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Objective Materials and Methods Results Conclusion In the present study, we aimed to compare serum CK‐MM levels in patients with and without adenomyosis and to investigate whether CK‐MM level can be a non‐invasive marker for myometrial damage due to adenomyosis.Our study was a prospective case‐control study in a tertiary center and consisted of 40 patients with a clinical/ultrasonographic diagnosis of adenomyosis and 40 patients without a clinical/ultrasonographic diagnosis of adenomyosis as the control group based on recently published morphological uterus sonographic assessment (MUSA) criteria. Individuals of similar age who signed a voluntary consent form were included in our study. Demographic, clinical, and laboratory findings of the patients in both groups were recorded. Blood serum samples were used for the determination of serum CK‐MM levels of the participants in our study. The samples were analyzed by using the human CK‐MM enzyme‐linked immunosorbent assay (ELISA) kit.In our study, the mean serum CK‐MM level was 16.2 ± 21.7 (ng/dL) in patients with adenomyosis and 2.6 ± 2.2 (ng/dL) in patients without adenomyosis. Serum CK‐MM level was statistically significantly higher in the patient group with adenomyosis than in the control group (p < 0.001). The CK‐MM threshold value of 3.43 ng/mL, with a sensitivity of 82.5% and specificity of 85%, has been found to be a valuable distinguishing level in patients with and without adenomyosis.In this study, we demonstrated that serum CK‐MM can be used as a non‐invasive diagnostic method in patients with adenomyosis. As the number of studies around this subject in the literature is insufficient, larger studies are needed to use CK‐MM as a diagnostic marker in adenomyosis. [ABSTRACT FROM AUTHOR]

Pregnancy of unknown location (PUL) is a temporary pathologic or physiologic phenomenon of early pregnancy that requires follow up to determine the final pregnancy outcome. Evidence indicated that PUL patients suffer a remarkably higher rate of adverse pregnancy outcomes, represented by ectopic gestation and early pregnancy loss, than the general population. In the past few decades, discussion about PUL has never stopped, and a variety of markers have been widely investigated for the early and accurate evaluation of PUL, including serum biomarkers, ultrasound imaging features, multivariate analysis, and the diagnosis of ectopic pregnancy based on risk stratification. So far, machine learning (ML) methods represented by M4 and M6 logistic regression have gained a level of recognition and are continually improving. Nevertheless, the heterogeneity of PUL markers, mainly caused by the limited sample size, the differences in population and technical maturity, etc., have hampered the management of PUL. With the advancement of multidisciplinary integration and cutting‐edge technologies (e.g. artificial intelligence, prediction model development, and telemedicine), novel markers, and strategies for the management of PUL are expected to be developed. In this review, we summarize both conventional and novel markers (represented by artificial intelligence) for PUL assessment and management, investigate their advancements, limitations and challenges, and propose insights on future research direction and clinical application. [ABSTRACT FROM AUTHOR]

One hundred eighty pairs of tissues of esophageal squamous cell carcinoma (ESCC) were tested by the transcriptome sequencing in order to explore etiology factors. The chi‐square test and correlation analysis demonstrated that the relative expression levels of keratin 17 (KRT17) and collagen type I α1 chain (COL1A1) were significantly higher in EC with diabetes. Expression of KRT17 was correlated with blood glucose (r = 0.204, p = 0.001) and tumor size (r = −0.177, p = 0.038) in patients. COL1A1 correlated with age (r = −0.170, p = 0.029) and blood glucose levels (r = 0.190, p = 0.015). Experimental results of qRT‐PCR: KRT17 and COL1A1 genes were highly expressed in ESCC (p < 0.05). When the two genes were used as a combination test, the positive detection rate of EC was 90.6%, and the ROC curve had greater power. The KRT17 and COL1A1 genes had the potential to be biomarkers for the diagnosis of ESCC. [ABSTRACT FROM AUTHOR]

Erect panicles with enhanced grain numbers can rationally utilize solar energy for dry matter accumulation. Only in japonica cultivars an inactive natural nonsense mutant allele of DEP1 has been reported to pleiotropically improve panicle architecture, nitrogen use efficiency, nitrogen and dry matter translocation and strength of the stem. Genomic sequence comparison of DEP1 in indica, aus and aromatic genotypes of West Bengal led to the identification of four natural allelic variants based on three single nucleotide polymorphisms (SNPs) on intron 1, two SNPs on exon 5 and two deletions on intron 2. Among them, a yield favourable missense mutant allele of DEP1 with two amino acid substitutions from Patnai 23 has been identified, and an allele‐specific co‐dominant marker based on the SNP (A/G) at 333rd position of exon 5 was designed. Assessment of DEP1Patnai 23 allele for yield improvement was examined in RILs and NILs developed from Patnai23 × N22 as N22 carries wild‐type allele. The relative abundance of DEP1 transcript in young panicles was twice as high in Patnai 23 than in N22. RIL‐DEP1Patnai 23 and NIL‐DEP1Patnai 23 showed enhanced grain number per panicle and total yield per plant compared to RIL‐DEP1N22 and NIL‐DEP1N22 allele. This newly identified DEP1 allele and marker will accelerate MAS to improve rice yield precisely. [ABSTRACT FROM AUTHOR]

Summary: The nutritional value of Hainan camellia oil is incomparable to other places, and Hainan camellia oil is expensive, so unscrupulous businessmen often mix other edible oils into them for illegal profit. This study detected the changes of volatile components in Hainan camellia oil adulterated with five edible oils (peanut, soybean, corn, rapeseed, and sunflower oils) using comprehensive two‐dimensional gas chromatography and quadrupole time‐of‐flight mass spectrometry (HS‐SPME‐GC × GC‐Q‐TOFMS). The principal component analysis (PCA) score plot showed that pure Hainan camellia oil (PHCO) and Hainan camellia oil samples were adulterated with other edible oils clearly to identify the adulteration separated from each other. The adulteration of PHCO could be accurately predicted using the developed PCA and OPLS‐DA models for concentrations as low as 5%. More importantly, several potential markers were found to identify the impersonate PHCO. Therefore, the volatile compound determination based on HS‐SPME‐GC × GC‐Q‐TOFMS proved to be an effective method for detecting adulteration of other edible oils in PHCO. [ABSTRACT FROM AUTHOR]

Amylose and resistant starch (RS) possess diverse health benefits besides serving as an important component in the starch industry. This study analyzed 48 subtropically‐adapted maize inbreds at multiple locations and characterized for specific starch genes using markers specific to SNPs. Significant variation for amylose (0.3–66.4%), RS (1.8–38.0%), and total starch (65.5–75.1%) is observed. Amylose showed a positive correlation with RS (r = 0.79**). Molecular analysis using 29 markers produced 40 alleles with an average major allele frequency of 0.84. Gene diversity, polymorphism information content (PIC), and genetic dissimilarity are 0.23, 0.19, and 0.33, respectively. The genotypes are categorized into six major clusters based on the markers, and high amylose and RS lines are assigned to cluster‐A and cluster‐B. The alleles associated with Sbe2b (84 bp Del) and Sbe1a (SNP “A”) showed positive correlations with amylose and RS. Additionally, allele “A” linked to the Sucrose transporter6 (Sut6) displayed a positive correlation with RS. Considering Sbe2b, Sbe1a and Sut6 genes, six haplotypes are observed, of these, hap‐A possessed the highest amylose and RS. The promising inbreds can be used as donors, while the validated markers for Sbe2b, Sbe1a and Sut6 genes can be effectively utilized for the improvement of amylose and RS through molecular breeding. [ABSTRACT FROM AUTHOR]

