Miracle-dz/UniFAR-FTUs huggingface dataset:
Bone density after teriparatide in patients with or without prior antiresorptive treatment: one-year results from the EUROFORS study*

Objective: Recombinant teriparatide, a bone anabolic agent, is given to treatment-naïve and pre-treated patients with severe osteoporosis, but few data exist comparing the response to teriparatide in these groups. EUROFORS (the EUROpean study of FORSteo‡) enrolled postmenopausal women with established osteoporosis who were either treatment-naïve or had prior antiresorptive (AR) treatment with or without documented inadequate clinical response. The objective of the secondary analysis described here was to evaluate the interim bone mineral density (BMD) response in these groups after one year of open-label teriparatide therapy. Research design and methods: Postmenopausal women with established osteoporosis who enrolled in a prospective, randomized, controlled trial received open-label teriparatide 20 µg/day for the first year. With respect to their prior osteoporosis treatment history, they were retrospectively allocated to one of three groups: treatment-naïve (n = 204), prior treatment with an antiresorptive drug (AR-pretreated) (n = 240), or prior antiresorptive treatment with inadequate response (inadequate AR-responders) (n = 421). BMD was measured by dual energy x-ray absorptiometry. Results: Lumbar spine BMD increased from baseline (p < 0.001) in the three groups (mean, 95% CI); treatment-naïve: 8.4% (7.4%, 9.3%); AR-pretreated: 7.1% (6.3%, 7.9%); inadequate AR-responders: 6.2% (5.6%, 6.9%). Total hip BMD increased from baseline in the treatment-naïve (p < 0.001): 1.8% (1.1%, 2.5%) but did not change in the AR-pretreated: 0.4% (−0.2%, 1.1%) or inadequate AR-responders: −0.3% (−0.9%, 0.2%). Treatment-emergent adverse events were similar in the three groups. Conclusion: One year of teriparatide significantly (p < 0.001) increased spine BMD in all groups, and total hip BMD in the treatment-naïve group. Because of the limitations of this interim analysis (most importantly, the short duration of treatment and lack of a control group), further study is needed to determine the optimal treatment duration to reach the potential BMD gains at the proximal femur in patients with prior antiresorptive drug use (mostly bisphosphonates). Clinical trial registration: clinicaltrials.gov, nct00191425
Neural Signatures of Spatial Statistical Learning: Characterizing the Extraction of Structure from Complex Visual Scenes

Behavioral evidence has shown that humans automatically develop internal representations adapted to the temporal and spatial statistics of the environment. Building on prior fMRI studies that have focused on statistical learning of temporal sequences, we investigated the neural substrates and mechanisms underlying statistical learning from scenes with a structured spatial layout. Our goals were twofold: (1) to determine discrete brain regions in which degree of learning (i.e., behavioral performance) was a significant predictor of neural activity during acquisition of spatial regularities and (2) to examine how connectivity between this set of areas and the rest of the brain changed over the course of learning. Univariate activity analyses indicated a diffuse set of dorsal striatal and occipitoparietal activations correlated with individual differences in participants' ability to acquire the underlying spatial structure of the scenes. In addition, bilateral medial-temporal activation was linked to participants' behavioral performance, suggesting that spatial statistical learning recruits additional resources from the limbic system. Connectivity analyses examined, across the time course of learning, psychophysiological interactions with peak regions defined by the initial univariate analysis. Generally, we find that task-based connectivity with these regions was significantly greater in early relative to later periods of learning. Moreover, in certain cases, decreased task-based connectivity between time points was predicted by overall posttest performance. Results suggest a narrowing mechanism whereby the brain, confronted with a novel structured environment, initially boosts overall functional integration and then reduces interregional coupling over time.
Mass propagation of Solanum surattense Bum. using direct adventitious shoot organogenesis from internode

An efficient and reproducible procedure was established for direct shoot regeneration of Solanum surattense Bum. using internodal explants. The shoot regeneration efficiency on Murashige and Skoog (MS) medium supplemented with 6-benzylaminopurine (BAP) was superior in compared to 6-furfurylaminopurine (Kn). The highest mean number of shoots per explant was recorded on MS medium containing 0.5 mgl-1 BAP. BAP alone was more effective for shoot regeneration than combination of BAP and -naphthaleneacetic acid (NAA). The number of shoot per explant was highest in the 4th subculture and then it was remained stable up to 6th subculture. The shoot number drastically reduced from 7th subculture when explants were repeated subculturing up to 8th subculture. Hundred percent adventitious shoots were rooted successively on half strength MS medium fortified with 0.05 mgl-1 NAA. At about 90% of the in vitro-propagated plantlets survived when they were transferred to ex vitro conditions for acclimatization.
Do children with falling blood lead levels have improved cognition?

