Miracle-dz/UniFAR-FTUs huggingface dataset:
Romosozumab in postmenopausal women with low bone mineral density

BACKGROUND Sclerostin is an osteocyte-derived inhibitor of osteoblast activity. The monoclonal antibody romosozumab binds to sclerostin and increases bone formation. METHODS In a phase 2, multicenter, international, randomized, placebo-controlled, parallel-group, eight-group study, we evaluated the efficacy and safety of romosozumab over a 12-month period in 419 postmenopausal women, 55 to 85 years of age, who had low bone mineral density (a T score of -2.0 or less at the lumbar spine, total hip, or femoral neck and -3.5 or more at each of the three sites). Participants were randomly assigned to receive subcutaneous romosozumab monthly (at a dose of 70 mg, 140 mg, or 210 mg) or every 3 months (140 mg or 210 mg), subcutaneous placebo, or an open-label active comparator--oral alendronate (70 mg weekly) or subcutaneous teriparatide (20 μg daily). The primary end point was the percentage change from baseline in bone mineral density at the lumbar spine at 12 months. Secondary end points included percentage changes in bone mineral density at other sites and in markers of bone turnover. RESULTS All dose levels of romosozumab were associated with significant increases in bone mineral density at the lumbar spine, including an increase of 11.3% with the 210-mg monthly dose, as compared with a decrease of 0.1% with placebo and increases of 4.1% with alendronate and 7.1% with teriparatide. Romosozumab was also associated with large increases in bone mineral density at the total hip and femoral neck, as well as transitory increases in bone-formation markers and sustained decreases in a bone-resorption marker. Except for mild, generally nonrecurring injection-site reactions with romosozumab, adverse events were similar among groups. CONCLUSIONS In postmenopausal women with low bone mass, romosozumab was associated with increased bone mineral density and bone formation and with decreased bone resorption. (Funded by Amgen and UCB Pharma; ClinicalTrials.gov number, NCT00896532.).
Data Visualization and Mining using the GPU

An exciting development in the computing industry has been the emergence of graphics processing units (the GPU) as a fast general purpose co-processor. Initially designed for gaming applications, todays GPUs demonstrate impressive computing power and high levels of parallelism and are now being used for a variety of applications far removed from traditional graphics rendering settings. Perhaps the most powerful use of the GPU has been in visualization, which couples the raw computing power of the GPU with its extensive capabilities for rendering scenes. The GPU provides the required computing power and real-time interactive rendering capabilities and there are now GPU-assisted algorithms for many fundamental problems in data visualization and analysis, including such basic primitives as matrix operations, FFTs, wavelet transforms, clustering and mining data streams. This is an exciting and fast developing area, and the tools and technique are now mature enough that researchers with no experience in using the GPU can use it to develop new data mining tools. The purpose of this tutorial is to introduce the KDD audience to the GPU and the programming model it represents, describe the ways in which one can program the GPU, and demonstrate a set of data mining primitives that have been implemented effectively on the GPU.
On the role of spatial resolution on snow estimates using a process‐based snow model across a range of climatology and elevation

Hydrological processes in mountainous settings depend on snow distribution, whose prediction accuracy is a function of model spatial scale. Although model accuracy is expected to improve with finer spatial resolution, an increase in resolution comes with modelling costs related to increased computational time and greater input data and parameter information. This computational and data collection expense is still a limiting factor for many large watersheds. Thus, this work's main objective is to question which physical processes lead to loss in model accuracy with regard to input spatial resolution under different climatic conditions and elevation ranges. To address this objective, a spatially distributed snow model, iSnobal, was run with inputs distributed at 50‐m—our benchmark for comparison—and 100‐m resolutions and with aggregated (averaged from the fine to the large resolution) inputs from the 50‐m model to 100‐, 250‐, 500‐, and 750‐m resolution for wet, average, and dry years over the Upper Boise River Basin (6,963 km2), which spans four elevation bands: rain dominated, rain–snow transition, and snow dominated below treeline and above treeline. Residuals, defined as differences between values quantified with high resolution (>50 m) models minus the benchmark model (50 m), of simulated snow‐covered area (SCA) and snow water equivalent (SWE) were generally slight in the aggregated scenarios. This was due to transferring the effects of topography on meteorological variables from the 50‐m model to the coarser scales through aggregation. Residuals in SCA and SWE in the distributed 100‐m simulation were greater than those of the aggregated 750 m. Topographic features such as slope and aspect were simplified, and their gradient was reduced due to coarsening the topography from the 50‐ to 100‐m resolution. Therefore, solar radiation was overestimated, and snow drifting was modified and caused substantial SCA and SWE underestimation in the distributed 100‐m model relative to the 50‐m model. Large residuals were observed in the wet year and at the highest elevation band when and where snow mass was large. These results support that model accuracy is substantially reduced with model scales coarser than 50 m.
Budgeted Influence Maximization for Multiple Products

