| 1. |
- Csenge, Szeverenyi, et al.
(author)
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Az ortopédiai nagymǔtétek során alkalmazott terápiás szuggesztiók hatása a beteg gyógyulására
- 2018
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In: Orvosi Hetilap. - : Akademiai Kiado Zrt.. - 0030-6002 .- 1788-6120. ; 159:48, s. 2011-2020
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Journal article (peer-reviewed)abstract
- Introduction and aim: Hip and knee replacement surgery is very demanding for patients. Medication consumption is further increased by perioperative anxiety. Besides pain killer and anxiolytic medications, patients' recovery can be enhanced by applying therapeutic suggestions, which are easily applicable during the patient-physician communication. Method: In our prospective, randomized, controlled study we examined the effects of positive suggestions on patients undergoing hip or knee arthroplasty in spinal anaesthesia. Members of the suggestion group received the therapeutic suggestions during a pre-surgery physician visit, and by listening to an audio recording during surgery. Results: Compared to the control group (n = 50), in the suggestion group (n = 45) the need of medication (pain killer and adjuvant pain medication) during the surgery was lower (p = 0.037), the mean change from baseline in the well-being of the patients was better on the 2nd [1.31 (0.57; 2.04); p<0.001] and 4th [0.97 (0.23; 1.7); p = 0.011] postoperative day and less transfusion had to be administered (OR: 2.37; p = 0.004). However, there was no difference between the two groups in the postoperative need of medications, in the length of hospitalisation and in the frequency of complications. Conslusion: Our results indicate that the administration of therapeutic suggestions in the perioperative period may be beneficial for orthopaedic surgery patients.
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| 2. |
- Maróti, Zoltán, et al.
(author)
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The genetic origin of Huns, Avars, and conquering Hungarians
- 2022
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In: Current Biology. - : Elsevier BV. - 0960-9822 .- 1879-0445. ; 32:13, s. 2858-2870, 2858–2870.e1–e7
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Journal article (peer-reviewed)abstract
- Huns, Avars, and conquering Hungarians were migration-period nomadic tribal confederations that arrived in three successive waves in the Carpathian Basin between the 5th and 9th centuries. Based on the historical data, each of these groups are thought to have arrived from Asia, although their exact origin and relation to other ancient and modern populations have been debated. Recently, hundreds of ancient genomes were analyzed from Central Asia, Mongolia, and China, from which we aimed to identify putative source populations for the above-mentioned groups. In this study, we have sequenced 9 Hun, 143 Avar, and 113 Hungarian conquest period samples and identified three core populations, representing immigrants from each period with no recent European ancestry. Our results reveal that this “immigrant core” of both Huns and Avars likely originated in present day Mongolia, and their origin can be traced back to Xiongnus (Asian Huns), as suggested by several historians. On the other hand, the “immigrant core” of the conquering Hungarians derived from an earlier admixture of Mansis, early Sarmatians, and descendants of late Xiongnus. We have also shown that a common “proto-Ugric” gene pool appeared in the Bronze Age from the admixture of Mezhovskaya and Nganasan people, supporting genetic and linguistic data. In addition, we detected shared Hun-related ancestry in numerous Avar and Hungarian conquest period genetic outliers, indicating a genetic link between these successive nomadic groups. Aside from the immigrant core groups, we identified that the majority of the individuals from each period were local residents harboring “native European” ancestry.
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| 3. |
- Szeverenyi, Csenge, et al.
(author)
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The use of adjunct psychosocial interventions can decrease postoperative pain and improve the quality of clinical care in orthopedic surgery. A systematic review and meta-analysis of randomized controlled trials
- 2018
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In: Journal of Pain. - : Elsevier BV. - 1526-5900. ; 19:11, s. 1231-1252
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Journal article (peer-reviewed)abstract
- This study aims to assess the effectiveness of psychosocial techniques to decrease postoperative pain and improve perioperative clinical care in orthopedic surgery. A systematic review and meta-analysis was performed to evaluate the effects of psychosocial methods among adults undergoing orthopedic surgeries. The systematic review included both randomized and nonrandomized trials, but only randomized controlled clinical trials (RCTs) were included in the meta-analysis. Key outcomes were postoperative pain, analgesic requirement, perioperative anxiety, quality of life, and recovery. After searching the databases from January 1980 to September 2016, a total of 62 RCTs were included with a pooled sample size of 4,908. Psychosocial interventions significantly reduced postoperative pain (Hedges’ g = 0.31 [95% confidence interval = 0.14, 0.48]), and preoperative and postoperative anxiety (g = 0.26 [0.11, 0.42] and g = 0.4 [0.21, 0.59], respectively). Furthermore, psychosocial interventions improved recovery (g = 0.38 [0.22, 0.54]). However, no significant effects were found for postoperative analgesic use (g = 0.16 [−0.01, 0.32]) and quality of life (g = 0.14 [−0.05, 0.33]). Patient education and relaxation techniques produced the most consistent positive effects, showing benefits on pain, anxiety, and recovery. Cognitive or behavioral techniques improved recovery. Furthermore, larger effects were found for studies that included acute surgeries compared to elective surgeries. The results indicate that psychosocial interventions, especially patient education and relaxation training, may reduce perioperative side effects and improve recovery in patients undergoing orthopedic procedures, but the quality of evidence is generally low. More well-powered, high-quality studies are needed to increase confidence.
