The usefulness of pharmacokinetic parameters for glioma grading has been reported based on the perfusion data from parts of entire-tumor volumes. However, the perfusion values may not reflect the ...entire-tumor characteristics. Our aim was to investigate the feasibility of glioma grading by using histogram analyses of pharmacokinetic parameters including the volume transfer constant, extravascular extracellular space volume per unit volume of tissue, and blood plasma volume per unit volume of tissue from T1-weighted dynamic contrast-enhanced perfusion MR imaging.
Twenty-eight patients (14 men, 14 women; mean age, 49.75 years; age range, 25-72 years) with histopathologically confirmed gliomas (World Health Organization grade II, n = 7; grade III, n = 8; grade IV, n = 13) were examined before surgery or biopsy with conventional MR imaging and T1-weighted dynamic contrast-enhanced perfusion MR imaging at 3T. Volume transfer constant, extravascular extracellular space volume per unit volume of tissue, and blood plasma volume per unit volume of tissue were calculated from the entire-tumor volume. Histogram analyses from these parameters were correlated with glioma grades. The parameters with the best percentile from cumulative histograms were identified by analysis of the area under the curve of the receiver operating characteristic analysis and were compared by using multivariable stepwise logistic regression analysis for distinguishing high- from low-grade gliomas.
All parametric values increased with increasing glioma grade. There were significant differences among the 3 grades in all parameters (P < .01). For the differentiation of high- and low-grade gliomas, the highest area under the curve values were found at the 98th percentile of the volume transfer constant (area under the curve, 0.912; cutoff value, 0.277), the 90th percentile of extravascular extracellular space volume per unit volume of tissue (area under the curve, 0.939; cutoff value, 19.70), and the 84th percentile of blood plasma volume per unit volume of tissue (area under the curve, 0.769; cutoff value, 11.71). The 98th percentile volume transfer constant value was the only variable that could be used to independently differentiate high- and low-grade gliomas in multivariable stepwise logistic regression analysis.
Histogram analysis of pharmacokinetic parameters from whole-tumor volume data can be a useful method for glioma grading. The 98th percentile value of the volume transfer constant was the most significant measure.
Microscopic split-ring-resonator (SRR) arrays are fabricated on 100 μm thick polyethylene naphthalate (PEN) films by femtosecond laser micro-lens array (MLA) lithography. The transmission properties ...of these metamaterials are characterized by THz Time Domain Spectroscopy (THz-TDS). Tunable resonance responses can be achieved by changing SRR structural design parameters. By stacking 2D PEN metamaterial films with different frequency responses together, a broadband THz filter with full width at half maximum (FWHM) of 0.38 THz is constructed. The bandwidth of the resonance response increases up to 4.2 times as compared to the bandwidths of single layer metamaterials. Numerical simulation reveals that SRR layers inside the multi-layer metamaterials are selectively excited towards specific frequencies within the broadband response. Meanwhile, more than one SRR layers respond to the chosen frequencies, resulting in the enhancement of the resonance properties. The multi-layer metamaterials provide a promising way to extend SRR based metamaterial operating region from narrowband to broadband with a tunable feature.
Hollow TiO2 hemispheres for application in dye‐sensitized solar cells are prepared by means of rf‐sputtering onto colloidal templated substrates. After removing the organic templates by thermal ...decomposition, quasi‐ordered networks of hollow TiO2 hemispheres were formed. This approach should open up new opportunities for processing material architectures with high surface activity and effective charge transport for high performance photovoltaic and photoelectrochemical cells.
Functions of many long noncoding RNAs (lncRNAs) depend on their ability to interact with multiple copies of specific RNA-binding proteins (RBPs). Here, we devised a workflow combining bioinformatics ...and experimental validation steps to systematically identify RNAs capable of multivalent RBP recruitment. This uncovered a number of previously unknown transcripts encoding high-density RBP recognition arrays within genetically normal short tandem repeats. We show that a top-scoring hit in this screen, lncRNA PNCTR, contains hundreds of pyrimidine tract-binding protein (PTBP1)-specific motifs allowing it to sequester a substantial fraction of PTBP1 in a nuclear body called perinucleolar compartment. Importantly, PNCTR is markedly overexpressed in a variety of cancer cells and its downregulation is sufficient to induce programmed cell death at least in part by stimulating PTBP1 splicing regulation activity. This work expands our understanding of the repeat-containing fraction of the human genome and illuminates a novel mechanism driving malignant transformation of cancer cells.