OBJECTIVE Exposure to lead at levels encountered by urban children impairs cognitive development. An observational study suggested improvement in IQ when blood lead level fell, but the only randomized trial of chelation showed no benefit in IQ. METHODS We did a new analysis of the data from the clinical trial using change in blood lead level as the independent variable. The 741 children began with blood lead levels between 20 and 44 microg/dL, and were 13 to 33 months old at randomization to chelation or placebo. Blood lead levels were measured repeatedly, and cognitive tests were given at baseline, 6 months, and 36 months follow-up. RESULTS By 6 months after randomization, blood lead levels had fallen by similar amounts in both chelated and placebo children, despite the immediate drops in the chelated group; there was no association between change in blood lead level and change in cognitive test score. Blood lead levels continued to fall. At 36 months follow-up, in the placebo group only, cognitive test scores had increased 4.0 points per 10 microg/dL fall in blood lead level from baseline to 36 months follow-up and 5.1 points from 6 to 36 months. CONCLUSIONS The improvement in scores in the placebo group only implies that factors other than declining blood lead levels per se are responsible for cognitive improvement; it is possible but less likely that succimer, the active drug, impairs cognition.
Indicator‐Dilution Measurement of Cardiac Output with Dissolved Hydrogen

Dissolved H2 has been used as an indicator for measuring cardiac output by the techniques of constant-rate injection and sudden, single injection indicator dilution. Because of its low solubility, H2 is eliminated essentially quantitatively in the lungs and recirculates negligibly. The constant-rate injection technique involves the gas chromatographic measurement of pulmonary (or systemic) arterial H2 concentration during an infusion of dissolved H2 into a vena cava (or the left atrium). Measurements in anesthetized dogs agreed well with simultaneous measurements by dye dilution, direct Fick, and direct volumetric techniques. Measurements could be repeated several times a minute, and using a linearly responding platinum electrode, intravascular H2 concentrations could be recorded continuously. In the sudden, single injection technique, dissolved H2 was injected into a vena cava (or the left atrium) while monitoring pulmonary (or systemic) arterial H2 concentration with a chromatographically calibrated platinum electrode. Measurements again agreed with simultaneous measurements by dye dilution, constant-rate injection of H2, and the direct volumetric technique. Hydrogen curves could be repeated rapidly and integrated instantaneously. Hydrogen appears to be a useful indicator for rapidly repeated determinations of cardiac output and for measurements of output in situations in which recirculation of conventional indicators limits their usefulness.
Efficient and effective matching of image sequences under substantial appearance changes exploiting GPS priors

The ability to localize a robot is an important capability and matching of observations under substantial changes is a prerequisite for robust long-term operation. This paper investigates the problem of efficiently coping with seasonal changes in image data. We present an extension of a recent approach [15] to visual image matching using sequence information. Our extension allows for exploiting GPS priors in the matching process to overcome the main computational bottleneck of the previous method and to handle loops within the image sequences. We present an experimental evaluation using real world data containing substantial seasonal changes and show that our approach outperforms the previous method in case a noisy GPS pose prior is available.
Selectivity for the Spatial and Nonspatial Attributes of Auditory Stimuli in the Ventrolateral Prefrontal Cortex

