Miracle-dz/UniFAR-FTUs huggingface dataset:
Emerging therapies for the treatment of osteoporosis

Osteoporosis is a chronic disease of the osseous system characterized by decreased bone strength and increased fracture risk. It is due to an imbalance in the dynamic ongoing processes of bone formation and bone resorption. Currently available osteoporosis therapies like bisphosphonates, selective estrogen receptor modulators (SERMs), and denosumab are anti-resorptive agents. Parathyroid hormone analogs like teriparatide are the only anabolic agents currently approved for osteoporosis treatment. The side-effects and limited efficacy of the presently available therapies has encouraged extensive research into the pathophysiology of the disease and newer drug targets for its treatment. The novel anti-resorptive agents being developed are newer SERMs, osteoprotegerin, c-src (cellular-sarcoma) kinase inhibitors, αVβ3 integrin antagonists, cathepsin K inhibitors, chloride channel inhibitors, and nitrates. Upcoming anabolic agents include calcilytics, antibodies against sclerostin and Dickkopf-1, statins, matrix extracellular phosphoglycoprotein fragments activin inhibitiors, and endo-cannabinoid agonists. Many of these new drugs are still in development. This article provides an insight into the emerging drugs for the treatment of osteoporosis.
The Dynamics of IS Adaptation in Multinational Corporations: A New Theoretical Lens

The specificities of multinational corporations (MNCs) have to date not been a focus area of IS research. Extant literature mostly proposes IS configurations for specific types of MNCs, following a static and prescriptive approach. Our research seeks to explain the dynamics of global IS design. It suggests a new theoretical lens for studying global IS design by applying the structural adjustment paradigm from organizational change theories. Relying on archetype theory, we conduct a longitudinal case study to theorize the dynamics of IS adaptation. We find that global IS design emerges as an organizational adaptation process to balance interpretative schemes (i.e. the organization’s values and beliefs) and structural arrangements (i.e. strategic, organizational, and IS configurations). The resulting insights can be used as a basis to further explore alternative global IS designs and movements between them.
Increase in Docetaxel-Resistance of Ovarian Carcinoma-Derived RMG-1 Cells with Enhanced Expression of Lewis Y Antigen

Epithelial carcinomas of the ovary exhibit the highest mortality rate among gynecologic malignancies. Studies found that the metabolism of glycolipids or carbohydrates is associated with acquirement of anticancer drug-resistance by cancer cells. This study was to characterize possible involvement of Lewis Y (LeY) antigen in the drug-resistance of cancer cells. We transfected the α1,2-fucosyltransferase gene into human ovarian carcinoma-derived RMG-1 cells and established RMG-1-hFUT cells with enhanced expression of LeY. We determined the effects of docetaxel on the survival of cells by MTT assaying and observed the apoptosis of cells in the presence of docetaxel by flow cytometric analysis and by transmission electron microscopy. Plasma membranes and intracellular granules in RMG-1-hFUT cells were stained with anti-LeY antibody, the intensity of the staining was higher than that in control cells. The RMG-1-hFUT cells exhibited higher resistance to docetaxel than the control cells with regard to the docetaxel concentration and time course. After treatment with 10 μg/mL docetaxel for 72 h, the control cells, but not RMG-1-hFUT, contained abundant positively stained cell debris due to disintegration of the cytoskeleton. On transmission electron microscopy, although the control cells treated with docetaxel as above showed the following morphology, i.e., absence of villi, cells shrunken in size, pyknosis, agglutinated chromatin and cell buds containing nuclei in the process of apoptosis, the RMG-1-hFUT cells showed only agglutinated chromatin and vacuoles in the cytoplasm. In summary, cells with enhanced expression of LeY were shown to acquire docetaxel-resistance, indicating the possible involvement of glycoconjugates in the drug-resistance.
Comparisons between topographically surveyed debris lines and modelled inundation levels from severe tropical cyclones Vance and Chris, and their geomorphic impact on the sand coast

