Revisiting the use of the EORTC QLQ-STO22 to assess health-related quality of life of patients with gastric cancer: incorporating updated treatment options and cross-cultural perspectives.

BACKGROUND: The EORTC QLQ-STO22 (QLQ-STO22) is a firmly established and validated measure of health-related quality of life (HRQoL) for people with gastric cancer (GC), developed over two decades ago. Since then there have been dramatic changes in treatment options for GC. Also, East Asian patients were not involved in the development of QLQ-STO22, where GC is most prevalent and the QLQ-STO22 is widely used. A review with appropriate updating of the measure was planned. This study aims to capture HRQoL issues associated with new treatments and the perspectives of patients and health care professionals (HCPs) from different cultural backgrounds, including East Asia. METHODS: A systematic literature review and open-ended interviews were preformed to identify potential new HRQoL issues relating to GC. This was followed by structured interviews where HCPs and patients reviewed the QLQ-STO22 alongside new issues regarding relevance, importance, and acceptability. RESULTS: The review of 267 publications and interviews with 104 patients and 18 HCPs (48 and 9 from East Asia, respectively) generated a list of 58 new issues. Three of these relating to eating small amounts, flatulence, and neuropathy were recommended for inclusion in an updated version of the QLQ-STO22 and covered by five additional questions. CONCLUSIONS: This study supports the content validity of the QLQ-STO22, suggesting its continued relevance to patients with GC, including those from East Asia. The updated version with additional questions and linguistic changes will enhance its specificity, but further testing is required.

Recombination of Protons Accelerated by a High Intensity High Contrast Laser.

Short pulse, high contrast, intense laser pulses incident onto a solid target are not known to generate fast neutral atoms. Experiments carried out to study the recombination of accelerated protons show a 200 times higher neutralization than expected. Fast neutral atoms can contribute to 80% of the fast particles at 10 keV, falling rapidly for higher energy. Conventional charge transfer and electron-ion recombination in a high density plasma plume near the target is unable to explain the neutralization. We present a model based on the copropagation of electrons and ions wherein recombination far away from the target surface accounts for the experimental measurements. A novel experimental verification of the model is also presented. This study provides insights into the closely linked dynamics of ions and electrons by which neutral atom formation is enhanced.

Enhanced x-ray emission from nano-particle doped bacteria.

Recently, it has been greatly appreciated that intense light matter interaction is modified due to the nano- and microstructures in the target by--surface plasmons, laser energy localization scattering etc. Extreme laser intensities produce dense plasmas and collective mechanisms generate energetic electrons, ions and hard x-rays. Recently, it is postulated that the anharmonic electron motion, driven by ultrashort, high-intensity laser pulses, provides a universal mechanism for the laser absorption. Here, we provide the first demonstration of anharmonic-resonance-aided high laser-absorption in a biological system. At intensities of ∼ 10¹6⁻¹8 W/cm², 40 fs pulses excite a plasma formed with E. coli bacteria. The density-inhomogeneities due to the micro- and nanostructures in the bacterial target increase anharmonic resonance (AHR) heating and result in a 104-fold enhancement in the hard x-ray yield compared to plain solid targets. These observations lead to novel high-energy x-ray sources that have implications to lithography, imaging and medical applications.

Photoionization of clusters in intense few-cycle near infrared femtosecond pulses.

In this article we present a perspective on the current state of the art in the photoionization of atomic clusters in few-cycle near-infrared laser pulses. Recently, several studies have reported intriguing phenomena associated with the photoionization of clusters by pulses as short as ~10 fs which approach the natural timescales of collective electronic motion in such nanoscale aggregates. In contrast to the dynamics occurring on few- and sub-picosecond timescales where ionic motion sets in and plays a key role marked by resonant plasmon oscillations, the few-cycle limit precludes cluster expansion due to the nuclear motion of ionic constituents. Thus, pulses lasting just a few optical cycles explore a new "impulsive" regime for the first time in cluster nanoplasmas wherein ions essentially remain "frozen". Along with the perspective on this new regime, we present first measurements of photoelectron distributions and temperatures.

2-[4-(Tri-fluoro-meth-yl)phen-yl]-1H-benzimidazole.

