A novel approach to tomographic data processing has been developed and evaluated using the Jagiellonian positron emission tomography scanner as an example. We propose a system in which there is no ...need for powerful, local to the scanner processing facility, capable to reconstruct images on the fly. Instead, we introduce a field programmable gate array system-on-chip platform connected directly to data streams coming from the scanner, which can perform event building, filtering, coincidence search, and region-of-response reconstruction by the programmable logic and visualization by the integrated processors. The platform significantly reduces data volume converting raw data to a list-mode representation, while generating visualization on the fly.
•Depression is associated with inflammatory markers•Galectin-3 is an inflammatory biomarker associated with cognitive disorders•Galectin-3 levels and depressive symptom severity were assessed in a ...community sample•Galectin-3 levels statistically significantly predicted depressive symptom severity•Galectin-3 appears to be a novel inflammatory biomarker associated with depression
Major depressive disorder is associated with pro-inflammatory markers, such as cytokines TNF-alpha, IL-6, IL-1ß, and C-reactive protein. Galectin-3 is a novel emerging biomarker with pro-inflammatory properties. It is a saccharide binding protein distributed throughout many tissues with varying functions and is a predictor of poor outcomes in patients with heart failure and stroke. However, its role as a predictor in depressive symptom severity remains undefined. Data from the community-based Dallas Heart Study (n = 2554) were examined using a multiple linear regression analysis to evaluate the relationship between galectin-3 and depressive symptom severity as assessed with Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR) scores. Additional covariates included age, sex, race/ethnicity, body mass index (BMI), years of education, serum creatinine, history of diabetes, and smoking history. Galectin-3 levels statistically significantly predicted QIDS-SR depressive symptom severity (β = 0.055, p = .015). Female sex, smoking status, and BMI were found to be statistically significant positive predictors of depression severity, while age, years of education, non-Hispanic White race, and Hispanic ethnicity were negative predictors of depressive symptom severity. In this large sample, higher galectin-3 levels were associated with higher levels of depressive symptoms. The findings suggest that galectin-3 may be a new and useful inflammatory biomarker associated with depression.
Approximately 30% of tumor biopsies from patients with advanced-stage lung adenocarcinomas yield insufficient tissue for successful molecular subtyping. We have analyzed the clinical utility of ...next-generation sequencing (NGS) of cell-free circulating tumor DNA (ctDNA) in patients with inadequate tumor samples for tissue genotyping.
We conducted the study in a multi-institutional prospective cohort of clinically unselected patients with advanced-stage lung adenocarcinomas with insufficient tissue for EGFR, ALK or ROS1 genotyping across 12 Spanish institutions (n = 93). ctDNA NGS was carried out by Guardant Health (Guardant360, Redwood City, CA), using a hybrid-capture-based 73-gene panel. Variants were deemed actionable if they were part of the OncoKB precision oncology knowledge database and classified in four levels of actionability based on their clinical or preclinical evidence for drug response.
Eighty-three out of 93 patients (89%) had detectable levels of ctDNA. Potentially actionable level 1–4 genomic alterations were detected in 53 cases (57%), of which 13 (14%) had level 1–2A alterations (Food and Drug Administration-approved and standard-care biomarkers according to lung cancer guidelines). Frequencies of each genomic alteration in ctDNA were consistent with those observed in unselected pulmonary adenocarcinomas. The majority of the patients (62%), particularly those with actionable alterations (87%), had more than one pathogenic variant in ctDNA. The median turnaround time to genomic results was 13 days. Twelve patients (13%) received genotype-matched therapies based on ctDNA results, deriving the expected clinical benefit. Patients with co-occurring pathogenic alterations had a significantly shorter median overall survival as compared with patients without co-occurring pathogenic alteration (multivariate hazard ratio = 5.35, P = 0.01).
Digital NGS of ctDNA in lung cancers with insufficient tumor samples for tissue sequencing detects actionable variants that frequently co-occur with other potentially clinically relevant genomic alterations, allowing timely initiation of genotype-matched therapies.
