Miracle-dz/UniFAR-FTUs huggingface dataset:
Modified power prior with multiple historical trials for binary endpoints

Including historical data may increase the power of the analysis of a current clinical trial and reduce the sample size of the study. Recently, several Bayesian methods for incorporating historical data have been proposed. One of the methods consists of specifying a so‐called power prior whereby the historical likelihood is downweighted with a weight parameter. When the weight parameter is also estimated from the data, the modified power prior (MPP) is needed. This method has been used primarily when a single historical trial is available. We have adapted the MPP for incorporating multiple historical control arms into a current clinical trial, each with a separate weight parameter. Three priors for the weights are considered: (1) independent, (2) dependent, and (3) robustified dependent. The latter is developed to account for the possibility of a conflict between the historical data and the current data. We analyze two real‐life data sets and perform simulation studies to compare the performance of competing Bayesian methods that allow to incorporate historical control patients in the analysis of a current trial. The dependent power prior borrows more information from comparable historical studies and thereby can improve the statistical power. Robustifying the dependent power prior seems to protect against prior‐data conflict.
Effects of host species and environmental factors on the prevalence of Batrachochytrium dendrobatidis in northern Europe

The fungal pathogen Batrachochytrium dendrobatidis (Bd) is a major threat to amphibian populations. Here we asked if the prevalence of Bd differs between amphibian species and whether it is related to local environmental factors in breeding habitats as well as landscape variables measured at three scales (500, 2000 and 5000 m radius) in southernmost Sweden. We sampled 947 anurans from six species in 31 ponds. Canopy cover, pond perimeter, pH and temperature were treated as local scale pond characteristics. Number of surrounding ponds, area of arable land, area of mature forest and number of resident people were treated as landscape variables. Bufo bufo and Rana temporaria had a prevalence of 0.5-1.0% which differed strongly from the other four species (Bombina bombina, Bufotes variabilis, Epidalea calamita, Rana arvalis) showing 13-64% prevalence. Bd prevalence in these four species was higher in ponds with higher pH, surrounded by a landscape with less mature forest and few wetlands. Our results show that the infection dynamics of Bd are complex and depend on local pond characteristics, host community composition and the spatial scale under investigation. Information on environmental factors associated with Bd and species differences in susceptibility may mitigate further spread of the disease through public information and guide conservational action plans, especially for the most threatened species.
The Embedding Transform. A Novel Analysis of Non-Stationarity in the EEG

We introduce a novel technique to analyze nonstationarity in single-channel Electroencephalogram (EEG) traces: the Embedding Transform. The approach is based on Walter J. Freeman's studies concerning active and rest stages and deviations from Gaussianity. Specifically, we generalize his idea in order to include cases where the neuromodulations are sparse in time. Specifically, the transform maps the temporal sequences to a set of $\ell ^{2}$-norms where modulated patters are emphasized. In this way, the background, chaotic activity can be modeled as the main lobe of the distribution, while the relevant synchronizations (or desynchronizations) fall on the right (or left) tail of the density of such norms. We test the algorithm on two different datasets: alpha bursts on synthetic data simulated in the BESA software and low-gamma oscillations in the motor cortex from the Brain-Computer Interface (BCI) Competition 4 Dataset 4. The results are promising and place the Embedding Transform as a quick, single-parameter tool to effectively assess which channels (or regions) are actively engaged in particular behaviors and which are in a more silent type of stage.
Older adults’ perceptions of wearable technology hip protectors: implications for further research and development strategies