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•Human genome encodes many transcripts enriched in short tandem repeats (strRNAs)•strRNA PNCTR recruits RNA-binding protein PTBP1 to a nuclear body called PNC•PNCTR antagonizes splicing regulation function of PTBP1 and promotes cell survival•PNCTR is dramatically upregulated in a wide range of cancer cells
Yap et al. show that several short tandem repeats (STRs) encoded in the human genome are transcribed at a readily detectable level. The STR-enriched RNA PNCTR sequesters multiple copies of PTBP1 in the perinucleolar compartment, thus modulating splicing regulation function of this RNA-binding protein and promoting cancer cell survival.
Retrospective and molecular biologic data suggest that sunitinib may be effective in patients with non-clear cell renal cell carcinoma (nccRCC).
Eligibility criteria included advanced nccRCC except ...for collecting duct carcinoma and sarcomatoid carcinoma without identifiable renal cell carcinoma subtypes. Patients were treated with 50 mg/day oral sunitinib for 4 weeks, followed by 2 weeks of rest. The primary end point was overall response rate (RR).
Thirty-one eligible patients were enrolled. Twenty-four patients (77%) had prior nephrectomy. By Memorial Sloan-Kettering Cancer Center criteria, 8 patients (26%) had poor risk and 14 (45%) had intermediate risk. Twenty-two patients had papillary renal cell carcinoma (RCC), and three had chromophobe RCC. Eleven patients had partial response with a RR of 36% (95% confidence interval (CI) 19% to 52%) and an additional 17 patients (55%) had stable disease. Median duration of response was 12.7 months (95% CI 6.3–19.1 months), and median progression-free survival was 6.4 months (95% CI 4.2–8.6 months). At a median follow-up duration of 18.7 months (95% CI 13.7–23.7 months), 13 patients (42%) had died, resulting in an estimated median survival of 25.6 months (95% CI 8.4–42.9 months). Toxicity profiles were commensurate with prior reports.
Sunitinib has promising activity in patients with nccRCC (NCT01219751).
Objective: To study the inter-relationships between sleeping hours, working hours and obesity in subjects from a working population. Research design: A cross-sectional observation study under the ...'Better Health for Better Hong Kong' Campaign, which is a territory-wide health awareness and promotion program. Subjects: 4793 subjects (2353 (49.1%) men and 2440 (50.9%) women). Their mean age (+/-s.d.) was 42.4+/-8.9 years (range 17-83 years, median 43.0 years). Subjects were randomly selected using computer-generated codes in accordance to the distribution of occupational groups in Hong Kong. Results: The mean daily sleeping time was 7.06+/-1.03 h (women vs men: 7.14+/-1.08 h vs 6.98+/-0.96 h, P<0.001). Increasing body mass index (BMI) was associated with reducing number of sleeping hours and increasing number of working hours reaching significance in the whole group as well as among male subjects. Those with short sleeping hour (6 h or less) and long working hours (>9 h) had the highest BMI and waist in both men and women. Based on multiple regression analysis with age, smoking, alcohol drinking, systolic and diastolic blood pressure, mean daily sleeping hours and working hours as independent variables, BMI was independently associated with age, systolic and diastolic blood pressure in women, whereas waist was associated with age, smoking and blood pressure. In men, blood pressure, sleeping hours and working hours were independently associated with BMI, whereas waist was independently associated with age, smoking, blood pressure, sleeping hours and working hours in men. Conclusion: Obesity is associated with reduced sleeping hours and long working hours in men among Hong Kong Chinese working population. Further studies are needed to investigate the underlying mechanisms of this relationship and its potential implication on prevention and management of obesity.
Summary
Background
Toluene diisocyanate (TDI) is the most important cause of occupational asthma, but the genetic mechanism of TDI‐induced asthma is still unknown.
Objective
The objective of the ...study was to identify susceptibility alleles associated with the TDI‐induced asthma phenotype.
Methods
We conducted a genome‐wide association study in 84 patients with TDI‐induced asthma and 263 unexposed healthy normal controls using Affymetrix 500K SNPchip. We also investigated the relationships between genetic polymorphisms and transcript levels in Epstein–Barr virus‐transformed lymphoblastoid cell lines from patients with TDI‐induced asthma enrolled in this study.
Results
Genetic polymorphisms of CTNNA3 (catenin alpha 3, alpha‐T catenin) were significantly associated with the TDI‐induced asthma phenotype (5.84 × 10−6 for rs10762058, 1.41 × 10−5 for rs7088181, 2.03 × 10−5 for rs4378283). Carriers with the minor haplotype, HT2 GG, of two genetic polymorphisms (rs10762058 and rs7088181) showed significantly lower PC20 methacholine level (P=0.041) and lower mRNA expression of CTNNA3 than non‐carriers (P=0.040). A genetic polymorphism in the 3′ downstream region of CTNNA3 (rs1786929), as identified by DNA direct sequencing, was significantly associated with the TDI‐induced asthma phenotype (P=0.015 in recessive analysis model) and the prevalence of serum‐specific IgG to cytokeratin 19 (P=0.031).