Comparisons of topographically surveyed debris lines and modelled inundation levels from two very intense cyclones in Western Australia (WA) show close agreement. The largest differences between model predictions and surveyed debris occurred where wave run-up did not overtop the frontal sand dunes and was registered in the coastal landscape. Excellent agreement was found where dune overtopping occurred, as the debris largely represented the height of the storm tide. The post-event field surveys also showed a clear relationship between the height of the inundation (about 7m in one instance), the height of the coastal sand dunes, and the extent of erosion of those dunes. Dunes were eroded vertically, and completely removed, where they were overtopped by the marine inundation (including wave run-up). Horizontal erosion or scarping and landward retreat of the dune occurred where the inundation was well below the dune crest. These observations are significant for policies on set-back distances and minimum habitable floor levels of coastal developments. The results show that these standards need to be above the level of the marine inundation, not the storm tide or storm ‘still water’ level, otherwise buildings erected on filled land behind frontal dunes could be undermined through wave attack and experience structural failure. The field observations and model comparisons of the components of these marine inundations in Western Australia provide confidence in estimates previously used to ascertain the intensity of prehistoric tropical cyclones. The proportion of wave run-up on much less permeable and smoother surfaces (sand versus gravel and coral shingle) was considerably less than that used for estimates of prehistoric cyclone intensities, suggesting that wave run-up may play a less important role in constructing long-term sedimentary records of tropical cyclones.
Enriching Parikh matrix mappings

In this paper, we define the Super-Parikh (S-Parikh) matrix mapping as an extension of the Parikh matrix mapping introduced by Mateescu et al. Like the Parikh matrix, the extension revolves around a certain type of square matrices, but instead of non-negative integers, its matrix-mapped elements are non-negative rationals (fractions). We study the basic properties of the newly defined formalism and later on we investigate the injectivity of the mapping. Also, we begin a search for the reverse mapping – that is a method for obtaining a word, given the S-Parikh matrix.
Antiretroviral genotypic resistance in plasma RNA and whole blood DNA in HIV‐1 infected patients failing HAART

The extent to which HIV‐1 proviral DNA mutations cause clinically relevant antiretroviral resistance is still controversial. Paired plasma HIV‐1 RNA and whole blood DNA were compared in patients failing HAART to investigate if the additional knowledge of archived mutations could improve the selection of potentially active drugs. Seventy‐three HIV‐1‐infected patients with first/second HAART failure were studied before starting a new regimen based on RNA genotyping. Follow‐up data after a 12‐week therapy were available. DNA genotyping was retrospectively performed on stored whole blood samples and mutational profiles were compared to those from RNA. The mean number of IAS pol mutations was significantly higher in RNA (4.45 ± 2.76) than in DNA (2.88 ± 2.47) (P < 0.001). DNA genotyping provided a 6% increase in detection of resistance‐associated mutations. Among 64/73 patients showing discordant DNA/RNA profiles, 54 (84%) also differed for predicted active drugs. 16/73 (22%) patients had ≥1 mutation revealed by DNA genotyping alone, probably affecting therapy success in 2/16. However, neither RNA/DNA discordance nor detection of isolated DNA mutations were statistically associated with outcome. In conclusion, plasma RNA remains the elective choice for HIV genotyping in patients with therapy failure, even if the detection of proviral resistance‐associated mutations, not simultaneously found in RNA, is a frequent event. Therefore, in some cases DNA plus RNA genotyping might assist in choosing more accurately subsequent antiretroviral regimens. J. Med. Virol. 80:1695–1706, 2008. © 2008 Wiley‐Liss, Inc.
Connection Scan Algorithm

We introduce the Connection Scan Algorithm (CSA) to efficiently answer queries to timetable information systems. The input consists, in the simplest setting, of a source position and a desired target position. The output consists of a sequence of vehicles such as trains or buses that a traveler should take to get from the source to the target. We study several problem variations such as the earliest arrival and profile problems. We present algorithm variants that only optimize the arrival time or additionally optimize the number of transfers in the Pareto sense. An advantage of CSA is that it can easily adjust to changes in the timetable, allowing the easy incorporation of known vehicle delays. We additionally introduce the Minimum Expected Arrival Time (MEAT) problem to handle possible, uncertain, future vehicle delays. We present a solution to the MEAT problem that is based on CSA. Finally, we extend CSA using the multilevel overlay paradigm to answer complex queries on nationwide integrated timetables with trains and buses.
Effect of Substrate Bias and Temperature on Friction and Wear Properties for ta-C Coating Prepared under Different Substrate Bias Voltages with Filtered Cathodic Vacuum Arc Deposition

