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This document provides concise summaries of several research studies related to medical imaging techniques and their applications in diagnosing and treating various diseases. The studies cover a wide range of topics, including the use of AI algorithms in breast cancer detection, the effectiveness of diffusion tensor imaging in diagnosing brain tumors, and the use of PET imaging in detecting neurodegenerative diseases. The studies offer valuable insights into the potential benefits and limitations of these imaging techniques, but further research and validation are needed to confirm these findings. [Extracted from the article]

Simple Summary: Trypanosoma cruzi infection causes Chagas disease in dogs and people by damaging the heart with inflammation and fibrosis, resulting in heart enlargement, abnormal function, and irregular heart rhythms. Cardiac magnetic resonance imaging can detect damage to the heart in people with Chagas disease even when other diagnostic tests cannot. The objectives of this study were to describe cardiac magnetic resonance imaging in naturally infected, asymptomatic dogs with chronic Chagas disease and the frequency of abnormalities for cardiac magnetic resonance imaging and other diagnostic tests, including cardiac ultrasound, electrocardiography, and the cardiac biomarker troponin I. In 10 chronically infected dogs. Abnormal findings were present most often with cardiac magnetic resonance imaging (seven dogs) followed by ultrasound (six dogs), electrocardiography (four dogs), and troponin (one dog). Cardiac magnetic resonance imaging abnormalities included increased fibrosis and abnormal wall motion of the heart. The results of this study suggest cardiac magnetic resonance imaging can provide useful information in dogs with T. cruzi infection and may support naturally infected dogs for future clinical investigation as an animal model for Chagas disease. Trypanosoma cruzi infection causes inflammation and fibrosis, resulting in cardiac damage in dogs. The objectives of this study were to describe cardiac magnetic resonance imaging (CMR) in naturally infected dogs with chronic Chagas disease and the frequency of abnormalities for CMR and cardiac diagnostic tests. Ten asymptomatic, client-owned dogs seropositive for T. cruzi were prospectively enrolled in an observational study evaluating echocardiography, ECG (standard and ambulatory), cardiac troponin I (cTnI), and CMR. Standard ECG measurements (3/10) and cTnI concentration (1/10) outside the reference range were uncommon. Ambulatory ECG abnormalities were documented more frequently (6/10 dogs) than with standard ECG and included ventricular arrhythmias (4), supraventricular premature beats (3), second-degree atrioventricular block (2), and sinus arrest (1). Echocardiographic abnormalities were documented in 6/10 dogs including mildly increased left ventricular internal dimension in diastole (1) and decreased right ventricular (RV) systolic function based on reductions in tricuspid annular plane systolic excursion (3) and RV S' (4). Abnormalities were detected with CMR in 7/10 dogs including delayed myocardial enhancement in 5 of which 2 also had increased extracellular volume, abnormal wall motion in 5, and loss of apical compact myocardium in 1. In conclusion, CMR abnormalities were common, and the results of this study suggest CMR can provide useful information in dogs with T. cruzi infection and may support naturally infected dogs for future clinical investigation as an animal model for Chagas disease. [ABSTRACT FROM AUTHOR]

