Miracle-dz/UniFAR-FTUs huggingface dataset:
Assessment of the Association of Health with the Liberalisation of Trade in Services under the World Trade Organisation

Background The liberalisation of trade in services which began in 1995 under the General Agreement on Trade in Services (GATS) of the World Trade Organisation (WTO) has generated arguments for and against its potential health effects. Our goal was to explore the relationship between the liberalisation of services under the GATS and three health indicators - life expectancy (LE), under-5 mortality (U5M) and maternal mortality (MM) - since the WTO was established. Methods and Findings This was a cross-sectional ecological study that explored the association in 2010 and 1995 between liberalisation and health (LE, U5M and MM), and between liberalisation and progress in health in the period 1995–2010, considering variables related to economic and social policies such as per capita income (GDP pc), public expenditure on health (PEH), and income inequality (Gini index). The units of observation and analysis were WTO member countries with data available for 2010 (n = 116), 1995 (n = 114) and 1995–2010 (n = 114). We conducted bivariate and multivariate linear regression analyses adjusted for GDP pc, Gini and PEH. Increased global liberalisation in services under the WTO was associated with better health in 2010 (U5M: −0.358 p<0.001; MM: −0.338 p = 0.001; LE: 0.247 p = 0.008) and in 1995, after adjusting for economic and social policy variables. For the period 1995–2010, progress in health was associated with income equality, PEH and per capita income. No association was found with global liberalisation in services. Conclusions The favourable association in 2010 between health and liberalisation in services under the WTO seems to reflect a pre-WTO association observed in the 1995 data. However, this liberalisation did not appear as a factor associated with progress in health during 1995–2010. Income equality, health expenditure and per capita income were more powerful determinants of the health of populations.
P2X Receptor-Stimulated Calcium Responses in Preglomerular Vascular Smooth Muscle Cells Involves 20-Hydroxyeicosatetraenoic Acid

The current study tested the hypothesis that endogenous 20-hydroxyeicosatetraenoic acid (20-HETE) contributes to the increase in intracellular calcium ([Ca2+]i) elicited by P2X receptor activation in renal microvascular smooth muscle cells. Vascular smooth muscle cells obtained from rats were loaded with fura-2 and studied using standard single cell fluorescence microscopy. Basal renal myocyte [Ca2+]i averaged 96 ± 5 nM. ATP (10 and 100 μM) increased vascular smooth muscle cell [Ca2+]i by 340 ± 88 and 555 ± 80 nM, respectively. The cytochrome P450 hydroxylase inhibitor, N-methylsulfonyl-12,12-dibromododec-11-enamide (DDMS), or the 20-HETE antagonist, 20-hydroxyeicosa-6(Z),15(Z)-dienoic acid (20-HEDE), significantly attenuated the peak myocyte [Ca2+]i responses to 10 and 100 μM ATP. ATP (100 μM) increased vascular smooth muscle cell [Ca2+]i by 372 ± 93 and 163 ± 55 nM in the presence of DDMS or 20-HEDE, respectively. The P2X receptor agonist, α,β-methylene-ATP (10 μM), increased myocyte [Ca2+]i by 78 ± 12 nM, and this response was significantly attenuated by DDMS (40 ± 15 nM). In contrast, the vascular smooth muscle cell [Ca2+]i evoked by the P2Y agonist, UTP (100 μM), was not altered by DDMS or 20-HEDE. The effect of 20-HETE on [Ca2+]i was also assessed, and the peak increases in [Ca2+]i averaged 62 ± 12 and 146 ± 70 nM at 20-HETE concentrations of 1 and 10 μM, respectively. These results demonstrate that 20-HETE plays a significant role in the renal microvascular smooth muscle cell [Ca2+]i response to P2X receptor activation.
The impact of serious adverse drug reactions: a population‐based study of a decade of hospital admissions in New South Wales, Australia

