Characterization of conception rate after embryo transfer in comparison with that after artificial insemination in dairy cattle.

Artificial insemination (AI) and embryo transfer (ET) are important in the reproduction of dairy cows. The conception rate after AI or ET is an essential indicator when selecting appropriate breeding methods. However, information on the environmental factors affecting ET conception rate when compared with AI is limited. We aimed to investigate environmental factors affecting ET conception rate and characterize the differences in environmental factors between AI and ET. Records of the first AI (n = 1,870,143) and ET (n = 29,922) from Holstein nulliparous, primiparous, and multiparous cows in Hokkaido, Japan, were analyzed using separate multivariable logistic regression models. For each breeding method, we grouped primiparous and multiparous cows according to milk yield at peak lactation (PY; < 25, 25-30, 30-35, ≥ 35 kg in primiparous, < 40, 40-45, 45-50, ≥ 50 kg in multiparous) and the interval from calving to first AI or ET (CFI/CFT; < 60, 60-79, 80-99, ≥ 100 d) to evaluate the effects of PY and CFI/CFT on conception rate. AI conception rate decreased with increasing PY in primiparous and multiparous cows, whereas ET conception rate did not decrease significantly. Additionally, the ET conception rate did not decrease even in primiparous and multiparous cows slightly earlier than 60 d in CFI/CFT when compared with those in CFI/CFT after 60 d, which differed from the AI conception rate. Collectively, breeding by ET leads to the avoidance of negative effects of high milk yield and calving on the conception rate, indicating that cows are fertile by ET within 60 d after calving.

Genetic relationship of energy balance predicted from milk traits with fertility in Japanese Holsteins.

We predicted the energy balance of cows from milk traits and estimated the genetic correlations of predicted energy balance (PEB) with fertility traits for the first three lactations. Data included 9,646,606 test-day records of 576,555 Holstein cows in Japan from 2015 to 2019. Genetic parameters were estimated with a multiple-trait model in which the records among lactation stages and parities were treated as separate traits. Fertility traits were conception rate at first insemination (CR), number of inseminations (NI), and days open (DO). Heritability estimates of PEB were 0.28-0.35 (first lactation), 0.15-0.29 (second), and 0.09-0.23 (third). Estimated genetic correlations among lactation stages were 0.85-1.00 (first lactation), 0.73-1.00 (second), and 0.64-1.00 (third). Estimated genetic correlations among parities were 0.82-0.96 (between first and second), 0.97-0.99 (second and third), and 0.69-0.92 (first and third). Estimated genetic correlations of PEB in early lactation with fertility were 0.04 to 0.19 for CR, -0.03 to -0.19 for NI, and -0.01 to -0.24 for DO. Genetic improvement of PEB is possible. Lower PEB in early lactation was associated with worse fertility, suggesting that improving PEB in early lactation may improve reproductive performance.

Comparison between CT volumetry, technetium99m galactosyl-serum-albumin scintigraphy, and gadoxetic-acid-enhanced MRI to estimate the liver fibrosis stage in preoperative patients.

