Citations

In this study, a mixed porcine–human bioengineered liver (MPH-BEL) was used in a preclinical setup of extracorporeal liver support devices as a treatment for a model of post-resection liver failure (PRLF). The potential for human clinical application is further illustrated by comparing the functional capacity of MPH-BEL grafts as assessed using this porcine PRLF model with fully human (FH-BEL) grafts which were perfused and assessed in vitro. BEL grafts were produced by reseeding liver scaffolds with HUVEC and primary porcine hepatocytes (MPH-BEL) or primary human hepatocytes (FH-BEL). PRLF was induced by performing an 85% liver resection in domestic white pigs and randomized into the following three groups 24 h after resection: standard medical therapy (SMT) alone, SMT + extracorporeal circuit (ECC), and SMT + MPH-BEL. The detoxification and metabolic functions of the MPH-BEL grafts were compared to FH-BEL grafts which were perfused in vitro. During the 24 h treatment interval, INR values normalized within 18 h in the MPH-BEL therapy group and urea synthesis increased as compared to the SMT and SMT + ECC control groups. The MPH-BEL treatment was associated with more rapid decline in hematocrit and platelet count compared to both control groups. Histological analysis demonstrated platelet sequestration in the MPH-BEL grafts, possibly related to immune activation. Significantly higher rates of ammonia clearance and metabolic function were observed in the FH-BEL grafts perfused in vitro than in the MPH-BEL grafts. The MPH-BEL treatment was associated with improved markers of liver function in PRLF. Further improvement in liver function in the BEL grafts was observed by seeding the biomatrix with human hepatocytes. Methods to reduce platelet sequestration within BEL grafts is an area of ongoing research.

Background: While the biomechanical properties of the native medial patellofemoral ligament (MPFL) have been well studied, there is no comprehensive summary of the biomechanics of MPFL reconstruction (MPFLR). An accurate understanding of the kinematic properties and functional behavior of current techniques used in MPFLR is imperative to restoring native biomechanics and improving outcomes. Purpose: To provide a comprehensive review of the biomechanical effects of variations in MPFLR, specifically to determine the effect of graft choice and reconstruction technique. Study Design: Systematic review. Methods: A systematic review was performed in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A total of 32 studies met inclusion criteria: (1) using ≥8 human cadaveric specimens, (2) reporting on a component of MPFLR, and (3) having multiple comparison groups. Results: Gracilis, semitendinosus, and quadriceps grafts demonstrated an ultimate load to failure (N) of 206.2, 102.8, and 190.0 to 205.0 and stiffness (N/mm) of 20.4, 8.5, and 21.4 to 33.6, respectively. Single-bundle and double-bundle techniques produced an ultimate load to failure (N) of 171 and 213 and stiffness (N/mm) of 13.9 and 17.1, respectively. Anchors placed centrally and superomedially in the patella produced the smallest degree of length changes throughout range of motion in contrast to anchors placed more proximally. Sutures, suture anchors, and transosseous tunnels all produced similar ultimate load to failure, stiffness, and elongation data. Femoral tunnel malpositioning resulted in significant increases in contact pressures, patellar translation, tilt, and graft tightening or loosening. Low tension grafts (2 N) most closely restored the patellofemoral contact pressures, translation, and tilt. Graft fixation angles variably and inconsistently altered contact pressures, and patellar translation and tilt. Conclusion: Data demonstrated that placement of the MPFLR femoral tunnel at the Schöttle point is critical to success. Femoral tunnel diameter should be ≥2 mm greater than graft diameter to limit graft advancement and overtensioning. Graft fixation, regardless of graft choice or fixation angle, is optimally performed under minimal tension with patellar fixation at the medial and superomedial patella. However, lower fixation angles may reduce graft strain, and higher fixation angles may exacerbate anisometry and length changes if femoral tunnel placement is nonanatomic.

