Isolation and genomic analysis of "Metallumcola ferriviriculae" MK1, a Gram-positive, Fe(III)-reducing bacterium from the Soudan Underground Mine, an iron-rich Martian analog site.

The Soudan Underground Mine State Park, found in the Vermilion Iron Range in northern Minnesota, provides access to a ~ 2.7 billion-year-old banded iron formation. Exploratory boreholes drilled between 1958 and 1962 on the 27th level (713 m underground) of the mine intersect calcium and iron-rich brines that have recently been subject to metagenomic analysis and microbial enrichments. Using concentrated brine samples pumped from a borehole depth of up to 55 m, a novel Gram-positive bacterium was enriched under anaerobic, acetate-oxidizing, and Fe(III) citrate-reducing conditions. The isolated bacterium, designated strain MK1, is non-motile, rod-shaped, spore-forming, anaerobic, and mesophilic, with a growth range between 24°C and 30°C. The complete circular MK1 genome was found to be 3,720,236 bp and encodes 25 putative multiheme cytochromes, including homologs to inner membrane cytochromes in the Gram-negative bacterium Geobacter sulfurreducens and cytoplasmic membrane and periplasmic cytochromes in the Gram-positive bacterium Thermincola potens. However, MK1 does not encode homologs of the peptidoglycan (CwcA) and cell surface-associated (OcwA) multiheme cytochromes proposed to be required by T. potens to perform extracellular electron transfer. The 16S rRNA gene sequence of MK1 indicates that its closest related isolate is Desulfitibacter alkalitolerans strain sk.kt5 (91% sequence identity), which places MK1 in a novel genus within the Desulfitibacteraceae family and Moorellales order. Within the Moorellales order, only Calderihabitans maritimus strain KKC1 has been reported to reduce Fe(III), and only D. alkalitolerans can also grow in temperatures below 40°C. Thus, MK1 represents a novel species within a novel genus, for which we propose the name "Metallumcola ferriviriculae" strain MK1, and provides a unique opportunity to study a cytochrome-rich, mesophilic, Gram-positive, spore-forming Fe(III)-reducing bacterium.IMPORTANCEThe Soudan Underground Mine State Park gives access to understudied regions of the deep terrestrial subsurface that potentially predate the Great Oxidation Event. Studying organisms that have been relatively unperturbed by surface conditions for as long as 2.7 billion years may give us a window into ancient life before oxygen dominated the planet. Additionally, studying microbes from anoxic and iron-rich environments can help us better understand the requirements of life in analogous environments, such as on Mars. The isolation and characterization of "Metallumcola ferriviriculae" strain MK1 give us insights into a novel genus and species that is distinct both from its closest related isolates and from iron reducers characterized to date. "M. ferriviriculae" strain MK1 may also act as a model organism to study how the processes of sporulation and germination are affected by insoluble extracellular acceptors, as well as the impact of spores in the deep terrestrial biosphere.

Resolution of Postoperative Cystoid Macular Edema with a Suprachoroidal Triamcinolone Acetonide Injectable Suspension.

AIM: To report a case of significant postoperative cystoid macular edema (CME) in a patient with no prior history of uveitis or systemic inflammatory disease, in which a suprachoroidal (SC) triamcinolone acetonide injectable suspension resulted in complete resolution of CME. DESIGN: Case report. METHODS: An 81-year-old man presented with a complex, dense brunescent cataract, floppy iris, and miotic pupil in the left eye. Six weeks following cataract extraction, the intraocular lens (IOL) was dislocated completely from the visual axis. He underwent a pars plana vitrectomy and IOL exchange with an anterior chamber IOL due to a three-piece IOL dislocation. Following the operation, the patient began treatment with prednisolone acetate and ketorolac. However, 2 weeks later, he was noted to be a steroid responder and glaucoma suspect. Therefore, the decision was made to taper and discontinue topical steroids. At 6 months postoperatively, ranibizumab was injected for persistent CME. However, following injection, there was intraocular pressure (IOP) elevation and increased CME. IOP improved 1 month later with dorzolamide hydrochloride and timolol maleate. At 8 months post-operation, there was persistent CME. The patient was then treated with an SC triamcinolone acetonide injection. There was complete resolution of CME by 14 weeks later, with improvement in visual acuity. Despite the patient's known steroid response with topical steroids, IOP remained within normal limits during the entire follow-up period after injection. CONCLUSION: SC triamcinolone acetonide injection is indicated for macular edema associated with uveitis; however, treatment for postoperative macular edema with this novel suprachoroidal injection may be considered.

