Autologous chondrocyte implantation for treatment of articular cartilage defects in the knee and ankle of football (soccer) players

Background: Autologous chondrocyte implantation (ACI) continues to evolve into one of the most efficient and common techniques for repair of articular cartilage defects. Significant progress has been made within the last decade regarding its application in the context of professional sports, such as football. This article provides a current overview of the application of ACI in the context of amateur and professional football. Methods: Clinical studies involving football players and other high-impact sports athletes treated with ACI were reviewed. The scientific and technical development of ACI was evaluated considering latest publications, and analyzed for treatment outcome parameters. Results: Football players reported good to excellent results after treatment with ACI or matrix-associated chondrocyte implantation (MACI). Activity scores and clinical knee and ankle scores were significantly improved after surgery. Great advances have been made in surgery specific rehabilitation algorithms, leading to shorter return to play times. New surgical techniques have been introduced, reducing the 2-stage design of ACI to only one surgical intervention, accelerating return to play time further while reducing morbidity. Conclusion: Surgical repair of focal articular cartilage defects via ACI in football players often provides successful return-to-competition and produces long lasting regeneration tissue, enabling players to continue their career on the pre-injury level of play. The technique itself is constantly evolving, addressing initial shortcomings and making it more widespread available to the recreational and professional athlete

Size of cartilage defects and the need for repair: a systematic review

Background: Cartilage defects are treated with a wide array of non-operative and surgical procedures. Optimal choice of treatment depends on lesion depth and size. Objectives: To review and summarize current data on the management of cartilage injuries in joints as it relates to defect size. Data sources: MEDLINE, Cochrane Central Register of Controlled Trials & Cochrane Library, CINHAL. Study eligibility criteria, participants, and interventions: Inclusion: (1) Studies investigating patients who underwent cartilage repair of the shoulder, elbow, hip, knee, and ankle. (2) Studies reporting outcome measures and treated lesion size. Exclusion: (1) No mention of defect size. (2) Joints not mentioned above. (3) 1.5 cm2 mostly addressed with cell-based therapies such as autologous cartilage implantation (ACI), or matrix associated cartilage implantation (MACI). Large lesions often are the domain of osteochondral autograft transfer system (OATS). Limitations: Prospective randomized controlled studies are not available for every joint and many studies represent case studies with limited implications for treatment decisions. Conclusions and implications of key findings: Evidence-based treatment selection based on cartilage defect size can be beneficial. Systematic review registration number: 276559

Proteogenomic analysis of acute myeloid leukemia associates relapsed disease with reprogrammed energy metabolism both in adults and children

Despite improvement of current treatment strategies and novel targeted drugs, relapse and treatment resistance largely determine the outcome for acute myeloid leukemia (AML) patients. To identify the underlying molecular characteristics, numerous studies have been aimed to decipher the genomic- and transcriptomic landscape of AML. Nevertheless, further molecular changes allowing malignant cells to escape treatment remain to be elucidated. Mass spectrometry is a powerful tool enabling detailed insights into proteomic changes that could explain AML relapse and resistance. Here, we investigated AML samples from 47 adult and 22 pediatric patients at serial time-points during disease progression using mass spectrometry-based in-depth proteomics. We show that the proteomic profile at relapse is enriched for mitochondrial ribosomal proteins and subunits of the respiratory chain complex, indicative of reprogrammed energy metabolism from diagnosis to relapse. Further, higher levels of granzymes and lower levels of the anti-inflammatory protein CR1/CD35 suggest an inflammatory signature promoting disease progression. Finally, through a proteogenomic approach, we detected novel peptides, which present a promising repertoire in the search for biomarkers and tumor-specific druggable targets. Altogether, this study highlights the importance of proteomic studies in holistic approaches to improve treatment and survival of AML patients.Peer reviewe

Osteochondritis Dissecans of the Knee Associated With Mechanical Overload

Background: Osteochondritis dissecans (OCD) of the knee is a rare but potentially incapacitating disorder in which subchondral bone detaches, leading to an osteochondral fragment that can become unstable and progress into a loose body. The exact cause is unknown, although several biological and mechanical factors have been described. Purpose: To provide insight into epidemiological data of a large cohort of patients affected by OCD of the knee and to identify potential factors contributing to the cause of this disorder. Study Design: Cross-sectional study; Level of evidence, 3. Methods: A total of 236 patients (259 knees) affected by OCD were included in our Knee Registry (2005-2022) and retrospectively analyzed. Patient characteristics were extracted from the medical records. Location and International Cartilage Regeneration & Joint Preservation Society grade (1-4) of OCD were assessed using magnetic resonance imaging. If available, a full-leg standing radiograph was used to assess alignment. Additionally, a statistical scoring system for instability risk was created. Results: A total of 263 OCD lesions were identified in 259 knees, 66.2% on the medial femoral condyle (MFC), 26.6% on the lateral femoral condyle (LFC), 3.8% on the trochlea, 2.7% on the patella, and 0.8% on the lateral tibia plateau. Male patients made up 57.6% of the sample, which had a mean age of 21.8 years. A very high percentage of patients (77.1%; n = 182) practiced sports, of whom 67.6% (n = 123) were engaged in high-impact sports. The location of the OCD lesions and the leg alignment (n = 110) were significantly correlated: MFC lesions were associated with more varus than valgus alignment (47.5% vs 11.3%) and patients with LFC lesions had more valgus than varus alignment (46.7% vs 20.0%; P =.002). Based on age, smoking, sports activity, and preceding trauma, a multivariable scoring system (0-11 points) was created. An increased risk of lesion instability was associated with an increased score: 29.0% at 0 points and 97.0% at 11 points. Conclusion: This study provides detailed epidemiological data for 236 patients affected by OCD of the knee. Older age, smoking, inactivity, and preceding trauma were predictive for instability of OCD lesions. There was an association between OCD of the MFC and varus malalignment and between OCD of the LFC and valgus malalignment. This finding, in combination with the high percentage of patients practicing high-impact sports, suggests an important role for mechanical overload in the pathogenesis of OCD

