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T. Meinel, D. Wilson, H. Gensicke, J. Scheitz, P. Ringleb, I. Goganau, J. Kaesmacher, H. Bae et al.

Key Points Question Is the recent use of direct oral anticoagulants (confirmed ingestion within 48 hours) associated with increased risk of symptomatic intracranial hemorrhage following intravenous thrombolysis for ischemic stroke? Findings In this cohort study including 33 207 patients with ischemic stroke who received intravenous thrombolysis at 64 centers in Europe, Asia, Australia, and New Zealand, the risk of symptomatic intracranial hemorrhage was lower among the 832 patients taking direct oral anticoagulant treatment compared with controls with no anticoagulation. This result was consistent among subgroups and different selection strategies. Meaning This study found insufficient evidence of excess harm associated with the use of off-label intravenous thrombolysis in selected patients who had taken a direct oral anticoagulant within the previous 48 hours.

Suncica Hadzidedic, A. Cristea, Derrick G. Watson

: The effect of emotions and personalisation on continuance use intentions in online health services is underexplored. Accordingly, we propose a research model for examining the impact of emotion- and personalisation-based factors on cancer website reuse intentions. We conducted a study using a real-world NGO cancer-support website, which was evaluated by 98 participants via an online questionnaire. Model relations were estimated using the PLS-SEM method. Our findings indicated that pre-use emotions did not significantly influence perceived personalisation. However, satisfaction with personalisation, and perceived usefulness mediated by satisfaction, increased reuse intentions. In addition, post-use positive emotions potentially influenced reuse intentions. Our paper, therefore, illustrates the applicability of theory regarding continuance use intentions to cancer-support websites and highlights the importance of personalisation for these purposes.

D. Zurak, D. Vlajsović, M. Duvnjak, K. Salajpal, K. Kljak

SUMMARY Maize, the most common energy feed ingredient in poultry diets, has a high starch proportion in the grain endosperm, ranging from 65 to 75% in various hybrids. The rate and extent of digestion are major determinants of maize starch nutritive value. Starch digestion follows the first-order kinetics, and according to the digestibility kinetics, starch can be divided into rapidly digestible (RDS), slowly digestible (SDS), and resistant starch (RS). Different intrinsic and extrinsic features of maize grain affect the rate and extent of starch digestibility. Differences in starch granule composition, such as amylose-to-amylopectin ratio, crystallisation, association with lipids and zeins, as well as shape, size and presence of surface pores affect starch digestibility kinetics. More so, an important factor affecting digestion is grain processing. Particle size affects feed intake, the passage of bolus and susceptibility to enzyme-starch binding, while hydrothermal processing leads to starch gelatinisation. However, too high temperatures can lead to RS formation. This review summarises the available literature data on factors identified as crucial in the digestibility kinetics of maize starch.

Victor Gonzalez, Ida Fazlic, M. Cotte, F. Vanmeert, Arthur Gestels, Steven De Meyer, Fréderique T H Broers, J. Hermans et al.

The Night Watch, painted in 1642 and on view in the Rijksmuseum in Amsterdam, is considered Rembrandt's most famous work. X-ray powder diffraction (XRPD) mapping at multiple length scales revealed the unusual presence of lead(II) formate, Pb(HCOO)2, in several areas of the painting. Until now, this compound was never reported in historical oil paints. In order to get insights into this phenomenon, one possible chemical pathway was explored thanks to the preparation and micro-analysis of model oil paint media prepared by heating linseed oil and lead(II) oxide (PbO) drier as described in 17th century recipes. Synchrotron radiation based micro-XRPD (SR-µ-XRPD) and infrared microscopy were combined to identify and map at the micro-scale various neo-formed lead-based compounds in these model samples. Both lead(II) formate and lead(II) formate hydroxide Pb(HCOO)(OH) were detected and mapped, providing new clues regarding the reactivity of lead driers in oil matrices in historical paintings.

Nikola Krneta, M. Hagiwara

This article presents a novel circuit configuration of a high-voltage direct current circuit breaker (HVdcCB) test bench that is based on a modified H-bridge modular multilevel cascaded converter (MMCC). The modified MMCC is composed of fewer H-bridge cells, and it can be reconfigured during operation to allow the proposed test bench to output large current or high voltage for the current breaking and dielectric withstand tests. Although simultaneous output of large current and high voltage is not possible, the maximum transient interrupt voltage (TIV) withstand test can be performed with reduced ratings. The controllable output allows generation of complex waveforms to simulate a wide range of fault conditions. Furthermore, the modified MMCC has some inherent safety features that can reduce the need for additional protective equipment in case of operational failure of the HVdcCB. In contrast, the conventional charged capacitor and inductor-based designs cannot generate arbitrary waveforms, are only suitable for current breaking tests, and require additional circuits to generate initial conditions for the HVdcCB. AC short-circuit generator-based designs offer one degree of freedom for control of the output waveforms and can sustain the maximum TIV withstand test. However, the ac output is unsuitable for the dielectric withstand test, and additional circuits are required to provide initial conditions for the HVdcCB. The proposed test bench circuit configuration is verified using a downscaled experimental test bench that consists of a total of nine H-bridge cells with an equivalent switching frequency of 92.5 kHz.

