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This service exclusively searches for literature that cites resources. Please be aware that the total number of searchable documents is limited to those containing RRIDs and does not include all open-access literature.
Radiologic imaging is important for evaluating extrahepatic bile duct (EHD) cancers; it is used for staging tumors and evaluating the suitability of surgical resection, as surgery may be contraindicated in some cases regardless of tumor stage. However, the published general recommendations for EHD cancer and recommendations guided by the perspectives of radiologists are limited. The Korean Society of Abdominal Radiology (KSAR) study group for EHD cancer developed key questions and corresponding recommendations for the radiologic evaluation of EHD cancer and organized them into 4 sections: nomenclature and definition, imaging technique, cancer evaluation, and tumor response. A structured reporting form was also developed to allow the progressive accumulation of standardized data, which will facilitate multicenter studies and contribute more evidence for the development of recommendations.
The Saccharomyces cerevisiae respiratory supercomplex factor 2 (Rcf2) is a 224-residue protein located in the mitochondrial inner membrane where it is involved in the formation of supercomplexes composed of cytochrome bc1 and cytochrome c oxidase. We previously demonstrated that Rcf2 forms a dimer in dodecylphosphocholine micelles, and here we report the solution NMR structure of this Rcf2 dimer. Each Rcf2 monomer has two soluble α helices and five putative transmembrane (TM) α helices, including an unexpectedly charged TM helix at the C terminus, which mediates dimer formation. The NOE contacts indicate the presence of inter-monomer salt bridges and hydrogen bonds at the dimer interface, which stabilize the Rcf2 dimer structure. Moreover, NMR chemical shift change mapping upon lipid titrations as well as molecular dynamics analysis reveal possible structural changes upon embedding Rcf2 into a native lipid environment. Our results contribute to the understanding of respiratory supercomplex formation and regulation.
Group 2 innate lymphoid cells (ILC2s) are the dominant innate lymphoid cell population in the lungs at steady state, and their release of type 2 cytokines is a central driver in responding eosinophil infiltration and increased airway hyperreactivity. Our laboratory has identified a unique subset of ILC2s in the lungs that actively produce IL-10 (ILC210s).
Changing the everyday food-related behaviours of consumers is a critical part of tackling the global food waste challenge. Comprehensive frameworks of household food waste and consumer behavior are needed to guide the development of targeted interventions and future research agendas. This study systematically reviews food waste and behaviour studies from developed nations to provide an overview of the current research field. It uses a multi-level perspective to organise the various factors influencing food-related behaviour and proposes a new, multi-level, framework of consumer behaviour and household food waste. A novel addition to the field, the framework gathers factors at micro (individual), meso (household), and macro (external to the household) levels and argues that behaviour and food waste emerge from their interactions. Our review also reveals a research domain with disciplinary and methodological 'bald spots' and an over-emphasis on individual level factors. A multi-level research agenda focusing on under-explored factors and interactions between factors across levels is presented, and consideration given to multi-level interventions that support consumer behaviour change to reduce household food waste.
Mendelian randomization (MR) of lipid traits in CAD has provided evidence for causal associations of LDL-C and TGs in CAD, but many lipid trait genetic variants have pleiotropic effects on other cardiovascular risk factors that may bias MR associations. The goal of this study was to evaluate pleiotropic effects of lipid trait genetic variants and to account for these effects in MR of lipid traits in CAD. We performed multivariable MR using inverse variance-weighted and MR-Egger methods in large (n ≥ 300,000) GWAS datasets. We found that 30% of lipid trait genetic variants have effects on metabolic syndrome traits, including BMI, T2D, and systolic blood pressure (SBP). Nonetheless, in multivariable MR analysis, LDL-C, HDL-C, TGs, BMI, T2D, and SBP are independently associated with CAD, and each of these associations is robust to adjustment for directional pleiotropy. MR at loci linked to direct effects on HDL-C and TGs suggests locus- and mechanism-specific causal effects of these factors on CAD.
Cancer patients are particularly vulnerable to COVID-19, partially owing to their compromised immune systems and curbed or cut cancer healthcare services caused by the pandemic. As a result, cancer caregivers may have to shoulder triple crises: the COVID-19 pandemic, pronounced healthcare needs from the patient, and elevated need for care from within. While technology-based health interventions have the potential to address unique challenges cancer caregivers face amid COVID-19, limited insights are available. Thus, to bridge this gap, we aim to identify technology-based interventions designed for cancer caregivers and report the characteristics and effects of these interventions concerning cancer caregivers' distinctive challenges amid COVID-19.