OBJECTIVES: To compare the efficacy of computed tomography volumetry (CTV), technetium99m galactosyl-serum-albumin (99mTc-GSA) scintigraphy, and gadolinium-ethoxybenzyl-diethylenetriamine-pentaacetic-acid-enhanced MRI (EOB-MRI) in estimating the liver fibrosis (LF) stage in patients undergoing liver resection. METHODS: This retrospective study included 91 consecutive patients who had undergone preoperative dynamic CT and 99mTc-GSA scintigraphy. EOB-MRI was performed in 76 patients. CTV was used to measure the total liver volume (TLV), spleen volume (SV), normalised to the body surface area (BSA), and liver-to-spleen volume ratio (TLV/SV). 99mTc-GSA scintigraphy provided LHL15, HH15, and GSA indices. The liver-to-spleen ratio (LSR) was calculated in the hepatobiliary phase of EOB-MRI. Hyaluronic acid and type 4 collagen levels were measured in 65 patients. Logistic regression and receiver operating characteristic (ROC) analyses were performed to identify useful parameters for estimating the LF stage and laboratory data. RESULTS: According to the multivariable logistic regression analysis, SV/BSA (odds ratio [OR], 1.01; 95% confidence interval [CI], 1.003-1.02; p = 0.011), LSR (OR, 0.06; 95%CI, 0.004-0.70; p = 0.026), and hyaluronic acid (OR, 1.01; 95%CI, 1.001-1.02; p = 0.024) were independent variables for severe LF (F3-4). Combined SV/BSA, LSR, and hyaluronic acid correctly estimated severe LF, with an AUC of 0.91, which was significantly larger than the AUCs of the GSA index (AUC = 0.84), SV/BSA (AUC = 0.83), or LSR (AUC = 0.75) alone. CONCLUSIONS: Combined CTV, EOB-MRI, and hyaluronic acid analyses improved the estimation accuracy of severe LF compared to CTV, EOB-MRI, or 99mTc-GSA scintigraphy individually. CLINICAL RELEVANCE STATEMENT: The combined analysis of spleen volume on CT volumetry, liver-to-spleen ratio on gadolinium-ethoxybenzyl-diethylenetriamine-pentaacetic-acid-enhanced MRI, and hyaluronic acid can identify severe liver fibrosis associated with a high risk of liver failure after hepatectomy and recurrence in patients with hepatocellular carcinoma. KEY POINTS: • Spleen volume of CT volumetry normalised to the body surface area, liver-to-spleen ratio of EOB-MRI, and hyaluronic acid were independent variables for liver fibrosis. • CT volumetry and EOB-MRI enable the detection of severe liver fibrosis, which may correlate with post-hepatectomy liver failure and complications. • Combined CT volumetry, gadolinium-ethoxybenzyl-diethylenetriamine-pentaacetic-acid-enhanced MRI (EOB-MRI), and hyaluronic acid analyses improved the estimation of severe liver fibrosis compared to technetium99m galactosyl-serum-albumin scintigraphy.

Extracellular volume by dual-energy CT, hepatic reserve capacity scoring, CT volumetry, and transient elastography for estimating liver fibrosis.

Our purpose was to compare the efficacy of liver and splenic volumetry (LV and SV), extracellular volume (ECV) on dual-layer spectral-detector CT scoring systems for estimating liver fibrosis (LF) in 45 patients with pathologically staged LF. ECV measured on CT value (HU-ECV), iodine density (ID-ECV), atomic number (Zeff-ECV), and electron density (ED-ECV), LV or SV/body surface area (BSA), albumin bilirubin grade (ALBI), model for end-stage liver disease (MELD) score, aspartate aminotransferase platelet ratio index (APRI), and fibrosis index based on the four factors (FIB-4) were recorded. Transient elastography was measured in 22 patients, and compared to ECV. No correlation was found between transient elastography and all ECVs. Area under the curve (AUC) for estimating F4 on transient elastography was 0.885 (95% CI 0.745-1.000). ALBI was weakly associated with LF (p = 0.451), while MELD (p < 0.001), APRI (p = 0.010), and FIB-4 (p = 0.010) were significantly associated with LF. SV/BSA had a higher AUC than MELD, APRI, and FIB-4 for estimating F4 (AUC = 0.815, 95% CI 0.63-0.999), but MELD (AUC = 0.799, 95% CI 0.634-0.965), APRI (AUC = 0.722, 95% CI 0.561-0.883), and FIB-4 (AUC = 0.741, 95% CI 0.582-0.899) had higher AUCs than ALBI. SV/BSA significantly contributed to differentiation for estimating F4; odds ratio (OR) was 1.304-1.353 (Reader 1-2; R1-R2), whereas MELD significantly contributed to the differentiation between F0-2 and F3-4; OR was 1.528-1.509 (R1-R2). AUC for SV/BSA and MELD combined was 0.877 (95% CI 0.748-1.000). In conclusion, SV/BSA allows for a higher estimation of liver cirrhosis (F4). MELD is more suitable for assessing severe LF (≥ F3-4). The combination of SV/BSA and MELD had a higher AUC than SV/BSA alone for liver cirrhosis (F4).

Comparison between Intravoxel Incoherent Motion and Splenic Volumetry to Predict Hepatic Fibrosis Staging in Preoperative Patients.

