Summary
Prior studies show vertebral strength from computed tomography-based finite element analysis may be associated with vertebral fracture risk. We found vertebral strength had a strong ...association with new vertebral fractures, suggesting that vertebral strength measures identify those at risk for vertebral fracture and may be a useful clinical tool.
Introduction
We aimed to determine the association between vertebral strength by quantitative computed tomography (CT)-based finite element analysis (FEA) and incident vertebral fracture (VF). In addition, we examined sensitivity and specificity of previously proposed diagnostic thresholds for fragile bone strength and low BMD in predicting VF.
Methods
In a case-control study, 26 incident VF cases (13 men, 13 women) and 62 age- and sex-matched controls aged 50 to 85 years were selected from the Framingham multi-detector computed tomography cohort. Vertebral compressive strength, integral vBMD, trabecular vBMD, CT-based BMC, and CT-based aBMD were measured from CT scans of the lumbar spine.
Results
Lower vertebral strength at baseline was associated with an increased risk of new or worsening VF after adjusting for age, BMI, and prevalent VF status (odds ratio (OR) = 5.2 per 1 SD decrease, 95% CI 1.3–19.8). Area under receiver operating characteristic (ROC) curve comparisons revealed that vertebral strength better predicted incident VF than CT-based aBMD (AUC = 0.804 vs. 0.715,
p
= 0.05) but was not better than integral vBMD (AUC = 0.815) or CT-based BMC (AUC = 0.794). Additionally, proposed fragile bone strength thresholds trended toward better sensitivity for identifying VF than that of aBMD-classified osteoporosis (0.46 vs. 0.23,
p
= 0.09).
Conclusion
This study shows an association between vertebral strength measures and incident vertebral fracture in men and women. Though limited by a small sample size, our findings also suggest that bone strength estimates by CT-based FEA provide equivalent or better ability to predict incident vertebral fracture compared to CT-based aBMD. Our study confirms that CT-based estimates of vertebral strength from FEA are useful for identifying patients who are at high risk for vertebral fracture.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Quantum-dot spin qubits characteristically use oscillating magnetic or electric fields, or quasi-static Zeeman field gradients, to realize full qubit control. For the case of three confined ...electrons, exchange interaction between two pairs allows qubit rotation around two axes, hence full control, using only electrostatic gates. Here, we report initialization, full control, and single-shot readout of a three-electron exchange-driven spin qubit. Control via the exchange interaction is fast, yielding a demonstrated 75 qubit rotations in less than 2 ns. Measurement and state tomography are performed using a maximum-likelihood estimator method, allowing decoherence, leakage out of the qubit state space, and measurement fidelity to be quantified. The methods developed here are generally applicable to systems with state leakage, noisy measurements and non-orthogonal control axes.
Full text
Available for:
IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Refractory or relapsed B lymphoblastic leukemia (B-ALL) patients have a dismal outcome with current therapy. We treated 42 primary refractory/hematological relapsed (R/R) and 9 refractory minimal ...residual disease by flow cytometry (FCM-MRD
) B-ALL patients with optimized second generation CD19-directed CAR-T cells. The CAR-T-cell infusion dosages were initially ranged from 0.05 to 14 × 10
/kg and were eventually settled at 1 × 10
/kg for the most recent 20 cases. 36/40 (90%) evaluated R/R patients achieved complete remission (CR) or CR with incomplete count recovery (CRi), and 9/9 (100%) FCM-MRD
patients achieved MRD
. All of the most recent 20 patients achieved CR/CRi. Most cases only experienced mild to moderate CRS. 8/51 cases had seizures that were relieved by early intervention. Twenty three of twenty seven CR/CRi patients bridged to allogeneic hematopoietic stem cell transplantation (allo-HCT) remained in MRD
with a median follow-up time of 206 (45-427) days, whereas 9 of 18 CR/CRi patients without allo-HCT relapsed. Our results indicate that a low CAR-T-cell dosage of 1 × 10
/kg, is effective and safe for treating refractory or relapsed B-ALL, and subsequent allo-HCT could further reduce the relapse rate.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
In organic light-emitting diodes (OLEDs), a stack of multiple organic layers facilitates charge flow from the low work function ~4.7 electron volts (eV) of the transparent electrode (tin-doped indium ...oxide, ITO) to the deep energy levels (~6 eV) of the active light-emitting organic materials. We demonstrate a chlorinated ITO transparent electrode with a work function of >6.1 eV that provides a direct match to the energy levels of the active light-emitting materials in state-of-the art OLEDs. A highly simplified green OLED with a maximum external quantum efficiency (EQE) of 54% and power efficiency of 230 lumens per watt using outcoupling enhancement was demonstrated, as were EQE of 50% and power efficiency of 110 lumens per watt at 10,000 candelas per square meter.