Conclusion
These findings suggested that multiple genetic polymorphisms of CTNNA3 may be determinants of susceptibility to TDI‐induced asthma.
Expert consensus on the systemic treatment of atopic dermatitis in special populations Adam, D. N.; Gooderham, M. J.; Beecker, J. R. ...
JEADV. Journal of the European Academy of Dermatology and Venereology/Journal of the European Academy of Dermatology and Venereology,
June 2023, 2023-Jun, 2023-06-00, 20230601, Letnik:
37, Številka:
6
Journal Article
Recenzirano
Odprti dostop
With the increasing number of options for the treatment of moderate‐to‐severe atopic dermatitis, clinicians need guidance on a practical approach to selecting a systemic agent for specific patient ...populations. We convened an expert panel consisting of 12 members to conduct a literature review and summarize relevant data related to six scenarios of clinical interest: comorbid asthma, ocular surface disease, history of cancer, past and ongoing infections of interest (including herpes simplex virus, herpes zoster, hepatitis B, and tuberculosis), pregnancy and lactation, and the elderly. We performed a literature search and examined each clinical scenario with respect to three major categories of available systemic agents: traditional systemics (azathioprine, cyclosporine A, methotrexate, and mycophenolate mofetil), Janus kinase inhibitors (abrocitinib, baricitinib, and upadacitinib), and biologics (dupilumab, lebrikizumab, and tralokinumab). The expert panel and steering committee met virtually to review the data and discuss the drafted consensus statements. A modified Delphi process was used to arrive at a set of final consensus statements related to the systemic treatment of AD in these specific patient populations. To provide practical guidance on the choice of systemic therapy for atopic dermatitis in these six topics of clinical interest, 25 expert consensus statements and a summary of the supporting data are presented herein.
Overview of nuclear data production system at RAON Ham, C.; Tshoo, K.; Lee, S. ...
Nuclear instruments & methods in physics research. Section B, Beam interactions with materials and atoms,
August 2023, 2023-08-00, Letnik:
541
Journal Article
Recenzirano
Nuclear Data Production System (NDPS), a fast neutron facility for nuclear science and applications, was constructed at the Rare Isotope Accelerator complex for ON-line experiments (RAON) in Korea. ...NDPS is designed to provide both white and quasi-monoenergetic neutrons using 98 MeV deuteron and 20 – 83 MeV proton beams with thick graphite and thin lithium targets, respectively. Neutron energy is determined by employing the Time-Of-Flight (TOF) technique, along with a pulsed deuteron (or proton) beam with a repetition rate of less than 200 kHz. Fast neutrons are produced in the target room and are guided to the TOF room through a 4 m long neutron collimator consisting of iron and 5% borated polyethylene. The neutron beam is monitored using a parallel plate avalanche counter (PPAC) and a micro-mesh gaseous (MICROMEGAS) detector installed in the TOF room, so as to measure the energy and the position of neutrons.
The diameters of the vertebral arteries (VAs) are very often unequal. Therefore, this study investigated if unequal VA flow contributes to the development of basilar artery (BA) curvature and if it ...is a link to the laterality of pontine or cerebellar infarcts occurring around the vertebrobasilar junction.
Radiological factors were analysed (infarct laterality, VA dominance, BA curvature and their directional relationships) in 91 patients with acute unilateral pontine or posterior inferior cerebellar artery (PICA) territory infarcts. The "dominant" VA side was defined as either that the VA was larger in diameter or the VA was connected with the BA in more of a straight line, if both VAs looked similar in diameter on CT angiography. Multiple regression analysis was performed to predict moderate to severe BA curvature.
The dominant VA was more frequent on the left side (p<0.01). Most patients had an opposite directional relationship between the dominant VA and BA curvature (p<0.01). Pontine infarcts were opposite to the side of BA curvature (p<0.01) and PICA infarcts were on the same side as the non-dominant VA side (p<0.01). The difference in VA diameters was the single independent predictor for moderate to severe BA curvature (OR per 1 mm, 2.70; 95% CI 1.22 to 5.98).
Unequal VA flow is an important haemodynamic contributor of BA curvature and development of peri-vertebrobasilar junctional infarcts.
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