In this paper, the tribological behaviors of 1 μm of tetrahedral amorphous carbon (ta-C) coatings deposited with a different substrate bias of -0 V, -100 V and -300 V are examined under elevated temperature up to 600°C. It is found that wear behavior could be divided into two distinct regions according to testing temperature. The variation trend of the specific wear rate of ta-C coatings in region I at 23, 100 and 200°C are affected by abrasive particles which coincide with sp content of ta-C coatings. In region II at 300, 400 and 500°C, the transfer layer play a major role in reduction of wear rate as a function of substrate bias.
Complete Resequencing of 40 Genomes Reveals Domestication Events and Genes in Silkworm (Bombyx)

The Taming of the Silkworm Silkworms, Bombyx mori, represent one of the few domesticated insects, having been domesticated over 10,000 years ago. Xia et al. (p. 433, published online 27 August) sequenced 29 domestic and 11 wild silkworm lines and identified genes that were most likely to be selected during domestication. These genes represent those that enhance silk production, reproduction, and growth. Furthermore, silkworms were probably only domesticated once from a large progenitor population, rather than on multiple occasions, as has been observed for other domesticated animals. Silkworm genomes show signatures of selection associated with domestication. A single–base pair resolution silkworm genetic variation map was constructed from 40 domesticated and wild silkworms, each sequenced to approximately threefold coverage, representing 99.88% of the genome. We identified ~16 million single-nucleotide polymorphisms, many indels, and structural variations. We find that the domesticated silkworms are clearly genetically differentiated from the wild ones, but they have maintained large levels of genetic variability, suggesting a short domestication event involving a large number of individuals. We also identified signals of selection at 354 candidate genes that may have been important during domestication, some of which have enriched expression in the silk gland, midgut, and testis. These data add to our understanding of the domestication processes and may have applications in devising pest control strategies and advancing the use of silkworms as efficient bioreactors.
Photobleaching and phototoxicity of KillerRed in tumor spheroids induced by continuous wave and pulsed laser illumination

The purpose of this study was to evaluate photobleaching of the genetically encoded photosensitizer KillerRed in tumor spheroids upon pulsed and continuous wave (CW) laser irradiation and to analyze the mechanisms of cancer cell death after the treatment. We observed the light‐dose dependent mechanism of KillerRed photobleaching over a wide range of fluence rates. Loss of fluorescence was limited to 80% at light doses of 150 J/cm2 and more. Based on the bleaching curves, six PDT regimes were applied for irradiation using CW and pulsed regimes at a power density of 160 mW/cm2 and light doses of 140 J/cm2, 170 J/cm2 and 200 J/cm2. Irradiation of KillerRed‐expressing spheroids in the pulsed mode (pulse duration 15 ns, pulse repetition rate 10 Hz) induced predominantly apoptotic cell death, while in the case of CW mode the cancer cells underwent necrosis. In general, these results improve our understanding of photobleaching mechanisms in GFP‐like proteins and show the importance of appropriate selection of treatment mode for PDT with KillerRed. Representative fluorescence image of two KillerRed‐expressing spheroids before and immediately after CW irradiation.
Driving Simulator Training Is Associated with Reduced Inhibitory Workload in Older Drivers