Hypophosphatasia (HPP) is the inherited error‐of‐metabolism caused by mutations in ALPL, reducing the function of tissue‐nonspecific alkaline phosphatase (TNAP/TNALP/TNSALP). HPP is characterized by defective skeletal and dental mineralization and is categorized into several clinical subtypes based on age of onset and severity of manifestations, though premature tooth loss from acellular cementum defects is common across most HPP subtypes. Genotype–phenotype associations and mechanisms underlying musculoskeletal, dental, and other defects remain poorly characterized. Murine models that have provided significant insights into HPP pathophysiology also carry limitations including monophyodont dentition, lack of osteonal remodeling of cortical bone, and differing patterns of skeletal growth. To address this, we generated the first gene‐edited large‐animal model of HPP in sheep via CRISPR/Cas9‐mediated knock‐in of a missense mutation (c.1077C>G; p.I359M) associated with skeletal and dental manifestations in humans. We hypothesized that this HPP sheep model would recapitulate the human dentoalveolar manifestations of HPP. Compared to wild‐type (WT), compound heterozygous (cHet) sheep with one null allele and the other with the targeted mutant allele exhibited the most severe alveolar bone, acellular cementum, and dentin hypomineralization defects. Sheep homozygous for the mutant allele (Hom) showed alveolar bone and hypomineralization effects and trends in dentin and cementum, whereas sheep heterozygous (Het) for the mutation did not exhibit significant effects. Important insights gained include existence of early alveolar bone defects that may contribute to tooth loss in HPP, observation of severe mantle dentin hypomineralization in an HPP animal model, association of cementum hypoplasia with genotype, and correlation of dentoalveolar defects with alkaline phosphatase (ALP) levels. The sheep model of HPP faithfully recapitulated dentoalveolar defects reported in individuals with HPP, providing a new translational model for studies into etiopathology and novel therapies of this disorder, as well as proof‐of‐principle that genetically engineered large sheep models can replicate human dentoalveolar disorders. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR). [ABSTRACT FROM AUTHOR]

Children obese at the age of 5 years are at greater risk of lifelong obesity. Because certain risks of obesity can be identified in early infancy, a tool for obesity risk prediction in early life would be clinically useful. We investigated predictors of obesity risk in a novel, prospectively collected healthy birth cohort recruited for demographic risks to develop iron deficiency at 1 year, a cohort leveraged because risk factors for iron deficiency and obesity overlap. Obesity at the age of 5 years was defined as age- and sex-specific body mass index Z -score (z BMI) >2SD. For each child, obesity risk factors were summed. Of 10 total risk factors, the following 4 key risks were identified: maternal obesity, maternal diabetes, large for gestational age, or breastfeeding <6 months. Childhood obesity was predicted by either ≥3 total number of risks (P <.033), any key risk (P <.002), or summing key risks (P <.0001). In clinical practice, summing early life risk factors may be a useful strategy for preemptive counseling. [ABSTRACT FROM AUTHOR]

Nerve agents (NAs) produce acute and long‐term brain injury and dysfunction, as evident from the Japan and Syria incidents. Magnetic resonance imaging (MRI) is a versatile technique to examine such chronic anatomical, functional, and neuronal damage in the brain. The objective of this study was to investigate long‐term structural and neuronal lesion abnormalities in rats exposed to acute soman intoxication. T2‐weighted MRI images of 10 control and 17 soman‐exposed rats were acquired using a Siemens MRI system at 90 days after soman exposure. Quantification of brain tissue volumes and T2 signal intensity was conducted using the Inveon Research Workplace software and the extent of damage was correlated with histopathology and cognitive function. Soman‐exposed rats showed drastic hippocampal atrophy with neuronal loss and reduced hippocampal volume (HV), indicating severe damage, but had similar T2 relaxation times to the control group, suggesting limited scarring and fluid density changes despite the volume decrease. Conversely, soman‐exposed rats displayed significant increases in lateral ventricle volumes and T2 times, signifying strong cerebrospinal fluid expansion in compensation for tissue atrophy. The total brain volume, thalamic volume, and thalamic T2 time were similar in both groups, however, suggesting that some brain regions remained more intact long‐term after soman intoxication. The MRI neuronal lesions were positively correlated with the histological markers of neurodegeneration and neuroinflammation 90 days after soman exposure. The predominant MRI hippocampal atrophy (25%) was highly consistent with massive reduction (35%) of neuronal nuclear antigen–positive (NeuN+) principal neurons and parvalbumin‐positive (PV+) inhibitory interneurons within this brain region. The HV was significantly correlated with both inflammatory markers of GFAP+ astrogliosis and IBA1+ microgliosis. The reduced HV was also directly correlated with significant memory deficits in the soman‐exposed cohort, confirming a possible neurobiological basis for neurological dysfunction. Together, these findings provide powerful insight on long‐term region‐specific neurodegenerative patterns after soman exposure and demonstrate the feasibility of in vivo neuroimaging to monitor neuropathology, predict the risk of neurological deficits, and evaluate response to medical countermeasures for NAs. [ABSTRACT FROM AUTHOR]

