## Παρασκευή, 3 Νοεμβρίου 2017

### Purpose

To explore whether integrated 18F-FDG PET/MRI can be used to predict pathological response to neoadjuvant chemotherapy (NAC) in patients with breast cancer.

### Methods

Between November 2014 and April 2016, 26 patients with breast cancer who had received NAC and subsequent surgery were prospectively enrolled. Each patient underwent 18F-FDG PET/MRI examination before and after the first cycle of NAC. Qualitative MRI parameters, including morphological descriptors and the presence of peritumoral oedema were assessed. Quantitatively, PET parameters, including maximum standardized uptake value, metabolic tumour volume and total lesion glycolysis (TLG), and MRI parameters, including washout proportion and signal enhancement ratio (SER), were measured. The performance of the imaging parameters singly and in combination in predicting a pathological incomplete response (non-pCR) was assessed.

### Results

Of the 26 patients, 7 (26.9%) exhibited a pathological complete response (pCR), and 19 (73.1%) exhibited a non-pCR. No significant differences were found between the pCR and non-pCR groups in the qualitative MRI parameters. The mean percentage reductions in TLG30% on PET and SER on MRI were significantly greater in the pCR group than in the non-pCR group (TLG30% −64.8 ± 15.5% vs. −25.4 ± 48.7%, P = 0.005; SER −34.6 ± 19.7% vs. −8.7 ± 29.0%, P = 0.040). The area under the receiver operating characteristic curve for the percentage change in TLG30% (0.789, 95% CI 0.614 to 0.965) was similar to that for the percentage change in SER (0.789, 95% CI 0.552 to 1.000; P = 1.000).The specificity of TLG30% in predicting pCR) was 100% (7/7) and that of SER was 71.4% (5/7). The sensitivity of TLG30% in predicting non-pCR was 63.2% (12/19) and that of SER was 84.2% (16/19). When the combined TLG30% and SER criterion was applied, sensitivity was 100% (19/19), and specificity was 71.4% (5/7).

### Conclusion

18F-FDG PET/MRI can be used to predict non-pCR after the first cycle of NAC in patients with breast cancer and has the potential to improve sensitivity by the addition of MRI parameters to the PET parameters.

### Purpose

The incidence of prostate cancer is 60% higher and the mortality rate is two- to three-times greater in black versus white men. We report on differences in 68Ga-PSMA-11 PET/CT imaging findings in 77 black South-African (BSAs) and 18 white South-African (WSAs) treatment-naïve primary prostate carcinoma (PPC) patients.

### Methods

68Ga-PSMA-11 PET/CT imaging findings were compared to histological, biochemical and morphological imaging data. Patients were grouped into three Gleason grade groups (GG), GG 1 (scores 3 + 3 and 3 + 4), GG2 (scores 4 + 3 and 4 + 4) and GG3 (scores 9 and 10), and the PSA difference among the groups was determined. Inter-racial difference in SUVmax of the primary tumor as well as its correlation with serum PSA were also determined.

### Results

Ninety-three out of 95 PPC where readily identified on 68Ga-PSMA-11 PET/CT imaging. Median PPC SUVmax and serum PSA values proved significantly higher (p = 0.033 and p = 0.003) in GG3 patients (median 16.4 and 180 ng/ml) when compared to GG1 patients (median 9.6 and 25.1 ng/ml) or GG2 patients (median 8.8 and 46.2 ng/ml). SUVmax significantly correlated with serum PSA-values (r = 0.377 (p = 0.0001)). Age, frequency of lymph node involvement and distant metastases, and GGs (p ≥ 0.153) were similar in BSAs and WSAs, both median serum PSA-values as well as SUVmax values proved significantly higher in BSAs when compared to WSAs, respectively, 81.6 ng/ml versus 14.5 ng/ml (p = 0.0001) and 11.9 versus 4.38 (p = 0.004). Moreover, Gleason-score normalized median SUVmax values proved 2.5 times higher in BSAs when compared to WSAs (p = 0.005).

### Conclusion

SUVmax values proved significantly related to GG and to be significantly higher in BSAs when compared to WSAs. Also, SUVmax significantly correlated with serum PSA values, which was significantly higher in BSAs when compared with WSAs.

### Impact of dose intensified salvage radiation therapy on urinary continence recovery after radical prostatectomy: Results of the randomized trial SAKK 09/10

Adjuvant radiation therapy (aRT) after radical prostatectomy (RP) is associated with impaired urinary continence recovery as compared to surveillance. Less is known regarding the effect of salvage radiation therapy (sRT) dose intensification on continence outcomes.

### Whole-body total lesion glycolysis is an independent predictor in patients with esophageal cancer treated with definitive chemoradiotherapy

To determine whether pretreatment whole-body total lesion glycolysis (TLGWB) and metabolic tumor volume (MTVWB) are associated with outcomes in patients with esophageal cancer treated with definitive chemoradiotherapy (dCRT).

### A preliminary immunohistochemical study of signal transducer and activator of transcription (STAT) proteins in primary oral malignant melanoma

Primary oral malignant melanoma (POMM) is a rare type of malignancy with a very poor prognosis, the molecular pathogenesis of which remains elusive. The aim of this study was to assess the expression status of signal transducers and activators of transcription (STAT) proteins in POMM.

### Drug-associated hyperpigmentation of the oral mucosa: report of 4 cases.

To describe four patients with oral mucosa hyperpigmentation associated with four drug classes and review the literature.

### Radiological survey of the covered and uncovered drilling mud depository

Publication date: Available online 2 November 2017
Author(s): Jácint Jónás, János Somlai, Anita Csordás, Edit Tóth-Bodrogi, Tibor Kovács

### Rapid in-situ radiometric assessment of the Mrima-Kiruku high background radiation anomaly complex of Kenya

Publication date: Available online 2 November 2017
Author(s): M.I. Kaniu, H.K. Angeyo, I.G. Darby, L.M. Muia
This paper presents the radiometric survey results of the Mrima-Kiruku high background radiation (HBR) anomaly complex of south coastal Kenya. Utilizing a portable γ-ray spectrometer consisting of a 2.0 l NaI(Tl) backpack detector integrated with GPS to perform the relevant in-situ radiometric measurements, a novel geospatial gating method was devised to represent the measurements. The goal of this study was to assess radiation exposure and associated natural radioactivity levels in the complex and to compare the results obtained with those from previous preliminary related studies. Absorbed dose-rates in air were found to range <60–2368 nGy h−1. These rates were observed to correspond with the spatial variability of the underlying geology and terrain, increasing toward the summits of both Mrima and Kiruku Hills which implies that the complex is a geogenic HBR anomaly. The activity concentrations of 232Th in the study area are generally higher than those of 40K and 238U: The means of 40K, 238U and 232Th ranged 235±19–603±28 Bq kg−1, 68±6–326±24 Bq kg−1 and 386±12–1817±51 Bq kg−1 respectively. It was concluded that the high air absorbed dose-rate values that were measured (>600 nGy h−1) are due to elevated activity concentrations of 232Th. Therefore there is significant (>1 mSv/y) radiological hazard to the inhabitants of the area particularly those who reside at the foothills of both Mrima and Kiruku Hills.

### Radiological survey of the covered and uncovered drilling mud depository

Publication date: Available online 2 November 2017
Author(s): Jácint Jónás, János Somlai, Anita Csordás, Edit Tóth-Bodrogi, Tibor Kovács

### Purpose

Identifying the elbow flexion–extension (F–E) movement axis is important for placing a hinged elbow external fixator. An X-ray fluoroscopy-based method is widely used in clinical practice, exposing the patient and surgeons to high doses of radiation. Additionally, the accuracy and repeatability of the fluoroscopy-based method are very low and affected by subjective factors.

### Methods

To solve this problem, an X-ray-free method based on kinematics analysis was proposed to identify the elbow F–E movement axis, and a navigation system was built to guide the placement of the elbow external fixator.

### Results

Our X-ray-free navigation method is more repeatable than the current X-ray fluoroscopy method used clinically. Both our algorithm and the NIST (National Institute of Standards and Technology) algorithm showed high accuracy and repeatability to identify the axis.

### Conclusions

The method proposed in this study is very promising to avoid a large dose of X-ray radiation and increases the repeatability and performance of identifying the elbow F–E movement axis for the placement of the hinged elbow external fixator.

### Purpose

To compare dosimetric data for the planning target volume (PTV) and organs at risk (OARs) between 3-dimensional conformal radiotherapy (3DCRT), volumetric modulated arc therapy (VMAT), and helical tomotherapy [1].

### Materials and methods

The dosimetric data for 15 gastric cancer patients treated with 3DCRT, VMAT, or HT techniques were used. Cumulative dosimetric parameters, homogeneity index (HI), and conformal index (CI) were compared for the PTV and OARs.

### Results

The average maximum doses of PTV were significantly higher in VMAT plans than in 3DCRT (p = 0.04) and HT (p = 0.02) plans, whereas minimum dose values were significantly lower in 3DCRT plans compared with VMAT (p < 0.001) and HT (p = 0.02) plans. Liver mean dose (D mean) and D mean values for both kidneys were significantly lower in HT plans than in 3DCRT and VMAT plans. The doses in high dose regions (V30–V45) using 3DCRT plans were significantly higher compared to both VMAT and HT plans. The bowel V5–V30 and V45 was significantly less in HT plans compared to VMAT plans. There were no significant differences in dose sparing of the spinal cord.

