Combinations of idelalisib with rituximab and/or bendamustine in patients with recurrent indolent non-Hodgkin lymphoma

Key Points Combining phosphatidylinositol-3-kinase δ inhibition with rituximab, bendamustine, or both is feasible and active in relapsed iNHL. The safety of novel combinations should be proven in phase 3 trials before adoption in clinical practice.</jats:p

Discrimination Task Reveals Differences in Neural Bases of Tinnitus and Hearing Impairment

We investigated auditory perception and cognitive processing in individuals with chronic tinnitus or hearing loss using functional magnetic resonance imaging (fMRI). Our participants belonged to one of three groups: bilateral hearing loss and tinnitus (TIN), bilateral hearing loss without tinnitus (HL), and normal hearing without tinnitus (NH). We employed pure tones and frequency-modulated sweeps as stimuli in two tasks: passive listening and active discrimination. All subjects had normal hearing through 2 kHz and all stimuli were low-pass filtered at 2 kHz so that all participants could hear them equally well. Performance was similar among all three groups for the discrimination task. In all participants, a distributed set of brain regions including the primary and non-primary auditory cortices showed greater response for both tasks compared to rest. Comparing the groups directly, we found decreased activation in the parietal and frontal lobes in the participants with tinnitus compared to the HL group and decreased response in the frontal lobes relative to the NH group. Additionally, the HL subjects exhibited increased response in the anterior cingulate relative to the NH group. Our results suggest that a differential engagement of a putative auditory attention and short-term memory network, comprising regions in the frontal, parietal and temporal cortices and the anterior cingulate, may represent a key difference in the neural bases of chronic tinnitus accompanied by hearing loss relative to hearing loss alone

Effects of Bosutinib Treatment on Renal Function in Patients With Philadelphia Chromosome-Positive Leukemias

Abstract Background The purpose of the study was to assess renal function in patients with Philadelphia chromosome-positive leukemias receiving bosutinib or imatinib. Patients and Methods Patients received first-line bosutinib (n = 248) or imatinib (n = 251; phase III trial), or second-line or later bosutinib (phase I/II trial; n = 570). Adverse events (AEs) and changes from baseline in estimated glomerular filtration rate (eGFR) and serum creatinine were assessed. Results Time from the last patient's first dose to data cutoff was ≥ 48 months. Renal AEs were reported in 73/570 patients (13%) receiving second-line or later bosutinib, and in 22/248 (9%) and 16/251 (6%) receiving first-line bosutinib and imatinib, respectively. eGFR in patients receiving bosutinib declined over time with more patients developing Grade ≥ 3b eGFR ( 2 according to the Modification of Diet in Renal Disease method) with second-line or later bosutinib (139/570, 24%) compared with first-line bosutinib (26/248, 10%) and imatinib (25/251, 10%); time to Grade ≥ 3b eGFR was shortest with second-line or later bosutinib. Similar proportions of patients receiving second-line or later bosutinib (74/139, 53%), first-line bosutinib (15/26, 58%), and first-line imatinib (15/25, 60%) improved to ≥ 45 mL/min/1.73 m 2 eGFR as of the last follow-up. In a regression analysis, first-line treatment with bosutinib versus imatinib was not a significant predictor of Grade ≥ 3b eGFR. Conclusion Long-term bosutinib treatment is associated with an apparently reversible decline in renal function with frequency and characteristics similar to renal decline observed with long-term imatinib treatment. Patients with risk factors for Grade ≥ 3b eGFR should be monitored closely

Integration and Implementation Strategies for AI Algorithm Deployment with Smart Routing Rules and Workflow Management

This paper reviews the challenges hindering the widespread adoption of artificial intelligence (AI) solutions in the healthcare industry, focusing on computer vision applications for medical imaging, and how interoperability and enterprise-grade scalability can be used to address these challenges. The complex nature of healthcare workflows, intricacies in managing large and secure medical imaging data, and the absence of standardized frameworks for AI development pose significant barriers and require a new paradigm to address them. The role of interoperability is examined in this paper as a crucial factor in connecting disparate applications within healthcare workflows. Standards such as DICOM, Health Level 7 (HL7), and Integrating the Healthcare Enterprise (IHE) are highlighted as foundational for common imaging workflows. A specific focus is placed on the role of DICOM gateways, with Smart Routing Rules and Workflow Management leading transformational efforts in this area. To drive enterprise scalability, new tools are needed. Project MONAI, established in 2019, is introduced as an initiative aiming to redefine the development of medical AI applications. The MONAI Deploy App SDK, a component of Project MONAI, is identified as a key tool in simplifying the packaging and deployment process, enabling repeatable, scalable, and standardized deployment patterns for AI applications. The abstract underscores the potential impact of successful AI adoption in healthcare, offering physicians both life-saving and time-saving insights and driving efficiencies in radiology department workflows. The collaborative efforts between academia and industry, are emphasized as essential for advancing the adoption of healthcare AI solutions.Comment: 13 pages, 6 figure

A Mediterranean Low-Glycemic-Load Diet alone or in Combination with a Medical Food Improves Insulin Sensitivity and Reduces Inflammation in Women with Metabolic Syndrome

