Miracle-dz/UniFAR-FTUs huggingface dataset:
Pamidronate to prevent bone loss during androgen-deprivation therapy for prostate cancer.

BACKGROUND Treatment with a gonadotropin-releasing hormone agonist decreases bone mineral density and increases the risk of fracture in men with prostate cancer. We conducted a controlled study of the prevention of osteoporosis in men undergoing treatment with a gonadotropin-releasing hormone agonist. METHODS In a 48-week, open-label study, we randomly assigned 47 men with advanced or recurrent prostate cancer and no bone metastases to receive either leuprolide alone or leuprolide and pamidronate (60 mg intravenously every 12 weeks). Bone mineral density of the lumbar spine and the proximal femur was measured by dual-energy x-ray absorptiometry. Trabecular bone mineral density of the lumbar spine was measured by quantitative computed tomography. Forty-one men completed the study. RESULTS In men treated with leuprolide alone, the mean (+/-SE) bone mineral density decreased by 3.3+/-0.7 percent in the lumbar spine, 2.1+/-0.6 percent in the trochanter, and 1.8+/-0.4 percent in the total hip, and the mean trabecular bone mineral density of the lumbar spine decreased by 8.5+/-1.8 percent (P<0.001 for each comparison with the base-line value). In contrast, the mean bone mineral density did not change significantly at any skeletal site in men treated with both leuprolide and pamidronate. There were significant differences between the two groups in the mean changes in bone mineral density at 48 weeks in the lumbar spine (P<0.001), trochanter (P = 0.003), total hip (P=0.005), and trabecular bone of the lumbar spine (P=0.02). CONCLUSIONS Pamidronate prevents bone loss in the hip and lumbar spine in men receiving treatment for prostate cancer with a gonadotropin-releasing hormone agonist.
Temporal Pattern Recognition in Gait Activities Recorded With a Footprint Imaging Sensor System

In this paper, we assess the capability of a unique unobtrusive footprint imaging sensor system, based on plastic optical fiber technology, to allow efficient gait analysis from time domain sensor data by pattern recognition techniques. Trial gait classification experiments are executed as ten manners of walking, affecting the amplitude and frequency characteristics of the temporal signals. The data analysis involves the design of five temporal features, subsequently analyzed in 14 different machine learning models, representing linear, non-linear, ensemble, and deep learning models. The model performance is presented as cross-validated accuracy scores for the best model-feature combinations, along with the optimal hyper-parameters for each of them. The best classification performance was observed for a random forest model with the adjacent mean feature, yielding a mean validation score of 90.84% ± 2.46%. We conclude that the floor sensor system is capable of detecting changes in gait by means of pattern recognition techniques applied in the time domain. This suggests that the footprint imaging sensor system is suitable for gait analysis applications ranging from healthcare to security.
Immune defense against pneumonic plague

Summary: Yersinia pestis is one of the world's most virulent human pathogens. Inhalation of this Gram‐negative bacterium causes pneumonic plague, a rapidly progressing and usually fatal disease. Extensively antibiotic‐resistant strains of Y. pestis exist and have significant potential for exploitation as agents of terrorism and biowarfare. Subunit vaccines comprised of the Y. pestis F1 and LcrV proteins are well‐tolerated and immunogenic in humans but cannot be tested for efficacy, because pneumonic plague outbreaks are uncommon and intentional infection of humans is unethical. In animal models, F1/LcrV‐based vaccines protect mice and cynomolgus macaques but have failed, thus far, to adequately protect African green monkeys. We lack an explanation for this inconsistent efficacy. We also lack reliable correlate assays for protective immunity. These deficiencies are hampering efforts to improve vaccine efficacy. Here, I review the immunology of pneumonic plague, focusing on evidence that humoral and cellular defense mechanisms collaborate to defend against pulmonary Y. pestis infection.
Prioritized independent contact regions for form closure grasps

