| 1. |
- Drake, TM, et al.
(author)
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Surgical site infection after gastrointestinal surgery in children: an international, multicentre, prospective cohort study
- 2020
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In: BMJ global health. - : BMJ. - 2059-7908. ; 5:12
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Journal article (peer-reviewed)abstract
- Surgical site infection (SSI) is one of the most common healthcare-associated infections (HAIs). However, there is a lack of data available about SSI in children worldwide, especially from low-income and middle-income countries. This study aimed to estimate the incidence of SSI in children and associations between SSI and morbidity across human development settings.MethodsA multicentre, international, prospective, validated cohort study of children aged under 16 years undergoing clean-contaminated, contaminated or dirty gastrointestinal surgery. Any hospital in the world providing paediatric surgery was eligible to contribute data between January and July 2016. The primary outcome was the incidence of SSI by 30 days. Relationships between explanatory variables and SSI were examined using multilevel logistic regression. Countries were stratified into high development, middle development and low development groups using the United Nations Human Development Index (HDI).ResultsOf 1159 children across 181 hospitals in 51 countries, 523 (45·1%) children were from high HDI, 397 (34·2%) from middle HDI and 239 (20·6%) from low HDI countries. The 30-day SSI rate was 6.3% (33/523) in high HDI, 12·8% (51/397) in middle HDI and 24·7% (59/239) in low HDI countries. SSI was associated with higher incidence of 30-day mortality, intervention, organ-space infection and other HAIs, with the highest rates seen in low HDI countries. Median length of stay in patients who had an SSI was longer (7.0 days), compared with 3.0 days in patients who did not have an SSI. Use of laparoscopy was associated with significantly lower SSI rates, even after accounting for HDI.ConclusionThe odds of SSI in children is nearly four times greater in low HDI compared with high HDI countries. Policies to reduce SSI should be prioritised as part of the wider global agenda.
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| 2. |
- Weinstock, Joshua S, et al.
(author)
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Aberrant activation of TCL1A promotes stem cell expansion in clonal haematopoiesis.
- 2023
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In: Nature. - 1476-4687. ; 616:7958, s. 755-763
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Journal article (peer-reviewed)abstract
- Mutations in a diverse set of driver genes increase the fitness of haematopoietic stem cells (HSCs), leading to clonal haematopoiesis1. These lesions are precursors for blood cancers2-6, but the basis of their fitness advantage remains largely unknown, partly owing to a paucity of large cohorts in which the clonal expansion rate has been assessed by longitudinal sampling. Here, to circumvent this limitation, we developed a method to infer the expansion rate from data from a single time point. We applied this method to 5,071 people with clonal haematopoiesis. A genome-wide association study revealed that a common inherited polymorphism in the TCL1A promoter was associated with a slower expansion rate in clonal haematopoiesis overall, but the effect varied by driver gene. Those carrying this protective allele exhibited markedly reduced growth rates or prevalence of clones with driver mutations in TET2, ASXL1, SF3B1 and SRSF2, butthis effect was not seen inclones withdriver mutations in DNMT3A. TCL1A was not expressed in normal or DNMT3A-mutated HSCs, but the introduction of mutations in TET2 or ASXL1 led to the expression of TCL1A protein and the expansion of HSCs in vitro. The protective allele restricted TCL1A expression and expansion of mutant HSCs, as did experimentalknockdown of TCL1A expression. Forced expression of TCL1A promoted the expansion of human HSCs in vitro and mouse HSCs in vivo. Our results indicate that the fitness advantage of several commonly mutated driver genes in clonal haematopoiesis may be mediated by TCL1A activation.
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| 3. |
- Miliucci, M., et al.
