Miracle-dz/UniFAR-FTUs huggingface dataset:
Subcellular Localization of YKL-40 in Normal and Malignant Epithelial Cells of the Breast

YKL-40 is a new prognostic biomarker in cancer. The biological function is only poorly understood. This study aimed at determining the subcellular localization of YKL-40, using immunogold labeling, in normal epithelial cells and in malignant tumor cells of the breast by immunoelectron microscopy. YKL-40 protein expression was redistributed in carcinoma versus normal glandular tissue of the breast. A reduced expression of YKL-40 in relation to intermediate filaments and desmosomes was found in tumor cells. Changes in YKL-40 expression suggest that the function of YKL-40 in cells of epithelial origin may be related to cell motility and cell–cell adhesion, features associated with invasion and migration potential of tumor cells.
Obesity Is Associated With an Increased Rate of Incidental Durotomy in Lumbar Spine Surgery

Study Design. Retrospective database analysis. Objective. To determine the impact of obesity on the rate of incidental durotomy in lumbar spine surgery. Summary of Background Data. There is a paucity of data on the overall impact of obesity on the rate of incidental durotomy in lumbar spine surgery, specifically with regard to the type of procedure performed. Methods. A large administrative database was queried for all patients who underwent lumbar spine surgery for decompression and/or fusion. They were then stratified into separate cohorts on the basis of body mass index and by procedural codes. Documentation of incidental durotomy was noted. Patient demographics and associated comorbidities were assessed. Odds ratios and 95% confidence intervals were calculated and &khgr;2 test was used to assess for statistical significance. Results. The incidental durotomy ranged from 0.5% to 2.6%, with the highest rates observed in multilevel laminectomies and revision decompressions in the obese and morbidly obese groups. For patients who underwent decompression only procedures, nonobese patients had a significantly lower rate of durotomy than the obese and morbidly obese cohorts. For patients who underwent fusion with or without decompression, there was a significantly increased rate of durotomy in obese patients compared with nonobese patients. The morbidly obese cohort also had significantly higher rates of incidental durotomy than the nonobese cohort in both revision decompression and revision fusion procedures. Conclusion. This analysis of a large administrative database demonstrates that obesity is associated with increased rates of incidental durotomy in lumbar spine surgery. Furthermore, obesity, in association with increasing complexity of the procedure, increases the rate of incidental durotomy in lumbar spine surgery. Surgeons must be aware of these increased risks as the rate of obesity increases in the population. Level of Evidence: 3
Chondrogenic and Fibrotic Process in the Ligamentum Flavum of Patients With Lumbar Spinal Canal Stenosis

Study Design. A histological, biological, and immunohisto-chemical study of human lumbar ligamentum flavum. Objective. To analyze changes in the hypertrophied ligamentum flavum and clarify their etiology. Summary of Background Data. Hypertrophy of the ligamentum flavum has been considered a major contributor to the development of lumbar spinal canal stenosis (LSCS). Although previous studies have reported some factors related to ligamentum flavum hypertrophy, its etiology is still unclear. Methods. Ligamentum flavum samples were collected from 20 patients with LSCS (LSCS group) and 10 patients with lumbar disc herniation (LDH group) as a control. The thickness of the ligamentum flavum was measured histologically. The amounts of elastic fibers and proteoglycans were assessed by Elastica-Masson staining and alcian blue staining, respectively. Gene and protein expressions related to fibrosis, inflammation, and chondrogenesis were analyzed by quantitative reverse transcription–polymerase chain reaction and immunohistochemistry. The total genes of the 2 groups were compared by DNA microarray analysis. Results. The ligamentum flavum was significantly thicker in the LSCS group, which had a smaller amount of elastic fibers and a larger amount of proteoglycans. The gene expression related to fibrosis was significantly higher in the LSCS group; however, the immunoreactivities of collagen types I and III were weaker on the dorsal side of the ligamentum flavum in the LSCS group. The gene expression related to chondrogenesis and proteoglycan synthesis was significantly higher in the LSCS group. There was no significant difference in the gene expression related to inflammation between the 2 groups. Conclusion. Synthesis of the collagenous fibers and degradation of the elastic and collagenous fibers are both accelerated in the ligamentum flavum of patient with LSCS, which may be the reason for hypertrophy of the tissue. In addition, chondrogenesis and proteoglycan synthesis may have critical roles in the pathogenesis of the ligamentum flavum hypertrophy. Level of Evidence: 5
Live cell imaging compatible immobilization of Chlamydomonas reinhardtii in microfluidic platform for biodiesel research