The concept of independent contact regions on a target object's surface, in order to compensate for shortcomings in the positioning accuracy of robotic grasping devices, is well known. However, the numbers and distributions of contact points forming such regions is not unique and depends on the underlying computational method. In this work we present a computation scheme allowing to prioritize contact points for inclusion in the independent regions. This enables a user to affect their shape in order to meet the demands of the targeted application. The introduced method utilizes frictionless contact constraints and is able to efficiently approximate the space of disturbances resistible by all grasps comprising contacts within the independent regions.
Design and evaluation of a novel variable stiffness spherical joint with application to MR-compatible robot design

In this paper, the design of a new variable stiffness spherical joint for MR-compatible robotics is presented. It is based on the use of prestressed cable-driven mechanisms in singular configurations to provide large stiffness variation ranges, including zero stiffness configuration as required by the medical context. An original implementation is proposed, with a prestress adjustment system using pneumatic energy and taking advantage of multimaterial additive manufacturing. The proposed component combines compactness, MR-compatibility and is lightweight. The system is evaluated on a dedicated experimental setup with validation of the expected behavior, with in particular a very large achievable range of stiffnesses. The approach is effective for the design of such device and constitutes a novel solution for the design of variable stiffness devices with complex motions.
Improving Superscalar Instruction Dispatch And Issue By Exploiting Dynamic Code Sequences

Superscalar processors currently have the potential to fetch multiple basic blocks per cycle by employing one of several recently proposed instruction fetch mechanisms. However, this increased fetch bandwidth cannot be exploited unless pipeline stages further downstream correspondingly improve. In particular, register renaming a large number of instructions per cycle is difficult. A large instruction window, needed to receive multiple basic blocks per cycle, will slow down dependence resolution and instruction issue. This paper addresses these and related issues by proposing (i) partitioning of the instruction window into multiple blocks, each holding a dynamic code sequence; (ii) logical partitioning of the register file into a global file and several local files, the latter holding registers local to a dynamic code sequence; (iii) the dynamic recording and reuse of register renaming information for registers local to a dynamic code sequence. Performance studies show these mechanisms improve performance over traditional superscalar processors by factors ranging from 1.5 to a little over 3 for the SPEC Integer programs. Next, it is observed that several of the loops in the benchmarks display vector-like behavior during execution, even if the static loop bodies are likely complex for compile-time vectorization. A dynamic loop vectorization mechanism that builds on top of the above mechanisms is briefly outlined. The mechanism vectorizes up to 60% of the dynamic instructions for some programs, albeit the average number of iterations per loop is quite small.
Income Gradient in Renal Disease Mortality in the United States

Background Non-communicable diseases and associated mortality follow a social gradient and chronic kidney disease is not an exception to this rule. Intermediate behavioral and medical factors that may explain such social gradients are, however, still unknown. Objectives Using nationally representative data in the United States, this study was conducted to investigate the mediating effect of medical and behavioral risk factors on the association between socioeconomic status (SES) and renal disease mortality. Patients and methods Americans’ Changing Lives Study (ACL), 1986–2011, is a 25-year nationally representative prospective cohort study. ACL followed 3,361 adults for up to 25 years. Income, education, and unemployment were the main predictors of interest. Death due to renal disease was the main outcome. Health behaviors (smoking, drinking, and exercise) and medical risk factors (diabetes, hypertension, and obesity) were the mediators. Cox proportional hazards models were used for data analysis. Results Higher income (HR = 0.75; 95% CI = 0.62–0.89) was associated with lower risk of death due to renal disease over the 25-year follow-up period. Although health behaviors and medical risk factors at baseline were also predictors of the outcome, they failed to explain the effect of income on death due to renal disease. That is, income was associated with death due to renal disease above and beyond all potential mediators including behavioral and medical risk factors. Conclusion Socioeconomic inequalities in the United States cause disparities in renal disease mortality; however, such differences are not due to health behaviors (smoking and drinking) and medical risk factors (hypertension and diabetes). To reduce disparities in renal disease mortality in the United States, policies should go beyond health behaviors and medical risk factors. While programs should help low-income individuals maintain exercise and avoid smoking, reduction of income disparities should be regarded as a strategy for reduction of disparities in renal disease mortality. By increasing minimum pay and minimizing the income gap, we may reduce disparities in renal disease mortality.
Is NF-kappaB a good target for cancer therapy? Hopes and pitfalls.