AIMS Adverse drug reactions (ADRs) have major impacts on patients and the hospital system. Methods identifying ADRs from selected International Classification of Diseases-10th revision (ICD-10) diagnosis and external cause codes can be applied to population-level hospital admissions data, enabling the study of rare, yet serious ADRs. The present study aimed to use ICD10-based methods to identify four types of serious idiosyncratic ADRs in Australia, and to assess changes in incidence and their impact on length of stay (LOS), readmission and in-hospital mortality. METHODS The study used a census of hospital admission data from New South Wales between July 2000 and June 2012. Changes in incidence rates over time relative to a control group were estimated using log-linear regression. To assess impacts on LOS, readmission and mortality, each ADR case was matched with five controls, and cases were compared with controls via generalized linear models appropriate to each outcome. RESULTS The incidence of three ADR types showed a significant increase over time relative to controls, while the fourth type showed no evidence of change. All ADR types were significantly associated with an increase in LOS of between 22% and 328%. Significant increases in risk of readmission or death were only observed for some ADR types. CONCLUSIONS Reducing the incidence of idiosyncratic ADRs is challenging. ICD10-based methods support population-level analyses that can provide important insights into the effects and changes in ADRs over time. This, combined with strategies related to both patient care and drug monitoring pre- and post-commercial release, provides ways forward.
A taxonomy of estimands for regulatory clinical trials with discontinuations

The National Research Council Panel on Handling Missing Data in Clinical Trials recommended that protocols for clinical trials ‘explicitly define. causal estimands of primary interest’. In discussions with sponsors of clinical trials since the publication of the National Research Council report, the expression causal estimands has been the subject of confusion. It may not be entirely clear what the National Research Council panel meant, and in any case, it has not been clear how this recommendation might be put in practice. This paper's purpose is to say how the working group understands it and how we think it should be put in practice. We classify possible choices of estimand according to their usefulness for regulatory purposes in various clinical settings. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.
Safety and Efficacy of Scanning Ultrasound Treatment of Aged APP23 Mice

Deposition of amyloid-β (Aβ) peptide leads to amyloid plaques that together with tau deposits characterize the brains of patients with Alzheimer's disease (AD). In modeling this pathology, transgenic animals such as the APP23 strain, that expresses a mutant form of the amyloid precursor protein found in familial cases of AD, have been instrumental. In previous studies, we have shown that repeated treatments with ultrasound in a scanning mode (termed scanning ultrasound or SUS) were effective in removing Aβ and restoring memory functions, without the need for a therapeutic agent such as an Aβ antibody. Considering that age is the most important risk factor for AD, we extended this study in which the mice were only 12 months old at the time of treatment by assessing a cohort of 2 year-old mice. Interestingly, at this age, APP23 mice are characterized by cerebral amyloid angiopathy (CAA) and the presence of occasional microbleeds. We found that SUS in aged mice that have been exposed to four SUS sessions that were spread out over 8 weeks and analyzed 4 weeks later did not show evidence of increased CAA or microbleeds. Furthermore, amyloid was reduced as assessed by methoxy-XO4 fluorescence. In addition, plaque-associated microglia were more numerous in SUS treated mice. Together this adds to the notion that SUS may be a treatment modality for human neurodegenerative diseases.
Performance Metrics for Storage-Based Transient Stability Control

In this work we investigate existing and new metrics for evaluating transient stability of power systems to quantify the impact of distributed control schemes. Specifically, an energy storage system (ESS)-based control scheme that builds on feedback linearization theory is implemented in the power system to enhance its transient stability. We study the value of incorporating such ESS-based distributed control on specific transient stability metrics that include critical clearing time, critical control activation time, system stability time, rotor angle stability index, rotor speed stability index, rate of change of frequency, and control power. The stability metrics are evaluated using the IEEE 68-bus test power system. Numerical results demonstrate the value of the distributed control scheme in enhancing the transient stability metrics of power systems.
Effect of Caffeine Supplementation on Quadriceps Performance After Eccentric Exercise