### Conclusions

The HT plans reduced the maximum dose applied to the target and improved the conformality and homogeneity of radiation, while providing sufficient PTV coverage.

### Purpose

Although new techniques and prostheses have been introduced in ventral hernia surgery, abdominal hernia repair still presents complications, such as recurrence, pain, and discomfort. Thus, this work implements a computational method aimed at evaluating biomechanical aspects of the abdominal hernia laparoscopic repair, which can support clinical research tailored to hernia surgery.

### Methods

A virtual solid model of the abdominal wall is obtained from MRI scans of a healthy subject. The mechanical behavior of muscular and fascial tissues is described by constitutive formulations with specific parameters. A defect is introduced to reproduce an incisional hernia. Laparoscopic repair is mimicked via intraperitoneal positioning of a surgical mesh. Numerical analyses are performed to evaluate the mechanical response of the abdominal wall in healthy, herniated and post-surgery configurations, considering physiological intra-abdominal pressures.

### Results

During the deformation of the abdominal wall at increasing pressures, a percentage displacement increment up to 6% is found in the herniated condition, while the mechanical behavior of the repaired abdomen is similar to the healthy one. In the pressure range between 8 mmHg and 55 mmHg, the herniated abdomen shows an incremental stiffness differing of 7% with respect to the healthy condition, while the post-surgery condition shows an increase of the incremental stiffness up to 58%.

### Conclusions

This computational approach may be exploited to investigate different aspects of abdominal wall surgical repair, including mesh mechanical characteristics and positioning. Numerical modeling offers a helpful support for selecting the best-fitting prosthesis for customize pre-surgery planning.

### Purpose

Current markerless registration methods for neurosurgical robotics use the facial surface to match the robot space with the image space, and acquisition of the facial surface usually requires manual interaction and constrains the patient to a supine position. To overcome these drawbacks, we propose a registration method that is automatic and does not constrain patient position.

### Methods

An optical camera attached to the robot end effector captures images around the patient's head from multiple views. Then, high coverage of the head surface is reconstructed from the images through multi-view stereo vision. Since the acquired head surface point cloud contains color information, a specific mark that is manually drawn on the patient's head prior to the capture procedure can be extracted to automatically accomplish coarse registration rather than using facial anatomic landmarks. Then, fine registration is achieved by registering the high coverage of the head surface without relying solely on the facial region, thus eliminating patient position constraints.

### Results

The head surface was acquired by the camera with a good repeatability accuracy. The average target registration error of 8 different patient positions measured with targets inside a head phantom was $$1.39\pm 0.33\,\hbox {mm}$$ , while the mean surface registration error was $$0.35\,\hbox {mm}$$ .

### Conclusion

The method proposed in this paper achieves automatic markerless registration in multiple patient positions and guarantees registration accuracy inside the head. This method provides a new approach for establishing the spatial relationship between the image space and the robot space.

### Visualization of the cavum septi pellucidi, cavum Vergae, and cavum veli interpositi using magnetic resonance imaging.

 Related Articles

Visualization of the cavum septi pellucidi, cavum Vergae, and cavum veli interpositi using magnetic resonance imaging.

Surg Radiol Anat. 2017 Nov 01;:

Authors: Tsutsumi S, Ishii H, Ono H, Yasumoto Y

Abstract
PURPOSE: The morphology of the cavum septi pellucidi (CSP), cavum Vergae (CV), and cavum veli interpositi (CVI) has been infrequently explored with neuroimaging. The aim of the present study was to delineate these cavities using magnetic resonance (MR) imaging.
METHODS: A total of 71 patients were enrolled in the present study. Following initial examinations with conventional MR sequences, constructive interference in steady-state (CISS) sequence was performed in the coronal and sagittal sections for 60 and 11 patients, respectively.
RESULTS: The coronal CISS images at the level of the aqueduct showed two distinct morphologies of the CV roof, one formed by the fornices with varying degrees of conjugation and the other formed by the corpus callosum with completely separated fornices. Appearance of the CSP was classified into four distinct types. Furthermore, the CVI presented two distinct appearances.
CONCLUSIONS: Typically, the CSP, CV, and CVI present with asymptomatic conditions with morphological variabilities. Visualization of the CSP, CV, and CVI using the CISS sequences may be useful when managing lesions affecting these cavities.

PMID: 29094193 [PubMed - as supplied by publisher]

### Editorial Board

Publication date: October 2017
Source:Journal of Neuroradiology, Volume 44, Issue 6

### Incidence and Imaging Findings of Costal Cartilage Fractures in Patients with Blunt Chest Trauma: A Retrospective Review of 1461 Consecutive Whole-Body CT Examinations for Trauma.

Incidence and Imaging Findings of Costal Cartilage Fractures in Patients with Blunt Chest Trauma: A Retrospective Review of 1461 Consecutive Whole-Body CT Examinations for Trauma.

Authors: Nummela MT, Bensch FV, Pyhältö TT, Koskinen SK

Abstract
Purpose To assess the incidence of costal cartilage (CC) fractures in whole-body computed tomographic (CT) examinations for blunt trauma and to evaluate distribution of CC fractures, concomitant injuries, mechanism of injury, accuracy of reporting, and the effect on 30-day mortality. Materials and Methods Institutional review board approval was obtained for this retrospective study. All whole-body CT examinations for blunt trauma over 36 months were reviewed retrospectively and chest trauma CT studies were evaluated by a second reader. Of 1461 patients who underwent a whole-body CT examination, 39% (574 of 1461) had signs of thoracic injuries (men, 74.0% [425 of 574]; mean age, 46.6 years; women, 26.0% [149 of 574]; mean age, 48.9 years). χ(2) and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Interobserver agreement was calculated by using Cohen kappa values. Results A total of 114 patients (men, 86.8% [99 of 114]; mean age, 48.6 years; women, 13.2% [15 of 114]; mean age, 45.1 years) had 221 CC fractures. The incidence was 7.8% (114 of 1461) in all whole-body CT examinations and 19.9% (114 of 574) in patients with thoracic trauma. Cartilage of rib 7 (21.3%, 47 of 221) was most commonly injured. Bilateral multiple consecutive rib fractures occurred in 36% (41 of 114) versus 14% (64 of 460) in other patients with chest trauma (OR, 3.48; 95% CI: 2.18, 5.53; P < .0001). Hepatic injuries were more common in patients with chest trauma with CC fractures (13%, 15 of 114) versus patients with chest trauma without CC fractures (4%, 18 of 460) (OR, 3.72; 95% CI: 1.81, 7.64; P = .0001), as well as aortic injuries (n = 4 vs n = 0; P = .0015; OR, unavailable). Kappa value for interobserver agreement in detecting CC fractures was 0.65 (substantial agreement). CC fractures were documented in 39.5% (45 of 114) of primary reports. The 30-day mortality of patients with CC fractures was 7.02% (eight of 114) versus 4.78% (22 of 460) of other patients with chest trauma (OR, 1.50; 95% CI: 0.65, 3.47; P = .3371). Conclusion CC fractures are common in high-energy blunt chest trauma and often occur with multiple consecutive rib fractures. Aortic and hepatic injuries were more common in patients with CC fractures than in patients without CC fractures. (©) RSNA, 2017.

PMID: 29095676 [PubMed - as supplied by publisher]

### Performance of a Deep-Learning Neural Network Model in Assessing Skeletal Maturity on Pediatric Hand Radiographs.

Performance of a Deep-Learning Neural Network Model in Assessing Skeletal Maturity on Pediatric Hand Radiographs.

Authors: Larson DB, Chen MC, Lungren MP, Halabi SS, Stence NV, Langlotz CP

Abstract
Purpose To compare the performance of a deep-learning bone age assessment model based on hand radiographs with that of expert radiologists and that of existing automated models. Materials and Methods The institutional review board approved the study. A total of 14 036 clinical hand radiographs and corresponding reports were obtained from two children's hospitals to train and validate the model. For the first test set, composed of 200 examinations, the mean of bone age estimates from the clinical report and three additional human reviewers was used as the reference standard. Overall model performance was assessed by comparing the root mean square (RMS) and mean absolute difference (MAD) between the model estimates and the reference standard bone ages. Ninety-five percent limits of agreement were calculated in a pairwise fashion for all reviewers and the model. The RMS of a second test set composed of 1377 examinations from the publicly available Digital Hand Atlas was compared with published reports of an existing automated model. Results The mean difference between bone age estimates of the model and of the reviewers was 0 years, with a mean RMS and MAD of 0.63 and 0.50 years, respectively. The estimates of the model, the clinical report, and the three reviewers were within the 95% limits of agreement. RMS for the Digital Hand Atlas data set was 0.73 years, compared with 0.61 years of a previously reported model. Conclusion A deep-learning convolutional neural network model can estimate skeletal maturity with accuracy similar to that of an expert radiologist and to that of existing automated models. (©) RSNA, 2017.