Background: In demanding cognitive tasks, older people mostly experience more problems than younger people, and their brain workload is higher. An overloaded or exhausted mental workload is frequently associated with unsafe driving behavior. In this paper, we hypothesize that 10 active training sessions in a driving simulator positively influence brain workload, which relates to a beneficial increase in on-road driving performance. Methods: Ninety-one healthy active drivers (62–87 years) were randomly assigned to: (a) a driving simulator-training group; (b) an attention-training group; or (c) a control group. The dependent variables of this training study were brain workload (theta Fz/alpha Pz), and performance in three tasks, for which inhibition of inadequate responses (Stroop, Negative Priming, and Flanker) is required. Seventy-seven participants (85% of the total sample) completed the training. Training gains were analyzed by using a multiple regression analysis with planned comparisons. Results: The results revealed that the driving simulator training reduced brain workload during performance of the inhibition tasks. The performance of the simulator group during the inhibition tasks did not improve, but the participants completed the tasks with less brain workload compared to the attention-training group. Conclusion: Adding to our first paper on the Drive-Wise project, this paper now focuses on the superiority of the driving simulator training, compared to attention-training in regards to reducing brain workload. The change in brain workload seems to be associated with a positive change in drivers’ behavior on the road. Hence, a driving simulator training lasting only ten sessions leads to beneficial neuroplastic changes. This demonstrates brain plasticity of older people and its possible positive influence in real driving behavior.
Diagnostic Accuracy of Handheld Echocardiography for Evaluation of Aortic Stenosis

Background: Symptomatic severe aortic stenosis is associated with increased mortality and morbidity. Early identification of these patients by echocardiography is crucial. We conducted this study to evaluate a handheld ultrasound device (HCU) in patients with suspected severe aortic stenosis (AS) in comparison to a standard echocardiography device (SE). Methods: A HCU (Vivid I; GE Healthcare) and a SE device (Philips iE 33) were used to evaluate 50 consecutive patients with suspected severe AS. Two consecutive echocardiographic studies were performed by two experienced and blinded examiners using HCU and SE device. AS was graded by mean transaortic pressure, aortic valve area (AVA), and indexed AVA (AVA adjusted for body surface area). Results: Mean difference for mean transaortic gradient, AVA and indexed AVA for the SE and HCU device were 1.28 mmHg (−0.70 to 3.26 mmHg), −0.02 cm2 (−0.06 to 0.01 cm2), and −0.01 cm2/m2 (−0.03 to 0.01 cm2/m2), respectively. Discrepancies between both devices were not associated with misinterpretation of the degree of AS. Conclusion: Our study demonstrates that HCU can be used to evaluate patients with suspected AS. (ECHOCARDIOGRAPHY 2010;27:481‐486)
Comparison of Different Attenuation Correction Methods for Dual Gating Myocardial Perfusion SPECT/CT

Dual respiratory-cardiac gating realizes motion-freeze myocardial perfusion single photon emission computed tomography (SPECT). The aim of this paper is to evaluate the performance of various attenuation maps for dual gating cardiac SPECT. We used extended cardiac-torso phantom with Tc-99m-sestamibi distribution to generate a dataset with both respiratory and cardiac motion and then grouped them based on six respiratory and eight cardiac phases. The corresponding attenuation correction (AC) maps were used to simulate different CT protocols: dual gating CT (DCT), respiratory gated CT (RCT), cine average CT (ACT), interpolated CT (ICT), helical CTs at end-inspiration (HCT-in), end-expiration (HCT-ex), and mid-respiration (HCT-mid), respectively. One hundred and twenty noise-free and realistic noisy projections were generated over 180° from RAO to LPO and reconstructed by OS-EM method using different AC maps. The reconstructed images in different respiratory phases were registered to one reference end-expiration phase and summed up as a cardiac image for each cardiac phase. The corresponding polar maps were generated and further analyzed using 17-segment plots. Relative difference (RD) of the average intensity was computed in each segment using the polar maps with DCT-AC as reference. Substantial artifacts could be found in HCT-in AC images in every cardiac phase. For all eight noise-free cardiac phases, the average RDmax for AC with ACT, HCT-ex, HCT-in, HCT-mid, RCT, and ICT comparing to DCT were 4.76%, 4.95%, 10.54%, 4.23%, 2.39%, and 2.76%, respectively. For all eight noisy cardiac phases, the average RDmax for AC with ACT, HCT-ex, HCT-in, HCT-mid, RCT, and ICT comparing to DCT were 4.09%, 5.04%, 9.24%, 4.02%, 3.22%, and 2.85%, respectively. The ICT and RCT have the best AC performance for dual gating SPECT, while HCT-ex, HCT-in, HCT-mid, and ACT show inferior results. Since RCT and DCT are not commonly used in clinics due to complex implementation and radiation concern, ICT is recommended, followed by HCT-mid or HCT-ex for AC in dual gating cardiac SPECT with good accuracy and relative low radiation dose.
IDENTIFYING CONTINUING AND NON-CONTINUING ADULT 4-H VOLUNTEERS: HOW HAVE THEY EVOLVED OVER TIME?