Background: Bone mesenchymal stem cells (BMSCs) are recognized for their intrinsic capacity for self‐renewal and differentiation into osteoblasts, adipocytes, and chondrocytes, making them pivotal entities within the field of bone research. Tescalcin (TESC) is known to play a role in specific cellular processes related to proliferation and differentiation. However, the precise involvement of TESC in the regulation of BMSCs remains unclear. The present study was designed to verify the functional implications of TESC in BMSCs. Methods: An adenovirus vector was engineered to downregulate TESC expression, and the Wnt/β‐catenin signaling pathway was activated using BML‐284. The assessment of mRNA was conducted by quantitative real‐time polymerase chain reaction (qRT‐PCR). The assessment of protein expression was conducted by Western blotting and immunofluorescence techniques (IF), respectively. Alkaline phosphatase (ALP) staining and activity assays were performed to verify ALP changes, while Alizarin Red S (ARS) staining and quantitative analysis were employed to assess mineralization capacity. Results: Initially, we observed an upregulation of TESC expression during osteogenic differentiation. Subsequently, TESC knockdown was demonstrated to decrease the osteogenic‐related genes expression and diminish BMSCs mineralization. Concomitantly, we identified the inhibition of Wnt/β‐catenin signaling following the TESC knockdown. Furthermore, the administration of BML‐284 effectively activated the Wnt/β‐catenin pathway, successfully rescuing the compromised TESC‐mediated osteogenic differentiation. Conclusion: Our findings indicate that TESC knockdown exerts an inhibitory effect on the osteogenic differentiation of BMSCs through the modulation of the Wnt/β‐catenin signaling pathway. This study unveils a novel target with potential applications for enhancing the regenerative potential of BMSCs in the realm of regenerative medicine. [ABSTRACT FROM AUTHOR]

Background: Immune recovery following allogeneic hematopoietic stem cell transplantation (allo‐HSCT) decisively influences the occurrence of opportunistic infections, one of the leading causes of death among this group of patients. Yet, today, there are no laboratory parameters mirroring immune function sufficiently. Torque teno virus (TTV) has already proven itself as a functional immune marker in other settings. Aims: In this analysis, we investigated whether monitoring of TTV‐DNA load in whole blood is able to provide additional information on the capacity of the immune system to control cytomegalovirus (CMV) replication in allo‐HSCT recipients. Methods: Whole blood samples from 59 patients were collected upon allo‐HSCT (between Day −7 and +10), on Day +14, +21, +28, +56, +90, and +365 post‐transplant. TTV‐DNA loads and other relevant clinical information were correlated with the risk of CMV infections or reactivations, defined by evidence of viral replication in blood. Results: CMV serostatus of the recipient and a TTV load below 1000 copies/mL upon allo‐HSCT were significantly associated with an increased incidence of CMV infection or reactivation. Conclusions: Quantification of TTV load in the early phase of allo‐HSCT procedure could provide additional information in order to identify patients at risk for CMV infection or reactivation. [ABSTRACT FROM AUTHOR]

Objectives: Rapid eye movement (REM) sleep behavior disorder (RBD) is proposed as an early diagnostic marker in Parkinson's disease (PD). We investigated the frequency of RBD during the progression of PD in the advanced stages and identified potential risk factors for developing RBD earlier or later. Patients and Methods: We performed a retrospective analysis and determined the frequency of RBD in all PD in‐patients (Hoehn and Yahr stages ≥3) with motor fluctuations who had undergone video‐polysomnography (vPSG) for a sleep complaint or daytime sleepiness. To correct for selection bias, we analyzed the prevalence of RBD in PD patients from the DeNoPa cohort. PD patients with RBD were compared with PD without RBD. To identify potential risk factors, we performed multiple regression modeling. Results: A total of 504 PD patients had vPSG. 37 were excluded due to missing REM or artifacts during REM. RBD was present in 406/467 (86.9%) PD patients. PD + RBD patients were older than PDnonRBD (69 ± 7.7 vs. 64 ± 9.2 years, P < 0.01), were more likely to have postural instability [234 (59.1%) vs. 19 (33.9%), P < 0.01], and were treated more often with antidepressants (other than SSRIs) [141 (34.7%) vs. 7 (13%), P < 0.01]. Multiple regression modeling identified predictors of RBD with an AUC of 0.78. Conclusion: The prevalence of RBD in patients with advanced PD is high and increases with disease severity, motor deficits, postural instability, orthostatic symptoms, and age. This suggests RBD is a progression marker of PD in patients with sleep complaints. [ABSTRACT FROM AUTHOR]

Kurzfassung: Ziel des Projektes ist es, durch ein mikrostrukturbasiertes Design einen nachhaltigen, nachverfolgbaren Beton „Sutracrete" herzustellen. Der Sutracrete soll durch die Wiederverwertung von Mauerwerksbruch in Form von Ziegelmehl und Ziegelgesteinskörnung hergestellt werden. Die Entwicklung soll auf rezklierten Ziegelvarietäten basieren, die durch eine hyperspektrale Sortierung sehr viel effizienter und stoffspezifisch verwertet werden könnten. Durch das neuartige Sortierverfahren wird erstmalig die Trennung zwischen niedriggebrannten, reaktiven Ziegelmehl und hochgebrannter, nicht reaktiver Ziegelgesteinskörnung möglich. Durch das mikrostrukturbasierte Design werden die Eigenschaften gezielt genutzt. In der Energieforschung sind der Ressourceneinsatz des Massenbaustoffs Beton und der damit verbundene Primärenergieeinsatz untrennbar. Kritische und weltweit stark nachgefragte Rohstoffe werden durch Ziegelmaterialien substituiert. Für die Herstellung des Sutracrete ergeben sich ein geringerer Gesamtenergieverbrauch im Vergleich zu Primärbaustoffen und damit eine Minderung der Treibhausgasemissionen. Der Einsatz von Markern ermöglicht erstmals die physikalische Korrelation zwischen Baumaterialien und einem in einer Datenbank hinterlegten digitalen Zwilling bzw. „Material Passport". [ABSTRACT FROM AUTHOR]

Background: The main therapy for rectal cancer patients is neoadjuvant therapy (NT) followed by surgery. Immune biomarkers are emerging as potential predictors of the response to NT. We performed a meta‐analysis to estimate their predictive significance. Methods: A systematic literature search of PubMed, Ovid MEDLINE and EMBASE databases was performed to identify eligible studies. Studies on patients with rectal cancer undergoing NT in which the predictive significance of at least one of the immunological markers of interest was assessed by immunohistochemistry (IHC) in pretreatment biopsies were included. Results: Seventeen studies reporting sufficient data met the inclusion criteria for meta‐analysis. High levels of total CD3+, CD4+ and CD8+ tumor infiltrating lymphocytes (TILs), as well as stromal and intraepithelial CD8+ compartments, significantly predicted good pathological response to NT. Moreover, high levels of total (tumoral and immune cell expression) PD‐L1 resulted associated to a good pathological response. On the contrary, high levels of intraepithelial CD4+ TILs were correlated with poor pathological response. FoxP3+ TILs, tumoral PD‐L1 and CTLA‐4 were not correlated to the treatment response. Conclusion: This meta‐analysis indicated that high‐density TILs might be predictive biomarkers of pathological response in patients that underwent NT for rectal cancer. [ABSTRACT FROM AUTHOR]

Background: Rheumatoid arthritis (RA) is a systemic autoimmune disease that chronically affects patients with episodes of inflammation. New inflammatory hematological markers were investigated for follow‐up, such as the neutrophil–monocyte ratio (NMR), lymphocyte monocyte ratio (LMR), and neutrophil–lymphocyte ratio (NLR). This study was conducted to determine the most useful marker based on studies of association with RA disease activity and correlation with the classical markers C‐reactive protein (CRP), erythrocyte sedimentation rate (ESR), and rheumatoid factor (RF). Methods: This case‐control study included 62 chronic RA patients who had previously been diagnosed and experienced episodes of symptoms while attending a variety of public and private rheumatology clinics in Ibb City, Republic of Yemen, for the period of September 1 to November 30, 2021. Twenty healthy volunteers were included in this study. Complete blood count, CRP, ESR, and RF levels were measured in all participants. Results: The total leukocyte count, neutrophil count, platelet count, NMR, LMR, and NLR were positively correlated with CRP and ESR, but the monocyte count was reversed. The area under the curve (AUC = 0.861, 95% confidence interval [CI] = 0.769–0.948) for the NMR cutoff value of 4.7 was equal to that of CRP and close to that of ESR. This NMR cutoff value had 87% sensitivity and 80% specificity. LMR and NLR cutoff values of 4.35 and 1.35, respectively, resulted in AUCs of (AUC = 0.807, 95% CI, 0.708–0.905) and (AUC = 0.699, 95% CI, 0.571–0.819); their sensitivity and specificity were 62.3%, 90%, 57.4%, and 80%, respectively. Conclusions: As a convenient and low‐cost inflammatory marker of RA activity, NMR outperformed LMR and NLR. [ABSTRACT FROM AUTHOR]