Full text
Available for:
BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Many patients who require allogeneic hematopoietic stem cell transplantation (allo-HSCT) lack a human leukocyte antigen (HLA)-matched donor. Here, we report a protocol for haploidentical allo-HSCT ...that combines granulocyte-colony stimulating factor primed bone marrow (G-BM) and peripheral blood stem cells (PBSC) without in vitro T-cell depletion (TCD). In this study, 171 patients, including 86 in high-risk group, underwent transplantation from haploidentical family donors. All patients achieved sustained, full donor chimerism. One hundred and eleven patients were alive in remission at a median of 682 (253-1502) days. The cumulative incidence of grade III-IV acute graft-versus-host disease (GVHD) was 23% and that of extensive chronic GVHD, 47%; these were not influenced by HLA disparity. Patients younger than 15 years had less grade III-IV acute GVHD than older patients (P=0.044). The 2-year probability of relapse was 12% for standard-risk disease and 39% for high-risk disease. The 2-year probability of leukemia-free survival (LFS) was 68% for standard-risk patients and 42% for high-risk patients (P=0.0009). Grade III-IV acute GVHD was associated with better LFS (P=0.0017). The results require confirmation and show that G-BM combined with PBSC from haploidentical family donors, without in vitro TCD, may be used as a good source of stem cells for allo-HSCT.
Full text
Available for:
DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The Galactic center supermassive black hole Sagittarius A* (Sgr A*) is one of the most promising targets to study the dynamics of black hole accretion and outflow via direct imaging with very long ...baseline interferometry (VLBI). At 3.5 mm (86 GHz), the emission from Sgr A* is resolvable with the Global Millimeter VLBI Array (GMVA). We present the first observations of Sgr A* with the phased Atacama Large Millimeter/submillimeter Array (ALMA) joining the GMVA. Our observations achieve an angular resolution of ∼87 as, improving upon previous experiments by a factor of two. We reconstruct a first image of the unscattered source structure of Sgr A* at 3.5 mm, mitigating the effects of interstellar scattering. The unscattered source has a major-axis size of 120 34 as (12 3.4 Schwarzschild radii) and a symmetrical morphology (axial ratio of ), which is further supported by closure phases consistent with zero within 3 . We show that multiple disk-dominated models of Sgr A* match our observational constraints, while the two jet-dominated models considered are constrained to small viewing angles. Our long-baseline detections to ALMA also provide new constraints on the scattering of Sgr A*, and we show that refractive scattering effects are likely to be weak for images of Sgr A* at 1.3 mm with the Event Horizon Telescope. Our results provide the most stringent constraints to date for the intrinsic morphology and refractive scattering of Sgr A*, demonstrating the exceptional contribution of ALMA to millimeter VLBI.
Bidirectional interactions between astrocytes and neurons have physiological roles in the central nervous system and an altered state or dysfunction of such interactions may be associated with ...neurodegenerative diseases, such as Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS). Astrocytes exert structural, metabolic and functional effects on neurons, which can be either neurotoxic or neuroprotective. Their neurotoxic effect is mediated via the senescence-associated secretory phenotype (SASP) involving pro-inflammatory cytokines (e.g., IL-6), while their neuroprotective effect is attributed to neurotrophic growth factors (e.g., NGF). We here demonstrate that the p53 isoforms Δ133p53 and p53β are expressed in astrocytes and regulate their toxic and protective effects on neurons. Primary human astrocytes undergoing cellular senescence upon serial passaging in vitro showed diminished expression of Δ133p53 and increased p53β, which were attributed to the autophagic degradation and the SRSF3-mediated alternative RNA splicing, respectively. Early-passage astrocytes with Δ133p53 knockdown or p53β overexpression were induced to show SASP and to exert neurotoxicity in co-culture with neurons. Restored expression of Δ133p53 in near-senescent, otherwise neurotoxic astrocytes conferred them with neuroprotective activity through repression of SASP and induction of neurotrophic growth factors. Brain tissues from AD and ALS patients possessed increased numbers of senescent astrocytes and, like senescent astrocytes in vitro, showed decreased Δ133p53 and increased p53β expression, supporting that our in vitro findings recapitulate in vivo pathology of these neurodegenerative diseases. Our finding that Δ133p53 enhances the neuroprotective function of aged and senescent astrocytes suggests that the p53 isoforms and their regulatory mechanisms are potential targets for therapeutic intervention in neurodegenerative diseases.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Typical high-efficiency organic light-emitting diodes (OLEDs) require exotic high-refractive-index (n ≥ 1.8) substrates to enhance the outcoupling of trapped light in the device. One of the exciting ...possibilities of OLEDs is the use of lightweight flexible plastic substrates, which unfortunately have a low refractive index (n ≤ 1.6). To unlock the full potential of OLEDs on flexible plastic, we report high-efficiency phosphorescent OLEDs using a thin-film outcoupling enhancement method that does not depend on high-index substrates. In these devices, multifunctional anode stacks, consisting of a high-index Ta2 O5 optical coupling layer, electrically conductive gold layer and hole-injection MoO3 layer, are collectively optimized to achieve high efficiency. The maximum external quantum efficiency reaches 63% for green, which remains as high as 60% at >10,000 cd m-2 .