Abstract Purpose: Hip fractures are an important public health issue. Ninety-five percent of hip fractures are caused by falls, with those at greatest risk including residents of long-term care facilities. Hip protectors can be effective in preventing hip fractures, but levels of acceptance and adherence may be low. We report on work to develop research into a new hip protector that aims to overcome some of the acceptance and adherence challenges. Methods: We held five patient and public consultation events involving 147 older adults and 10 long-term care sector staff in the Midlands and North West of England. At each event, participants were shown the Fall-Safe Assist hip protector, which includes built-in mobile technology to record information about falls and summon help from caregivers. Results: Participants were positive about the product’s potential utility and impact upon confidence in moving around. However, many participants held highly personal perceptions of their vulnerability and need, and expressed concerns about the esthetics and practicality of the accompanying underwear. Participants highlighted potential challenges from poor mobile connectivity, and expressed concerns about product cost. Conclusions: Future research will need to ensure flexible and sensitive approaches to recruitment. Further refinement to the product design may be useful. Individual interviews and questionnaires would help capture participants’ perceptions on personal topics, and measures of changes in confidence. Research sites will need to be compatible with technological functionality. It will be necessary to have a robust protocol in place for withdrawal of the product at the end of any clinical research. Implications for Rehabilitation Hip protectors can be effective in preventing hip fractures, but levels of acceptance and adherence may be low and may contribute to low-quality research. A new type of hip protector has been designed to overcome some of the acceptance and adherence challenges. Older adults suggested that the product was potentially useful, but expressed highly personal concerns about perceived need; aesthetics; practical and technological challenges; and cost, all of which may affect future research design. Research designs will need to be flexible enough to consider sensitive approaches to recruitment, multiple methods of data collection, site compatibility with technological functionality, and product withdrawal at end of study.
Quantifying Learning Guarantees for Convex but Inconsistent Surrogates

We study consistency properties of machine learning methods based on minimizing convex surrogates. We extend the recent framework of Osokin et al. (2017) for the quantitative analysis of consistency properties to the case of inconsistent surrogates. Our key technical contribution consists in a new lower bound on the calibration function for the quadratic surrogate, which is non-trivial (not always zero) for inconsistent cases. The new bound allows to quantify the level of inconsistency of the setting and shows how learning with inconsistent surrogates can have guarantees on sample complexity and optimization difficulty. We apply our theory to two concrete cases: multi-class classification with the tree-structured loss and ranking with the mean average precision loss. The results show the approximation-computation trade-offs caused by inconsistent surrogates and their potential benefits.
Complex Gated Recurrent Neural Networks

Complex numbers have long been favoured for digital signal processing, yet complex representations rarely appear in deep learning architectures. RNNs, widely used to process time series and sequence information, could greatly benefit from complex representations. We present a novel complex gated recurrent cell, which is a hybrid cell combining complex-valued and norm-preserving state transitions with a gating mechanism. The resulting RNN exhibits excellent stability and convergence properties and performs competitively on the synthetic memory and adding task, as well as on the real-world tasks of human motion prediction.
Does the use of rotational atherectomy procedure during percutaneous coronary interventions influence the frequency of procedure-related myocardial injury assessed by cardiac magnetic resonance?

The usage of gadolinium-enhanced cardiac magnetic resonance (CMR) in the differentiation of heart failure related to dilated cardiomyopathy and coronary artery disease has been demonstrated in previously published studies. It currently remains one of the basic methods for assessing myocardial ischemia, which has been reflected in many international guidelines, including those of the European Society of Cardiology (1-3). Also, T2 mapping for myocardial edema, cine CMR for regional wall motion abnormalities, rest first pass and adenosine stress perfusion are well sanctioned methods of myocardial ischemia assessment, also used in patients with acute coronary syndromes (4-6).
Multi-Modal Sequence Fusion via Recursive Attention for Emotion Recognition

Natural human communication is nuanced and inherently multi-modal. Humans possess specialised sensoria for processing vocal, visual, and linguistic, and para-linguistic information, but form an intricately fused percept of the multi-modal data stream to provide a holistic representation. Analysis of emotional content in face-to-face communication is a cognitive task to which humans are particularly attuned, given its sociological importance, and poses a difficult challenge for machine emulation due to the subtlety and expressive variability of cross-modal cues. Inspired by the empirical success of recent so-called End-To-End Memory Networks and related works, we propose an approach based on recursive multi-attention with a shared external memory updated over multiple gated iterations of analysis. We evaluate our model across several large multi-modal datasets and show that global contextualised memory with gated memory update can effectively achieve emotion recognition.
Characterization of Stimulation Artifact Behavior in Simultaneous Electrocorticography Grid Stimulation and Recording