Spatial and nonspatial auditory processing is hypothesized to occur in parallel dorsal and ventral pathways, respectively. In this study, we tested the spatial and nonspatial sensitivity of auditory neurons in the ventrolateral prefrontal cortex (vPFC), a cortical area in the hypothetical nonspatial pathway. We found that vPFC neurons were modulated significantly by both the spatial and nonspatial attributes of an auditory stimulus. When comparing these responses with those in anterolateral belt region of the auditory cortex, which is hypothesized to be specialized for processing the nonspatial attributes of auditory stimuli, we found that the nonspatial sensitivity of vPFC neurons was poorer, whereas the spatial selectivity was better than anterolateral neurons. Also, the spatial and nonspatial sensitivity of vPFC neurons was comparable with that seen in the lateral intraparietal area, a cortical area that is a part of the dorsal pathway. These data suggest that substantial spatial and nonspatial processing occurs in both the dorsal and ventral pathways.
Fiber-Reinforced Polymer Jacketed and Shape-Modified Compression Members: II – Model

This paper presents a confinement model for different types of fiber-reinforced polymer (FRP)-confined concrete, including bonded FRP composite jackets for square and rectangular column sections, and shape-modified circular and elliptical sections confined with post-tensioned FRP shells. The model uses a combined strength-based and strain-based method to describe the axial stress versus axial strain behavior of FRP-confined concrete. The model is based on a plasticity theory using the Willam-Warnke five-parameter concrete model and the Pantazopoulou-Mills theory of degradation of concrete elastic modulus. The Popovics concrete model for hardening behavior and the Saenz model for softening behavior are applied in the formulation. The confinement model is implemented by an incremental approach which accounts for the variable FRP confinement and dilation behavior as axial stress is increased. Medium- and large-scale tests of FRP-confined concrete compression members with bonded FRP jackets or post-tensioned FRP shells are used to verify the model. The proposed model is shown to perform better than existing models in predicting the axial strength of FRP-confined concrete for a wide range of effective confining stresses.
Cyclophosphamide for treating rheumatoid arthritis.

OBJECTIVES To assess the short-term effects of cyclophosphamide for the treatment of rheumatoid arthritis. SEARCH STRATEGY We searched the Cochrane Musculoskeletal Group's Register, the Cochrane Controlled Trials Register (issue 3, 2000), Medline and Embase up to and including August 2000. We also carried out a handsearch of the reference lists of the trials retrieved from the electronic search. SELECTION CRITERIA All randomized controlled trials (RCTs) and controlled clinical trials (CCTs) comparing oral cyclophosphamide against placebo (or an active drug at a dosage considered to be ineffective) in patients with rheumatoid arthritis. DATA COLLECTION AND ANALYSIS Data abstraction was carried out independently by two reviewers. The same two reviewers using a validated checklist (Jadad 1996) assessed the methodological quality of the RCTs and CCTs. Rheumatoid arthritis outcome measures were extracted from the publications for baseline and end-of-study. The pooled analysis was performed using standardized mean differences (SMDs) for joint counts. Weighted mean differences (WMDs) were used for erythrocyte sedimentation rate (ESR). Toxicity was evaluated with pooled odds ratios for withdrawals. A chi-square test was used to assess heterogeneity among trials. Fixed effects models were used throughout. MAIN RESULTS A total of 70 patients were included in the pooled analysis of two trials, 31 receiving cyclophosphamide. A statistically significant benefit was observed for cyclophosphamide when compared to placebo for tender and swollen joint scores: SMDs were -0.57 and -0.59 respectively. The difference in ESR also favoured the active drug but did not reach statistical significance (-12 mm, 95%CI: -26 to 2.5). One trial reported the number of patients developing new or worse erosions: the OR for cyclophosphamide compared to placebo was 0.17 (95% CI: 0.05 to 0.57). Patients receiving placebo were six times more likely to discontinue treatment because of lack of efficacy than patients receiving cyclophosphamide. Withdrawals from adverse reactions were higher in the cyclophosphamide group (Odds ratio=2.9), although this difference was not statistically significant. Side effects from cyclophosphamide included hemorrhagic cystitis, nausea, vomiting, leucopenia, thrombocytopenia, alopecia, amenorrhea and herpes zoster infections. REVIEWER'S CONCLUSIONS Cyclophosphamide appears to have a clinically and statistically significant benefit on the disease activity of patients with RA, similar to some disease modifying antirheumatic drugs (DMARDs) such as antimalarials or sulfasalazine, but lower than methotrexate. Toxicity however is severe, limiting its use given the low benefit-risk ratio compared to other antirheumatic agents.
Neuronal activity in the primate hippocampal formation during a conditional association task based on the subject's location

