Proportion of physicians who treat patients with greater social and clinical risk and physician inclusion in Medicare Advantage networks

IMPORTANCE: Medicare Advantage (MA) plans are expanding rapidly, now serving 50% of all Medicare enrollees. Little is known about how inclusion rates of physicians in MA plan networks vary by the social and clinical risks of their patients. OBJECTIVE: To examine the association of physicians caring for patients with higher levels of social and clinical risk in traditional Medicare (TM) with the likelihood of inclusion in MA plan networks. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study evaluated the number of patients of physicians participating in TM Part B in 2019. The data analysis was conducted between June 2022 and March 2023. EXPOSURES: Quintiles of the proportion of patients who were dually eligible for Medicare and Medicaid and average beneficiary hierarchical condition category (HCC) score (a measure of a patient\u27s chronic disease burden that is used in risk adjustment and MA plan payment, where higher scores indicate higher risk) in the Part B TM program. MAIN OUTCOMES AND MEASURES: The main outcomes were the proportion of MA plans and enrollees for which physicians were in network. RESULTS: The analysis sample included 259 932 physicians billing Medicare Part B in 2019. After adjusting for physician, patient, and county characteristics, physicians with the highest quintile of patients with dual eligibility were associated with a lower likelihood of being included in MA plans and being in network with MA enrollees than the lowest quintile physicians (MA inclusion rate, -3.0% [95% CI, -3.2% to -2.8%]; P \u3c .001; in-network enrollee proportion, -6.5% [95% CI, -7.0% to -6.0%]; P \u3c .001). Similarly, physicians with the highest quintile HCC score were associated with a lower likelihood of being included in MA plans and being in network with MA enrollees than the lowest quintile physicians (MA inclusion rate, -7.5% [95% CI, -7.9% to -7.2%]; P \u3c .001; in-network enrollee proportion, -18.7% [95% CI, -19.5% to -18.1%]; P \u3c .001). Physicians in medical specialties in the highest clinical risk group (highest quintile HCC score) were associated with a significantly lower likelihood of being in network with MA enrollees than those in the lowest clinical risk group (in-network enrollee proportion, -20.4% [95% CI, -21.1% to -19.8%]; P \u3c .001). CONCLUSIONS AND RELEVANCE: This cross-sectional study of physicians participating in TM Part B in 2019 found that physicians with higher numbers of patients with social and medical risks in TM were significantly less likely to be associated with MA plans

Zebrafish behavioural profiling identifies GABA and serotonin receptor ligands related to sedation and paradoxical excitation.

Anesthetics are generally associated with sedation, but some anesthetics can also increase brain and motor activity-a phenomenon known as paradoxical excitation. Previous studies have identified GABAA receptors as the primary targets of most anesthetic drugs, but how these compounds produce paradoxical excitation is poorly understood. To identify and understand such compounds, we applied a behavior-based drug profiling approach. Here, we show that a subset of central nervous system depressants cause paradoxical excitation in zebrafish. Using this behavior as a readout, we screened thousands of compounds and identified dozens of hits that caused paradoxical excitation. Many hit compounds modulated human GABAA receptors, while others appeared to modulate different neuronal targets, including the human serotonin-6 receptor. Ligands at these receptors generally decreased neuronal activity, but paradoxically increased activity in the caudal hindbrain. Together, these studies identify ligands, targets, and neurons affecting sedation and paradoxical excitation in vivo in zebrafish

Prunella vulgaris Suppresses HG-Induced Vascular Inflammation via Nrf2/HO-1/eNOS Activation

Vascular inflammation is an important factor which can promote diabetic complications. In this study, the inhibitory effects of aqueous extract from Prunella vulgaris (APV) on high glucose (HG)-induced expression of cell adhesion molecules in human umbilical vein endothelial cells (HUVEC) are reported. APV decreased HG-induced expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin. APV also dose-dependently inhibited HG-induced adhesion of HL-60 monocytic cells. APV suppressed p65 NF-κB activation in HG-treated cells. APV significantly inhibited the formation of intracellular reactive oxygen species (ROS). HG-stimulated HUVEC secreted gelatinases, however, APV inhibited it. APV induced Akt phosphorylation as well as activation of heme oxygenase-1 (HO-1), eNOS, and nuclear factor E2-related factor 2 (Nrf2), which may protect vascular inflammation caused by HG. In conclusion, APV exerts anti-inflammatory effect via inhibition of ROS/NF-κB pathway by inducing HO-1 and eNOS expression mediated by Nrf2, thereby suggesting that Prunella vulgaris may be a possible therapeutic approach to the inhibition of diabetic vascular diseases

Triplet host engineering for triplet exciton management in phosphorescent organic light-emitting diodes

The device performances of green phosphorescent organic light-emitting diodes with a triplet mixed host emitting layer were correlated with the energy levels and composition of the host materials. Two hole-transport-type host materials, (4,4-N,N -dicarbazole)biphenyl (CBP) and 4,4 ,4 - tris(N-carbazolyl)triphenylamine (TCTA), were combined with two electron-transport-type host materials, 1,3,5-tris(N-phenylbenzimidazole-2-yl)benzene (TPBI) and PH1. The maximum quantum efficiency was obtained in the 5:5 mixed host in the case of TCTA:TPBI and TCTA:PH1, while CBP:PH1 showed the best performances in the 9:1 mixed host. The quantum efficiency of the green mixed host devices was improved by more than 50% compared with that of the corresponding single host devices.Grant No. RTI04-01-02 from the Regional Technology Innovation Program of the Ministry of Commerce, Industry and Energy (MOCIE

