scholarly journals Identification of novel candidate factor SNX5 specific for pregnancy failure in Holstein heifers

2021 ◽  
Author(s):  
Kazuya Kusama ◽  
Rulan Bai ◽  
Yuta Matsuno ◽  
Atsushi Ideta ◽  
Toshihiro Sakurai ◽  
...  
Keyword(s):  
Early Pregnancy ◽  
Pregnancy Loss ◽  
Molecular Mechanisms ◽  
Characteristic Curve ◽  
Area Under The Curve ◽  
Metabolome Analysis ◽  
Itraq Analysis ◽  
Embryonic Loss ◽  
Extraembryonic Membranes ◽  
Serum Components

Abstract Pregnancy loss predominantly occurs during periods between blastocyst hatching and conceptus (embryo plus extraembryonic membranes) implantation to the endometrium in cattle. Insufficient biochemical communication between conceptus and endometrium has been suspected as the primary cause for early embryonic losses. If molecules regulating this communication were identified, molecular mechanisms associated with early pregnancy success or loss could be better understood. To identify novel factors as detection markers of non-pregnant or females undergoing embryonic loss, blood sera from embryo-transferred heifers on day 7 (day 0 = day of estrus) were collected on day 17, 20, or 22, which were subjected to metabolome and global proteome iTRAQ analyses. On each sample, the metabolome analysis partly divided serum components into pregnant or not. In the iTRAQ analysis, heatmap analysis with 25 unique proteins separated into pregnant or not on day 20 or 22. Furthermore, receiver operating characteristic curve (ROC) analysis identified five candidate proteins detecting non-pregnant heifers, of which SNX5 in day 22 sera had the highest area under the curve (AUC), 0.983. We also detected SNX5 in day 22 sera from non-pregnant heifers using western blotting. These results suggest that high SNX5 in day 22 sera could predict early pregnancy loss in heifers.

scholarly journals Identification of an 8-miRNA signature as a potential prognostic biomarker for glioma

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9943 ◽  
Author(s):  
Baowei Ji ◽  
Lihua Chen ◽  
Qiang Cai ◽  
Qiao Guo ◽  
Zhibiao Chen ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Molecular Mechanisms ◽  
Cox Regression ◽  
Characteristic Curve ◽  
Area Under The Curve ◽  
Gene Expression Omnibus ◽  
Related Factor ◽  
Lasso Regression ◽  
Mirna Signature ◽  
Cox Regression Analysis

Background Glioma is the most common form of primary malignant intracranial tumor. Methods In the current study, miRNA matrix were obtained from the Chinese Glioma Genome Atlas (CGGA), and then univariate Cox regression analysis and Lasso regression analysis were utilized to select candidate miRNAs and multivariate Cox regression analysis was applied to establish a miRNA signature for predicting overall survival (OS) of glioma. The signature was assessed with the area under the curve (AUC) of the receiver operating characteristic curve (ROC) and validated by data from Gene Expression Omnibus (GEO). Results Eight miRNAs (miR-1246, miR-148a, miR-150, miR-196a, miR-338-3p, miR-342-5p, miR-548h and miR-645) were included in the miRNA signature. The AUC of ROC analysis for 1- and 3-year OS in the CGGA dataset was 0.747 and 0.905, respectively. In the GEO dataset, The AUC for 1- and 3-year was 0.736 and 0.809, respectively. The AUC in both the CGGA and GEO datasets was similar to that based on WHO 2007 classification (0.736 and 0.799) and WHO 2016 classification (0.663 and 0.807). Additionally, Kaplan–Meier plot revealed that high-risk score patients had a poorer clinical outcome. Multivariate Cox regression analysis suggested that the miRNA signature was an independent prognosis-related factor [HR: 6.579, 95% CI [1.227−35.268], p = 0.028]. Conclusion On the whole, in the present study, based on eight miRNAs, a novel prognostic signature was developed for predicting the 1- and 3- year survival rate in glioma. The results may be conducive to predict the precise prognosis of glioma and to elucidate the underlying molecular mechanisms. However, further experimental researches of miRNAs are needed to validate the findings of this study.