The typical algorithmic problem in viral marketing aims to identify a set of influential users in a social network, who, when convinced to adopt a product, shall influence other users in the network and trigger a large cascade of adoptions. However, the host (the owner of an online social platform) often faces more constraints than a single product, endless user attentions, unlimited budget and unbounded time; in reality, multiple products need to be advertised, each user can tolerate only a small number of recommendations, influencing user has a cost and advertisers have only limited budgets, and the adoptions need to be maximized within a short time window. Given theses myriads of user, monetary, and timing constraints, it is extremely challenging for the host to design principled and efficient viral market algorithms with provable guarantees. In this paper, we provide a novel solution by formulating the problem as a submodular maximization in a continuous-time diffusion model under an intersection of a matroid and multiple knapsack constraints. We also propose an adaptive threshold greedy algorithm which can be faster than the traditional greedy algorithm with lazy evaluation, and scalable to networks with million of nodes. Furthermore, our mathematical formulation allows us to prove that the algorithm can achieve an approximation factor of $k_a/(2+2 k)$ when $k_a$ out of the $k$ knapsack constraints are active, which also improves over previous guarantees from combinatorial optimization literature. In the case when influencing each user has uniform cost, the approximation becomes even better to a factor of $1/3$. Extensive synthetic and real world experiments demonstrate that our budgeted influence maximization algorithm achieves the-state-of-the-art in terms of both effectiveness and scalability, often beating the next best by significant margins.
Endosseous implant anchorage is critically dependent on mechanostructural determinants of peri‐implant bone trabeculae

Low bone mass is highly prevalent among patients receiving endosseous implants. In turn, the implantation prognosis in low‐density skeletal sites is poor. However, little is known about the mechanostructural determinants of implant anchorage. Using metabolic manipulations that lead to low bone density and to its rescue, we show here that anchorage is critically dependent on the peri‐implant bone (PIB). Titanium implants were inserted horizontally into the proximal tibial metaphysis of adult rats 6 weeks after orchiectomy (ORX) or sham ORX. Systemic intermittent administration of human parathyroid hormone (1–34) [iahPTH(1–34)] or vehicle commenced immediately thereafter for 6 weeks. The bone‐implant apparatus was then subjected to image‐guided failure assessment, which assesses biomechanical properties and microstructural deformation concomitantly. Anchorage failure occurred mainly in PIB trabeculae, 0.5 to 1.0 mm away from the implant. Mechanically, the anchorage performed poorly in ORX‐induced low‐density bone, attributable mainly to decreased trabecular number. iahPTH(1–34) rescued the PIB density and implant mechanical function by augmenting trabecular thickness (Tb.Th). However, implant biomechanical properties in low‐density bone were relatively insensitive to implant surface treatment that affected only the osseointegration (%bone‐implant contact). These results support a model wherein anchorage failure involves buckling of the weakest trabecular struts followed by sequential failure of the stronger trabeculae. Treatment with iahPTH(1–34) induced thicker struts, which were able to delay and even prevent failure of individual elements, thus implicating trabecular thickness as a prime target for enhancing implant anchorage by systemic bone anabolic therapy. © 2010 American Society for Bone and Mineral Research.
Corporate Governance and Risk Taking: Evidence from the U.K. and German Insurance Markets