Background: SOX17 (SRY‐box transcription factor 17) was recently identified as a highly sensitive and specific marker for ovarian and endometrial carcinomas in surgical specimens. In this study, validation of the utility of SOX17 immunohistochemistry (IHC) in diagnosing metastatic gynecologic carcinomas in cytology specimens was sought. Methods: The study cohort included 84 cases of metastatic carcinomas that included 29 metastatic gynecologic carcinomas (24 ovarian high‐grade serous carcinomas, two endometrial serous carcinomas, one low‐grade serous carcinoma, one ovarian clear cell carcinoma, and one endometrial endometrioid carcinoma) and 55 cases of metastatic nongynecologic carcinomas (10 clear cell renal cell carcinomas, 10 papillary thyroid carcinomas, 11 gastrointestinal adenocarcinomas, 10 breast carcinomas, 10 lung adenocarcinomas, and four urothelial carcinomas). Cytology specimen types included peritoneal fluid (n = 44), pleural fluid (n = 25), and fine‐needle aspiration (n = 15). SOX17 IHC was performed on the cell block sections. The intensity of staining and percent positivity of the tumor cells were evaluated. Results: SOX17 was highly expressed in all tested metastatic gynecologic carcinomas with diffuse and strong nuclear expression (29 of 29; 100%). SOX17 was negative in other metastatic nongynecologic carcinomas (54 of 55; 98.18%) except for one papillary thyroid carcinoma that showed low positivity (<10%). Conclusions: SOX17 is a highly sensitive (100%) and specific (98.2%) marker for the differential diagnosis of metastatic gynecologic carcinomas in cytology specimens. Therefore, SOX17 IHC should be included in the workup of differential diagnosis of metastatic gynecologic carcinomas in cytology specimens. The results of this study showed that SOX17 was highly expressed in all tested metastatic gynecologic carcinomas with diffuse (100%) and strong nuclear expression (29 of 29) and was negative in 54 of 55 metastatic nongynecologic carcinomas. SOX17 is a highly sensitive (100%) and specific (98.2%) marker for the diagnosis of metastatic gynecologic carcinomas in cytology specimens. [ABSTRACT FROM AUTHOR]

Background: Decreased cerebrovascular reactivity, measured as changes in blood‐oxygen‐level‐dependent (BOLD) signal, is a potential new cerebral amyloid angiopathy (CAA) severity marker. Before clinical application, the effect of aging on BOLD parameters, and reproducibility and test–retest reliability of these parameters should be assessed. Purpose: Assess the effect of healthy aging on cerebrovascular reactivity (BOLD amplitude, time to peak, and time to baseline). And determine reproducibility and test–retest reliability of these parameters. Study Type: Prospective‐observational. Population: Eighty‐six healthy adults (mean age 56 years, 55% female), 10 presymptomatic D‐CAA mutation carriers (mean age 34 years, 70% female), and 10 symptomatic D‐CAA mutation carriers (mean age 54 years, 70% female). Field Strength/Sequence: 3‐T, three‐dimensional (3D) T1‐weighted MRI and gradient echo BOLD fMRI. Assessment: To assess test–retest reliability of BOLD parameters, i.e. BOLD amplitude, time to peak, and time to baseline, BOLD fMRI scans were repeated three times immediately after each other, in both controls and mutation carriers. To assess reproducibility, BOLD fMRI scans were repeated with a 3‐week interval for each subject. Statistical Tests: Linear regression analyses and two‐way mixed absolute agreement intra‐class correlation approach. Results: Healthy aging was associated with decreased BOLD amplitude (β = −0.711) and prolonged time to baseline (β = 0.236) in the visual cortex after visual stimulation Reproducibility of BOLD amplitude was excellent (ICC 0.940) in the subgroup of healthy adults. Test–retest reliability for BOLD amplitude was excellent in healthy adults (ICC 0.856–0.910) and presymptomatic D‐CAA mutation carriers (ICC 0.959–0.981). In symptomatic D‐CAA mutation carriers, test–retest reliability was poor for all parameters (ICCs < 0.5). Data Conclusion: Healthy aging is associated with decreased cerebrovascular reactivity, measured by changes in BOLD response to visual stimulation. The BOLD amplitude appears to be a robust measurement in healthy adults and presymptomatic D‐CAA mutation carriers, but not in symptomatic D‐CAA mutation carriers. [ABSTRACT FROM AUTHOR]

The diagnosis of internal neoplasia in horses is challenging. Increased production of hormones physiologic for adult animals (e.g., adrenocorticotropin, norepinephrine, and erythropoietin) or typical for the foetal phase (alpha‐fetoprotein, anti‐Müllerian hormone, and parathyroid‐hormone‐related protein) might aid in tumour diagnostics. Thymidine kinase‐1 and alkaline phosphatase are examples of intracellular enzymes, whose activity in the blood may increase in some neoplasia cases. Furthermore, inappropriate production of abnormal monoclonal or autologous antibodies can accompany lymphoma and multiple myeloma. Many of those tumour markers lead to clinical or laboratory changes, called paraneoplastic syndromes, such as hypercalcaemia and erythrocytosis. The interpretation of the results of the tumour marker measurements in horses is complicated due to many factors affecting the markers' concentration or activity (e.g., young age, pregnancy, and inflammation) and other diseases triggering the same changes. Moreover, the presence of paraneoplastic syndromes is inconsistent, which leads to low sensitivity of those substances as tumour markers. In conclusion, screening for neoplasia in horses is not recommended. The measurement of tumour markers should be performed only in risk groups with suspicious clinical or laboratory findings, and the results should be interpreted with caution. It is advisable to add inflammatory markers to the tumour profile or repeat the measurements. [ABSTRACT FROM AUTHOR]

Summary: Visualization of root colonization by arbuscular mycorrhizal fungi (AMF) is the most elementary experiment in the field of mycorrhizal symbiosis. The most widely used approach for evaluating levels of AMF colonization is staining with trypan blue or ink, which is scored using the time‐consuming grid intersection method. Here we demonstrate the use of an anthocyanin‐based visual marker system for visualizing AMF colonization of Medicago truncatula roots.Expression of MtLAP1, a transcription factor which regulates the production of anthocyanins, from the AMF‐induced Kunitz Protease Inhibitor 106 promoter, allowed the visualization of arbuscules in live plant tissues without microscopy or staining.This marker system allowed straightforward qualitative evaluation of the ram1, vpy and dmi3 AMF phenotypes using Agrobacterium rhizogenes hairy‐root transformation. For the strigolactone biosynthesis mutant carotenoid cleavage dioxygenase 8a and a novel mutant scooby, which show quantitative AMF symbiotic phenotypes, the amount of anthocyanins in the roots estimated by spectrophotometry correlated very well with colonization levels estimated by staining and scoring using the grid intersection method.The LAP1‐based marker system therefore provides a highly efficient approach for mutant screening and monitoring of AMF colonization in live tissues by eye, or for quantitative assessment using a simple and quick photometric assay. [ABSTRACT FROM AUTHOR]

