Deletion 20q12 is associated with histological transformation of nodal marginal zone lymphoma to diffuse large B-cell lymphoma.

The genetic and molecular abnormalities underlying histological transformation (HT) of nodal marginal zone lymphoma (NMZL) to diffuse large B-cell lymphoma (DLBCL) are not well known. While del(20q12) is commonly deleted in myelodysplastic syndrome it has not previously been associated with DLBCL. We recently described a case of DLBCL harboring del(20q12) in a patient with a history of MZL involving lymph nodes and skin. Here we report eight matched cases of transformed MZL(tMZL): six from nodal MZL (tNMZL) and two from splenic MZL (tSMZL). We found >20% del(20q12) in 4/6 tNMZL, but not in tSMZL, nor in unmatched DLBCL, MZL with increased large cells (MZL-ILC), or MZL cases. To examine whether transformation is associated with a specific gene signature, the matched cases were analyzed for multiplexed gene expression using the Nanostring PanCancer Pathways panel. The differential gene expression signature revealed enrichment of inflammatory markers, as previously observed in MZL. Also, tMZL and de novo DLBCL were enriched for extracellular matrix proteins such as collagen and fibronectin, vascular development protein PDGFRß, DNA repair protein RAD51, and oncogenic secrete protein Wnt11. A subset of genes is expressed differentially in del(20q12) tMZL cases vs non-del(20q12) tMZL cases. These results suggest a specific pathway is involved in the histological transformation of NMZL, which could serve as an indicator of aggressive clinical course in this otherwise indolent neoplasm.

Conformational preferences of furan- and thiophene-based arylamides: a combined computational and experimental study.

We examine the conformational preferences of the furan- and thiophene-based arylamides, N-methylfuran-2-carboxamide (3) and N-methylthiophene-2-carboxamide (4), using a combination of computational methods and NMR experiments. The compound choice stems from their use as foldamer building blocks. We quantify the differences in the conformational rigidity of the two compounds, which governs corresponding foldamer conformations. Specifically, we demonstrate the effects of intramolecular hydrogen bonding (H-bonding), geometrical patterns and solvent polarity on arylamide conformations by comparing 3, 4 and previously studied ortho-methoxy N-methylbenzamide (1) and ortho-methylthio N-methylbenzamide (2). The study reveals that compound 3, despite its non-optimal S(5)-type H-bond geometry, retains a large portion of the H-bonded (eclipsed) conformation even in polar protic solvents. This behaviour is consistent with the quantum mechanical (QM) torsional energy profile. The percentages of H-bonded conformers that 3 retains are just slightly smaller than those of 1, which has a stronger S(6)-type H-bond. As for 2 and 4, the replacement of the O atom in 1 by an S atom in 2 results in a 70­90% loss of the H-bonded conformer in solution. However, the equivalent O to S replacement in 3 (leading to 4) causes only 15­30% loss of the eclipsed conformers in 4. Therefore, conformational preferences of 4 are very different from 2, in contrast to the similarity between 3 and 1. This study shows how the interplay of several forces modulates the conformational flexibility of arylamides. It also attests the strategy we are developing, which leads to accurate prediction of foldamer structure. The vital component of this strategy is the re-parameterization of critical force field parameters based on QM potential energy profiles, as well as validation of these parameters using experimental data in solution.

Saliva versus Upper Respiratory Swabs: Equivalent for Severe Acute Respiratory Syndrome Coronavirus 2 University Screening while Saliva Positivity Is Prolonged After Symptom Onset in Coronavirus Disease 2019 Hospitalized Patients.