scholarly journals Active Enhancer Assessment by H3K27ac ChIP-seq Reveals Claudin-1 as a Biomarker for Radiation Resistance in Colorectal Cancer

Dose-Response ◽  
2021 ◽  
Vol 19 (4) ◽  
pp. 155932582110589
Author(s):  
Zu-Xuan Chen ◽  
He-Qing Huang ◽  
Jia-Ying Wen ◽  
Li-Sha Qin ◽  
Yao-Dong Song ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Radiation Resistance ◽  
Molecular Mechanisms ◽  
Pearson Correlation ◽  
Characteristic Curve ◽  
Area Under The Curve ◽  
Mean Deviation ◽  
Summary Receiver Operating Characteristic ◽  
Radiation Resistant ◽  
Boost Radiation

Background Colorectal cancer (CRC) represents the third most common malignant tumor in the worldwide. Radiotherapy is the common therapeutic treatment for CRC, but radiation resistance is often encountered. ChIP-seq of Histone H3K27 acetylation (H3K27ac) has revealed enhancers that play an important role in CRC. This study examined the relationship between an active CRC enhancer and claudin-1 (CLDN1), and its effect on CRC radiation resistance. Methods The target CRC genes of active enhancers were obtained from public H3K27ac ChIP-seq, and the genes highly expressed in radio-resistant CRC were screened and intersected with enhancer-driven genes. The clinical roles of CLDN1 in radiation resistance were examined using the t-test, standard mean deviation (SMD), summary receiver operating characteristic curve and Kaplan-Meier curves. The co-expressed genes of CLDN1 were calculated using Pearson Correlation analysis, and Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes and Gene Set Variation Analysis (GSVA) analyses were used to examine the molecular mechanisms of CLDN1. Results Total 13 703 CRC genes were regulated by enhancers using 58 H3K27ac ChIP-seq. Claudin-1 (CLDN1) was enhancer-driven and notably up-regulated in CRC tissues compared to non-CRC controls, with a SMD of 3.45 (95 CI % = .56-4.35). CLDN1 expression was increased in radiation-resistant CRC with a SMD of .42 (95% CI = .16-.68) and an area under the curve of .74 (95% CI = .70-.77). The cell cycle and immune macrophage levels were the most significant pathways associated with CLDN1. Conclusion CLDN1 as an enhancer-regulated gene that can boost radiation resistance in patients with CRC.

scholarly journals Preconception antiphospholipid antibodies and risk of subsequent early pregnancy loss

Lupus ◽  
2018 ◽  
Vol 27 (9) ◽  
pp. 1437-1445 ◽  
Author(s):  
K J Gibbins ◽  
S L Mumford ◽  
L A Sjaarda ◽  
D W Branch ◽  
N J Perkins ◽  
...  
Keyword(s):  
Early Pregnancy ◽  
Antiphospholipid Antibodies ◽  
Pregnancy Loss ◽  
Cardiac Activity ◽  
Subsequent Pregnancy ◽  
Early Pregnancy Loss ◽  
Case Control Studies ◽  
Clinical Trial Registration ◽  
Live Births ◽  
Embryonic Loss

