: Synovial WBC count was significantly increased in the dislocation vs aseptic THA revision group (P = .015), as well as between the septic revision group vs dislocation and aseptic THA revision group (both P < .001). The PMN% did not differ significantly between the dislocation and aseptic revision groups (P = .294). Mean C-reactive protein values were 12.4 ± 14.9 mg/dL in THA dislocation, 24.1 ± 37.7 mg/dL in THA without infection compared to 85.7 ± 84.9 mg/dL in THA infection group (P < .001).Conclusion: This study shows that THA dislocation has a significant impact on synovial WBC count in joint aspiration. Our data suggest that in the setting of THA dislocation, synovial WBC and PMN% may not be the best method to evaluate for PJI. Further research should be performed to establish new thresholds for these synovial inflammatory markers in the setting of THA dislocation and PJI.Level Of Evidence: Level III; retrospective trial. [ABSTRACT FROM AUTHOR]

The bovine digital cushion is a compression pad between the distal phalanx and sole and has been associated with claw horn disruption lesions. Digital cushion thickness (DCT) is estimated to be moderately heritable. Therefore, the objectives of our study were to examine influences of management and environment on DCT and to identify genetic markers and candidate genes associated with DCT. In a cohort of 502 Holsteins from 5 farms in New York State, DCT and body condition score (BCS) were collected twice, at <137 d prepartum and from 86 to 127 d in milk, corresponding to periods when the digital cushion is thickest and thinnest, respectively, as determined by previous research. Cows underwent sonographic examination of the digital cushion evaluated at the typical sole ulcer site for the right front and hind foot. Linear mixed models were conducted on DCT with the fixed effects of time point, digit, wither height, sacral height, BCS group, and multiple farm system variables separately and included random effects to control for the random subset of cows per farm, repeated measures, and multiple measurements from each cow. The phenotypic results indicated that DCT varied by sample time point, sacral height, parity, digit, BCS group, and wither height. For the genotypic study, 447 DNA samples were genotyped on the Illumina BovineHD 777K BeadChip (Illumina Inc., San Diego, CA). Quality assessment of markers and samples provided a final data set of 431 samples and 579,449 markers. Genome-wide association studies were conducted for DCT testing inheritance models and genetic variation of digit, foot, time point, and average thickness. One marker passed the Bonferroni correction threshold and 26 passed false discovery rate from 4 genome-wide association studies with covariates of sequencing batch plate, parity group, BCS, wither height, and sacral height. Ten candidate genes were identified, with 2 genes on Bos taurus autosomes 24 and 29 involved in biological functions related to the digital cushion: MC4R and DLG2 were related to fat deposition and bone growth, respectively. The genetic markers discovered in this study have the opportunity to be used in breeding programs using genomic selection to select against claw horn disruption lesions and lameness due to associations between the markers and DCT. Further studies on the biologically plausible candidate genes may identify causative genetic variants and how they relate to DCT through gene regulation, expression, structure, or copy number variation. [ABSTRACT FROM AUTHOR]