(author)
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Kaonic Deuterium Precision Measurement at DA Φ NE : The SIDDHARTA-2 Experiment
- 2020
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In: Recent Progress in Few-Body Physics : Proceedings of the 22nd International Conference on Few-Body Problems in Physics, FB22 2018 - Proceedings of the 22nd International Conference on Few-Body Problems in Physics, FB22 2018. - Cham : Springer International Publishing. - 0930-8989 .- 1867-4941. - 9783030323561 - 9783030323578 ; 238, s. 965-969
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Book chapter (peer-reviewed)abstract
- Light kaonic atoms spectroscopy offers the unique opportunity to perform experiments equivalent to scattering at vanishing relative energies. This allows the determination of the antikaon-nucleus interaction at threshold, without the need of extrapolation to zero energy, as in the case of scattering experiments. In this framework, the SIDDHARTA-2 collaboration aims to perform the first measurement of kaonic deuterium transition to the fundamental level, which is mandatory to extract the isospin dependent antikaon—nucleon scattering lengths. The experiment will be carried out at the DA(formula presented)NE collider of LNF-INFN in 2019–2020.
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| 4. |
- Young, William J., et al.
(author)
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Genetic analyses of the electrocardiographic QT interval and its components identify additional loci and pathways
- 2022
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In: Nature Communications. - : Springer Nature. - 2041-1723. ; 13
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Journal article (peer-reviewed)abstract
- The QT interval is a heritable electrocardiographic measure associated with arrhythmia risk when prolonged. Here, the authors used a series of genetic analyses to identify genetic loci, pathways, therapeutic targets, and relationships with cardiovascular disease. The QT interval is an electrocardiographic measure representing the sum of ventricular depolarization and repolarization, estimated by QRS duration and JT interval, respectively. QT interval abnormalities are associated with potentially fatal ventricular arrhythmia. Using genome-wide multi-ancestry analyses (>250,000 individuals) we identify 177, 156 and 121 independent loci for QT, JT and QRS, respectively, including a male-specific X-chromosome locus. Using gene-based rare-variant methods, we identify associations with Mendelian disease genes. Enrichments are observed in established pathways for QT and JT, and previously unreported genes indicated in insulin-receptor signalling and cardiac energy metabolism. In contrast for QRS, connective tissue components and processes for cell growth and extracellular matrix interactions are significantly enriched. We demonstrate polygenic risk score associations with atrial fibrillation, conduction disease and sudden cardiac death. Prioritization of druggable genes highlight potential therapeutic targets for arrhythmia. Together, these results substantially advance our understanding of the genetic architecture of ventricular depolarization and repolarization.
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| 5. |
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| 6. |
- Haider, A, et al.
(author)
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Translational molecular imaging and drug development in Parkinson's disease
- 2023
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In: Molecular neurodegeneration. - : Springer Science and Business Media LLC. - 1750-1326. ; 18:1, s. 11-
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Journal article (peer-reviewed)abstract
- Parkinson’s disease (PD) is a progressive neurodegenerative disorder that primarily affects elderly people and constitutes a major source of disability worldwide. Notably, the neuropathological hallmarks of PD include nigrostriatal loss and the formation of intracellular inclusion bodies containing misfolded α-synuclein protein aggregates. Cardinal motor symptoms, which include tremor, rigidity and bradykinesia, can effectively be managed with dopaminergic therapy for years following symptom onset. Nonetheless, patients ultimately develop symptoms that no longer fully respond to dopaminergic treatment. Attempts to discover disease-modifying agents have increasingly been supported by translational molecular imaging concepts, targeting the most prominent pathological hallmark of PD, α-synuclein accumulation, as well as other molecular pathways that contribute to the pathophysiology of PD. Indeed, molecular imaging modalities such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT) can be leveraged to study parkinsonism not only in animal models but also in living patients. For instance, mitochondrial dysfunction can be assessed with probes that target the mitochondrial complex I (MC-I), while nigrostriatal degeneration is typically evaluated with probes designed to non-invasively quantify dopaminergic nerve loss. In addition to dopaminergic imaging, serotonin transporter and N-methyl-D-aspartate (NMDA) receptor probes are increasingly used as research tools to better understand the complexity of neurotransmitter dysregulation in PD. Non-invasive quantification of neuroinflammatory processes is mainly conducted by targeting the translocator protein 18 kDa (TSPO) on activated microglia using established imaging agents. Despite the overwhelming involvement of the brain and brainstem, the pathophysiology of PD is not restricted to the central nervous system (CNS). In fact, PD also affects various peripheral organs such as the heart and gastrointestinal tract – primarily via autonomic dysfunction. As such, research into peripheral biomarkers has taken advantage of cardiac autonomic denervation in PD, allowing the differential diagnosis between PD and multiple system atrophy with probes that visualize sympathetic nerve terminals in the myocardium. Further, α-synuclein has recently gained attention as a potential peripheral biomarker in PD. This review discusses breakthrough discoveries that have led to the contemporary molecular concepts of PD pathophysiology and how they can be harnessed to develop effective imaging probes and therapeutic agents. Further, we will shed light on potential future trends, thereby focusing on potential novel diagnostic tracers and disease-modifying therapeutic interventions.