Abstract Green, MS, Martin, TD, and Corona, BT. Effect of caffeine supplementation on quadriceps performance after eccentric exercise. J Strength Cond Res 32(10): 2863–2871, 2018—Caffeine use is common among athletes seeking to capitalize on its potential ergogenic effects. Limited research has examined caffeine's effects when used after activities that resulted in exercise-induced muscle damage (EIMD). This study examined the effect of caffeine supplementation on uninjured and injured muscle. Eight men and women (N = 16) who were physically active individuals participated in this study (age: 24.3 ± 4.3 years; height: 173.0 ± 7.0 cm, mass: 75.2 ± 11.5 kg; body fat: 18.2 ± 15.9%). One leg was assessed under uninjured and injured (100 eccentric quadriceps contractions) conditions after caffeine supplementation (6 mg·kg−1), with the other leg assessed under both conditions after placebo supplementation. Compared with the placebo, caffeine increased peak isokinetic torque by 6.8 ± 2.3 and 9.4 ± 2.5% in uninjured and injured muscle, respectively, but had no effect on maximal voluntary isometric torque or fatigue index in uninjured or injured muscle, with treatments exhibiting similar (p > 0.05) alterations in isometric torque (−11.9 ± 2.2%), fatigue index (−13.9 ± 3.4%), and soreness (+44.0 ± 4.7) after eccentric contractions. The results of this study suggest that caffeine possesses a similar ergogenic effect on isokinetic torque in both uninjured and injured states, but no effect on the production of isometric torque, perception of soreness, or degree of relative fatigue. Athletes should consider the potential caffeine supplementation possesses during recovery from activities that resulted in EIMD.
Role of the Hof1–Cyk3 interaction in cleavage-furrow ingression and primary-septum formation during yeast cytokinesis

In Saccharomyces cerevisiae, it is well established that Hof1, Cyk3, and Inn1 contribute to septum formation and cytokinesis. Because hof1∆ and cyk3∆ single mutants have relatively mild defects but hof1∆ cyk3∆ double mutants are nearly dead, it has been hypothesized that these proteins contribute to parallel pathways. However, there is also evidence that they interact physically. In this study, we examined this interaction and its functional significance in detail. Our data indicate that the interaction 1) is mediated by a direct binding of the Hof1 SH3 domain to a proline-rich motif in Cyk3; 2) occurs specifically at the time of cytokinesis but is independent of the (hyper)phosphorylation of both proteins that occurs at about the same time; 3) is dispensable for the normal localization of both proteins; 4) is essential for normal primary-septum formation and a normal rate of cleavage-furrow ingression; and 5) becomes critical for growth when either Inn1 or the type II myosin Myo1 (a key component of the contractile actomyosin ring) is absent. The similarity in phenotype between cyk3∆ mutants and mutants specifically lacking the Hof1–Cyk3 interaction suggests that the interaction is particularly important for Cyk3 function, but it may be important for Hof1 function as well.
A drug development perspective on targeting tumor‐associated myeloid cells

Despite decades of research, cancer remains a devastating disease and new treatment options are needed. Today cancer is acknowledged as a multifactorial disease not only comprising of aberrant tumor cells but also the associated stroma including tumor vasculature, fibrotic plaques, and immune cells that interact in a complex heterotypic interplay. Myeloid cells represent one of the most abundant immune cell population within the tumor stroma and are equipped with a broad functional repertoire that promotes tumor growth by suppressing cytotoxic T cell activity, stimulating neoangiogenesis and tissue remodeling. Therefore, myeloid cells have become an attractive target for pharmacological intervention. In this review, we summarize the pharmacological approaches to therapeutically target tumor‐associated myeloid cells with a focus on advanced programs that are clinically evaluated. In addition, for each therapeutic strategy, the preclinical rationale as well as advantages and challenges from a drug development perspective are discussed.
Ranolazine Attenuates Trastuzumab-Induced Heart Dysfunction by Modulating ROS Production

The ErbB2 blocker trastuzumab improves survival in oncologic patients, but can cause cardiotoxicity. The late Na+ current inhibitor ranolazine has been shown to counter experimental HF, including doxorubicin cardiotoxicity (a condition characterized by derangements in redox balance), by lowering the levels of reactive oxygen species (ROS). Since ErbB2 can modulate ROS signaling, we tested whether trastuzumab cardiotoxicity could be blunted by ranolazine via redox-mediated mechanisms. Trastuzumab decreased fractional shortening and ejection fraction in mice, but ranolazine prevented heart dysfunction when co-administered with trastuzumab. Trastuzumab cardiotoxicity was accompanied by elevations in natriuretic peptides and matrix metalloproteinase 2 (MMP2) mRNAs, which were not elevated with co-treatment with ranolazine. Trastuzumab also increased cleavage of caspase-3, indicating activation of the proapoptotic machinery. Again, ranolazine prevented this activation. Interestingly, Neonatal Rat Ventricular Myocytes (NRVMs), labeled with MitoTracker Red and treated with trastuzumab, showed only a small increase in ROS compared to baseline conditions. We then stressed trastuzumab-treated cells with the beta-agonist isoproterenol to increase workload, and we observed a significant increase of probe fluorescence, compared with cells treated with isoproterenol alone, reflecting induction of oxidative stress. These effects were blunted by ranolazine, supporting a role for INa inhibition in the regulation of redox balance also in trastuzumab cardiotoxicity.
Finite‐difference calculation of traveltimes in three dimensions

