Molecular Targeted Therapy for the Bone Loss Secondary to Pyogenic Spondylodiscitis Using Medications for Osteoporosis: A Literature Review

Pyogenic spondylodiscitis can cause severe osteolytic and destructive lesions in the spine. Elderly or immunocompromised individuals are particularly susceptible to infectious diseases; specifically, infections in the spine can impair the ability of the spine to support the trunk, causing patients to be bedridden, which can also severely affect the physical condition of patients. Although treatments for osteoporosis have been well studied, treatments for bone loss secondary to infection remain to be elucidated because they have pathological manifestations that are similar to but distinct from those of osteoporosis. Recently, we encountered a patient with severely osteolytic pyogenic spondylodiscitis who was treated with romosozumab and exhibited enhanced bone formation. Romosozumab stimulated canonical Wnt/β-catenin signaling, causing robust bone formation and the inhibition of bone resorption, which exceeded the bone loss secondary to infection. Bone loss due to infections involves the suppression of osteoblastogenesis by osteoblast apoptosis, which is induced by the nuclear factor-κB and mitogen-activated protein kinase pathways, and osteoclastogenesis with the receptor activator of the nuclear factor-κB ligand-receptor combination and subsequent activation of the nuclear factor of activated T cells cytoplasmic 1 and c-Fos. In this study, we review and discuss the molecular mechanisms of bone loss secondary to infection and analyze the efficacy of the medications for osteoporosis, focusing on romosozumab, teriparatide, denosumab, and bisphosphonates, in treating this pathological condition.     

Hydrogen production through dry reforming of biogas using a porous electrochemical cell: Effects of a cobalt catalyst in the electrode and mixing of air with biogas

This paper reports the performance of porous Gd-doped ceria (GDC) electrochemical cells with Co metal in both electrodes (cell No. 1) and with Ni metal in the cathode and Co metal in the anode (cell No. 2) for CO₂ decomposition, CH₄ decomposition, and the dry reforming reaction of a biogas with CO₂ gas (CH₄ + CO₂ → 2H₂ + 2CO) or with O₂ gas in air (3CH₄ +?1.875CO₂ +?1.314O₂ → 6H₂ +?4.875CO +?0.7515O₂). GDC cell No. 1 produced H₂ gas at formation rates of 0.055 and 0.33?mL-H₂/(min?m²-electrode) per 1?mL-supplied gas/(min?m²-electrode) at 600?°C and 800?°C, respectively, by the reforming of the biogas with CO₂ gas. Similarly, cell No. 2 produced H₂ gas at formation rates of 0.40?mL-H₂/(min?m²) per 1?mL-supplied gas/(min?m²) at 800?°C from a mixture of biogas and CO₂ gas. The dry reforming of a real biogas with CO₂ or O₂ gas at 800?°C proceeded thermodynamically over the Co or Ni metal catalyst in the cathode of the porous GDC cell. Faraday's law controlled the dry reforming rate of the biogas at 600?°C in cell No. 2. This paper also clarifies the influence of carbon deposition, which originates from CH₄ pyrolysis (CH₄ → C + 2H₂) and disproportionation of CO gas (2CO → C + CO₂), on the cell performance during dry reforming. The dry reforming of a biogas with O₂ molecules from air exhibits high durability because of the oxidation of the deposited carbon by supplied air.     

Effectiveness of spatial representation in the formation of network communities: experimental study on community organizer

In this paper, we present and discuss Community Organizer, a system designed to support network communities. The main characteristic of Community Organizer is the use of spatial representations for the relationships among community members including the communications exchanged among these members. These spatial representations reflect the degree of closeness of interests and concerns among the members, and are intended to provide users with clues on how to form network communities. In order to investigate the effectiveness of the proposed spatial representations, we conducted experiments with two different versions of the software. One version offered meaningful spatial representations while the other version did not. The subjects who used the former software version felt a greater sense of ‘community’, enjoyed using the software more, and actively used it longer than the subjects using the latter software version (control condition). These results indicated that the proposed spatial representations are effective in supporting network community formation.     