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Mutations of Wnt/β-catenin signaling pathway has essential roles in development and cancer. Although β-catenin and adenomatous polyposis coli (APC) gene mutations are well established and are known ...to drive tumorigenesis, discoveries of mutations in other components of the pathway lagged, which hinders the understanding of cancer mechanisms. Here we report that δ-catenin (gene designation: CTNND2), a primarily neural member of the β-catenin superfamily that promotes canonical Wnt/β-catenin/LEF-1-mediated transcription, displays exonic mutations in human prostate cancer and promotes cancer cell survival adaptation and metabolic reprogramming. When overexpressed in cells derived from prostate tumor xenografts, δ-catenin gene invariably gives rise to mutations, leading to sequence disruptions predicting functional alterations. Ectopic δ-catenin gene integrating into host chromosomes is locus nonselective. δ-Catenin mutations promote tumor development in mouse prostate with probasin promoter (ARR2PB)-driven, prostate-specific expression of Myc oncogene, whereas mutant cells empower survival advantage upon overgrowth and glucose deprivation. Reprogramming energy utilization accompanies the downregulation of glucose transporter-1 and poly (ADP-ribose) polymerase cleavage while preserving tumor type 2 pyruvate kinase expression. δ-Catenin mutations increase β-catenin translocation to the nucleus and hypoxia-inducible factor 1α (HIF-1α) expression. Therefore, introducing δ-catenin mutations is an important milestone in prostate cancer metabolic adaptation by modulating β-catenin and HIF-1α signaling under glucose shortage to amplify its tumor-promoting potential.
Full text
Available for:
DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Summary
It is of great significance to develop and evaluate noninvasive indexes predicting the level of liver fibrosis. The aim of this study was to comparatively evaluate gamma‐glutamyl ...transpeptidase‐to‐platelet ratio (GPR) versus aspartate aminotransferase‐to‐platelet ratio index (APRI) and fibrosis index based on 4 factors (FIB‐4) in predicting different levels of liver fibrosis of chronic hepatitis B (CHB) within the framework of HBeAg‐positive and HBeAg‐negative patients. A total of 1157 HBeAg‐positive and 859 HBeAg‐negative CHB patients were enrolled, among whom the pathological stage ≥S2, ≥S3, ≥S4 were defined as significant fibrosis, extensive fibrosis and cirrhosis, respectively. Receiver operating characteristic (ROC) curves were used to evaluate the performance of GPR, APRI and FIB‐4 in predicting different levels of liver fibrosis. In HBeAg‐positive patients, the area under ROC curves (AUROCs) of GPR in predicting extensive fibrosis and cirrhosis were both significantly larger than those of APRI (P = .0001 and P < .0001). In HBeAg‐negative patients, the AUROCs of GPR in predicting significant fibrosis and cirrhosis were significantly larger than those of FIB‐4 (P = .0006 and P = .0041). The AUROC of GPR in predicting extensive fibrosis was significantly larger than that of APRI and FIB‐4 (P = .0320 and P = .0018). Using a cut‐off of GPR > 0.500 as standard, the sensitivities and specificities of GPR in predicting significant fibrosis in HBeAg‐positive patients were 59.6% and 81.2%, and for cirrhosis 80.9% and 63.8%, respectively; and those of HBeAg‐negative patients were 60.3% and 78.3%, 84.5% and 66.1%, respectively. Regardless of HBeAg‐positive or HBeAg‐negative status, GPR had the best performance in predicting different levels of liver fibrosis.
Full text
Available for:
BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
PDF
