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Previous reports have documented an attenuated p53 response to DNA damage in hepatocytes isolated from enzyme-altered foci (EAF). Here, we have studied this p53 response in vivo in rats with EAF. These animals received repeated doses of diethylnitrosamine (DEN) for 6 weeks and a challenging dose 24 h before death. Liver sections were then analysed using an immunohistochemical procedure for p53, or a double-staining procedure for p53 and glutathione-S-transferase pi (GST-P). In control rats or rats with EAF not given the challenging dose of DEN, there was no p53 staining. In control rats, only given the challenging dose of DEN, there was a centrilobular p53 nuclear staining that co-localized with TUNEL staining. In an experiment involving four rats with EAF 389 ± 39 hepatocytes/mm2 of non-EAF tissue stained positively for p53, while the corresponding value for EAF tissue was 27.6 ± 7.5. Thus, p53-positive cells were 14.6-fold more frequent in non-EAF than in EAF tissue. In many EAF no p53-positive cells were seen at all and 83% of the EAF demonstrated <20% of the number of p53-positive cells seen in non-EAF tissue. Very few EAF had as high a proportion of p53-positive cells as did the average non-EAF tissue. EAF >0.06 mm2 had significantly fewer p53-positive cells than smaller EAF. The ratio of p53 expression in non-EAF tissue and larger EAF was 32.6. In a control experiment, four EAF-bearing rats were used as donors to prepare primary cultures of hepatocytes. After 24 h of exposure to DEN, many of the cultured cells became p53-positive. Among GST-P-negative hepatocytes, 12.8% were p53-positive, whereas only 0.25% of the GST-P-positive hepatocytes were p53-positive. Literature data suggest that the altered xenobiotic metabolism in EAF may give rise to a 3-4 fold difference in DNA damage between non-EAF and EAF tissues. It is concluded that GST-P-positive EAF hepatocytes have an attenuated p53 response to DNA damage. This attenuated response may facilitate clonal expansion of EAF under stress induced by DNA-damaging chemicals. [ABSTRACT FROM PUBLISHER]

Abstract Background Many practical tasks in biomedicine require accessing specific types of information in scientific literature; e.g. information about the results or conclusions of the study in question. Several schemes have been developed to characterize such information in scientific journal articles. For example, a simple section-based scheme assigns individual sentences in abstracts under sections such as Objective, Methods, Results and Conclusions. Some schemes of textual information structure have proved useful for biomedical text mining (BIO-TM) tasks (e.g. automatic summarization). However, user-centered evaluation in the context of real-life tasks has been lacking. Methods We take three schemes of different type and granularity - those based on section names, Argumentative Zones (AZ) and Core Scientific Concepts (CoreSC) - and evaluate their usefulness for a real-life task which focuses on biomedical abstracts: Cancer Risk Assessment (CRA). We annotate a corpus of CRA abstracts according to each scheme, develop classifiers for automatic identification of the schemes in abstracts, and evaluate both the manual and automatic classifications directly as well as in the context of CRA. Results Our results show that for each scheme, the majority of categories appear in abstracts, although two of the schemes (AZ and CoreSC) were developed originally for full journal articles. All the schemes can be identified in abstracts relatively reliably using machine learning. Moreover, when cancer risk assessors are presented with scheme annotated abstracts, they find relevant information significantly faster than when presented with unannotated abstracts, even when the annotations are produced using an automatic classifier. Interestingly, in this user-based evaluation the coarse-grained scheme based on section names proved nearly as useful for CRA as the finest-grained CoreSC scheme. Conclusions We have shown that existing schemes aimed at capturing information structure of scientific documents can be applied to biomedical abstracts and can be identified in them automatically with an accuracy which is high enough to benefit a real-life task in biomedicine.