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

The urinary steroid profile established for the monitoring of eventual testosterone or testosterone precursor application by athletes includes concentrations and ratios of various endogenously produced steroidal hormones and metabolites. Due to enzymatic activities in urine specimens, the concentrations of these endogenous steroids and consequently their ratios may alter, leading to potential misinterpretation of analytical results. Microbiological contamination in athletes' urine samples can occur due to urinary tract infections or due to contamination by the non‐sterile sample collection conditions. Depending on the duration of transportation of urine samples, the transport and storage conditions may favour microorganisms' growth, and therefore, the enzymatic activity can be accelerated. Degradation effects on endogenous steroids caused by microorganisms have been observed, such as hydrolysis of steroid conjugates, increase of testosterone in the free fraction or modification of the steroid structure by oxidoreductive reactions. The World Anti‐Doping Agency (WADA) implemented criteria to check for signs of microbial degradation in a technical document dealing with the detection, analysis and reporting of endogenous androgenic anabolic steroids (TD EAAS) in urine samples. During the endogenous steroid profile confirmation procedures (CPs) of the WADA accredited Seibersdorf Laboratory, significant differences in the concentrations of markers of the steroid profile were observed compared to the initial testing procedures (ITPs). The changes in concentrations of the urinary steroid profile were attributed to the reduction of the 17‐keto group to a 17β‐hydroxy group caused by increased enzymatic activity during the hydrolysis step. In order to monitor the 17‐keto reduction activity in athletes' urine specimens, possible marker substances containing a 17‐keto group were synthesised and added in the internal standards mixture (ISTD) of the ITP. The presence of the reduced 17β‐hydroxy form of the marker substance indicated enzymatic activity leading to 17‐keto reduction reactions. The substance 3β‐ethoxy‐5α‐androstane‐17‐one was defined to be suitable to indicate 17‐keto reduction reactions occurring during hydrolysis carried out at moderate temperatures. [ABSTRACT FROM AUTHOR]

Introduction: The additional sex combs like 1 (ASXL1) gene is frequently mutated in a number of haematological neoplasms. The c.1934dupG, known to be the most common alteration in ASXL1, is associated with poor clinical outcome. A systematic determination of ASXL1 mutational status in myeloid malignancies is therefore necessary for prognostic stratification. Methods: Because direct sequencing is not sensitive and next‐generation sequencing (NGS) is time‐consuming, expensive and sometimes does not allow the detection of the c.1934dupG, we have developed a fragment analysis assay, complementary to NGS, that allows the detection of c.1934dupG mutation in addition to other nearby insertions/deletions of ASXL1 located close to it. We called this assay the "PCR‐Fluo‐ASXL1‐FA." Results: First, we evaluated the efficiency of our approach compared to NGS and Sanger. We showed that "PCR‐Fluo‐ASXL1‐FA" could detect all insertional mutations of ASXL1 located on its area, with a high sensitivity (1.5%). Then, we have illustrated the interest of this technique by three concrete cases. Discussion: In summary, we have established a fragment analysis approach, which can detect most ASXL1 mutations, in particular the c.1934dupG, in a sensitive, fast and inexpensive manner. We therefore recommend the synchronous use of this method with NGS, to ensure complete detection of all clinically relevant ASXL1 mutations in patients suffering with myeloid neoplasms. [ABSTRACT FROM AUTHOR]

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

Food fraud is currently a growing global concern with far‐reaching consequences. Food authenticity attributes, including biological identity, geographical origin, agricultural production, and processing technology, are susceptible to food fraud. Metabolic markers and their corresponding authentication methods are considered as a promising choice for food authentication. However, few metabolic markers were available to develop robust analytical methods for food authentication in routine control. Untargeted metabolomics by liquid chromatography‐mass spectrometry (LC‐MS) is increasingly used to discover metabolic markers. This review summarizes the general workflow, recent applications, advantages, advances, limitations, and future needs of untargeted metabolomics by LC‐MS for identifying metabolic markers in food authentication. In conclusion, untargeted metabolomics by LC‐MS shows great efficiency to discover the metabolic markers for the authenticity assessment of biological identity, geographical origin, agricultural production, processing technology, freshness, cause of animals' death, and so on, through three main steps, namely, data acquisition, biomarker discovery, and biomarker validation. The application prospects of the selected markers by untargeted metabolomics require to be valued, and the selected markers need to be eventually applicable at targeted analysis assessing the authenticity of unknown food samples. [ABSTRACT FROM AUTHOR]

This document is a response letter from Peter T. Nelson, Andras Sziraki, and Junyue Cao in the journal Neuropathology & Applied Neurobiology. The authors acknowledge that their literature search failed to cite an important paper by Drs. Gurler and Yemisci on retinal pericytes. They also highlight that pericyte markers may differ across different organs and species, and that specific markers for pericytes are crucial in research. The authors express gratitude for the letter and express interest in learning more about pericytes in various contexts. [Extracted from the article]

Accurate diagnosis of the differentially aggressive fungi Leptosphaeria maculans 'brassicae' and L. biglobosa 'brassicae' causing blackleg disease in Brassica crops is crucial. Prior to the availability of fungal whole‐genome sequences, gene‐specific markers were designed on specific genes. But, the availability of the whole‐genome sequences of several isolates now offers a greater opportunity to develop more precise and novel markers. The draft genomes of L. maculans and L. biglobosa that are available in the repository were aligned, and species‐specific primers were designed from the variable sequences that encode for effector proteins. Three primer sets namely, Lm1, Lm2 and Lm5 and two primer sets namely Lb1' and Lb3 specifically detected the isolates of target species in PCR assay. The primers Lm5 and Lb1' were multiplexed for detection of L. maculans 'brassicae' and L. biglobosa 'brassicae', respectively, from a single PCR reaction. The markers were highly sensitive in amplifying target species from crude 'pseudothecia and ascospore suspension' without requiring DNA extraction. These markers, solitarily or in combination, could be used for precise, sensitive and rapid detection of L. maculans 'brassicae' and L. biglobosa 'brassicae' species and will be helpful for surveillance, management and transboundary quarantine of the devastating blackleg disease. [ABSTRACT FROM AUTHOR]

Summary: In the European rabbit (Oryctolagus cuniculus), a polytocous livestock species, the number of teats indirectly impacts the doe reproduction efficiency and, in turn, the sustainable production of rabbit meat. In this study, we carried out a genome‐wide association study (GWAS) for the total number of teats in 247 Italian White does included in the Italian White rabbit breed selection program, by applying a selective genotyping approach. Does had either 8 (n = 121) or 10 teats (n = 126). All rabbits were genotyped with the Affymetrix Axiom OrcunSNP Array. Genomic data from the two extreme groups of rabbits were also analysed with the single‐marker fixation index statistic and combined with the GWAS results. The GWAS identified 50 significant SNPs and the fixation index analysis identified a total of 20 SNPs that trespassed the 99.98th percentile threshold, 19 of which confirmed the GWAS results. The most significant SNP (P = 4.31 × 10−11) was located on OCU1, close to the NUDT2 gene, a breast carcinoma cells proliferation promoter. Another significant SNP identified as candidate gene NR6A1, which is well known to play an important role in affecting the correlated number of vertebrae in pigs. Other significant markers were close to candidate genes involved in determining body length in mice. Markers associated with increased number of teats could be included in selection programmes to speed up the improvement for this trait in rabbit lines that need to increase maternal performances. [ABSTRACT FROM AUTHOR]

The role of cancer‐associated fibroblasts (CAFs) has been thoroughly investigated in tumour microenvironments but not in bladder urothelial carcinoma (BLCA). The cell fraction of CAFs gradually increased with BLCA progression. Weighted gene co‐expression network analysis (WGCNA) revealed a specific gene expression module of CAFs that are relevant to cancer progression and survival status. Fifteen key genes of the module were consistent with a fibroblast signature in single‐cell RNA sequencing, functionally related to the extracellular matrix, and significant in survival analysis and tumour staging. A comparison of the luminal‐infiltrated versus luminal‐papillary subtypes and fibroblast versus urothelial carcinoma cell lines and immunohistochemical data analysis demonstrated that the key genes were specifically expressed in CAFs. Moreover, these genes are highly correlated with previously reported CAF markers. In summary, CAFs play a major role in the progression of BLCA, and the 15 key genes act as BLCA‐specific CAF markers and can predict CAF changes. WGCNA can, therefore, be used to sort CAF‐specific gene set in cancer tissues. [ABSTRACT FROM AUTHOR]