Feed efficiency (FE) is one of the most important traits in pig production. However, it is difficult and costly to measure it, limiting the collection of large amount of data for an accurate selection for better FE. Therefore, the identification of single-nucleotide polymorphisms (SNPs) associated with FE-related traits to be used in the genetic evaluation is of great interest of pig breeding programs for increasing the prediction accuracy and the genetic progress of these traits. The objective of this study was to identify SNPs significantly associated with FE-related traits: average daily gain (ADG), average daily feed intake (ADFI) and feed conversion ratio (FCR). We also aimed to identify potential candidate genes for these traits. Phenotypic information recorded on a population of 2386 three-way crossbreed pigs that were genotyped for 51 468 SNPs was used. We identified three loci of quantitative trait (QTL) regions associated with ADG and three QTL regions associated with ADFI; however, no significant association was found for FCR. A false discovery rate (FDR) ≤ 0.005 was used as the threshold for declaring an association as significant. The QTL regions associated with ADG on Sus scrofa chromosome (SSC) 1 were located between 177.01 and 185.47 Mb, which overlaps with the QTL regions for ADFI on SSC1 (173.26 and 185.47 Mb). The other QTL region for ADG was located on SSC12 (2.87 and 3.22 Mb). The most significant SNPs in these QTL regions explained up to 3.26% of the phenotypic variance of these traits. The non-identification of genomic regions associated with FCR can be explained by the complexity of this trait, which is a ratio between ADG and ADFI. Finally, the genes CDH19, CDH7, RNF152, MC4R, PMAIP1, FEM1B and GAA were the candidate genes found in the 1 Mb window around the QTL regions identified in this study. Among them, the MC4R gene (SSC1) has a well-known function related to ADG and ADFI. In this study, we identified three QTL regions for ADG (SSC1 and SSC12) and three for ADFI (SSC1). These regions were previously described in purebred pig populations; however, to our knowledge, this is the first study to confirm the relevance of these QTL regions in a crossbred pig population. The potential use of the SNPs and genes identified in this study in prediction models that combine genomic selection and marker-assisted selection should be evaluated for increasing the prediction accuracy of these traits in this population. [ABSTRACT FROM AUTHOR]

Low-molecular-mass isoelectric point (p I) markers are a reasonable alternative to commonly used peptide and protein p I markers in the field of isoelectric focusing. We present a comparative study dealing with characterization of 44 nitrophenol-based compounds synthesized by the Mannich reaction which p I values cover a pH range from 3.2 to 10.4. The values of p I s of all the presented nitrophenol-based compounds were precisely determined by capillary isoelectric focusing technique (cIEF) when a standard deviation of measurement reached a value of a few hundredths of a pH unit (n ≥ 3). Differences have been found between in silico analysis of acid-base properties of the investigated compounds and the experimental cIEF data especially at the basic pH region. The data from the acidic pH range showed better correlation between these methods. Only three compounds were excluded from the group of p I markers because they contained impurities originating from the synthesis or long-term storage. Based on the presented results we identified 41 nitrophenol-based pI markers (NPIMs) which can fulfill requirements of the most applications in a field of isoelectric focusing analyses. Image 1 • 44 UV–vis absorbing nitrophenol-based compounds designed as possible p I markers. • p I s and acid-base properties of the p I marker structures studied in silico. • cIEF used for marker p I value determination and marker purity analysis. • 41 compounds covering a pH range from 3.2 to 10.4 proved to be suitable p I standards. [ABSTRACT FROM AUTHOR]

The objective of the study was to test the associations between backfat fatty acid composition (FAC) in a sample of 536 Italian Large White pigs and single nucleotide polymorphisms (SNPs) located in candidate genes, using univariate and multivariate approaches. The strongest associations were identified for the SNP AY183428 c.265T>C in Fatty acid synthase (FASN) gene, with the T allele linked to lower backfat contents of stearic (P = 0.003) and arachidic (P < 0.0001) acids, and increased amounts of dihomo-γ-linolenic (P = 0.003) and arachidonic (P = 0.009) acids. These associations were in agreement with the results of a multivariate analysis performed on backfat FAC, and an in silico analysis of the sequence flanking FASN SNP suggested that the T allele may disrupt a putative exonic splicing enhancer sequence therefore possibly affecting FASN activity. If the results will be further confirmed, the studied FASN SNP could be of particular interest for better understanding the regulative patterns controlling porcine backfat FAC. • Backfat fatty acid composition influences the quality of pig meat products. • FASN rs324640280 SNP was associated with porcine backfat fatty acid composition. • FASN SNP changes the content of myristic, stearic, arachidic and arachidonic acids. • FASN rs324640280 may be a promising marker for improving fatty acid composition. • The T allele of FASN SNP carries a mismatch in a putative ESE sequence. [ABSTRACT FROM AUTHOR]