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| 4. |
- Varga, Gábor, et al.
(author)
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Cu(II)-amino acid–CaAl-layered double hydroxide complexes, recyclable, efficient catalysts in various oxidative transformations
- 2016
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In: Journal of Molecular Catalysis A: Chemical. - : Elsevier BV. - 1381-1169. ; 423, s. 49-60
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Journal article (peer-reviewed)abstract
- Intercalated composite materials were prepared with CaAl-layered double hydroxide as host and Cu(II)-amino acid (L-cysteine, L-histidine and L-tyrosine) complex anions as guests. Two methods (intercalation of the ligand first followed by constructing the complex; preforming the complex first, then introducing it among the layers of the host) and optimization of the synthesis conditions were performed to obtain composites having the complex exclusively among the layers. The composite materials were structurally characterized by powder X-ray diffractometry, mid infrared (IR) spectroscopy with ATR (attenuated total reflectance) or photoacoustic detections, transmission and scanning electron microscopies and X-ray photoelectron spectroscopy. Structural features of the intercalant (coordination number, coordination sites) were elucidated by classical chemical and energy dispersive X-ray analyses, EPR (electron paramagnetic spectroscopy), X-ray absorption and far IR spectroscopies. Structural models based on these methods are also given. Catalytic activities, selectivities and recycling abilities of the substances were studied in the oxidation reactions of cyclohexene with peracetic acid and in situ formed iodosylbenzene as oxidants in the liquid phase. The catalysts were active in the Ullmann coupling reaction as well. The intercalated substances were found to be efficient and highly selective catalysts with very good recycling abilities.
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| 5. |
- Bott, Lukas Thomas, et al.
(author)
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Coulomb dissociation of O-16 into He-4 and C-12
- 2023
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In: NUCLEAR PHYSICS IN ASTROPHYSICS - X, NPA-X 2022. - : EDP Sciences. - 2100-014X. ; 279
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Conference paper (peer-reviewed)abstract
- We measured the Coulomb dissociation of O-16 into He-4 and C-12 within the FAIR Phase-0 program at GSI Helmholtzzentrum fur Schwerionenforschung Darmstadt, Germany. From this we will extract the photon dissociation cross section O-16(alpha,gamma)C-12, which is the time reversed reaction to C-12(alpha,gamma)O-16. With this indirect method, we aim to improve on the accuracy of the experimental data at lower energies than measured so far. The expected low cross section for the Coulomb dissociation reaction and close magnetic rigidity of beam and fragments demand a high precision measurement. Hence, new detector systems were built and radical changes to the (RB)-B-3 setup were necessary to cope with the high-intensity O-16 beam. All tracking detectors were designed to let the unreacted O-16 ions pass, while detecting the C-12 and He-4.
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| 6. |
- Cinege, Gyöngyi, et al.
