Miracle-dz/UniFAR-FTUs huggingface dataset:
Evolution and Translation of Research Findings: From Bench to Where?

The credibility and replication of research findings evolve over time, as data accumulate. However, translation of postulated research promises to real-life biomedical applications is uncommon. In some fields of research, we may observe diminishing effects for the strength of research findings and rapid alternations of exaggerated claims and extreme contradictions--the "Proteus Phenomenon. " While these phenomena are probably more prominent in the basic sciences, similar manifestations have been documented even in clinical trials and they may undermine the credibility of clinical research. Significance-chasing bias may be in part responsible, but the greatest threat may come from the poor relevance and scientific rationale and thus low pre-study odds of success of research efforts. Given that we currently have too many research findings, often with low credibility, replication and rigorous evaluation become as important as or even more important than discovery. Credibility, replication, and translation are all desirable properties of research findings, but are only modestly correlated. In this essay, I discuss some of the evidence (or lack thereof) for the process of evolution and translation of research findings, with emphasis on the biomedical sciences.
Understanding the occupational and organizational boundaries to safe hospital discharge

Objective Safe hospital discharge relies upon communication and coordination across multiple occupational and organizational boundaries. Our aim was to understand how these boundaries can exacerbate health system complexity and represent latent sociocultural threats to safe discharge. Methods An ethnographic study was conducted in two local health and social care systems (health economies) in England, focusing on two clinical areas: stroke and hip fracture patients. Data collection involved 345 hours of observations and 220 semi-structured interviews with health and social care professionals, patients and their lay carers. Results Hospital discharge involves a dynamic network of interactions between heterogeneous health and social care actors, each characterized by divergent ways of organizing discharge activities; cultures of collaboration and interaction and understanding of what discharge involves and how it contributes to patient recovery. These interrelated dimensions elaborate the occupational and organisational boundaries that can influence communication and coordination in hospital discharge. Conclusions Hospital discharge relies upon the coordination of multiple actors working across occupational and organizational boundaries. Attention to the sociocultural boundaries that influence communication and coordination can help inform interventions that might support enhanced discharge safety.
Mixed-ADC Massive MIMO

Motivated by the demand for energy-efficient communication solutions in the next generation cellular network, a mixed-ADC architecture for massive multiple-input-multiple-output (MIMO) systems is proposed, which differs from previous works in that herein one-bit analog-to-digital converters (ADCs) partially replace the conventionally assumed high-resolution ADCs. The information-theoretic tool of generalized mutual information (GMI) is exploited to analyze the achievable data rates of the proposed system architecture and an array of analytical results of engineering interest are obtained. For fixed single-input-multiple-output (SIMO) channels, a closed-form expression of the GMI is derived, based on which the linear combiner is optimized. The analysis is then extended to ergodic fading channels, for which tight lower and upper bounds of the GMI are obtained. Impacts of dithering and imperfect channel state information (CSI) are also investigated, and it is shown that dithering can remarkably improve the system performance while imperfect CSI only introduces a marginal rate loss. Finally, the analytical framework is applied to the multiuser access scenario. Numerical results demonstrate that the mixed-ADC architecture with a relatively small number of high-resolution ADCs is able to achieve a large fraction of the channel capacity of conventional architecture, while reduce the energy consumption considerably even compared with antenna selection, for both single-user and multiuser scenarios.
The RNA Exosome Component hRrp6 Is a Target for 5-Fluorouracil in Human Cells

The drug 5-fluorouracil (5-FU) is a widely used chemotherapeutic in the treatment of solid tumors. Recently, the essential 3′-5′ exonucleolytic multisubunit RNA exosome was implicated as a target for 5-FU in yeast. Here, we show that this is also the case in human cells. HeLa cells depleted of the inessential exosome component hRrp6, also called PM/Scl100, are significantly growth impaired relative to control cells after 5-FU administration. The selective stabilization of bona fide hRrp6 RNA substrates on 5-FU treatment suggests that this exosome component is specifically targeted. Consistently, levels of hRrp6 substrates are increased in two 5-FU–sensitive cell lines. Interestingly, whereas down-regulation of all tested core exosome components results in decreased hRrp6 levels, depletion of hRrp6 leaves levels of other exosome components unchanged. Taken together, our data position hRrp6 as a promising target for antiproliferative intervention. (Mol Cancer Res 2008;6(6):990–5)
Clinical Outcomes With Rivaroxaban in Patients Transitioned From Vitamin K Antagonist Therapy