The hippocampal formation (HF) functions in two domains of memory: spatial and nonspatial associative memory. The HF includes the hippocampus proper, the dentate gyrus, and the subicular complex. Studies of spatial correlates of HF neuronal activity have revealed that a subject's location in space can impose critical constraints on patterns of neuronal activity in the HF. This report compares monkey HF neuronal responses in two kinds of stimulus-response association tasks (go/no-go tasks with symmetrical reinforcement). In a place-dependent, conditional, stimulus-response association (PCA) task, the subject's location was the condition upon which stimulus (object)-behavioral response association depended. In a place-in-dependent, simple, stimulus-response association (ISA) task, the object-behavioral response contingency was independent of the subject's location. Of 329 neurons recorded, the activity of 88 increased or decreased significantly in response to the presentation of an object during the PCA task. Responses of 17 neurons depended differentially on specific combinations of object, place, and behavior in the PCA task (specific- combination neurons). These specific-combination responses do not simply reflect object-behavioral response association in the PCA task, since neuronal responses in the same object-behavioral response association were not restored in the ISA task in which there was no dependence on the subject's location. This suggests the influence of location on HF neuronal responses in object-behavioral response association when the subject's location is imposed as a condition. Responses of 12 neurons differentiated the kind of object in the PCA task (object-differential neurons). In the ISA task, most object- differential responses diminished or disappeared. Since the HF object- differential responses elicited by the conditions imposed by the PCA task. Characteristics of the two neuron types suggest that HF neurons encode both stimulus percept and attributes such as the place where the stimulus is presented and the conditional relation imposed in the task.
Saposin C: Neuronal Effect and CNS Delivery by Liposomes

Abstract: Saposin C is one of four small lipid‐binding proteins that derive from a single precursor protein, named prosaposin (PSAP). PSAP has several neuronal effects, including neurite outgrowth stimulation, neuron preservation, and nerve regeneration enhancement. A minimal domain required for PSAP's neurotrophic function is located in the amino‐terminal half of saposin C. Genetic defects of the PSAP gene in humans and mice lead to a complex lysosomal storage disease. The skin fibroblasts from PSAP‐ and saposin C‐deficient patients have a massive accumulation of multivesicular bodies (MVBs). Incorporation of exogenous saposin C‐containing liposomes into the cultured PSAP−/− cells reduced the accumulated MVBs to normal levels. Internalized saposin C was localized to late endosomes and lysosomes. MVBs are crucial for maintaining the cellular homeostasis required for neuronal development and growth. PSAP−/− mice have a short life span (30 days) and central nervous system (CNS) neuronal degeneration. Similar to PSAP−/− fibroblasts, excessive MVBs accumulated in CNS neurons and brain tissues of PSAP‐null mice. Cultured cortical and hippocampal neurons from PSAP−/− mice had poor survival and displayed a neurite degenerative pattern. Delivery of saposin C ex vivo into cultured neurons and in vivo into brain neuronal cells in mice across the blood‐brain barrier was accomplished with intravenously administered dioleoylphosphatidylserine (DOPS) liposomes. These studies may yield a new therapeutic approach for neuron protection, preservation, and regeneration.
Nonclassical Protein Secretion by Bacillus subtilis in the Stationary Phase Is Not Due to Cell Lysis

ABSTRACT The carboxylesterase Est55 has been cloned and expressed in Bacillus subtilis strains. Est55, which lacks a classical, cleavable N-terminal signal sequence, was found to be secreted during the stationary phase of growth such that there is more Est55 in the medium than inside the cells. Several cytoplasmic proteins were also secreted in large amounts during late stationary phase, indicating that secretion in B. subtilis is not unique to Est55. These proteins, which all have defined cytoplasmic functions, include GroEL, DnaK, enolase, pyruvate dehydrogenase subunits PdhB and PdhD, and SodA. The release of Est55 and those proteins into the growth medium is not due to gross cell lysis, a conclusion that is supported by several lines of evidence: constant cell density and secretion in the presence of chloramphenicol, constant viability count, the absence of EF-Tu and SecA in the culture medium, and the lack of effect of autolysin-deficient mutants. The shedding of these proteins by membrane vesicles into the medium is minimal. More importantly, we have identified a hydrophobic α-helical domain within enolase that contributes to its secretion. Thus, upon the genetic deletion or replacement of a potential membrane-embedding domain, the secretion of plasmid gene-encoded mutant enolase is totally blocked, while the wild-type chromosomal enolase is secreted normally in the same cultures during the stationary phase, indicating differential specificity. We conclude that the secretion of Est55 and several cytoplasmic proteins without signal peptides in B. subtilis is a general phenomenon and is not a consequence of cell lysis or membrane shedding; instead, their secretion is through a process(es) in which protein domain structure plays a contributing factor.
Pathlength Determination for Gas in Scattering Media Absorption Spectroscopy