PMID: 29095675 [PubMed - as supplied by publisher]

### Bone Marrow Metastases: T2-weighted Dixon Spin-Echo Fat Images Can Replace T1-weighted Spin-Echo Images.

Bone Marrow Metastases: T2-weighted Dixon Spin-Echo Fat Images Can Replace T1-weighted Spin-Echo Images.

Authors: Maeder Y, Dunet V, Richard R, Becce F, Omoumi P

Abstract
Purpose To test the potential of Dixon T2-weighted fat-only sequences to replace T1-weighted sequences for the detection of bone metastases, with the hypothesis that diagnostic performance with an alternative magnetic resonance (MR) imaging protocol (sagittal spin-echo Dixon T2-weighted fat-only and water-only imaging) would not be inferior to that with the standard protocol (sagittal spin-echo T1-weighted and spin-echo Dixon T2-weighted water-only imaging). Materials and Methods A total of 121 consecutive whole-spine MR imaging examinations (63 men; mean age ± standard deviation, 61.4 years ± 11.8) performed for suspected vertebral bone metastases were included in this retrospective, institutional review board-approved study. Quantitative image analysis was performed for 30 randomly selected spine levels. Qualitative analysis was performed separately by two musculoskeletal radiologists, who registered the number of metastases for each spine level. Areas under the curve with the protocols were compared on the basis of nonparametric receiver operating characteristic curve estimations by using a noninferiority test on paired data, with a best valuable comparator as a reference. Interobserver and interprotocol agreement was assessed by using κ statistics. Results Contrast-to-noise ratio was significantly higher on the alternative protocol images than on the standard protocol images (181.1 [95% confidence interval: 140.4, 221.7] vs 84.7 [95% confidence interval: 66.3, 103.1] respectively; P < .001). Diagnostic performance was not significantly inferior with the alternative protocol than with the standard protocol for both readers in a per-patient analysis (sensitivity, 97.9%-98.9% vs 93.6%-97.9%; specificity, 85.2%-92.6% vs 92.6%-96.3%; area under the curve, 0.92-0.96 vs 0.95, respectively; all P ≤ .02) and a per-spine level analysis (all P < .01). Interobserver and interprotocol agreement was good to very good (κ = 0.70-0.81). Conclusion Dixon T2-weighted fat-only and water-only imaging provide, in one sequence, diagnostic performance similar to that of the standard combination of morphologic sequences for the detection of probable spinal bone metastases, thereby providing an opportunity to reduce imaging time by eliminating the need to perform T1 sequences. (©) RSNA, 2017.

PMID: 29095674 [PubMed - as supplied by publisher]

### Intravoxel Incoherent Motion and Quantitative Non-Gaussian Diffusion MR Imaging: Evaluation of the Diagnostic and Prognostic Value of Several Markers of Malignant and Benign Breast Lesions.

Intravoxel Incoherent Motion and Quantitative Non-Gaussian Diffusion MR Imaging: Evaluation of the Diagnostic and Prognostic Value of Several Markers of Malignant and Benign Breast Lesions.

Authors: Iima M, Kataoka M, Kanao S, Onishi N, Kawai M, Ohashi A, Sakaguchi R, Toi M, Togashi K

Abstract

PMID: 29095673 [PubMed - as supplied by publisher]

### Biodiversity of bacteriophages infecting Lactococcus lactis starter cultures

Publication date: Available online 2 November 2017
Source:Journal of Dairy Science
Author(s): Joana Oliveira, Jennifer Mahony, Laurens Hanemaaijer, Thijs R.H.M. Kouwen, Douwe van Sinderen
In the current study, we characterized 137 Lactococcus lactis bacteriophages that had been isolated between 1997 and 2012 from whey samples obtained from industrial facilities located in 16 countries. Multiplex PCR grouping of these 137 phage isolates revealed that the majority (61.31%) belonged to the 936 group, with the remainder belonging to the P335 and c2 groups (23.36 and 15.33%, respectively). Restriction profile analysis of phage genomic DNA indicated a high degree of genetic diversity within this phage collection. Furthermore, based on a host-range survey of the phage collection using 113 dairy starter strains, we showed that the c2-group isolates exhibited a broader host range than isolates of the 936 and P335 groups.

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### Effect of supplemental yeast culture and dietary starch content on rumen fermentation and digestion in dairy cows

Publication date: Available online 2 November 2017
Source:Journal of Dairy Science
Author(s): A.L.G. Dias, J.A. Freitas, B. Micai, R.A. Azevedo, L.F. Greco, J.E.P. Santos
The objectives of this experiment were to evaluate the effect of feeding a culture of Saccharomyces cerevisiae on rumen metabolism and digestibility when cows are fed diets varying in starch content. Four lactating Holstein cows were assigned to a 4 × 4 Latin square design with a 2 × 2 factorial arrangement of treatments. Treatments were low starch (LS; 23% of diet DM) and no yeast culture (YC; LS-control), LS and 15 g of YC/d (LS-YC), high starch (HS; 29% of diet DM) and no YC (HS-control), and HS and 15 g of YC/d (HS-YC). Periods lasted 28 d, with the last 9 d for data collection. Days 20 to 24 were used to determine production, nutrient flow, and digestibility. On d 25, 3 kg of corn grain DM was placed in the rumen 1 h before the morning feeding, and yields of milk and milk components were measured after the challenge. Blood was sampled −1, 3, 7, and 11 h relative to the morning feeding on d 24 and 25. Rumen pH was measured continuously on d 24 and 25. Rumen papillae were collected on d 24 and 28 to quantify mRNA expression of select genes. Supplementing YC increased yields of milk (26.3 vs. 29.6 kg/d), energy-corrected milk (ECM; 26.5 vs. 30.3 kg/d), fat (0.94 vs. 1.08 kg/d), true protein (0.84 vs. 0.96 kg/d), and ECM/dry matter intake (1.15 vs. 1.30) compared with the control but did not affect dry matter intake (22.6 vs. 22.9 kg/d). Cows fed HS had increased milk true protein percentage (3.18 vs. 3.31%) and yield (0.87 vs. 0.94 kg/d) compared with cows fed LS. Feeding HS-YC increased the proportion of dietary N incorporated into milk true protein from 24.9% in the other 3 treatments to 29.6%. Feeding HS increased the concentration of propionate (21.7 vs. 32.3 mM) and reduced that of NH3-N (8.3 vs. 6.7 mg/dL) in rumen fluid compared with the control, and combining HS with YC in HS-YC tended to increase microbial N synthesis compared with LS-YC (275 vs. 322 g/d). Supplementing YC to cows fed HS reduced plasma haptoglobin and rumen lactate concentrations, increased mean rumen pH, reduced the time with pH <6.0, and prevented the decrease in rumen neutral detergent fiber digestion caused by HS. Cows fed HS had less total-tract digestion of organic matter (73.9 vs. 72.4%) because of reduced acid detergent fiber (57.6 vs. 51.7%) and neutral detergent fiber (60.9 vs. 56.7%) digestibility. Production performance after the challenge was similar to that before the challenge, and YC improved yield of ECM. After the challenge, supplementing YC tended to reduce rumen lactate concentration compared with the control and reduced haptoglobin in cows fed HS. Feeding HS but not YC increased expression in rumen papillae of genes for receptors (FFAR2 and FFAR3) and transporter (SLC16A3) of short-chain fatty acids but did not affect genes involved in transport of Na+/H+ or water or in inflammatory response. Supplementing YC to dairy cows improved lactation performance in diets containing low or high starch, and mechanisms might be partially attributed to improvements in rumen pH, digestion of fiber, microbial N synthesis, and reduction in acute phase response.

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### Survey of disbudding practice on Czech dairy farms

Publication date: Available online 2 November 2017
Source:Journal of Dairy Science
Author(s): S. Staněk, R. Šárová, E. Nejedlá, S. Šlosárková, O. Doležal
Disbudding is a routine practice in many dairy herds due to the effort to decrease the risk of injuries. Although the disbudding practice is regulated, it can vary among farms. The variation may be caused by many factors, such as herd size or type of breed, but also by farmers' perception of pain caused by disbudding. Hence, the aim of this study was to specify the disbudding practice on dairy farms in the Czech Republic and to assess these practices, including the use of pain mitigation medication, by breed, herd size, and sex of the disbudded calves. We analyzed data from 106 Czech dairy farms, which were collected by a trained interviewer at dairy meetings in 2014–2015. The farmers answered questions regarding the farm's basic characteristics, disbudding practice, and his/her attitude to the pain caused by disbudding. To test the influence of breed, herd size, and sex of disbudded calves on different variables, logistic regression models were used. Disbudding was performed in 92.5% of the surveyed farms; 63.3% of dairy calves were disbudded before 4 wk of age, and Czech Fleckvieh calves were 2.8 times more likely to be disbudded before 4 wk of age than Holstein calves. The hot-iron method was the most used method (69.4%). Calves were 4.5 times more likely to be disbudded by hot iron in herds where both heifers and bulls were disbudded than in herds where only heifers were disbudded. Most (>90%) surveyed farms did not use any pre- or post-procedure medication to mitigate the pain caused by disbudding. The disbudding procedure was performed mainly by farm personnel (94.9%), who were trained by a veterinarian or veterinary technician (46.9%) or by other farm personnel (37.8%) or were not trained (15.3%). Two-thirds of farmers observed behavioral changes in calves after disbudding. Most farmers estimated the pain caused by disbudding to be mild or moderate (20.4 or 45.9%, respectively) and 15.3% of farmers estimated it to be severe. Almost a quarter of interviewed farmers were unable to assess the duration of pain, 39.8% farmers estimated that the pain lasts only several minutes, and 20.4% estimated that the pain lasts up to 6 h. We detected a tendency that farmers of larger herds estimated pain duration to be shorter (odds ratio = 1.2). To improve calves' welfare, training is needed in disbudding practice, focusing on the advantage of pain mitigation.

