Miracle-dz/UniFAR-FTUs huggingface dataset:
Label‐free relative quantification of secreted proteins as a non‐invasive method for the quality control of chondrogenesis in bioengineered substitutes for cartilage repair

Cartilage tissue engineering is making progress, but the competing available strategies still leave room for improvement and consensual overviews regarding the best combinations of scaffolds and cell sources are limited by the capacity to compare them directly. In addition, because most strategies involve autologous cell transfer, once these are optimized, the resulting implants require individual quality control prior to grafting in order to emphasize patient‐to‐patient differential responsiveness to engineering processes. Here, cartilage substitutes prepared from human mesenchymal stem cells undergoing chondrogenic differentiation within distinct scaffolds were used as pilot samples to investigate the pertinence of a novel method with the aim of characterizing the implants. The limits and advantages of analysing, by label‐free liquid chromatography‐coupled matrix‐assisted laser desorption and ionization (LC‐MALDI) mass spectrometry, the secreted proteome released into culture medium by engineered cartilage tissues were investigated and compared with more classically used methods for biomaterial characterization. This method did not require sacrificing the biomaterials and robustly evidenced their chondrogenic statuses. In more detail, the method highlighted differences between batches prepared from distinct donors. It was adapted to distinct scaffolds and allowed a comparison of the influence of individual engineering steps, such as growth factor combinations and oxygen tension. Finally, it evidenced subtle changes between replicate substitutes within a series, thereby distinguishing the least and most accomplished ones. We conclude that relative quantification of secreted proteins through label‐free LC‐MALDI will be useful, not only to orientate engineering methodologies, but also to ultimately provide non‐invasive quality control of engineered tissue substitutes for the repair of cartilage and possibly other connective tissues.
Lower Risk of Revision With Patellar Tendon Autografts Compared With Hamstring Autografts

Background: A number of studies have found comparable results after anterior cruciate ligament (ACL) reconstruction with patellar tendon autografts and hamstring autografts; however, few studies have been large enough to reveal differences in risk of revision with regard to clinical and demographic factors. Purpose: To present the distribution of grafts for ACL reconstruction based on data in the Scandinavian ACL registries and to compare the risk of revision between patellar tendon autografts and hamstring autografts. Potential associations with other clinical and demographic factors were also explored. Study design: Cohort study; Level of evidence, 2. Methods: A total of 45,998 primary ACL reconstructions, including 6736 patellar tendon autografts and 38,666 hamstring autografts, were identified in the Scandinavian ACL registries. The overall median follow-up time was 3 years (range, 0-8 years). To compare the risk of revision between groups of patients, univariate Kaplan-Meier analysis (with log-rank test) and the Cox proportional hazard regression model were applied. The hazard rate ratio with 95% CI was reported as a measure of effect. Results: Patellar tendon and hamstring autografts were used in 14.6% and 84.1% of the patients, respectively. The remaining patients received allografts, direct sutures, or other graft types (1.3%). The primary ACL injury occurred during soccer, team handball, or alpine activities in 67.5% of the patients in the patellar tendon group and 66.2% in the hamstring group. A total of 156 patients in the patellar tendon group and 1042 patients in the hamstring group underwent revision. The overall risk of revision was significantly lower in the patellar tendon group versus the hamstring group (hazard rate ratio = 0.63; 95% CI, 0.53-0.74), and it decreased with increasing age at surgery, although not strictly linearly. The lower risk of revision in the patellar tendon group was consistently observed across subgroups of patient sex, age, and concomitant cartilage injury (P > .05, test for interaction) but seemed to be slightly more pronounced for patients injured during certain pivoting activities (soccer, team handball, and alpine activities) compared with other activities (hazard rate ratio = 0.57 vs 0.81; P = .058, test for interaction). Conclusion: The majority of primary ACL reconstructions in Scandinavia are performed with hamstring autografts. Results from the present large prospective study show that patients receiving patellar tendon autografts have a statistically significantly lower risk of revision compared with patients receiving hamstring autografts.
Does Limited Internal Femoral Rotation Increase Peak Anterior Cruciate Ligament Strain During a Simulated Pivot Landing?