Hydroxybenzothiazoles as New Nonsteroidal Inhibitors of 17β-Hydroxysteroid Dehydrogenase Type 1 (17β-HSD1)

17β-estradiol (E2), the most potent estrogen in humans, known to be involved in the development and progession of estrogen-dependent diseases (EDD) like breast cancer and endometriosis. 17β-HSD1, which catalyses the reduction of the weak estrogen estrone (E1) to E2, is often overexpressed in breast cancer and endometriotic tissues. An inhibition of 17β-HSD1 could selectively reduce the local E2-level thus allowing for a novel, targeted approach in the treatment of EDD. Continuing our search for new nonsteroidal 17β-HSD1 inhibitors, a novel pharmacophore model was derived from crystallographic data and used for the virtual screening of a small library of compounds. Subsequent experimental verification of the virtual hits led to the identification of the moderately active compound 5. Rigidification and further structure modifications resulted in the discovery of a novel class of 17β-HSD1 inhibitors bearing a benzothiazole-scaffold linked to a phenyl ring via keto- or amide-bridge. Their putative binding modes were investigated by correlating their biological data with features of the pharmacophore model. The most active keto-derivative 6 shows IC50-values in the nanomolar range for the transformation of E1 to E2 by 17β-HSD1, reasonable selectivity against 17β-HSD2 but pronounced affinity to the estrogen receptors (ERs). On the other hand, the best amide-derivative 21 shows only medium 17β-HSD1 inhibitory activity at the target enzyme as well as fair selectivity against 17β-HSD2 and ERs. The compounds 6 and 21 can be regarded as first benzothiazole-type 17β-HSD1 inhibitors for the development of potential therapeutics

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Deciphering lipid structures based on platform-independent decision rule sets

We developed decision rule sets for Lipid Data Analyzer (LDA; http://genome.tugraz.at/lda2), enabling automated and reliable annotation of lipid species and their molecular structures in high-throughput data from chromatography-coupled tandem mass spectrometry. Platform independence was proven in various mass spectrometric experiments, comprising low- and high-resolution instruments and several collision energies. We propose that this independence and the capability to identify novel lipid molecular species render current state-of-the-art lipid libraries now obsolete

Structural and Functional Hierarchy in Photosynthetic Energy Conversion—from Molecules to Nanostructures

Basic principles of structural and functional requirements of photosynthetic energy conversion in hierarchically organized machineries are reviewed. Blueprints of photosynthesis, the energetic basis of virtually all life on Earth, can serve the basis for constructing artificial light energy-converting molecular devices. In photosynthetic organisms, the conversion of light energy into chemical energy takes places in highly organized fine-tunable systems with structural and functional hierarchy. The incident photons are absorbed by light-harvesting complexes, which funnel the excitation energy into reaction centre (RC) protein complexes containing redox-active chlorophyll molecules; the primary charge separations in the RCs are followed by vectorial transport of charges (electrons and protons) in the photosynthetic membrane. RCs possess properties that make their use in solar energy-converting and integrated optoelectronic systems feasible. Therefore, there is a large interest in many laboratories and in the industry toward their use in molecular devices. RCs have been bound to different carrier matrices, with their photophysical and photochemical activities largely retained in the nano-systems and with electronic connection to conducting surfaces. We show examples of RCs bound to carbon-based materials (functionalized and non-functionalized single- and multiwalled carbon nanotubes), transitional metal oxides (ITO) and conducting polymers and porous silicon and characterize their photochemical activities. Recently, we adapted several physical and chemical methods for binding RCs to different nanomaterials. It is generally found that the P(+)(Q(A)Q(B))(−) charge pair, which is formed after single saturating light excitation is stabilized after the attachment of the RCs to the nanostructures, which is followed by slow reorganization of the protein structure. Measuring the electric conductivity in a direct contact mode or in electrochemical cell indicates that there is an electronic interaction between the protein and the inorganic carrier matrices. This can be a basis of sensing element of bio-hybrid device for biosensor and/or optoelectronic applications

Information and digital literacies; a review of concepts

A detailed literature reviewing, analysing the multiple and confusing concepts around the ideas of information literacy and digital literacy at the start of the millennium. The article was well-received, and is my most highly-cited work, with over 1100 citations