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### Feed substrates influence biofilm formation on reverse osmosis membranes and their cleaning efficiency

Publication date: Available online 2 November 2017
Source:Journal of Dairy Science
Author(s): Sowmya Marka, Sanjeev Anand
The dairy industry is increasingly using reverse osmosis (RO) membranes for concentration of various fluid feed materials such as whey and ultrafiltration (UF) permeate. This study compared the effect of UF permeate and whey on membrane biofilm formation. A Bacillus sp., previously isolated in our laboratory from a cleaning-resistant membrane biofilm, was used to develop 48-h-old static biofilms on RO membrane pieces, using the different feed substrates (UF permeate, whey, and an alternating whey/UF feed). Biofilms were analyzed for viable counts by the swab technique, and we used scanning electron and atomic force microscopy for microstructure imaging. The membrane cleaning process included 6 sequential steps. We observed differences in the resistance pattern of the 3 types of biofilms to the typical cleaning process. The mean pretreatment counts of the 48-h UF permeate biofilms were 5.39 log cfu/cm2, much higher than the whey biofilm counts of 3.44 log, and alternating whey/UF biofilm counts of 4.54 log. After a 6-step cleaning cycle, we found 2.54 log survivors of the Bacillus isolate on UF biofilms, whereas only 1.82 log survivors were found in whey biofilm, and 2.14 log survivors on whey/UF permeate biofilms. In conclusion, the UF permeate biofilms was more resistant to the biofilm cleaning process compared with the whey or whey/UF permeate biofilms. Scanning electron micrographs showed different microstructures of biofilms based on the type of feed. For UF permeate and whey/UF permeate biofilms, bacilli were present in multilayers of cells in aggregates or irregular clusters with foulant layers. In contrast, those in whey biofilms were in monolayers, with a smoother, flatter appearance. Atomic force microscopy analysis indicated that UF permeate biofilms had the greatest surface roughness among the biofilms, reflecting intensified bacterial colonization. The biofilm micro- and nanostructure variations for the 2 feed substrates and their combination may have resulted in differences in their resistance to the cleaning process.

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### Effect of post-pasteurization contamination on fluid milk quality

Publication date: Available online 2 November 2017
Source:Journal of Dairy Science
Author(s): Nicole H. Martin, Kathryn J. Boor, Martin Wiedmann
Fluid milk quality in the United States has improved steadily over the last 2 decades, in large part due to the reduction in post-pasteurization contamination (PPC). Despite these improvements, some studies suggest that almost 50% of fluid milk still shows evidence of PPC with organisms that are able to grow at 6°C, even though PPC may be much less frequent in some facilities. Several gram-negative bacteria, when introduced as PPC, can grow rapidly at refrigeration temperatures around 6°C and can lead to bacterial levels above 20,000 cfu/mL (the regulatory limit for bacterial numbers in fluid milk in the United States) and spoilage that can be detected sensorially within 7 to 10 d of processing. Importantly, however, storage temperature can have a considerable effect on microbial growth, and fluid milk stored at 4°C and below may show considerably delayed onset of microbial growth and spoilage compared with samples stored at what may be considered mild abuse (6°C and above). Notable organisms that cause PPC and grow at refrigeration temperatures include psychrotolerant Enterobacteriaceae and coliforms, as well as Pseudomonas. These organisms are known to produce a variety of enzymes that lead to flavor, odor, and body defects that can ultimately affect consumer perception and willingness to buy. Detecting PPC in high temperature, short time, freshly pasteurized fluid milk can be challenging because PPC often occurs sporadically and at low levels. Additionally, indicator organisms typically used in fluid milk (i.e., coliforms) have been shown to represent only a fraction of the total PPC. Recent studies indicate that coliforms account for less than 20% of the total gram-negative organisms introduced into fluid milk after pasteurization. In contrast, Pseudomonas, which is not a coliform and therefore is not detected using coliform media, is the most commonly isolated genus in PPC fluid milk. To reduce PPC, processors must (1) use testing methods that can detect both coliforms and non-coliform gram-negatives (i.e., Pseudomonas) to understand true contamination rates and patterns, and (2) establish cleaning and sanitation protocols and employee and management behaviors that target persistent and transient PPC organisms.

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### The effects of increasing amounts of milk replacer powder added to whole milk on mammary gland measurements using ultrasound in dairy heifers

Publication date: Available online 2 November 2017
Source:Journal of Dairy Science
Author(s): P.M. Furini, R.A. Azevedo, S.R.A. Rufino, F.S. Machado, M.M. Campos, L.G.R. Pereira, T.R. Tomich, B.C. Carvalho, G.B. Santos, S.G. Coelho
The aim of this study was to determine the effect of increasing total solids (TS) in the liquid diet during the preweaning phase on mammary gland development in dairy heifers. The increase in TS was obtained with the addition of milk replacer powder to whole milk. Crossbreed Holstein-Gyr heifers (n = 60) were distributed in 4 treatments with different TS concentrations: 13.5% (n = 15), 16.1% (n = 15), 18.2% (n = 15), and 20.4% (n = 15). The liquid diets were provided from 5 to 55 d of age. From 56 to 59 d of age, the total amount of liquid feed was reduced by half. Heifers were weaned at 60 d and monitored until 90 d of age. Ultrasound mammary gland evaluations were performed weekly between 5 to 11 wk of age, using a B-mode ultrasound equipped with microconvex transducer at a frequency of 6 MHz. In those same weeks, the manual palpation of mammary parenchyma (PAR) was performed. Increased TS concentration of liquid diet during the preweaning period increased body weight of heifers, but did not alter PAR growth and the deposition of adipose tissue in the mammary gland evaluated by ultrasonography. The oval-shaped structure of PAR was altered after 2 mo of age. In the evaluated period, PAR growth was isometric with respect to the body growth rate. Palpation scoring of PAR had a strong correlation with the ultrasound evaluation of the PAR.

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### Short communication: Heat treatment and souring do not affect milk estrone and 17β-estradiol concentrations

Publication date: Available online 2 November 2017
Source:Journal of Dairy Science
Author(s): T. Snoj, M.C. Zuzek, N. Cebulj-Kadunc, G. Majdic
The aim of our study was to establish whether heat treatment and souring of milk affect its estrone (E1) and 17β-estradiol (E2) concentrations. Milk samples were collected from 10 Holstein cows in late pregnancy. Concentrations of E1 and E2 were measured in milk samples that were previously heated to 70 and 95°C for 5 min. Additionally, E1 and E2 concentrations were determined in the same milk samples after 2 d of spontaneous souring at room temperature, and these samples were compared with E1 and E2 levels in raw, unprocessed milk. Concentrations of both hormones were determined by commercial ELISA kits. Concentrations of E1 in unprocessed and processed milk (milk heated to 70 and 95°C and soured milk) were (mean ± SE) 47.25 ± 4.16, 44.84 ± 3.47, 41.00 ± 4.55, and 44.92 ± 3.91 pg/mL, respectively. Concentrations of E2 in the same milk samples were 36.11 ± 10.01, 32.46 ± 9.88, 31.78 ± 9.56, and 31.43 ± 8.00 pg/mL, respectively. Concentrations of E1 and E2 in heat-treated milk did not differ significantly from those in unprocessed milk. Similarly, E1 and E2 concentrations in soured milk did not differ significantly from those in unprocessed milk samples. These results indicate that E1 and E2 are stable in milk and that milk processing (heating and souring) does not influence their degradation. Therefore, E1 and E2 concentrations are expected to be similar between commercial full-fat milk and the raw milk from which it was produced.

