Journal of investigative medicine : the official publication of the American Federation for Clinical Research
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Acute lymphoblastic leukemia (ALL) is the second most common acute leukemia in adults with a poor prognosis with relapsed or refractory (R/R) B-cell lineage ALL (B-ALL). Anti-CD19 chimeric antigen receptor (CAR) T-cell therapy has shown excellent response rates in RR B-ALL, but most patients relapse due to poor persistence of CAR T-cell therapy or other tumor-associated escape mechanisms. ⋯ In this review, we will discuss novel CAR targets, CAR constructs, and various strategies to boost CARs for the treatment of RR B-ALL. In addition, we discuss a few novel strategies developed to reduce the side effects of CAR.
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The generalizability of artificial intelligence (AI) models is a major issue in the field of AI applications. Therefore, we aimed to overcome the generalizability problem of an AI model developed for a particular center for pneumothorax detection using a small dataset for external validation. Chest radiographs of patients diagnosed with pneumothorax (n = 648) and those without pneumothorax (n = 650) who visited the Ankara University Faculty of Medicine (AUFM; center 1) were obtained. ⋯ The positive predictive value increased from 0.525 to 0.886 after external validation (p = 0.041). The physicians' sensitivity and specificity for detecting pneumothorax were 0.585 and 0.988, respectively. The performance scores of the algorithms were increased with a small dataset; however, further studies are required to determine the optimal amount of external validation data to fully address the generalizability issue.
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Observational Study
Metformin Prescription for U.S. Veterans with Prediabetes, 2010-2019.
Affecting an estimated 88 million Americans, prediabetes increases the risk for developing type 2 diabetes mellitus (T2DM), and independently, cardiovascular disease, retinopathy, nephropathy, and neuropathy. Nevertheless, little is known about the use of metformin for diabetes prevention among patients in the Veterans Health Administration, the largest integrated healthcare system in the U. S. ⋯ In a multivariable model, metformin was more likely to be prescribed for those with BMI ≥35 kg/m2 incidence rate ratio [IRR] 2.6 [95% confidence intervals (CI): 2.1-3.3], female sex IRR, 2.4 [95% CI: 1.8-3.3], HbA1c≥6% IRR, 1.93 [95% CI: 1.5-2.4], age <60 years IRR, 1.7 [95% CI: 1.3-2.3], hypertriglyceridemia IRR, 1.5 [95% CI: 1.2-1.9], hypertension IRR, 1.5 [95% CI: 1.1-2.1], Major Depressive Disorder IRR, 1.5 [95% CI: 1.1-2.0], or schizophrenia IRR, 2.1 [95% CI: 1.2-3.8]. Over 20% of Veterans with prediabetes attended a comprehensive structured lifestyle modification clinic or program. Among Veterans with prediabetes, metformin was prescribed to 1.1% overall, a proportion that marginally increased to 1.6% in the subset of individuals at highest risk for progression to T2DM.
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Dysregulated cholesterol metabolism represents an increasingly recognized feature of autism spectrum disorder (ASD). Children with fetal valproate syndrome caused by prenatal exposure to valproic acid (VPA), an anti-epileptic and mood-stabilizing drug, have a higher incidence of developing ASD. However, the role of VPA in cholesterol homeostasis in neurons and microglial cells remains unclear. ⋯ VPA exposure significantly reduced protein levels of ABCA1 in a dose-dependent manner, but increased the ABCG1 protein level at the highest dose in SH-SY5Y cells. In addition, VPA treatment significantly increased cholesterol efflux in SH-SY5Y, but had no impact on efflux in HMC3. VPA differentially controls the expression of ABCA1 and ABCG1, but regulation at the transcriptional and translational levels are not consistent and changes in the expression of these genes do not correlate with cholesterol efflux in vitro.
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Atrial fibrillation (AF) frequently occurs concurrently with heart failure (HF). The two conditions can exacerbate each other, resulting in higher morbidity and mortality. In our analysis, we evaluated mortality trends related to AF in individuals with underlying HF. ⋯ Our results demonstrate existing disparities among age, gender, racial, and geographic subgroups related to AF mortality among individuals with comorbid HF. Although decreased overall mortality was observed within younger populations compared to older populations, the prominent AAPC seen in younger populations warrants further investigation. Detection of AF among younger adults with comorbid HF should prompt the intensification of preventative and treatment measures.