Growth charts are essential for monitoring the postnatal growth of preterm infants. The preterm postnatal follow-up study (PPFS) of the Intergrowth-21st Project provides new growth standards based on a longitudinal study. This study was conducted to investigate the prevalence of extrautrine growth restriction (EUGR) and the associated factors of EUGR in preterm infants, using the PPFS charts and the Fenton charts. Data of 1,356 infants with gestational age (GA) less than 28 weeks from the Korean Neonatal Network were analysed. The prevalence of small for gestational age (SGA) of weight and length was higher with the Intergrowth charts than with the Fenton charts. EUGR in weight and length was more prevalent when using the Fenton charts. Multivariate analysis showed that low GA, high birthweight z score, male, treated patent ductus arteriosus (PDA), necrotizing enterocolitis, intraventricular haemorrhage and duration of parenteral nutrition (PN) were associated with EUGR in weight by the Intergrowth charts. High birthweight z score, treated PDA and PN duration were associated with EUGR defined by the Fenton charts.Conclusion: Compared to the Fenton charts, SGA was more defined and EUGR was less prevalent in extremely low gestational infants, while EUGR defined by the Intergrowth charts categorized infants with adverse clinical courses more elaborately. What is Known: • Preterm infants are at risk of postnatal growth restriction (PGR), although optimal postnatal growth is important for the long-term outcomes. • Growth charts are essential tools to monitor the postnatal growth of preterm infants. What is New: • PGR of weight and length were less defined with the Intergrowth charts than the Fenton charts. • PGR defined by the Intergrowth preterm postnatal follow-up study (PPFS) chart categorized preterm infants with morbidities more elaborately than the Fenton charts.
Contemporary, original research should be utilised to inform guidelines in urology relating to the COVID-19 pandemic. This comprehensive review aimed to: identify all up-to-date original publications relating to urology and COVID-19, characterise where publications were from, and outline what topics were investigated.
Brain activity during natural walking outdoors can be captured using mobile electroencephalography (EEG). However, EEG recorded during gait is confounded with artifacts from various sources, possibly obstructing the interpretation of brain activity patterns. Currently, there is no consensus on how the amount of artifact present in these recordings should be quantified, or is there a systematic description of gait artifact properties. In the current study, we expand several features into a seven-dimensional footprint of gait-related artifacts, combining features of time, time-frequency, spatial, and source domains. EEG of N = 26 participants was recorded while standing and walking outdoors. Footprints of gait-related artifacts before and after two different artifact attenuation strategies (after artifact subspace reconstruction (ASR) and after subsequent independent component analysis [ICA]) were systematically different. We also evaluated topographies, morphologies, and signal-to-noise ratios (SNR) of button-press event-related potentials (ERP) before and after artifact handling, to confirm gait-artifact reduction specificity. Morphologies and SNR remained unchanged after artifact attenuation, whereas topographies improved in quality. Our results show that the footprint can provide a detailed assessment of gait-related artifacts and can be used to estimate the sensitivity of different artifact reduction strategies. Moreover, the analysis of button-press ERPs demonstrated its specificity, as processing did not only reduce gait-related artifacts but ERPs of interest remained largely unchanged. We conclude that the proposed footprint is well suited to characterize individual differences in gait-related artifact extent. In the future, it could be used to compare and optimize recording setups and processing pipelines comprehensively.
A subset of patients with Covid-19 presents with negative RT-PCR screening but suspect CT findings. Using four commercially available anti-SARS-CoV-2 IgG immuno-assays, we found this subset constituted 9.2% of all consecutively admitted outpatients with Covid-19 in our hospital. Clinical specificity for Covid-19 of some N protein-based immuno-assays was suboptimal, as positive results were observed in control patients with recent common human coronavirus, influenza B and adenovirus infections.
Knowledge about neurological complications of COVID-19 in children is limited due to the paucity of data in the existing literature. Some systematic reviews are available describing overall clinical features of COVID-19 in children and neurological complications of COVID-19 in adults. But to the best of our knowledge, no systematic review has been performed to determine neurological manifestations of COVID-19.
Oncogenic BRAF and NRAS mutations drive human melanoma initiation. We used transgenic zebrafish to model NRAS-mutant melanoma, and the rapid tumor onset allowed us to study candidate tumor suppressors. We identified P38α-MAPK14 as a potential tumor suppressor in The Cancer Genome Atlas melanoma cohort of NRAS-mutant melanomas, and overexpression significantly increased the time to tumor onset in transgenic zebrafish with NRAS-driven melanoma. Pharmacological activation of P38α-MAPK14 using anisomycin reduced in vitro viability of melanoma cultures, which we confirmed by stable overexpression of p38α. We observed that the viability of MEK inhibitor resistant melanoma cells could be reduced by combined treatment of anisomycin and MEK inhibition. Our study demonstrates that activating the p38α-MAPK14 pathway in the presence of oncogenic NRAS abrogates melanoma in vitro and in vivo. SIGNIFICANCE: The significance of our study is in the accountability of NRAS mutations in melanoma. We demonstrate here that activation of p38α-MAPK14 pathway can abrogate NRAS-mutant melanoma which is contrary to the previously published role of p38α-MAPK14 pathway in BRAF mutant melanoma. These results implicate that BRAF and NRAS-mutant melanoma may not be identical biologically. We also demonstrate the translational benefit of our study by using a small molecule compound-anisomycin (already in use for other diseases in clinical trials) to activate p38α-MAPK14 pathway.