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### Effects of supplementing yeast culture to diets differing in starch content on performance and feeding behavior of dairy cows

Publication date: Available online 2 November 2017
Source:Journal of Dairy Science
Author(s): A.L.G. Dias, J.A. Freitas, B. Micai, R.A. Azevedo, L.F. Greco, J.E.P. Santos
The objectives were to evaluate the effects of a culture of Saccharomyces cerevisiae (YC) on lactation performance of cows fed diets differing in starch content. Fifty-six Holstein cows at 42 d postpartum were blocked by parity and milk production and randomly assigned to 1 of 4 treatments, low starch (23% diet DM) and no YC (LS-control), low starch and 15 g/d of YC (LS-YC), high starch (29% diet DM) and no YC (HS-control), and high starch and 15 g/d of YC (HS-YC). The experiment lasted 14 wk. Blood was sampled twice weekly during the first 5 wk in the experiment. Feeding behavior was evaluated in 2 consecutive days when cows were 33 d in the experiment. On d 92 in the experiment, cows were challenged with 3 kg of corn grain DM immediately before the morning feeding. Blood was sampled in the first 12 h after the challenge. Rumen fluid was collected 5 h after the challenge, and pH, ammonia N, short-chain fatty acids, and lactate concentrations were quantified. Lactation performance was measured daily before and after the challenge. Supplementation with YC increased yields of 3.5% fat-corrected milk and energy-corrected milk by 2.2 and 2.0 kg/d, and the increments were observed in both low- and high-starch diets. Feeding HS tended to decrease milk fat content (LS = 3.88 vs. HS = 3.73%), but increased concentration (LS = 2.87 vs. HS = 3.00%) and yield (LS = 1.11 vs. HS = 1.20 kg/d) of milk true protein. Feeding YC increased yields of fat and true protein in milk by 100 and 60 g/d. Energy balance, body weight, and feed efficiency did not differ with treatments. Feeding HS reduced eating time (LS = 177 vs. HS = 159 min/12 h) and intermeal interval (LS = 103 vs. HS = 82 min), but tended to increase eating rate (LS = 139 vs. HS = 150 g/min). Interactions were detected between level of starch and YC for ruminating time, meal duration, and meal size because within LS, feeding YC increased ruminating time 23 min/12 h, but reduced meal duration 6 min/meal and meal size 0.7 kg/meal. Concentrations of glucose in plasma increased (LS = 62.1 vs. HS = 63.8 mg/dL), whereas those of urea N decreased (LS = 10.1 vs. HS = 9.4 mg/dL) with feeding HS compared with LS in the first 5 wk in the experiment, and the same responses were observed after the challenge with corn grain. After the challenge, rumen pH was less and short-chain fatty acid concentrations were greater in cows fed HS compared with those fed LS; however, supplementing YC to high-starch diets increased rumen pH (HS-control = 5.72 vs. HS-YC = 6.12) and reduced concentrations of lactate in rumen fluid (HS-control = 7.72 vs. HS-YC = 1.33 mM) and haptoglobin in plasma 28%. Feeding YC improved lactation performance irrespective of the level of dietary starch and reduced the risk of subacute rumen acidosis induced by a grain challenge when cows were fed a high-starch ration.

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### Using models to establish the financially optimum strategy for Irish dairy farms

Publication date: Available online 2 November 2017
Source:Journal of Dairy Science
Author(s): E. Ruelle, L. Delaby, M. Wallace, L. Shalloo
Determining the effect of a change in management on farm with differing characteristics is a significant challenge in the evaluation of dairy systems due to the interacting components of complex biological systems. In Ireland, milk production is increasing substantially following the abolition of the European Union milk quota regime in 2015. There are 2 main ways to increase the milk production on farm (within a fixed land base): either increase the number of animals (thus increasing the stocking rate) or increase the milk production per animal through increased feeding or increased lactation length. In this study, the effect of increased concentrate feeding or an increase in grazing intensity was simulated to determine the effect on the farm system and its economic performance. Four stocking rates (2.3, 2.6, 2.9, and 3.2 cow/ha) and 5 different concentrate supplementation strategies (0, 180, 360, 600, and 900 kg of dry matter/lactation) resulting in 20 different scenarios were evaluated across different milk, concentrate, and silage purchase prices. Each simulation was run across 10 yr of meteorological data, which had been recorded over the period 2004 to 2013. Three models—the Moorepark and St Gilles grass growth model, the pasture-based herd dynamic milk model, and the Moorepark dairy systems model—were integrated and applied to simulate the different scenarios. Overall, this study has demonstrated that the most profitable scenario was a stocking rate of 2.6 cow/ha with a concentrate supplementation of 600 kg of dry matter/cow. The factor that had the greatest influence on profitability was variability of milk price.

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### Predicting manure volatile solid output of lactating dairy cows

Publication date: Available online 2 November 2017
Source:Journal of Dairy Science
Author(s): J.A.D.R.N. Appuhamy, L.E. Moraes, C. Wagner-Riddle, D.P. Casper, E. Kebreab
Organic matter (OM) in livestock manure consisting of biodegradable and nonbiodegradable fractions is known as volatile solids (VS). According to the Intergovernmental Panel on Climate Change (IPCC) Tier 2 guidelines, methane produced by stored manure is determined based on VS. However, only biodegradable OM generates methane production. Therefore, estimates of biodegradable VS (dVS; dVS = VS − lignin) would yield better estimates of methane emissions from manure. The objective of the study was to develop mathematical models for estimating VS and dVS outputs of lactating dairy cows. Dry matter intake, dietary nutrient contents, milk yield and composition, body weight, and days in milk were used as potential predictor variables. Multicollinearity, model simplicity, and random study effects were taken into account during model development that used 857 VS and dVS measurements made on individual cows (kg/cow per day) from 43 metabolic trials conducted at the USDA Energy and Metabolism laboratory in Beltsville, Maryland. The new models and the IPCC Tier 2 model were evaluated with an independent data set including 209 VS and dVS measurements (kg/cow per day) from 2 metabolic trials conducted at the University of California, Davis. Organic matter intake (kg/d) and dietary crude protein and neutral detergent fiber contents (% of dry matter) were significantly associated with VS. A new model including these variables fitted best to data. When evaluated with independent data, the new model had a root mean squared prediction error as a percentage of average observed value (RMSPE) of 12.5%. Mean and slope biases were negligible at <1% of total prediction bias. When energy digestibility of the diet was assumed to be 67%, the IPCC Tier 2 model had a RMSPE of 13.7% and a notable mean bias for VS to be overpredicted by 0.4 kg/cow per day. A separate model including OM intake as well as dietary crude protein and neutral detergent fiber contents as predictor variables fitted best to dVS data and performed well on independent data (RMSPE = 12.7%). The Cornell Net Carbohydrate and Protein System model relying on fat-corrected milk yield and body weight more successfully predicted dry matter intake (DMI; RMSPE = 14.1%) than the simplified (RMSPE = 16.9%) and comprehensive (RMSPE = 23.4%) models to predict DMI in IPCC Tier 2 methodology. New models and the IPCC Tier 2 model using DMI from the Cornell Net Carbohydrate and Protein System model predicted VS (RMSPE = 17.7–19.4%) and dVS (RMSPE = 20%) well with small systematic bias (<10% of total bias). The present study offers empirical models that can accurately predict VS and dVS of dairy cows using routinely available data in dairy farms and thereby assist in efficiently determining methane emissions from stored manure.

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### Comparison of DNA quality in raw and reconstituted milk during sterilization

Publication date: Available online 2 November 2017
Source:Journal of Dairy Science
Author(s): J. Liao, L. Yang, A.M. Sheppard, Y.F. Liu
Responses to milk sterilization are usually evaluated only in terms of physicochemical properties and microbial safety, thus undervaluing the importance of DNA quality in an authentication process by methods based on PCR. Because DNA is a heat-sensitive molecule, we hypothesized that the heating process may impair the detection or quantification of DNA in raw fresh milk (FM) or reconstituted milk (RM), and that differences in DNA quality might exist between FM and RM. We thus investigated the effects of sterilization on the quality of DNA extracted from FM or RM; differences in DNA quality between FM and RM were also evaluated. The quality of extracted DNA from FM or RM was assessed by the specific detection of FM or RM composition in goat milk mixtures using primers targeting the bovine 12S gene, as well as by monitoring DNA yield, purity, ratio of mitochondrial (mt) to nuclear (n) DNA, and the level of DNA degradation. Polymerase chain reaction readily detected both untreated and heat-treated FM or RM in cow-goat milk mixtures, and gave a good sensitivity threshold (0.1%) under all sterilization conditions. The DNA yield and mtDNA:nDNA ratio of FM and RM varied significantly during the sterilization process. These results demonstrated that the sterilization altered the quantification of DNA in FM or RM during sterilization, but DNA could still be readily detected in sterilized FM or RM by PCR. Furthermore, we noted significant differences in DNA integrity, yield, and mtDNA:nDNA ratio between FM and RM during sterilization, which may have potential as a means to distinguish FM and RM.

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### Short communication: Cold atmospheric plasma inactivation of Prototheca zopfii isolated from bovine milk

Publication date: Available online 2 November 2017
Source:Journal of Dairy Science
Author(s): E. Tyczkowska-Sieron, J. Markiewicz, B. Grzesiak, H. Krukowski, A. Glowacka, J. Tyczkowski
Mastitis is a serious bovine diseases that can be caused by Prototheca zopfii, yeast-like algae belonging to the family Chlorellaceae. The substantial economic losses and health damage associated with bovine mastitis emphasize the need to develop effective strategies aimed at control of the infection. Unfortunately, P. zopfii is highly resistant to most common antibacterial and antifungal agents, as well as to heat treatment. We report here the first attempt to use cold atmospheric plasma to inactivate this pathogen. We studied 20 strains of P. zopfii isolated from milk samples taken from cows with clinical or subclinical mastitis. The studies confirmed the high level of resistance of P. zopfii to typical antifungal agents, such as voriconazole, fluconazole, amphotericin B, caspofungin, anidulafungin, and micafungin. In contrast, each of the strains revealed high susceptibility to cold atmospheric plasma, >2-fold higher compared with a reference strain of Candida albicans. The obtained results are promising and open up a new approach in the fight against P. zopfii.