BACKGROUND In ROCKET AF (Rivaroxaban Once-Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation), a large randomized, clinical trial, rivaroxaban was noninferior to warfarin in preventing stroke or systemic embolism in patients with atrial fibrillation. OBJECTIVE To determine the efficacy and safety of rivaroxaban compared with warfarin among vitamin K antagonist (VKA)-naive and VKA-experienced patients. DESIGN Prespecified subgroup analysis. (ClinicalTrials.gov: NCT00403767). SETTING Global. PATIENTS 14,264 persons with atrial fibrillation. MEASUREMENTS Interaction of the relative treatment effect of rivaroxaban and warfarin on stroke or systemic embolism among VKA-naive and VKA-experienced patients. RESULTS Overall, 7897 (55.4%) patients were VKA-experienced and 6367 (44.6%) were VKA-naive. The effect of rivaroxaban versus warfarin on stroke or systemic embolism was consistent: Rates per 100 patient-years of follow-up were 2.32 versus 2.87 for VKA-naive patients (hazard ratio [HR], 0.81 [95% CI, 0.64 to 1.03]) and 1.98 versus 2.09 for VKA-experienced patients (HR, 0.94 [CI, 0.75 to 1.18]; interaction P = 0.36). During the first 7 days, rivaroxaban was associated with more bleeding than warfarin (HR in VKA-naive patients, 5.83 [CI, 3.25 to 10.44], and in VKA-experienced patients, 6.66 [CI, 3.83 to 11.58]; interaction P = 0.53). After 30 days, rivaroxaban was associated with less bleeding than warfarin in VKA-naive patients (HR, 0.84 [CI, 0.74 to 0.95]) and similar bleeding in VKA-experienced patients (HR, 1.06 [CI, 0.96 to 1.17]; interaction P = 0.003). LIMITATION The trial was not designed to detect differences in these subgroups. CONCLUSION The efficacy of rivaroxaban in VKA-experienced and VKA-naive patients was similar to that of the overall trial. There were more bleeding events within 7 days of study drug initiation with rivaroxaban, but after 30 days, rivaroxaban was associated with less bleeding in VKA-naive patients and similar bleeding in VKA-experienced patients. This information may be useful to clinicians considering a transition to rivaroxaban for patients receiving VKA therapy. PRIMARY FUNDING SOURCE Johnson & Johnson and Bayer HealthCare.
A field-programmable pin-constrained digital microfluidic biochip

As digital microfluidic biochips (DMFBs) have matured over the last decade, efforts have been made to 1. ) reduce the cost, and 2. ) produce general-purpose chips. While work done to generalize DMFBs typically depends on the flexibility of individually controlled electrodes, such devices have high wiring complexity, which requires costly multi-layer printed circuit boards (PCBs). In contrast, pin-constrained DMFBs reduce the wiring complexity, but reduce the flexibility of droplet coordination. We present a field-programmable pin-constrained DMFB that leverages the cost-savings of pin-constrained designs, but is general-purpose, rather than assay-specific. We show that with just a few more pins than the state-of-the-art pin-constrained designs, we can execute arbitrary assays almost as fast as the most recent general-purpose DMFB designs.
A Dendrite-Autonomous Mechanism for Direction Selectivity in Retinal Starburst Amacrine Cells