Intravoxel incoherent motion (IVIM) and splenic volumetry (SV) for hepatic fibrosis (HF) prediction have been reported to be effective. Our purpose is to compare the HF prediction of IVIM and SV in 67 patients with pathologically staged HF. SV was divided by body surface area (BSA). IVIM indices, such as slow diffusion-coefficient related to molecular diffusion (D), fast diffusion-coefficient related to perfusion in microvessels (D*), apparent diffusion-coefficient (ADC), and perfusion related diffusion-fraction (f), were calculated by two observers (R1/R2). D (p = 0.718 for R1, p = 0.087 for R2) and D* (p = 0.513, p = 0.708, respectively) showed a poor correlation with HF. ADC (p = 0.034, p = 0.528, respectively) and f (p < 0.001, p = 0.007, respectively) decreased as HF progressed, whereas SV/BSA increased (p = 0.015 for R1). The AUCs of SV/BSA (0.649-0.698 for R1) were higher than those of f (0.575-0.683 for R1 + R2) for severe HF (≥F3-4 and ≥F4), although AUCs of f (0.705-0.790 for R1 + R2) were higher than those of SV/BSA (0.628 for R1) for mild or no HF (≤F0-1). No significant differences to identify HF were observed between IVIM and SV/BSA. SV/BSA allows a higher estimation for evaluating severe HF than IVIM. IVIM is more suitable than SV/BSA for the assessment of mild or no HF.

Tumor stiffness measurement using magnetic resonance elastography can predict recurrence and survival after curative resection of hepatocellular carcinoma.

BACKGROUND: Tumor stiffness measurement using magnetic resonance elastography can assess tumor mechanical properties and predict hepatocellular carcinoma recurrence. This study aimed to investigate preoperative tumor stiffness on magnetic resonance elastography as a predictor of overall survival and recurrence-free survival in patients with solitary nodular hepatocellular carcinoma who underwent curative resection. METHODS: Seventy-eight patients with solitary nodular hepatocellular carcinoma who underwent preoperative magnetic resonance elastography and curative resection were retrospectively analyzed. Potential associations of tumor stiffness and other clinicopathological variables with overall survival and recurrence-free survival were analyzed in both univariate and multivariate Cox proportional hazards analyses. The optimal tumor stiffness cutoff value was determined using the minimal P value approach. RESULTS: In multivariate analysis, tumor stiffness (hazard ratio 1.31; 95% confidence interval, 1.07-1.59; P = .008) and vascular invasion (hazard ratio 2.62; 95% confidence interval, 1.27-5.17; P = .010) were independent predictors of recurrence-free survival. For overall survival, tumor stiffness (hazard ratio, 1.33; 95% confidence interval, 1.02-1.76; P = .037) was the only independent predictor. The optimal tumor stiffness cutoff value was 5.81 kPa for both overall survival and recurrence-free survival. Patients with tumor stiffness ≥5.81 kPa had a significantly greater risk of death (hazard ratio 6.10; 95% confidence interval, 2.11-21.90; P < .001) than those with tumor stiffness <5.81 kPa. CONCLUSION: Preoperative tumor stiffness as measured by magnetic resonance elastography was a predictor of overall survival and recurrence-free survival in hepatocellular carcinoma patients who underwent curative resection. Higher tumor stiffness was associated with higher risk of recurrence and death.

Acute Liver Failure and Acute-on-Chronic Liver Failure in COVID-19 Era.

Acute liver failure (ALF) and acute-on-chronic liver failure (ACLF), respectively, occur in patients with normal liver and patients with chronic liver diseases, including cirrhosis [...].

Environmental factors affecting the conception rates of nulliparous and primiparous dairy cattle.

Dairy cattle must allocate energy to milk production and reproduction. Therefore, understanding the environmental factors that affect conception rates in nulliparous and primiparous cows is helpful in appropriate feeding management strategies before and after calving. Accordingly, the aim of this study was to investigate the influence of environmental factors before and after the first calving on the conception rate, representing the starting point of milk production. The records of the first artificial insemination (AI) from Holstein nulliparous cows (n = 533,672) and primiparous cows (n = 516,710) in Hokkaido, Japan, were analyzed using separate multivariable logistic regression models. The mean conception rates for nulliparous and primiparous cows from 2012 to 2018 were 55.2 and 39.2%, respectively. In both nulliparous and primiparous cows, the conception rate of crossbreeding using Japanese Black (JB) semen was significantly higher than that for purebred Holstein breeding. The conception rate using sexed semen decreased in the warmer months only in nulliparous cows. Moreover, we grouped primiparous cows according to milk yield during peak lactation (PY; < 25, 25-30, 30-35, ≥35 kg) and the interval from calving to first insemination (CFI; < 60, 60-79, 80-99, ≥100 d), and evaluated their combined effect on the conception rate. Both PY and CFI strongly affected the conception rate in primiparous cows, which decreased with an increase in PY, even for the group with CFI ≥100 d; however, the conception rate increased for a CFI ≥60 d regardless of PY. Taken together, this study demonstrates the long-term effect of PY and an independent effect of CFI on the conception rate of cows. These results provide guidance for management to execute appropriate AI implementation strategies before and after lactation.