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### Alterations in ruminal bacterial populations at induction and recovery from diet-induced milk fat depression in dairy cows

Publication date: Available online 2 November 2017
Source:Journal of Dairy Science
Author(s): D.W. Pitta, N. Indugu, B. Vecchiarelli, D.E. Rico, K.J. Harvatine
Ten ruminally cannulated Holstein cows were used in a crossover design that investigated changes in ruminal bacterial populations in response to induction and recovery from diet-induced milk fat depression (MFD). Further, the effect on the ruminal microbiota of the cows with diet-induced milk fat depression inoculated with rumen contents from non-milk fat-depressed donor cows was evaluated. Milk fat depression was induced during the first 10 d of each period by feeding a low-fiber, high-starch, and high-polyunsaturated fatty acid diet (26.1% neutral detergent fiber, 28.1% starch, 5.8% total fatty acids, and 1.9% C18:2), resulting in a 30% decrease in milk fat yield. Induction was followed by a recovery phase, where all cows were switched to a high-fiber, low-starch, and low-polyunsaturated fatty acid diet (31.8% neutral detergent fiber, 23% starch, 4.2% total fatty acids, and 1.2% C18:2) and were allocated to (1) control (no inoculation) or (2) ruminal inoculation with donor cow digesta (8 kg/d for 6 d). Ruminal samples were collected at the end of induction (d 10) and during recovery (d 13, 16, and 28), separated to solid and liquid fractions, extracted for DNA, PCR- amplified for the V1-V2 region of the 16S rRNA gene, and analyzed for bacterial diversity. Results indicated that bacterial communities were different between fractions. In each fraction, differences were significant between the induction (d 10) and recovery (d 13, 16, and 28) periods; however, differences were less apparent with time during the recovery period. The MFD (d 10) was typified by a reduction in the relative sequence abundance of Bacteroidetes and an increase in the relative sequence abundance of Firmicutes and Actinobacteria across both fractions. At the genus level, relative sequence abundance of unclassified Lachnospiraceae, Butyrivibrio, Bulleidia, and Coriobacteriaceae were higher on d 10 and were positively correlated with trans-10,cis-12 CLA and the trans-10 isomer, suggesting their potential role in altered biohydrogenation reactions. A switch to the recovery diet resulted in a sharp increase in the Bacteroidetes lineages and a decrease in Firmicutes members on d 13; however, this shift appears to stabilize by d 28, indicating the restoration process for ruminal bacteria from an altered state is gradual and complex. Inoculation of 10% of rumen contents from non-MFD donor cows to MFD cows revealed this procedure had transient effects on only a few bacterial populations, and such effects disappeared after d 16 following cessation of inoculation. It can be concluded that alterations in milk FA profiles at induction are preceded by microbial alterations in the rumen driven by dietary changes.

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### Association of immediate postpartum plasma calcium concentration with early-lactation clinical diseases, culling, reproduction, and milk production in Holstein cows

Publication date: Available online 2 November 2017
Source:Journal of Dairy Science
Author(s): R.C. Neves, B.M. Leno, M.D. Curler, M.J. Thomas, T.R. Overton, J.A.A. McArt
The objective of this study was to evaluate the association of postpartum plasma Ca concentration with early-lactation disease outcomes, culling within 60 d in milk, pregnancy to first service, and milk production. A total of 1,453 cows from 5 commercial dairy farms in New York State were enrolled in a prospective cohort study from February to November 2015. Blood samples were collected within 12 h of parturition, and plasma was submitted to a diagnostic laboratory for total Ca measurement. Early-lactation disease, reproductive performance, and milk production from Dairy Herd Improvement Association (DHIA) test-day data were compiled from each farm's management software. Multivariable Poisson regression models were built to evaluate the association of plasma Ca with the risks of retained placenta (RP), metritis, displaced abomasum (DA), clinical mastitis, culling within 60 d in milk, and pregnancy to first service. Repeated-measures ANOVA were used to evaluate the association of Ca at parturition with milk production across the first 9 DHIA tests. Herd was considered a random effect in all models. Primiparous cows were modeled separately from multiparous cows if differential responses were observed. Calcium was not associated with the risk of RP, metritis, clinical mastitis, or pregnancy to first service in primiparous or multiparous cows. For multiparous cows only, higher Ca concentration tended to be associated with increased culling within the first 60 d in milk. Multiparous cows with Ca ≤1.85 mmol/L had an increased risk of being diagnosed with a DA compared with cows with Ca >1.85 mmol/L. For the milk production models, Ca was not associated with the amount of milk produced within the first 9 DHIA tests in primiparous cows; however, multiparous cows with Ca ≤1.95 mmol/L produced, on average, 1.1 kg more milk per day across the 9 DHIA tests than their multiparous counterparts with Ca >1.95 mmol/L. Our results indicate that plasma Ca concentration measured within 12 h of parturition is a poor predictor of early-lactation health outcomes. Reduced Ca concentration in the immediate postpartum period was associated with higher milk production in multiparous cows. From these results, we caution that studies attempting to categorize subclinical hypocalcemia based on a single sample in the immediate postpartum period could misclassify the disorder.

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### Effect of milk replacer feeding rate, age at weaning, and method of reducing milk replacer to weaning on digestion, performance, rumination, and activity in dairy calves to 4 months of age

Publication date: Available online 2 November 2017
Source:Journal of Dairy Science
Author(s): T.S. Dennis, F.X. Suarez-Mena, T.M. Hill, J.D. Quigley, R.L. Schlotterbeck, L. Hulbert

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### A mathematical model of the interaction between bovine blastocyst developmental stage and progesterone-stimulated uterine factors on differential embryonic development observed on Day 15 of gestation

Publication date: Available online 2 November 2017
Source:Journal of Dairy Science
Author(s): Paul R. Shorten, Anita M. Ledgard, Martyn Donnison, Peter L. Pfeffer, Robin M. McDonald, Debra K. Berg
A complex interaction between the developing bovine embryo and the growth potential of the uterine milieu it inhabits results in an embryo capable of developing past the maternal recognition stage and on to a successful pregnancy. Previously, we observed variation in the lengths of embryos recovered 8 d after bulk transfer of Day 7 in vitro-produced (IVP) blastocysts into the same uterus. Potential causes of the differential embryonic growth were examined and modeled using 2 rounds of bulk (n = 4–6) IVP transfers and recovery of these embryos 8 d later. Morphological and gene expression measurements of the embryos were determined and the progesterone concentration of the cows was measured throughout the reproductive cycle as a reflection of the status of the uterine environment. These data were used to develop and evaluate a model that describes the interaction between the uterine environment and the growth rate of the developing embryo. Expression of 6 trophectoderm genes (IFNT, TKDP1, PAG11, PTGS2, DKK1, and PDPN) was correlated with conceptus length. The model determined that if the embryo develops to blastocyst stage, the uterine environment, driven by progesterone, is a more important component than blastocyst size in the stimulation of embryonic growth rate to ensure adequate interferon tau (IFNT) for pregnancy recognition. We detected an effect of Day 7 progesterone on the expression of all 6 genes, embryonic disc size, and trophectoderm length on Day 15. We also found effects of embryo transfer size on trophectoderm length and expression of IFNT and PAG11 on Day 15. Lower energy balance over the period from transfer to recovery was associated with reduced embryo growth to Day 15, and this effect was independent of progesterone. Energy balance also affected expression of PDPN and TKDP1 on Day 15. We observed an effect of energy balance from transfer to recovery on embryo survival in cows with partial embryo losses, where embryo factors dominate embryo survival, with cows with greater energy balance having lower embryo losses. This effect was independent of energy balance 40 d before transfer and suggests that energy balance has direct, immediate effects on the embryo and maternal environment during this period. Furthermore, energy balance effects on embryo survival in cows with partial embryo losses were largely mediated by expression of TKDP1, PAG11, and PDPN. These results provide candidate signaling pathways for the effect of progesterone and energy balance on embryo growth and survival.

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### Complexes of lutein with bovine and caprine caseins and their impact on lutein chemical stability in emulsion systems: Effect of arabinogalactan

Publication date: Available online 2 November 2017
Source:Journal of Dairy Science
Author(s): A. Mora-Gutierrez, R. Attaie, M.T. Núñez de González, Y. Jung, S. Woldesenbet, S.A. Marquez
Lutein is an important xanthophyll carotenoid with many benefits to human health. Factors affecting the application of lutein as a functional ingredient in low-fat dairy-like beverages (pH 6.0–7.0) are not well understood. The interactions of bovine and caprine caseins with hydrophobic lutein were studied using UV/visible spectroscopy as well as fluorescence. Our studies confirmed that the aqueous solubility of lutein is improved after binding with bovine and caprine caseins. The rates of lutein solubilization by the binding to bovine and caprine caseins were as follows: caprine αS1-II-casein 34%, caprine αS1-I-casein 10%, and bovine casein 7% at 100 μM lutein. Fluorescence of the protein was quenched on binding supporting complex formation. The fluorescence experiments showed that the binding involves tryptophan residues and some nonspecific interactions. Scatchard plots of lutein binding to the caseins demonstrated competitive binding between the caseins and their sites of interaction with lutein. Competition experiments suggest that caprine αS1-II casein will bind a larger number of lutein molecules with higher affinity than other caseins. The chemical stability of lutein was largely dependent on casein type and significant increases occurred in the chemical stability of lutein with the following pattern: caprine αS1-II-casein > caprine αS1-I-casein > bovine casein. Addition of arabinogalactan to lutein-enriched emulsions increases the chemical stability of lutein-casein complexes during storage under accelerated photo-oxidation conditions at 25°C. Therefore, caprine αS1-II-casein alone and in combination with arabinogalactan can have important applications in the beverage industry as carrier of this xanthophyll carotenoid (lutein).