The traveltimes of first arriving seismic rays through most velocity structures can be computed rapidly on a three-dimensional numerical grid by finite-difference extrapolation. Head waves are properly treated and shadow zones are filled by the appropriate diffractions. Differences of less than 0.11 percent are found between the results of this technique and ray tracing for a complex but smooth model. This scheme has proven useful for earthquake location and shows promise as an inexpensive, well-behaved substitute for ray tracing in forward-modeling and Kirchhoff inversion applications.
Statistical modeling of heterogeneous robotic assembly time with Weibull regression

It is critical to model the relationships between robotic control parameters and the performance of the robotic systems. Existing modeling methods generally assume homogeneously distributed performance data. However, such homogeneity assumption may not be realistic in industrial practices. With explicit consideration of potential data heterogeneity, this paper proposes a Weibull regression and an EM algorithm to model the impacts of robotic control parameters on the time for robots to successfully complete a task. A numerical case study shows the high accuracy of the model parameter estimation. It demonstrates that the proposed method without homogeneity assumption is effective and can be applied in many real-world problems.
Marginal regression models for clustered count data based on zero‐inflated Conway–Maxwell–Poisson distribution with applications

Community water fluoridation is an important public health measure to prevent dental caries, but it continues to be somewhat controversial. The Iowa Fluoride Study (IFS) is a longitudinal study on a cohort of Iowa children that began in 1991. The main purposes of this study (http://www.dentistry.uiowa.edu/preventive‐fluoride‐study) were to quantify fluoride exposures from both dietary and nondietary sources and to associate longitudinal fluoride exposures with dental fluorosis (spots on teeth) and dental caries (cavities). We analyze a subset of the IFS data by a marginal regression model with a zero‐inflated version of the Conway–Maxwell–Poisson distribution for count data exhibiting excessive zeros and a wide range of dispersion patterns. In general, we introduce two estimation methods for fitting a ZICMP marginal regression model. Finite sample behaviors of the estimators and the resulting confidence intervals are studied using extensive simulation studies. We apply our methodologies to the dental caries data. Our novel modeling incorporating zero inflation, clustering, and overdispersion sheds some new light on the effect of community water fluoridation and other factors. We also include a second application of our methodology to a genomic (next‐generation sequencing) dataset that exhibits underdispersion.
Motion robust PPG-imaging through color channel mapping

Photoplethysmography (PPG)-imaging is an emerging noninvasive technique that maps spatial blood-volume variations in living tissue with a video camera. In this paper, we clarify how cardiac-related (i.e., ballistocardiographic; BCG) artifacts occur in this imaging modality and address these using algorithms from the remote-PPG literature. Performance is assessed under stationary conditions at the immobilized hand. Our proposal outperforms the state-of-the-art, blood pulsation imaging [Biomed. Opt. Express 5, 3123 (2014)25401026. ], even in our best attempt to create diffused illumination. BCG-artifacts are suppressed to an order of magnitude below PPG-signal strength, which is sufficient to prevent interpretation errors.
The impact of the latest echocardiographic chamber quantification recommendations on the prediction of left atrial appendage thrombus presence by transthoracic echocardiography