Aim: To determine the effects of a Mediterranean-style low-glycemic load diet alone or in combination with a medical food (MF) on insulin resistance and inflammation in women with metabolic syndrome (MetS). Study design: Two groups, Parallel study with control. Place and Duration of Study: Department of Nutritional Sciences, University of Connecticut, Storrs, CT; Department of Emergency Medicine, University of Florida, Jacksonville, FL; Department of Medicine, University of California, Irvine, CA. The study was carried out from September of 2009 to May 2010. Methodology: Eighty three women (20-75 y) with MetS. Participants were randomly allocated to consume diet alone (control group) or the diet plus the MF (MF group) for 12 wk. Body composition was measured at baseline, week 8 and week 12 by use of bioelectrical impedance in all participants while Dual-emission X-ray absorptiometry was used for 37 of the subjects. Insulin resistance, plasma insulin, leptin, adiponectin and the inflammatory cytokines, tumor necrosis factor (TNF)-α, interleukin-6 (IL-6), adhesion molecules, sICAM-1 and sVCAM-1, were measured at the same time points. Results: Independent of group allocation, women had decreases in body mass index (p \u3c 0.0001) and body and trunk fat (p \u3c 0.0001). Plasma insulin, insulin resistance, and leptin were also significantly decreased over time (p \u3c 0.0001), while plasma adiponectin levels did not change. Regarding inflammatory markers, significant reductions were found in TNF-α (p \u3c 0.0001) and sICAM-1 levels (p \u3c 0.001), but not in IL-6 or sVCAM-1. At 12 wk, sICAM was reduced only in the MF group (

Quantum interference experiments, modular variables and weak measurements

We address the problem of interference using the Heisenberg picture and highlight some new aspects through the use of pre-selection, post-selection, weak measurements, and modular variables, We present a physical explanation for the different behaviors of a single particle when the distant slit is open or closed: instead of having a quantum wave that passes through all slits, we have a localized particle with non-local interactions with the other slit(s). We introduce a Gedankenexperiment to measure this non-local exchange. While the Heisenberg picture and the Schrodinger pictures are equivalent formulations of quantum mechanics, nevertheless, the results discussed here support a new approach which has led to new insights, new intuitions, new experiments, and even the possibility of new devices that were missed from the old perspective

A Magnetic Bead-Integrated Chip for the Large Scale Manufacture of Normalized esiRNAs

The chemically-synthesized siRNA duplex has become a powerful and widely used tool for RNAi loss-of-function studies, but suffers from a high off-target effect problem. Recently, endoribonulease-prepared siRNA (esiRNA) has been shown to be an attractive alternative due to its lower off-target effect and cost effectiveness. However, the current manufacturing method for esiRNA is complicated, mainly in regards to purification and normalization on a large-scale level. In this study, we present a magnetic bead-integrated chip that can immobilize amplification or transcription products on beads and accomplish transcription, digestion, normalization and purification in a robust and convenient manner. This chip is equipped to manufacture ready-to-use esiRNAs on a large-scale level. Silencing specificity and efficiency of these esiRNAs were validated at the transcriptional, translational and functional levels. Manufacture of several normalized esiRNAs in a single well, including those silencing PARP1 and BRCA1, was successfully achieved, and the esiRNAs were subsequently utilized to effectively investigate their synergistic effect on cell viability. A small esiRNA library targeting 68 tyrosine kinase genes was constructed for a loss-of-function study, and four genes were identified in regulating the migration capability of Hela cells. We believe that this approach provides a more robust and cost-effective choice for manufacturing esiRNAs than current approaches, and therefore these heterogeneous RNA strands may have utility in most intensive and extensive applications

The Angular Correlation Function of Galaxies from Early SDSS Data

The Sloan Digital Sky Survey is one of the first multicolor photometric and spectroscopic surveys designed to measure the statistical properties of galaxies within the local Universe. In this Letter we present some of the initial results on the angular 2-point correlation function measured from the early SDSS galaxy data. The form of the correlation function, over the magnitude interval 18<r*<22, is shown to be consistent with results from existing wide-field, photographic-based surveys and narrower CCD galaxy surveys. On scales between 1 arcminute and 1 degree the correlation function is well described by a power-law with an exponent of ~ -0.7. The amplitude of the correlation function, within this angular interval, decreases with fainter magnitudes in good agreement with analyses from existing galaxy surveys. There is a characteristic break in the correlation function on scales of approximately 1-2 degrees. On small scales, < 1', the SDSS correlation function does not appear to be consistent with the power-law form fitted to the 1'< theta <0.5 deg data. With a data set that is less than 2% of the full SDSS survey area, we have obtained high precision measurements of the power-law angular correlation function on angular scales 1' < theta < 1 deg, which are robust to systematic uncertainties. Because of the limited area and the highly correlated nature of the error covariance matrix, these initial results do not yet provide a definitive characterization of departures from the power-law form at smaller and larger angles. In the near future, however, the area of the SDSS imaging survey will be sufficient to allow detailed analysis of the small and large scale regimes, measurements of higher-order correlations, and studies of angular clustering as a function of redshift and galaxy type