(author)
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Distinctive features of Zaprionus indianus hemocyte differentiation and function revealed by transcriptomic analysis
- 2023
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In: Frontiers in Immunology. - : Frontiers Media S.A.. - 1664-3224. ; 14
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Journal article (peer-reviewed)abstract
- Background: Insects have specialized cell types that participate in the elimination of parasites, for instance, the lamellocytes of the broadly studied species Drosophila melanogaster. Other drosophilids, such as Drosophila ananassae and the invasive Zaprionus indianus, have multinucleated giant hemocytes, a syncytium of blood cells that participate in the encapsulation of the eggs or larvae of parasitoid wasps. These cells can be formed by the fusion of hemocytes in circulation or originate from the lymph gland. Their ultrastructure highly resembles that of the mammalian megakaryocytes.Methods: Morphological, protein expressional, and functional features of blood cells were revealed using epifluorescence and confocal microscopy. The respective hemocyte subpopulations were identified using monoclonal antibodies in indirect immunofluorescence assays. Fluorescein isothiocyanate (FITC)-labeled Escherichia coli bacteria were used in phagocytosis tests. Gene expression analysis was performed following mRNA sequencing of blood cells.Results: D. ananassae and Z. indianus encapsulate foreign particles with the involvement of multinucleated giant hemocytes and mount a highly efficient immune response against parasitoid wasps. Morphological, protein expressional, and functional assays of Z. indianus blood cells suggested that these cells could be derived from large plasmatocytes, a unique cell type developing specifically after parasitoid wasp infection. Transcriptomic analysis of blood cells, isolated from naïve and wasp-infected Z. indianus larvae, revealed several differentially expressed genes involved in signal transduction, cell movements, encapsulation of foreign targets, energy production, and melanization, suggesting their role in the anti-parasitoid response. A large number of genes that encode proteins associated with coagulation and wound healing, such as phenoloxidase activity factor-like proteins, fibrinogen-related proteins, lectins, and proteins involved in the differentiation and function of platelets, were constitutively expressed. The remarkable ultrastructural similarities between giant hemocytes and mammalian megakaryocytes, and presence of platelets, and giant cell-derived anucleated fragments at wound sites hint at the involvement of this cell subpopulation in wound healing processes, in addition to participation in the encapsulation reaction.Conclusion: Our observations provide insights into the broad repertoire of blood cell functions required for efficient defense reactions to maintain the homeostasis of the organism. The analysis of the differentiation and function of multinucleated giant hemocytes gives an insight into the diversification of the immune mechanisms.
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| 7. |
- Feitosa, Mary F., et al.
(author)
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Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries
- 2018
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In: PLOS ONE. - : Public library science. - 1932-6203. ; 13:6
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Journal article (peer-reviewed)abstract
- Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association study accounting for gene-alcohol consumption interaction for BP might identify additional BP loci and contribute to the understanding of alcohol-related BP regulation. We conducted a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions. In Stage 1, genome-wide discovery meta-analyses in approximate to 131 K individuals across several ancestry groups yielded 3,514 SNVs (245 loci) with suggestive evidence of association (P <1.0 x 10(-5)). In Stage 2, these SNVs were tested for independent external replication in individuals across multiple ancestries. We identified and replicated (at Bonferroni correction threshold) five novel BP loci (380 SNVs in 21 genes) and 49 previously reported BP loci (2,159 SNVs in 109 genes) in European ancestry, and in multi-ancestry meta-analyses (P < 5.0 x 10(-8)). For African ancestry samples, we detected 18 potentially novel BP loci (P< 5.0 x 10(-8)) in Stage 1 that warrant further replication. Additionally, correlated meta-analysis identified eight novel BP loci (11 genes). Several genes in these loci (e.g., PINX1, GATA4, BLK, FTO and GABBR2 have been previously reported to be associated with alcohol consumption. These findings provide insights into the role of alcohol consumption in the genetic architecture of hypertension.
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| 8. |
- Jakli, Antal, et al.
(author)
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Method for preparing anisotropic particles and devices thereof
- 2010
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Patent (pop. science, debate, etc.)abstract
- The invention provides a simple and cost-effective method for preparing particles such as anisotropic semiconductor nanoparticles (e.g. CdS) and devices thereof. The method comprises (i) dispersing at least part of particle-forming reactants in a self-organized medium such as surfactant-aqueous solution system, and (ii) conducting a particle-forming reaction using the particle-forming reactants dispersed in the self-organized medium under shear condition to form the particles. The anisotropic property of the particles is controlled at least partially by the shear condition. The invention may be used to prepare quantum dots in a liquid crystal, and various devices such as nonlinear optics, optoelectronic devices, and solar cells, among others.
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| 9. |
- Kasos, Krisztian, et al.
(author)
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Bilateral electrodermal activity in the active-alert hypnotic induction
- 2018
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In: International Journal of Clinical and Experimental Hypnosis. - : Informa UK Limited. - 0020-7144 .- 1744-5183. ; 66:3, s. 282-297
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Journal article (peer-reviewed)abstract
- Shifts in hemispheric dominance were previously proposed to play a role in hypnosis. Participants (N = 32) were exposed to an active–alert hypnosis induction and a music-control condition while electrodermal activity was registered bilaterally, providing information on alterations in hemispheric dominance. The results suggest that highly hypnotizable participants show a shift to right-sided and low hypnotizable participants demonstrated a shift to left-sided electrodermal dominance in response to the induction, whereas no change in laterality is present in the control condition. Additionally, the authors found that self-reported hypnosis experiences were also associated with a shift in laterality. These results underline the importance of the shift to right hemispheric activity in hypnosis and underscore the importance of hemispheric changes in shaping subjective experience.
