A predictive model for therapy failure in chronic myeloid leukemia patients receiving tyrosine kinase inhibitor therapy.

Although tyrosine kinase inhibitor (TKI) therapy has markedly improved the survival of people with chronic-phase chronic myeloid leukemia (CML), 20-30% of people still experienced therapy failure. Data from 1,955 consecutive subjects with chronic-phase CML diagnosed by the European LeukemiaNet (ELN) recommendations from 1 center receiving initial TKI imatinib or a second-generation (2G-) TKI therapy were interrogated to develop a clinical prediction model for TKI therapy failure. This model was subsequently validated in 3,454 subjects from 76 other centers. Using the predictive clinical co-variates associated with TKI therapy failure, we developed a model that stratified subjects into low-, intermediate- and high-risk subgroups with significantly different cumulative incidences of therapy failure (p < 0.001). There was good discrimination and calibration in the external validation dataset, and the performance was consistent with that of the training dataset. Our model had the better prediction discrimination than the Sokal and ELTS scores did, with the greater time-dependent area under the receiver-operator characteristic curve (AUROC) values and a better ability to re-defined the risk of therapy failure. Our model could help physicians estimate the likelihood of initial imatinib or 2G-TKI therapy failure in people with chronic-phase CML.

Pretreatment prediction for IVF outcomes: generalized applicable model or centre-specific model?

STUDY QUESTION: What was the performance of different pretreatment prediction models for IVF, which were developed based on UK/US population (McLernon 2016 model, Luke model, Dhillon model, and McLernon 2022 model), in wider populations? SUMMARY ANSWER: For a patient in China, the published pretreatment prediction models based on the UK/US population provide similar discriminatory power with reasonable AUCs and underestimated predictions. WHAT IS KNOWN ALREADY: Several pretreatment prediction models for IVF allow patients and clinicians to estimate the cumulative probability of live birth in a cycle before the treatment, but they are mostly based on the population of Europe or the USA, and their performance and applicability in the countries and regions beyond these regions are largely unknown. STUDY DESIGN, SIZE, DURATION: A total of 26 382 Chinese patients underwent oocyte pick-up cycles between January 2013 and December 2020. PARTICIPANTS/MATERIALS, SETTING, METHODS: UK/US model performance was externally validated according to the coefficients and intercepts they provided. Centre-specific models were established with XGboost, Lasso, and generalized linear model algorithms. Discriminatory power and calibration of the models were compared as the forms of the AUC of the Receiver Operator Characteristic and calibration curves. MAIN RESULTS AND THE ROLE OF CHANCE: The AUCs for McLernon 2016 model, Luke model, Dhillon model, and McLernon 2022 model were 0.69 (95% CI 0.68-0.69), 0.67 (95% CI 0.67-0.68), 0.69 (95% CI 0.68-0.69), and 0.67 (95% CI 0.67-0.68), respectively. The centre-specific yielded an AUC of 0.71 (95% CI 0.71-0.72) with key predictors including age, duration of infertility, and endocrine parameters. All external models suggested underestimation. Among the external models, the rescaled McLernon 2022 model demonstrated the best calibration (Slope 1.12, intercept 0.06). LIMITATIONS, REASONS FOR CAUTION: The study is limited by its single-centre design and may not be representative elsewhere. Only per-complete cycle validation was carried out to provide a similar framework to compare different models in the sample population. Newer predictors, such as AMH, were not used. WIDER IMPLICATIONS OF THE FINDINGS: Existing pretreatment prediction models for IVF may be used to provide useful discriminatory power in populations different from those on which they were developed. However, models based on newer more relevant datasets may provide better calibrations. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the National Natural Science Foundation of China [grant number 22176159], the Xiamen Medical Advantage Subspecialty Construction Project [grant number 2018296], and the Special Fund for Clinical and Scientific Research of Chinese Medical Association [grant number 18010360765]. TRIAL REGISTRATION NUMBER: N/A.

Ambient air pollution decreased normal fertilization rate via the mediation of seminal prosaposin.