Sepsis leads to coagulopathy by the activation of inflammatory mediators and vascular endothelial cell injury. A number of biomarkers are used to evaluate coagulopathy on sepsis. Fibrinogen and antithrombin activity have been reported as biomarkers of coagulopathy; however, the utility of these two markers has not been well established. This study aimed to evaluate the detailed association between these two markers and clinical outcomes in sepsis patients. This was a post hoc analysis of a multicenter, prospective cohort study conducted in 59 intensive care units throughout Japan from January 2016 to March 2017. We included 1103 adult patients with severe sepsis based on the Sepsis-2 criteria. The associations between the coagulation markers and in-hospital mortality were examined using linear and non-linear logistic regression analyses. We also evaluated the associations between the coagulation markers and disseminated intravascular coagulation (DIC) scores. The International Society on Thrombosis and Haemostasis overt DIC score was calculated after subtracting the fibrinogen component. The decreased levels of the fibrinogen and antithrombin activity were significantly associated with an increase in mortality (P = 0.011 and 0.002, respectively). In addition, cubic spline regression demonstrated that mortality sharply increased at a fibrinogen level of approximately <200 mg/dL and at an antithrombin activity of approximately <50%. Similarly, the decreased levels of the two markers non-linearly correlated with the elevation of DIC score. The fibrinogen level and antithrombin activity should be reconsidered as unique biomarkers for sepsis and sepsis-induced DIC. • A cubic spline model assessed nonlinear associations between markers and outcomes. • Fibrinogen levels of <200 mg/dL sharply increased the risk of mortality. • Antithrombin activity of <50% sharply increased the risk of mortality. • Fibrinogen and antithrombin were also non-linearly associated with DIC severity. [ABSTRACT FROM AUTHOR]

An ideal digesta marker for use in feeding studies is inert, unabsorbable, and moves with the portion of the digesta it is intended to mark. Both chromium (III) and cobalt (III) salts of EDTA (CrEDTA and CoEDTA, respectively) have been used as digesta liquid markers in studies with dairy cattle. Although a small portion of these markers is known to be absorbed and excreted in urine, the markers are assumed to remain ionically bound in the digesta. The degree to which these salts remain bound in solution can be determined through spectrophotometric measurement at the wavelength (λ) of peak absorbance of these colored compounds. The objective of this study was to evaluate whether CrEDTA and CoEDTA dissociate during incubation in autoclaved, clarified rumen fluid (ACRF), as indicated by changes in absorbance. In a complete block design with separate replicated analytical runs, approximately 40 mg/L of Cr from CrEDTA or Co from CoEDTA were incubated in 2 separate preparations of ACRF from 2 lactating Holstein cows, in water (CrEDTA), or in MES buffer (CoEDTA), and appropriate reagent blanks. Solution pH were approximately 6.0. Samples were incubated for 24 h at 39°C with absorbance measurements recorded at 0, 1, 2, 4, 6, 22, and 24. The CrEDTA was measured at λ = 541 nm, CoEDTA at λ = 535 nm, and both were measured with wavescans of λ = 330 to 700 nm. At their peak λ, both CrEDTA in water and CoEDTA in MES buffer maintained absorbance values throughout the incubation, whereas, in ACRF, CrEDTA absorbance decreased by 9% at 0 h, and by up to 14% by 24 h; CoEDTA showed a gradual decline over time, with approximately 4% loss in absorbance by 24 h. Responses differed by ACRF preparation. Both markers in ACRF showed increases and decreases over time in absorbance at λ = 330 and 380 nm, though the changes were more marked for CrEDTA; markers not in ACRF showed no change in absorbance at these λ. Changes in the absorbance values at λ = 330 and 380 nm suggest that soluble phenolic compounds may be involved in the exchange of metals with EDTA, but that does not preclude involvement of other components in rumen fluid. Both CrEDTA and CoEDTA incubated in ACRF showed declines over time in absorbance at their peak λ, suggesting that the metals dissociated from EDTA. The apparent dissociation indicates that these liquid markers are not inert as had been assumed. [ABSTRACT FROM AUTHOR]