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### Mild and severe udder cleft dermatitis—Prevalence and risk factors in Swedish dairy herds

Publication date: Available online 2 November 2017
Source:Journal of Dairy Science
Author(s): L. Ekman, A.-K. Nyman, H. Landin, U. Magnusson, K. Persson Waller
Udder cleft dermatitis (UCD) is an inflammatory skin condition affecting the anterior parts of the udder of dairy cows. The lesions may present as mild or severe skin lesions and have been associated with mastitis and digital dermatitis. The full etiology and pathogenesis are not understood and no large-scale studies have investigated prevalence and risk factors. Therefore, the main objectives of the study were to investigate the prevalence of mild and severe UCD in Swedish dairy herds and to identify risk factors associated with such lesions. We also wanted to investigate risk factors for all cases of UCD and to determine whether UCD increases the risk for mastitis and culling. A random sample of 100 freestall dairy herds were included in the study, and each herd was visited once. Cows were registered as having no, mild, or severe UCD. Additional cow and herd data were obtained via observations, interviews, and the Swedish Official Milk Recording Scheme. The data were analyzed using logistic regression models to identify risk factors for mild and severe UCD. In total, data from 3,479 cows in 99 herds were analyzed. The prevalence of mild and severe UCD was 19 and 9%, respectively. Lesions were found in 98 of 99 herds but the within-herd prevalence of mild (0–43%) and severe (0–33%) UCD varied notably between herds. Breed (Swedish Red compared with Swedish Holstein), certain udder conformation traits, and higher parity were risk factors associated with increased risk of UCD. In addition, cows with hock lesions and cows in herds with high incidence of culling due to hoof and leg diseases had a higher risk for mild UCD. More days in milk and high milk yield were cow-related risk factors associated with severe UCD. Three housing-related factors (shorter cubicles, mattress as cubicle base, and cubicles installed before 2001 compared with 2001–2005), a high incidence of veterinary-treated clinical mastitis and culling due to udder diseases, and a low incidence of culling of first-parity cows in early lactation were herd-related risk factors associated with increased risk for severe UCD. In addition, cows in herds with a high proportion of heifers older than 17 mo that were not inseminated were associated with lower risk of all UCD. Finally, UCD was not associated with the outcomes milk somatic cell count, veterinary-treated clinical mastitis, or culling in the multivariable analyses. The etiology of UCD is most likely multifactorial, involving udder conformation traits and other cow-related risk factors as well as herd-related risk factors. The high prevalence of severe UCD lesions in Swedish dairy cows emphasizes the need for preventive measures and efficient treatments.

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### Genetic analysis of efficiency traits in Austrian dairy cattle and their relationships with body condition score and lameness

Publication date: Available online 2 November 2017
Source:Journal of Dairy Science
Author(s): A. Köck, M. Ledinek, L. Gruber, F. Steininger, B. Fuerst-Waltl, C. Egger-Danner
This study is part of a larger project whose overall objective was to evaluate the possibilities for genetic improvement of efficiency in Austrian dairy cattle. In 2014, a 1-yr data collection was carried out. Data from 6,519 cows kept on 161 farms were recorded. In addition to routinely recorded data (e.g., milk yield, fertility, disease data), data of novel traits [e.g., body weight (BW), body condition score (BCS), lameness score, body measurements] and individual feeding information and feed quality were recorded on each test-day. The specific objective of this study was to estimate genetic parameters for efficiency (related) traits and to investigate their relationships with BCS and lameness in Austrian Fleckvieh, Brown Swiss, and Holstein cows. The following efficiency (related) traits were considered: energy-corrected milk (ECM), BW, dry matter intake (DMI), energy intake (INEL), ratio of milk output to metabolic BW (ECM/BW0.75), ratio of milk output to DMI (ECM/DMI), and ratio of milk energy output to total energy intake (LE/INEL, LE = energy in milk). For Fleckvieh, the heritability estimates of the efficiency (related) traits ranged from 0.11 for LE/INEL to 0.44 for BW. Heritabilities for BCS and lameness were 0.19 and 0.07, respectively. Repeatabilities were high and ranged from 0.30 for LE/INEL to 0.83 for BW. Heritability estimates were generally lower for Brown Swiss and Holstein, but repeatabilities were in the same range as for Fleckvieh. In all 3 breeds, more-efficient cows were found to have a higher milk yield, lower BW, slightly higher DMI, and lower BCS. Higher efficiency was associated with slightly fewer lameness problems, most likely due to the lower BW (especially in Fleckvieh) and higher DMI of the more-efficient cows. Body weight and BCS were positively correlated. Therefore, when selecting for a lower BW, BCS is required as additional information because, otherwise, no distinction between large animals with low BCS and smaller animals with normal BCS would be possible.

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### Purpose of Review

Stage IV melanoma is an aggressive malignancy with the median survival historically being less than 1 year. Approximately 50% of melanomas contain an activating mutation in a targetable component of the mitogen-activated protein kinase (MAPK) pathway called BRAF. Melanoma growth is modulated by activating and inhibitory immune checkpoints. Advances in the management of distantly metastatic and stage III melanoma are reviewed.

### Recent Findings

Targeting BRAF signaling in patients with metastatic V600 BRAF mutated melanoma and modulation of immune checkpoints confer survival benefit to patients with distantly metastatic melanoma. CTLA-4 blockade confers survival benefit as adjuvant therapy in patients with stage III melanoma.

### Summary

The efficacy of systemic therapy to treat stage IV melanoma is improving. Advances are being made to improve efficacy of adjuvant therapy for high-risk stage III melanoma patients and to determine optimal surgical management of patients with sentinel lymph node-positive melanoma.

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### Introduction

Post hoc analyses (two single-arm studies) were conducted to determine the impact of once-monthly injection of paliperidone palmitate on functioning in adult patients with schizophrenia in the Asia–Pacific region.

### Methods

Study 1 enrolled hospitalized patients with acute exacerbation of schizophrenia, and study 2 enrolled patients with recently diagnosed schizophrenia unsatisfactorily treated with oral antipsychotics. Patients received paliperidone palmitate, 150 mg eq. on day 1, 100 mg eq. on day 8, then once monthly (50–150 mg eq.) (study 1, days 36 and 64; study 2, 18 months). Functional status was evaluated by Personal and Social Performance score in both studies and employment only in study 2.

### Results

In study 1, 54 of 184 patients (29.4%) with an unfavorable level of functioning at the baseline improved to a favorable level (Personal and Social Performance score greater than 70) at day 92. This improvement was significantly greater among patients with recently diagnosed schizophrenia (5 years or less) compared with patients with chronic schizophrenia (more than 5 years): 40% versus 22% (p < 0.0001). Improvements were observed in all four domains (socially useful activities, personal and social relationships, self-care, disturbing/aggressive behavior). In study 2, significant (p < 0.0001) improvement in functioning was observed at all visits, beginning at week 5. Almost half (48.7%, 247/507) of patients showed clinically meaningful improvement in functioning (i.e., 10 point or greater increase in Personal and Social Performance score) at month 18. The proportion of patients fully/partially employed was greater at all postbaseline visits (134 of 280, 47.9%, at month 18) as compared with the baseline.

### Conclusion

Functioning, including employment, was improved after short-term, once-monthly paliperidone palmitate injection, and was sustained to 18 months in Asia–Pacific patients with schizophrenia.

### Funding

Janssen-Cilag Asia–Pacific Medical Affairs.

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### Introduction

This study aimed to investigate the influence of three muscle relaxants on intraocular pressure (IOP), ocular pulse amplitude (OPA), and vis-à-tergo (VAT) in patients undergoing penetrating keratoplasty (PKP) under general anesthesia.

### Methods

Ninety-five patients undergoing PKP were included in this prospective single-center interventional study. IOP and OPA were measured with a dynamic contour tonometer before and 5 min after onset of general anesthesia. Mivacurium (n = 30), atracurium (n = 35), and rocuronium (n = 30) were administered as nondepolarizing muscle relaxants. VAT was assessed 15 min after surgery had begun.