OBJECTIVE: This study focuses on the association between seminal concentration of prosaposin and ambient air pollutants and whether the association affects the normal fertilization rate in vitro fertilization (IVF) treatment. METHODS: The cohort of 323 couple participants aged 22-46 was recruited from Jan. 2013 to Jun. 2018. At enrollment, resident address information was obtained and semen parameters of male counterparts were evaluated according to WHO criteria. We used inverse distance weighting interpolation to estimate the levels of ambient pollutants (SO2, O3, CO, NO2, PM2.5, and PM10) in the surrounding area. The exposure of each participant was estimated based on the data gathered from air quality monitoring stations and their home address over various periods (0-9, 10-14, and 0-90 days) before semen sampling. The generalized linear regression model (GLM) and the Bayesian kernel machine regression (BKMR) were used to analyze the associations between pollutants, semen parameters, prosaposin, and normal fertilization. Additionally, the mediating effect of prosaposin and semen parameters on the link between pollutants and normal fertilization was investigated. RESULTS: GLM and BKMR showed exposure to ambient air pollutants was all associated with the concentration of seminal prosaposin, among them, O3 and CO were also associated with normal fertilization (-0.10, 95 %CI: -0.13, -0.06; -26.43, 95 %CI: -33.79, -19.07). Among the semen parameters, only the concentration of prosaposin and total motile sperm count (TMC) was associated with normal fertilization (0.059, 95 %CI: 0.047, 0.071; 0.016, 95 %CI: 0.012, 0.020). Mediation analysis showed that prosaposin played a stronger mediating role than TMC in the relationship between short-term exposure to O3 and fertilization (66.83 %, P<0.001 versus 3.05 %, P>0.05). CONCLUSION: Seminal plasma prosaposin showed a stronger meditating effect reflect the correlation between ambient air pollutants and normal fertilization rate than conventional semen parameters, which may be used as one of the indicators between pollution and fertilization in IVF.

Indications affect neonatal outcomes following early rescue ICSI: a retrospective study.

PURPOSE: To investigate the impact of heterogeneity in patient indications or insemination protocols on neonatal outcomes of singletons following early rescue ICSI (rICSI) treatments. METHODS: A retrospective study was conducted. Propensity score matching and multivariable logistic regression were used to adjust for confounders and biases. RESULTS: A total of 9095 IVF patients, 2063 ICSI patients, and 642 early rICSI patients were included in the study. No differences were detected in neonatal outcomes except small for gestational age (SGA) which increased in early rICSI patients compared with both unmatched and matched IVF groups with the risk ratio (RR) of 1.31 (95% CI: 1.05, 1.64) and 1.49 (95% CI: 1.05, 2.12). Further analysis showed that SGA increased significantly in partial fertilization failure (PFF) cycles with RRs of 1.56 (95% CI: 1.08, 2.27) and 1.78 (95% CI: 1.22, 2.59) compared with both unmatched and matched IVF patients but not in TFF patients. A positive association between fertilization rate via IVF and birth weight z-score was revealed in the PFF patients. CONCLUSION: Early rICSI in patients with total fertilization failure (TFF) appeared to be safe in terms of neonatal outcomes. However, when expanding the indications of rICSI to PFF patients, the SGA in the offspring increased, suggesting a potential effect on long-term health. Since other treatment options, such as using only the IVF-origin embryos still exist for these patients, further studies were needed to confirm the optimal decision for these patients.

Does cleavage stage morphology increase the discriminatory power of prediction in blastocyst transfer outcome?