Comparison between CT volumetry and extracellular volume fraction using liver dynamic CT for the predictive ability of liver fibrosis in patients with hepatocellular carcinoma.

OBJECTIVES: To compare the predictive ability of liver fibrosis (LF) by CT-volumetry (CTV) for liver and spleen and extracellular volume fraction (ECV) for liver in patients undergoing liver resection. METHODS: We retrospectively analysed 90 consecutive patients who underwent CTV and ECV. Manually placed region-of-interest ECV (manual-ECV), rigid-registration ECV (rigid-ECV), and nonrigid-registration ECV (nonrigid-ECV) were calculated as ECV(%) = (1-haematocrit) × (ΔHUliver/ΔHUaorta), where ΔHU = subtraction of unenhanced phase from equilibrium phase (240 s). Manual-ECV was compared with CTV for the estimation of LF. The total liver volume to body surface area (TLV/BSA), splenic volume to BSA (SV/BSA), ratio of TLV to SV (TLV/SV), ratio of right liver volume to SV (RV/SV), and liver segmental volume ratio (LSVR) were measured. ROC analyses were performed for ECV and CTV. RESULTS: After excluding 10 patients, seventy-eight (97.5%) out of 80 patients had a Child-Pugh score of 5 points, and two (2.5%) patients had a Child-Pugh score of 6 points. AUC of ECV showed no significant difference among manual-ECV, rigid-ECV, and nonrigid-ECV. TLV/BSA, SV/BSA, TLV/SV, and RV/SV had a higher correlation with LF grades than manual-ECV. AUC of SV/BSA was significantly higher than that of manual-ECV in F0-1 vs F2-4 and F0-2 vs F3-4. AUC of SV/BSA (0.76-0.83) was higher than that of manual-ECV (0.61-0.75) for all LF grades, although manual-ECV could differentiate between F0-3 and F4 at high AUC (0.75). CONCLUSIONS: In patients undergoing liver resection, SV/BSA is a better method for estimating severe LF grades, although manual-ECV has the ability to estimate cirrhosis (≥ F4). KEY POINTS: The splenic volume is a better method for estimating liver fibrosis grades. The extracellular volume fraction is also a candidate for the estimation of severe liver fibrosis.

Fine-tuning of ß-catenin in mouse thymic epithelial cells is required for postnatal T-cell development.

In the thymus, the thymic epithelium provides a microenvironment essential for the development of functionally competent and self-tolerant T cells. Previous findings showed that modulation of Wnt/ß-catenin signaling in mouse thymic epithelial cells (TECs) disrupts embryonic thymus organogenesis. However, the role of ß-catenin in TECs for postnatal T-cell development remains to be elucidated. Here, we analyzed gain-of-function (GOF) and loss-of-function (LOF) of ß-catenin highly specific in mouse TECs. We found that GOF of ß-catenin in TECs results in severe thymic dysplasia and T-cell deficiency beginning from the embryonic period. By contrast, LOF of ß-catenin in TECs reduces the number of cortical TECs and thymocytes modestly and only postnatally. These results indicate that fine-tuning of ß-catenin expression within a permissive range is required for TECs to generate an optimal microenvironment to support postnatal T-cell development.

A proposed model on MR elastography for predicting postoperative major complications in patients with hepatocellular carcinoma.