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| 10. |
- Kekecs, Zoltan, et al.
(author)
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Guidelines for the Assessment of Efficacy of Clinical Hypnosis Applications
- 2022
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In: International Journal of Clinical and Experimental Hypnosis. - : Informa UK Limited. - 0020-7144 .- 1744-5183. ; 70:2, s. 104-122
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Journal article (peer-reviewed)abstract
- Research on the efficacy of hypnosis applications continues to grow, but there remain major gaps between the science and clinical practice. One challenge has been a lack of consensus on which applications of hypnosis are efficacious based on research evidence. In 2018, 6 major hypnosis organizations collaborated to form the Task Force for Establishing Efficacy Standards for Clinical Hypnosis. This paper describes a Guideline for the Assessment of Efficacy of Clinical Hypnosis Applications developed by the Task Force, which makes 10 specific recommendations. The guideline is intended to be a tool for those who want to assess the quality of existing evidence on the efficacy of clinical hypnosis for any particular indication. The paper also discusses methodological issues in the interpretation and implementation of these guidelines. Future papers will report on the other products of the Hypnosis Efficacy Task Force, such as best practice recommendations for outcomes research in hypnosis and an international survey of researchers and clinicians on current practice and attitudes about hypnosis.
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| 11. |
- Marouli, Eirini, et al.
(author)
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Rare and low-frequency coding variants alter human adult height
- 2017
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 542:7640, s. 186-190
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Journal article (peer-reviewed)abstract
- Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.
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| 12. |
- Megyesfalvi, Zsolt, et al.
(author)
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Expression patterns and prognostic relevance of subtype-specific transcription factors in surgically resected small-cell lung cancer : an international multicenter study
- 2022
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In: Journal of Pathology. - : Wiley. - 0022-3417 .- 1096-9896. ; 257:5, s. 674-686
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Journal article (peer-reviewed)abstract
- The tissue distribution and prognostic relevance of subtype-specific proteins (ASCL1, NEUROD1, POU2F3, YAP1) present an evolving area of research in small-cell lung cancer (SCLC). The expression of subtype-specific transcription factors and P53 and RB1 proteins were measured by immunohistochemistry (IHC) in 386 surgically resected SCLC samples. Correlations between subtype-specific proteins and in vitro efficacy of various therapeutic agents were investigated by proteomics and cell viability assays in 26 human SCLC cell lines. Besides SCLC-A (ASCL1-dominant), SCLC-AN (combined ASCL1/NEUROD1), SCLC-N (NEUROD1-dominant), and SCLC-P (POU2F3-dominant), IHC and cluster analyses identified a quadruple-negative SCLC subtype (SCLC-QN). No unique YAP1-subtype was found. The highest overall survival rates were associated with non-neuroendocrine subtypes (SCLC-P and SCLC-QN) and the lowest with neuroendocrine subtypes (SCLC-A, SCLC-N, SCLC-AN). In univariate analyses, high ASCL1 expression was associated with poor prognosis and high POU2F3 expression with good prognosis. Notably, high ASCL1 expression influenced survival outcomes independently of other variables in a multivariate model. High POU2F3 and YAP1 protein abundances correlated with sensitivity and resistance to standard-of-care chemotherapeutics, respectively. Specific correlation patterns were also found between the efficacy of targeted agents and subtype-specific protein abundances. In conclusion, we investigated the clinicopathological relevance of SCLC molecular subtypes in a large cohort of surgically resected specimens. Differential IHC expression of ASCL1, NEUROD1, and POU2F3 defines SCLC subtypes. No YAP1-subtype can be distinguished by IHC. High POU2F3 expression is associated with improved survival in a univariate analysis, whereas elevated ASCL1 expression is an independent negative prognosticator. Proteomic and cell viability assays of human SCLC cell lines revealed distinct vulnerability profiles defined by transcription regulators.
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| 13. |
- Palsson, Olafur S., et al.