This review offers an overview of the current status and the most recent advances in liquid chromatography–mass spectrometry (LC‐MS) techniques with both high‐resolution and low‐resolution tandem mass analyzers applied to the identification and detection of heat‐stable species‐specific peptide markers of meat in highly processed food products. We present sets of myofibrillar and sarcoplasmic proteins, which turned out to be the source of 105 heat‐stable peptides, detectable in processed meat using LC‐MS/MS. A list of heat‐stable species‐specific peptides was compiled for eleven types of white and red meat including chicken, duck, goose, turkey, pork, beef, lamb, rabbit, buffalo, deer, and horse meat, which can be used as markers for meat authentication. Among the 105 peptides, 57 were verified by multiple reaction monitoring, enabling identification of each species with high specificity and selectivity. The most described and monitored species by LC‐MS/MS so far are chicken and pork with 26 confirmed heat‐stable peptide markers for each meat. In thermally processed samples, myosin, myoglobin, hemoglobin, l‐lactase dehydrogenase A and β‐enolase are the main protein sources of heat‐stable markers. © 2019 John Wiley & Sons Ltd. Mass Spec Rev [ABSTRACT FROM AUTHOR]

Anogenital distance (AGD) is the length between the genitals and anus which shows an androgenic activity in the evolution of the reproductive system in the uterine life. For prostatic evolution and development during the embryological stage, androgen exposure is required. In this study, we aimed to investigate the relationship between AGD and benign prostate hyperplasia (BPH)‐related lower urinary tract symptoms (LUTS). A total of 70 patients who were admitted to our urology clinics with LUTS due to BPH (LUTS group) and 70 patients without LUTS (control group) were included. All patients were administered an International Prostate Symptom Score form. Data including height, weight, body mass index, total prostate‐specific antigen, prostate volume and uroflowmetry Qmax values of all patients were evaluated. The AGD of the LUTS and control groups was measured. The mean AGDAS values of the LUTS group were significantly lower than the control group (p =.013). There was no statistically significant difference between the two groups in terms of the mean adjusted AGDAP values (p =.241). However, the mean adjusted AGDAS values were significantly lower in the LUTS group than the control group (p =.002). Our study results suggest that AGD may be a useful marker in BPH‐related LUTS. [ABSTRACT FROM AUTHOR]

The objective of this study was to predict the value of lymphocyte subsets in cancer progression. Peripheral blood was obtained from 327 untreated patients with cancer and 158 healthy volunteers. Levels of lymphocyte subsets were determined by flow cytometry. There were decreased levels of natural killer (NK) cells, CD8+ T cells, and naïve CD4+/CD4+ T cells in untreated patients with cancer compared to those in healthy controls. Inversely, there were elevated levels of the following T‐cell percentages in cancer patients compared to those in healthy controls: memory CD4+/CD4+, CD8+ T cells, HLA‐DR/CD8+, CD8+ CD38+/CD8+, and CD4+/CD8+. In addition, there are a decreasing trend in terms of CD4+ T‐cell counts and an increase CD8+ HLA‐DR/CD8+ T‐cell and CD8+ CD38+/CD8+ T‐cell percentages in the advanced stage. An increasing trend with advanced tumor stage and the percentages of CD8+ HLA‐DR/CD8+ T cells and CD8+ CD38+/CD8+ T cells was shown in this study. There are a negative correlation for CD4+ T‐cell counts and positive correlation for percentages of CD8+ HLA‐DR/CD8+ T cell and CD8+ CD38+/CD8+ T cells with the lymph node metastasis. In the presence of distant metastatic spread, we observed higher NK‐cell counts, CD8+ HLA‐DR/CD8+ T‐cell percentages, CD8+ CD38+/CD8+ T‐cell percentages, as well as lower CD4+ T‐cell counts than those in the absence of distant metastases spread. Abnormal levels of NK cell, CD8+ T cells, memory CD4+/CD4+, naïve CD4+/ CD4+, CD8+ HLA‐DR/CD8+, CD8+ CD38+/CD8+, and CD4+/CD8+ can be a potential blood biomarkers of cancer development. CD4+ T‐cell counts and percentages of CD8+ HLA‐DR/ CD8+ and CD8+ CD38+/ CD8+ can predict the cancer progression. [ABSTRACT FROM AUTHOR]

Objective: Despite recent advances in molecular biology and genetics, the development of intracranial aneurysms (IA) is still poorly understood. Elucidation of the processes occurring in the IA wall is essential for a better understanding of IA pathophysiology. We sought to analyze the current evidence from histological, molecular and genetic studies of IA. Methods: We systematically searched PubMed, Scopus, Web of Science and Cochrane Library for articles published before Mar 1, 2019 reporting on different diagnostic markers in human IA specimens. Expression of the markers in IA wall (vs. healthy arterial wall) and association with the rupture status were analyzed. The quality of the included studies and the level of the evidence for the markers were incorporated into the final data assessment. Results: We included 123 studies reporting on analyses of 3476 IA (median 19 IA/study) published between 1966 and 2018. Based on microscopic, biochemical, genetic and biomechanical analyses, data on 358 diagnostic targets in the IA wall were collected. We developed a scale to distribute the diagnostic markers according to their specificity for IA or healthy arterial wall, as well as for ruptured or unruptured IA. We identified different functional pathways, which might reflect the intrinsic and extrinsic processes underlying IA pathophysiology. Conclusions: Multiple histological and molecular markers and the related functional pathways contributing to the development of IA might present promising targets for future therapeutic interventions. Because of small numbers of IA samples in each study, 89% of the analyzed diagnostic markers presented with the lowest level of evidence. This underlines the need for the initiation of a multi‐centric prospective histological IA register for pooled data analysis. [ABSTRACT FROM AUTHOR]

Increased cyclooxygenase‐2 (COX‐2) expression is thought to support tumorigenesis through various mechanisms and is analyzed as a potential cancer marker. In 18 studies, COX‐2 expression in melanocytic lesions of human skin was examined immunohistochemically. However, results obtained by individual research groups differ in terms of detection frequency and level of this protein, as well as localization of stained cells within tumor. Possible reasons for the discrepancies are analyzed in this review: the application of different antibodies, the use of standard histopathological sections or tissue microarrays and the analyzes of staining results based on different algorithms. COX‐2 level is significantly lower in nevi than in melanomas, increases gradually with progression of these malignant cancers and reaches the highest values in metastases. These gradual changes in COX‐2 expression appear to be difficult to analyze based only on subjective assessment of staining intensity. The most convergent data were obtained using antibodies for N‐terminal fragments of COX‐2 protein and analyzing results based on calculation of percentage fraction of positive cells. The extent of stained area in specimen thus appears to be more important than the intensity of staining in terms of evaluation of COX‐2 performance as a diagnostic and prognostic marker of cutaneous melanoma. [ABSTRACT FROM AUTHOR]

Background: Valproic acid (VPA) is a clinical medicine primarily prescribed to control epileptic symptoms. VPA has potential side‐effects, such as hepatotoxicity. Fibroblast growth factor 21 (FGF21) is a functional cytokine for metabolic regulation. In this article, we aimed to evaluate the possible clinical application of FGF21 in VPA‐treated livers in early undetected liver injury (EULI). Methods: Methodologically, plasma samples of VPA‐treated epileptic patients were isolated for biochemical and high‐performance liquid chromatography tests. In addition, VPA‐dosed mice were subjected to determinations of serological parameters, key regulatory effectors and FGF21 expressions through biochemical analyses, enzyme‐linked immunosorbent assay, immunohistochemistry stain, immunofluorescence stain, and reverse transcription‐polymerase chain reaction (RT‐PCR) test, respectively. Results: The serological data suggested that VPA‐treated epileptic patients showed visibly elevated FGF21 contents in plasma samples. However, other diagnostic parameters showed inconspicuous changes. As revealed in animal study, VPA‐dosed mice exhibited undetected morphological alterations and hormonal changes in the liver, pancreas, and kidneys. Furthermore, serological parameters and key regulatory proteins in VPA‐dosed livers and controls showed inconspicuous changes. Interestingly, endogenous FGF21 expressions in VPA‐dosed mice were increased in sera. In further experiments, the findings showed that intracellular expressions of FGF21 mRNA and protein were upregulated in VPA‐dosed livers as revealed in RT‐PCR and immunoassay. Conclusions: Taken together, these preliminary data reveal that functional FGF21 cytokine may serve as a potent predictor in VPA‐related EULI. [ABSTRACT FROM AUTHOR]