Single-center Outcomes After Liver Transplantation With SARS-CoV-2-Positive Donors: An Argument for Increased Utilization.

Background: The COVID-19 pandemic has led to an increase in SARS-CoV-2-test positive potential organ donors. The benefits of life-saving liver transplantation (LT) must be balanced against the potential risk of donor-derived viral transmission. Although emerging evidence suggests that the use of COVID-19-positive donor organs may be safe, granular series thoroughly evaluating safety are still needed. Results of 29 consecutive LTs from COVID-19-positive donors at a single center are presented here. Methods: A retrospective cohort study of LT recipients between April 2020 and December 2022 was conducted. Differences between recipients of COVID-19-positive (n = 29 total; 25 index, 4 redo) and COVID-19-negative (n = 472 total; 454 index, 18 redo) deceased donor liver grafts were compared. Results: COVID-19-positive donors were significantly younger (P = 0.04) and had lower kidney donor profile indices (P = 0.04) than COVID-19-negative donors. Recipients of COVID-19-positive donor grafts were older (P = 0.04) but otherwise similar to recipients of negative donors. Donor SARS-CoV-2 infection status was not associated with a overall survival of recipients (hazard ratio, 1.11; 95% confidence interval, 0.24-5.04; P = 0.89). There were 3 deaths among recipients of liver grafts from COVID-19-positive donors. No death seemed virally mediated because there was no qualitative association with peri-LT antispike antibody titers, post-LT prophylaxis, or SARS-CoV-2 variants. Conclusions: The utilization of liver grafts from COVID-19-positive donors was not associated with a decreased overall survival of recipients. There was no suggestion of viral transmission from donor to recipient. The results from this large single-center study suggest that COVID-19-positive donors may be used safely to expand the deceased donor pool.

Patient-Derived Models of Cancer in the NCI PDMC Consortium: Selection, Pitfalls, and Practical Recommendations.

For over a century, early researchers sought to study biological organisms in a laboratory setting, leading to the generation of both in vitro and in vivo model systems. Patient-derived models of cancer (PDMCs) have more recently come to the forefront of preclinical cancer models and are even finding their way into clinical practice as part of functional precision medicine programs. The PDMC Consortium, supported by the Division of Cancer Biology in the National Cancer Institute of the National Institutes of Health, seeks to understand the biological principles that govern the various PDMC behaviors, particularly in response to perturbagens, such as cancer therapeutics. Based on collective experience from the consortium groups, we provide insight regarding PDMCs established both in vitro and in vivo, with a focus on practical matters related to developing and maintaining key cancer models through a series of vignettes. Although every model has the potential to offer valuable insights, the choice of the right model should be guided by the research question. However, recognizing the inherent constraints in each model is crucial. Our objective here is to delineate the strengths and limitations of each model as established by individual vignettes. Further advances in PDMCs and the development of novel model systems will enable us to better understand human biology and improve the study of human pathology in the lab.

Chromatin Remodeling in Patient-Derived Colorectal Cancer Models.