This paper describes a novel surface immobilization method for live‐cell imaging of Chlamydomonas reinhardtii for continuous monitoring of lipid droplet accumulation. Microfluidics allows high‐throughput manipulation and analysis of single cells in precisely controlled microenvironment. Fluorescence imaging based quantitative measurement of lipid droplet accumulation in microalgae had been difficult due to their intrinsic motile behavior. We present a simple surface immobilization method using gelatin coating as the “biological glue. ” We take advantage of hydroxyproline (Hyp)‐based non‐covalent interaction between gelatin and the outer cell wall of microalgae to anchor the cells inside the microfluidic device. We have continuously monitored single microalgal cells for up to 6 days. The immobilized microalgae remain viable (viability was comparable to bulk suspension cultured controls). When exposed to wall shear stress, most of the cells remain attached up to 0.1 dyne/cm2. Surface immobilization allowed high‐resolution, live‐cell imaging of mitotic process in real time‐which followed previously reported stages in mitosis of suspension cultured cells. Use of gelatin coated microfluidics devices can result in better methods for microalgae strain screening and culture condition optimization that will help microalgal biodiesel become more economically viable. Biotechnol. Bioeng. 2015;112: 494–501. © 2014 Wiley Periodicals, Inc.
Long‐term three‐dimensional perfusion culture of human adult bone marrow mononuclear cells in bioreactors

The construction and long‐term maintenance of three‐dimensional in vitro bone marrow models is of great interest but still quite challenging. Here we describe the use of a multi‐compartment hollow‐fiber membrane based three‐dimensional perfusion bioreactor for long‐term culture of whole human bone marrow mononuclear cells. We also investigated bioreactors with incorporated open‐porous foamed hydroxyapatite scaffolds, mimicking the in vivo bone matrix. Cells in bioreactors with and without scaffolds were cultured to 6 weeks and compared to Petri dish controls. Cells were analyzed for gene expression, surface markers by flow cytometry, metabolic activity, hematopoietic potential, viability, and attachment by immunocytochemistry. Cells in bioreactors were metabolic active during long‐term culture. The percentages of hematopoietic stem cell and mature endothelial cell fractions were maintained in bioreactors. The expression of most of the analyzed genes stabilized and increased after long‐term culture of 6 weeks. Compared to Petri dish culture controls, bioreactor perfusion culture improved in both the short and long‐term, the colony formation unit capacity of hematopoietic progenitors. Cells attached to the ample surface area provided by hydroxyapatite scaffolds. The implementation of a hydroxyapatite scaffold did not influence colony formation capacity, percentages of cell type specific fractions, gene expression, cell viability or metabolic turnover when compared to control cells cultured in bioreactors without scaffolds. In conclusion, three‐dimensional perfusion bioreactor culture enables long‐term maintenance of primary human bone marrow cells, with hydroxyapatite scaffolds providing an in vivo‐like scaffold for three‐dimensional culture. Biotechnol. Bioeng. 2015;112: 801–810. © 2014 Wiley Periodicals, Inc.
The Movement Assessment Battery for Children—Second Edition (MABC-2): A Review and Critique

The Movement Assessment Battery for Children—Second Edition (MABC-2) is a recent revision of the well-known Movement Assessment Battery for Children (MABC). The MABC-2 is designed to identify and describe impairments in motor performance of children and adolescents 3 through 16 years of age. The Performance Test and the Checklist have been standardized using a larger, more representative normative sample. The evolution of the MABC-2 and research using the MABC is presented to provide a context for the MABC-2. The content of the MABC-2 is described including the scoring format, standardization sample, reliability, and validity. The MABC-2 includes four new items, the revision of some items, the creation of a 3- through 6-year and 11- through 16-year age bands, the combination of the 7- through 8- and 9- through 10-year age bands, and a system to assist with score interpretation. The Checklist has been reorganized and the total number of items reduced to 30. The primary weakness of the MABC-2 is the lack of evidence on reliability and validity. The quality, comprehensiveness, and rigor of reliability and validity studies reported in the test manual are variable. Considering the strengths and weakness of the MABC-2, it appears to be a clinically useful instrument, however, until further reliability and validity studies are completed, therapists should be guarded when basing their clinical decisions solely on MABC-2 test results.
Hand Function in a Population-Based Sample of Young Children with Unilateral or Bilateral Cerebral Palsy