Bi-directional brain-computer interfaces (BCIs) require simultaneous stimulation and recording to achieve closed-loop operation. It is therefore important that the interface be able to distinguish between neural signals of interest and stimulation artifacts. Current bi-directional BCIs address this problem by temporally multiplexing stimulation and recording. This approach, however, is suboptimal in many BCI applications. Alternative artifact mitigation methods can be devised by investigating the mechanics of artifact propagation. To characterize stimulation artifact behaviors, we collected and analyzed electrocorticography (ECoG) data from eloquent cortex mapping. Ratcheting and phase-locking of stimulation artifacts were observed, as well as dipole-like properties. Artifacts as large as ±1,100 μV appeared as far as 15-37 mm away from the stimulating channel when stimulating at 10 mA. Analysis also showed that the majority of the artifact power was concentrated at the stimulation pulse train frequency (50 Hz) and its super-harmonics (100, 150, 200 Hz). Lower frequencies (0-32 Hz) experienced minimal artifact contamination. These findings could inform the design of future bi-directional ECoG-based BCIs.
Residual kidney function in twice-weekly hemodialysis: irreplaceable contribution to dialysis adequacy.

Over time, there has been increasing recognition of the importance of preservation of residual kidney function (RKF) in dialysis patients (1). The presence of RKF has been shown to contribute to the overall health and well-being of dialysis patients including improved survival, better nutrition, and reduced inflammation (2-4).
Mitochondrial and Contractile Function of Human Right Atrial Tissue in Response to Remote Ischemic Conditioning

Background Remote ischemic preconditioning (RIPC) by repeated brief cycles of limb ischemia/reperfusion attenuates myocardial ischemia/reperfusion injury. We aimed to identify a functional parameter reflecting the RIPC‐induced protection in human. Therefore, we measured mitochondrial function in right atrial tissue and contractile function of isolated right atrial trabeculae before and during hypoxia/reoxygenation from patients undergoing coronary artery bypass grafting with RIPC or placebo, respectively. Methods and Results One hundred thirty‐seven patients under isoflurane anesthesia underwent RIPC (3×5 minutes blood pressure cuff inflation on the left upper arm/5 minutes deflation, n=67) or placebo (cuff uninflated, n=70), and right atrial appendages were harvested before ischemic cardioplegic arrest. Myocardial protection by RIPC was assessed from serum troponin I/T concentrations over 72 hours after surgery. Atrial tissue was obtained for isolation of mitochondria (RIPC/placebo: n=10/10). Trabeculae were dissected for contractile function measurements at baseline and after hypoxia/reoxygenation (60 min/30 min) and for western blot analysis after hypoxia/reoxygenation (RIPC/placebo, n=57/60). Associated with cardioprotection by RIPC (26% decrease in the area under the curve of troponin I/T), mitochondrial adenosine diphosphate–stimulated complex I respiration (+10%), adenosine triphosphate production (+46%), and calcium retention capacity (+37%) were greater, whereas reactive oxygen species production (−24%) was less with RIPC than placebo. Contractile function was improved by RIPC (baseline, +7%; reoxygenation, +24%). Expression and phosphorylation of proteins, which have previously been associated with cardioprotection, were not different between RIPC and placebo. Conclusions Cardioprotection by RIPC goes along with improved mitochondrial and contractile function of human right atrial tissue. Clinical Trial Registration URL: https://www.clinicaltrials. gov. Unique identifier: NCT01406678.
Mediterranean Diet and Particulate Matter Exposure Are Associated With LINE-1 Methylation: Results From a Cross-Sectional Study in Women