The identification of the ubiquitous spore‐forming bacterium Brevibacillus laterosporus, whose interest in pharma, agriculture, and other industrial sectors is raising, mostly relies on 16S ribosomal RNA gene sequence analysis. However, due to bacterial gene homology, this method appears insufficient for a proper discrimination of this species, so that the availability of other target genes is necessary. Leveraging the morphological and genetic feature uniqueness of B. laterosporus, a sensitive and reliable detection and quantification method based on polymerase chain reaction (PCR) and quantitative PCR assays, respectively, was developed. Targeting a highly conserved spore surface protein‐related gene, B. laterosporus could be easily found in different matrices including soil, food, and insect body. Primer set selectivity was confirmed to be very specific and no false positives or negatives were observed using DNA of different bacterial species as a template. The method developed is also suitable for the rapid identification of newly isolated B. laterosporus strains. [ABSTRACT FROM AUTHOR]

Tumour budding has emerged as a promising prognostic marker in many cancers. We systematically reviewed all studies that evaluated tumour budding in diagnostic biopsies. We conducted a systematic review of PubMed, MEDLINE, Scopus, Web of Science and Cochrane library for all articles that have assessed tumour budding in diagnostic (i.e. pretreatment or pre‐operative) biopsies of any tumour type. Two independent researchers screened the retrieved studies, removed duplicates, excluded irrelevant studies and extracted data from the eligible studies. A total of 13 reports comprising 11 cohorts were found to have studied tumour budding in diagnostic biopsies. All these reports showed that evaluation of tumour budding in diagnostic biopsies was easily applicable. A strong association was observed between tumour budding score in diagnostic biopsies and corresponding surgical samples. Evaluation of tumour budding in diagnostic biopsies had a significant prognostic value for lymph node metastasis and patient survival. In all studies, tumour budding was a valuable marker of tumour aggressiveness and can be evaluated in technically satisfactory diagnostic biopsies. Thus, the assessment of tumour budding seems to identify the behaviour of cancer, and therefore to facilitate treatment planning. [ABSTRACT FROM AUTHOR]

Aim: This study aims to evaluate the association of salivary S100A8 and A9 proteins with periodontitis and its screening ability for periodontitis cross‐sectionally. Material and Methods: We selected 326 participants from the Yangpyeong Cohort: 218 participants with periodontitis and 108 participants without periodontitis. Stage II‐IV periodontitis according to the modification of new international classification of periodontitis was considered as periodontitis. S100A8 and A9 were assayed using enzyme‐linked immunosorbent assay kit. Age, sex, education, smoking, drinking, exercise, and metabolic syndrome were factored as confounders. Analyses of covariance and logistic regression analysis were applied to evaluate the association of S100A8 and A9 with periodontitis. Receiver operating characteristic curve was applied for screening ability. Results: Those with periodontitis compared to those without periodontitis showed higher adjusted amount of S100A8 (3694 versus 6757 ng/ml, p < 0.001), but less adjusted amount of S100A9 (1341 versus 1030 ng/ml, p = 0.015). The screening ability of S100A8 and A9 on periodontitis was c‐statistics of 0.69 (p < 0.001) for both S100A8 and A9, 0.67 for S100A8 and 0.63 (p < 0.001) for S100A9. Conclusions: Overall, salivary S100A8 and S100A9 could be practical markers for periodontitis. Its screening ability for periodontitis could be beneficial in clinics and at home. [ABSTRACT FROM AUTHOR]

The systemic inflammatory response is associated with survival in patients with a variety of cancers. This inflammatory response is measured in the peripheral blood, and can be monitored using two categories of indices: concentration of specific serum proteins (albumin, C‐reactive protein) and differential blood cell count (neutrophils, lymphocytes and platelets). Furthermore, combinations of these indices, such as the Glasgow Prognostic Score, which consists of the serum C‐reactive protein and albumin level; the neutrophil‐to‐lymphocyte ratio; the platelet‐to‐lymphocyte ratio; and the prognostic nutritional index, which is based on peripheral blood lymphocyte count and serum albumin level, have also been evaluated and compared in cancer research. To date, there are hundreds of studies that have shown the prognostic value of systemic inflammatory response markers in patients with urological cancer. Most studies have evaluated the prognostic and predictive role of the pretreatment value of the markers, although some have focused on the role of the post‐treatment value at specific points during the clinical course. The advantages of systemic inflammatory response markers are that they are easily measurable and inexpensive in the clinical setting. However, it is important to consider how clinicians use these markers in clinical practice. The present review provides a concise overview regarding systemic inflammatory markers in urological cancers, specifically C‐reactive protein, Glasgow Prognostic Score/modified Glasgow Prognostic Score, neutrophil‐to‐lymphocyte ratio, platelet‐to‐lymphocyte ratio and prognostic nutritional index. [ABSTRACT FROM AUTHOR]

Background: Immune checkpoint inhibitors (ICIs) have revolutionized the clinical treatment of multiple cancers. Recent studies revealed the potential prognostic value of the neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) in patients receiving ICIs; however, the results were inconsistent. We conducted a meta‐analysis to identify the prognostic significance of baseline NLR and PLR in cancer patients treated with ICIs. Methods: We conducted a thorough literature search of PubMed, Embase, and Cochrane databases for studies dealing with the prognostic impact of pretreatment NLR and/or PLR levels in cancer patients treated with ICIs. The clinical outcomes were progression‐free survival (PFS) and overall survival (OS). Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated, and sensitivity and subgroup analyses were performed to investigate heterogeneity. Results: Seventeen articles involving 2092 patients were included in the final analysis. The pooled HRs of PFS and OS for NLR were 1.81(95% CI 1.36–2.41) and 2.26 (95% CI 1.68–3.03), respectively, suggesting that patients with higher baseline NLRs had significantly poorer PFS and OS. Similar results were detected in sensitivity and subgroup analyses. However, no significant relevance was found between PLR and clinical endpoints in patients treated with ICIs (HR = 1.14, 95% CI 0.88–1.48 for PFS; HR = 1.35, 95% CI 0.86–2.12 for OS). Conclusion: These results indicate that high pretreatment NLR but not PLR level, as a routinely obtained hematological parameter, is a potential prognostic predictor for poor PFS and OS in cancer patients receiving ICIs. [ABSTRACT FROM AUTHOR]

Background: Markers of kidney dysfunction and damage have potential to detect chronic kidney disease (CKD) in early stages. However, data on long‐term variation of these markers in healthy dogs is lacking and is crucial for the interpretation of results. Hypothesis/Objectives: To determine temporal variations of serum cystatin C (sCysC) and urinary retinol‐binding protein (uRBP), neutrophil gelatinase‐associated lipocalin (uNGAL), immunoglobulin G (uIgG), and C‐reactive protein (uCRP) in healthy dogs. Animals Eight clinically healthy adult Beagles were evaluated. Methods: Longitudinal observational study. Serum cystatin C was determined by particle‐enhanced nephelometric immunoassay. Urinary retinol‐binding protein, uNGAL, uIgG and uCRP were determined by ELISA and concentrations were indexed to urinary creatinine. Within‐ and between‐dog variance components (VC) and within‐dog coefficients of variation (CV) were determined from blood and urine collected at eight time points over 1.5 years. Results: Urinary C‐reactive protein (uCRP) concentrations were consistently below the detection limit (5.28 ng/mL). Mean ± within‐dog standard deviation for sCysC, uRBP/c, uNGAL/c and uIgG/c was 0.15 ± 0.01 mg/L, 0.09 ± 0.03 mg/g, 2.32 ± 2.03 μg/g and 12.47 ± 10.98 mg/g, respectively. Within‐dog CV for sCysC, uRBP/c, uNGAL/c and uIgG/c was 8.1%, 33.7%, 87.2% and 88.1%, respectively. Conclusions and clinical importance: Serum cystatin C, uRBP/c, uNGAL/c and uIgG/c exhibit a wide range of long‐term within‐dog variability. Researchers and veterinarians might need to take this into account when interpreting their results. To assess their diagnostic and predictive ability, future studies need to establish reference ranges for healthy dogs and dogs with CKD. [ABSTRACT FROM AUTHOR]