The Spt-Ada-Gcn5 Acetyltransferase (SAGA) chromatin modifying complex is a critical regulator of gene expression and is highly conserved across species. Subunits of SAGA arrange into discrete modules with lysine aceyltransferase and deubiquitinase activities housed separately. Mutation of the SAGA deubiquitinase module can lead to substantial biological misfunction and diseases such as cancer, neurodegeneration, and blindness. Here, we review the structure and functions of the SAGA deubiquitinase module and regulatory mechanisms acting to control these.
We present the first in-human brain PET imaging data of the new α4β2 nicotinic acetylcholine receptor (nAChR)-targeting radioligand (+)-[18F]Flubatine. Aims were to develop a kinetic modeling-based approach to quantify (+)-[18F]Flubatine and compare the data of healthy controls (HCs) and patients with Alzheimer's disease (AD); to investigate the partial volume effect (PVE) on regional (+)-[18F]Flubatine binding; and whether (+)-[18F]Flubatine binding and cognitive test data respective β-amyloid radiotracer accumulation were correlated.
Gene therapies that chronically suppress vascular endothelial growth factor (VEGF) represent a new approach for managing retinal vascular leakage and neovascularization. However, constitutive suppression of VEGF in the eye may have deleterious side effects. Here, we developed a novel strategy to introduce Flt23k, a decoy receptor that binds intracellular VEGF, fused to the destabilizing domain (DD) of Escherichia coli dihydrofolate reductase (DHFR) into the retina. The expressed DHFR(DD)-Flt23k fusion protein is degraded unless "switched on" by administering a stabilizer; in this case, the antibiotic trimethoprim (TMP). Cells transfected with the DHFR(DD)-Flt23k construct expressed the fusion protein at levels correlated with the TMP dose. Stabilization of the DHFR(DD)-Flt23k fusion protein by TMP was able to inhibit intracellular VEGF in hypoxic cells. Intravitreal injection of self-complementary adeno-associated viral vector (scAAV)-DHFR(DD)-Flt23k and subsequent administration of TMP resulted in tunable suppression of ischemia-induced retinal neovascularization in a rat model of oxygen-induced retinopathy (OIR). Hence, our study suggests a promising novel approach for the treatment of retinal neovascularization. Schematic diagram of the tunable system utilizing the DHFR(DD)-Flt23k approach to reduce VEGF secretion. a The schematic shows normal VEGF secretion. b Without the ligand TMP, the DHFR(DD)-Flt23k protein is destabilized and degraded by the proteasome. c In the presence of the ligand TMP, DHFR(DD)-Flt23k is stabilized and sequestered in the ER, thereby conditionally inhibiting VEGF. Green lines indicate the intracellular and extracellular distributions of VEGF. Blue lines indicate proteasomal degradation of the DHFR(DD)-Flt23k protein. Orange lines indicate the uptake of cell-permeable TMP. TMP, trimethoprim; VEGF, vascular endothelial growth factor; ER, endoplasmic reticulum.
Primary mechanosensory neurons play an important role in converting mechanical forces into the sense of touch. In zebrafish, Rohon-Beard (RB) neurons serve this role at embryonic and larval stages of development. Here we examine the morphology and physiology of RBs in larval zebrafish to better understand how mechanosensory stimuli are represented along the spinal cord. We report that the morphology of RB neurons differs along the rostrocaudal body axis. Rostral RB neurons arborize in the skin near the cell body whereas caudal cells arborize at a distance posterior to their cell body. Using a novel electrophysiological approach, we also found longitudinal differences in the mechanosensitivity and physiological properties of RB neurons. Rostral RB neurons respond to mechanical stimulations close to the soma and produce up to three spikes with increasing stimulus intensity, whereas caudal cells respond at more distal locations and can produce four or more spikes when the intensity of the mechanical stimulus increases. The mechanosensory properties of RB neurons are consistent with those of rapidly adapting mechanoreceptors and can signal the onset, offset and intensity of mechanical stimulation. This is the first report of the intensity encoding properties of RB neurons, where an increase in spike number and a decrease in spike latency are observed with increasing stimulation intensity. This study reveals an unappreciated complexity of the larval zebrafish mechanosensory system and demonstrates how differences in the morphological and physiological properties of RBs related to their rostrocaudal location can influence the signals that enter the spinal cord.
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