Patient-Derived Organoids (PDO) and Xenografts (PDX) are the current gold standards for patient-derived models of cancer (PDMC). Nevertheless, how patient tumor cells evolve in these models and the impact on drug response remains unclear. Herein, the transcriptomic and chromatin accessibility landscapes of matched colorectal cancer (CRC) PDO, PDX, PDO-derived PDX (PDOX), and original patient tumors (PT) are compared. Two major remodeling axes are discovered. The first axis delineates PDMC from PT, and the second axis distinguishes PDX and PDO. PDOX are more similar to PDX than PDO, indicating the growth environment is a driving force for chromatin adaptation. Transcription factors (TF) that differentially bind to open chromatins between matched PDO and PDOX are identified. Among them, KLF14 and EGR2 footprints are enriched in PDOX relative to matched PDO, and silencing of KLF14 or EGR2 promoted tumor growth. Furthermore, EPHA4, a shared downstream target gene of KLF14 and EGR2, altered tumor sensitivity to MEK inhibitor treatment. Altogether, patient-derived CRC cells undergo both common and distinct chromatin remodeling in PDO and PDX/PDOX, driven largely by their respective microenvironments, which results in differences in growth and drug sensitivity and needs to be taken into consideration when interpreting their ability to predict clinical outcome.

MDMA enhances positive affective responses to social feedback.

BACKGROUND: The prosocial compound ± 3,4-methylenedioxymethamphetamine (MDMA) is an amphetamine derivative that has shown promise as an adjunct to psychotherapy in the treatment of post-traumatic stress disorder. MDMA increases positive responses to social images, and it has been suggested that the ability of MDMA to positively bias social perception may underlie its therapeutic efficacy as a psychotherapy adjunct. However, the effect of the compound on affective responses to positive or negative social feedback has not been tested. AIMS: In this study, we aimed to test the effects of MDMA compared to placebo and the prototypical stimulant, methamphetamine (MA), on responses to positive and negative social feedback. METHODS: This was a double-blind, placebo-controlled, crossover trial (NCT03790618), comparing the effects of two doses of MDMA (0.75 mg/kg, 1.5 mg/kg) to both placebo and MA (20 mg) on responses to a personalized social feedback task, similar to a dating app, in healthy adult volunteers ages 18-40 (N = 36, 18 women, 18 men). RESULTS/OUTCOMES: The high dose of MDMA increased positive affective responses to social feedback. CONCLUSIONS/INTERPRETATIONS: These findings suggest one process by which MDMA may facilitate social connection. Further work is needed to understand how MDMA affects responses to more generalized types of social feedback and to understand these effects in clinical populations.

Orbitofrontal and striatal metabolism, volume, thickness and structural connectivity in relation to social anhedonia in depression: A multimodal study.

BACKGROUND: Social anhedonia is common within major depressive disorder (MDD) and associated with worse treatment outcomes. The orbitofrontal cortex (OFC) is implicated in both reward (medial OFC) and punishment (lateral OFC) in social decision making. Therefore, to understand the biology of social anhedonia in MDD, medial/lateral OFC metabolism, volume, and thickness, as well as structural connectivity to the striatum, amygdala, and ventral tegmental area/nucleus accumbens were examined. A positive relationship between social anhedonia and these neurobiological outcomes in the lateral OFC was hypothesized, whereas an inverse relationship was hypothesized for the medial OFC. The association between treatment-induced changes in OFC neurobiology and depression improvement were also examined. METHODS: 85 medication-free participants diagnosed with MDD were assessed with Wisconsin Schizotypy Scales to assess social anhedonia and received pretreatment simultaneous fluorodeoxyglucose positron emission tomography (FDG-PET) and magnetic resonance imaging (MRI), including structural and diffusion. Participants were then treated in an 8-week randomized placebo-controlled double-blind course of escitalopram. PET/MRI were repeated following treatment. Metabolic rate of glucose uptake was quantified from dynamic FDG-PET frames using Patlak graphical analysis. Structure (volume and cortical thickness) was quantified from structural MRI using Freesurfer. To assess structural connectivity, probabilistic tractography was performed on diffusion MRI and average FA was calculated within the derived tracts. Linear mixed models with Bonferroni correction were used to examine the relationships between variables. RESULTS: A significantly negative linear relationship between pretreatment social anhedonia score and structural connectivity between the medial OFC and the amygdala (estimated coefficient: -0.006, 95 % CI: -0.0108 - -0.0012, p-value = 0.0154) was observed. However, this finding would not survive multiple comparisons correction. No strong evidence existed to show a significant linear relationship between pretreatment social anhedonia score and metabolism, volume, thickness, or structural connectivity to any of the regions examined. There was also no strong evidence to suggest significant linear relationships between improvement in depression and percent change in these variables. CONCLUSIONS: Based on these multimodal findings, the OFC likely does not underlie social anhedonia in isolation and therefore should not be the sole target of treatment for social anhedonia. This is consistent with previous reports that other areas of the brain such as the amygdala and the striatum are highly involved in this behavior. Relatedly, amygdala-medial OFC structural connectivity could be a future target. The results of this study are crucial as, to our knowledge, they are the first to relate structure/function of the OFC with social anhedonia severity in MDD. Future work may need to involve a whole brain approach in order to develop therapeutics for social anhedonia.