Preface NF- B transcription factors play a key role in many physiological processes, such as innate and adaptive immune responses, cell κ proliferation, cell death, and inflammation. It has become clear that aberrant regulation of NF- B and the signaling pathways that κ control its activity are involved in cancer development and progression, as well as in resistance to chemo- and radiotherapy. This review discusses recent cancer-genetics and cancer-genome evidence for the involvement of NF- B in human cancer, and discusses the κ therapeutic potential and benefit of targeting NF- B in cancer and the possible complications and pitfalls of such an approach. κ cIAP1/2 degradative
Architectures for Synchronous Groupware

Synchronous groupware systems allow physically separated users to interact with one another and with shared computational objects in real time. Such systems are problematic to build since their user interfaces must support multiple, concurrent users, and both their application logic and their user interfaces must be distributed across multiple platforms. This survey explores the range of software architectures that have been proposed to solve this problem. The presentation includes three distinct architectural views: reference models, which divide complete systems into named functional elements and specify data flow between those elements; architectural styles, which prescribe component and connector types and their allowed patterns of interaction; and distribution architectures, which represent the distribution of system functionality across connected computing platforms. The distribution architectures are presented using a new descriptive framework called Interlace. The architectural presentation is complemented by a brief overview of consistency maintenance mechanisms for groupware.
The Spectrum of Hypoxanthine-Guanine Phosphoribosyltransferase (HPRT) Deficiency: Clinical Experience Based on 22 Patients from 18 Spanish Families

The enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT) catalyzes the reutilization of hypoxanthine and guanine to the purine nucleotides IMP and GMP, respectively. HPRT deficiency is an X-linked disorder characterized by uric acid overproduction and variable neurologic impairment. The complete deficiency of HPRT is diagnostic of Lesch-Nyhan syndrome manifested by choreoathetosis, spasticity, mental retardation, and self-injurious behavior. In some HPRT-deficient patients the enzyme defect appeared to be "partial" and the neurologic symptoms mild to severe (Kelley-Seegmiller syndrome). This has prompted the classification of HPRT deficiency in 2 distinct groups: Lesch-Nyhan syndrome and Kelley-Seegmiller syndrome, which has created much confusion. A spectrum of clinical consequences of HPRT deficiency has been recognized in small series of patients, but the complete spectrum of the neurologic disorder has not been described in a single series of patients examined by the same observers. We analyzed our experience with 22 patients belonging to 18 different families with HPRT deficiency diagnosed at "La Paz" University Hospital in Madrid over the past 16 years. The clinical spectrum of these HPRT-deficient Spanish patients was similar to the different phenotypes occasionally reported in the literature, in some cases diagnosed as Lesch-Nyhan "variants. " The clinical, biochemical, enzymatic, and molecular genetic studies on these 22 patients allowed us to delineate a new classification of HPRT deficiency. Based on the neurologic symptoms, dependency for personal care, HPRT activity in hemolysate and in intact erythrocytes, and predicted protein size, patients were classified into 4 groups: Group 1 (2 patients), normal development with no neurologic symptoms, HPRT activity was detectable in hemolysates and in intact erythrocytes, and the mutation did not affect the predicted protein size. Group 2 (3 patients) mild neurologic symptoms that did not prevent independent lives, HPRT activity was detectable in intact erythrocytes, and the protein size was normal. Group 3 (2 patients), severe neurologic impairment that precluded an independent life, no residual HPRT activity, and normal protein size. Group 4 (15 patients), clinical characteristics of Lesch-Nyhan syndrome (some may not show self-injurious behavior), no residual HPRT activity, and in most (7 of 8 patients in whom the mutation could be detected) the mutation affected the predicted protein size. This classification of HPRT deficiency into 4 groups may be more useful in terms of accuracy, reproducibility, assessment for treatment trials and prognosis. The study of this Spanish series allows us to conclude that HPRT deficiency may be manifested by a wide spectrum of neurologic symptoms; the overall severity of the disease is associated with mutations permitting some degree of residual enzyme activity; and mutation analysis provides a valuable tool for prognosis, carrier identification, and prenatal diagnosis.
A three-dimensional model of endothelin-converting enzyme (ECE) based on the X-ray structure of neutral endopeptidase 24.11 (NEP).