PURPOSE: To evaluate the contribution of the cleavage stage morphological parameters to the prediction of blastocyst transfer outcomes. METHODS: A retrospective study was conducted on 8383 single-blastocyst transfer cycles including 2246 fresh and 6137 vitrified-warmed cycles. XGboost, LASSO, and GLM algorithms were employed to establish models for assessing the predictive value of the cleavage stage morphological parameters in transfer outcomes. Four models were developed using each algorithm: all-in model with or without day 3 morphology and embryo quality-only model with or without day 3 morphology. RESULTS: The live birth rate was 48.04% in the overall cohort. The AUCs of the models with the algorithm of XGboost were 0.83, 0.82, 0.63, and 0.60; with LASSO were 0.66, 0.66, 0.61, and 0.60; and with GLM were 0.66, 0.66, 0.61, and 0.60 respectively. In models 1 and 2, female age, basal FSH, peak E2, endometrial thickness, and female BMI were the top five critical features for predicting live birth; In models 3 and 4, the most crucial factor was blastocyst formation on D5 rather than D6. In model 3, incorporating cleavage stage morphology, including early cleavage, D3 cell number, and fragmentation, was significantly associated with successful live birth. Additionally, the live birth rates for blastocysts derived from on-time, slow, and fast D3 embryos were 49.7%, 39.5%, and 52%, respectively. CONCLUSIONS: The value of cleavage stage morphological parameters in predicting the live birth outcome of single blastocyst transfer is limited.

Spatially Offset Raman Spectroscopy Combined with Attention-Based LSTM for Freshness Evaluation of Shrimp.

Optical detection of the freshness of intact in-shell shrimps is a well-known difficult task due to shell occlusion and its signal interference. The spatially offset Raman spectroscopy (SORS) is a workable technical solution for identifying and extracting subsurface shrimp meat information by collecting Raman scattering images at different distances from the offset laser incidence point. However, the SORS technology still suffers from physical information loss, difficulties in determining the optimum offset distance, and human operational errors. Thus, this paper presents a shrimp freshness detection method using spatially offset Raman spectroscopy combined with a targeted attention-based long short-term memory network (attention-based LSTM). The proposed attention-based LSTM model uses the LSTM module to extract physical and chemical composition information of tissue, weight the output of each module by an attention mechanism, and come together as a fully connected (FC) module for feature fusion and storage dates prediction. Modeling predictions by collecting Raman scattering images of 100 shrimps within 7 days. The R2, RMSE, and RPD of the attention-based LSTM model achieved 0.93, 0.48, and 4.06, respectively, which is superior to the conventional machine learning algorithm with manual selection of the optimal spatially offset distance. This method of automatically extracting information from SORS data by Attention-based LSTM eliminates human error and enables fast and non-destructive quality inspection of in-shell shrimp.

Does conventional morphological evaluation still play a role in predicting blastocyst formation?

BACKGROUND: Advanced models including time-lapse imaging and artificial intelligence technologies have been used to predict blastocyst formation. However, the conventional morphological evaluation of embryos is still widely used. The purpose of the present study was to evaluate the predictive power of conventional morphological evaluation regarding blastocyst formation. METHODS: Retrospective evaluation of data from 15,613 patients receiving blastocyst culture from January 2013 through December 2020 in our institution were reviewed. Generalized estimating equations (GEE) were used to establish the morphology-based model. To estimate whether including more features regarding patient characteristics and cycle parameters improve the predicting power, we also establish models including 27 more features with either LASSO regression or XGbosst. The predicted number of blastocyst were associated with the observed number of the blastocyst and were used to predict the blastocyst transfer cancellation either in fresh or frozen cycles. RESULTS: Based on early cleavage and routine observed morphological parameters (cell number, fragmentation, and symmetry), the GEE model predicted blastocyst formation with an AUC of 0.779(95%CI: 0.77-0.787) and an accuracy of 74.7%(95%CI: 73.9%-75.5%) in the validation set. LASSO regression model and XGboost model based on the combination of cycle characteristics and embryo morphology yielded similar predicting power with AUCs of 0.78(95%CI: 0.771-0.789) and 0.754(95%CI: 0.745-0.763), respectively. For per-cycle blastocyst yield, the predicted number of blastocysts using morphological parameters alone strongly correlated with observed blastocyst number (r = 0.897, P < 0.0001) and predicted blastocyst transfer cancel with an AUC of 0.926((95%CI: 0.911-0.94). CONCLUSION: The data suggested that routine morphology observation remained a feasible tool to support an informed decision regarding the day of transfer. However, models based on the combination of cycle characteristics and embryo morphology do not increase the predicting power significantly.

The effect of epididymal sperm cryopreservation on neonatal birthweight following PESA-ICSI.