Rehabilitation after an anterior cruciate ligament (ACL) reconstruction requires patience, devotion, and discipline. Rehabilitation should be individualized to each patient's specific need and sport. Return to sport is a continuum throughout the rehabilitation, and patients should not return to performance before passing a battery of muscle function tests and patient-reported outcomes, as well as change of direction-specific tests. Return to full participation should be an agreement between the patient, physical therapist, surgeon, and coach. For minimal risk for second ACL injury, patients should continue with maintenance and prevention training even after returning to sport., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The relationship between hamstring strength and hop performance after anterior cruciate ligament (ACL) reconstruction with hamstring tendon (HT) autografts has not been well elucidated. The aim was to investigate the relationship between eccentric hamstring strength, assessed with the NordBord, and concentric hamstring strength, assessed with the Biodex, with hop performance at 8 and 12 months after ACL reconstruction., Methods: Registry study. Patients ≥ 16 years who had undergone primary ACL reconstruction with HT autograft, followed by muscle strength and hop tests at 8 and 12 months were included. Correlations of the relative hamstring strength (Nm/kg or N/kg) and limb symmetry index (LSI) with hop performance were analyzed. Pearson's correlation coefficient, and coefficient of determination (r 2 ) were used for statistical analysis., Results: A total of 90 patients were included, of which 48 (53%) were women. The mean age at ACL reconstruction was 27.0 ± 8.0 years. Relative hamstring strength had significant positive correlations with hop performance, ranging from r = 0.25-0.66, whereas hamstring strength LSI had significant positive correlations which ranged from r = 0.22-0.37 at 8 and 12 months after ACL reconstruction. At 12 months, the relative hamstring strength in the Biodex explained 32.5-43.6% of the hop performance in vertical hop height, hop for distance relative to height, and the total number of side hops, whereas the relative hamstring strength in the NordBord explained 15.2-23.0% of the hop performance., Conclusion: The relative hamstring strength in the Biodex test explained 32.5-43.6% of the hop performance, whereas the relative hamstring strength in the NordBord explained 15.2-23.0%. Thus, our findings suggest that relative hamstring strength, especially in the hip-flexed position may be a better indicator of hop performance at 8 and 12 months after ACL reconstruction in patients treated with HT autograft., (© 2024. The Author(s).)

Objective: Comparison of knee flexor strength limb symmetry index (LSI) between the NordBord-test and the Biodex-test, and to determine the relationship between knee flexor strength and function in patients 2 and 5 years after anterior cruciate ligament reconstruction (ACL-R) with hamstring tendon (HT) autografts., Design: Observational registry study., Setting: Primary care., Patients: Cross-sectional data from 96 patients (55% women) participating in a rehabilitation-registry after ACL-R with HT autografts., Main Outcome Measures: Comparison of knee flexor strength symmetry between the Biodex-test and the NordBord-test. Secondly, the relationship between knee flexor strength test and perceived knee function, activity level, and hop performance., Results: The NordBord-test demonstrated greater strength deficits compared to the Biodex-test with a mean difference of 12.5% ± 15.1% 95 % CI [8.1; 16.9%] at 2 years, and 11.1% ± 11.9% 95 % CI [7.7; 14.6 %] at 5 years after ACL-R. Relative concentric knee flexor strength (Nm/kg) in the Biodex demonstrated significant weak-to-moderate correlations with activity level and hop performance (r = 0.33-0.67) at 2 and 5 years., Conclusion: The NordBord-test identified deficits in knee flexor strength LSI not seen with the Biodex-test at 2 and 5 years after ACL-R. No significant correlations were found between the persistent knee flexor strength asymmetry and perceived function, activity level or hop performance., Competing Interests: Declaration of Competing interest KS is a board member of Getinge AB. The authors declare that they have no conflict of interest in the content of the present study., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Whether there is a difference in harvesting the semitendinosus tendon alone (S) or in combination with the gracilis tendon (SG) for the recovery of knee flexor strength after anterior cruciate ligament (ACL) reconstruction remains inconclusive. Therefore, this study aimed to assess the recovery of knee flexor strength based on the autograft composition, S or SG autograft at 6, 12, and ≥ 24 months after ACL reconstruction., Methods: A systematic review and meta-analysis was conducted following the PRISMA guidelines. A comprehensive search was performed encompassing the Cochrane Library, Embase, Medline, PEDRo and AMED databases from inception to January 2023. Inclusion criteria were human clinical trials published in English, comprised of randomized controlled trials (RCTs), longitudinal cohort-, cross-sectional and case-control studies that compared knee flexor strength recovery between S and SG autografts in patients undergoing primary ACL reconstruction. Isokinetic peak torques were summarized for angular velocities of 60°/s, 180°/s, and across all angular velocities, assessed at 6, 12, and ≥ 24 months after ACL reconstruction. A random-effects model was used with standardized mean differences and 95% confidence intervals. Risk of bias was assessed with the RoBANS for non-randomized studies and the Cochrane RoB 2 tool for RCTs. Certainty of evidence was appraised using the GRADE working group methodology., Results: Among the 1,227 patients from the 15 included studies, 604 patients received treatment with S autograft (49%), and 623 received SG autograft (51%). Patients treated with S autograft displayed lesser strength deficits at 6 months across all angular velocities d = -0.25, (95% CI -0.40; -0.10, p = 0.001). Beyond 6 months after ACL reconstruction, no significant difference was observed between autograft compositions., Conclusion: The harvest of S autograft for ACL reconstruction yields superior knee flexor strength recovery compared to SG autograft 6 months after ACL reconstruction, irrespective of angular velocity at isokinetic testing. However, the clinical significance of the observed difference in knee flexor strength between autograft compositions at 6 months is questionable, given the very low certainty of evidence and small effect size. There was no significant difference in knee flexor strength recovery between autograft compositions beyond 6 months after ACL reconstruction., Trial Registration: CRD42022286773., (© 2024. The Author(s).)