(author)
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Current Practices, Experiences, and Views in Clinical Hypnosis : Findings of an International Survey
- 2023
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In: International Journal of Clinical and Experimental Hypnosis. - : Informa UK Limited. - 0020-7144 .- 1744-5183. ; 71:2, s. 92-114
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Journal article (peer-reviewed)abstract
- An online survey of 691 clinicians who use hypnosis was conducted in 31 countries to gain a broad real-world picture of current practices, views, and experiences in clinical hypnosis. Among 36 common clinical uses, stress reduction, wellbeing and self-esteem-enhancement, surgery preparations, anxiety interventions, mindfulness facilitation, and labor and childbirth applications were the most frequently rated as highly effective (each by ≥70% of raters) in the clinicians’ own experience. Adverse hypnosis-associated effects had been encountered by 55% of clinicians but were generally short-lived and very rarely judged as serious. The most common hypnosis approaches used were Ericksonian (71%), hypnotic relaxation therapy (55%), and traditional hypnosis (50%). Almost all respondents reported regularly using other therapeutic modalities alongside hypnosis. Among a range of client variables potentially affecting therapy, most clinicians rated hypnotist-client rapport (88%) and client motivation (75%) as very or extremely important factors for successful hypnotherapy. The majority of respondents had conducted hypnosis treatment via teletherapy, and 54% of those estimated it to be as effective as in-person treatment.
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| 14. |
- Sung, Yun Ju, et al.
(author)
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A multi-ancestry genome-wide study incorporating gene-smoking interactions identifies multiple new loci for pulse pressure and mean arterial pressure
- 2019
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In: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 28:15, s. 2615-2633
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Journal article (peer-reviewed)abstract
- Elevated blood pressure (BP), a leading cause of global morbidity and mortality, is influenced by both genetic and lifestyle factors. Cigarette smoking is one such lifestyle factor. Across five ancestries, we performed a genome-wide gene–smoking interaction study of mean arterial pressure (MAP) and pulse pressure (PP) in 129 913 individuals in stage 1 and follow-up analysis in 480 178 additional individuals in stage 2. We report here 136 loci significantly associated with MAP and/or PP. Of these, 61 were previously published through main-effect analysis of BP traits, 37 were recently reported by us for systolic BP and/or diastolic BP through gene–smoking interaction analysis and 38 were newly identified (P < 5 × 10−8, false discovery rate < 0.05). We also identified nine new signals near known loci. Of the 136 loci, 8 showed significant interaction with smoking status. They include CSMD1 previously reported for insulin resistance and BP in the spontaneously hypertensive rats. Many of the 38 new loci show biologic plausibility for a role in BP regulation. SLC26A7 encodes a chloride/bicarbonate exchanger expressed in the renal outer medullary collecting duct. AVPR1A is widely expressed, including in vascular smooth muscle cells, kidney, myocardium and brain. FHAD1 is a long non-coding RNA overexpressed in heart failure. TMEM51 was associated with contractile function in cardiomyocytes. CASP9 plays a central role in cardiomyocyte apoptosis. Identified only in African ancestry were 30 novel loci. Our findings highlight the value of multi-ancestry investigations, particularly in studies of interaction with lifestyle factors, where genomic and lifestyle differences may contribute to novel findings.
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| 15. |
- Szabados, Márton, et al.
(author)
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Ultrasonically-enhanced preparation, characterization of CaFe-layered double hydroxides with various interlayer halide, azide and oxo anions (CO3 2−, NO3 −, ClO4 −)
- 2018
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In: Ultrasonics Sonochemistry. - : Elsevier BV. - 1350-4177. ; 40, s. 853-860
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Journal article (peer-reviewed)abstract
- An ultrasonically-enhanced mechanochemical method was developed to synthesize CaFe-layered double hydroxides (LDHs) with various interlayer anions (CO3 2−, NO3 −, ClO4 −, N3 −, F−, Cl−, Br− and I−). The duration of pre-milling and ultrasonic irradiation and the variation of synthesis temperature in the wet chemical step were investigated to obtain the optimal parameters of preparation. The main method to characterize the products was X-ray diffractometry, but infrared and synchrotron-based X-ray absorption spectroscopies as well as thermogravimetric measurements were also used to learn about fine structural details. The synthesis method afforded successful intercalation of the anions, among others the azide anion, a rarely used counter ion providing a system, which enables safe handling the otherwise highly reactive anion. The X-ray absorption spectroscopic measurements revealed that the quality of the interlayered anions could modulate the spatial arrangement of the calcium ions around the iron(III) ions, but only in the second coordination sphere.
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| 16. |
- Szigyártó, Imola Cs, et al.
