Computational simulation of the predicted dosimetric impact of adjuvant yttrium-90 PET/CT-guided percutaneous ablation following radioembolization

Background: 90Y PET/CT post-radioembolization imaging has demonstrated that the distribution of 90Y in a tumor can be non-uniform. Using computational modeling, we predicted the dosimetric impact of post-treatment 90Y PET/CT-guided percutaneous ablation of the portions of a tumor receiving the lowest absorbed dose. A cohort of fourteen patients with non-resectable liver cancer previously treated using 90Y radioembolization were included in this retrospective study. Each patient exhibited potentially under-treated areas of tumor following treatment based on quantitative 90Y PET/CT. 90Y PET/CT was used to guide electrode placement for simulated adjuvant radiofrequency ablation in areas of tumor receiving the lowest dose. The finite element method was used to solve Penne’s bioheat transport equation, coupled with the Arrhenius thermal cell-death model to determine 3D thermal ablation zones. Tumor and unablated tumor absorbed-dose metrics (average dose, D50, D70, D90, V100) following ablation were compared, where D70 is the minimum dose to 70% of tumor and V100 is the fractional tumor volume receiving more than 100 Gy. Results: Compared to radioembolization alone, 90Y radioembolization with adjuvant ablation was associated with predicted increases in all tumor dose metrics evaluated. The mean average absorbed dose increased by 11.2 ± 6.9 Gy. Increases in D50, D70, and D90 were 11.0 ± 6.9 Gy, 13.3 ± 10.9 Gy, and 11.8 ± 10.8 Gy, respectively. The mean increase in V100 was 7.2 ± 4.2%. All changes were statistically significant (P \u3c 0.01). A negative correlation between pre-ablation tumor volume and D50, average dose, and V100 was identified (ρ \u3c − 0.5, P \u3c 0.05) suggesting that adjuvant radiofrequency ablation may be less beneficial to patients with large tumor burdens. Conclusions: This study has demonstrated that adjuvant 90Y PET/CT-guided radiofrequency ablation may improve tumor absorbed-dose metrics. These data may justify a prospective clinical trial to further evaluate this hybrid approach

The Role of Genes in Proton Radiation-Induced Lung Injury

By Lin Abigail Tan , Medical Sciences Advisor: Kyle Key Abstract: Lung cancer is the second most common cancer in American men and women, with about 200,000 new cases estimated to occur in 2020. One of the treatments for cancer is radiation therapy. Although radiation can kill cancer cells by damaging their DNA, they can also cause damage to the lung tissue in which it was targeted. I worked in the Kalin Lab at Cincinnati ChildrenÕs studying the role of FOXM1, a proton-coding gene, in proton radiation-induced pneumonitis and fibrosis. During my time in the lab, IÕve learned more about the research process and thinking like a scientist: integrating material learned from textbooks into a viable scientific experiment, constantly making inquiries, testing a hypothesis, and more. Additionally, I was introduced to a variety of basic laboratory techniques, from PCR to cell culture to animal surgeries, to overall execute the experimental procedure. I want to continue doing research; I enjoy how itÕs a process of constantly learning--sometimes failing, but always re-trying. I had expected to stay in the Kalin Lab during the summer for SURF, but the COVID-19 situation is still fluid. If IÕm not allowed to return to the lab this summer, I hope to complete a RaMP continuation this fall

Novel role for the innate immune receptor toll-like receptor 4 (TLR4) in the regulation of the wnt signaling pathway and photoreceptor apoptosis

Recent evidence has implicated innate immunity in regulating neuronal survival in the brain during stroke and other neurodegenerations. Photoreceptors are specialized light-detecting neurons in the retina that are essential for vision. In this study, we investigated the role of the innate immunity receptor TLR4 in photoreceptors. TLR4 activation by lipopolysaccharide (LPS) significantly reduced the survival of cultured mouse photoreceptors exposed to oxidative stress. With respect to mechanism, TLR4 suppressed Wnt signaling, decreased phosphorylation and activation of the Wnt receptor LRP6, and blocked the protective effect of the Wnt3a ligand. Paradoxically, TLR4 activation prior to oxidative injury protected photoreceptors, in a phenomenon known as preconditioning. Expression of TNFα and its receptors TNFR1 and TNFR2 decreased during preconditioning, and preconditioning was mimicked by TNFα antagonists, but was independent of Wnt signaling. Therefore, TLR4 is a novel regulator of photoreceptor survival that acts through the Wnt and TNFα pathways. © 2012 Yi et al

Anti-müllerian hormone is not associated with cardiometabolic risk factors in adolescent females

