bnstruct: an R package for Bayesian Network structure learning in the presence of missing data.

Abstract Motivation A Bayesian Network is a probabilistic graphical model that encodes probabilistic dependencies between a set of random variables. We introduce bnstruct, an open source R package to (i) learn the structure and the parameters of a Bayesian Network from data in the presence of missing values and (ii) perform reasoning and inference on the learned Bayesian Networks. To the best of our knowledge, there is no other open source software that provides methods for all of these tasks, particularly the manipulation of missing data, which is a common situation in practice. Availability and Implementation The software is implemented in R and C and is available on CRAN under a GPL licence. Supplementary information Supplementary data are available at Bioinformatics online

Results of Gamma Knife Radiosurgery in Acromegaly

Objective. Single-session radiosurgery with Gamma Knife (GK) may be a potential adjuvant treatment in acromegaly. We analyzed the safety and efficacy of GK in patients who had previously received maximal surgical debulking at our hospital. Methods. The study was a retrospective analysis of hormonal, radiological, and ophthalmologic data collected in a predefined protocol from 1994 to 2009. The mean age at treatment was 42.3 years (range 22–67 yy). 103 acromegalic patients participated in the study. The median follow-up was 71 months (IQ range 43–107). All patients were treated with GK for residual or recurrent GH-secreting adenoma. Results. Sixty-three patients (61.2%) reached the main outcome of the study. The rate of remission was 58.3% at 5 years (95% CI 47.6–69.0%). Other 15 patients (14.6%) were in remission after GK while on treatment with somatostatin analogues. No serious side effects occurred after GK. Eight patients (7.8%) experienced a new deficit of pituitary function. New cases of hypogonadism, hypothyroidism, and hypoadrenalism occurred in 4 of 77 patients (5.2%), 3 of 95 patients (3.2%), and 6 of 100 patients at risk (6.0%), respectively. Conclusion. In a highly selected group of acromegalic patients, GK treatment had good efficacy and safety

Decellularized diaphragmatic muscle drives a constructive angiogenic response in vivo

Skeletal muscle tissue engineering (TE) aims to efficiently repair large congenital and acquired defects. Biological acellular scaffolds are considered a good tool for TE, as decellularization allows structural preservation of tissue extracellular matrix (ECM) and conservation of its unique cytokine reservoir and the ability to support angiogenesis, cell viability, and proliferation. This represents a major advantage compared to synthetic scaffolds, which can acquire these features only after modification and show limited biocompatibility. In this work, we describe the ability of a skeletal muscle acellular scaffold to promote vascularization both ex vivo and in vivo. Specifically, chicken chorioallantoic membrane assay and protein array confirmed the presence of pro-angiogenic molecules in the decellularized tissue such as HGF, VEGF, and SDF-1\u3b1. The acellular muscle was implanted in BL6/J mice both subcutaneously and ortotopically. In the first condition, the ECM-derived scaffold appeared vascularized 7 days post-implantation. When the decellularized diaphragm was ortotopically applied, newly formed blood vessels containing CD31+, \u3b1SMA+, and vWF+ cells were visible inside the scaffold. Systemic injection of Evans Blue proved function and perfusion of the new vessels, underlying a tissue-regenerative activation. On the contrary, the implantation of a synthetic matrix made of polytetrafluoroethylene used as control was only surrounded by vWF+ cells, with no cell migration inside the scaffold and clear foreign body reaction (giant cells were visible). The molecular profile and the analysis of macrophages confirmed the tendency of the synthetic scaffold to enhance inflammation instead of regeneration. In conclusion, we identified the angiogenic potential of a skeletal muscle-derived acellular scaffold and the pro-regenerative environment activated in vivo, showing clear evidence that the decellularized diaphragm is a suitable candidate for skeletal muscle tissue engineering and regeneration

Fracture-dislocation of the thoracic spine during second trimester of pregnancy: case report and literature review

Spinal fractures associated with spinal cord injury rarely affect pregnant patients. The authors present the case of a 20-year-old woman in her 20th week of pregnancy, who suffered fracture-dislocation of the thoracic spine (T4-T5) and underwent decompression, reduction and posterior fusion with pedicle screws. Despite the complete spinal cord injury presented, the pregnancy progressed uneventfully and resulted in birth via normal delivery of a healthy newborn at term. Some particular features of this case, like the care needed in using ionizing radiation, the surgical approach and delivery, use of steroids and pregnancy complications in such patients are discussed here. Only a multidisciplinary team composed by physicians from different specialties (spinal surgeons, obstetricians and physiatrists), nurses and physiotherapists is capable of assisting pregnant patients with spinal cord injuries satisfactorily.Fraturas da coluna vertebral associadas à lesão medular raramente acometem pacientes gestantes. Os autores apresentam o caso de uma mulher de 20 anos de idade, com gestação de 20 semanas, que sofreu fratura-luxação da coluna torácica (T4-T5) e foi submetida a descompressão, redução e artrodese posterior com parafusos pediculares. Apesar de apresentar lesão medular completa, a gestação evoluiu sem intercorrências e resultou no nascimento, por parto normal, de uma criança saudável a termo. Algumas particularidades, como o cuidado com o uso de radiação ionizante, via de acesso cirúrgico e de parto, corticoterapia e complicações gestacionais em pacientes nessas condições são discutidas neste artigo. Somente uma equipe multidisciplinar, formada por médicos de diferentes especialidades (cirurgiões de coluna, obstetras e fisiatras), enfermeiras e fisioterapeutas é capaz de assistir a essas pacientes de modo satisfatório.Universidade Federal de São Paulo (UNIFESP)Universidade Metropolitana de SantosUNIFESPSciEL