ABSTRACT Aim: To describe aspects of hand function in a population-based sample of young children with clinical signs of unilateral or bilateral cerebral palsy (CP). Method: A cross-sectional study with data from national CP registers in Norway. Manual ability was classified with the Manual Ability Classification System (MACS) or Mini-MACS. Hand use in bimanual activities was measured with the Assisting Hand Assessment (AHA) for unilateral CP or the newly developed Both Hands Assessment (BoHA) for bilateral CP. Results: From 202 children, 128 (57 females) were included (Mini-MACS/MACS levels I–V, mean age 30.4 months; SD = 12.1). Manual abilities were distributed across levels I–III in unilateral CP and levels I–V in bilateral CP. Variations in AHA and BoHA units were large. One-way ANOVA revealed associations between higher AHA or BoHA units and Mini-MACS/MACS levels of higher ability (p < 0.01) and higher age (p < 0.04). Conclusions: Compared with young children with unilateral CP, children with bilateral CP showed greater variation in Mini-MACS/MACS levels, and both sub-groups showed large variations in AHA or BoHA units. The classifications and assessments used in this study are useful to differentiate young children's ability levels. Such information is important to tailor upper limb interventions to the specific needs of children with CP.
Engineered microstructure granules for tailored drug release rate

Biomaterials developed for controlled drug delivery have demonstrated excellent results in the present study. A biomaterial prepared using hydroxyapatite (HAp) was shown to have a hollow structure with the presence of interconnected pores to house drug carriers. The poly(lactic‐co‐glycolic acid) particles were used as drug carriers loaded with dexamethasone, a corticosteroid that is known to promote osteoinduction. The surface of the drug carriers was modified using polyethyleneimine, and then conjugated to the surface of HAp granules. The hollow HAp granules had drug carriers on both their inner and outer surfaces and showed a controlled drug release rate that was comparable to that of granules containing drug carriers on their outer surface alone. The pores were designed for insertion of drug carriers and preosteoblasts. Consequently, the biomaterials influenced cellular behavior by first promoting cell proliferation and then inducing early stage osteogenic differentiation. The effects of controlled release rate were evidenced for up to two weeks after cell seeding, resulting in an increase of osteogenic differentiation. In summary, drug carriers loaded onto hollow HAp granules were shown to be suitable for patients who require replacement of missing bone for repair of bone fractures that are extremely complex, pose a significant health risk to the patient, or fail to heal properly. Biotechnol. Bioeng. 2015;112: 1936–1947. © 2015 Wiley Periodicals, Inc.
Continuous downstream processing for high value biological products: A Review

There is growing interest in the possibility of developing truly continuous processes for the large‐scale production of high value biological products. Continuous processing has the potential to provide significant reductions in cost and facility size while improving product quality and facilitating the design of flexible multi‐product manufacturing facilities. This paper reviews the current state‐of‐the‐art in separations technology suitable for continuous downstream bioprocessing, focusing on unit operations that would be most appropriate for the production of secreted proteins like monoclonal antibodies. This includes cell separation/recycle from the perfusion bioreactor, initial product recovery (capture), product purification (polishing), and formulation. Of particular importance are the available options, and alternatives, for continuous chromatographic separations. Although there are still significant challenges in developing integrated continuous bioprocesses, recent technological advances have provided process developers with a number of attractive options for development of truly continuous bioprocessing operations. Biotechnol. Bioeng. 2016;113: 465–475. © 2015 Wiley Periodicals, Inc.
Developing the Total Disability Index Based on an Analysis of the Interrelationships and Limitations of Oswestry and Neck Disability Index