Recently, there has been an increased interest in developing statistical methodologies for analyzing single case experimental design (SCED) data to supplement visual analysis. Some of these are ...simulation-driven such as Bayesian methods because Bayesian methods can compensate for small sample sizes, which is a main challenge of SCEDs. Two simulation-driven approaches: Bayesian unknown change-point model (BUCP) and simulation modeling analysis (SMA) were compared in the present study for three real datasets that exhibit "clear" immediacy, "unclear" immediacy, and delayed effects. Although SMA estimates can be used to answer some aspects of functional relationship between the independent and the outcome variables, they cannot address immediacy or provide an effect size estimate that considers autocorrelation as required by the What Works Clearinghouse (WWC) Standards. BUCP overcomes these drawbacks of SMA. In final analysis, it is recommended that both visual and statistical analyses be conducted for a thorough analysis of SCEDs.
Major depressive disorder (MDD) is a common, disabling, and heterogeneous condition that responds unpredictably to current treatments. We previously showed an association between depressive symptoms ...and plasma concentrations of two cholesterol precursors, desmosterol and 7-dehydrocholesterol (7DHC). Here, we measured total cholesterol and sterol concentrations with mass spectrometry in postmortem brain samples from depressed and control subjects. Mean (±SEM) desmosterol concentration was 8.9 ± 0.97 ng/mg in the depressed versus 10.7 ± 0.72 ng/mg in the control group. The mean of the posterior probability distribution for the difference in desmosterol concentration between the two groups was 2.36 (95% highest density interval HDI 0.59-4.17). Mean 7DHC concentrations, 12.5 ± 4.1 ng/mg in the depressed versus 5.4 ± 0.74 ng/mg in the control group, were unlikely to be different (95% HDI, -1.37-0.34). We found that presence of trazodone in the peri-mortem toxicology screen accounted for the observed difference in desmosterol concentrations. We also observed extremely high 7DHC levels in all 4 subjects who had taken trazodone. Trazodone has been recently found to inhibit 7-dehydrocholesterol reductase and alter sterol concentrations in rodents, cell culture, human fibroblasts, and blood. In this study, we demonstrate for the first time that trazodone alters human brain sterol composition. Given congenital deficiency of 7-dehydrocholesterol reductase results in Smith-Lemli-Opitz syndrome, our findings support the hypothesis that this commonly used medication may have previously unappreciated risks.
Anorexia nervosa is a complex psychiatric illness that includes severe low body weight with cognitive distortions and altered eating behaviors. Brain structures, including cortical thicknesses in ...many regions, are reduced in underweight patients who are acutely ill with anorexia nervosa. However, few studies have examined adult outpatients in the process of recovering from anorexia nervosa. Evaluating neurobiological problems at different physiological stages of anorexia nervosa may facilitate our understanding of the recovery process.
Magnetic resonance imaging (MRI) images from 37 partially weight-restored women with anorexia nervosa (pwAN), 32 women with a history of anorexia nervosa maintaining weight restoration (wrAN), and 41 healthy control women were analyzed using FreeSurfer. Group differences in brain structure, including cortical thickness, areas, and volumes, were compared using a series of factorial f-tests, including age as a covariate, and correcting for multiple comparisons with the False Discovery Rate method.
The pwAN and wrAN cohorts differed from each other in body mass index, eating disorder symptoms, and social problem solving orientations, but not depression or self-esteem. Relative to the HC cohort, eight cortical thicknesses were thinner for the pwAN cohort; these regions were predominately right-sided and in the cingulate and frontal lobe. One of these regions, the right pars orbitalis, was also thinner for the wrAN cohort. One region, the right parahippocampal gyrus, was thicker in the pwAN cohort. One volume, the right cerebellar white matter, was reduced in the pwAN cohort. There were no differences in global white matter, gray matter, or subcortical volumes across the cohorts.