(author)
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Flow Alignment of Extracellular Vesicles: Structure and Orientation of Membrane-Associated Bio-macromolecules Studied with Polarized Light
- 2018
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In: ChemBioChem. - : Wiley. - 1439-7633 .- 1439-4227. ; 19:6, s. 545-551
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Journal article (peer-reviewed)abstract
- Extracellular vesicles (EVs) are currently in scientific focus, as they have great potential to revolutionize the diagnosis and therapy of various diseases. However, numerous aspects of these species are still poorly understood, and thus, additional insight into their molecular-level properties, membrane–protein interactions, and membrane rigidity is still needed. We here demonstrate the use of red-blood-cell-derived EVs (REVs) that polarized light spectroscopy techniques, linear and circular dichroism, can provide molecular-level structural information on these systems. Flow-linear dichroism (flow-LD) measurements show that EVs can be oriented by shear force and indicate that hemoglobin molecules are associated to the lipid bilayer in freshly released REVs. During storage, this interaction ceases; this is coupled to major protein conformational changes relative to the initial state. Further on, the degree of orientation gives insight into vesicle rigidity, which decreases in time parallel to changes in protein conformation. Overall, we propose that both linear dichroism and circular dichroism spectroscopy can provide simple, rapid, yet efficient ways to track changes in the membrane–protein interactions of EV components at the molecular level, which may also give insight into processes occurring during vesiculation.
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| 17. |
- Szigyártó, Imola Cs, et al.
(author)
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Membrane active Janus-oligomers of β 3 -peptides
- 2020
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In: Chemical Science. - : Royal Society of Chemistry (RSC). - 2041-6539 .- 2041-6520. ; 11:26, s. 6868-6881
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Journal article (peer-reviewed)abstract
- Self-assembling peptides offer a versatile set of tools for bottom-up construction of supramolecular biomaterials. Among these compounds, non-natural peptidic foldamers experience increased focus due to their structural variability and lower sensitivity to enzymatic degradation. However, very little is known about their membrane properties and complex oligomeric assemblies-key areas for biomedical and technological applications. Here we designed short, acyclic β3-peptide sequences with alternating amino acid stereoisomers to obtain non-helical molecules having hydrophilic charged residues on one side, and hydrophobic residues on the other side, with the N-terminus preventing formation of infinite fibrils. Our results indicate that these β-peptides form small oligomers both in water and in lipid bilayers and are stabilized by intermolecular hydrogen bonds. In the presence of model membranes, they either prefer the headgroup regions or they insert between the lipid chains. Molecular dynamics (MD) simulations suggest the formation of two-layered bundles with their side chains facing opposite directions when compared in water and in model membranes. Analysis of the MD calculations showed hydrogen bonds inside each layer, however, not between the layers, indicating a dynamic assembly. Moreover, the aqueous form of these oligomers can host fluorescent probes as well as a hydrophobic molecule similarly to e.g. lipid transfer proteins. For the tested, peptides the mixed chirality pattern resulted in similar assemblies despite sequential differences. Based on this, it is hoped that the presented molecular framework will inspire similar oligomers with diverse functionality.
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| 18. |
- Szilágyi, Adrienn K., et al.
(author)
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Therapeutic suggestions with critically ill in palliative care
- 2018
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In: Annals of Palliative Medicine. - : AME Publishing Company. - 2224-5820 .- 2224-5839. ; 7:1, s. 159-169
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Journal article (peer-reviewed)abstract
- Suggestions can be used without formal hypnosis, especially with critically ill patients, due to their spontaneous trance state. In this paper we outline data on the effectiveness of therapeutic suggestions. We interpret the possible mechanism of therapeutic suggestions in the context of stress cognition. Basic principles of formulating suggestions are discussed and some recommended versions of non-pharmacological pain control are provided. Case vignettes are given of how suggestions are used with critically ill ICU patients.
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| 19. |
- Szucs, Edina, et al.
(author)
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Synthesis, biochemical, pharmacological characterization and in silico profile modelling of highly potent opioid orvinol and thevinol derivatives
- 2020
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In: European Journal of Medicinal Chemistry. - : ELSEVIER. - 0223-5234 .- 1768-3254. ; 191
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Journal article (peer-reviewed)abstract
- Morphine and its derivatives play inevitably important role in the m-opioid receptor (MOR) targeted antinociception. A structure-activity relationship study is presented for novel and known orvinol and thevinol derivatives with varying 3-O, 6-O, 17-N and 20-alkyl substitutions starting from agonists, antagonists and partial agonists. In vitro competition binding experiments with [H-3]DAMGO showed low subnanomolar affinity to MOR. Generally, 6-O-demethylation increased the affinity toward MOR and decreased the efficacy changing the pharmacological profile in some cases. In vivo tests in osteoarthritis inflammation model showed significant antiallodynic effects of thevinol derivatives while orvinol derivatives did not. The pharmacological character was modelled by computational docking to both active and inactive state models of MOR. Docking energy difference for the two states separates agonists and antagonists well while partial agonists overlapped with them. An interaction pattern of the ligands, involving the interacting receptor atoms, showed more efficient separation of the pharmacological profiles. In rats, thevinol derivatives showed antiallodynic effect in vivo. The orvinol derivatives, except for 6-O-desmethyl-dihydroetorfin (2c), did not show antiallodynic effect.