Rreze Halili, F. Z. Yousaf, Nina Slamnik-Kriještorac, G. M. Yilma, M. Liebsch, Rafael Berkvens, M. Weyn

Edge computing is one of the key features of the 5G technology-scape that is realizing new and enhanced automotive use cases for improving road safety and emergency response management. Back Situation Awareness (BSA) is such a use case that provides an advance notification to the vehicles of an arriving emergency vehicle (EmV). This paper presents an algorithm for enhancing the accuracy of the advanced Estimated Time of Arrival (ETA) notification of an approaching EmV towards the other vehicles on the highway. The notification is expected to ensure timely reaction by the vehicles to create a clear corridor for the EmV to pass through unhindered, thereby saving critical time to reach the emergency event in a safe manner. The main features of the presented solution are i) the self-correcting algorithm, ii) adaptive and dynamic dissemination areas size allocation, as a response to traffic changes, and iii) the evaluation of the ETA estimation accuracy. We have used the real travel time data measurements collected on the E313 highway (Antwerp, Belgium), to evaluate the performance of the algorithm. The performance is evaluated and compared in terms of accuracy and run-time complexity, using different methods such as Kalman filter, Filter-less method, Moving Average, and Exponential Moving Average filters. It is observed that the Kalman filter provides better accuracy on the ETA estimation, thereby reducing the estimation error by around 14% on average.

M. Jusufbegović, A. Pandžić, M. Busuladžić, Lejla M Čiva, A. Gazibegović-Busuladžić, A. Šehić, S. Vegar-Zubović, R. Jašić et al.

Computed tomography (CT) is a diagnostic imaging process that uses ionising radiation to obtain information about the interior anatomic structure of the human body. Considering that the medical use of ionising radiation implies exposing patients to radiation that may lead to unwanted stochastic effects and that those effects are less probable at lower doses, optimising imaging protocols is of great importance. In this paper, we used an assembled 3D-printed infant head phantom and matched its image quality parameters with those obtained for a commercially available adult head phantom using the imaging protocol dedicated for adult patients. In accordance with the results, an optimised scanning protocol was designed which resulted in dose reductions for paediatric patients while keeping image quality at an adequate level.

F. Sacirbegovic, M. Günther, A. Greco, Daqiang Zhao, Xi Wang, Meng Zhou, Sarah Rosenberger, M. Oberbarnscheidt et al.

Nea Korvenlaita, Mireia Gómez-Budia, Flavia Scoyni, C. Pistono, L. Giudice, S. Eamen, Sanna Loppi, Ana Hernández de Sande et al.

Abstract Hypoxia induces changes in the secretion of extracellular vesicles (EVs) in several non‐neuronal cells and pathological conditions. EVs are packed with biomolecules, such as microRNA(miR)‐21‐5p, which respond to hypoxia. However, the true EV association of miR‐21‐5p, and its functional or biomarker relevance, are inadequately characterised. Neurons are extremely sensitive cells, and it is not known whether the secretion of neuronal EVs and miR‐21‐5p are altered upon hypoxia. Here, we characterised the temporal EV secretion profile and cell viability of neurons under hypoxia. Hypoxia induced a rapid increase of miR‐21a‐5p secretion in the EVs, which preceded the elevation of hypoxia‐induced tissue or cellular miR‐21a‐5p. Prolonged hypoxia induced cell death and the release of morphologically distinct EVs. The EVs protected miR‐21a‐5p from enzymatic degradation but a remarkable fraction of miR‐21a‐5p remained fragile and non‐EV associated. The increase in miR‐21a‐5p secretion may have biomarker potential, as high blood levels of miR‐21‐5p in stroke patients were associated with significant disability at hospital discharge. Our data provides an understanding of the dynamic regulation of EV secretion from neurons under hypoxia and provides a candidate for the prediction of recovery from ischemic stroke.