Background: Basidiobolomycosis is a rare fungal infection caused by Basidiobolus ranarum. Case Presentation: A 53-year-old man from Saudi Arabia with a known history of diverticulosis presented with severe abdominal pain and diarrhea. A CT scan revealed circumferential wall thickening of the descending and sigmoid colon with surrounding fat stranding, suggesting a diagnosis of complicated diverticulitis. Additional thick fluid was observed around the affected area. Surgical excision was pursued. A gross examination of two received large bowel segments disclosed marked ulcerated mucosa and wall thickening with exudate-covered serosal surfaces and adhesions. Microscopic examination unveiled significant infiltration by eosinophils, polymorphonuclear leukocytes, and granulomatous inflammation. Thin-walled, broad fungal hyphae of Basidiobolus, surrounded by eosinophilic material, were identified. Granulomas displayed abundant multinucleated giant cells and palisading histiocytes around central necrosis or abscess formation. Thin-walled, broad fungal hyphae of Basidiobolus, with sparse septations, are surrounded by a radiating, intensely eosinophilic cuff (Splendore-Hoeppli phenomenon). These hyphae, visible with hematoxylin and eosin staining, were further highlighted with periodic acid-Schiff and Gomori methenamine silver staining. Discussion: Basidiobolomycosis may mimic neoplastic lesions. Histologically, the characteristic features include broad, thin-walled septate hyphae surrounded by eosinophilic material, a finding that is accentuated by the Splendore-Hoeppli phenomenon. Microscopic examination, along with special stains such as periodic acid-Schiff (PAS) and Gomori methenamine silver, is essential for accurate diagnosis. Conclusion: Prompt recognition and appropriate antifungal therapy are vital for favorable patient outcomes. This report highlights the distinctive features of Basidiobolomycosis to raise awareness and understanding of this infrequent yet clinically significant fungal infection.

AbstractThe bond between humans and dogs is precious and has been treasured since ancient times. Dog ownership is linked to numerous health benefits, such as increased physical activity and social functioning and decreased depression and cardiovascular events. However, dogs can transmit zoonotic diseases to humans, many of which present with cutaneous findings. This review summarizes the dermatologic manifestations, transmission routes, diagnosis, and treatment of zoonotic diseases transmitted by dogs, including vector‐borne, bacterial, viral, fungal, and parasitic infections. This review emphasizes the significance of clinicians obtaining a comprehensive exposure history when patients exhibit a rash of unknown origin. Such an approach can provide valuable epidemiological clues related to diagnosing a zoonotic disease transmitted by a pet dog. Furthermore, identifying the dog as an infection source and subsequent veterinary treatment can help prevent recurrent infections in dermatologic patients.

AbstractObjectivesThe main goal of presurgical evaluation in drug‐resistant focal epilepsy is to identify a seizure onset zone (SOZ). Of the noninvasive, yet resource‐intensive tests available, ictal single‐photon emission computed tomography (SPECT) aids SOZ localization by measuring focal increases in blood flow within the SOZ via intravenous peri‐ictal radionuclide administration. Recent studies indicate that geographic and center‐specific factors impact utilization of these diagnostic procedures. Our study analyzed successful ictal SPECT acquisition (defined as peri‐ictal injection during inpatient admission) using surgery‐related data from the Pediatric Epilepsy Research Consortium (PERC) surgery database. We hypothesized that a high seizure burden, longer duration of video EEG monitoring (VEEG), and more center‐specific hours of SPECT availability would increase the likelihood of successful ictal SPECT.MethodsWe identified study participants (≤18 years of age) who underwent SPECT as part of their phase 1 VEEG from January 2018 to June 2022. We assessed association between ictal SPECT outcomes (success vs. failure) and variables including patient demographics, epilepsy history, and center‐specific SPECT practices.ResultsPhase 1 VEEG monitoring with ictal SPECT injection was planned in 297 participants and successful in 255 participants (85.86%). On multivariable analysis, the likelihood of a successful SPECT injection was higher in patients of non‐Hispanic ethnicity (p = 0.040), shorter duration VEEG (p = 0.004), and higher hours of available SPECT services (p < 0.001). Higher seizure frequency (p = 0.033) was significant only in bivariate analysis. Patients treated at centers with more operational hours were more likely to experience pre‐admission protocols prior to VEEG (p = 0.002).SignificanceThere is inter‐center variability in protocols and SPECT acquisition capabilities. Shorter duration of EEG monitoring, non‐Hispanic ethnicity (when on private insurance), extended operational hours of nuclear medicine as noted on multivariate analysis and higher seizure frequency in bivariate analysis are strongly associated with successful ictal SPECT injection.Plain Language SummaryIn pediatric patients with drug‐resistant epilepsy, single‐photon emission computed tomography (SPECT) scans can be helpful in localizing seizure onset zone. However, due to many logistical challenges described below, which include not only the half‐life of the technetium isotope used to inject intravenously during a seizure (called the ictal SPECT scan) but also available nuclear scanner time in addition to the unpredictability of seizures, obtaining an ictal SPECT during a planned elective inpatient hospital stay is not guaranteed. Thus, as healthcare costs increase, planning a prolonged hospital stay during which an ictal SPECT scan is not feasible is not optimal. We leveraged our prospective surgery database to look at center‐specific factors and patient‐specific factors associated with an ictal SPECT injection in the first, pediatric‐focussed, large‐scale, multicenter, prospective, SPECT feasibility study. We found that longer availability of the scanner is the most important center‐specific factor in assuring ictal SPECT injection. Although seizure frequency is an important patient‐specific factor on bivariate analysis, this factor lost statistical significance when other factors like patient insurance status and video EEG duration were also considered in our multivariable logistical model.