We analyze the impact of factors related to corporate governance (i.e., compensation, monitoring, and ownership structure) on risk taking in the insurance industry. We measure asset, product, and financial risk in insurance companies and employ a structural equation model in which corporate governance is modeled as a latent factor. Based on this model, we present empirical evidence on the link between corporate governance and risk taking, considering insurers from two large European insurance markets. Higher levels of compensation, increased monitoring (more independent boards with more meetings), and more blockholders are associated with lower risk taking. Our empirical results provide justification for including factors related to corporate governance in insurance regulation.
Genetic susceptibility to increased bacterial translocation influences the response to biological therapy in patients with Crohn's disease

Objective The aetiology of Crohn's disease (CD) has been related to nucleotide-binding oligomerisation domain containing 2 (NOD2) and ATG16L1 gene variants. The observation of bacterial DNA translocation in patients with CD led us to hypothesise that this process may be facilitated in patients with NOD2/ATG16L1-variant genotypes, affecting the efficacy of anti-tumour necrosis factor (TNF) therapies. Design 179 patients with Crohn's disease were included. CD-related NOD2 and ATG16L1 variants were genotyped. Phagocytic and bactericidal activities were evaluated in blood neutrophils. Bacterial DNA, TNFα, IFNγ, IL-12p40, free serum infliximab/adalimumab levels and antidrug antibodies were measured. Results Bacterial DNA was found in 44% of patients with active disease versus 23% of patients with remitting disease (p=0.01). A NOD2-variant or ATG16L1-variant genotype was associated with bacterial DNA presence (OR 4.8; 95% CI 1.1 to 13.2; p=0.001; and OR 2.4; 95% CI 1.4 to 4.7; p=0.01, respectively). This OR was 12.6 (95% CI 4.2 to 37.8; p=0.001) for patients with a double-variant genotype. Bacterial DNA was associated with disease activity (OR 2.6; 95% CI 1.3 to 5.4; p=0.005). Single and double-gene variants were not associated with disease activity (p=0.19). Patients with a NOD2-variant genotype showed decreased phagocytic and bactericidal activities in blood neutrophils, increased TNFα levels in response to bacterial DNA and decreased trough levels of free anti-TNFα. The proportion of patients on an intensified biological therapy was significantly higher in the NOD2-variant groups. Conclusions Our results characterise a subgroup of patients with CD who may require a more aggressive therapy to reduce the extent of inflammation and the risk of relapse.
Dynamic association for load balancing and interference avoidance in multi-cell networks

Next-generation cellular networks will provide higher cell capacity by adopting advanced physical layer techniques and broader bandwidth. Even in such networks, boundary users would suffer from low throughput due to severe intercell interference and unbalanced user distributions among cells, unless additional schemes to mitigate this problem are employed. In this paper, we tackle this problem by jointly optimizing partial frequency reuse and load-balancing schemes in a multicell network. We formulate this problem as a network-wide utility maximization problem and propose optimal offline and practical online algorithms to solve this. Our online algorithm turns out to be a simple mixture of inter- and intra-cell handover mechanisms for existing users and user association control and cell-site selection mechanisms for newly arriving users. A remarkable feature of the proposed algorithm is that it uses a notion of expected throughput as the decision making metric, as opposed to signal strength in conventional systems. Extensive simulations demonstrate that our online algorithm can not only closely approximate network-wide proportional fairness but also provide two types of gain, interference avoidance gain and load balancing gain, which yield 20~100% throughput improvement of boundary users (depending on traffic load distribution), while not penalizing total system throughput.We also demonstrate that this improvement cannot be achieved by conventional systems using universal frequency reuse and signal strength as the decision making metric.
Inactive learning?: difficulties employing active learning in practice

Despite the tremendous level of adoption of machine learning techniques in real-world settings, and the large volume of research on active learning, active learning techniques have been slow to gain substantial traction in practical applications. This reluctance of adoption is contrary to active learning's promise of reduced model-development costs and increased performance on a model-development budget. This essay presents several important and under-discussed challenges to using active learning well in practice. We hope this paper can serve as a call to arms for researchers in active learning--an encouragement to focus even more attention on how practitioners might actually use active learning.
Simvastatin Induces Heme Oxygenase-1: A Novel Mechanism of Vessel Protection