Reopening of schools and workplaces during the ongoing coronavirus disease 2019 (COVID-19) pandemic requires affordable and convenient population-wide screening methods. Although upper respiratory swab is considered the preferable specimen for testing, saliva offers several advantages, such as easier collection and lower cost. In this study, we compared the performance of saliva with upper respiratory swab for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection. Paired saliva and anterior nares specimens were collected from a largely asymptomatic cohort of students, faculty, and staff from the University of Pennsylvania. Paired saliva and combined nasopharyngeal/oropharyngeal (NP/OP) specimens were also collected from hospitalized patients with symptomatic COVID-19 following confirmatory testing. All study samples were tested by real-time PCR in the Hospital of the University of Pennsylvania. In the university cohort, positivity rates were 37 of 2500 for saliva (sensitivity, 86.1%) and 36 of 2500 for anterior nares (sensitivity, 83.7%), with an overall agreement of 99.6%. In the hospital study cohort, positivity rates were 35 of 49 for saliva (sensitivity, 89.3%) and 28 of 49 for NP/OP (sensitivity, 75.8%), with an overall agreement of 75.6%. A larger proportion of saliva than NP/OP samples tested positive after 4 days of symptom onset in hospitalized patients. Our results show that saliva has an acceptable sensitivity and is comparable to upper respiratory swab, supporting the use of saliva for SARS-CoV-2 detection in both symptomatic and asymptomatic populations.

Dynamic changes of elasticity, cross-sectional area, and fat infiltration of multifidus at different postures in men with chronic low back pain.

BACKGROUND CONTEXT: Multifidus cross-sectional area was often measured in chronic low back pain (LBP) patients to estimate the muscle activity for spinal stability. However, such estimation may be inadequate as the contribution of muscle elasticity in muscle activity is ignored. In vivo quantitative data on multifidus elasticity is therefore important for the study of muscle contractile function in response to motor control for spinal stability in chronic LBP patients. PURPOSE: The purpose of this study was to quantify the elasticity, cross-sectional area, and fat area of the multifidus for the contractile function and the distribution of deformable muscle tissue and nondeformable fat tissue at different postures in patients with and without chronic LBP. STUDY DESIGN/SETTING: This is a prospective study. Force-deformation data of the multifidus were acquired using ultrasound elastography. The anatomical changes of the multifidus were measured on the cross-sectional images of the multifidus acquired using B-mode ultrasound imaging. PATIENT SAMPLE: The sample comprised 12 adult male patients with chronic LBP and 12 asymptomatic male controls. OUTCOME MEASURES: The outcome measure was the elasticity of the multifidus at the L4 level for the assessment of muscle contractile function when patients were in the prone, upright, and 25° and 45° forward stooping positions. The cross-sectional area and fat area were also measured on the B-mode ultrasound images of the multifidus acquired at the same vertebral level and the postures. METHODS: With the patients in each of the prone, upright, and 25° and 45° forward stooping positions, ultrasound elastography and B-mode ultrasound imaging were performed on the left and right multifidus at the L4 level. The elasticity of multifidus indicated by the effective Young's modulus was derived from the force-deformation data acquired using ultrasound elastography. The cross-sectional area and fat area were assessed on the B-mode ultrasound images. The effective Young's modulus, cross-sectional area, and fat area were analyzed with multivariate general linear model analysis to investigate the possible effects of LBP and posture. RESULTS: There was an increasing stiffness of multifidus demonstrated by increasing effective Young's modulus from the prone to upright position and 25° and 45° forward stooping positions. Differences in multifidus stiffness between chronic LBP patients and asymptomatic controls were shown in the upright and 25° and 45° forward stooping positions but not in the prone position. The cross-sectional area of the multifidus increased from the prone position to the greatest value in the upright position and decreased in 25° and 45° forward stooping positions. Smaller multifidus cross-sectional area was demonstrated in chronic LBP patients than that in controls at all postures. No effect of posture on fat area within the multifidus was shown although the fat area within the multifidus was larger in chronic LBP patients. CONCLUSIONS: Different, changing patterns of elasticity and cross-sectional area were identified in the multifidus in relation to posture. Increased stiffness of multifidus in response to the physiologic range of static loads and smaller cross-sectional area was characterized in the chronic LBP condition for spinal stability. Ultrasound elastography offers in vivo assessment of muscle contractile function of deep trunk muscles, which benefits the future investigation of the neuromuscular regulating mechanism in LBP. It can also be applied to refine the palpatory skill for the physical assessment in sports training and physical therapy.