Contents Summary 45 I. Introduction 45 II. Targeted chromosome‐based cloning via long‐range assembly (TACCA) 46 III. Resistance gene cloning through mutational mapping (MutMap) 47 IV. Cloning through mutant chromosome sequencing (MutChromSeq) 47 V. Rapid cloning through resistance gene enrichment and sequencing (RenSeq) 49 VI. Cloning resistance genes through transcriptome profiling (RNAseq) 49 VII. Resistance gene deployment strategies 49 VIII. Conclusions 50 Acknowledgements 50 References 50 Summary: Genetically encoded resistance is a major component of crop disease management. Historically, gene loci conferring resistance to pathogens have been identified through classical genetic methods. In recent years, accelerated gene cloning strategies have become available through advances in sequencing, gene capture and strategies for reducing genome complexity. Here, I describe these approaches with key emphasis on the isolation of resistance genes to the cereal crop diseases that are an ongoing threat to global food security. Rapid gene isolation enables their efficient deployment through marker‐assisted selection and transgenic technology. Together with innovations in genome editing and progress in pathogen virulence studies, this creates further opportunities to engineer long‐lasting resistance. These approaches will speed progress towards a future of farming using fewer pesticides. [ABSTRACT FROM AUTHOR]

Aims: Oral tongue squamous cell carcinoma (OTSCC) has a relatively poor outcome, and there is a need to identify better prognostic factors. Recently, tumour–stroma ratio (TSR) has been associated with prognosis in several cancers. The aim of this multi‐institutional study was to evaluate the prognostic value of TSR from original haematoxylin and eosin (HE)‐stained tumour‐resection slides in a series of early‐stage (cT1‐2N0) OTSCC patients. Methods and results: A TSR cutoff value of 50% was used to divide the patients into stroma‐rich (≥50%) and stroma‐poor (<50%) groups. The relationships between TSR and clinicopathological characteristics of 311 early‐stage OTSCC cases were analysed. The prognostic value of TSR in OTSCC was calculated separately and in combination with a previously published cancer cell budding and depth of invasion (BD) prognostic model. A total of 89 cases (28.6%) belonged to the stroma‐rich group. In a multivariate analysis, the stroma‐rich group had worse disease‐free survival, with a hazard ratio (HR) of 1.81 [95% confidence interval (CI) 1.17–2.79, P = 0.008], and higher cancer‐related mortality (HR 1.71, 95% CI 1.02–2.86, P = 0.03). The combination of the highest‐risk parameter scores of TSR and the BD model showed significant correlations with recurrence rate (HR 3.42, 95% CI 1.71–6.82, P = 0.004) and cancer‐related mortality (HR 11.63, 95% CI 3.83–35.31, P < 0.001). Conclusions: We conclude that TSR is a simple histopathological feature that is useful for prognostication of early‐stage OTSCC, and suggest that TSR analyses in association with BD score could be included in routine clinical pathology reports for HE‐stained slides. [ABSTRACT FROM AUTHOR]

Abstract: Aims: Signal peptide‐CUB‐EGF (epidermal growth factor‐like protein) domain‐containing protein 1 (SCUBE1) is an experimental marker of ischemia that has been previously studied both in rat models and humans. In this study, we aim to investigate the importance of SCUBE1 levels in ovarian torsion using an ovarian torsion model in rats. Methods: A total of 18 Sprague–Dawley rats were equally divided into three groups. Group 1 (n = 6) was the Sham group and was only given a laparotomy procedure. Group 2 (n = 6) underwent bilateral ovarian torsion and ovarian ischemia lasting 8 h. Group 3 (n = 6) was subjected to bilateral ovarian torsion and ischemia lasting 24 h. Blood samples were collected from all three groups after the operations, and SCUBE1 levels were studied. Ovarian samples were collected, and microscopic evaluation was performed. The correlation of SCUBE1 levels and histopathological findings were investigated. Results: The mean SCUBE1 level of group 3 was statistically higher than other groups (P < 0.01). Follicular degeneration and infiltration of inflammatory cells were, respectively, statistically significant in groups 2 and 3 (P = 0.002 and P = 0.045, respectively). Conclusion: SCUBE1 can be useful in diagnosing ovarian torsion during the first 24 h, but more randomized controlled studies are necessary in order to implement it in clinical settings. [ABSTRACT FROM AUTHOR]

Small geometric misalignments of micro computed tomography (CT) system will cause geometric artefacts in the reconstructed image. A new correction method of geometrical artefacts based on marker and non‐linear optimisation model is proposed. In this method, the simple balls marker and the measured objects are scanned simultaneously, and the geometric parameters of the micro‐CT system are precisely estimated by solving the non‐linear optimisation model which is based on the scanning data. The geometric artefacts caused by geometric parameters are corrected and the authors can reconstruct the image correctly. In addition to estimating geometric parameters for the traditional scanning mode, the proposed method can also be used for the limited angle CT scanning and the half detector CT scanning. Simulated experiments and real experiments verify that the correction method effectively decrease the geometric artefacts of micro‐CT images. [ABSTRACT FROM AUTHOR]

Abstract: Background: Elevated levels of C‐reactive protein (CRP), a sensitive marker of inflammation, have been consistently reported in chronic spontaneous urticaria (CSU). Here, we retrospectively analyzed data from 1253 CSU patients from 2 centers to answer the following questions: (i) What is the prevalence of elevated levels of CRP in CSU? (ii) Why do CSU patients show elevated levels of CRP? (iii) Are elevated CRP levels relevant? Methods: Serum levels of CRP were measured by the nephelometric method. We collected information regarding various laboratory tests including ESR, CBC with differential, D‐dimer, fibrinogen, C3, C4, IL‐6, etc. For most patients, we also collected data on age, gender, duration of CSU, presence of angioedema, activity (UAS at the time of blood sampling and for 7 days), quality of life (CU‐Q2oL and/or DLQI), comorbidities and possible causes of CSU, and autologous serum skin test (ASST) response. The efficacy of second‐generation antihistamines was evaluated on the day of blood collecting. Results: One‐third of CSU patients had elevated levels of CRP. Higher levels of CRP were associated with ASST positivity (P = .009) and arterial hypertension (P = .005), but not with other possible causes or comorbidities of CSU. C‐reactive protein correlated with urticaria activity (P < .001), quality of life impairment (P = .026), and inflammatory and coagulation markers (P < .001). C‐reactive protein levels were significantly higher in nonresponders to antihistamines as compared to responders (P < .001). Conclusion: Elevated levels of CRP are common and relevant in CSU patients. The assessment of CRP levels may help to optimize the management of patients with CSU. [ABSTRACT FROM AUTHOR]

Summary: The effect of dietary particle size on gastrointestinal transit in carnivores has not been studied and might offer more insight into their digestive physiology. This study evaluated the effect of two dietary particle sizes (fine = 7.8 mm vs. coarse = 13 mm) of chunked day‐old chicks on transit parameters in dogs. Six beagle dogs were fed both dietary treatments in a crossover design of 7 days with transit testing on the fifth day. Transit parameters were assessed using two markers, that is a wireless motility capsule (IntelliCap®) and titanium oxide (TiO2). Dietary particle size did not affect gastric emptying time (GRT), small bowel transit time (SBTT), colonic transit time (CTT) and total transit time (aTTT) of the capsule (p > .05). There was no effect of dietary particle size on TiO2 mean retention time (MRT) (p > .05). The time of last TiO2 excretion (MaxRT) differed (p = .013) between diets, being later for the coarse diet. Both MRT (R = 0.617, p = .032) and MaxRT (R = 0.814; p = .001) were positively correlated to aTTT. The ratio MRT/aTTT tended towards a difference between diets (p = .059) with the coarse diet exceeding fine diet values. Results show that the difference between capsule measurements and TiO2 is larger for the fine than the coarse diet suggesting that the capsule becomes more accurate when dietary particle size approaches marker size. Dietary particle size might have affected transit parameters but differences are too small to claim major physiological consequences. [ABSTRACT FROM AUTHOR]