Many regional structural differences were observed in the pwAN cohort with minimal differences in the wrAN cohort. These data support a treatment focus on achieving and sustaining full weight restoration to mitigate possible neurobiological sequela of AN. In addition, the regions showing cortical thinning are similar to structural changes reported elsewhere for suicide attempts, anxiety disorders, and autistic spectrum disorder. Understanding how brain structure and function are related to clinical symptoms expressed during the course of recovering from AN is needed.
Research has examined the association between contact with media coverage of mass trauma events and various psychological outcomes, including depression. Disaster-related depression research is ...complicated by the relatively high prevalence of the major depressive disorder in general populations even without trauma exposure. The extant research is inconclusive regarding associations between disaster media contact and depression outcomes, in part, because most studies have not distinguished diagnostic and symptomatic outcomes, differentiated postdisaster incidence from prevalence, or considered disaster trauma exposures. This study examined these associations in a volunteer sample of 254 employees of New York City businesses after the 11 September 2001, terrorist attacks. Structured interviews and questionnaires were administered 35 months after the attacks. Poisson and logistic regression analyses revealed that post-9/11 news contact significantly predicted the number of postdisaster persistent/recurrent and incident depressive symptoms in the full sample and in the indirect and unexposed groups. The findings suggest that clinical and public health approaches should be particularly alert to potential adverse postdisaster depression outcomes related to media consumption in disaster trauma-unexposed or indirectly-exposed groups.
Research conducted in the framework of the Jagiellonian-PET (J-PET) project aims to develop a cost-effective total-body positron emission tomography scanner. As a first step on the way to construct a ...full-scale J-PET tomograph from long strips of plastic scintillators, a 24-strip prototype was built and tested. The prototype consists of detection modules arranged axially forming a cylindrical diagnostic chamber with the inner diameter of 360 mm and the axial field-of-view of 300 mm. Promising perspectives for a low-cost construction of a total-body PET scanner are opened due to an axial arrangement of strips of plastic scintillators, which have a small light attenuation, superior timing properties, and the possibility of cost-effective increase of the axial field-of-view. The presented prototype comprises dedicated solely digital front-end electronic circuits and a triggerless data acquisition system which required the development of new calibration methods including time, thresholds, and gain synchronization. The system and elaborated calibration methods, including first results of the 24-module J-PET prototype, are presented and discussed. The achieved coincidence resolving time equals to <inline-formula> <tex-math notation="LaTeX">{\mathrm {CRT}}=490\pm 9 </tex-math></inline-formula> ps. This value can be translated to the position reconstruction accuracy <inline-formula> <tex-math notation="LaTeX">\sigma (\Delta l) =18 </tex-math></inline-formula> mm, which is fairly position independent.
Abstract
Background
Problems in social cognition and social support contribute to eating disorders (ED). Group therapy provides an ideal format to create an experiential learning environment focused ...on understanding social interactions. This pilot study examined the qualitative content of the participants’ experiences in the Self-Blame and Perspective-Taking Intervention (SBPI) for ED.
Methods
The SBPI was a 4-week group therapy intervention involving art therapy and psychoeducation that focused on social behaviors in ED patients. Participants received surveys immediately after the intervention and at 1 to 4 weeks after the post-intervention. Thematic analyses of qualitative feedback were performed using Braun and Clarke’s thematic analysis framework.
Results
Inductive analyses revealed three main themes: (1) Developing self-acceptance through emotional reflection, (2) Changing expectations with neurosocial knowledge, and (3) Bonding and vulnerability in social interactions; all concepts intentionally targeted by the SBPI. Participants varied in their support of a guideline to exclude personal discussion of ED-related cognitions and behaviors in the group.
Conclusions
As a whole, patients valued the combination of psychosocial education with group experientials focused on social behavior. Positive feedback from the SBPI suggests that adjunctive treatments that target mental-wellness constructs indirectly related to ED pathology may be helpful by allowing patients to see themselves as separable from the illness.
Trial registration
ClinicalTrials.gov, NCT0487758. Registered 7 May 2021—Retrospectively registered.
https://clinicaltrials.gov/ct2/show/NCT04877158
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