Neighborhood disadvantage and intellectual development in youth with epilepsy.

RATIONALE: Recent cross-sectional investigations have demonstrated an adverse impact of socioeconomic disadvantage on cognition and behavior in youth and adults with epilepsy. The goal of this study is to investigate the impact of disadvantage on prospective intellectual development in youth with epilepsy. METHOD: Participants were youth, aged 8-18 years, with recent onset epilepsy (n = 182) and healthy first-degree cousin controls (n = 106). The Wechsler Abbreviated Scale of Intelligence (WASI) was administered at baseline and 2 years later. The Neighborhood Atlas identified each family's Area Deprivation Index via state deciles and national percentiles. WASI data were analyzed by mixed group by time ANOVAs followed by regression analysis to identify other baseline predictors of time 2 outcomes. RESULTS: Youth with epilepsy demonstrated significant interactions between group and time for both verbal (F = 4.02, df = 1,215, p =.05) and nonverbal (F = 4.57, df = 1,215, p =.04) reasoning, demonstrating that disadvantage was associated with slower cognitive development compared to advantaged youth with epilepsy. Similar interactions were not observed for controls. CONCLUSIONS: In youth with new and recent onset epilepsies, neighborhood-level disadvantage is associated with a negative impact on the development of verbal and nonverbal reasoning skills.

Effects and Eradication of Mycoplasma Contamination on Patient-derived Colorectal Cancer Organoid Cultures.

Patient-derived organoids are a useful platform for identification and testing of novel precision oncology approaches. Patient-derived organoids are generated by direct culture of patient samples. However, prior to development into patient-derived organoids, these samples are often processed for clinical use, opening the potential for contamination by Mycoplasma and other microbes. While most microbes can be detected by visual inspection, Mycoplasma can go undetected and have substantial impacts on assay results. Given the increased use of patient-derived organoids, there is a growing need for a standardized protocol to detect and remove Mycoplasma from organoid models. In the current study, we report a procedure for Mycoplasma removal by passaging organoids through mice as patient-derived organoid xenografts. In vivo passage of patient-derived organoids followed by re-establishment was 100% effective at decontaminating colorectal patient-derived organoids (n = 9), based on testing with the Sigma LookOut Mycoplasma PCR Detection Kit. This process can serve as a method to re-establish contaminated patient-derived organoids, which represent precious models to study patient-specific genomic features and treatment responses. SIGNIFICANCE: Organoids are valuable models of cancer. Mycoplasma contamination can alter organoid drug sensitivity, so there is a need for a standardized protocol to detect and remove Mycoplasma from organoids. We report a simple procedure for removing Mycoplasma from organoids via in vivo passaging through mice followed by re-establishment of organoids.