Detection of image motion direction begins in the retina, with starburst amacrine cells (SACs) playing a major role. SACs generate larger dendritic Ca2+ signals when motion is from their somata towards their dendritic tips than for motion in the opposite direction. To study the mechanisms underlying the computation of direction selectivity (DS) in SAC dendrites, electrical responses to expanding and contracting circular wave visual stimuli were measured via somatic whole-cell recordings and quantified using Fourier analysis. Fundamental and, especially, harmonic frequency components were larger for expanding stimuli. This DS persists in the presence of GABA and glycine receptor antagonists, suggesting that inhibitory network interactions are not essential. The presence of harmonics indicates nonlinearity, which, as the relationship between harmonic amplitudes and holding potential indicates, is likely due to the activation of voltage-gated channels. [Ca2+] changes in SAC dendrites evoked by voltage steps and monitored by two-photon microscopy suggest that the distal dendrite is tonically depolarized relative to the soma, due in part to resting currents mediated by tonic glutamatergic synaptic input, and that high-voltage–activated Ca2+ channels are active at rest. Supported by compartmental modeling, we conclude that dendritic DS in SACs can be computed by the dendrites themselves, relying on voltage-gated channels and a dendritic voltage gradient, which provides the spatial asymmetry necessary for direction discrimination.
Nonalcoholic Fatty Liver Disease Is Associated With Atherosclerosis in Middle-Aged and Elderly Chinese

Objective—To evaluate the associations between nonalcoholic fatty liver disease (NAFLD) and atherosclerosis. Methods and Results—A total of 8632 participants aged ≥40 years from Jiading district, Shanghai, were included in the present study. The presence of NAFLD was evaluated by ultrasonography. Carotid intima-media thickness (CIMT) and brachial-ankle pulse wave velocity (ba-PWV) were measured in each participant. The prevalence of NAFLD was 30.0% in the total population, with 30.3% in men and 29.9% in women, respectively. Subjects with NAFLD had remarkably higher CIMT and ba-PWV compared with those without NAFLD (0.594±0.105 mm versus 0.578±0.109 mm, P<0.0001; 1665±424 cm/s versus 1558±430 cm/s, P<0.0001). Subjects with both NAFLD and metabolic syndrome had significantly higher CIMT and ba-PWV compared with those with neither or either of these 2 diseases after adjustment for age and sex (all P<0.05). Logistic regressions also revealed that NAFLD conferred 35% and 30% increased odds ratios of elevated CIMT and ba-PWV, independent of conventional risk factors and the presence of metabolic syndrome. Conclusion—NAFLD was associated with elevated CIMT and ba-PWV, independent of conventional cardiovascular disease risk factors and metabolic syndrome. The effects of NAFLD and metabolic syndrome on atherosclerosis might not fully overlap.
Why is Posterior Sampling Better than Optimism for Reinforcement Learning?

Computational results demonstrate that posterior sampling for reinforcement learning (PSRL) dramatically outperforms algorithms driven by optimism, such as UCRL2. We provide insight into the extent of this performance boost and the phenomenon that drives it. We leverage this insight to establish an $\tilde{O}(H\sqrt{SAT})$ Bayesian expected regret bound for PSRL in finite-horizon episodic Markov decision processes, where $H$ is the horizon, $S$ is the number of states, $A$ is the number of actions and $T$ is the time elapsed. This improves upon the best previous bound of $\tilde{O}(H S \sqrt{AT})$ for any reinforcement learning algorithm.
Masterclass A proposed new classification system for whiplash associated disorders — implications for assessment and management

The development of chronic symptoms following whiplash injury is common and contributes substantially to costs associated with this condition. The currently used Quebec Task Force classification system of whiplash associated disorders is primarily based on the severity of signs and symptoms following injury and its usefulness has been questioned. Recent evidence is emerging that demonstrates differences in physical and psychological impairments between individuals who recover from the injury and those who develop persistent pain and disability. Motor dysfunction, local cervical mechanical hyperalgesia and psychological distress are present soon after injury in all whiplash injured persons irrespective of recovery. In contrast those individuals who develop persistent moderate/severe pain and disability show a more complex picture, characterized by additional impairments of widespread sensory hypersensitivity indicative of underlying disturbances in central pain processing as well as acute posttraumatic stress reaction, with these changes present from soon after injury. Based on this heterogeneity a new classification system is proposed that takes into account measurable disturbances in motor, sensory and psychological dysfunction. The implications for the management of this condition are discussed. r 2004 Elsevier Ltd. All rights reserved.
The Kinetics of Lymphocyte Subsets and Macrophages in Subarachnoid Space After Subarachnoid Hemorrhage in Rats