Endothelin-converting enzyme 1 (ECE-1, EC 3.4.24.71) is a zinc-dependent type II mammalian membrane protein comprising the active site in the ectodomain. It exists in multiple splice variants that all catalyze the last and rate-limiting step in the activation of preproendothelin to the highly potent vasoconstrictor endothelin. There is high interest in finding small and potent inhibitors for this enzyme that could be used in numerous indications, e.g. hypertension. Since there is no structural information available for this important enzyme, we built a model of the complete ectodomain using the recently solved structure of human NEP as template. The naturally derived metalloproteinase inhibitor phosphoramidon was docked in the active site of this model and comparisons with the respective NEP complex were made.
U/Th dating of a Cladocora caespitosa from Capo S. Marco marine Quaternary deposits (Sardinia, Italy)

A whole specimen, not reworked and well preserved of Cladocora caespitosa has been found within the marine Quaternary deposits, outcropping along the eastern coast of the Capo San Marco Promontory. The U/Th dating of this sample has provided a minimum age of 70 ± 4 ka B.P. This dating allows to state that these marine deposits, containing the coral, are not Holocene in age.
Digital Signal Processing

Local Binary Pattern (LBP) only encodes the ﬁrst order directional derivatives of a center pixel but it does not consider higher order derivatives. This paper proposes a rotation and scale invariant local binary pattern by jointly taking into account high order directional derivatives, circular shift sub-uniform, and scale space. Each order directional derivatives are independently encoded in a similar way of the ﬁrst order derivatives to generate a code for the center pixel. Different order derivatives produce different codes that result in several histograms over an image, and then all the histograms multiplied by weights are concatenated together to fully utilize information of different order derivatives. To further improve performance, circular shift sub-uniform and scale space techniques are used to obtain rotation and scale invariant local binary patterns. Extensive experiments show that the high order derivatives based LBP can achieve good performance and obviously outperforms existing methods.
Cost-Effectiveness Analysis of Tdap in the Prevention of Pertussis in the Elderly

Objectives Health benefits and costs of combined reduced-antigen-content tetanus, diphtheria, and pertussis (Tdap) immunization among adults ≥65 years have not been evaluated. In February 2012, the Advisory Committee on Immunization Practices (ACIP) recommended expanding Tdap vaccination (one single dose) to include adults ≥65 years not previously vaccinated with Tdap. Our study estimated the health and economic outcomes of one-time replacement of the decennial tetanus and diphtheria (Td) booster with Tdap in the 10% of individuals aged 65 years assumed eligible each year compared with a baseline scenario of continued Td vaccination. Methods We constructed a model evaluating the cost-effectiveness of vaccinating a cohort of adults aged 65 with Tdap, by calculating pertussis cases averted due to direct vaccine effects only. Results are presented from societal and payer perspectives for a range of pertussis incidences (25–200 cases per 100,000), due to the uncertainty in estimating true annual incidence. Cases averted were accrued throughout the patient 's lifetime, and a probability tree used to estimate the clinical outcomes and costs (US$ 2010) for each case. Quality-adjusted life-years (QALYs) lost to acute disease were calculated by multiplying cases of mild/moderate/severe pertussis by the associated health-state disutility; QALY losses due to death and long-term sequelae were also considered. Incremental costs and QALYs were summed over the cohort to derive incremental cost-effectiveness ratios. Scenario analyses evaluated the effect of alternative plausible parameter estimates on results. Results At incidence levels of 25, 100, 200 cases/100,000, vaccinating adults aged 65 years costs an additional $336,000, $63,000 and $17,000/QALY gained, respectively. Vaccination has a cost-effectiveness ratio less than $50,000/QALY if pertussis incidence is >116 cases/100,000 from societal and payer perspectives. Results were robust to scenario analyses. Conclusions Tdap immunization of adults aged 65 years according to current ACIP recommendations is a cost-effective health-care intervention at plausible incidence assumptions.
Multi-Agent Cooperative Area Coverage: Case Study Ploughing (Extended Abstract)