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| 7. |
- Hasab, Hashim Ali, et al.
(author)
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Monitoring and Assessment of Salinity and Chemicals in Agricultural Lands by a Remote Sensing Technique and Soil Moisture with Chemical Index Models
- 2020
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In: Geosciences. - Switzerland : MDPI. - 2076-3263. ; 10:6
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Journal article (peer-reviewed)abstract
- Agricultural land in the south of Iraq provides habitat for several types of living creatures. This land has a significant impact on the ecosystem. The agricultural land of Al-Hawizeh marsh covers an area of more than 3500 km2 and is considered an enriched resource to produce several harvests. A total of 74% of this area suffers from a high degree of salinity and chemical pollution, which needs to be remedied. Several human-made activities and post-war-related events have caused radical deterioration in soil quality in the agricultural land. The goal of this research was to integrate mathematical models, remote sensing data, and GIS to provide a powerful tool to predict, assess, monitor, manage, and map the salinity and chemical parameters of iron (Fe), lead (Pb), copper (Cu), chromium (Cr), and zinc (Zn) in the soils of agricultural land in Al-Hawizeh marsh in southern Iraq during the four seasons of 2017. The mathematical model consists of four parts. The first depends on the B6 and B11 bands of Landsat-8, to calculate the soil moisture index (SMI). The second is the salinity equation (SE), which depends on the SMI result to retrieve the salinity values from Landsat-8 images. The third part depends on the B6 and B7 bands of Landsat-8, which calculates the clay chemical index (CCIs). The fourth part is the chemical equation (CE), which depends on the CCI to retrieve the chemical values (Fe, Pb, Cu, Cr, and Zn) from Landsat-8 images. The average salinity concentrations during autumn, summer, spring, and winter were 1175, 1010, 1105, and 1789 mg/dm3, respectively. The average Fe concentrations during autumn, summer, spring and winter were 813, 784, 842, and 1106 mg/dm3, respectively. The average Pb concentrations during autumn, summer, spring, and winter were 4.85, 3.79, 4.74, and 7.2 mg/dm3, respectively. The average Cu concentrations during autumn, summer, spring, and winter were 3.9, 3.1, 4.45, and 7.5 mg/dm3, respectively. The average Cr concentrations during autumn, summer, spring, and winter seasons were 1.28, 0.73, 1.03, and 2.91 mg/dm3, respectively. Finally, the average Zn concentrations during autumn, summer, spring, and winter were 8.25, 6, 7.05, and 12 mg/dm3, respectively. The results show that the concentrations of salinity and chemicals decreased in the summer and increased in the winter. The decision tree (DT) classification depended on the output results for salinity and chemicals for both SE and CE equations. This classification refers to all the parameters simultaneously in one stage. The output of DT classification results can display all the soil quality parameters (salinity, Fe, Pb, Cu, Cr, and Zn) in one image. This approach was repeated for each season in this study. In conclusion, the developed systematic and generic approach may constitute a basis for determining soil quality parameters in agricultural land worldwide.
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