### Results

When mivacurium was used, IOP decreased by 2.2 mmHg [standard deviation (SD) ±2.2 mmHg; p < 0.001]. Atracurium decreased the IOP by an average of 5.8 mmHg (SD ±1.8 mmHg; p < 0.001) and rocuronium caused an IOP reduction of 7.2 mmHg (SD ±2 mmHg; p < 0.001). The relative IOP decrease was 12% with mivacurium, 29% with atracurium, and 37% with rocuronium (p < 0.001). OPA decreased by 0.6 mmHg with mivacurium (SD ±0.6 mmHg; 26%; p < 0.001), 1.3 mmHg with atracurium (SD ±1.3 mmHg; 40%; p < 0.001), and 1.2 mmHg with rocuronium (SD ±0.7 mmHg; 42%; p < 0.001). The relative OPA decrease was 26% with mivacurium, 40% with atracurium, and 42% with rocuronium (p < 0.001). VAT occurred in 36% of cases. Mivacurium was used in 77% of these cases, atracurium in 26%, and rocuronium in 6.6% (p < 0.001).

### Conclusions

Mivacurium is associated with a higher risk of VAT during PKP. Therefore, atracurium or rocuronium may minimize complications in ocular surgery with large incisions.

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### Introduction

We sought to characterize changes in healthcare spending associated with the onset of 22 endometriosis-related comorbidities.

### Methods

Women aged 18–49 years with endometriosis (N = 180,278) were extracted from 2006–2015 de-identified Clinformatics® DataMart claims data. For 22 comorbidities, comorbidity patients were identified on the basis of having a first comorbidity diagnosis after their initial endometriosis diagnosis. Controls were identified on the basis of having no comorbidity diagnosis and were matched 1:1 to comorbidity patients on demographics and baseline spending. Total medical and pharmacy spending was measured during 12 months before and after each patient’s index date (first comorbidity diagnosis for comorbidity patients, and equal number of days after earliest endometriosis claim for controls). Pre–post spending differences were compared using difference-in-differences linear regression. Total and comorbidity-related cumulative spending per patient for all endometriosis patients were calculated annually for the 5 years following endometriosis diagnosis.

### Results

The number of endometriosis patients with each comorbidity varied between 121 for endometrial cancer and 16,177 for fatigue. Healthcare spending increased significantly with the onset of eight comorbidities: breast cancer, ovarian cancer, pregnancy complications, systemic lupus erythematosus/rheumatoid arthritis/Sjogren’s/multiple sclerosis, infertility, uterine fibroids, ovarian cyst, and headache [p < 0.001 except for headache (p = 0.045)]. Spending decreased significantly for fatigue, cystitis/UTI, and eczema [p < 0.001 except for fatigue (p = 0.048)] and was not statistically different for the other 11 comorbidities. Difference-in-differences estimates were significantly higher for comorbidity patients for all comorbidities except eczema (p ≤ 0.003). Mean 5-year total cumulative spending was \$58,191 per endometriosis patient, of which between 11% and 23% was attributable to comorbidity-related medical claims.

### Conclusion

For all but one of the 22 comorbidities associated with endometriosis, comorbidity onset was associated with a relative increase in total healthcare spending.

### Funding

AbbVie Inc.

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### The role of cognitive abilities in decisions from experience: Age differences emerge as a function of choice set size

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### Macro-pro-B-type natriuretic peptide (proBNP) and hidden macro-N-terminal proBNP: Case report

Publication date: Available online 2 November 2017
Source:Clinical Biochemistry
Author(s): Yasuaki Nakagawa, Toshio Nishikimi, Hiroshi Sakai, Seiko Ohno, Hideyuki Kinoshita, Hideaki Inazumi, Kenji Moriuchi, Koichiro Kuwahara, Minoru Horie, Takeshi Kimura
B-type natriuretic peptide (BNP) is a cardiac hormone widely used as a biomarker for heart failure. Here, we present the first report of extremely high levels of immunoreactive BNP caused by formation of macro-proBNP.A 70-year-old woman with left ventricular hypertrophy and normal systolic function presented with extremely high plasma levels of BNP (35,374pg/ml) and N-terminal proBNP (NT-proBNP; 30,600pg/ml). Our recently developed proBNP immunoassay showed that nearly 100% of her immunoreactive BNP was proBNP. Polyethylene glycol precipitation tests reported extremely low BNP recovery (1.3%), while protein G addition tests also reported a remarkably low BNP fraction (3.3%). Gel filtration chromatography with normal elution buffer combined with BNP immunoassays showed a BNP peak with a retention time slightly shorter than that of IgG. With acidic elution buffer (pH3.0), however this peak disappeared and a new BNP peak consistent with glycosylated human proBNP appeared. These results suggest that in this case most BNP immunoreactivity consisted of macro-proBNP, which is an immune complex composed of proBNP and an anti-proBNP autoantibody. Gel filtration chromatography combined with NT-proBNP immunoassays revealed that the NT-proBNP assay cross-reacts with both the proBNP-IgG complex and proBNP. In addition, with acidic buffer, a new large peak appeared with a retention time the same as that of glycosylated NT-proBNP.These results suggest spuriously high levels of BNP and NT-proBNP are caused by macro-proBNP. Macro-NT-proBNP is not detected by the currently available NT-proBNP assay system.

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### IJMS, Vol. 18, Pages 2319: Regulation of Human Breast Cancer by the Long Non-Coding RNA H19

IJMS, Vol. 18, Pages 2319: Regulation of Human Breast Cancer by the Long Non-Coding RNA H19

International Journal of Molecular Sciences doi: 10.3390/ijms18112319

Authors: Jordan Collette Xuefen Le Bourhis Eric Adriaenssens

Breast cancer is one of the most common causes of cancer related deaths in women. Despite the progress in early detection and use of new therapeutic targets associated with development of novel therapeutic options, breast cancer remains a major problem in public health. Indeed, even if the survival rate has improved for breast cancer patients, the number of recurrences within five years and the five-year relative survival rate in patients with metastasis remain dramatic. Thus, the discovery of new molecular actors involved in breast progression is essential to improve the management of this disease. Numerous data indicate that long non-coding RNA are implicated in breast cancer development. The oncofetal lncRNA H19 was the first RNA identified as a riboregulator. Studying of this lncRNA revealed its implication in both normal development and diseases. In this review, we summarize the different mechanisms of action of H19 in human breast cancer.

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### IJMS, Vol. 18, Pages 2321: Recent Advances in Comprehending the Signaling Pathways Involved in the Progression of Breast Cancer

IJMS, Vol. 18, Pages 2321: Recent Advances in Comprehending the Signaling Pathways Involved in the Progression of Breast Cancer

International Journal of Molecular Sciences doi: 10.3390/ijms18112321

Authors: Andrea Nicolini Paola Ferrari Lucrezia Diodati Angelo Carpi

This review describes recent advances in the comprehension of signaling pathways involved in breast cancer progression. Calcium sensing receptor (CaSR), caveolae signaling, signaling referred to hypoxia-inducing factors and disturbances in the apoptotic machinery are related to more general biological mechanisms and are considered first. The others refer to signaling pathways of more specific biological mechanisms, namely the heparin/heparin-sulfate interactome, over-expression of miRNA-378a-5p, restriction of luminal and basal epithelial cells, fatty-acid synthesis, molecular pathways related to epithelial to mesenchimal transition (EMT), HER-2/neu gene amplification and protein expression, and the expression of other members of the epithelial growth factor receptor family. This progress in basic research is fundamental to foster the ongoing efforts that use the new genotyping technologies, and aim at defining new prognostic and predictive biomarkers for a better personalized management of breast cancer disease.

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### Are Inflammatory Cytokines Associated with Pain during Acute Myocardial Infarction?

Objective: Pain and inflammation during acute myocardial infarction (AMI) have been associated with the development of posttraumatic stress disorder and may also impact negatively on somatic outcome. We investigated the relationship between pain during AMI and levels of circulating proinflammatory (tumor necrosis factor [TNF]-α, interleukin [IL]-6) and anti-inflammatory (IL-33 and tissue growth factor [TGF]-β1) cytokines. Methods: Data were collected as part of the Myocardial Infarction - Stress Prevention Intervention (MI-SPRINT) study. We included 140 patients (mean age 59.6 years, 82.1% male) with high acute psychological distress within 48 h after MI. Fasting blood samples were drawn thereafter to measure cytokine levels. Sociodemographic factors, psychological and medical data, as well as cardiometabolic markers were assessed with questionnaires and patient interviews. Results: Linear regression models showed a significant positive correlation of pain with TGF-β1 (b = 770.91, p = 0.031) and a significant inverse correlation of pain with IL-33 (b = -0.11, p = 0.015) after controlling for age, gender, body mass index, lifetime depression, acute stress disorder symptoms, and the prognostic Global Registry of Acute Coronary Events (GRACE) score. Pain was not associated with IL-6 but with the GRACE score (b = 0.01, p = 0.003). Pain showed no significant association with TNF-α. Conclusion: Pain during MI was associated with anti- but not proinflammatory cytokines. As IL-33 has been shown to be cardioprotective, lower IL-33 levels with more intense pain may suggest a pathway through which increased pain during MI may have an impact on the medical prognosis.
Neuroimmunomodulation

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### Developing reliable dietary guidelines

The National Academy of Sciences (NAS) recently published two reports critiquing the process used to develop the US dietary guidelines.12 The reports identify important deficiencies in the process,...

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