PURPOSE: To compare the neonatal birthweight of singletons derived from ICSI cycles with fresh or frozen-thawed epididymal sperm in patients with obstructive azoospermia. METHODS: A total of 436 singletons derived from ICSI cycles with fresh (n = 220) or frozen-thawed (n = 216) epididymal sperm in obstructive azoospermia evaluated from 2012 to 2018 in the retrospective study. Multivariate generalized linear model was used to analyze the association between epididymal sperm cryopreservation and neonatal birthweight. RESULTS: The crude birthweight and z-score in neonates derived from frozen-thawed epididymal sperm were significantly lower than those from fresh epididymal sperm (3186.57 g vs 3303.61 g and - 0.18 vs 0.08, respectively), with a mean difference of 117.04 (95% CI 32.36-201.72) g and 0.25 (95% CI 0.06-0.45). Adjusted for confounders including parental age and BMI, maternal ovarian reserve, paternal FSH and T levels, peak E2 during OPU cycles, frozen-thawed embryo transfer, embryo development stage, gestational age, maternal parity and child gender, the multivariate model suggested that singletons conceived from ICSI with fresh epididymal sperm was on average 91.21 g heavier than those conceived from ICSI with frozen-thawed epdidiymal sperm (95% CI 12.72 to 166.7, P = 0.016). CONCLUSION: Cryopreservation of epididymal sperm may negatively affect birthweight.

Line-scan Raman scattering image and multivariate analysis for rapid and noninvasive detection of restructured beef.

The mean spectral (MS) features were extracted from Raman scattering images (RSI) of beef samples over the region of interest covering the spectral range of 789-1710cm-1 and the spatial offset range of 0-5 mm (for two sides of the incident laser). The RSI monitored the main change in the protein, amide bands, lipids, and amino acid residues. The classification model performance based on MS features compared the conventional Raman spectral features and confirmed the usefulness of RSI. Finally, the results showed that RSI technology is a reliable tool for rapid and noninvasive detection of restructured beef.

Detection of adulterated sugar with plastic packaging based on spatially offset Raman imaging.

BACKGROUND: The application of optical sensing technology in food adulteration detection has been extensively studied. However, due to the impact of packaging materials on the penetration depth of photons in foods and the interference from the optical properties of the packaging materials themselves, the use of optical sensing technology to detect packaged foods adulteration is still a well-known problem. RESULTS: The line-scan Raman imaging system was used to collect Raman hyperspectral images of adulterated sugars, made by mixing soft sugar and cheap glucose in seven different ratios. With the 0 and 3 mm (optimal offset distance) between line-laser source and scanning line, the Raman hyperspectral images of adulterated sugars covered by packaging plastic were acquired respectively. Using adulterated samples un-covered by packaging plastic as training samples, the Random Forest prediction model was developed, and excellent prediction performance was achieved for adulterated samples un-covered by packaging plastics. Compared with Raman data acquired with 0 mm offset distance, the performance of the prediction model was significantly improved, with 0.957 for coefficient of determination (R2 ), 0.413 for root mean square error of prediction (RMSEP), and 4.846 for residual predictive deviation (RPD), for adulterated samples with plastic packaging acquired with the 3 mm offset distance. CONCLUSIONS: The novel non-destructive method based on spatially offset Raman imaging technology, which can reduce the interference of packaging materials and enhance the signal of internal interesting materials, was proposed for detection of adulterated sugar with plastic packaging. The experiment results show that spatially offset imaging technology provides a candidate method for detecting adulteration of packaged foods. © 2021 Society of Chemical Industry.

Does the transfer of a poor quality embryo with a good quality embryo benefit poor prognosis patients?