Objectives To prospectively estimate the association of preconception antiphospholipid antibodies (aPL) with subsequent pregnancy loss using a cohort design. aPL have been associated with recurrent early pregnancy loss (EPL) prior to 10 weeks in previous case-control studies. Prospective ascertainment of pregnancy loss is challenging, as most women do not seek care prior to EPL. Methods Secondary analysis of the Effects of Aspirin in Gestation and Reproduction trial of preconception low-dose aspirin. Preconception anticardiolipin (aCL) and anti-β2-glycoprotein-I (a-β2-I) were assessed in 1208 women with one or two prior pregnancy losses and no more than two prior live births. Comparison cohorts were defined by positive aPL (+aPL) or negative aPL (–aPL) status. All women were followed for six menstrual cycles while trying to conceive; if successful, they underwent an ultrasound at 6–7 weeks’ gestation. EPL was defined as loss prior to 10 weeks’ gestation; embryonic loss was loss after visualization of an embryo but prior to 10 weeks; clinical loss was any loss after visualization of an embryo (with or without fetal cardiac activity detected). Results In total, 14/1208 (1%) tested positive for +aPL. 786/1208 (65%) women had positive human chorionic gonadotropin during the study period, of which 9/786 (1%) had +aPL. Of the 786 pregnant women, 589 (75%) had live births and 24% had pregnancy losses. Women with +aPL experienced EPL at similar rates as women with –aPL, 44% vs 21% (aRR 2.4, 95% confidence interval (CI) 0.5–10.9). Embryonic loss was more common in women with +aCL IgM (aRR 4.8, 95% CI 1.0–23.0) and in women with two positive aPL. Clinical pregnancy loss was more common in women with positive a-β2-I IgM (50% vs 16.5%, aRR 3.7, 95% CI 1.3–10.8). Conclusion Positive levels of aPL are rare in women with one or two prior pregnancy losses and are not clearly associated with an increased rate of subsequent loss. Clinical trial registration The original source study was registered at ClinicalTrials.gov (#NCT00467363).

Production of interferon by red deer (Cervus elaphus) conceptuses and the effects of roIFN-tau on the timing of luteolysis and the success of asynchronous embryo transfer

Reproduction ◽  
2000 ◽  
pp. 387-395 ◽  
Author(s):  
KJ Demmers ◽  
HN Jabbour ◽  
DW Deakin ◽  
AP Flint
Keyword(s):  
Embryo Transfer ◽  
Early Pregnancy ◽  
Cervus Elaphus ◽  
Pregnancy Loss ◽  
Red Deer ◽  
Interferon Tau ◽  
Recombinant Interferon ◽  
Uterine Flushing ◽  
Calving Rate

The role of interferon in early pregnancy in red deer was investigated by (a) measuring production of interferon by the conceptus, (b) testing the anti-luteolytic effect of recombinant interferon-tau in non-pregnant hinds, and (c) treatment of hinds with interferon after asynchronous embryo transfer. Blastocysts were collected from 34 hinds by uterine flushing 14 (n = 2), 16 (n = 2), 18 (n = 8), 20 (n = 13) or 22 (n = 9) days after synchronization of oestrus with progesterone withdrawal. Interferon anti-viral activity was detectable in uterine flushings from day 16 to day 22, and increased with duration of gestation (P < 0.01) and developmental stage (P < 0.01). When interferon-tau was administered daily between day 14 and day 20 to non-pregnant hinds to mimic natural blastocyst production, luteolysis was delayed by a dose of 0.2 mg day(-1) (27.3 +/- 1.3 days after synchronization, n = 4 versus 21 +/- 0 days in control hinds, n = 3; P < 0.05). Interferon-tau was administered to hinds after asynchronous embryo transfer to determine whether it protects the conceptus against early pregnancy loss. Embryos (n = 24) collected on day 6 from naturally mated, superovulated donors (n = 15) were transferred into synchronized recipients on day 10 or day 11. Interferon-tau treatment (0.2 mg daily from day 14 to 20) increased calving rate from 0 to 64% in all recipients (0/11 versus 7/11, P < 0.005), and from 0 to 67% in day 10 recipients (0/8 versus 6/9, P < 0.01). The increased success rate of asynchronous embryo transfer after interferon-tau treatment in cervids may be of benefit where mismatched embryo-maternal signalling leads to failure in the establishment of pregnancy.