OBJECTIVE: To develop a model for predicting post-operative major complications in patients with hepatocellular carcinoma (HCC). METHODS: In all, 186 consecutive patients with pre-operative MR elastography were included. Complications were categorised using Clavien‒Dindo classification, with major complications defined as ≥Grade 3. Liver-stiffness measurement (LSM) values were measured on elastogram. The indocyanine green clearance rate of liver remnant (ICG-Krem) was based on the results of CT volumetry, intraoperative data, and ICG-K value. For an easy application to the prediction model, the continuous variables were converted to categories. Moreover, logistic regression analysis and fivefold cross-validation were performed. The prediction model's discriminative performance was evaluated using the area under the receiver operating characteristic curve (AUC), and the calibration of the model was assessed by the Hosmer‒Lemeshow test. RESULTS: 43 of 186 patients (23.1%) had major complications. The multivariate analysis demonstrated that LSM, albumin-bilirubin (ALBI) score, intraoperative blood loss, and ICG-Krem were significantly associated with major complications. The median AUC of the five validation subsets was 0.878. The Hosmer-Lemeshow test confirmed no evidence of inadequate fit (p = 0.13, 0.19, 0.59, 0.59, and 0.73) on the fivefold cross-validation. The prediction model for major complications was as follows: -2.876 + 2.912 [LSM (>5.3 kPa)]+1.538 [ALBI score (>-2.28)]+0.531 [Intraoperative blood loss (>860 ml)]+0.257 [ICG-Krem (<0.10)]. CONCLUSION: The proposed prediction model can be used to predict post-operative major complications in patients with HCC. ADVANCES IN KNOWLEDGE: The proposed prediction model can be used in routine clinical practice to identify post-operative major complications in patients with HCC and to strategise appropriate treatments of HCC.

Magnetic resonance elastography-based prediction of hepatocellular carcinoma recurrence after curative resection.

BACKGROUND: Liver stiffness measurement using magnetic resonance elastography can assess the severity of liver fibrosis, which is significantly associated with recurrence after curative resection for hepatocellular carcinoma. The aim of this prospective study was to investigate whether preoperative liver stiffness measurement by magnetic resonance elastograhy can predict recurrence after curative resection for hepatocellular carcinoma. METHODS: Patients who underwent preoperative liver stiffness measurement and curative resection for hepatocellular carcinoma were enrolled in this study. Potential associations between liver stiffness measurement, along with other clinical and pathologic variables, and intrahepatic hepatocellular carcinoma recurrence were analyzed. RESULTS: In total, 156 patients were included in this study. During a median follow-up period of 25.1 months (range, 6.0-60.5 months), 72 (46.1%) patients with hepatocellular carcinoma had an intrahepatic recurrence. The median disease-free period after resection was 17.9 months (range, 1.0-60.5 months). In the multivariate analysis, liver stiffness measurement (hazard ratio, 1.27; 95% confidence interval, 1.11-1.43; P <.001) and vascular invasion (hazard ratio, 1.96; 95% confidence interval, 1.15-3.25; P = .013) were identified as independent predictors of recurrence. When the optimal cutoff point was set at 4.53 kPa using the minimal P value approach, the disease-free period after curative resection in 71 patients with a liver stiffness measurement value ≥4.53 kPa (11.3 months [range, 2.0-60.5 months]) was significantly shorter than that of 85 patients with a liver stiffness measurement value <4.53 kPa (22.5 months [range, 1.1-60.5 months]; P <.001). CONCLUSION: Liver stiffness measurement using magnetic resonance elastography is a useful preoperative predictor of intrahepatic recurrence after curative resection for hepatocellular carcinoma.

Predictive value of combined computed tomography volumetry and magnetic resonance elastography for major complications after liver resection.

PURPOSE: To retrospectively compare the predictive value of computed tomography volumetry (CTV), magnetic resonance elastography (MRE) of the liver, and their combination for major complications after liver resection. METHODS: We enrolled 108 consecutive patients who underwent anatomical liver resection for liver tumors and preoperative contrast-enhanced CT and MRE. The future liver remnant (FLR) ratio was calculated by CTV, while the liver stiffness measurement (LSM) was obtained by MRE. FLR ratio alone, LSM alone, and combined FLR ratio and LSM were evaluated to predict major complications (Clavien-Dindo grade ≥ IIIa). Univariate and multivariate analyses of hepatic biochemical parameters and imaging data were performed to identify predictors of major complications. Receiver operating characteristic analyses of FLR ratio, LSM, and their combination were performed, and the sensitivity and specificity were calculated. RESULTS: Twenty-two (20.4%) of the 108 patients experienced major complications. According to multiple regression analysis, the FLR ratio (odds ratio [OR] 0.96, 95% confidence interval [CI] 0.91-0.99, p = 0.040) and LSM (OR 1.72, 95% CI 1.01-2.94, p = 0.047) were independent predictors of major complications. The combined FLR ratio and LSM were predictive of major complications, with an area under the curve (AUC) of 0.818, sensitivity of 68.2%, and specificity of 84.9%. The AUC and specificity for combined FLR ratio and LSM were larger than those for FLR ratio (AUC: 0.711, specificity: 80.2%) and LSM (AUC: 0.793, specificity: 80.2%). CONCLUSION: Combined CTV and MRE analysis can improve the AUC and specificity for predicting major complications after anatomical liver resection.

