bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proximal Tibial Opening Wedge Osteotomy as the Initial Treatment for Chronic Posterolateral Corner Deficiency in the Varus Knee
Authors: Arthur Andrew , LaPrade Robert F. , Agel Julie 
Published: August 2007

Background Nonoperative treatment of posterolateral knee injuries tends to yield poor results. In patients with chronic posterolateral knee injuries, failure to correct genu varus alignment will often result in failure of the posterolateral knee repair or reconstruction. Purpose To prospectively assess the functional outcomes of patients with combined grade 3 posterolateral instability and genu varus alignment initially treated with a proximal tibial opening wedge osteotomy. Study Design Cohort study (prognosis); Level of evidence, 2. Methods Twenty-one patients with combined chronic posterolateral corner deficiency and genu varus alignment were initially treated with a proximal tibial opening wedge osteotomy and observed prospectively. Second-stage ligamentous reconstruction was performed in patients with continued clinical and functional instability after the osteotomies had healed and they had undergone at least 3 months of rehabilitation. Results At a mean follow-up of 37 months, 8 of 21 patients (38%) had sufficient improvement in knee function that a subsequent posterolateral corner reconstruction was not necessary. There was a significant difference in coronal alignment between the preoperative and postoperative mechanical axis action point. There were no significant differences in the preoperative and postoperative posterior tibial slope. Thirteen patients underwent a second-stage ligament reconstruction at an average of 13.8 months after the initial osteotomy procedure. Final postoperative Cincinnati Knee Rating System scores were significantly lower for those patients who required a subsequent posterolateral corner reconstruction than for those patients who did not have a reconstruction. The P value for the preoperative differences between groups was not significant (P = .11). Seven of 9 patients with high-velocity knee injuries required a second-stage reconstruction. Ten of 14 patients (71%) with multiligament knee injuries required a posterolateral corner reconstruction. In contrast, 4 of 6 patients (67%) with an isolated posterolateral corner injury did not require a second-stage ligament reconstruction. Conclusion Proximal tibial opening wedge osteotomy can be an effective first method of treatment for patients with chronic combined posterolateral knee injuries and genu varus alignment. Patients with low-velocity knee injuries and isolated chronic posterolateral knee injuries may not require a second-stage soft tissue ligament reconstruction after healing the osteotomy and undergoing a program of rehabilitation.
Analysis of Cartilage Tissue on a Cellular Level in Fresh Osteochondral Allograft Retrievals
Authors: Williams Seth K. , Amiel David , Ball Scott T. , Allen R. Todd , Tontz William L. , Emmerson Bryan C. , Badlani Neil M. , Emery Shawn C. , Haghighi Parviz , Bugbee William D. 
Published: August 2007

Background Fresh human osteochondral allografting is a biological cartilage replacement technique used to treat articular and osteoarticular defects in the knee. A small number of grafts fail, and we analyzed every retrieved graft during a 4-year period in order to learn more about the potential causes of failure. Hypothesis A large percentage of chondrocytes still remain viable many years after fresh osteochondral allografting. Study Design Descriptive laboratory study. Methods Retrieval specimens were obtained at the time of revision surgery and immediately analyzed. Chondrocyte viability and viable cell density were determined using a live/dead staining technique followed by confocal microscopy. Glycosaminoglycan content was a measure of the cartilage matrix. Radiolabeled sulfate uptake served as a biochemical marker of chondrocyte metabolic activity. Cartilage and subchondral bone were examined histologically. Results Fourteen patients yielded a total of 26 retrieval specimens that had been originally implanted as individual fresh osteochondral allografts. Average graft survival was 42 months. Chondrocyte viability was 82% ± 17%, and chondrocyte viable cell density was 15 590 ± 5900 viable cells/mm3. Retrieved tissue demonstrated radiolabeled sulfate uptake of 437 ± 270 counts per minute and 3.5% ± 0.8% hexosamine per dry weight. Histologically, all specimens showed some degree of cartilage fibrillation. There was evidence of bone allograft incorporation in most specimens, as well as pannus formation in 4 specimens, but no evidence of immune rejection. Conclusion A small percentage of fresh osteochondral allografts fail, but the precise cause is unknown. The main theories for failure investigated here include immunologic rejection, failure of bony incorporation, and chondrocyte death causing breakdown of the cartilage matrix. We show that chondrocytes remain viable many years after transplantation, allograft bone incorporates, and immune rejection does not seem to play a primary role in failure. Clinical Relevance Fresh osteochondral allografting is becoming more common in the treatment of articular cartilage defects in the knee. Our findings support the paradigm of fresh osteochondral allografting, the transplantation of hyaline cartilage with biological incorporation of the underlying bone scaffold. The reasons for failure of a small percentage of grafts remain unclear.
Arthroscopic Autologous Osteochondral Grafting for Cartilage Defects of the Knee
Authors: Marcacci Maurilio , Kon Elizaveta , Delcogliano Marco , Filardo Giuseppe , Busacca Maurizio , Zaffagnini Stefano 
Published: August 2007