Abstract Estimates of plant traits derived from hyperspectral reflectance data have the potential to efficiently substitute for traits, which are time or labor intensive to manually score. Typical workflows for estimating plant traits from hyperspectral reflectance data employ supervised classification models that can require substantial ground truth datasets for training. We explore the potential of an unsupervised approach, autoencoders, to extract meaningful traits from plant hyperspectral reflectance data using measurements of the reflectance of 2151 individual wavelengths of light from the leaves of maize ( Zea mays ) plants harvested from 1658 field plots in a replicated field trial. A subset of autoencoder‐derived variables exhibited significant repeatability, indicating that a substantial proportion of the total variance in these variables was explained by difference between maize genotypes, while other autoencoder variables appear to capture variation resulting from changes in leaf reflectance between different batches of data collection. Several of the repeatable latent variables were significantly correlated with other traits scored from the same maize field experiment, including one autoencoder‐derived latent variable (LV8) that predicted plant chlorophyll content modestly better than a supervised model trained on the same data. In at least one case, genome‐wide association study hits for variation in autoencoder‐derived variables were proximal to genes with known or plausible links to leaf phenotypes expected to alter hyperspectral reflectance. In aggregate, these results suggest that an unsupervised, autoencoder‐based approach can identify meaningful and genetically controlled variation in high‐dimensional, high‐throughput phenotyping data and link identified variables back to known plant traits of interest.

IntroductionAlzheimer's disease (AD) is a neurodegenerative disease with neurogenic fiber tangles caused by amyloid-β protein plaques and tau protein hyperphosphorylation as the pathological manifestations. This study was based on multi-omics to investigate the mechanisms and immune characterization of AD.Material and methodsBased on bulk RNA-seq (GSE122063 and GSE97760), we screened potential biomarkers for AD by differential expression analysis and machine learning algorithms. Then, we elaborated the expression characteristics and immune functions of the above biomarkers by scRNA-seq (single-cell RNA sequencing) data analysis (GSM4996463 and GSM4996462) and immune infiltration analysis.ResultsFive biomarkers (RBM3, GOLGA8A, ALS2, FSD2, and LOC100287628) were identified using machine learning algorithms. Single-cell analysis revealed distinct expression patterns of these biomarkers in astrocytes from AD samples compared to normal samples. Additionally, three key biomarkers were selected based on interaction networks, and the diagnostic models indicated high diagnostic efficacy for these biomarkers. Based on immune infiltration and correlation analyses, RBM3, GOLGA8A, and ALS2 were all highly correlated with CD8 T cell content in the immune microenvironment of AD.ConclusionsThe biomarkers identified in this study demonstrate significant diagnostic potential for AD. Notably, the downregulation of RBM3 in astrocytes and the decreased presence of CD8 T cells infiltrating brain tissue are potential risk factors for AD.