The initial component of a volunteer administration model is identification. Potential volunteers must be identified before they can be recruited, screened, selected, oriented, educated, empowered, recognized, evaluated or retained. Identifying who is most likely to volunteer is a key component of a volunteer recruitment initiative. Additionally, it is important to determine if differences exist between those individuals who continue their service of volunteerism for an extended period of time and those who terminate their service of volunteerism after three years of service or less. Moreover, it is important for Extension Educators to be aware of volunteer demographics and how these descriptive profiles may either remain constant or change over time. The purpose of this study was to identify the people most likely to volunteer for service as an adult 4-H leader. Findings from this study revealed that the profile of a typical Indiana 4-H volunteer during 1994 was remarkably similar to profiles of other 4-H and youth organizational volunteers from across the United States since 1950.
Interventions for preventing unintended pregnancies among adolescents.

BACKGROUND Unintended pregnancy among adolescents represent an important public health challenge in developed and developing countries. Numerous prevention strategies such as health education, skills-building and improving accessibility to contraceptives have been employed by countries across the world, in an effort to address this problem. However, there is uncertainty regarding the effects of these intervention, and hence the need to review their evidence-base OBJECTIVES To assess the effects of primary prevention interventions (school-based, community/home-based, clinic-based, and faith-based) on unintended pregnancies among adolescents. SEARCH STRATEGY We searched electronic databases (CENTRAL, PubMed, EMBASE) ending December 2008. Cross-referencing, hand-searching, and contacting experts yielded additional citations. SELECTION CRITERIA We included both individual and cluster randomized controlled trials (RCTs) evaluating any interventions that aimed to increase knowledge and attitudes relating to risk of unintended pregnancies, promote delay in the initiation of sexual intercourse and encourage consistent use of birth control methods to reduce unintended pregnancies in adolescents aged 10-19 years. DATA COLLECTION AND ANALYSIS Two reviewers independently assessed trial eligibility and risk of bias in studies that met the inclusion criteria. Where appropriate, binary outcomes were pooled using random effects model with a 95% confidence interval (Cl). MAIN RESULTS Forty one RCTs that enrolled 95,662 adolescents were included. Participants were ethnically diverse. Eleven studies randomized individuals, twenty seven randomized clusters (schools (19), classrooms (5), and communities/neighbourhoods (3). Three studies were mixed (individually and cluster randomized). The length of follow up varied from 3 months to 4.5 years. Data could only be pooled for a number of studies (15) because of variations in the reporting of outcomes. Results showed that multiple interventions (combination of educational and contraceptive interventions) lowered the rate of unintended pregnancy among adolescents. Evidence on the possible effects of interventions on secondary outcomes (initiation of sexual intercourse, use of birth control methods, abortion, childbirth, sexually transmitted diseases) is not conclusive.Methodological strengths included a relatively large sample size and statistical control for baseline differences, while limitations included lack of biological outcomes, possible self-report bias, analysis neglecting clustered randomization and the use of different statistical test in reporting outcomes. AUTHORS' CONCLUSIONS Combination of educational and contraceptive interventions appears to reduce unintended pregnancy among adolescents. Evidence for program effects on biological measures is limited. The variability in study populations, interventions and outcomes of included trials, and the paucity of studies directly comparing different interventions preclude a definitive conclusion regarding which type of intervention is most effective.