Study Design. Retrospective. Objective. This study assessed the feasibility of combining Oswestry and Neck Disability Index (ODI and NDI) into 1 shorter “Total Disability Index” (TDI) from which reconstructed scores could be computed. Summary of Background Data. ODI and NDI are not pure assessments of disability related to back and neck, respectively. Because of similarities/redundancies of questions, ODI scores may be elevated in neck-pain patients and the converse is true for NDI in back-pain patients. Methods. Spine patients completed ODI and NDI, and complaints were recorded as back pain (BP), neck pain (NP), or both (BNP). Questionnaire scores were compared across cohorts via descriptives and Spearman (&rgr;) correlations. In exploring the feasibility of merging ODI/NDI, TDI was constructed from 9 ODI and 5 NDI items. Extracting questions from TDI, reconstructed 9-item rODI and 10-item rNDI indices were formed and compared with true ODI/NDI. Results. There were a total of 1207 patients: 741 BP, 134 NP, and 268 BNP. Mean ODI was 37 ± 21 and mean NDI was 32 ± 21. Patients with concurrent BP and NP had significantly more disability. Seventy-eight patients of 134 (58%) patients with NP only had at least “moderate disability” by ODI and 297 of 741 (40%) patients with back pain only, had at least “moderate disability” by NDI. ODI versus NDI correlation was &rgr; = 0.755; ODI versus reconstructed rODI correlated at &rgr; = 0.985, and NDI versus reconstructed rNDI correlated at &rgr; = 0.967 (P < 0.01). Conclusion. Elevated ODI/NDI scores in patients with isolated complaints show that disability in 1 region affects scores on both surveys. This study constructed a 14-item TDI that represents every domain of ODI/NDI with exception of ODI “Sex Life. ” From this TDI, reconstructed scores correlated near perfectly with true scores. TDI provides a more global assessment of spinal disability and is a questionnaire that reduces the time burden to patients. The TDI allows for simultaneous assessment of back, neck, and global spinal disability. Level of Evidence: 2
Numerical investigation of dynamic microorgan devices as drug screening platforms. Part II: Microscale modeling approach and validation

The authors have previously reported a rigorous macroscale modeling approach for an in vitro 3D dynamic microorgan device (DMD). This paper represents the second of a two‐part model‐based investigation where the effect of microscale (single liver cell‐level) shear‐mediated mechanotransduction on drug biotransformation is deconstructed. Herein, each cell is explicitly incorporated into the geometric model as single compartmentalized metabolic structures. Each cell's metabolic activity is coupled with the microscale hydrodynamic Wall Shear Stress (WSS) simulated around the cell boundary through a semi‐empirical polynomial function as an additional reaction term in the mass transfer equations. Guided by the macroscale model‐based hydrodynamics, only 9 cells in 3 representative DMD domains are explicitly modeled. Dynamic and reaction similarity rules based on non‐dimensionalization are invoked to correlate the numerical and empirical models, accounting for the substrate time scales. The proposed modeling approach addresses the key challenge of computational cost towards modeling complex large‐scale DMD‐type system with prohibitively high cell densities. Transient simulations are implemented to extract the drug metabolite profile with the microscale modeling approach validated with an experimental drug flow study. The results from the author's study demonstrate the preferred implementation of the microscale modeling approach over that of its macroscale counterpart. Biotechnol. Bioeng. 2016;113: 623–634. © 2015 Wiley Periodicals, Inc.
The histone deacetylase inhibitor Entinostat enhances polymer‐mediated transgene expression in cancer cell lines