Background and Purpose Although it has been suggested that humoral immunity plays a role in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage, there has been no quantitative assay for cellular immunity. We studied the kinetics of immune cells in the subarachnoid space after subarachnoid hemorrhage in the rat. Methods One hundred fourteen Sprague-Dawley rats were used in this study. The animals were divided into two groups and injected with either autologous blood (03 mL) or saline into the major cistern. They were killed at the specified time: 10 minutes or 1, 2, 3, 5, or 7 days after subarachnoid hemorrhage. For immunohistochemical analysis, the rats' whole brains were frozen, and cryostat sections were prepared. For flow cytometric analysis of immune cell presence, their whole brains underwent enzymatic digestion. Results Histopathologic study revealed pathological change of the arterial wall, and immunohistochemical study revealed the existence of macrophages and T cells in the subarachnoid space in animals with a survival time of 2 to 5 days after subarachnoid hemorrhage. A flow cytometric study revealed the peak of appearance of T cells and macrophages 2 days after subarachnoid hemorrhage. The helper-suppressor T cell ratio also reached a peak 2 days after subarachnoid hemorrhage. Conclusions A serial response of immunoreactive cells, which resembles that of the chronic allergic reaction observed in autoimmune diseases or delayed-type hypersensitivity, exists in the subarachnoid space after subarachnoid hemorrhage. The present results suggest that the initial response in cellular immunity, which is followed by humoral immunity and eicosanoid reactions, plays a role in eliciting the development of cerebral vasospasm.
Audio-based context awareness - acoustic modeling and perceptual evaluation

The paper concerns the development of a system for the recognition of a context or an environment based on acoustic information only. Our system uses Mel-frequency cepstral coefficients and their derivatives as features, and continuous density hidden Markov models (HMM) as acoustic models. We evaluate different model topologies and training methods for HMMs and show that discriminative training can yield a 10% reduction in error rate compared to maximum-likelihood training. A listening test is made to study the human accuracy in the task and to obtain a baseline for the assessment of the performance of the system. Direct comparison to human performance indicates that the system performs somewhat worse than human subjects do in the recognition of 18 everyday contexts and almost comparably in recognizing six higher level categories.
Design Maps for the Hyperthermic Treatment of Tumors with Superparamagnetic Nanoparticles

A plethora of magnetic nanoparticles has been developed and investigated under different alternating magnetic fields (AMF) for the hyperthermic treatment of malignant tissues. Yet, clinical applications of magnetic hyperthermia are sporadic, mostly due to the low energy conversion efficiency of the metallic nanoparticles and the high tissue concentrations required. Here, we study the hyperthermic performance of commercially available formulations of superparamagnetic iron oxide nanoparticles (SPIOs), with core diameter of 5, 7 and 14 nm, in terms of absolute temperature increase ΔT and specific absorption rate (SAR). These nanoparticles are operated under a broad range of AMF conditions, with frequency f varying between 0.2 and 30 MHz; field strength H ranging from 4 to 10 kA m−1; and concentration cMNP varying from 0.02 to 3.5 mg ml−1. At high frequency field (∼30 MHz), non specific heating dominates and ΔT correlates with the electrical conductivity of the medium. At low frequency field (<1 MHz), non specific heating is negligible and the relaxation of the SPIO within the AMF is the sole energy source. We show that the ΔT of the medium grows linearly with cMNP, whereas the SARMNP of the magnetic nanoparticles is independent of cMNP and varies linearly with f and H2. Using a computational model for heat transport in a biological tissue, the minimum requirements for local hyperthermia (Ttissue >42°C) and thermal ablation (Ttissue >50°C) are derived in terms of cMNP, operating AMF conditions and blood perfusion. The resulting maps can be used to rationally design hyperthermic treatments and identifying the proper route of administration – systemic versus intratumor injection – depending on the magnetic and biodistribution properties of the nanoparticles.
On distance scales, embeddings, and efficient relaxations of the cut cone