BACKGROUND: While single embryo transfer (SET) is widely advocated, double embryo transfer (DET) remains preferable in clinical practice to improve IVF success rate, especially in poor prognosis patients with only poor quality embryos (PQEs) available in addition to one or no good quality embryos (GQEs). Furthermore, previous studies suggest PQE might adversely affect the implantation of a GQE when transferred together. This study aims to evaluate the effect of transferring an additional PQE with a GQE on the outcomes in poor prognosis patients. METHODS: A total of 5037 frozen-thawed blastocyst transfer (FBT) cycles between January 2012 and May 2019 were included. Propensity score matching was applied to control for potential confounders, and we used generalized estimating equations (GEE) models to identify the association between the effect of an additional PQE and the outcomes. RESULTS: Overall, transferring a PQE with GQE (Group GP) achieved significantly higher pregnancy rate (PR), live birth rate (LBR) and multiple pregnancy rate (MPR) than GQE only (group G). The addition of a PQE increased LBR in patients aged 35 and over and in patients who received over 3 cycles of embryo transfer (ET) (48.1% vs 27.2%, OR:2.56, 95% CI: 1.3-5.03 and 46.6% vs 35.4%, OR:1.6, 95% CI: 1.09-2.35), but not in women under 35 and in women who received less than 3 cycles of ET (48.7% vs 43.9%, OR:1.22, 95% CI: 0.93-1.59 and 48.3% vs 41.4%, OR:1.33, 95% CI: 0.96-1.85). Group GP resulted in significantly higher MPR than group G irrespective of age and the number of previous IVF cycles. CONCLUSIONS: An additional PQE does not negatively affect the implantation potential of the co-transferred GQE. Nevertheless, the addition of a PQE contributes to both live birth and multiple birth in poor prognosis patients. Physicians should still balance the benefits and risks of DET.

High manganese exposure decreased the risk of high triglycerides in workers: a cross-sectional study.

BACKGROUND: Manganese (Mn) participates in lipid metabolism. However, the associations between Mn exposure and dyslipidaemia is unclear. METHODS: This was a cross-sectional study. Data were collected from the 2017 the Mn-exposed workers healthy cohort (MEWHC). Finally, 803 occupationally Mn-exposed workers included in the study. The workers were divided into two groups. The grouping of this study was based on Mn-Time Weighted Averages (Mn-TWA). The high-exposure group included participants with Mn-TWA greater than 0.15 mg/m3. The low-exposure group included participants with Mn-TWA less than or equal to 0.15 mg/m3. Mn-TWA levels and dyslipidaemia were assessed. RESULTS: After adjustment for seniority, sex, cigarette consumption, alcohol consumption, high-fat diet frequency, medicine intake in the past two weeks, egg intake frequency, drinking tea, WHR, and hypertension, Mn-TWA levels was negatively correlated with high triglycerides (TG) risk in workers overall (OR = 0.51; 95% CI: 0.36, 0.73; p <  0.01). The results of males and females were consistent (OR = 0.53; 95% CI: 0.34, 0.81; p <  0.01) and (OR = 0.47; 95% CI: 0.24, 0.94; p <  0.01), respectively. By performing interactions analyses of workers overall, we observed no significant interactions among confounders. Mn-TWA levels and pack-years on high TG risk (relative excess risk for the interactions (RERI = 2.29, 95% CI: - 2.07, 6.66), (RERI) = 2.98, 95% CI: - 2.30, 8.26). Similarly, smoking status, drinking status, high-fat diet frequency, and Waist-to-Hip Ratio (WHR) showed non-significant interactions with Mn-TWA levels on high TG risk. CONCLUSIONS: This research indicates that high Mn exposure was negatively related to high TG risk in workers.

Analgesic Effect of Dizocine Combined with Ropivacaine on Recurrent Neuropathic Pain in Peripheral Nerve Compression Rats.

To explore the analgesic effect of dizocine combined with ropivacaine on recurrent neuropathic pain in rat model of peripheral nerve compression. Rats were randomly divided into 5 groups: sham control group (S), peripheral nerve compression model group (M), dizocine group (D), ropivacaine group (R), and combined drug group (DR). Rat peripheral nerve compression model was constructed to observe the symptoms of the rats before and after surgery. Mechanical withdrawal threshold was measured on the 21st day after surgery. The electrophysiological changes of rat peripheral nerve were measured by biopotential recording system, including proximal latency, distal latency, and compound muscle action potential. The incubation period and nerve conduction velocity were further obtained. Histological changes were observed by HE staining and toluidine blue staining. Axon number and myelin damage grade were performed, and the ultrastructure was observed by transmission electron microscopy (TEM). The mechanical withdrawal threshold, nerve conduction velocity, and compound muscle action potential were effectively increased in combination group. However, the proximal latency, distal latency, and incubation period were significantly reduced. Furthermore, dizocine combined with ropivacaine can effectively reduce the degree of myelination. TEM shown that the DR group had the best therapeutic effect, and the histological appearance of the cross section was quite similar to that of the S group. Dizocine combined with ropivacaine has a significant analgesic effect in rat model of peripheral nerve compression.