Background: Many factors contributing to anterior cruciate ligament (ACL) injury risk have been investigated. Recently, some ACL-injured individuals have presented with a decreased range of hip internal rotation compared with controls. The pathomechanics of why decreased hip range of motion increases risk of ACL injury have not yet been studied. Hypothesis: Peak relative strain of the anteromedial bundle of the ACL (AM-ACL) during a simulated single-leg pivot landing is inversely related to the available range of internal femoral rotation. Study Design: Controlled laboratory study. Methods: A series of pivot landings were simulated in 10 female and 10 male human knee specimens with a testing apparatus that applied a 2-bodyweight impulsive load, inducing knee compression, flexion moment, and internal tibial torque. The range of internal femoral rotation was (1) locked at ~0°, (2) limited with a hard stop to ~7°, (3) limited with a hard stop to ~11°, or (4) free, with rotation resisted by 2 springs to simulate the resistance of the active hip rotator muscles to stretch. The AM-ACL strain was quantified with a differential variable reluctance transducer. A linear mixed model was used to determine whether a significant linear relation existed between peak AM-ACL relative strain and range of internal femoral rotation. Results: Peak AM-ACL relative strain was inversely related to the available range of internal femoral rotation (R 2 = 0.91; P < .001), with strain increasing 1.3% for every 10° decrease in rotation; this represented a 20% increase in peak relative strain, given an average range of femoral rotation of 15° upon landing in healthy athletes. Conclusion: Peak AM-ACL relative strain was inversely proportional to the available range of internal femoral rotation during simulated single-leg pivot landings. Clinical Relevance: Decreased range of internal femoral rotation results in greater ACL strain and may therefore increase the susceptibility to ACL rupture with athletic cutting and pivoting activities. Screening for a limited range of hip internal rotation should therefore become a component of not only ACL injury prevention programs but also evaluation protocols for those with ACL injuries and/or reconstructions.
Neutrino Spectroscopy Can Probe the Dark Matter Content in the Sun

Dark matter in the center of the Sun would affect its internal structure and lead to a distinctive neutrino emission pattern. After being gravitationally captured, low-mass cold dark-matter particles (mass range from 5 to ~50 × 109 electron volts) are thought to drift to the center of the Sun and affect its internal structure. Solar neutrinos provide a way to probe the physical processes occurring in the Sun’s core. Solar neutrino spectroscopy, in particular, is expected to measure the neutrino fluxes produced in nuclear reactions in the Sun. Here, we show how the presence of dark-matter particles inside the Sun will produce unique neutrino flux distributions in 7Be-ν and 8B-ν, as well as 13N-ν, 15O-ν, and 17F-ν.
Patient Predictors of Early Revision Surgery After Anterior Cruciate Ligament Reconstruction