Gas in scattering media absorption spectroscopy (GASMAS) has been extensively studied and applied during recent years in, e.g., food packaging, human sinus monitoring, gas diffusion studies, and pharmaceutical tablet characterization. The focus has been on the evaluation of the gas absorption pathlength in porous media, which a priori is unknown due to heavy light scattering. In this paper, three different approaches are summarized. One possibility is to simultaneously monitor another gas with known concentration (e.g., water vapor), the pathlength of which can then be obtained and used for the target gas (e.g., oxygen) to retrieve its concentration. The second approach is to measure the mean optical pathlength or physical pathlength with other methods, including time-of-flight spectroscopy, frequency-modulated light scattering interferometry and the frequency domain photon migration method. By utilizing these methods, an average concentration can be obtained and the porosities of the material are studied. The last method retrieves the gas concentration without knowing its pathlength by analyzing the gas absorption line shape, which depends upon the concentration of buffer gases due to intermolecular collisions. The pathlength enhancement effect due to multiple scattering enables also the use of porous media as multipass gas cells for trace gas monitoring. All these efforts open up a multitude of different applications for the GASMAS technique.
Mir-34a Is Upregulated during Liver Regeneration in Rats and Is Associated with the Suppression of Hepatocyte Proliferation

Background MicroRNAs are a class of small regulatory RNAs that modulate a variety of biological processes, including cellular differentiation, apoptosis, metabolism and proliferation. This study aims to explore the effect of miR-34a in hepatocyte proliferation and its potential role in liver regeneration termination. Methodology/Principal Finding MiR-34a was highly induced after partial hepatectomy. Overexpression of miR-34a in BRL-3A cells could significantly inhibit cell proliferation and down-regulate the expression of inhibin βB (INHBB) and Met. In BRL-3A cells, INHBB was identified as a direct target of miR-34a by luciferase reporter assay. More importantly, INHBB siRNA significantly repressed cell proliferation. A decrease of INHBB and Met was detected in regenerating liver. Conclusion/Significance MiR-34a expression was upregulated during the late phase of liver regeneration. MiR-34a-mediated regulation of INHBB and Met may collectively contribute to the suppression of hepatocyte proliferation.
Validity of the ICFT R-matrix method: Be-like Al 9+ a case study

We have carried out 98-level configuration-interaction/close-coupling (CI/CC) intermediate coupling frame transformation (ICFT) and Breit–Pauli R-matrix calculations for the electron-impact excitation of Be-like Al 9+. The close agreement that we find between the two sets of effective collision strengths demonstrates the continued robustness of the ICFT method. On the other hand, a comparison of this data with previous 238-level CI/CC ICFT effective collision strengths shows that the results for excitation up to n = 4 levels are systematically and increasingly underestimated over a wide range of temperatures by R-matrix calculations whose CC expansion extends only to n = 4 (98-levels). Thus, we find to be false a recent conjecture that the ICFT approach may not be completely robust. The conjecture was based upon a comparison of 98-level CI/CC Dirac R-matrix effective collision strengths for Al 9+ with those from the 238-level CI/CC ICFT R-matrix calculations. The disagreement found recently is due to a lack of convergence of the CC expansion in the 98-level CI/CC Dirac work. The earlier 238-level CI/CC ICFT work has a superior target to the 98-level CI/CC Dirac one and provides more accurate atomic data. Similar considerations need to be made for other Be-like ions and for other sequences.