Novel pulp capping material based on sodium trimetaphosphate: synthesis, characterization, and antimicrobial properties

Objectives: To evaluate the mechanical, physicochemical, and antimicrobial properties of four different formulations containing micro- or nanoparticles of sodium trimetaphosphate (mTMP and nTMP, respectively). Methodology: Four experimental groups were used in this investigation: two mTMP groups and two nTMP groups, each containing zirconium oxide (ZrO2), and solution containing either chitosan or titanium oxide (TiO2) nanoparticles (NPs). Setting time, compression resistance, and radiopacity were estimated. The agar diffusion test was used to assess the antimicrobial activity of the formulations against five different microbial strains: Streptococcus mutans, Lactobacillus casei, Actinomyces israelii, Candida albicans, and Enterococcus faecalis. Parametric and nonparametric tests were performed after evaluating homoscedasticity data (p<0.05). Results: From the properties evaluated, nTMP cements required less setting time and showed greater resistance to compression. Cements containing TiO2 showed greater radiopacity for both nTMP and mTMP. All four cement formulations showed antimicrobial activity against S. mutans and L. casei.  Conclusion: Formulations containing nTMP have shorter setting times and higher compressive strength, and those with TiO2 nanoparticles showed antimicrobial activities. Clinical relevance: The cement containing nTMP, ZrO2, and TiO2 could be an alternative material for protecting the pulp complex

Epidermal growth factor receptor expression identifies functionally and molecularly distinct tumor-initiating cells in human glioblastoma multiforme and is required for gliomagenesis

Epidermal growth factor receptor (EGFR) is a known diagnostic and, although controversial, prognostic marker of human glioblastoma multiforme (GBM). However, its functional role and biological significance in GBM remain elusive. Here, we show that multiple GBM cell subpopulations could be purified from the specimens of patients with GBM and from cancer stem cell (CSC) lines based on the expression of EGFR and of other putative CSC markers. All these subpopulations are molecularly and functionally distinct, are tumorigenic, and need to express EGFR to promote experimental tumorigenesis. Among them, EGFR-expressing tumor-initiating cells (TIC) display the most malignant functional and molecular phenotype. Accordingly, modulation of EGFR expression by gain-of-function and loss-of-function strategies in GBM CSC lines enhances and reduces their tumorigenic ability, respectively, suggesting that EGFR plays a fundamental role in gliomagenesis. These findings open up the possibility of new therapeutically relevant scenarios, as the presence of functionally heterogeneous EGFR(pos) and EGFR(neg) TIC subpopulations within the same tumor might affect clinical response to treatment

Clonal Characterization of Rat Muscle Satellite Cells: Proliferation, Metabolism and Differentiation Define an Intrinsic Heterogeneity

Satellite cells (SCs) represent a distinct lineage of myogenic progenitors responsible for the postnatal growth, repair and maintenance of skeletal muscle. Distinguished on the basis of their unique position in mature skeletal muscle, SCs were considered unipotent stem cells with the ability of generating a unique specialized phenotype. Subsequently, it was demonstrated in mice that opposite differentiation towards osteogenic and adipogenic pathways was also possible. Even though the pool of SCs is accepted as the major, and possibly the only, source of myonuclei in postnatal muscle, it is likely that SCs are not all multipotent stem cells and evidences for diversities within the myogenic compartment have been described both in vitro and in vivo. Here, by isolating single fibers from rat flexor digitorum brevis (FDB) muscle we were able to identify and clonally characterize two main subpopulations of SCs: the low proliferative clones (LPC) present in major proportion (∼75%) and the high proliferative clones (HPC), present instead in minor amount (∼25%). LPC spontaneously generate myotubes whilst HPC differentiate into adipocytes even though they may skip the adipogenic program if co-cultured with LPC. LPC and HPC differ also for mitochondrial membrane potential (ΔΨm), ATP balance and Reactive Oxygen Species (ROS) generation underlying diversities in metabolism that precede differentiation. Notably, SCs heterogeneity is retained in vivo. SCs may therefore be comprised of two distinct, though not irreversibly committed, populations of cells distinguishable for prominent differences in basal biological features such as proliferation, metabolism and differentiation. By these means, novel insights on SCs heterogeneity are provided and evidences for biological readouts potentially relevant for diagnostic purposes described

An Integer Programming approach to Bayesian Network Structure Learning

We study the problem of learning a Bayesian Network structure from data using an Integer Programming approach. We study the existing approaches, an in particular some recent works that formulate the problem as an Integer Programming model. By discussing some weaknesses of the existing approaches, we propose an alternative solution, based on a statistical sparsification of the search space. Results show how our approach can lead to promising results, especially for large network