Corrigendum: Psymberin, a marine-derived natural product, induces cancer cell growth arrest and protein translation inhibition.

[This corrects the article DOI: 10.3389/fmed.2022.999004.].

Utilization of Instagram by Ophthalmology Residency Programs in the Era of COVID-19.

Purpose: The aim of this research is to describe the use of the social media platform, Instagram, by academic ophthalmology residency programs in the United States over time and consider the impact of the COVID-19 pandemic on ophthalmology's social media presence. Methods and Subjects: This cross-sectional study was conducted online by reviewing the publicly accessible Instagram accounts of all accredited US academic ophthalmology residency programs. Main Outcomes and Measures: Number of US ophthalmology residency programs with an affiliated Instagram account were analyzed by year of creation. The content of the top six accounts with the most followers was analyzed by evaluating amount of engagement within defined post categories. Results: Of the 124 ophthalmology residency programs, 78 (62.9%) were identified as having an affiliated Instagram account, 60 accounts (48.4%) were created during the years 2020 or 2021, and 62 (50.0%) accounts focused specifically on promoting the residency training program. Of the top six accounts with the most followers, post categories that received the most engagement were "Medical" and "Group Photo", while those that received the least engagement were "Department Bulletin" and "Miscellaneous." User engagement on posts as measured by likes and comments increased across multiple post categories after January 2020. Conclusion: Social media presence of ophthalmology residency programs on Instagram increased substantially in 2020 and 2021. As a result of the COVID-19 pandemic restricting in-person interactions, residency programs have used alternative platforms to reach applicants. Given the increasing use of such applications, social media will likely continue to become an important aspect of professional engagement in ophthalmology.

Protein Folding Stability Profiling of Colorectal Cancer Chemoresistance Identifies Functionally Relevant Biomarkers.

Reported here is the application of three protein folding stability profiling techniques (including the stability of proteins from rates of oxidation, thermal protein profiling, and limited proteolysis approaches) to identify differentially stabilized proteins in six patient-derived colorectal cancer (CRC) cell lines with different oxaliplatin sensitivities and eight CRC patient-derived xenografts (PDXs) derived from two of the patient derived cell lines with different oxaliplatin sensitivities. Compared to conventional protein expression level analyses, which were also performed here, the stability profiling techniques identified both unique and novel proteins and cellular components that differentiated the sensitive and resistant samples including 36 proteins that were differentially stabilized in at least two techniques in both the cell line and PDX studies of oxaliplatin resistance. These 36 differentially stabilized proteins included 10 proteins previously connected to cancer chemoresistance. Two differentially stabilized proteins, fatty acid synthase and elongation factor 2, were functionally validated in vitro and found to be druggable protein targets with biological functions that can be modulated to improve the efficacy of CRC chemotherapy. These results add to our understanding of CRC oxaliplatin resistance, suggest biomarker candidates for predicting oxaliplatin sensitivity in CRC, and inform new strategies for overcoming chemoresistance in CRC.

Trends in Receipt of Adjuvant Chemotherapy and its Impact on Survival in Resected Biliary Tract Cancers.