A central open problem in the field of finite metric spaces is to find an efficient relaxation of the cut cone---the collection of positive linear combinations of cut pseudo-metrics on a finite set. In particular, it has been asked how well squared-Euclidean metrics (the so-called metrics of "negative type") embed into <i>L</i><inf>1</inf>, and it is known that the answer to this question coincides with the integrality gap of a folklore semi-definite relaxation for computing the Sparsest Cut of a graph.Bourgain's classical embedding theorem implies that any <i>n</i>-point metric space embeds into <i>L</i><inf>2</inf> with <i>O</i>(log <i>n</i>) distortion. We give the first embeddings for metrics of negative type which beat Bourgain's bound. Specifically, we show that for every ∈ > 0, there exists a Δ > 0 such that every <i>n</i>-point metric of negative type embeds into <i>L</i><inf>2+∈</inf>, with distortion <i>O</i>(log <i>n</i>)<sup>1-Δ</sup>. We also exhibit the first <i>o</i>(log <i>n</i>) bounds on the Euclidean distortion of finite subsets of <i>L<inf>p</inf></i>, for 1 < <i>p</i> < 2. These spaces naturally interpolate between <i>L</i><inf>1</inf> and <i>L</i><inf>2</inf>, and thus provide a necessary first step in resolving the long-standing open question on the Euclidean distortion of finite subsets of <i>L</i><inf>1</inf>. In proving these results, we introduce a number of new techniques for the construction of low-distortion embeddings. These include a generic Gluing Lemma which avoids the overhead that typically arises from the naïve concatenation of different scales, and which provides new insights into the cut structure of finite graphs. We also exhibit the utility of Lipschitz extension theorems from Functional Analysis to the embedding of finite metric spaces. Finally, we prove the "Big Core" Theorem---a significantly improved and quantitatively optimal version of the main structural theorem in [ARV04] about random projections. The latter result offers a simplified hyperplane rounding algorithm for the computation of an <i>O</i>(√log<i>n</i>)-approximation to the Sparsest Cut problem with uniform demands.
Comparison of the ability to bind lipids of β-lactoglobulin and serum albumin of milk from ruminant and non-ruminant species

Summary The interaction of sheep, horse, pig, human and guinea-pig whey proteins with fatty acids has been studied. Using gel filtration and autoradiography, it was found that sheep β-lactoglobulin and serum albumin from all species had the ability to bind fatty acids in vitro. Sheep β-lactoglobulin, isolated from milk, had ˜ 0·5 mol fatty acids bound per mol monomer protein, and albumin from sheep, horse and pig contained ˜ 4·5, 2·9 and 4·7 mol fatty acids/mol protein respectively. However, β-lactoglobulin from horse and pig milk had neither fatty acids physiologically bound nor the ability to bind them in vitro. Albumin was the only whey protein detected with bound fatty acids in these species as well as in human and guinea pig. This suggests that the ability of ruminant β-lactoglobulin to bind fatty acids was not shared by the same protein of non-ruminants.
Reliable quantification of bite-force performance requires use of appropriate biting substrate and standardization of bite out-lever

Bite-force performance is an ecologically important measure of whole-organism performance that shapes dietary breadth and feeding strategies and, in some taxa, determines reproductive success. It also is a metric that is crucial to testing and evaluating biomechanical models. We reviewed nearly 100 published studies of a range of taxa that incorporate direct in vivo measurements of bite force. Problematically, methods of data collection and processing vary considerably among studies. In particular, there is little consensus on the appropriate substrate to use on the biting surface of force transducers. In addition, the bite out-lever, defined as the distance from the fulcrum (i.e. jaw joint) to the position along the jawline at which the jaws engage the transducer, is rarely taken into account. We examined the effect of bite substrate and bite out-lever on bite-force estimates in a diverse sample of lizards. Results indicate that both variables have a significant impact on the accuracy of measurements. Maximum bite force is significantly greater using leather as the biting substrate compared with a metal substrate. Less-forceful bites on metal are likely due to inhibitory feedback from mechanoreceptors that prevent damage to the feeding apparatus. Standardization of bite out-lever affected which trial produced maximum performance for a given individual. Indeed, maximum bite force is usually underestimated without standardization because it is expected to be greatest at the minimum out-lever (i.e. back of the jaws), which in studies is rarely targeted with success. We assert that future studies should use a pliable substrate, such as leather, and use appropriate standardization for bite out-lever.