Rapid and comprehensive indicator for evaluation of performance of treatment processes and of river waters.

Naturally occurring UV active compounds, commonly present in almost all source waters, can be rapidly monitored by their ultraviolet absorbance at 260 nm (E260). Herein, the extent of correlation between the E260 and the removal efficiency of the hazardous contaminants, endocrine disrupters and dioxins, were investigated using various treatment and river source waters. The detection of various types of hazardous contaminants using sophisticated analytical methods, such as high resolution gas chromatography (HRGC)/high resolution mass spectrometry (HRMS) and high performance liquid chromatography (HPLC)/inductively coupled plasma (ICP)/mass spectrometry (MS), as well as various short-term bioassays, can require hours or even days for results to be obtained. The removal of the E260 correlated well with those of individual contaminants, such as endocrine disruptor chemicals and dioxins, with the various treatment processes employed. In the plots of the endocrine disrupters against the DOC/E260, a correlation was found with the endocrine activity of the Korean/Japanese river waters employed in this study.     

Gene regulation of trkB and trkC in the chick retina by light/darkness exposure

The trk gene family members; the neurotrophic receptors for neurotrophins, are implicated in the survival and the differentiation of neurons. The roles of these protooncogenes have been argued in the pathological conditions and in the specific developmental stage when the programmed cell death occurs to neurons. Here we studied a physiological role of the trk family members in the retina through observations of their gene regulation by light/darkness exposure. Northern blot analysis and immunohistochemistry demonstrate that trkB and trkC are up-regulated by light exposure and down-regulated by darkness in the rod/cone layer, the outer nuclear layer, and the ganglion cell layer. This physiological regulation suggests that these trk family members play a protective role from the damaging effect of light exposure in the retinal neurons.     

Temperature Dependence of Thermal Reflection Behavior of Al2O3–TiO2 Multilayer Thermal Energy Window Coating

An Al₂O₃–TiO₂ multilayer-coated sapphire thermal energy window coating has been fabricated using an ultra-high-speed vacuum sputtering method. Thermal reflection spectra of the coated material in the wavelength range from 1.43 to 3.33 μm are measured in ambient air at temperatures of 298, 773, and 1173 K. The result shows that the light reflectance of ∼70% is achieved using a layered structure and this performance continues up to 1173 K. Thermal reflection energy of the coated material at T =1173 K is estimated to be about three times higher than that of uncoated sapphire, suggesting the potential of this coating to control thermal radiation energy.     

Studying high impact fix-inducing changes

As software systems continue to play an important role in our daily lives, their quality is of paramount importance. Therefore, a plethora of prior research has focused on predicting components of software that are defect-prone. One aspect of this research focuses on predicting software changes that are fix-inducing. Although the prior research on fix-inducing changes has many advantages in terms of highly accurate results, it has one main drawback: It gives the same level of impact to all fix-inducing changes. We argue that treating all fix-inducing changes the same is not ideal, since a small typo in a change is easier to address by a developer than a thread synchronization issue. Therefore, in this paper, we study high impact fix-inducing changes (HIFCs). Since the impact of a change can be measured in different ways, we first propose a measure of impact of the fix-inducing changes, which takes into account the implementation work that needs to be done by developers in later (fixing) changes. Our measure of impact for a fix-inducing change uses the amount of churn, the number of files and the number of subsystems modified by developers during an associated fix of the fix-inducing change. We perform our study using six large open source projects to build specialized models that identify HIFCs, determine the best indicators of HIFCs and examine the benefits of prioritizing HIFCs. Using change factors, we are able to predict 56 % to 77 % of HIFCs with an average false alarm (misclassification) rate of 16 %. We find that the lines of code added, the number of developers who worked on a change, and the number of prior modifications on the files modified during a change are the best indicators of HIFCs. Lastly, we observe that a specialized model for HIFCs can provide inspection effort savings of 4 % over the state-of-the-art models. We believe our results would help practitioners prioritize their efforts towards the most impactful fix-inducing changes and save inspection effort.     