BACKGROUND: Resection remains the cornerstone of curative-intent treatment for biliary tract cancers (BTCs). However, recent randomized data also support a role for adjuvant chemotherapy (AC). This study aimed to characterize trends in the use of AC and subsequent outcomes in gallbladder cancer and cholangiocarcinoma (CCA). METHODS: The National Cancer Database (NCDB) was queried for patients with resected, localized BTC from 2010 to 2018. Trends in AC were compared among BTC subtypes and stages of disease. Multivariable logistic regression was used to identify factors associated with receipt of AC. Survival analysis was performed with Kaplan-Meier and multivariable Cox proportional hazards methods. RESULTS: The study identified 7039 patients: 4657 (66%) with gallbladder cancer, 1159 (17%) with intrahepatic CCA (iCCA), and 1223 (17%) with extrahepatic CCA (eCCA). Adjuvant chemotherapy was administered to 2172 (31%) patients, increasing from 23% in 2010 to 41% in 2018. Factors associated with AC included female sex, year of diagnosis, private insurance, care at an academic center, higher education, eCCA (vs iCCA), positive margins, and stage II or III disease (vs stage I). Alternatively, increasing age, higher comorbidity score, gallbladder cancer (vs iCCA), and farther travel distance for treatment were associated with reduced odds of AC. Overall, AC was not associated with a survival advantage. However, subgroup analysis showed that AC was associated with a significant reduction in mortality among patients with eCCA. CONCLUSIONS: Among the patients with resected BTC, those who received AC were in the minority. In the context of recent randomized data and evolving recommendations, emphasis on guideline concordance with a focus on at-risk populations may improve outcomes.

Disadvantage and neurocognitive comorbidities in childhood idiopathic epilepsies.

OBJECTIVE: This study was undertaken to characterize the relationship between neighborhood disadvantage and cognitive function as well as clinical, sociodemographic, and family factors in children with new onset idiopathic epilepsy and healthy controls. METHODS: Research participants were 288 children aged 8-18 years with recent onset epilepsy (CWE; n = 182; mean age = 12.2 ± 3.2 years), healthy first-degree cousin controls (HC; n = 106; mean age = 12.5 ± 3.0), and one biological or adopted parent per child (n = 279). All participants were administered a comprehensive neuropsychological battery (reasoning, language, memory, executive function, motor function, and academic achievement). Family residential addresses were entered into the Neighborhood Atlas to determine each family's Area Deprivation Index (ADI), a metric used to quantify income, education, employment, and housing quality. A combination of parametric and nonparametric (χ2 ) tests examined the effect of ADI by group (epilepsy and controls) across cognitive, academic, clinical, and family factors. RESULTS: Disadvantage (ADI) was equally distributed between groups (p = .63). For CWE, high disadvantage was associated with lower overall intellectual quotient (IQ; p = .04), visual naming/expressive language (p = .03), phonemic (letter) fluency (p < .01), passive inattention (omission errors; p = .03), delayed verbal recall (p = .04), and dominant fine motor dexterity and speed (p < .01). Cognitive status of the HC group did not differ by level of disadvantage (p = .40). CWE exhibited greater academic difficulties in comparison to HC (p < .001), which were exacerbated by disadvantage in CWE (p = .02) but not HC (p < .05). High disadvantage was associated with a threefold risk for academic challenges prior to epilepsy onset (odds ratio = 3.31, p = .024). SIGNIFICANCE: Socioeconomic hardship (increased neighborhood disadvantage) exerts a significant adverse impact on the cognitive and academic status of youth with new and recent onset epilepsies, an impact that needs to be incorporated into etiological models of the neurobehavioral comorbidities of epilepsy.

Real-world, long-term evaluation of the tolerability and therapy retention of Epidiolex® (cannabidiol) in patients with refractory epilepsy.