Emerging evidence suggests that air pollution increases the risk of cardiovascular disease (CVD) and metabolic disorders, adding to the global burden of disease attributable to lifestyle and behavioral factors. Although long interspersed nucleotide elements 1 (LINE-1) methylation has been associated with these disorders, no studies have simultaneously examined the effects of diet and air pollution exposure on DNA methylation. Herein, we evaluated the association of particulate matter (PM with aerodynamic diameters of less than 10 mm) exposure and adherence to Mediterranean Diet (MD) with LINE-1 methylation. Healthy women (n = 299), aged 15 to 80 years, were enrolled in a cross-sectional study. Dietary data and adherence to MD were assessed by a Food Frequency Questionnaire (FFQ) and Mediterranean Diet Score (MDS). PM10 levels during 1-month before recruitment were recorded by monitoring stations and assigned to each woman based on their residential address and day of recruitment. LINE-1 methylation in blood samples was assessed by pyrosequencing and reported as percentage of 5-methylcytosine (5mC). The Mann–Whitney U test, Spearman’s rank correlation test and linear regression models were applied. Our results demonstrated, for the first time, an inverse association between adherence to MD and exposure to PM10 with LINE-1 methylation: while higher monthly PM10 exposure decreases LINE-1 methylation level (β = −0.121; p = 0.037), the adherence to MD increases it (β = 0.691; p < 0.001). MDS seemed to interact with PM10 levels (p = 0.002) on LINE-1 methylation, as such we confirmed that the effect of MD decreased with increasing PM10 levels (β = 0.657; p < 0.001 in the first tertile; β = 0.573; p < 0.001 in the second tertile; β = 0.551; p < 0.001 in the third tertile). Thus, we suggest that LINE-1 methylation is a possible mechanism underpinning environment-related health effects, and encourage further research to evaluate whether the adherence to the MD could counteract the negative effect of PM10 exposure.
Towards Robust Deep Neural Networks

We investigate the topics of sensitivity and robustness in feedforward and convolutional neural networks. Combining energy landscape techniques developed in computational chemistry with tools drawn from formal methods, we produce empirical evidence indicating that networks corresponding to lower-lying minima in the optimization landscape of the learning objective tend to be more robust. The robustness estimate used is the inverse of a proposed sensitivity measure, which we define as the volume of an over-approximation of the reachable set of network outputs under all additive $l_{\infty}$-bounded perturbations on the input data. We present a novel loss function which includes a sensitivity term in addition to the traditional task-oriented and regularization terms. In our experiments on standard machine learning and computer vision datasets, we show that the proposed loss function leads to networks which reliably optimize the robustness measure as well as other related metrics of adversarial robustness without significant degradation in the classification error. Experimental results indicate that the proposed method outperforms state-of-the-art sensitivity-based learning approaches with regards to robustness to adversarial attacks. We also show that although the introduced framework does not explicitly enforce an adversarial loss, it achieves competitive overall performance relative to methods that do.
LncRNA DANCR promotes cervical cancer progression by upregulating ROCK1 via sponging miR‐335‐5p

Emerging evidence highlights the key regulatory roles of long noncoding RNAs (lncRNAs) in the initiation and progression of numerous malignancies. The lncRNA identified as differentiation antagonizing nonprotein coding RNA (DANCR) is a novel lncRNA widely involved in the development of multiple human cancers. However, the function of DANCR and its potential molecular mechanism in cervical cancer remain unclear. In this study, we discovered that DANCR was significantly elevated in cervical cancer tissues and cells, and was closely correlated with poor prognosis of cervical cancer patients. In addition, knockdown of DANCR inhibited proliferation, migration, and invasion of cervical cancer cells in vitro, indicating that DANCR functioned as an oncogene in cervical cancer. Moreover, we verified that DANCR could directly bind to miR‐335‐5p, isolating miR‐335‐5p from its target gene Rho‐associated coiled‐coil containing protein kinase 1 (ROCK1). Functional analysis showed that DANCR regulated ROCK1 expression by competitively binding to miR‐335‐5p. Further cellular behavioral experiments revealed that miR‐335‐5p mimics and ROCK1 knockdown reversed the effects of upregulated DANCR on proliferation, migration, invasion, and epithelial‐mesenchymal transition (EMT) of cervical cancer cells by rescue assays. In summary, this study demonstrated that DANCR promoted cervical cancer progression by functioning as a competing endogenous RNA (ceRNA) to regulate ROCK1 expression via sponging miR‐335‐5p, suggesting a novel potential therapeutic target for cervical cancer.
Transmembrane exchange of fluorosugars: characterization of red cell GLUT1 kinetics using 19F NMR