Background: The stress on the anterior cruciate ligament (ACL) induced by the quadriceps can be attenuated by activation of the hamstrings by exerting an opposing torque to the anterior translation of tibia. Consequently, considering the ratio between strength of the hamstrings-to-quadriceps (HQ-ratio) may be of value to reduce the odds of second ACL injuries. The objective was therefore to evaluate (1) the association between HQ-ratio and the occurrence of a second ACL injury in patients after ACL-reconstruction within 2 years of return to preinjury sport level and (2) to compare the HQ-ratio between males and females after ACL reconstruction., Methods: Patients who had undergone primary ACL reconstruction and participated in knee-strenuous activity preinjury were included. Demographics, the occurrence of a second ACL injury, and muscle strength test results before returning to preinjury sport level were extracted from a rehabilitation registry. The endpoint was set at a second ACL injury or 2 years after return to preinjury sport level. A multivariable logistic regression was used to analyze the association between the HQ-ratio and a second ACL injury., Results: A total of 574 patients (50.0% female) with a mean age of 24.0 ± 9.4 years at primary ACL reconstruction were included. In the univariable logistic regression analysis, the odds of sustaining a second ACL injury decreased by 3% for every 1% increase in the HQ-ratio (OR 0.97 [95% CI 0.95-1.00], p = 0.025). After adjusting for the time from reconstruction to return to preinjury sport level, sex, preinjury sport level, graft choice, age, and body mass index, the results were no longer significant (OR 0.98 [95% CI 0.95-1.01], p = 0.16). Females had a higher HQ-ratio compared with males for both the ACL-reconstructed and uninjured side (3.7% [95% CI 5.7; 1.8%], p = 0.0002 and 3.3% [95% CI 4.6; 2.1], p < 0.001, respectively)., Conclusion: The HQ-ratio did not significantly affect the odds for sustaining a second ACL injury upon return to preinjury sports level after primary ACL reconstruction. Females had a significant higher HQ-ratio than males for both the ACL reconstructed and uninjured side., (© 2024. The Author(s).)

Background: The Otsu method and the Chan-Vese model are two methods proven to perform well in determining volumes of different organs and specific tissue fractions. This study aimed to compare the performance of the two methods regarding segmentation of active thyroid gland volumes, reflecting different clinical settings by varying the parameters: gland size, gland activity concentration, background activity concentration and gland activity concentration heterogeneity., Methods: A computed tomography was performed on three playdough thyroid phantoms with volumes 20, 35 and 50 ml. The image data were separated into playdough and water based on Hounsfield values. Sixty single photon emission computed tomography (SPECT) projections were simulated by Monte Carlo method with isotope Technetium-99 m ([Formula: see text]Tc). Linear combinations of SPECT images were made, generating 12 different combinations of volume and background: each with both homogeneous thyroid activity concentration and three hotspots of different relative activity concentrations (48 SPECT images in total). The relative background levels chosen were 5 %, 10 %, 15 % and 20 % of the phantom activity concentration and the hotspot activities were 100 % (homogeneous case) 150 %, 200 % and 250 %. Poisson noise, (coefficient of variation of 0.8 at a 20 % background level, scattering excluded), was added before reconstruction was done with the Monte Carlo-based SPECT reconstruction algorithm Sahlgrenska Academy reconstruction code (SARec). Two different segmentation algorithms were applied: Otsu's threshold selection method and an adaptation of the Chan-Vese model for active contours without edges; the results were evaluated concerning relative volume, mean absolute error and standard deviation per thyroid volume, as well as dice similarity coefficient., Results: Both methods segment the images well and deviate similarly from the true volumes. They seem to slightly overestimate small volumes and underestimate large ones. Different background levels affect the two methods similarly as well. However, the Chan-Vese model deviates less and paired t-testing showed significant difference between distributions of dice similarity coefficients (p-value [Formula: see text])., Conclusions: The investigations indicate that the Chan-Vese model performs better and is slightly more robust, while being more challenging to implement and use clinically. There is a trade-off between performance and user-friendliness., (© 2024. The Author(s).)