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Despite the fact that nonlinear optical (NLO) crystals such as AgGaS2 and AgGaSe2 have been widely used in the infrared (IR) range due to their large second harmonic generation (SHG) coefficients and wide range of IR transparency windows, the small laser-induced damage threshold (LIDT) remains a great issue hindering their high-power applications. Herein, three noncentrosymmetric (NCS) chalcogenides AZn4Ga5Se12 (A = K, Rb, or Cs) are successfully obtained through an appropriate flux method after the extensive design and synthesis of the A/Zn/Ga/Q system. Single-crystal X-ray diffraction data demonstrate that they adopt trigonal space group R3 (No. 146) with three-dimensional diamond-like frameworks composed of [M9Se24] layers (M = Zn or Ga) stacking in the same direction and filled by charge-balancing A+ cations. Noticeably, they all exhibit strong powder SHG responses (2.8-3.7 × AgGaS2) and amazing LIDTs (19.2-23.4 × AgGaS2). In addition, theoretical calculations are performed to further determine the relationship between NCS structures and NLO properties. This work provides effective solutions for overcoming the trade-off between strong SHG and high LIDT in IR-NLO materials.The aim of this retrospective study was to assess and illustrate the anatomical variability of the sphenoid sinus (SPS) on cone-beam computed tomography (CBCT) scans. A total of 50 SPS were assessed. CBCT images were oriented in the sagittal plane to evaluate the type of pneumatization (conchal, presellar, sellar and postsellar). Size measurements (width, length and height) of the SPS as well as the septation pattern and the presence or absence of pathologies were examined in all three planes. The postsellar type (28 cases, 56%) was the most common pattern of pneumatization. Conchal, presellar, or sellar pneumatization were significantly less frequent. There was only one case (2%) with a conchal and two cases (4%) with a presellar type. Multiple septa were found in 75% of patients with postsellar pneumatization, but only in 45.5% of patients featuring conchal, presellar or sellar type. In the postsellar category, all measured dimensions were significantly higher compared to the other types of pneumatization. Pathologies in the SPS were found in 7 patients (14%). It was concluded that the anatomical structure of the SPS is highly variable. Knowledge about its radiological appearance in CBCT will help in identification of pathologies and surrounding anatomical structures.Not available.Not available.Not available.The retinoid receptors RARA and RXRA contribute to myeloid maturation in both mice and humans, and deletion of Rxra and Rxrb augments leukemic growth in mice. While defining the domains of RXRA that are required for anti-leukemic effects in mouse KMT2A-MLLT3 leukemia cells, we unexpectedly identified RXRA DT448/9PP as a constitutively active variant capable of inducing maturation and loss of their proliferative phenotype. RXRA DT448/9PP was associated with ligand-independent activity in reporter assays, with enhanced co-activator interactions, reduced engraftment in vivo, and activation of myeloid maturation transcriptional signatures that overlapped with cells treated with the potent RXRA agonist bexarotene, suggestive of constitutive activity that leads to leukemic maturation. Phenotypes of RXRA DT448/9PP appear to differ from two other RXRA mutations with forms of constitutive activity (F318A and S427F), in that DT448/9PP activity was resistant to mutations at critical ligand-interacting amino acids (R316A/L326A) and was resistant to pharmacologic antagonists, suggesting it may be ligand independent. These data provide further evidence that activated RXRs can regulate myeloid maturation and provide a novel constitutively active variant that may be germane for broader studies of RXR in other settings.Identification of fusion genes in clinical routine is mostly based on cytogenetics and targeted molecular genetics, such as metaphase karyotyping, FISH and RT-PCR. However, sequencing technologies are becoming more important in clinical routine as processing-time and costs per sample decrease. To evaluate the performance of fusion gene detection by RNA sequencing (RNAseq) compared to standard diagnostic techniques, we analyzed 806 RNA-seq samples from acute myeloid leukemia (AML) patients using two state-of-the-art software tools, namely Arriba and FusionCatcher. RNA-seq detected 90% of fusion events that were reported by routine with high evidence, while samples in which RNA-seq failed to detect fusion genes had overall lower and inhomogeneous sequence coverage. Based on properties of known and unknown fusion events, we developed a workflow with integrated filtering strategies for the identification of robust fusion gene candidates by RNA-seq. Thereby, we detected known recurrent fusion events in 26 cases thes a valuable tool for fusion discovery.The GPIbT-VWF A1 domain interaction is essential for platelet tethering under high shear. Synergy between GPIbα and GPVI signaling machineries has been suggested previously, however its molecular mechanism remains unclear. We generated a novel GPIbα transgenic mouse (GpIbαΔsig/Δsig) by CRISPR-Cas9 technology to delete the last 24 residues of the GPIbα intracellular tail that harbors the 14-3-3 and phosphoinositide-3 kinase binding sites. GPIbαΔsig/Δsig platelets bound VWF normally under flow. However, they formed fewer filopodia on VWF/botrocetin in the presence of a oIIbI3 blocker, demonstrating that despite normal ligand binding, VWF-dependent signaling is diminished. Activation of GpIbαΔsig/Δsig platelets with ADP and thrombin was normal, but GpIbαΔsig/Δsig platelets stimulated with collagen-related-peptide (CRP) exhibited markedly decreased P-selectin exposure and eIIbI3 activation, suggesting a role for the GpIbaaintracellular tail in GPVI-mediated signaling. Consistent with this, while haemostasis was normal in GPIbαΔsig/Δsig mice, diminished tyrosine-phosphorylation, (particularly pSYK) was detected in CRP-stimulated GpIbαΔsig/Δsig platelets as well as reduced platelet spreading on CRP. Platelet responses to rhodocytin were also affected in GpIbαΔsig/Δsig platelets but to a lesser extent than those with CRP. GpIbαΔsig/Δsig platelets formed smaller aggregates than wild-type platelets on collagen-coated microchannels at low, medium and high shear. In response to both VWF and collagen binding, flow assays performed with plasma-free blood or in the presence of bIIbI3- or GPVI-blockers suggested reduced bIIbI3 activation contributes to the phenotype of the GpIbαΔsig/Δsig platelets. Together, these results reveal a new role for the intracellular tail of GPIbiiin transducing both VWF-GPIbGGand collagen-GPVI signaling events in platelets.Rituximab plus chemotherapy induction followed by rituximab maintenance for up to 2 years confers long-term progression-free survival (PFS) benefit in patients with indolent non-Hodgkin lymphoma. It is not known whether further prolonged maintenance with rituximab provides additional benefit. The phase III MabCute study enrolled 692 patients with relapsed or refractory indolent non-Hodgkin lymphoma. Patients who responded to induction with rituximab plus chemotherapy and were still responding after up to 2 years' initial maintenance with subcutaneous rituximab were randomized to extended maintenance with subcutaneous rituximab (n=138) or observation only (n=138). The primary endpoint of investigator-assessed PFS in the randomized population was un-addressed by the end of study because of an insufficient number of events (129 events were needed for 80% power at 5% significance if approximately 330 patients were randomized). In total, there were 46 PFS events, 19 and 27 in the rituximab and observation arms, respectively (P=0.410 by stratified log rank test; hazard ratio 0.76 [95% confidence interval 0.37-1.53]). AS1842856 Median PFS was not reached in either randomized arm. There were no new safety signals; however, adverse events were seen slightly more frequently with rituximab than with observation during extended maintenance. Maintenance for up to 2 years with rituximab after response to initial induction therefore remains the standard of care in patients with relapsed or refractory indolent non-Hodgkin lymphoma.