Subcuticular Sutures Versus Staples for Wound Closure in Open Liver Resection: A Randomised Clinical Trial.

BACKGROUND: Subcuticular sutures reduce wound complication rates only in clean surgeries. Repeat resection is frequently required in liver surgery, due to the high recurrence rate (30-50%) of liver cancers. The aim of this study is to assess that subcuticular sutures is superior to staples in liver surgery. METHODS: This single-centre, single-blinded, randomised controlled trial was conducted at a university hospital between January 2015 and October 2018. Patients were randomly assigned (1:1) to receive either subcuticular sutures or staples for skin closure. Three risk factors (repeat resection, diabetes mellitus and liver function) were matched preoperatively for equal allocation. The primary endpoint was the wound complication rate, while secondary endpoints were surgical site infection (SSI), duration of postoperative hospitalisation and total medical cost. Subset analyses were performed only for the 3 factors allocated as secondary endpoints. RESULTS: Of the 581 enrolled patients, 281 patients with subcuticular sutures and 283 patients with staples were analysed. As the primary outcome, the wound complication rate with subcuticular sutures (12.5%) did not differ from that with staples [15.9%; odds ratio (OR), 1.33; 95% confidence interval (CI), 0.83-2.15; p = 0.241]. As secondary outcomes, no significant differences were identified between the two procedures in the overall cohort while overall wound complications [7 patients (8.5%) vs. 17 patients (20.0%); OR, 2.68; 95% CI, 1.08-7.29; p = 0.035] with repeat incision were significantly less frequent with subcuticular sutures. CONCLUSION: Subcuticular sutures were not shown to reduce wound complications compared to staples in open liver resection, but appear beneficial for repeat incisions.

Predictive value of perfusion CT for blood loss in liver resection.

Blood loss is associated with the degree of damage in liver stiffness. Severe liver steatosis is a matter of concern in liver surgery, but does not correlate with liver stiffness. This study aimed to assess the relationship between blood perfusion of the liver and blood loss in liver pathologies. Data from elective liver resection for liver cancer were analyzed. All patients underwent preoperative assessments including perfusion CT. Patients were divided into 4 groups in accordance with the pathological background of liver parenchyma. Relationships between portal flow as assessed by perfusion CT and perioperative variables were compared. Factors correlating with blood loss were analyzed. In 166 patients, portal flow from perfusion CT correlated positively with platelet count and negatively with indocyanine green retention rate at 15 min. Background liver pathology was normal liver (NL) in 43 cases, chronic hepatitis (CH) in 56, liver cirrhosis (LC) in 42, and liver steatosis (LS) in 25. Rates of hepatitis viral infection and pathological hepatocellular carcinoma were more frequent in LC and CH groups than in the other groups (p < 0.05). LC and LS showed significantly worse liver function than the NL and CH groups. Portal flow from perfusion CT correlated positively with damage to liver parenchyma and negatively with blood loss at liver transection. Low portal flow on perfusion CT predicts blood loss during liver transection.

Effects of Pyrrole-Imidazole Polyamides Targeting Human TGF-ß1 on the Malignant Phenotypes of Liver Cancer Cells.

Synthetic pyrrole-imidazole (PI) polyamides bind to the minor groove of double-helical DNA with high affinity and specificity, and inhibit the transcription of corresponding genes. In liver cancer, transforming growth factor (TGF)-ß expression is correlated with tumor grade, and high-grade liver cancer tissues express epithelial-mesenchymal transition markers. TGF-ß1 was reported to be involved in cancer development by transforming precancer cells to cancer stem cells (CSCs). This study aimed to evaluate the effects of TGF-ß1-targeting PI polyamide on the growth of liver cancer cells and CSCs and their TGF-ß1 expression. We analyzed TGF-ß1 expression level after the administration of GB1101, a PI polyamide that targets human TGF-ß1 promoter, and examined its effects on cell proliferation, invasiveness, and TGF-ß1 mRNA expression level. GB1101 treatment dose-dependently decreased TGF-ß1 mRNA levels in HepG2 and HLF cells, and inhibited HepG2 colony formation associated with downregulation of TGF-ß1 mRNA. Although GB1101 did not substantially inhibit the proliferation of HepG2 cells compared to untreated control cells, GB1101 significantly suppressed the invasion of HLF cells, which displayed high expression of CD44, a marker for CSCs. Furthermore, GB1101 significantly inhibited HLF cell sphere formation by inhibiting TGF-ß1 expression, in addition to suppressing the proliferation of HLE and HLF cells. Taken together, GB1101 reduced TGF-ß1 expression in liver cancer cells and suppressed cell invasion; therefore, GB1101 is a novel candidate drug for the treatment of liver cancer.