• A unique aberrant miRNA-gene regulatory network and the related PPI network were constructed in PBMCs of individuals with LTBI. • The analysis of networks may provide insight into the molecular mechanisms of the immune response to LTBI. • MAPK1 expression was correlated with the clinicopathological characteristics of LTBI and it may be a potential marker during LTBI. • In consideration that MAPK1 and hsa-miR-212-3p might strongly activate the PI3K-Akt signaling pathway for LTBI. Tuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis (M. tb). New cases are now mainly caused by the progression of latent tuberculosis infection (LTBI). Thus, methods to diagnose and treat LTBI are urgently needed to prevent the development of active TB in infected individuals and the subsequent spread of the disease. In this study, a systems biology approach was utilized to obtain numerous microarray data sets for mRNAs and microRNAs (miRNAs) expressed in the peripheral blood mononuclear cells (PBMCs) of TB patients and individuals with LTBI. Within these data sets, we identified the differentially expressed mRNAs and miRNAs and further investigated which differentially expressed genes and miRNAs were uniquely expressed during LTBI. The Database for Annotation, Visualization and Integrated Discovery (DAVID) was employed to analyze the functional annotations and pathway classifications of the identified genes. To further understand the unique miRNA-gene regulatory network of LTBI, we constructed a protein–protein interaction (PPI) network for the targeted genes. The PPI network included 39 genes that were differentially and uniquely expressed in PBMCs of individuals with LTBI, and KEGG pathway enrichment analysis showed that these genes were predominantly involved in the PI3K-Akt signaling pathway, which plays an important role in chronic inflammation. DIANA TOOLs-mirPath analysis revealed that the identified miRNAs in the miRNA–gene regulatory network for LTBI were mainly associated with the Hippo signaling pathway, which functions in the development of inflammation. Quantitative real-time PCR verified the up expression of hsa-miR-212-3p and its predicted target gene — MAPK1 which had low expression and was a major component of the PPI network, and MAPK1 expression was correlated with the clinicopathological characteristics of LTBI by receiver operating characteristic (ROC) curve analysis. Therefore, MAPK1 has potential to be a new investigable marker during LTBI, which merits our further study and solution. The unique aberrant miRNA–gene regulatory network and the related PPI network identified in this study provide insight into the molecular mechanisms of the immune response to LTBI, and thus, may aid in the development of a novel treatment strategy. [ABSTRACT FROM AUTHOR]

• The model presented here shows two distinct environmentally induced biofilm phenotypes in orthodontic patients. • Biofilm around brackets showed increased glucosidase activity and biofilm in gingival margin showed higher protease activity. • Plaque from brackets showed increased glucosidase activity in subjects with WSL compared to patients without WSL. Approximately 25% of the adolescents in the Scandinavian population are treated with a fixed orthodontic appliance (FOA). Adverse effects such as enamel decalcification (white spot lesions – WSL), seem to affect over 30% of patients. WSL have only a limited ability to improve, thus seriously jeopardising the treatment outcome. The aim of present study was to explore the biofilm phenotype by investigating plaque collected: 1) adjacent to brackets, and 2) in gingival margin of maxillary incisors in adolescents with FOA. Incidence of WSL after treatment was also assessed. In eight adolescent patients treated with FOA, supra-gingival plaque formed on: 1) brackets, and 2) along the gingival margin of the maxillary incisors, was collected after 6–8 months of treatment. The patients were documented before and after treatment by intraoral photos. Plaque samples were tested for glycosidase- (fluorogenic substrates) and protease (FITC-labelled casein substrate) activities. The plaque samples were visualised by Live/Dead BacLight stain, following which cells were investigated by confocal scanning laser microscopy. In the collected plaque samples, all enzymes tested displayed small variations in activity between the individuals, except glucosidases, which varied significantly. Four patients developed WSL. The patients displayed higher glucosidase activity in plaque of brackets compared to patients without WSL. In seven patients, plaque at the gingival margin displayed higher protease activity than plaque of brackets. The current study shows two distinct environmentally induced biofilm phenotypes: 1) brackets with higher glucosidase activity, and 2) gingival margin with higher protease activity. Glucosidase activity might thus be used as a putative biomarker for risk of WSL. [ABSTRACT FROM AUTHOR]