Objective  Obesity during pregnancy impedes fetal iron endowment. In adults, both iron depletion and hypoxia stimulate erythropoietin (Epo) production, while hepcidin, the primary iron regulator, is inhibited by Epo and stimulated by obesity. To understand this relationship in fetuses, we investigated obesity, inflammation, and fetal iron status on fetal Epo and hepcidin levels. Study Design  Epo, hepcidin, C-reactive protein (CRP), and ferritin levels were measured in 201 newborns of 35 to 40 weeks' gestation with historical risk factors for a low fetal iron endowment, including half with maternal obesity. Results  Epo was unrelated to fetal size, but Epo was directly related to maternal body mass index (BMI; kg/m 2) (p  < 0.03) and CRP (p  < 0.0005) at delivery. Epo levels were twice as likely to be elevated (≥50 IU/L) while comparing the lowest quartile of ferritin with the upper three quartiles (p  < 0.01). Hepcidin was directly related to ferritin (p  < 0.001) and indirectly related to maternal BMI (p  < 0.015), but BMI became nonsignificant when undergoing multivariate analysis. Hepcidin was unrelated to Epo. Conclusion  Although some of the fetal responses involving Epo were similar to adults, we did not find a hepcidin–Epo relationship like that of adults, where fetal liver is the site of both hepcidin and Epo production. [ABSTRACT FROM AUTHOR]

The availability of tools to accurately replicate the clinical phenotype of rare human diseases is a key step toward improved understanding of disease progression and the development of more effective therapeutics. We successfully generated the first large animal model of a rare human bone disease, hypophosphatasia (HPP) using CRISPR/Cas9 to introduce a single point mutation in the tissue nonspecific alkaline phosphatase (TNSALP) gene (ALPL) (1077 C > G) in sheep. HPP is a rare inherited disorder of mineral metabolism that affects bone and tooth development, and is associated with muscle weakness. Compared to wild-type (WT) controls, HPP sheep have reduced serum alkaline phosphatase activity, decreased tail vertebral bone size, and metaphyseal flaring, consistent with the mineralization deficits observed in human HPP patients. Computed tomography revealed short roots and thin dentin in incisors, and reduced mandibular bone in HPP vs. WT sheep, accurately replicating odonto-HPP. Skeletal muscle biopsies revealed aberrant fiber size and disorganized mitochondrial cristae structure in HPP vs. WT sheep. These genetically engineered sheep accurately phenocopy human HPP and provide a novel large animal platform for the longitudinal study of HPP progression, as well as other rare human bone diseases. [ABSTRACT FROM AUTHOR]

Purpose: Metabolic dysfunction in Duchenne muscular dystrophy (DMD) is characterized by reduced glycolytic and oxidative enzymes, decreased and abnormal mitochondria, decreased ATP, and increased oxidative stress. We analyzed glucose metabolism as a potential disease biomarker in the genetically homologous golden retriever muscular dystrophy (GRMD) dog with molecular, biochemical, and in vivo imaging.Procedures: Pelvic limb skeletal muscle and left ventricle tissue from the heart were analyzed by mRNA profiling, qPCR, western blotting, and immunofluorescence microscopy for the primary glucose transporter (GLUT4). Physiologic glucose handling was measured by fasting glucose tolerance test (GTT), insulin levels, and skeletal and cardiac positron emission tomography/X-ray computed tomography (PET/CT) using the glucose analog 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG).Results: MRNA profiles showed decreased GLUT4 in the cranial sartorius (CS), vastus lateralis (VL), and long digital extensor (LDE) of GRMD vs. normal dogs. QPCR confirmed GLUT4 downregulation but increased hexokinase-1. GLUT4 protein levels were not different in the CS, VL, or left ventricle but increased in the LDE of GRMD vs. normal. Microscopy revealed diffuse membrane expression of GLUT4 in GRMD skeletal but not cardiac muscle. GTT showed higher basal glucose and insulin in GRMD but rapid tissue glucose uptake at 5 min post-dextrose injection in GRMD vs. normal/carrier dogs. PET/ CT with [18F]FDG and simultaneous insulin stimulation showed a significant increase (p = 0.03) in mean standard uptake values (SUV) in GRMD skeletal muscle but not pelvic fat at 5 min post-[18F]FDG /insulin injection. Conversely, mean cardiac SUV was lower in GRMD than carrier/normal (p < 0.01).Conclusions: Altered glucose metabolism in skeletal and cardiac muscle of GRMD dogs can be monitored with molecular, biochemical, and in vivo imaging studies and potentially utilized as a biomarker for disease progression and therapeutic response. [ABSTRACT FROM AUTHOR]