OBJECTIVE: Epidiolex® (CBD) is FDA-approved for seizures associated with Lennox-Gastaut syndrome (LGS), Dravet syndrome (DS), and tuberous sclerosis complex (TSC). Phase III studies suggest that certain adverse effects (AEs), possibly linked to pharmacokinetic/pharmacodynamic (PK/PD) interactions may be therapy-limiting. We sought to identify these factors that contribute to treatment success and retention of therapy. METHODS: A single-center, retrospective review of patients with refractory epilepsy taking Epidiolex® was performed. Kaplan-Meier analysis was performed to describe Epidiolex® retention, as a measure of overall effectiveness. RESULTS: One hundred and twelve patients were screened; 4 were excluded due to loss to follow-up or never starting Epidiolex®. Of 108 patients, mean age was 20.3 years (13.1, range 2 to 63), and 52.8% were female. Mean initial and maintenance doses were 5.3 mg/kg/day (1.3) and 15.3 mg/kg/day (5.8), respectively. At the final evaluation, 75% of patients remained on Epidiolex®. The 25th percentile for discontinuation was 19 months. 46.3% of patients experienced at least one treatment-emergent adverse effect (TEAE) with 14.5% d/c Epidiolex® due to treatment emerging adverse effects (TEAE). The most common reasons for discontinuation were lack of efficacy (37%), increased seizure activity (22%), worsened behavior (22%), and sedation (22%). One out of 27 discontinuations was due to liver function test (LFT) elevations (3.7%). At initiation, 47.2% were concurrently taking clobazam, and 39.2% of those patients had an initial clobazam dose decrease. 53% of patients were able to either discontinue or lower the dose of at least one other antiseizure medication. SIGNIFICANCE: Epidiolex® is generally well-tolerated and the majority continued long-term treatment. Patterns of adverse effects were similar to clinical trials, however gastrointestinal complaints, and significant LFT elevations were less common. Our data suggest most patients discontinue within the first several months of treatment and suggest that further studies designed to evaluate early identification and potential mitigation of adverse effects and including drug interactions are warranted.

EPViz: A flexible and lightweight visualizer to facilitate predictive modeling for multi-channel EEG.

Scalp Electroencephalography (EEG) is one of the most popular noninvasive modalities for studying real-time neural phenomena. While traditional EEG studies have focused on identifying group-level statistical effects, the rise of machine learning has prompted a shift in computational neuroscience towards spatio-temporal predictive analyses. We introduce a novel open-source viewer, the EEG Prediction Visualizer (EPViz), to aid researchers in developing, validating, and reporting their predictive modeling outputs. EPViz is a lightweight and standalone software package developed in Python. Beyond viewing and manipulating the EEG data, EPViz allows researchers to load a PyTorch deep learning model, apply it to EEG features, and overlay the output channel-wise or subject-level temporal predictions on top of the original time series. These results can be saved as high-resolution images for use in manuscripts and presentations. EPViz also provides valuable tools for clinician-scientists, including spectrum visualization, computation of basic data statistics, and annotation editing. Finally, we have included a built-in EDF anonymization module to facilitate sharing of clinical data. Taken together, EPViz fills a much needed gap in EEG visualization. Our user-friendly interface and rich collection of features may also help to promote collaboration between engineers and clinicians.

Defining left ventricular remodeling using lean body mass allometry: a UK Biobank study.

PURPOSE: The geometric patterns of ventricular remodeling are determined using indexed left ventricular mass (LVM), end-diastolic volume (LVEDV) and concentricity, most often measured using the mass-to-volume ratio (MVR). The aims of this study were to validate lean body mass (LBM)-based allometric coefficients for scaling and to determine an index of concentricity that is independent of both volume and LBM. METHODS: Participants from the UK Biobank who underwent both CMR and dual-energy X-ray absorptiometry (DXA) during 2014-2015 were considered (n = 5064). We excluded participants aged ≥ 70 years or those with cardiometabolic risk factors. We determined allometric coefficients for scaling using linear regression of the logarithmically transformed ventricular remodeling parameters. We further defined a multiplicative allometric relationship for LV concentricity (LVC) adjusting for both LVEDV and LBM. RESULTS: A total of 1638 individuals (1057 female) were included. In subjects with lower body fat percentage (< 25% in males, < 35% in females, n = 644), the LBM allometric coefficients for scaling LVM and LVEDV were 0.85 ± 0.06 and 0.85 ± 0.03 respectively (R2 = 0.61 and 0.57, P < 0.001), with no evidence of sex-allometry interaction. While the MVR was independent of LBM, it demonstrated a negative association with LVEDV in (females: r = - 0.44, P < 0.001; males: - 0.38, P < 0.001). In contrast, LVC was independent of both LVEDV and LBM [LVC = LVM/(LVEDV0.40 × LBM0.50)] leading to increased overlap between LV hypertrophy and higher concentricity. CONCLUSIONS: We validated allometric coefficients for LBM-based scaling for CMR indexed parameters relevant for classifying geometric patterns of ventricular remodeling.