Discriminating Malignancy in Thyroid Nodules: The Nomogram Versus the Kwak and ACR TI-RADS

2020 ◽  
Vol 163 (6) ◽  
pp. 1156-1165
Author(s):  
Juan Xiao ◽  
Qiang Xiao ◽  
Wei Cong ◽  
Ting Li ◽  
Shouluan Ding ◽  
...  
Keyword(s):  
Thyroid Nodules ◽  
Characteristic Curve ◽  
Area Under The Curve ◽  
Diagnostic Study ◽  
Diagnostic Efficiency ◽  
Training Set ◽  
Multivariable Logistic Regression Model ◽  
Predictive Values ◽  
Validation Set ◽  
Sensitivity Specificity

Objective To develop an easy-to-use nomogram for discrimination of malignant thyroid nodules and to compare diagnostic efficiency with the Kwak and American College of Radiology (ACR) Thyroid Imaging, Reporting and Data System (TI-RADS). Study Design Retrospective diagnostic study. Setting The Second Hospital of Shandong University. Subjects and Methods From March 2017 to April 2019, 792 patients with 1940 thyroid nodules were included into the training set; from May 2019 to December 2019, 174 patients with 389 nodules were included into the validation set. Multivariable logistic regression model was used to develop a nomogram for discriminating malignant nodules. To compare the diagnostic performance of the nomogram with the Kwak and ACR TI-RADS, the area under the receiver operating characteristic curve, sensitivity, specificity, and positive and negative predictive values were calculated. Results The nomogram consisted of 7 factors: composition, orientation, echogenicity, border, margin, extrathyroidal extension, and calcification. In the training set, for all nodules, the area under the curve (AUC) for the nomogram was 0.844, which was higher than the Kwak TI-RADS (0.826, P = .008) and the ACR TI-RADS (0.810, P < .001). For the 822 nodules >1 cm, the AUC of the nomogram was 0.891, which was higher than the Kwak TI-RADS (0.852, P < .001) and the ACR TI-RADS (0.853, P < .001). In the validation set, the AUC of the nomogram was also higher than the Kwak and ACR TI-RADS ( P < .05), each in the whole series and separately for nodules >1 or ≤1 cm. Conclusions When compared with the Kwak and ACR TI-RADS, the nomogram had a better performance in discriminating malignant thyroid nodules.

scholarly journals Development of a practical prediction score for acute renal injury after surgery for Stanford type A aortic dissection

2020 ◽  
Vol 30 (5) ◽  
pp. 746-753
Author(s):  
Ning Dong ◽  
Hulin Piao ◽  
Yu Du ◽  
Bo Li ◽  
Jian Xu ◽  
...  
Keyword(s):  
Aortic Dissection ◽  
Risk Score ◽  
Scoring System ◽  
Characteristic Curve ◽  
Area Under The Curve ◽  
Kidney Injury ◽  
Type A ◽  
Postoperative Management ◽  
Prediction Score ◽  
Improve Patient

Abstract OBJECTIVES Acute kidney injury (AKI) is a common complication of cardiovascular surgery that is associated with increased mortality, especially after surgeries involving the aorta. Early detection and prevention of AKI in patients with aortic dissection may help improve outcomes. The objective of this study was to develop a practical prediction score for AKI after surgery for Stanford type A acute aortic dissection (TAAAD). METHODS This was a retrospective cohort study that included 2 independent hospitals. A larger cohort of 326 patients from The Second Hospital of Jilin University was used to identify the risk factors for AKI and to develop a risk score. The derived risk score was externally validated in a separate cohort of 102 patients from the other hospital. RESULTS The scoring system included the following variables: (i) age &gt;45 years; (ii) body mass index &gt;25 kg/m2; (iii) white blood cell count &gt;13.5 × 109/l; and (iv) lowest perioperative haemoglobin &lt;100 g/l, cardiopulmonary bypass duration &gt;150 min and renal malperfusion. On receiver operating characteristic curve analysis, the score predicted AKI with fair accuracy in both the derivation [area under the curve 0.778, 95% confidence interval (CI) 0.726–0.83] and the validation (area under the curve 0.747, 95% CI 0.657–0.838) cohorts. CONCLUSIONS We developed a convenient scoring system to identify patients at high risk of developing AKI after surgery for TAAAD. This scoring system may help identify patients who require more intensive postoperative management and facilitate appropriate interventions to prevent AKI and improve patient outcomes.

scholarly journals Utility of recombinant human TSH stimulation test in the follow-up of patients with differentiated thyroid cancer depending on basal thyroglobulin results