Eukaryotic cells maintain an immense amount of genetic information by tightly wrapping their DNA around positively charged histones. While this strategy allows human cells to maintain more than 25,000 genes, histone binding can also block gene expression. Consequently, cells express histone acetyl transferases (HATs) to acetylate histone lysines and release DNA for transcription. Conversely, histone deacetylases (HDACs) are employed for restoring the positive charge on the histones, thereby silencing gene expression by increasing histone‐DNA binding. It has previously been shown that histones bind and silence viral DNA, while hyperacetylation of histones via HDAC inhibition restores viral gene expression. In this study, we demonstrate that treatment with Entinostat, an HDAC inhibitor, enhances transgene (luciferase) expression by up to 25‐fold in human prostate and murine bladder cancer cell lines when used with cationic polymers for plasmid DNA delivery. Entinostat treatment altered cell cycle progression, resulting in a significant increase in the fraction of cells present in the G0/G1 phase at low micromolar concentrations. While this moderate G0/G1 arrest disappeared at higher concentrations, a modest increase in the fraction of apoptotic cells and a decrease in cell proliferation were observed, consistent with the known anticancer effects of the drug. DNase accessibility studies revealed no significant change in plasmid transcriptional availability with Entinostat treatment. However, quantitative PCR studies indicated that Entinostat treatment, at the optimal dose for enhancing transgene expression, led to an increase in the amount of plasmid present in the nucleus in two cancer cell lines. Taken together, our results show that Entinostat enhances polymer‐ mediated transgene expression and can be useful in applications related to transient protein expression in mammalian cells. Biotechnol. Bioeng. 2016;113: 1345–1356. © 2015 Wiley Periodicals, Inc.
ANOMALY DETECTION IN DISTRIBUTED COMPUTER COMMUNICATION SYSTEMS

Anomaly detection is a basic functionality of intrusion detection systems. The aim of such systems in distributed computer communication systems is to recognize and notify about various events that influence a system's security. In a gain to assure efficiency, flexibility, and a quality of detection of systems security violation in a distributed environment, required detection systems should be responsive, adaptive, proactive, and less centralized than those currently deployed. Such required properties are offered by agents and multiagent systems, i.e., agent-based technology has the continuously increasing potential to offer a solution to the growing problem of designing intelligent, efficient, and flexible management systems. An agent-based approach offers the potential to develop advanced and effective distributed, network-based strategies replacing traditional node-based approaches by more perspective network-based approaches. This article is devoted to present various architectures of anomaly detection systems, which may be implemented as multiagent systems supporting the classification of observed activities as normal or abnormal. Some simple example presents hierarchical architecture of a distributed anomaly detection system, which may be implemented in the form of a multiagent decision supporting system.
Efficient enzymatic cyclization of an inhibitory cystine knot‐containing peptide

Disulfide‐rich peptides isolated from cone snails are of great interest as drug leads due to their high specificity and potency toward therapeutically relevant ion channels and receptors. They commonly contain the inhibitor cystine knot (ICK) motif comprising three disulfide bonds forming a knotted core. Here we report the successful enzymatic backbone cyclization of an ICK‐containing peptide κ‐PVIIA, a 27‐amino acid conopeptide from Conus purpurascens, using a mutated version of the bacterial transpeptidase, sortase A. Although a slight loss of activity was observed compared to native κ‐PVIIA, cyclic κ‐PVIIA is a functional peptide that inhibits the Shaker voltage‐gated potassium (Kv) channel. Molecular modeling suggests that the decrease in potency may be related to the loss of crucial, but previously unidentified electrostatic interactions between the N‐terminus of the peptide and the Shaker channel. This hypothesis was confirmed by testing an N‐terminally acetylated κ‐PVIIA, which shows a similar decrease in activity. We also investigated the conformational dynamics and hydrogen bond network of cyc‐PVIIA, both of which are important factors to be considered for successful cyclization of peptides. We found that cyc‐PVIIA has the same conformational dynamics, but different hydrogen bond network compared to those of κ‐PVIIA. The ability to efficiently cyclize ICK peptides using sortase A will enable future protein engineering for this class of peptides and may help in the development of novel therapeutic molecules. Biotechnol. Bioeng. 2016;113: 2202–2212. © 2016 Wiley Periodicals, Inc.
Amphotericin B Formulation Confusion and Mortality in an HIV-Seropositive Patient

Amphotericin B (AmB) is commonly used in patients with a human immunodeficiency virus (HIV)-positive diagnosis for the treatment of disseminated fungal infections such as Histoplasma spp. or Cryptococcus spp. Newer liposomal formulations of AmB have been introduced to the market to avoid the toxic effects of the traditional agent. With the introduction of these new agents, there is a risk of confusion between the agents in regards to dosing, which may lead to toxicity. We report the case of an HIV-seropositive patient who inadvertently received five times the dose of AmB deoxycholate for disseminated Histoplasma capsulatum and died.