Background Articular cartilage lesions, with their inherent limited healing potential, remain a challenging problem for orthopaedic surgeons. Various approaches have been proposed to treat these lesions; nevertheless, opinions on indications and clinical efficacy of these techniques are still controversial. Purpose To evaluate the outcome of osteochondral autografts for treatment of femoral condyle cartilage lesions at a medium-to long-term follow-up. Study Design Case series; Level of evidence, 4. Methods We prospectively evaluated 30 patients (mean age, 29.3 years) with full-thickness knee chondral lesions (<2.5 cm2) treated with arthroscopic autologous osteochondral transplantation. Thirteen patients underwent previous surgery, while 17 patients were operated on for the first time. In 19 patients, associated procedures were performed. All patients were evaluated at 2- and 7-year follow-up. The International Cartilage Repair Society form, Tegner score, and magnetic resonance imaging were used for clinical evaluation. Results The International Cartilage Repair Society objective evaluation showed 76.7% of patients had good or excellent results at 7-year follow-up, and International Knee Documentation Committee subjective score significantly improved from preoperative (34.8) to 7-year follow-up (71.8). The Tegner evaluation showed a significant improvement after the surgery at 2- and 7-year follow-up (from 2.9 to 6.2 and 5.6, respectively); however, we noticed reduced sports activity from 2- to 7-year follow-up. Magnetic resonance imaging evaluation showed good integration of the graft in the host bone and complete maintenance of the grafted cartilage in more than 60% of cases. Conclusion The results of this technique at medium- to long-term follow-up are encouraging. This arthroscopic 1-step surgery appears to be a valid solution for treatment of small, grade III to IV cartilage defects.
Long-term Follow-up and Knee Osteoarthritis Change after Medial Patellofemoral Ligament Reconstruction for Recurrent Patellar Dislocation
Authors: Nomura Eiki , Inoue Motoyasu , Kobayashi Shigeru 
Published: August 2007

BackgroundProximal or distal realignment procedures have long been selected as treatment for recurrent patellar dislocation, but associated knee osteoarthritis has been a substantial problem that leads to poor results. A new approach, medial patellofemoral ligament reconstruction, has recently started, but there have been no reports on the long-term follow-up.HypothesisAnatomical medial patellofemoral ligament reconstruction can lead to satisfactory long-term outcome and a low association rate of knee osteoarthritis.Study DesignCase series; Level of evidence, 4.MethodsTwenty-four knees from 22 patients who underwent medial patellofemoral ligament reconstruction for recurrent patellar dislocation were reviewed at a mean follow-up of 11.9 years (range, 8.5-17.2 years). A lateral release was done on 14 of 24 knees. The clinical/physical outcome and the association of knee osteoarthritis were investigated. Patellofemoral and femorotibial osteoarthritis on the radiographs was evaluated using the Crosby/Insall and the Kellgren/Lawrence grading systems.ResultsAccording to the Crosby/Insall criteria, 11 knees (46%) were classified as excellent, 10 (42%) as good, 3 (12%) as fair/poor, and none as worse at follow-up. Further lateral subluxation or dislocation occurred in only 2 knees. The mean Kujala score improved significantly from 63.2 points preoperatively to 94.2 points at follow-up (P < .0001). According to the Crosby/Insall grading system, patellofemoral osteoarthritis was none to mild in 23 of the 24 knees and moderate in 1 knee, preoperatively. At the final follow-up, 21 knees were none to mild, and 3 knees were moderate. There were only 2 knees that had definite progression from none to mild to a moderate grade.ConclusionThe association of definite knee osteoarthritis in medial patellofemoral ligament reconstruction with or without lateral release was small in the long-term follow-up. The conclusion is that medial patellofemoral ligament reconstruction not only prevents further patellar dislocation but also shows no or only slight progression of knee osteoarthritis.
Acquired hematopoietic stem-cell disorders and mammalian size
Authors: Lopes Joao V. , Pacheco Jorge M. , Dingli David 
Published: August 2007