2020 ◽  
Vol 1 (1) ◽  
Author(s):  
Amaia Sandúa ◽  
Monica Macias ◽  
Carolina Perdomo ◽  
Juan Carlos Galofre ◽  
Roser Ferrer ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Differentiated Thyroid Cancer ◽  
Characteristic Curve ◽  
Area Under The Curve ◽  
High Sensitivity ◽  
Thyroid Stimulating Hormone ◽  
Stimulation Test ◽  
Human Thyroid ◽  
Antithyroglobulin Antibodies ◽  
Structural Disease

AbstractBackgroundThyroglobulin (Tg) is fundamental for differentiated thyroid cancer (DTC) monitoring. Tg detection can be enhanced using recombinant human thyroid-stimulating hormone (TSH) (rhTSH). This study is aimed to evaluate the use of the rhTSH stimulation test when using a high-sensitivity Tg assay.MethodsWe retrospectively studied 181 rhTSH tests from 114 patients with DTC and negative for antithyroglobulin antibodies (anti-TgAb). Image studies were performed in all cases. Serum Tg and anti-TgAb were measured using specific immunoassays.ResultsrhTSH stimulation in patients with basal serum Tg (b-Tg) concentrations lower than 0.2 ng/mL always resulted in rhTSH-stimulated serum Tg (s-Tg) concentrations lower than 1.0 ng/mL and negative structural disease. In patients with b-Tg concentration between 0.2 and 1.0 ng/mL, s-Tg detected one patient (1/30) who showed biochemical incomplete response. Patients with negative images had lower s-Tg than those with nonspecific or abnormal findings (p<0.05). Receiver operating characteristic curve analysis of the s-Tg to detect altered images showed an area under the curve of 0.763 (p<0.05). With an s-Tg cutoff of 0.85 ng/mL, the sensitivity was 100%, decreasing to 96.15% with an s-Tg cutoff of 2 ng/mL.ConclusionsPatients with DTC with b-Tg concentrations equal or higher than 0.2 ng/mL can benefit from the rhTSH stimulation test.

scholarly journals Optimal Utility of H-Reflex RDD as a Biomarker of Spinal Disinhibition in Painful and Painless Diabetic Neuropathy

Diagnostics ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1247
Author(s):  
Anne Worthington ◽  
Alise Kalteniece ◽  
Maryam Ferdousi ◽  
Luca Donofrio ◽  
Shaishav Dhage ◽  
...  
Keyword(s):  
Diabetic Neuropathy ◽  
Characteristic Curve ◽  
Area Under The Curve ◽  
Initial Response ◽  
Healthy Controls ◽  
Painful Diabetic Neuropathy ◽  
Stimulus Response ◽  
Rate Dependent ◽  
Potential Biomarker ◽  
Spinal Inhibition

Impaired rate-dependent depression of the Hoffman reflex (HRDD) is a potential biomarker of impaired spinal inhibition in patients with painful diabetic neuropathy. However, the optimum stimulus-response parameters that identify patients with spinal disinhibition are currently unknown. We systematically compared HRDD, performed using trains of 10 stimuli at five stimulation frequencies (0.3, 0.5, 1, 2 and 3 Hz), in 42 subjects with painful and 62 subjects with painless diabetic neuropathy with comparable neuropathy severity, and 34 healthy controls. HRDD was calculated using individual and mean responses compared to the initial response. At stimulation frequencies of 1, 2 and 3 Hz, HRDD was significantly impaired in patients with painful diabetic neuropathy compared to patients with painless diabetic neuropathy for all parameters and for most parameters when compared to healthy controls. HRDD was significantly enhanced in patients with painless diabetic neuropathy compared to controls for responses towards the end of the 1 Hz stimulation train. Receiver operating characteristic curve analysis in patients with and without pain showed that the area under the curve was greatest for response averages of stimuli 2–4 and 2–5 at 1 Hz, AUC = 0.84 (95%CI 0.76–0.92). Trains of 5 stimuli delivered at 1 Hz can segregate patients with painful diabetic neuropathy and spinal disinhibition, whereas longer stimulus trains are required to segregate patients with painless diabetic neuropathy and enhanced spinal inhibition.

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