Background: Revision surgery is one of the most important endpoints during follow-up after anterior cruciate ligament (ACL) reconstruction. Purpose: To investigate if commonly known patient factors can predict revision surgery after ACL reconstruction. Study Design: Cohort study; Level of evidence, 2. Methods: This prospective cohort study was based on data from the Swedish National Knee Ligament Register during the period of January 1, 2005, through December 31, 2013. Patients who underwent primary ACL reconstruction with hamstring tendon or bone–patellar tendon–bone autografts were included. Follow-up started on the date of primary ACL reconstruction, and follow-up ended with ACL revision surgery, after 24 months of follow-up, or on December 31, 2013, whichever occurred first. The analyzed patient variables were activity at the time of injury, sex, age, height, weight, body mass index, smoking, and the use of smokeless tobacco. The primary study endpoint was revision surgery, defined as replacement of a primary ACL reconstruction. Relative risk (RR) and 95% CIs were calculated and adjusted for confounding factors using multivariate statistics. Results: A total of 16,930 patients were included (males, n = 9767 [57.7%]; females, n = 7163 [42.3%]). The 2-year revision rate was 1.82% (95% CI, 1.62%-2.02%). There was no significant difference between male and female revision rates (1.74% [95% CI, 1.48%-2.00%] vs 1.93% [95% CI, 1.61%-2.25%], P = .383). In both males and females there was a significantly increased risk of revision surgery associated with soccer playing and adolescence (age 13-19 years) (males: RR = 1.58 [95% CI, 1.12-2.23], P = .009 and RR = 2.67 [95% CI, 1.91-3.73], P < .001, respectively; females: RR = 1.43 [1.01-2.04], P = .045 and RR = 2.25 [95% CI, 1.57-3.24], P < .001, respectively). A combination of these predictors were associated with a further increased risk of revision surgery (males: RR = 2.87 [95% CI, 1.79-4.60], P < .001; females: RR = 2.59 [95% CI, 1.69-3.96], P < .001). Conclusion: Soccer players and adolescents had an increased risk of revision surgery after ACL reconstruction, with a respective factor of 1.5 and 2.5. Individuals with a combination of these 2 predictors carried an almost 3-fold higher risk of revision surgery. There were no significant associations for sex, height, weight, body mass index, or tobacco use.
Concussion Management in United States College Sports

Background: In 2010, the National Collegiate Athletic Association (NCAA) adopted its Concussion Policy and Legislation, which applies to more than 450,000 collegiate athletes annually. To date, there has been no examination of school-level compliance with the NCAA Concussion Policy. Purpose: To examine whether stakeholders at NCAA schools report that their school has a concussion management plan and whether existing plans are consistent with the NCAA policy. Also examined were stakeholders’ perceptions regarding concussion management at their institution and possible areas for improvement. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Surveys were sent by e-mail to coaches, sports medicine clinicians, and compliance administrators at all 1066 NCAA member institutions. Surveys asked population-specific questions about institutional concussion management. Individuals (N = 2880) from 907 unique schools participated in this survey. Results: Most respondents (n = 2607; 92.7%) indicated their school had a concussion management plan. Most schools had all (82.1%) or some (15.2%) respondents indicate a concussion management plan was present. When asked to indicate all individuals who could have final responsibility for returning athletes to play after a concussion, 83.4% selected team doctor, 72.8% athletic trainer, 31.0% specialist physician, 6.8% coach, and 6.6% athlete. Most respondents (76.1%) indicated that their institution had a process for annual athlete concussion education; 91.2% required athletes to acknowledge their responsibility to report concussion symptoms. Nearly all respondents (98.8%) thought their school’s concussion management plan protected athletes “well” or “very well. ” Top categories suggested for improvement included better coach education (39.7%), increasing sports medicine staffing (37.2%), and better athlete education (35.2%). Conclusion: Although a large majority of respondents indicated that their school has a concussion management plan, improvement is needed. Compliance with specified components (eg, annual athlete education) lags behind the presence of the plan itself, and stakeholders had suggestions for areas in which improvements are needed. Increasing scientific evidence supporting the seriousness of concussion underscores the need for the NCAA to use its regulatory capabilities to ensure that athletes’ brains are safe.
Tissue engineering of a composite trachea construct using autologous rabbit chondrocytes

The repair of large tracheal segmental defects remains an unsolved problem. The goal of this study is to apply tissue engineering principles for the fabrication of large segmental trachea replacements. Engineered tracheal replacements composed of autologous cells (neotracheas) were tested in a New Zealand White rabbit model. Neotracheas were formed in the rabbit neck by wrapping a silicone tube with consecutive layers of skin epithelium, platysma muscle, and an engineered cartilage sheet and allowing the construct to mature for 8–12 weeks. In total, 28 rabbits were implanted and the neotracheas assessed for tissue morphology. In 11 cases, neotracheas deemed sufficiently strong were used to repair segmental tracheal defects. Initially, the success rate of producing structurally sound neotracheas was impeded by physical disruption of the cartilage sheets during animal handling, but by the end of the study, 15 of 18 neotracheas (83.3%) were structurally sound. Of the 15 structurally sound neotracheas, 11 were used for segmental reconstruction and were left in place for up to 21 days. Histological examination showed the presence of variable amounts of viable epithelium, a vascularized platysma flap, and a layer of safranin O‐positive cartilage along with evidence of endochondral ossification. Rabbits that had undergone segmental reconstruction showed good tracheal integration, had a viable epithelium with vascular support, and the cartilage was sufficiently strong to maintain a lumen when palpated. The results demonstrated that viable, trilayered, scaffold‐free neotracheas could be constructed from autologous cells and could be integrated into native trachea to repair a segmental defect.
Surface modification of a biodegradable composite by UV laser ablation: in vitro biological performance