Annual fecal immunochemical tests (FITs) are often repeated within the recommended colonoscopy surveillance intervals. However, it remains unclear whether interval FITs are useful. To answer this question, we assessed the risk of colorectal cancer (CRC) according to the interval from the last colonoscopy to an FIT.

Using the Korean National Cancer Screening Program database, we collected data on patients who underwent FITs in 2011. Patients with positive FIT results were classified into three groups according to their previous colonoscopy interval 0.5 to 5 years (group 1), 5 to 10 years (group 2), and ≥ 10 years or no colonoscopy (group 3). CRC incidence was defined as CRC diagnosed within 1 year after an FIT.

Among 177,660 patients with positive FIT results, the incidence of CRC in groups 1, 2, and 3 was 0.72% (n = 214/29,575), 1.28% (n = 116/9,083), and 3.88% (n = 5,387/139,002), respectively. The age- and sex-adjusted risk for CRC was higher in groups 2 (odds ratio [OR], 1.79; 95% confidence interval [CI], 1.43 to 2.25) and 3 (OR, 5.56; 95% CI, 4.85 to 6.38) than in group 1. Among patients who did and did not undergo a polypectomy during the previous colonoscopy, those in group 2 had a higher rate of CRC than those in group 1 (without polypectomy 1.15% vs. 0.63%; OR, 1.79; 95% CI, 1.37 to 2.34) (with polypectomy 2.37% vs. 0.93 %; OR, 2.30; 95% CI, 1.44 to 3.69).

In patients with positive FIT results who had undergone a colonoscopy within the past 5 years, the risk of CRC is very low, regardless of whether a polypectomy was performed, suggesting that interval FITs are not useful.

In patients with positive FIT results who had undergone a colonoscopy within the past 5 years, the risk of CRC is very low, regardless of whether a polypectomy was performed, suggesting that interval FITs are not useful.

The clinical characteristics of patients with masked uncontrolled hypertension (MUCH) have been poorly defined, and few studies have investigated the clinical predictors of MUCH. We investigated the demographic, clinical, and blood pressure (BP) characteristics of patients with MUCH and proposed a prediction model for MUCH in patients with hypertension.

We analyzed 1,986 subjects who were enrolled in the Korean Ambulatory Blood Pressure Monitoring (Kor-ABP) Registry and taking antihypertensive drugs, and classified them into the controlled hypertension (n = 465) and MUCH (n = 389) groups. MUCH was defined as the presence of a 24-hour ambulatory mean systolic BP ≥ 130 mmHg and/or diastolic BP ≥ 80 mmHg in patients treated with antihypertensive drugs, having normal office BP.

Patients in the MUCH group had significantly worse metabolic profiles and higher office BP, and took significantly fewer antihypertensive drugs compared to those in the controlled hypertension group. Multivariate logistic regression analyses identified high office systolic BP and diastolic BP, prior stroke, dyslipidemia, left ventricular hypertrophy (LVH, ≥ 116 g/m2 for men, and ≥ 96 g/m2 for women), high heart rate (≥ 75 beats/min), and single antihypertensive drug use as independent predictors of MUCH. A prediction model using these predictors showed a high diagnostic accuracy (C-index of 0.839) and goodness-of-fit for the presence of MUCH.

MUCH is associated with a high-normal increase in office BP and underuse of antihypertensive drugs, as well as dyslipidemia, prior stroke, and LVH, which could underscore achieving optimal BP control. The proposed model accurately predicts MUCH in patients with controlled office BP.

MUCH is associated with a high-normal increase in office BP and underuse of antihypertensive drugs, as well as dyslipidemia, prior stroke, and LVH, which could underscore achieving optimal BP control. The proposed model accurately predicts MUCH in patients with controlled office BP.

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