We developed a novel approach for quantifying the equilibrium-exchange kinetics of carrier-mediated transmembrane transport of fluorinated substrates. Our method is based on an adapted kinetic theory describing the concentration dependence of the transmembrane-exchange rates of two simultaneously transported species. Using the new approach, we quantified the kinetics of membrane transport of both anomers of three monofluorinated glucose analogues in human erythrocytes (red blood cells: RBCs) using 19F nuclear magnetic resonance (NMR) exchange spectroscopy (EXSY). An inosine-based glucose-free medium was shown to promote survival and stable metabolism of RBCs over the duration of the experiments (a few hours). Earlier NMR studies only yielded the apparent rate constants and transmembrane fluxes of the anomeric species, whereas we were able to categorize the two anomers in terms of the catalytic activity (specificity constants) of the glucose transport protein GLUT1 towards them. Differences in the membrane permeability of the three glucose analogues were qualitatively interpreted in terms of local perturbations in the bonding of substrates to amino-acid residues in the active site of GLUT1. The methodology of this work will be applicable to studies of other carrier-mediated membrane transport processes, especially those with competition between simultaneously transported species. The GLUT1-specific results will apply to the design of probes of glucose transport, or inhibitors of glucose metabolism in cells including those exhibiting the Warburg effect. ABBREVIATIONS EXSY exchange spectroscopy FDG fluoro-deoxy-glucose FDG-n n-fluoro-n- deoxy-D-glucose (n = 2, 3, 4) FID free induction decay Glc D-glucose NMR nuclear magnetic resonance RBC red blood cell
Incidence of tuberculosis and the need of prophylactic treatment in persons living with HIV in Stockholm during the era of anti-retroviral therapy 1996–2013

Abstract Background: The aim of this observational cohort study was to determine the incidence and risk factors of active tuberculosis (TB) in persons living with HIV in a low endemic setting over a 17-year time period when combination antiretroviral therapy (ART) has been available. We thereby aimed to understand the usefulness of TB chemoprophylaxis among HIV patients with latent TB. Methods: All 2127 adult patients diagnosed with HIV January 1996–December 2013 at the Karolinska University Hospital in Stockholm County were eligible. After exclusion of 259 patients transferred to other clinics, 1868 were followed until TB diagnosis, death or end of study period (December 2013). The median follow-up time was 7.9 years (interquartile range, 3.9–11.5). Results: Active TB was diagnosed in 92 patients, corresponding to an incidence rate of 6.2 cases (95% CI 5.1–7.6) per 1000 person-years with a significant decline over time. The majority (52%) of TB cases were diagnosed within 1 month from HIV diagnosis. Being a migrant from a TB-endemic region, was the only patient characteristic associated with significantly higher risk of active TB (Hazard Ration, HR: 8.54, 95% confidence interval, CI: 3.09–23.61 in a multivariate regression analysis controlling for route of HIV transmission, year of HIV diagnosis and CD4-cell count and viral load at HIV diagnosis. The number needed to treat to prevent one case of TB among patients in this high-risk group was 22 (95% CI 26–47). Conclusion: The incidence of active TB in persons living with HIV in Stockholm County declined significantly after the introduction of ART but was still 80 times higher than in the general population at the end of the study period. The therapeutic gain of chemoprophylaxis in low endemic settings should be weighed against costs and side effects.