Abstract Introduction: The latest recommendations for echocardiographic chamber quantification have implemented updated normal values for all cardiac chambers. Purpose: To evaluate the incidence of normal and abnormal values of routine echocardiographic parameters such as left ventricular ejection fraction (LVEF) and left atrial volume indexed to body surface area (LAVi) in patients with non-valvular atrial fibrillation (AF) and to determine the influence of LVEF and LAVi reclassification on the prediction of LAAT by transthoracic echocardiography. Methods: We retrospectively analysed the database of 1674 transesophageal echocardiograms performed between 2012 and 2015 in our echo lab. The study involved patients (mean age 70 ± 7 years, 80% men) with paroxysmal or persistent AF (35 patients with left atrial appendage thrombus [LAAT] and 35 sex- and age-matched controls without LAAT). LVEF and LAVi were categorised in two ways: semi-quantitative using four-degree scale (normal or abnormal graded from mild and moderate to severe) and qualitative (normal vs. abnormal). Results: We reclassified 6 (9%) and 4 (6%) patients with regard to LVEF as well as 38 (54%) and 16 (23%) with regard to LAVi on semi-quantitative and qualitative scale, respectively. After adjustment for effective anticoagulation and approved risk factors in the multivariate models, we identified LVEF categorised in semi-quantitative manner according to both documents, LAVi categorised in a binary manner by new guidelines and semi-quantitative scale by both recommendations as independently associated with LAAT. Conclusions: Differentiation between normal and abnormal value enhanced the diagnostic meaning of LAVi in the aspect of higher LAAT risk. LVEF reclassification had no significant influence.
Object recognition based on human description ontology for service robots

We are developing a helper robot able to fetch objects requested by users. This robot tries to recognize objects through verbal interaction with the user concerning the objects that it cannot detect autonomously. We have shown that the system can recognize objects based on an ontology for interaction. In this paper, we extend a human description ontology to link a "human description" to "attributes of objects" for our interactive object recognition framework. We develop an interactive object recognition system based on this ontology. Experimental results confirmed that the system could efficiently recognize objects by utilizing this ontology.
Oxidative Stress and Vascular Function

Many drug-induced complications and diseases are known to be associated with or even based on a dysequilibrium between the formation of reactive oxygen or nitrogen species (RONS) and the expression/activity of antioxidant enzymes that catalyze the breakdown of these harmful reactive species. The “kindling radical” concept is based on the initial formation of RONS that in turn activate additional sources of RONS in certain pathological conditions. Recently, we and others have demonstrated such “cross-talk” between NADPH oxidases and mitochondria in the setting of nitroglycerin-induced nitrate tolerance, the aging process and angiotensin-II triggered arterial hypertension via redox pathways compromising the mitochondrial, ATP-sensitive potassium channel (mKATP), the mitochondrial permeability transition pore (mPTP), cSrc and protein kinases and the NADPH oxidase isoform Nox2 (and eventually Nox1). This review will focus on the uncoupling of endothelial nitric oxide synthase (eNOS) by initially formed “kindling radicals” (RONS) and on the different “redox switches” that are involved in the uncoupling process of eNOS. S-glutathionylation of the eNOS reductase domain, adverse phosphorylation of eNOS, and of course the oxidative depletion of tetrahydrobiopterin (BH4) will be highlighted as potential “redox switches” in eNOS. In addition, RONS-triggered increases in levels of asymmetric dimethylarginine (ADMA) and L-arginine depletion will be discussed as alternative reasons for dysfunctional eNOS. Finally, we present the clinical perspectives of eNOS uncoupling (and dysfunction) for the development and progression of cardiovascular disease and discuss the important prognostic value of the measurement of endothelial function (e.g. by flow-mediated dilation or forearm plethysmography) for patients with cardiovascular disease.
Introducing remote attestation and hardware-based cryptography to OPC UA

In this paper we investigate whether and how hardware-based roots of trust, namely Trusted Platform Modules (TPMs) can improve the security of the communication protocol OPC UA (Open Platform Communications Unified Architecture) under reasonable assumptions, i.e. the Dolev-Yao attacker model. Our analysis shows that TPMs may serve for generating (RNG) and securely storing cryptographic keys, as cryptocoprocessors for weak systems, as well as for remote attestation. We propose to include these TPM functions into OPC UA via so-called ConformanceUnits, which can serve as building blocks of profiles that are used by clients and servers for negotiating the parameters of a session. Eventually, we present first results regarding the performance of a client-server communication including an additional OPC UA server providing remote attestation of other OPC UA servers.