AbstractHematopoietic stem cells (HSCs) can both self renew and differentiate into precursors of all types of blood cells. HSCs are divided into an active pool and a quiescent reserve. Cells selected for the active pool contribute to hematopoiesis for many years. Mutations in HSCs can lead to neoplasms such as chronic myeloid leukemia, although the risk of neoplastic HSC disorders varies across mammals. We use allometric scaling relations combined with mutation-selection evolutionary dynamics to determine which mammalian species is most resistant to HSC disorders. We find that the advantage of large mammals at escaping the selective pressure of cancer cells is insufficient to overcome the increased risk of acquiring mutations. Hence, mutation dominates, which favors smaller stem-cell pools and, consequently, smaller mammals, since these minimize the development of mutations in the active stem-cell pool. Consequently, the smaller the active stem-cell pools, the better.
Modular co-evolution of metabolic networks
Authors: Zhao Jing , Ding Guo-Hui , Tao Lin , Yu Hong , Yu Zhong-Hao , Luo Jian-Hua , Cao Zhi-Wei , Li Yi-Xue 
Published: August 2007

Abstract

Background
The architecture of biological networks has been reported to exhibit high level of modularity, and to some extent, topological modules of networks overlap with known functional modules. However, how the modular topology of the molecular network affects the evolution of its member proteins remains unclear.

Results
In this work, the functional and evolutionary modularity of Homo sapiens (H. sapiens) metabolic network were investigated from a topological point of view. Network decomposition shows that the metabolic network is organized in a highly modular core-periphery way, in which the core modules are tightly linked together and perform basic metabolism functions, whereas the periphery modules only interact with few modules and accomplish relatively independent and specialized functions. Moreover, over half of the modules exhibit co-evolutionary feature and belong to specific evolutionary ages. Peripheral modules tend to evolve more cohesively and faster than core modules do.

Conclusion
The correlation between functional, evolutionary and topological modularity suggests that the evolutionary history and functional requirements of metabolic systems have been imprinted in the architecture of metabolic networks. Such systems level analysis could demonstrate how the evolution of genes may be placed in a genome-scale network context, giving a novel perspective on molecular evolution.
A comprehensive system for evaluation of remote sequence similarity detection
Authors: Qi Yuan , Sadreyev Ruslan I , Wang Yong , Kim Bong-Hyun , Grishin Nick V 
Published: August 2007

Abstract

Background
Accurate and sensitive performance evaluation is crucial for both effective development of better structure prediction methods based on sequence similarity, and for the comparative analysis of existing methods. Up to date, there has been no satisfactory comprehensive evaluation method that (i) is based on a large and statistically unbiased set of proteins with clearly defined relationships; and (ii) covers all performance aspects of sequence-based structure predictors, such as sensitivity and specificity, alignment accuracy and coverage, and structure template quality.

Results
With the aim of designing such a method, we (i) select a statistically balanced set of divergent protein domains from SCOP, and define similarity relationships for the majority of these domains by complementing the best of information available in SCOP with a rigorous SVM-based algorithm; and (ii) develop protocols for the assessment of similarity detection and alignment quality from several complementary perspectives. The evaluation of similarity detection is based on ROC-like curves and includes several complementary approaches to the definition of true/false positives. Reference-dependent approaches use the 'gold standard' of pre-defined domain relationships and structure-based alignments. Reference-independent approaches assess the quality of structural match predicted by the sequence alignment, with respect to the whole domain length (global mode) or to the aligned region only (local mode). Similarly, the evaluation of alignment quality includes several reference-dependent and -independent measures, in global and local modes. As an illustration, we use our benchmark to compare the performance of several methods for the detection of remote sequence similarities, and show that different aspects of evaluation reveal different properties of the evaluated methods, highlighting their advantages, weaknesses, and potential for further development.