Abstract A simple and environmentally approach using untargeted imaging of volatile substances combined with chemometrics and markers response was proposed for discriminating different species of honey with headspace gas-chromatography-ion-mobility (HS-GC-IMS). The 3D HS-GC-IMS imaging and their response differences enabled the clear discrimination between winter honey and sapium honey. Principal component analysis (PCA) and partial least-squares discrimination analysis (PLS-DA) were employed to discriminate different honey. Markers of two kinds of honey were identified and confirmed with a user-built imaging database combined with multivariate analysis. Benzaldehyde dimer and phenylacetaldehyde dimer were found to be reliable markers of winter honey, and phenylethyl acetate dimer was of sapium honey. Adulteration identification of the honey samples with different adulteration ratios were subjected to this triple-locked strategy analysis. The results demonstrate that HS-GC-IMS imaging coupled with chemometrics and marker identification is a useful triple-locked strategy to discriminate honey from different floral origins and adulterated honey. Graphical abstract Unlabelled Image Highlights • HS-GC-IMS was used to discriminate honey species and adulterated honey. • An untargeted imaging of volatile substances was applied to discriminate honey. • The user-built imaging database by HS-GC-IMS was built to discriminate honey. • PCA, PLS-DA, volcano plot and VIP were applied to find potential markers of honey. • The intensity of ion signal for each marker was assessed to ensure its veracity. [ABSTRACT FROM AUTHOR]

Abstract Polyethylenglycole (PEG) is a widespread linear polymer which can be utilized as a solute digestive and intestinal permeability marker in nutritional physiology studies depending on chain length/molecular mass. PEG 400 is proposed to be an ideal permeability marker. Due to its molecular mass (238–590 g/mol) and characteristics, PEG 400 is suggested to be used as a surrogate for studying the paracellular permeability of small hydrophilic molecules. For this purpose, a liquid chromatographic-tandem mass spectrometric method has been developed for the determination of the major oligomers of PEG 400 in porcine plasma. The analysis included a simple and rapid clean-up step where proteins were precipitated. The most intense ions corresponding to seven PEG 400 oligomers were separated within 7 min. Validation of the optimized method was performed in the range of 500–18,000 ng/mL. Mean recoveries between 93 and 105% were achieved using spiked plasma samples in three different concentration levels. The limit of quantification ranged between 11 and 244 ng/mL. The applicability of the method was demonstrated by the analysis of porcine plasma samples obtained from an animal experiment with barrows. The kinetic course of administrated PEG 400 was shown based on the dataset of two barrows selected from the control group, and it was figured out that relative proportion of each PEG oligomer in portal plasma decreased with increasing molecular mass. Highlights • PEG 400 as a paracellular permeability marker of small hydrophilic molecules • Development of a LC-MS/MS method of PEG 400 oligomers • Method includes a simple and rapid sample preparation. • Application by the analysis of porcine plasma [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • CdSe quantum dots tested as fuel markers for diesel oil. • Nanocrystals produced by one step colloidal growth in hexadecane. • Nanomarker detected either by electronic absorption or fluorescence spectroscopy. • Fluorescent nanoparticles detected down to 1 mg/kg level. Abstract Markers are regularly used to detect fraud and adulteration in fuel as well as to track products in a distribution chain. Herein, we tested the use of CdSe semiconductor fluorescent nanocrystals, quantum dots, as a new class of fuel markers. Quantum dots show bright fluorescence and they can be excited by light sources covering a broad spectral range, from ultraviolet up to the near infrared region. This class of markers presents great advantages over conventional ones, such as high detectability potential, fluorescence emission in multicolor wavelengths, high photostability, and easy preparation procedures. In this work, we prepared CdSe quantum dots by colloidal controlled growth in an organic medium to be used for evaluation of diesel oil. The detection method was either by electronic absorption or fluorescence spectroscopies. The nanomarkers could be detected down to 1 mg/kg level in diesel fuel. The overall results indicated that CdSe quantum dots have the potential for use as a new class of fuel nanomarkers. [ABSTRACT FROM AUTHOR]