Studying re-opened bugs in open source software

Bug fixing accounts for a large amount of the software maintenance resources. Generally, bugs are reported, fixed, verified and closed. However, in some cases bugs have to be re-opened. Re-opened bugs increase maintenance costs, degrade the overall user-perceived quality of the software and lead to unnecessary rework by busy practitioners. In this paper, we study and predict re-opened bugs through a case study on three large open source projects—namely Eclipse, Apache and OpenOffice. We structure our study along four dimensions: (1) the work habits dimension (e.g., the weekday on which the bug was initially closed), (2) the bug report dimension (e.g., the component in which the bug was found) (3) the bug fix dimension (e.g., the amount of time it took to perform the initial fix) and (4) the team dimension (e.g., the experience of the bug fixer). We build decision trees using the aforementioned factors that aim to predict re-opened bugs. We perform top node analysis to determine which factors are the most important indicators of whether or not a bug will be re-opened. Our study shows that the comment text and last status of the bug when it is initially closed are the most important factors related to whether or not a bug will be re-opened. Using a combination of these dimensions, we can build explainable prediction models that can achieve a precision between 52.1–78.6 % and a recall in the range of 70.5–94.1 % when predicting whether a bug will be re-opened. We find that the factors that best indicate which bugs might be re-opened vary based on the project. The comment text is the most important factor for the Eclipse and OpenOffice projects, while the last status is the most important one for Apache. These factors should be closely examined in order to reduce maintenance cost due to re-opened bugs.     

Microdosimetric specification of the radiation quality of a d(48.5)+Be fast neutron therapy beam produced by a superconducting cyclotron

The proportional counter microdosimetric technique has been employed to quantify variations in the quality of a d(48.5)+Be fast neutron beam passing through a homogeneous water phantom. Single event spectra have been measured as a function of spatial location in the water phantom and field size. The measured spectra have been separated into component spectra corresponding to the gamma, recoil proton and alpha plus heavy recoil ion contribution to the total absorbed dose. The total absorbed dose normalized to the "monitor units" used in daily clinical use has been calculated from the measured spectra and compared to the data measured with calibrated ion chambers. The present measurements agree with the ion chamber data to within 5%. The RBE of the neutron beam is assumed to be proportional to the microdosimetric parameter y* for the dose ranges pertinent to fractionated neutron therapy. The relative variations in y*, assumed to be representative of variations in the RBE are mapped as a function of field size and spatial location in the phantom. A variation in the RBE of about 4% for points within and 8% for points outside a 10 cm x 10 cm field is observed. The variations in the RBE within the beam are caused by an increase in the gamma component with depth. An increase in the RBE of about 4% is observed with increasing field size which is attributed to a change in the neutron spectrum. Compared to the uncertainties in the prescribed dose, associated with uncertainties in the clinically used RBE, variation in the RBE between various tissues, and other dosimetric uncertainties caused by factors such as patient inhomogeneities, patient setup errors, patient motion, etc., the measured spatial RBE variations are not considered significant enough to be incorporated into the treatment planning scheme.     

Proteome of human endometrium: Identification of differentially expressed proteins in proliferative and secretory phase endometrium

Purpose: To exploit the potential of proteomics to identify and study additional yet‐unidentified important proteins present in human endometrium. Experimental design: The proteome of human endometrium would be established using 2‐DE and MALDI and the data analyzed to identify differential protein expression in the proliferative and secretory phase of the menstrual cycle using PDQuest software and MALDI. Results: In the present work, 2‐DE of human endometrium protein led to the resolution of over 200 spots. Subsequent MALDI analysis of 215 spots allowed the identification of 194 proteins. A total of 57 out of the 215 spots were found to be differentially expressed, out of which 49 could be identified using MALDI. These differentially expressed proteins included structural proteins, molecular chaperones, signaling proteins, metabolic proteins, proteins related to immunity, RNA biogenesis, protein biosynthesis and others. The differential expressions of seven representative proteins in secretory and proliferative phase endometrium tissue were confirmed by immunoblot analysis. Conclusion and clinical relevance: This study establishes the 2‐D proteome of human endometrium represented by 194 identified protein spots. The present data provides an important clue towards determining the function of these proteins with respect to endometrium related diseases.