Background—Evidence from experimental and clinical studies indicates that statins can protect the vessel wall through cholesterol-independent mechanisms. The “pleiotropic” effects include the prevention of inflammation and proliferation of vascular cells. Here, we studied whether heme oxygenase-1 (HO-1), an important cytoprotective molecule, is induced by simvastatin and the role of HO-1 in the pleiotropic effects of simvastatin. Methods and Results—Human and rat aortic smooth muscle cells treated with simvastatin showed an elevated level of HO-1 for up to 24 hours. The induction of HO-1 by simvastatin was not found in cultured endothelial cells and macrophages. Injecting C57BL/6J mice intraperitoneally with simvastatin increased the level of HO-1 in vascular SMCs (VSMCs) in the tunica media. Treating VSMCs with zinc protoporphyrin, an HO-1 inhibitor, or HO-1 small interfering RNA (siRNA) blocked the antiinflammatory effect of simvastatin, including the inhibition of nuclear factor-&kgr;B activation and nitric oxide production. Blockade of HO-1 also abolished the simvastatin-induced p21Waf1 and the associated antiproliferative effect. Simvastatin activated p38 and Akt in VSMCs, and the respective inhibitor of p38 and phosphoinositide 3-kinase (PI3K) greatly reduced the level of simvastatin-induced HO-1, which suggests the involvement of p38 and the PI3K-Akt pathway in HO-1 induction. Conclusions—Simvastatin activates HO-1 in VSMCs in vitro and in vivo. The antiinflammatory and antiproliferative effects of simvastatin occur largely through the induced HO-1.
Feature generation for textual information retrieval using world knowledge

Imagine an automatic news filtering system that tracks company news. Given the news item "FDA approves ciprofloxacin for victims of anthrax inhalation", how can the system know that the drug mentioned is an antibiotic produced by Bayer? Or consider an information professional searching for data on RFID technology -- how can a computer understand that the item "Wal-Mart supply chain goes real time" is relevant for the search? Algorithms we present can do just that.
Bacteriology and drug susceptibility analysis of pus from patients with severe intra-abdominal infection induced by abdominal trauma

The aim of the present study was to retrospectively analyze the bacteriology and drug susceptibility of pus flora from abdominal trauma patients with severe intra-abdominal infection (SIAI). A total of 41 patients with SIAI induced by abdominal trauma were enrolled in the study, from which 123 abdominal pus samples were obtained. The results from laboratory microbiology and drug sensitivity were subjected to susceptibility analysis using WHONET software. A total of 297 strains were isolated in which Gram-negative bacteria, Gram-positive bacteria and fungi accounted for 53.5 (159/297), 44.1 (131/297) and 0.7% (2/297), respectively. Anaerobic bacteria accounted for 1.7%. The five predominant bacteria were Escherichia coli (E. coli), Staphylococcus aureus (S. aureus), Klebsiella pneumoniae (K. pneumoniae), Enterococcus faecalis and Pseudomonas aeruginosa (P. aeruginosa). E. coli was highly susceptible to cefoperazone (91%) and imipenem (98%), while Gram-positive cocci were highly susceptible to teicoplanin (100%) and linezolid (100%). S. aureus was 100% susceptible to vancomycin and K. pneumoniae was highly susceptible to imipenem (100%) and amikacin (79%). P. aeruginosa was the most susceptible to ciprofloxacin (90%). Gram-negative bacterial infection was present in the majority of cases of SIAI. However, a large number of patients were infected by Gram-positive bacteria, particularly S. aureus that exhibited significant resistance to penicillin (100%), oxacillin (100%) and a third-generation cephalosporin antibiotic cefotaxime (95%). Amongst the pathogenic bacteria that cause SIAI, both Gram-negative and Gram-positive bacteria account for a high proportion, so high-level and broad-spectrum antibiotics should be initially used.
Bicarbonate does not improve hemodynamics in critically ill patients who have lactic acidosis. A prospective, controlled clinical study.