Melt blends of chitosan and biodegradable aliphatic polyester have been physically and biologically studied, presenting great potential for biomedical applications. Structurally, poly(butylene succinate)–chitosan (PBS/Cht) composite scaffolds are covered by a thin PBS layer, preventing the desired interaction of cells/tissues with the chitosan particules. In the present work, a selective and controlled ablation of this skin layer was induced by UV laser processing. X‐ray photoelectron spectroscopy (XPS) and time‐of‐flight secondary ion mass spectrometry (ToF–SIMS) data demonstrated an increment of chitosan components and others resulting from the laser ablation process. The biological activity (i.e. cell viability and proliferation) on the inner regions of the composite scaffolds is not significantly different from those of the external layer, despite the observed differences in surface roughness (determined by interferometric optical profilometry) and wettability (water contact angle). However, the morphology of human osteoblastic cells was found to be considerably different in the case of laser‐processed samples, since the cells tend to aggregate in multilayer columnar structures, preferring the PBS surface and avoiding the chitosan‐rich areas. Thus, UV laser ablation can be considered a model technique for the physical surface modification of biomaterials without detrimental effects on cellular activity. Copyright © 2010 John Wiley & Sons, Ltd.
Isolation and Characterization of Human Mesenchymal Stem Cells Derived From Synovial Fluid in Patients With Osteochondral Lesion of the Talus

Background: Recently, mesenchymal stem cells (MSCs) have been suggested as a source for cell-based treatment of cartilage lesions based on the ability of these cells to differentiate into chondrocytes. Purpose: To characterize MSCs derived from the synovial fluid in ankle joints with osteochondral lesion of the talus (OLT). Study Design: Controlled laboratory study. Methods: Synovial fluid was collected from the ankle joints of 28 patients with OLT who underwent arthroscopic marrow stimulation between September 2011 and April 2012. Epitope profiles and multilineage differentiation were assessed to characterize the synovial fluid MSCs. To clarify the origin of synovial fluid MSCs, we assessed gene profiles of MSCs derived from various mesenchymal tissues by reverse transcription–polymerase chain reaction (RT-PCR) analysis. Results: Synovial fluid MSCs expressed CD90 and CD105, showed low expression of CD14 and CD34, and underwent multilineage differentiation in vitro. The RT-PCR revealed strong expression of CD90, CD44, and CD73, whereas CD45 and CD133 were not detected. The colony number of synovial fluid MSCs from OLT significantly increased in stages C and D, as defined by arthroscopic classification. Gene expression profiles indicated that synovial fluid MSCs derived from the patients with OLT were more similar to MSCs from synovium than to MSCs from bone marrow and adipose tissue. Conclusion: This study confirmed that human synovial fluid is a good source of MSCs, with the capacity to differentiate toward several cell lineages. Further study with matched controls of synovial fluid MSCs derived from ankle joints without OLT is required for a more accurate evaluation of synovial fluid MSCs. Clinical Relevance: The findings of this study provide a platform for exploring the potential role of synovial fluid MSCs in OLT and their therapeutic potential in novel joint regeneration strategies.
Sleep Disturbance and Neurocognitive Function During the Recovery From a Sport-Related Concussion in Adolescents