Effects of use of conventional and sexed semen on the conception rate in heifers: A comparison study.

Conception rate with the use of sexed semen is lower than that with the use of conventional semen, posing a major problem in the dairy industry. The aim of this study was to understand the risk factors that affect the conception rate after artificial insemination (AI) with conventional and sexed semen using field data. The records of the first insemination in Holstein heifers with conventional (n = 41,857) and sexed semen (n = 45,465) in Hokkaido, Japan were analyzed. The mean conception rate after AI from 2012 to 2016 was 56.9% with conventional semen and 47.3% with sexed semen. A multivariable logistic regression model including the effects of year, heifer age, time of the year, semen type, service sire, and their interactions was used to evaluate the interaction effect of heifer age and time of the year by semen type on the conception rate. In the analysis using heifer age, we found that heifers inseminated with sexed semen were approximately 21 days younger than those inseminated with conventional semen. Interestingly, in early, warmer months (Jun, Jul, and Aug), the conception rate after AI with sexed semen significantly decreased compared with that after AI with conventional semen (P < 0.01). Our results showed that more careful implementation of AI is required for a stable conception using sexed semen, particularly during warmer months.

Genetic parameters for mastitis incidence and its indicators based on somatic cell score for Holsteins in Hokkaido, Japan.

The objectives of this study were to estimate the heritability of mastitis incidence and genetic correlations between the mastitis and the somatic cell score (SCS) statistics, and to compare the practicability between different models. We used test-day records with the mastitis incidence and SCS collected from Holstein cows calving from 1988 to 2015 in Hokkaido, Japan. As indicators of mastitis, the average SCS (avSCS), the standard deviation of SCS (sdSCS), and the maximum SCS (maxSCS) were calculated using test-day records up to the first 305 days in milk within a lactation. We compared a four-trait repeatability animal model (MTRP) with a four-trait multiple-lactation animal model (MTML). The heritability for mastitis was equal to or lower than 0.05 in all the models. Genetic correlations between lactations with MTML within the same trait were positive and close to 1. With MTRP, the estimated genetic correlations of the mastitis incidence with avSCS, sdSCS, and maxSCS were 0.66, 0.79, and 0.82, respectively. A joint evaluation with SCS statistics is expected to give an extra reliability for mastitis because of high and positive genetic correlations among the traits.

Prediction of esophageal varices by liver and spleen MR elastography.

OBJECTIVES: We aimed to assess the diagnostic performance of MR elastography (MRE) in predicting esophageal varices (EVs) in patients with chronic liver disease. METHODS: We prospectively performed liver (LSM) and spleen stiffness measurements (SSM) using MRE and endoscopic screening for EVs to determine if patients with hepatocellular carcinoma were eligible for resection. We investigated whether LSM, SSM, and other non-invasive preoperative parameters were associated with the presence of EVs. In order to predict EVs, 211 patients were divided into training (n = 140) and test (n = 71) groups. A nomogram was built using independent factors based on logistic regression analysis in the training group and its accuracy was validated using an independent cohort. RESULTS: Forty-six patients (21.8%) were diagnosed as having EVs (mild, n = 36; severe, n = 10). According to multiple regression analysis, LSM (odds ratio, 2.362; 95% confidence interval [CI], 1.341-4.923; p = 0.001) and SSM (1.489; 1.095-2.235; p = 0.010) were independent predictors of EVs in the training group. The nomogram showed good discrimination, with a C-index of 0.942 (95% CI, 0.892-0.974) through internal validation, and good calibration. Application of the nomogram in the test group still gave good discrimination (C-index, 0.948; 95% CI, 0.868-0.995). CONCLUSIONS: The combination of LSM and SSM using MRE is an accurate tool to identify patients at risk for EVs. KEY POINTS: • Performance of MR elastography can estimate the presence of esophageal varices non-invasively. • Liver and spleen stiffness measurements are independent predictors for esophageal varices. • The nomogram using a combination of liver and spleen stiffness measurements allows for the risk of esophageal varices.