Abstract The pose of an articulated machine includes the position and orientation of not only the machine base (e.g., tracks or wheels), but also its major articulated components (e.g., stick and bucket). To automatically estimate this pose is a crucial component of technical innovations aimed at improving both safety and productivity in many construction tasks. Based on computer vision, an automatic observation and analysis platform using a network of cameras and markers is designed to enable such a capability for articulated machines. To model such a complex system, a theoretical framework termed camera marker network is proposed. A graph abstraction of such a network is developed to both systematically manage observations and constraints, and efficiently find the optimal solution. An uncertainty analysis without time-consuming simulation enables optimization of network configurations to reduce estimation uncertainty, leading to several empirical rules for better camera calibration and pose estimation. Through extensive uncertainty analyses and field experiments, this approach is shown to achieve centimeter level bucket depth tracking accuracy from as far as 15 m away with only two ordinary cameras (1.1 megapixels each) and a few markers, providing a flexible and cost-efficient alternative to other commercial products that use infrastructure dependent sensors like GPS. A working prototype has been tested on several active construction sites confirming the method's effectiveness. Graphical abstract Unlabelled Image Highlights • A theoretical framework for machine pose estimation by camera and marker networks • Infrastructure independent excavation assistance with cm-level tracking accuracy • An efficient uncertainty analysis method to optimize network configurations • Empirical rules for better network designs, calibrations, and operations [ABSTRACT FROM AUTHOR]

Chagas disease is a widespread neglected disease in Latin America. Trypanosoma cruzi , the causative agent of the disease, is currently subdivided into six DTUs (discrete typing units) named TcI-TcVI, and although no clear association has been found between parasite genetics and different clinical outcomes of the disease or different transmission cycles, genetic characterization of T. cruzi strains remains crucial for integrated epidemiological studies. Numerous markers have been used for this purpose, although without consensus. These include mitochondrial genes, single or multiple-copy nuclear genes, ribosomal RNA genes, and the intergenic region of the repeated mini-exon gene. To increase our knowledge of these gene sequences and their usefulness for strain typing, we sequenced fragments of three mitochondrial genes, nine single-copy nuclear genes, and the repeated intergenic part of the mini-exon gene by Next Generation Sequencing (NGS) on a sample constituted of 16 strains representative of T. cruzi genetic diversity, to which we added the corresponding genetic data of the 38 T. cruzi genomes fully sequenced until 2022. Our results show that single-copy nuclear genes remain the gold standard for characterizing T. cruzi strains; the phylogenetic tree from concatenated genes (3959 bp) confirms the six DTUs previously recognized and provides additional information about the alleles present in the hybrid strains. In the tree built from the three mitochondrial concatenated genes (1274 bp), three main clusters are identified, including one with TcIII, TcIV, TcV, and TcVI DTUs which are not separated. Nevertheless, mitochondrial markers remain necessary for detecting introgression and heteroplasmy. The phylogenetic tree built from the sequence alignment of the repeated mini-exon gene fragment (327 bp) displayed six clusters, but only TcI was associated with a single cluster. The sequences obtained from strains belonging to the other DTUs were scattered into different clusters. Therefore, while the mini-exon marker may bring, for some biological samples, some advantages in terms of sensibility due to its repeated nature, mini-exon sequences must be used with caution and, when possible, avoided for T. cruzi typing and phylogenetic studies. • The best marker for T. cruzi DTU identification is based on nuclear single-copy genes. • Sequences of the intergenic region of the mini-exon gene do not allow for unequivocal DTU identification. • Sequence concatenation is an effective way to make the identification more accurate. • NGS allows identifying all haplotypes at once, which is key for hybrid strain identification. [ABSTRACT FROM AUTHOR]