Abstract: In this study, a general simple and inexpensive method is introduced for the preparation of a paper‐based selective disk‐type solid phase extraction (SPE) technique, appropriate for fast and high throughput monitoring of target compounds. An ion exchange molecularly imprinted polymer (MIP) was synthesized for the extraction and analysis of acesulfame, an anthropogenic water quality marker. Acesulfame imprinting was used as an example for demonstrating the benefits of a nanosized, swellable MIP extraction sorbents integrated in an on‐site compatible concept for water quality monitoring. Compared with an 8 mL standard SPE cartridge, the paper‐based MIP disk (47 mm ø) format allowed (1) high sample flow rates up to 30 mL•min−1 without losing extraction efficiency (2) extracting sample volumes up to 500 mL in much shorter times than with standard SPE, (3) the reuse of the disks (up to 3 times more than SPE cartridge) due to high robustness and an efficient post‐cleaning, and (4) reducing the sampling time from 100 minutes (using the standard SPE format) to about 2 minutes with the MIP paper disk for 50 mL water sample. Different parameters like cellulose fiber/polymer ratios, sample volume, sample flow‐rate, washing, and elution conditions were evaluated and optimized. Using developed extraction technique with high‐performance liquid chromatography–tandem mass spectrometry (HPLC–MS–MS) analysis, a new protocol was established that provides detection and quantification limits of 0.015 μg•L−1 and 0.05 μg•L−1, respectively. The developed paper disks were used in‐field for the selective extraction of target compounds and transferred to the laboratory for further analysis. [ABSTRACT FROM AUTHOR]

Abstract: There is growing evidence of the presence of cancer stem cells in urothelial carcinoma. Cancer stem cells have the ability to self‐renew and to differentiate into all cell types of the original heterogeneous tumor. A panel of diverse cancer stem cell markers might be suitable for simulation studies of urothelial cancer stem cells and for the development of optimized treatment protocols. The present review focuses on the advances in recognizing the markers of urothelial cancer stem cells and possible therapeutic targets. The commonly reported markers and pathways that were evaluated include CD44, CD133, ALDH1, SOX2 & SOX4, BMI1, EZH1, PD‐L1, MAGE‐A3, COX2/PGE2/STAT3, AR, and autophagy. Studies on the epithelial–mesenchymal transition‐related pathways (Shh, Wnt/β‐catenin, Notch, PI3K/Akt, TGF‐β, miRNA) are also reviewed. Most of these markers were recognized through the expression patterns of cancer stem cell‐rich side populations. Their regulative role in the development and differentiation of urothelial cancer stem cells was confirmed in vitro by functional analyses (e.g. cell migration, colony formation, sphere formation), and in vivo in xenograft experiments. Although a small number of these pathways are targeted by currently available drugs or drugs that are the currently being tested in clinical trials, a clear treatment approach has not been developed for most pathways. A greater understanding of the mechanisms that control the proliferation and differentiation of cancer stem cells is expected to lead to improvements in targeted therapy. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the potential application of DDX4 gene expression in cell-free seminal mRNA as a noninvasive biomarker for the identification of the presence of germ cells in men with nonobstructive azoospermia and to correlate this factor with testicular biopsy. Male reproductive organ-specific genes were chosen: DDX4, which is a germ cell-specific gene and transglutaminase 4, which is a prostate-specific gene that was used as a control gene. Thirty-nine azoospermic males and twenty-eight normospermic fertile males (serving as a control group) participated in the study. Histopathological examination of testicular biopsies categorised azoospermic males into 20.5% with maturation arrest, 17.9% with incomplete Sertoli cell-only syndrome and 61.5% with complete Sertoli cell-only syndrome. Using real-time polymerase chain reaction, positivity for DDX4 gene was detected in 17 of 39 males with NOA which was due to maturation arrest in 35.3% ( n = 6/17) of cases, due to incomplete Sertoli cell only in 23.5% ( n = 4/17) and due to complete Sertoli cell only in 41.2% ( n = 7/17). The study recommends joint utilisation of molecular transcripts as noninvasive biomarkers and histopathological examination of testicular biopsies in management of cases with azoospermia of the nonobstructive type. [ABSTRACT FROM AUTHOR]

SUMMARY It is becoming important for working robots to be able to identify and pick objects in various tasks. As in the recent Amazon Picking Challenge, using a marker for the picking task is a more practicable approach. However, a common maker code for working robots does not exist so far. Conventional maker codes as represented by QR code or ARToolKit marker cannot be reliably detected from various viewpoints. Thus, in this paper, we propose a new encoded marker which is flexible to the marker's position and blur. The proposed marker can be detected by an approach based on the scale space theory independent from such conditions. In addition, the representation of data by M-sequence makes the encoded marker robust to blur. Experimental results showed the effectiveness of the proposed marker compared to the ARToolKit marker. Since the marker is more robust against ground clutter noise, various positions of markers and blur, it is more practicable. [ABSTRACT FROM AUTHOR]

General theories (GT) are reductionist explications of apparently independent facts. Here, in reviewing the literature, I develop a GT to simplify the cluttered landscape of cancer therapy targets by revealing they cluster parsimoniously according to only a few underlying principles. The first principle is that targets can be only exploited by either or both of two fundamentally different approaches: causality-inhibition, and 'acausal' recognition of some marker or signature. Nonetheless, each approach must achieve both of two separate goals, efficacy (reduction in cancer burden) and selectivity (sparing of normal cells); if the mechanisms are known, this provides a definition of rational treatment. The second principle is target fragmentation, whereby the target may perform up to three categoric functions (cytoreduction, modulation, cytoprotection), potentially mediated by physically different target molecules, even on different cell types, or circulating freely. This GT remains incomplete until the minimal requirements for cure, or alternatively, proof that cure is impossible, become predictable. [ABSTRACT FROM AUTHOR]

Gastric cancer is one of the most incident and deadliest malignancies in the world. Gastric cancer is a heterogeneous disease and the end point of a long and multistep process, which results from the stepwise accumulation of numerous (epi)genetic alterations, leading to dysregulation of oncogenic and tumor suppressor pathways. Gastric cancer stem cells have emerged as fundamental players in cancer development and as contributors to gastric cancer heterogeneity. For this special issue, we will report last year's update on the gastric cancer molecular classification, and in particular address the gastric cancer groups who could benefit from immune checkpoint therapy. We will also review the latest advances on gastric cancer stem cells, their properties as gastric cancer markers and therapeutic targets, and associated signaling pathways. The understanding of the molecular basis underlying gastric cancer heterogeneity and of the role played by gastric cancer stem cells in cancer development and heterogeneity is of major significance, not only for identifying novel targets for cancer prevention and treatment, but also for clinical management and patient stratification for targeted therapies. [ABSTRACT FROM AUTHOR]

Background: Application of in-shoe multi-segment foot kinematic analyses currently faces a number of challenges, including: (i) the difficulty to apply regular markers onto the skin, (ii) the necessity for an adequate shoe which fits various foot morphologies and (iii) the need for adequate repeatability throughout a repeated measure condition. The aim of this study therefore was to design novel magnet based 3D printed markers for repeated in-shoe measurements while using accordingly adapted modified shoes for a specific multi-segment foot model. Methods: Multi-segment foot kinematics of ten participants were recorded and kinematics of hindfoot, midfoot and forefoot were calculated. Dynamic trials were conducted to check for intra and inter-session repeatability when combining novel markers and modified shoes in a repeated measures design. Intraclass correlation coefficients were calculated to determine reliability. Results: Both repeatability and reliability were proven to be good to excellent with maximum joint angle deviations of 1.11° for intra-session variability and 1.29° for same-day inter-session variability respectively and ICC values of >0.91. Conclusion: The novel markers can be reliably used in future research settings using in-shoe multi-segment foot kinematic analyses with multiple shod conditions. [ABSTRACT FROM AUTHOR]