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| 20. |
- Turcot, Valerie, et al.
(author)
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Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity
- 2018
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In: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:1, s. 26-41
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Journal article (peer-reviewed)abstract
- Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are similar to 10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed similar to 7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.
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| 21. |
- Udyavara Nagaraj, Vignesh, et al.
(author)
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Stimuli-Responsive Membrane Anchor Peptide Nanofoils for Tunable Membrane Association and Lipid Bilayer Fusion
- 2022
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In: ACS Applied Materials & Interfaces. - : American Chemical Society (ACS). - 1944-8252 .- 1944-8244. ; 14:50, s. 55320-55331
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Journal article (peer-reviewed)abstract
- Self-assembled peptide nanostructures with stimuli-responsive features are promising as functional materials. Despite extensive research efforts, water-soluble supramolecular constructs that can interact with lipid membranes in a controllable way are still challenging to achieve. Here, we have employed a short membrane anchor protein motif (GLFD) and coupled it to a spiropyran photoswitch. Under physiological conditions, these conjugates assemble into ∼3.5 nm thick, foil-like peptide bilayer morphologies. Photoisomerization from the closed spiro (SP) form to the open merocyanine (MC) form of the photoswitch triggers rearrangements within the foils. This results in substantial changes in their membrane-binding properties, which also varies sensitively to lipid composition, ranging from reversible nanofoil reformation to stepwise membrane adsorption. The formed peptide layers in the assembly are also able to attach to various liposomes with different surface charges, enabling the fusion of their lipid bilayers. Here, SP-to-MC conversion can be used both to trigger and to modulate the liposome fusion efficiency.
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| 22. |
- Varga, Gábor, et al.
(author)
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Mn(II)-amino acid complexes intercalated in CaAl-layered double hydroxide - Well-characterized, highly efficient, recyclable oxidation catalysts
- 2016
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In: Journal of Catalysis. - : Elsevier BV. - 0021-9517. ; 335, s. 125-134
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Journal article (peer-reviewed)abstract
- Intercalated composite materials were prepared with CaAl-layered double hydroxide as the host and Mn(II)-amino acid (l-cysteine, l-histidine and l-tyrosine) complex anions as the guest. Two methods (intercalation of the ligand first followed by constructing the complex; preforming the complex first, then introducing it among the layers of the host) and optimization of the auxiliary conditions were performed to arrive at composites having the complex exclusively among the layers. The obtained substances were structurally characterized by powder X-ray diffractometry, mid IR spectroscopy in diffuse reflectance mode and with ATR or photoacoustic detections, and scanning electron microscopy. The structural features of the intercalant (coordination number, coordination sites) were elucidated by classical chemical and energy dispersive X-ray analyses, EPR, X-ray absorption and far IR spectroscopies. Structural models are also given. The catalytic activities, selectivities and recycling abilities of the substances were studied in the oxidation reactions of cyclohexene with peracetic acid and in situ formed iodosylbenzene as oxidants and allylic alcohol with peracetic acid, in the liquid phase. The intercalated substances proved to be efficient and highly selective (with peracetic acid: outstanding epoxide, with iodosylbenzene superior diol selectivities) catalysts with very good recycling abilities.
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| 23. |
- Varga, Gábor, et al.
(author)
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Ni-Amino Acid–CaAl-Layered Double Hydroxide Composites : Construction, Characterization and Catalytic Properties in Oxidative Transformations
- 2017
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In: Topics in Catalysis. - : Springer Science and Business Media LLC. - 1022-5528 .- 1572-9028. ; 60:17-18, s. 1429-1438
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Journal article (peer-reviewed)abstract
- Host–guest composite materials were prepared applying the anionic forms of Ni(II)-amino acid (l-histidine, l-cysteine, and l-tyrosine) as the guests and CaAl-layered double hydroxide (CaAl-LDH) as the host. The syntheses were performed either by introducing the amino acid anions first and then constructing the metal ion–amino acid complexes or intercalating the pre-prepared complexes in anionic forms. The pristine as well as the composite LDH samples were structurally characterized by X-ray diffractometry, mid IR spectroscopy and scanning electron microscopy. The structural features of the interlayer complexes were studied by UV–Vis, inductively coupled plasma optical emission, mid and far IR and X-ray absorption spectroscopies as well as energy-dispersed X-ray analysis. On the basis of the acquired data, structural models were constructed. The composites were applied as catalysts in the liquid-phase oxidation of cyclohexene applying peracetic acid and the in situ formed iodosyl benzene as oxidants. Using peracetic acid afforded epoxide, while applying iodosyl benzene provided cis diol as the major or exclusive oxidation product. The catalysts displayed good recycling properties.