Occupational exposure to manganese and risk of creatine kinase and creatine kinase-MB elevation among ferromanganese refinery workers.

BACKGROUND: Elevated exposure to manganese (Mn) could induce cardiovascular dysfunction. However, limited research is available on the effects of occupational Mn exposure on myocardial enzymes. We aimed to evaluate the relationships between Mn exposure and myocardial enzyme elevation among Mn-exposed workers. METHODS: Data were from a follow-up investigation of a Mn-exposed workers healthy cohort in 2017. A total of 744 workers were divided into low-exposure and high-exposure groups according to Mn time-weighted average (Mn-TWA) of less than or equal to 0.15 mg/m3 or greater than 0.15 mg/m3 , respectively. Serum levels of myocardial enzymes, including creatine kinase (CK) and creatine kinase-MB (CK-MB), lactic dehydrogenase, α-hydroxybutyrate dehydrogenase, and aspartate transaminase, were assessed, as well as airborne Mn exposure levels. RESULTS: After adjustment for sex, body mass index, seniority, education, current smoking status, current drinking status, and hypertension, Mn-TWA levels were positively associated with the risk of CK elevation (odds ratio [OR] = 1.47 (95% confidence interval [CI]: 1.18-1.83) per interquartile range [IQR] increase), and risk of CK-MB elevation [OR = 1.57 (95% CI: 1.03-2.38) per IQR increase]. In a stratified analysis, Mn-TWA levels were positively correlated with CK elevation in workers of seniority greater than 19 years, male workers, current smokers, and drinkers. CONCLUSION: Our results suggest that occupational exposure to Mn is associated with increased risk of CK and CK-MB elevation. The potential mechanisms of the associations between airborne exposure to Mn and increased risk of these myocardial enzyme elevations warrant further investigation.

LncRNA LEF1-AS1 regulates the migration and proliferation of vascular smooth muscle cells by targeting miR-544a/PTEN axis.

Long noncoding RNAs (lncRNAs) play important roles in endothelium development. A lncRNA, LEF1-AS1, is recently emerging as a potent mediator of the proliferation and migration of a number of cells, including smooth muscle cells. However, the effects of LEF1-AS1 in atherosclerosis remains largely unknown. Specimens from patients with coronary artery atherosclerosis were collected. The quantitative real-time polymerase chain reaction was used to analyze levels of LEF1-AS1 and microRNA-544a (miR-544a). Western blot analysis was used to assess PTEN, P-Akt, and T-Akt protein expression. Proliferation, migration, and invasion of cells were analyzed by cell counting kit-8 assay, scratch wound assay, and transwell assay, respectively. The interaction between LEF1-AS1, miR-544a, and PTEN was probed using bioinformatical analysis and dual-luciferase assay. In plasma and tissue of patients with coronary artery atherosclerosis, LEF1-AS1 was upregulated and miR-544a was downregulated. A negative correlation was found between LEF1-AS1 and miR-544a. miR-544a overexpression reversed the inhibition of LEF1-AS1 in smooth muscle cell proliferation and invasion, which were mediated through the PTEN pathway. LEF1-AS1 regulates smooth muscle cell proliferation and migration through the miR-544a/PTEN axis, indicating that LEF1-AS1 may be a potential therapeutic target in atherosclerosis.

Day 6 blastocyst is associated with increased birth weight in full-term singleton newborns after frozen-thawed transfer.