Liver cancer is one of the most common malignancies in human digestive system. Despite the recent therapeutic methods, there is a high rate of mortality among liver cancer patients. Late diagnosis in the advanced tumor stages can be one of the main reasons for the poor prognosis in these patients. Therefore, investigating the molecular mechanisms of liver cancer can be helpful for the early stage tumor detection and treatment. Vascular expansion in liver tumors can be one of the important reasons for poor prognosis and aggressiveness. Therefore, anti-angiogenic drugs are widely used in liver cancer patients. MicroRNAs (miRNAs) have key roles in the regulation of angiogenesis in liver tumors. Due to the high stability of miRNAs in body fluids, these factors are widely used as the non-invasive diagnostic and prognostic markers in cancer patients. Regarding, the importance of angiogenesis during liver tumor growth and invasion, in the present review, we discussed the role of miRNAs in regulation of angiogenesis in these tumors. It has been reported that miRNAs mainly exert an anti-angiogenic function by regulation of tumor microenvironment, transcription factors, and signaling pathways in liver tumors. This review can be an effective step to suggest the miRNAs for the non-invasive early detection of malignant and invasive liver tumors. [ABSTRACT FROM AUTHOR]

• In chickens, fractionation of digesta complicates digestibility measurements. • Tracer selection is critical and depends on the segment and nutrient of interest. • TiO 2 yields sound ileal digestibility estimates for most nutrients, except nitrogen. • Dual-tracer methods should be considered for ileal protein/amino acid digestibility. Fractionation of digesta, as occurs during gastrointestinal transit in chickens, complicates accurate measurements of ileal digestibility using tracers. Dual-tracer methods using separate tracers for solid and fluid digesta phases may improve the accuracy of digestibility measurements when assumptions of the single tracer method are violated. The aim of the present study was to compare the apparent ileal digestibility (AID) of nutrients calculated with single- and dual-tracer methods in chickens fed diets varying in particle size, anticipating digesta phase separation in the proximal gastrointestinal tract. A total of 112 Dekalb White (BW: 1.53 ± 0.107 kg) and 112 Bovans Black (BW: 1.79 ± 0.127 kg) 29-week-old laying hens were distributed over 32 pens (seven birds/pen). Within breed, pens were randomly assigned to one of two experimental diets (coarse vs fine oat hulls; n = 8 replicate pens per diet/breed combination). Diets were supplemented with TiO 2 (3 g/kg) and Co-EDTA (2 g/kg). On days 34, 35, or 36, birds were euthanised and digesta from the ileum was collected for tracer and nutrient analyses. Apparent ileal digestibility was subsequently calculated by single- and dual-tracer methods. Although coarse oat hulls were hypothesised to increase the fractionation of solid and fluid digesta phases, no breed or diet × method interactions were found. Using a single tracer method based on TiO 2 , AID of nitrogen (N) was overestimated by 3%-units (P < 0.01) compared with the dual-tracer method, whereas AID estimates of DM, starch, fat, and non-starch polysaccharides did not differ (P > 0.09) and precision of all AID estimates was improved. In conclusion, these results show that although from a conceptual perspective, dual-tracer methods are presumed to better account for the variation in flow behaviour of different digesta phases, AID estimates obtained by the commonly used single tracer method using solid-phase tracer TiO 2 were more precise and only marginally differed from estimates obtained by a dual-tracer method using distinct tracers for solid (TiO 2) and liquid (Co-EDTA) digesta phases. Considering technical and economical constraints, the single tracer method may thus be the method of choice in many situations. Only when digestibility of proteins or amino acids is of specific interest, single tracer methods using a solid-phase tracer may not suffice. Nevertheless, for both single- and dual-tracer methods, tracer selection is critical, and the choice of tracers should depend on the nutrient(s) of interest. [ABSTRACT FROM AUTHOR]