STUDY OBJECTIVE To determine whether correction of acidemia using bicarbonate improves hemodynamics in patients who have lactic acidosis. DESIGN Prospective, randomized, blinded, crossover study. Each patient sequentially received sodium bicarbonate and equimolar sodium chloride. The order of the infusions was randomized. SETTING Intensive care unit of a tertiary care hospital. PATIENTS Fourteen patients who had metabolic acidosis (bicarbonate less than 17 mmol/L and base excess less than -10) and increased arterial lactate (mean, 7.8 mmol/L). All had pulmonary artery catheters and 13 were receiving catecholamines. MEASUREMENTS AND MAIN RESULTS Sodium bicarbonate (2 mmol/kg body weight over 15 minutes) increased arterial pH (7.22 to 7.36, P less than 0.001), serum bicarbonate (12 to 18 mmol/L, P less than 0.001), and partial pressure of CO2 in arterial blood (PaCO2) (35 to 40 mm Hg, P less than 0.001) and decreased plasma ionized calcium (0.95 to 0.87 mmol/L, P less than 0.001). Sodium bicarbonate and sodium chloride both transiently increased pulmonary capillary wedge pressure (15 to 17 mm Hg, and 14 to 17 mm Hg, P less than 0.001) and cardiac output (18% and 16%, P less than 0.01). The mean arterial pressure was unchanged. Hemodynamic responses to sodium bicarbonate and sodium chloride were the same. These data have more than 90% power of detecting a 0.5 L/min (7%) change in mean cardiac output after administration of sodium bicarbonate compared with that after sodium chloride. Even the 7 most acidemic patients (mean pH, 7.13; range, 6.90 to 7.20) had no significant hemodynamic changes after either infusion. CONCLUSIONS Correction of acidemia using sodium bicarbonate does not improve hemodynamics in critically ill patients who have metabolic acidosis and increased blood lactate or the cardiovascular response to infused catecholamines in these patients. Sodium bicarbonate decreases plasma ionized calcium and increases PaCO2.
Resting-State Time-Varying Analysis Reveals Aberrant Variations of Functional Connectivity in Autism

Recently, studies based on time-varying functional connectivity have unveiled brain states diversity in some neuropsychiatric disorders, such as schizophrenia and major depressive disorder. However, time-varying functional connectivity analysis of resting-state functional Magnetic Resonance Imaging (fMRI) have been rarely performed on the Autism Spectrum Disorder (ASD). Hence, we performed time-varying connectivity analysis on resting-state fMRI data to investigate brain states mutation in ASD children. ASD showed an imbalance of connectivity state and aberrant ratio of connectivity with different strengths in the whole brain network, and decreased connectivity associated precuneus/posterior cingulate gyrus with medial prefrontal gyrus in default mode network. As compared to typical development children, weak relevance condition (the strength of a large number of connectivities in the state was less than means minus standard deviation of all connection strength) was maintained for a longer time between brain areas of ASD children, and ratios of weak connectivity in brain states varied dramatically in the ASD. In the ASD, the abnormal brain state might be related to repetitive behaviors and stereotypical interests, and macroscopically reflect disruption of gamma-aminobutyric acid at the cellular level. The detection of brain states based on time-varying functional connectivity analysis of resting-state fMRI might be conducive for diagnosis and early intervention of ASD before obvious clinical symptoms.
A Novel Fatty Acid-Binding Protein-Like Carotenoid-Binding Protein from the Gonad of the New Zealand Sea Urchin Evechinus chloroticus

A previously uncharacterized protein with a carotenoid-binding function has been isolated and characterized from the gonad of the New Zealand sea urchin Evechinus chloroticus. The main carotenoid bound to the protein was determined by reversed phase-high performance liquid chromatography to be 9′-cis-echinenone and hence this 15 kDa protein has been called an echinenone-binding protein (EBP). Purification of the EBP in quantity from the natural source proved to be challenging. However, analysis of EBP by mass spectrometry combined with information from the Strongylocentrotus purpuratus genome sequence and the recently published E. chloroticus transcriptome database, enabled recombinant expression of wild type EBP and also of a cysteine61 to serine mutant that had improved solubility characteristics. Circular dichroism data and ab initio structure prediction suggests that the EBP adopts a 10-stranded β-barrel fold consistent with that of fatty acid-binding proteins. Therefore, EBP may represent the first report of a fatty acid-binding protein in complex with a carotenoid.