Background: Sleep disturbances are a hallmark sign after a sport-related concussion (SRC). Poor sleep has been shown to adversely affect baseline neurocognitive test scores, but it is not comprehensively understood how neurocognitive function is affected by disrupted sleep during recovery from a concussion. Purpose: To identify the correlation between adolescent athletes’ neurocognitive function and their self-reported sleep quantity and sleep disturbance symptoms during recovery from SRC. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Immediate Post-Concussion Assessment and Cognition Testing (ImPACT) data were retrospectively collected for 545 adolescent athletes treated for SRC at a sports medicine concussion clinic. Patients were stratified into groups based on 2 criteria: self-reported sleep duration and self-reported sleep disturbance symptoms during postinjury ImPACT testing. Sleep duration was classified as short (<7 hours), intermediate (7-9 hours), and long (>9 hours). Sleep disturbance symptoms were self-reported as part of the Post-Concussion Symptom Scale (PCSS) as either sleeping less than normal, sleeping more than normal, or having trouble falling asleep. One-way analyses of variance were conducted to examine the effects that sleep duration as well as self-reported sleep disturbance symptoms had on composite scores. A total of 1067 ImPACT tests were analyzed: test 1, 545; test 2, 380; and test 3, 142. Results: Sleeping fewer than 7 hours the night before testing correlated with higher PCSS scores (P < .001), whereas sleeping longer than 9 hours correlated with worse visual memory (P = .01), visual motor speed (P <.001), and reaction time (P = .04) composite scores. With regard to self-reported sleep disturbance symptoms, patients demonstrated worse composite scores during ImPACT testing when they self-reported sleeping more than normal (ImPACT test 1: verbal memory, P < .001; visual motor speed, P = .05; reaction time, P = .01; ImPACT test 2: verbal memory, P < .001; visual memory, P < .001; visual motor speed, P < .001; reaction time, P = .01). Adolescent patients recovering from SRC demonstrated higher (worse) PCSS scores (P < .001) when they sensed that their sleep had been disrupted. Conclusion: Adolescent patients who perceive that their sleep is somehow disrupted after SRC may report a greater number of concussion symptoms during their recovery. In addition, the study results suggest that sleeping more than normal may identify an individual who continues to be actively recovering from concussion, given the correlation between lower neurocognitive function and this self-reported symptom.
Hamstring Tendon Regeneration After Harvesting

Background: Hamstring tendons are often used as autografts for anterior cruciate ligament (ACL) reconstruction. However, no systematic review has been performed describing consequences such as hamstring tendon regeneration rate and determinants of hamstring tendon regeneration. Purpose: To summarize the current literature regarding hamstring tendon rate regeneration, the time course of regeneration, and determinants of hamstring regeneration. Study design: Systematic review. Methods: A search was performed in the Embase, Medline (OvidSP), Web of Science, Cochrane, PubMed, and Google Scholar databases up to June 2014 to identify relevant articles. A study was eligible if it met the following inclusion criteria: tendons were harvested, regeneration at harvest site was assessed, population size was at least 10 human subjects, full-text article was available, and the study design was either a randomized controlled trial, prospective cohort study, retrospective cohort study, or case control study. A risk of bias assessment of the eligible articles was determined. Data describing hamstring tendon regeneration rates were pooled per time period. Results: A total of 18 publications met the inclusion criteria. The mean regeneration rate for the semitendinosus and gracilis tendons was, in all cases, 70% or higher. More than 1 year after harvesting, 79% (median [IQR], 80 [75.5-90]) of the semitendinosus tendons and 72% (median [IQR], 80 [61-88.5]) of the gracilis tendons were regenerated. No significant differences in regeneration rate could be found considering patient sex, age, height, weight, or duration of immobilization. Results did not clearly show whether absence of regeneration disadvantages the subsequent hamstring function. Five studies measured the regeneration rate at different moments in time. Conclusion: Hamstring tendons regenerated in the majority of patients after ACL reconstruction. The majority of the hamstring tendon regeneration was found to occur between 1 month and 1 year after harvest. No significant determinants for hamstring tendon regeneration could be identified because of a lack of research. The function and strength of the regenerated hamstring remained unclear.