M. Capala, K. Pachler, I. Lauwers, Maarten A de Korte, N. Verkaik, H. Mast, B. Jonker, A. Sewnaik et al.

Simple Summary The treatment outcomes in patients with head and neck cancer vary greatly, and serious side effects are often observed. Being able to predict therapy effects is therefore crucial for choosing the best treatment option for each patient. In this study, we developed an assay to evaluate how head and neck tumor cells respond to radiation and chemotherapy. Treatment of thin patient-derived cancer tissue slices in the laboratory (in vitro) resulted in large differences in individual tumor’s reactions to treatment. In the sensitive tumors, cancer cells repaired the DNA damage inflicted by therapy only partially, stopped multiplying, and showed increased levels of cell death. On the other hand, resistant tumors were able to recover from the damage caused by the treatment. The next crucial step is to investigate whether the differences we observed in vitro can indeed predict the treatment outcomes; this is currently being tested in an ongoing clinical trial. Abstract Background: Head and neck squamous cell carcinoma (HNSCC) displays a large heterogeneity in treatment response, and consequently in patient prognosis. Despite extensive efforts, no clinically validated model is available to predict tumor response. Here we describe a functional test for predicting tumor response to radiation and chemotherapy on the level of the individual patient. Methods: Resection material of 17 primary HNSCC patients was cultured ex vivo, irradiated or cisplatin-treated, after which the effect on tumor cell vitality was analyzed several days after treatment. Results: Ionizing radiation (IR) affected tumor cell growth and viability with a clear dose-response relationship, and marked heterogeneity between tumors was observed. After a single dose of 5Gy, proliferation in IR-sensitive tumors dropped below 30% of the untreated level, while IR-resistant tumors maintained at least 60% of proliferation. IR-sensitive tumors showed on average a twofold increase in apoptosis, as well as an increased number and size of DNA damage foci after treatment. No differences in the homologous recombination (HR) proficiency between IR-sensitive and –resistant tumors were detected. Cisplatin caused a decrease in proliferation, as well as induction of apoptosis, again with marked variation between the samples. Conclusions: Our functional ex vivo assay discriminated between IR-sensitive and IR-resistant HNSCC tumors, and may also be suitable for predicting response to cisplatin. Its predictive value is currently under investigation in a prospective clinical study.

Amar Causevic, N. Haque, Matthew LoCastro, S. Selvakkumaran, Sasja Beslik, S. Causevic

Abstract:In order to address the research gaps on climate finance dynamics in developing countries, especially those with low governance scores, this study assesses the 2016–2020 bilateral climate finance to these countries. The total disbursed bilateral climate finance was US$1.3 billion (92 percent for mitigation, 7 percent for adaptation, and 1 percent for mitigation and adaptation simultaneously). Development-focused loans were the prevailing financial instrument cumulatively, and grants were the prevailing instrument on a per-country level. Japan was the biggest provider of bilateral climate finance (US$1 billion) to fund Uzbekistan's natural gas-fired electric power plants. All major bilateral climate finance providers ranked high on governance scores compared to the ten examined countries. Countries examined in this study will need to receive higher amounts of bilateral climate change finance in order to improve their readiness to address this issue and reduce their vulnerability to climate change impacts.

Florian Teichmann, Ines Kirchengast, A. Korjenic

The positive effects of green infrastructure in the urban environment are nowadays widely known and proven by research. Yet, greening, which serves to improve the indoor climate and people’s well-being, is integrated very limited in public facilities such as schools. Reasons for this are seen in a lack of knowledge and financing opportunities. A focus, among others, of the MehrGrüneSchulen research project is the interdisciplinary development of cost-effective greening solutions for schools. The designs were developed in close collaboration with students of a technical college (HTL) and a horticultural school. This study describes the development process and presents the results of the first implementations of greening systems at the HTL-building complex and at nine other schools in Austria.

Ananth Hari, Qinghui Zhou, Nina Gonzaludo, J. Harting, S. Scott, X. Qin, S. Scherer, S. C. Sahinalp et al.

High-throughput sequencing provides sufficient means for determining genotypes of clinically important pharmacogenes that can be used to tailor medical decisions to individual patients. However, pharmacogene genotyping, also known as star-allele calling, is a challenging problem that requires accurate copy number calling, structural variation identification, variant calling, and phasing within each pharmacogene copy present in the sample. Here we introduce Aldy 4, a fast and efficient tool for genotyping pharmacogenes that uses combinatorial optimization for accurate star-allele calling across different sequencing technologies. Aldy 4 adds support for long reads and uses a novel phasing model and improved copy number and variant calling models. We compare Aldy 4 against the current state-of-the-art star-allele callers on a large and diverse set of samples and genes sequenced by various sequencing technologies, such as whole-genome and targeted Illumina sequencing, barcoded 10x Genomics, and Pacific Biosciences (PacBio) HiFi. We show that Aldy 4 is the most accurate star-allele caller with near-perfect accuracy in all evaluated contexts, and hope that Aldy remains an invaluable tool in the clinical toolbox even with the advent of long-read sequencing technologies.

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