We present two cooperative strategies in area coverage that are aimed to be applied in agricultural robotics domain. Current strategies in this domain rely on explicit forms of communication for task allocation and coordination. One issue with these approaches is the loss of communicating signal. This paper presents two approaches (FIFO, and LIFO) for task allocation and coordination that relies only on local information of the robots.
Attenuated Salmonella Typhimurium Lacking the Pathogenicity Island-2 Type 3 Secretion System Grow to High Bacterial Numbers inside Phagocytes in Mice

Intracellular replication within specialized vacuoles and cell-to-cell spread in the tissue are essential for the virulence of Salmonella enterica. By observing infection dynamics at the single-cell level in vivo, we have discovered that the Salmonella pathogenicity island 2 (SPI-2) type 3 secretory system (T3SS) is dispensable for growth to high intracellular densities. This challenges the concept that intracellular replication absolutely requires proteins delivered by SPI-2 T3SS, which has been derived largely by inference from in vitro cell experiments and from unrefined measurement of net growth in mouse organs. Furthermore, we infer from our data that the SPI-2 T3SS mediates exit from infected cells, with consequent formation of new infection foci resulting in bacterial spread in the tissues. This suggests a new role for SPI-2 in vivo as a mediator of bacterial spread in the body. In addition, we demonstrate that very similar net growth rates of attenuated salmonellae in organs can be derived from very different underlying intracellular growth dynamics.
Visual Integration of Data and Model Space in Ensemble Learning

Ensembles of classifier models typically deliver superior performance and can outperform single classifier models given a dataset and classification task at hand. However, the gain in performance comes together with the lack in comprehensibility, posing a challenge to understand how each model affects the classification outputs and where the errors come from. We propose a tight visual integration of the data and the model space for exploring and combining classifier models. We introduce a workflow that builds upon the visual integration and enables the effective exploration of classification outputs and models. We then present a use case in which we start with an ensemble automatically selected by a standard ensemble selection algorithm, and show how we can manipulate models and alternative combinations.
Taking Sides with Pain – Lateralization aspects Related to Cerebral Processing of Dental Pain

The current fMRI study investigated cortical processing of electrically induced painful tooth stimulation of both maxillary canines and central incisors in 21 healthy, right-handed volunteers. A constant current, 150% above tooth specific pain perception thresholds was applied and corresponding online ratings of perceived pain intensity were recorded with a computerized visual analog scale during fMRI measurements. Lateralization of cortical activations was investigated by a region of interest analysis. A wide cortical network distributed over several areas, typically described as the pain or nociceptive matrix, was activated on a conservative significance level. Distinct lateralization patterns of analyzed structures allow functional classification of the dental pain processing system. Namely, certain parts are activated independent of the stimulation site, and hence are interpreted to reflect cognitive emotional aspects. Other parts represent somatotopic processing and therefore reflect discriminative perceptive analysis. Of particular interest is the observed amygdala activity depending on the stimulated tooth that might indicate a role in somatotopic encoding.