DeepEZ: A Graph Convolutional Network for Automated Epileptogenic Zone Localization From Resting-State fMRI Connectivity.

OBJECTIVE: Epileptogenic zone (EZ) localization is a crucial step during diagnostic work up and therapeutic planning in medication refractory epilepsy. In this paper, we present the first deep learning approach to localize the EZ based on resting-state fMRI (rs-fMRI) data. METHODS: Our network, called DeepEZ, uses a cascade of graph convolutions that emphasize signal propagation along expected anatomical pathways. We also integrate domain-specific information, such as an asymmetry term on the predicted EZ and a learned subject-specific bias to mitigate environmental confounds. RESULTS: We validate DeepEZ on rs-fMRI collected from 14 patients with focal epilepsy at the University of Wisconsin Madison. Using cross validation, we demonstrate that DeepEZ achieves consistently high EZ localization performance (Accuracy: 0.88 ± 0.03; AUC: 0.73 ± 0.03) that far outstripped any of the baseline methods. This performance is notable given the variability in EZ locations and scanner type across the cohort. CONCLUSION: Our results highlight the promise of using DeepEZ as an accurate and noninvasive therapeutic planning tool for medication refractory epilepsy. SIGNIFICANCE: While prior work in EZ localization focused on identifying localized aberrant signatures, there is growing evidence that epileptic seizures affect inter-regional connectivity in the brain. DeepEZ allows clinicians to harness this information from noninvasive imaging that can easily be integrated into the existing clinical workflow.

Combined liver transplantation and sleeve gastrectomy: Report of a brief-interval staged approach.

Pretransplantation bariatric surgery in patients with high Model for End-Stage Liver Disease (MELD) score is fraught with risks. Bariatric surgery after liver transplantation (LT) may be complicated by surgical adhesions but could have advantages if performed at the time of transplantation. We investigated a method of brief-interval staging combining LT and sleeve gastrectomy (SG). LT recipients with a body mass index (BMI) > 40 kg/m 2 received an SG during the same hospitalization as the LT (LT/SG), at the same time as a planned brief-interval return to the operating room for biliary anastomosis. Differences in intraoperative attributes of the LT (Stage 1) versus SG (Stage 2) procedures were analyzed using Wilcoxon signed-rank test with significance p < 0.05 and compared with patients with obesity having a two-stage LT without SG. A total of 14 cases {median MELD score 33 (interquartile range [IQR], 18-40)} were compared with 28 controls; 60% were critically ill prior to surgery with mechanical ventilation, vasopressors, or continuous renal replacement therapy. Median interval between procedures was 16.1 (IQR, 12.5-22.7) hours for cases and 12.2 (IQR, 11.1-16.6) hours for controls, p  = 0.27. Median BMI at LT/SG was 47.0 (IQR, 41.7-51.3) kg/m 2 versus 38.1 (IQR, 35.7-39.8) kg/m 2 for controls, p < 0.001. At 1 year, median excess body weight loss was 74.0% (IQR, 46.2%-78.7%) in cases and 15.8% (IQR, -5.4% to 62.6%) in controls, p  = 0.13; total weight loss was 38.1% (IQR, 23.9-42.9) in cases versus 7.7% (IQR, -2.4% to 27.6%) for controls, p  = 0.03. Graft survival at 1 year was 92.9% for cases and 89.3% for controls with similar early postoperative outcomes. This proof-of-concept study revealed that a brief-interval SG during LT is feasible in patients with high MELD and resulted in sustained weight loss at 1 year with similar graft survival. Further studies are needed to determine an optimal strategy.