Conclusion
The presented benchmark provides a new tool for a statistically unbiased assessment of methods for remote sequence similarity detection, from various complementary perspectives. This tool should be useful both for users choosing the best method for a given purpose, and for developers designing new, more powerful methods. The benchmark set, reference alignments, and evaluation codes can be downloaded from ftp://iole.swmed.edu/pub/evaluation/.
Exonization of the LTR transposable elements in human genome
Authors: Piriyapongsa Jittima , Polavarapu Nalini , Borodovsky Mark , McDonald John 
Published: August 2007

Abstract

Background
Retrotransposons have been shown to contribute to evolution of both structure and regulation of protein coding genes. It has been postulated that the primary mechanism by which retrotransposons contribute to structural gene evolution is through insertion into an intron or a gene flanking region, and subsequent incorporation into an exon.

Results
We found that Long Terminal Repeat (LTR) retrotransposons are associated with 1,057 human genes (5.8%). In 256 cases LTR retrotransposons were observed in protein-coding regions, while 50 distinct protein coding exons in 45 genes were comprised exclusively of LTR RetroTransposon Sequence (LRTS). We go on to reconstruct the evolutionary history of an alternatively spliced exon of the Interleukin 22 receptor, alpha 2 gene (IL22RA2) derived from a sequence of retrotransposon of the Mammalian apparent LTR retrotransposons (MaLR) family. Sequencing and analysis of the homologous regions of genomes of several primates indicate that the LTR retrotransposon was inserted into the IL22RA2 gene at least prior to the divergence of Apes and Old World monkeys from a common ancestor (~25 MYA). We hypothesize that the recruitment of the part of LTR as a novel exon in great ape species occurred prior to the divergence of orangutans and humans from a common ancestor (~14 MYA) as a result of a single mutation in the proto-splice site.

Conclusion
Our analysis of LRTS exonization events has shown that the patterns of LRTS distribution in human exons support the hypothesis that LRTS played a significant role in human gene evolution by providing cis-regulatory sequences; direct incorporation of LTR sequences into protein coding regions was observed less frequently. Combination of computational and experimental approaches used for tracing the history of the LTR exonization process of IL22RA2 gene presents a promising strategy that could facilitate further studies of transposon initiated gene evolution.
Dimerization of inositol monophosphatase Mycobacterium tuberculosis SuhB is not constitutive, but induced by binding of the activator Mg2+
Authors: Brown Alistair K , Meng Guoyu , Ghadbane Hemza , Scott David J , Dover Lynn G , Nigou Jérôme , Besra Gurdyal S , Fütterer Klaus 
Published: August 2007

Abstract

Background
The cell wall of Mycobacterium tuberculosis contains a wide range of phosphatidyl inositol-based glycolipids that play critical structural roles and, in part, govern pathogen-host interactions. Synthesis of phosphatidyl inositol is dependent on free myo-inositol, generated through dephosphorylation of myo-inositol-1-phosphate by inositol monophosphatase (IMPase). Human IMPase, the putative target of lithium therapy, has been studied extensively, but the function of four IMPase-like genes in M. tuberculosis is unclear.

Results
We determined the crystal structure, to 2.6 Å resolution, of the IMPase M. tuberculosis SuhB in the apo form, and analysed self-assembly by analytical ultracentrifugation. Contrary to the paradigm of constitutive dimerization of IMPases, SuhB is predominantly monomeric in the absence of the physiological activator Mg2+, in spite of a conserved fold and apparent dimerization in the crystal. However, Mg2+ concentrations that result in enzymatic activation of SuhB decisively promote dimerization, with the inhibitor Li+ amplifying the effect of Mg2+, but failing to induce dimerization on its own.