PURPOSE: The purpose of the study is to compare the newborns weight in singleton term birth following transfer of thawed blastocysts-frozen on either day 5 or day 6 after in vitro fertilization. METHOD: The retrospective study included 1444 frozen-thawed blastocyst transfer (FBT) cycles resulting in live singleton births between Jan 2013 and Dec 2016. The main outcomes measured were absolute birth weight, z-score adjusted for gestational age and gender, and incidence of large-for-gestational-age (LGA) newborns. Generalized linear model (GLM) and logistic regression were used in multivariate analyses. RESULT(S): Both the absolute birth weight (3416.49 ± 404.74 vs 3349.22 ± 416.17) and the z-score (0.6 ± 0.93 vs 0.41 ± 0.93) were significantly higher on day 6 FBT in comparison with day 5 FBT. The incidence of LGA newborns was also increased on day 6 FBT (22.8 vs 14.7%, P = 0.006). Adjusted for maternal age, BMI, PCOS diagnosis, present of vanishing twin, and embryo quality, the odds ratio (95% confidence interval) for LGA on day 6 FBT comparing with day 5 FBT was 1.76 (1.18-2.64). CONCLUSION(S): Day 6 FBT is associated with increased birth weight and contributes to the incidence of LGA newborns in FBT.

Comparative Proteomic Analysis of Mature and Immature Oocytes of the Swamp Buffalo (Bubalus bubalis).

Maternal protein components change markedly during mammalian oogenesis. Many of these proteins have yet to be characterized and verified. In this study, a proteomics approach was used to evaluate changes in proteins during oogenesis in the Swamp Buffalo (Bubalus bubalis). Proteins from 500 immature oocytes and 500 in vitro matured oocytes were subjected to two-dimensional electrophoresis, and more than 400 spots were detected. Image analysis indicated that 17 proteins were differentially expressed between the two groups. Eight proteins were identified by mass spectrometry. In mature oocytes, three proteins were down-regulated: major vault protein (MVP), N-acetyllactosaminide ß-1,6-N-acetylglucosaminyl-transferase (GCNT-2), and gem-associated protein (GEMIN)8, whereas five other proteins, heat shock protein (HSP)60, Ras-responsive element-binding protein 1 (RREB-1), heat shock cognate 71 kDa protein (HSC71), hemoglobin subunit α (HBA), and BMP-2-inducible protein kinase (BMP-2K), were up-regulated. The expression profiles of HSP60 and GEMIN8 were further verified by Western blotting. The changes in HSP60 protein expression demonstrate the increasing need for mitochondrial protein importation to facilitate macromolecular assembly during oocyte maturation. The down-regulation of GEMIN8 production implies that RNA splicing is impaired in mature oocytes.

Favorable prognosis of biallelic CEBPA gene mutations in acute myeloid leukemia patients: a meta-analysis.

OBJECTIVES: Increasing number of studies suggested that biallelic CEBPA (bi CEBPA) mutations were associated with favorable prognosis in patients with acute myeloid leukemia (AML), but the results remain inconclusive. We therefore present a meta-analysis to evaluate the prognostic value of bi CEBPA mutations in patients with AML. METHODS: A comprehensive literature search was undertaken through August 2014 looking for eligible studies. Pooled hazard ratios (HRs) estimates and 95% confidence intervals (95% CIs) in overall survival (OS) and event-free survival (EFS) were used to calculate estimated effect. RESULTS: Ten studies covering a total of 6219 subjects were included in this analysis. Overall, bi CEBPA mutations were associated with favorable clinical outcome in patients with AML (HR for EFS: 0.41, 95% CI: 0.32-0.52; for OS: 0.37, 95% CI: 0.27-0.50), in cytogenetically normal (CN)-AML (HR for EFS: 0.38, 95% CI: 0.29-0.49; for OS: 0.32, 95% CI: 0.23-0.43). When took the cohort of monoallelic CEBPA (mo CEBPA) mutated and wild-type CEBPA (wt CEBPA) AML as a reference group, bi CEBPA mutated AML also shown beneficial outcomes (HR for OS: 0.52, 95% CI: 0.37-0.72). No significant difference was found between mo CEBPA mutation and wt CEBPA in patients with AML or CN-AML (P > 0.05). CONCLUSION: Bi CEBPA mutations in patients with AML are strongly associated with a favorable prognosis, which suggested that bi CEBPA mutations would potentially serve as a novel prognostic marker in AML.