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| 24. |
- Varga, Gábor, et al.
(author)
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Syntheses, characterization and catalytic activities of CaAl-layered double hydroxide intercalated Fe(III)-amino acid complexes
- 2018
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In: Catalysis Today. - : Elsevier BV. - 0920-5861. ; 306, s. 42-50
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Journal article (peer-reviewed)abstract
- Synthesis of intercalated composites were carried out using CaAl-LDH (layered double hydroxide) as host and the anionic form of Fe(III)-amino acid complexes as guest materials. Intercalation was attempted with two methods either introducing the preformed complexes or constructing the complex among the layers of the LDH. After optimization of the synthesis parameters, structural characterization was performed by X-ray diffractometry, scanning electron microscopy as well as mid and far infrared spectroscopies. Quantitative data about the intercalated complexes were collected by chemical analysis and X-ray absorption spectroscopy investigating the near edge region as well as the extended fine structure. Structural models based on characterization measurements are also given. Catalytic activities, selectivities and recycling abilities of the substances were studied in the oxidation reactions of cyclohexene with peracetic acid and . in situ formed iodosylbenzene as oxidants in the liquid phase. The catalysts were active in the Ullmann-type etherification coupling reaction as well. The intercalated substances were found to be efficient and highly selective catalysts with very good recycling abilities.
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| 25. |
- Vida, Ádám, et al.
(author)
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A Sequence of Phase Transformations and Phases in NiCoFeCrGa High Entropy Alloy
- 2021
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In: Materials. - : MDPI. - 1996-1944. ; 14(5):1076
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Journal article (peer-reviewed)abstract
- The present investigation is directed to phase transitions in the equimolar NiCoFeCrGa high entropy alloy, which is a mixture of face-centered cubic (FCC) and body-centered cubic (BCC) crystalline phases. The microstructure of the samples was investigated by using scanning electron microscopy (SEM), time-of-flight secondary ion mass spectroscopy (TOF-SIMS), transmission electron microscopy-based energy-dispersive spectroscopy (EDS) and electron energy loss spectroscopy (EELS), as well as X-ray diffraction (XRD) measurements. Based on the phases observed in different temperature ranges, a sequence of the phase transitions can be established, showing that in a realistic process, when freely cooling the sample with the furnace from high to room temperature, a microstructure having spinodal-like decomposition can also be expected. The elemental mapping and magnetic behaviors of this decomposed structure are also studied.
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| 26. |
- Wan, Guihong, et al.
(author)
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Development and validation of time-to-event models to predict metastatic recurrence of localized cutaneous melanoma
- 2024
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In: Journal of the American Academy of Dermatology. - 0190-9622. ; 90:2, s. 288-298
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Journal article (peer-reviewed)abstract
- Background: The recent expansion of immunotherapy for stage IIB/IIC melanoma highlights a growing clinical need to identify patients at high risk of metastatic recurrence and, therefore, most likely to benefit from this therapeutic modality. Objective: To develop time-to-event risk prediction models for melanoma metastatic recurrence. Methods: Patients diagnosed with stage I/II primary cutaneous melanoma between 2000 and 2020 at Mass General Brigham and Dana-Farber Cancer Institute were included. Melanoma recurrence date and type were determined by chart review. Thirty clinicopathologic factors were extracted from electronic health records. Three types of time-to-event machine-learning models were evaluated internally and externally in the distant versus locoregional/nonrecurrence prediction. Results: This study included 954 melanomas (155 distant, 163 locoregional, and 636 1:2 matched nonrecurrences). Distant recurrences were associated with worse survival compared to locoregional/nonrecurrences (HR: 6.21, P < .001) and to locoregional recurrences only (HR: 5.79, P < .001). The Gradient Boosting Survival model achieved the best performance (concordance index: 0.816; time-dependent AUC: 0.842; Brier score: 0.103) in the external validation. Limitations: Retrospective nature and cohort from one geography. Conclusions: These results suggest that time-to-event machine-learning models can reliably predict the metastatic recurrence from localized melanoma and help identify high-risk patients who are most likely to benefit from immunotherapy.
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| 27. |
- Welsh, Joshua A., et al.
(author)
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Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches
- 2024
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In: Journal of Extracellular Vesicles. - : John Wiley and Sons Inc. - 2001-3078. ; 13:2
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Journal article (peer-reviewed)abstract
- Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its ‘Minimal Information for Studies of Extracellular Vesicles’, which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly.
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| 28. |
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