Conclusion
The correlation of Mg2+-driven enzymatic activity with dimerization suggests that catalytic activity is linked to the dimer form. Current models of lithium inhibition of IMPases posit that Li+ competes for one of three catalytic Mg2+ sites in the active site, stabilized by a mobile loop at the dimer interface. Our data suggest that Mg2+/Li+-induced ordering of this loop may promote dimerization by expanding the dimer interface of SuhB. The dynamic nature of the monomer-dimer equilibrium may also explain the extended concentration range over which Mg2+ maintains SuhB activity.
PROUD: Effects of preoperative long-term immunonutrition in patients listed for liver transplantation
Authors: Nickkholgh Arash , Schneider Heinz , Encke Jens , Büchler Markus W , Schmidt Jan , Schemmer Peter 
Published: August 2007

Abstract

Background
Patients with end stage liver disease are characteristically malnourished which is associated with poor outcome. Formulas enriched with arginine, ω-3 fatty acids, and nucleotides, "immunonutrients", potentially improve their nutritional status. This study is designed to evaluate the clinical outcome of long-term "immunonutrition" of patients with end-stage liver disease while on the waiting list for liver transplantation.

Methods/design
A randomized controlled double blind multi-center clinical trial with two parallel groups comprising a total of 142 newly registered patients for primary liver transplantation has been designed to assess the safety and efficacy of the long-term administration of ORAL IMPACT®, an "immunonutrient" formula, while waiting for a graft. Patients will be enrolled the day of registration on the waiting list for liver transplantation. Study ends on the day of transplantation. Primary endpoints include improved patients' nutritional and physiological status, as measured by mid-arm muscle area, triceps skin fold thickness, grip strength, and fatigue score, as well as patients' health related quality of life. Furthermore, patients will be followed for 12 postoperative weeks to evaluate anabolic recovery after transplantation as shown by reduced post-transplant mechanical ventilation, hospital stay, wound healing, infectious morbidities (pneumonia, intraabdominal abscess, sepsis, line sepsis, wound infection, and urinary tract infection), acute and chronic rejection, and mortality.

Discussion
Formulas enriched with arginine, ω-3 fatty acids, and nucleotides have been proven to be beneficial in reducing postoperative infectious complications and length of hospital stay among the patients undergoing elective gastrointestinal surgery. Possible mechanisms include downregulation of the inflammatory responses to surgery and immune modulation rather than a sole nutritional effect.

Trial registration
ClinicalTrials.gov NCT00495859
No supra-additive effects of goserelin and radiotherapy on clonogenic survival of prostate carcinoma cells in vitro
Authors: Hermann Robert M , Schwarten Dag , Fister Stefanie , Grundker Carsten , Rave-Frank Margret , Nitsche Mirko , Hille Andrea , Thelen Paul , Schmidberger Heinz , Christiansen Hans 
Published: August 2007

Abstract
Background
Oncological results of radiotherapy for locally advanced prostate cancer (PC) are significantly improved by simultaneous application of LHRH analoga (e.g. goserelin). As 85% of PC express LHRH receptors, we investigated the interaction of goserelin incubation with radiotherapy under androgen-deprived conditions in vitro.

Methods
LNCaP and PC-3 cells were stained for LHRH receptors. Downstream the LHRH receptor, changes in protein expression of c-fos, phosphorylated p38 and phosphorylated ERK1/2 were analyzed by means of Western blotting after incubation with goserelin and irradiation with 4 Gy. Both cell lines were incubated with different concentrations of goserelin in hormone-free medium. 12 h later cells were irradiated (0 – 4 Gy) and after 12 h goserelin was withdrawn. Endpoints were clonogenic survival and cell viability (12 h, 36 h and 60 h after irradiation).

Results
Both tested cell lines expressed LHRH-receptors. Changes in protein expression demonstrated the functional activity of goserelin in the tested cell lines. Neither in LNCaP nor in PC-3 any significant effects of additional goserelin incubation on clonogenic survival or cell viability for all tested concentrations in comparison to radiation alone were seen.

Conclusion
The clinically observed increase in tumor control after combination of goserelin with radiotherapy in PC cannot be attributed to an increase in radiosensitivity of PC cells by goserelin in vitro.