<p>Objectives: Epidemiological evidence for associations of Anti-Müllerian hormone (AMH) with cardiometabolic risk factors is lacking. Existing evidence comes from small studies in select adult populations, and findings are conflicting. We aimed to assess whether AMH is associated with cardiometabolic risk factors in a general population of adolescent females.</p> <p>Methods: AMH, fasting insulin, glucose, HDLc, LDLc, triglycerides and C-reactive protein (CRP) were measured at a mean age 15.5 years in 1,308 female participants in the Avon Longitudinal Study of Parents and Children (ALSPAC). Multivariable linear regression was used to examine associations of AMH with these cardiometabolic outcomes.</p> <p>Results: AMH values ranged from 0.16–35.84 ng/ml and median AMH was 3.57 ng/ml (IQR: 2.41, 5.49). For females classified as post-pubertal (n = 848) at the time of assessment median (IQR) AMH was 3.81 ng/ml (2.55, 5.82) compared with 3.25 ng/ml (2.23, 5.05) in those classed as early pubertal (n = 460, P≤0.001). After adjusting for birth weight, gestational age, pubertal stage, age, ethnicity, socioeconomic position, adiposity and use of hormonal contraceptives, there were no associations with any of the cardiometabolic outcomes. For example fasting insulin changed by 0% per doubling of AMH (95%CI: −3%,+2%) p = 0.70, with identical results if HOMA-IR was used. Results were similar after additional adjustment for smoking, physical activity and age at menarche, after exclusion of 3% of females with the highest AMH values, after excluding those that had not started menarche and after excluding those using hormonal contraceptives.</p> <p>Conclusion: Our results suggest that in healthy adolescent females, AMH is not associated with cardiometabolic risk factors.</p&gt

Synthetic Design and Anisotropic Conductivities of Polymeric Mixed Ion- Electron Conductors

Our project documented, in extensive detail, the liquid crystalline (LC) assembly pathway from solution to solid state in the supramolecular complexes of the mixed ionic-electronic conducting polymers (MIECPs) prepared from carboxylated poly(3-alkylthiophene) and ionic liquid surfactant. Using UV-visible spectroscopy we have shown that the complexation is accompanied by the surfactochromism showing colorimetric response and conformational transitions as a function of the IL surfactant mole ratio. Additionally, we have demonstrated via Polarized Optical Microscopy (POM), that the equimolar solution exhibits rodlike conformation and its hydrogel spontaneously forms a 2D smectic LC mesophase with a lamellar periodicity. Defect-free LC domains were produced by a method of mechanical shearing, and uniform LC alignment was retained in the solid- state film that possesses a unidirecXonal electronic transport channel along the conjugatedbackbone and ionic transport channel along IL moieties in the smectic layer, leading to the high anisotropy in electronic conductivities and ionic conductivities. The system demonstrated high mixed-conduction with electronic conductivities on the order of 10-3 S/m and ionic conductivities on the order of 10-4 S/m at ambient temperature. This project has produced significant results of broad merit, as the supramolecular LC design and the LC assembly pathway from solution to solid state in this work would provide useful methodologies for construction of film morphologies and structures in MIECPs that can simultaneously achieve fast electronic and ionic transport. Hence, the conclusions of this project will allow for the production of high-performance electrochemical devices

The Association Between Frequency of Alcohol Drinking and Neurobehaviors

Drinking culture is very prevalent in colleges across the United States. The effects of binge drinking and mindfulness habits/overall mood of students in college and their correlation have yet to be researched. An anonymous online survey was administered through GroupMe and iMessage chats. The survey included basic demographic questions of each participant and questions on their drinking, diet, resilience, exercise patterns, and overall mood. Pearson’s Correlation Analysis was utilized using SPSS version 28.0. Results suggest that there is a relationship between alcohol consumption, mental distress state, and mindfulness among college students. With college students, reducing alcohol consumption may modulate neurobehaviors.https://orb.binghamton.edu/research_days_posters_2024/1066/thumbnail.jp

Mediators of the Association Between Cognitive Function and Self-care Behaviors in Patients Hospitalized With an Exacerbation of Heart Failure

Background: Patients with heart failure (HF) must engage in self-care, yet their self-care is often poor. Cognitive function commonly is impaired in HF and is associated with poor self-care. Heart failure knowledge and self-care confidence also are needed to preform self-care. Few investigators have examined mediators of the association of cognitive function with self-care. Objectives: The aim of this study was to determine whether HF knowledge and self-care confidence mediated the association of cognitive function with self-care maintenance and management among patients with HF. Methods: This was a cross-sectional observational study of 164 patients with HF. Cognitive function was assessed using the Montreal Cognitive Assessment. Self-care maintenance and self-care management behaviors and self-care confidence were measured using the Self-care of Heart Failure Index. Heart failure knowledge was measured using the Dutch Heart Failure Knowledge Scale. We conducted 2 parallel mediation analyses using the PROCESS macro in SPSS, one for self-care maintenance and one for self-care management. Results: Cognitive function was indirectly associated with self-care maintenance through HF knowledge (indirect effect, 0.54; 95% confidence interval, 0.10–1.02) and self-care confidence (indirect effect, 0.26; 95% confidence interval, 0.04–0.54). Those with better cognitive function had more HF knowledge and self-care confidence. Better cognitive function was not directly associated with self-care management but indirectly associated with better self-care management through higher self-care confidence (indirect effect, 0.50; 95% confidence interval, 0.04–1.05). Conclusions: Both HF knowledge and self-care confidence mediated the association of cognitive function with self-care maintenance, and only self-care confidence mediated the association between cognitive function and self-care management. Interventions targeting HF knowledge and self-care confidence may improve self-care even for those with lower cognitive function and need to be developed and tested