In the title compound, C14H9F3N2, the mean planes of the benzimidazole ring system and the tri-fluoro-methyl-substituted benzene ring form a dihedral angle of 30.1 (1)°. In the crystal, mol-ecules are linked by N-H⋯N hydrogen bonds into chains along [010]. Weak C-H⋯F hydrogen bonds and a weak C-H⋯π inter-action connect the chains into a two-dimensional network parallel to (001).

Crystal structure of ethyl 2-(2-fluoro-benzyl-idene)-5-(4-fluoro-phen-yl)-7-methyl-3-oxo-2,3-di-hydro-5H-1,3-thia-zolo[3,2-a]pyrimidine-6-carb-oxy-late.

In the title mol-ecule, C23H18F2N2O3S, the 4-fluoro-substituted and 2-fluoro-substituted benzene rings form dihedral angles of 88.16 (8) and 23.1 (1)°, respectively, with the thia-zole ring. The pyrimidine ring adopts a flattened sofa conformation with the sp (3)-hydridized C atom forming the flap. In the crystal, pairs of weak C-H⋯O hydrogen bonds link mol-ecules related by twofold rotation axes, forming R (2) 2(10) rings, which are in turn linked by weak C-H⋯N inter-actions to form chains of rings along [010]. In addition, weak C-H⋯π(arene) inter-actions link the chains into layers parallel to (001) and π-π inter-actions with a centroid-centroid distance of 3.836 (10) Šconnect these layers into a three-dimensional network.

Crystal structure of ethyl 5-(3-fluoro-phen-yl)-2-[(4-fluoro-phen-yl)methyl-idene]-7-methyl-3-oxo-2H,3H,5H-[1,3]thia-zolo[3,2-a]pyrimidine-6-carboxyl-ate.

In the title mol-ecule, C23H18F2N2O3S, the pyrimidine ring is in a half-chair conformation and the 3-fluoro-phenyl group is in the axial position. The thia-zole ring (r.m.s. deviation = 0.0252 Å) forms dihedral angles of 84.8 (7) and 9.6 (7)° with the 3-fluoro-substituted and 4-fluoro-substituted benzene rings, respectively. In the crystal, weak C-H⋯F and C-H⋯O hydrogen bonds connect mol-ecules, forming zigzag chains along the b axis. In addition π-π stacking inter-actions with a centroid-centroid distance of 3.7633 (9) Šconnect these chains into ladders via inversion-related 4-fluoro-phenyl groups.

Crystal structure of 2-acetyl-5-(3-methoxyphenyl)-3,7-dimethyl-5H-1,3-thiazolo[3,2-a]pyrimidine-6-carboxylate.

In the title mol-ecule, C20H22N2O4S, the pyrimidine ring is in a flattened half-chair conformation and the 3-meth-oxyphenyl substituent is in an axial arrangement. The thia-zole ring forms a dihedral angle of 81.3 (1)° with the benzene ring. In the crystal, weak C-H⋯S inter-actions link mol-ecules into chains along [001]. In addition, there are π-π inter-actions between inversion-related thia-zole rings with a centroid-centroid distance of 3.529 (2) Å. The ethyl group was refined as disordered over two sets of sites with an occupancy ratio of 0.52 (3):0.48 (2).

Evaluation of fluoride levels in areca nut, tobacco, and commercial smokeless tobacco products: a pilot study.

Oral submucous fibrosis (OSMF) is a premalignant condition associated with chewing areca nut and tobacco products. We observed increased fluoride levels in some OSMF-endemic regions,and the observation suggested that fluoride exposure may contribute to its pathogenesis. This study aimed to assess the fluoride content of various smokeless tobacco items as a potential influencing source. Fluoride concentration was analysed in commercial areca nut products, including gutkha, pan masala, and raw areca nut, along with tobacco, slaked lime, and catechu samples from Karnataka, India. Fluoride was measured using alkali fusion and the ion selective electrode method. All products showed high fluoride, with catechu having the highest mean concentration at 51.20 mg/kg, followed by tobacco, gutkha, pan masala, processed areca nut, and raw areca nut. Fluoride was also elevated in soil, but not in water. The findings demonstrate substantial fluoride levels in popular types of smokeless tobacco, and highlight an overlooked source of exposure among consumers of gutkha, pan masala and similar oral tobacco-products. The fluoride content warrants an investigation of potential links with the occurrence and severity of OSMF.

Anomalous ion charge distribution from cluster nanoplasmas.