Objective:Maternal iron needs increase sixfold during pregnancy, but obesity interferes with iron absorption. We hypothesized that maternal obesity impairs fetal iron status.Study Design:Three hundred and sixteen newborns with risk factors for infantile iron deficiency anemia (IDA) were studied to examine obesity during pregnancy and neonatal iron status. Erythrocyte iron was assessed by cord blood hemoglobin (Hb), zinc protoporphyrin/heme (ZnPP/H) and reticulocyte-ZnPP/H, and storage iron by serum ferritin.Result:Women with body mass index (BMI) ⩾30 kg m−2, as compared with non-obese women, delivered larger offspring with higher reticulocyte-ZnPP/H and lower serum ferritin concentrations (P<0.05 for both). With increasing BMI, the estimated body iron was relatively lower (mg kg−1) and the ratio of total Hb-bound iron (mg) per total body iron (mg) increased. Maternal diabetes compromised infant iron status, but multivariate analysis demonstrated that obesity was an independent predictor.Conclusion:Obesity during pregnancy and excessive weight gain are independent risk factors for iron deficiency in the newborn. [ABSTRACT FROM AUTHOR]

Much of the literature on team learning views experience as a unidimensional concept captured by the cumulative production volume of, or the number of projects completed by, a team. Implicit in this approach is the assumption that teams are stable in their membership and internal organization. In practice, however, such stability is rare, because the composition and structure of teams often change over time (e.g., between projects). In this paper, we use detailed data from an Indian software services firm to examine how such changes may affect the accumulation of experience within, and the performance of, teams. We find that the level of team familiarity (i.e., the average number of times that each member has worked with every other member of the team) has a significant positive effect on performance, but we observe that conventional measures of the experience of individual team members (e.g., years at the firm) are not consistently related to performance. We do find, however, that the role experience of individuals in a team (i.e., years in a given role within a team) is associated with better team performance. Our results offer an approach for capturing the experience held by fluid teams and highlight the need to study context-specific measures of experience, including role experience. In addition, our findings provide insight into how the interactions of team members may contribute to the development of broader firm capabilities. [ABSTRACT FROM AUTHOR]

This article provides an overview of neuroimaging biomarkers in experimental epileptogenesis and refractory epilepsy. Neuroimaging represents a gold standard and clinically translatable technique to identify neuropathological changes in epileptogenesis and longitudinally monitor its progression after a precipitating injury. Neuroimaging studies, along with molecular studies from animal models, have greatly improved our understanding of the neuropathology of epilepsy, such as the hallmark hippocampus sclerosis. Animal models are effective for differentiating the different stages of epileptogenesis. Neuroimaging in experimental epilepsy provides unique information about anatomic, functional, and metabolic alterations linked to epileptogenesis. Recently, several in vivo biomarkers for epileptogenesis have been investigated for characterizing neuronal loss, inflammation, blood-brain barrier alterations, changes in neurotransmitter density, neurovascular coupling, cerebral blood flow and volume, network connectivity, and metabolic activity in the brain. Magnetic resonance imaging (MRI) is a sensitive method for detecting structural and functional changes in the brain, especially to identify region-specific neuronal damage patterns in epilepsy. Positron emission tomography (PET) and single-photon emission computerized tomography are helpful to elucidate key functional alterations, especially in areas of brain metabolism and molecular patterns, and can help monitor pathology of epileptic disorders. Multimodal procedures such as PET-MRI integrated systems are desired for refractory epilepsy. Validated biomarkers are warranted for early identification of people at risk for epilepsy and monitoring of the progression of medical interventions. [ABSTRACT FROM AUTHOR]