Diagnostic proficiency test using digital cytopathology and comparative assessment of whole slide images of cytologic samples for quality assurance program in Korea

Background The Korean Society for Cytopathology introduced a digital proficiency test (PT) in 2021. However, many doubtful opinions remain on whether digitally scanned images can satisfactorily present subtle differences in the nuclear features and chromatin patterns of cytological samples. Methods We prepared 30 whole-slide images (WSIs) from the conventional PT archive by a selection process for digital PT. Digital and conventional PT were performed in parallel for volunteer institutes, and the results were compared using feedback. To assess the quality of cytological assessment WSIs, 12 slides were collected and scanned using five different scanners, with four cytopathologists evaluating image quality through a questionnaire. Results Among the 215 institutes, 108 and 107 participated in glass and digital PT, respectively. No significant difference was noted in category C (major discordance), although the number of discordant cases was slightly higher in the digital PT group. Leica, 3DHistech Pannoramic 250 Flash, and Hamamatsu NanoZoomer 360 systems showed comparable results in terms of image quality, feature presentation, and error rates for most cytological samples. Overall satisfaction was observed with the general convenience and image quality of digital PT. Conclusions As three-dimensional clusters are common and nuclear/chromatin features are critical for cytological interpretation, careful selection of scanners and optimal conditions are mandatory for the successful establishment of digital quality assurance programs in cytology

High-precision RNS-CKKS on fixed but smaller word-size architectures: theory and application

A prevalent issue in the residue number system (RNS) variant of the Cheon-Kim-Kim-Song (CKKS) homomorphic encryption (HE) scheme is the challenge of efficiently achieving high precision on hardware architectures with a fixed, yet smaller, word-size of bit-length $W$, especially when the scaling factor satisfies $\log\Delta > W$. In this work, we introduce an efficient solution termed composite scaling. In this approach, we group multiple RNS primes as $q_\ell:= \prod_{j=0}^{t-1} q_{\ell,j}$ such that $\log q_{\ell,j} < W$ for $0\le j < t$, and use each composite $q_\ell$ in the rescaling procedure as $\mathsf{ct}\mapsto \lfloor \mathsf{ct} / q_\ell\rceil$. Here, the number of primes, denoted by $t$, is termed the composition degree. This strategy contrasts the traditional rescaling method in RNS-CKKS, where each $q_\ell$ is chosen as a single $\log\Delta$-bit prime, a method we designate as single scaling. To achieve higher precision in single scaling, where $\log\Delta > W$, one would either need a novel hardware architecture with word size $W\u27 > \log\Delta$ or would have to resort to relatively inefficient solutions rooted in multi-precision arithmetic. This problem, however, doesn\u27t arise in composite scaling. In the composite scaling approach, the larger the composition degree $t$, the greater the precision attainable with RNS-CKKS across an extensive range of secure parameters tailored for workload deployment. We have integrated composite scaling RNS-CKKS into both OpenFHE and Lattigo libraries. This integration was achieved via a concrete implementation of the method and its application to the most up-to-date workloads, specifically, logistic regression training and convolutional neural network inference. Our experiments demonstrate that single and composite scaling approaches are functionally equivalent, both theoretically and practically

Preoperative serum HER2 extracellular domain levels in primary invasive breast cancer

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.Abstract Background Despite the preclinical outcomes and biologic significance of the presence of the human epidermal growth factor receptor-2 (HER2) extracellular domain (ECD), there is little evidence supporting the measurement of ECD levels in any clinical setting. The aim of this study was to determine the prevalence of elevated serum HER2 ECD levels, the association between these levels and tissue HER2 overexpression, and the potential clinical prognostic value of HER2 ECD in primary invasive breast cancer. Methods Serum HER2 ECD levels were examined preoperatively in 2,862 consecutive stage I–III primary breast cancer patients between 2007 and 2009. Serum HER2 ECD levels were measured by chemiluminescence immunoassay (ADVIA Centaur), and the tissue HER2 status was assessed by immunohistochemistry and fluorescence in situ hybridization. The cutoff value for the serum level of HER2 ECD was set at 15.2 ng/ml. Results Among the 2,862 patients, 126 (4.4%) had elevated serum HER2 ECD levels, and HER2 was overexpressed in the tumor tissue of 692 patients (24.2%), with a concordance of 78.7%. Multivariate analysis revealed that elevated serum HER2 ECD was a significant independent prognostic factor for worse distant-metastasis-free survival [DMFS; hazard ratio (HR) = 2.50, 95% confidence interval (CI) = 1.5–4.3, P = 0.001] and breast-cancer-specific survival (BCSS; HR = 2.0, 95% CI = 1.1–3.8, P = 0.036), which were much stronger in patients with tissue HER2-positive tumors (DMFS: HR = 3.8, 95% CI = 2.0–7.0, P < 0.001; BCSS: HR = 2.6, 95% CI = 1.2-5.3, P = 0.012). Conclusions Given the prevalence of HER2 expression, its measurement as an independent prognostic factor can be clinically useful, particularly in patients with tissue HER2-positive tumors