Phase Separation of C9orf72 Dipeptide Repeats Perturbs Stress Granule Dynamics

Liquid-liquid phase separation (LLPS) of RNA-binding proteins plays an important role in the formation of multiple membrane-less organelles involved in RNA metabolism, including stress granules. Defects in stress granule homeostasis constitute a cornerstone of ALS/FTLD pathogenesis. Polar residues (tyrosine and glutamine) have been previously demonstrated to be critical for phase separation of ALS-linked stress granule proteins. We now identify an active role for arginine-rich domains in these phase separations. Moreover, arginine-rich dipeptide repeats (DPRs) derived from C9orf72 hexanucleotide repeat expansions similarly undergo LLPS and induce phase separation of a large set of proteins involved in RNA and stress granule metabolism. Expression of arginine-rich DPRs in cells induced spontaneous stress granule assembly that required both eIF2α phosphorylation and G3BP. Together with recent reports showing that DPRs affect nucleocytoplasmic transport, our results point to an important role for arginine-rich DPRs in the pathogenesis of C9orf72 ALS/FTLD

Drivers of genetic diversity in secondary metabolic gene clusters within a fungal species

Drivers of genetic diversity in secondary metabolic gene clusters within a fungal speciesFilamentous fungi produce a diverse array of secondary metabolites (SMs) critical for defense, virulence, and communication. The metabolic pathways that produce SMs are found in contiguous gene clusters in fungal genomes, an atypical arrangement for metabolic pathways in other eukaryotes. Comparative studies of filamentous fungal species have shown that SM gene clusters are often either highly divergent or uniquely present in one or a handful of species, hampering efforts to determine the genetic basis and evolutionary drivers of SM gene cluster divergence. Here, we examined SM variation in 66 cosmopolitan strains of a single species, the opportunistic human pathogen Aspergillus fumigatus. Investigation of genome-wide within-species variation revealed 5 general types of variation in SM gene clusters: nonfunctional gene polymorphisms; gene gain and loss polymorphisms; whole cluster gain and loss polymorphisms; allelic polymorphisms, in which different alleles corresponded to distinct, nonhomologous clusters; and location polymorphisms, in which a cluster was found to differ in its genomic location across strains. These polymorphisms affect the function of representative A. fumigatus SM gene clusters, such as those involved in the production of gliotoxin, fumigaclavine, and helvolic acid as well as the function of clusters with undefined products. In addition to enabling the identification of polymorphisms, the detection of which requires extensive genome-wide synteny conservation (e.g., mobile gene clusters and nonhomologous cluster alleles), our approach also implicated multiple underlying genetic drivers, including point mutations, recombination, and genomic deletion and insertion events as well as horizontal gene transfer from distant fungi. Finally, most of the variants that we uncover within A. fumigatus have been previously hypothesized to contribute to SM gene cluster diversity across entire fungal classes and phyla. We suggest that the drivers of genetic diversity operating within a fungal species shown here are sufficient to explain SM cluster macroevolutionary patterns.National Science Foundation (grant number DEB-1442113). Received by AR. U.S. National Library of Medicine training grant (grant number 2T15LM007450). Received by ALL. Conselho Nacional de Desenvolvimento Cientı´fico e 573 Tecnológico. Northern Portugal Regional Operational Programme (grant number NORTE-01- 0145-FEDER-000013). Received by FR. Fundação de Amparo à Pesquisa do 572 Estado de São Paulo. Received by GHG. National Institutes of Health (grant number R01 AI065728-01). Received by NPK. National Science Foundation (grant number IOS-1401682). Received by JHW. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.info:eu-repo/semantics/publishedVersio

Dual coding with STDP in a spiking recurrent neural network model of the hippocampus.

The firing rate of single neurons in the mammalian hippocampus has been demonstrated to encode for a range of spatial and non-spatial stimuli. It has also been demonstrated that phase of firing, with respect to the theta oscillation that dominates the hippocampal EEG during stereotype learning behaviour, correlates with an animal's spatial location. These findings have led to the hypothesis that the hippocampus operates using a dual (rate and temporal) coding system. To investigate the phenomenon of dual coding in the hippocampus, we examine a spiking recurrent network model with theta coded neural dynamics and an STDP rule that mediates rate-coded Hebbian learning when pre- and post-synaptic firing is stochastic. We demonstrate that this plasticity rule can generate both symmetric and asymmetric connections between neurons that fire at concurrent or successive theta phase, respectively, and subsequently produce both pattern completion and sequence prediction from partial cues. This unifies previously disparate auto- and hetero-associative network models of hippocampal function and provides them with a firmer basis in modern neurobiology. Furthermore, the encoding and reactivation of activity in mutually exciting Hebbian cell assemblies demonstrated here is believed to represent a fundamental mechanism of cognitive processing in the brain