In nearly all the intense laser experiments with nanoclusters, the key observation has been that immense ionization drives highly charged ions to highest energies while low charge ions, if any, have lower kinetic energies. We show experimental measurements that are contrary to this established notion. The active role of outer-ionized electrons in a multicluster interaction is shown to effectively reduce high charge ions to low charge states with no loss of momentum. The role of Rydberg excited clusters, intrinsic in dense cluster ensembles, is identified and a quantitative analysis is shown to comprehensively explain the anomalous charge distribution and ion energies observed in experiments.

2-[4-(Trifluoro-meth-oxy)phen-yl]-1H-benzimidazole.

In the title compound, C(14)H(9)F(3)N(2)O, the best planes of the benzimidazole group and benzene ring form a dihedral angle of 26.68 (3)°. In the crystal, N-H⋯N hydrogen bonds link the mol-ecules into infinite chains parallel to the c axis. Stacking inter-actions between the benzimidazole groups [centroid-centroid distance = 3.594 (5) Å] assemble the mol-ecules into layers parallel to (100). The trifluoro-methyl group is disordered over three sets of sites with site-occupancy factors of 0.787 (4), 0.107 (7) and 0.106 (7).

2-(3,4-Di-fluoro-phen-yl)-1H-benzimidazole.

In the title mol-ecule, C13H8F2N2, the dihedral angle between the benzimidazole ring system and the di-fluoro-substituted benzene ring is 30.0 (1)°. In the crystal, mol-ecules are linked by N-H⋯N hydrogen bonds, forming chains along [010]. In addition, weak C-H⋯F hydrogen bonds connect chains into a two-dimensional network parallel to (001). A weak C-H⋯π inter-action is observed between an H atom of the benzimidazole ring sytem and the π system of the di-fluoro-substituted benzene ring.

A bright point source of ultrashort hard x-ray pulses using biological cells.

We demonstrate that the interaction of intense femtosecond light on a plain solid substrate can be substantially altered by a few micron layer coating of bacterial cells, live or dead. Using E. Coli cells, we show that at an intensity of 10(16)W cm(-2), the bremsstraahlung hard x-ray emission (up to 300 keV), is increased by more than two orders of magnitude as compared to a plain glass slab. Particle-in-cell simulations carried out by modeling the bacterial cells as ellipsoidal particles show that the hot electron generation is indeed enhanced by the presence of microstructures. This new methodology should pave way for using microbiological systems of varied shapes to control intense laser produced plasmas for EUV/x-ray generation.

Conditional ß1-integrin-deficient mice display impaired pancreatic ß cell function.

ß1-Integrin, a critical regulator of ß cell survival and function, has been shown to protect against cell death and promote insulin expression and secretion in rat and human islet cells in vitro. The aim of the present study was to examine whether the knockout of ß1-integrin in collagen I-producing cells would have physiological and functional implications in pancreatic endocrine cells in vivo. Using adult mice with a conditional knockout of ß1-integrin in collagen I-producing cells, the effects of ß1-integrin deficiency on glucose metabolism and pancreatic endocrine cells were examined. Male ß1-integrin-deficient mice display impaired glucose tolerance, with a significant reduction in pancreatic insulin content (p < 0.01). Morphometric analysis revealed a significant reduction in ß cell mass (p < 0.001) in ß1-integrin-deficient mice, along with a significant decrease in ß cell proliferation, Pdx-1 and Nkx6.1 expression when compared with controls. Interestingly, these physiological and morphometric alterations in female ß1-integrin-deficient mice were less significant. Furthermore, ß1-integrin-deficient mice displayed decreased FAK (p < 0.05) and ERK1/2 (p < 0.001) phosphorylation, reduced cyclin D1 levels (p < 0.001) and increased caspase 3 cleavage (p < 0.01), while no changes in Akt phosphorylation were observed, indicating that the ß1-integrin signals through the FAK-MAPK-ERK pathway in vivo. Our results demonstrate that ß1-integrin is involved in the regulation of glucose metabolism and contributes to the maintenance of ß cell survival and function in vivo.

Luminous, relativistic, directional electron bunches from an intense laser driven grating plasma.

Bright, energetic, and directional electron bunches are generated through efficient energy transfer of relativistic intense (~ 1019 W/cm2), 30 femtosecond, 800 nm high contrast laser pulses to grating targets (500 lines/mm and 1000 lines/mm), under surface plasmon resonance (SPR) conditions. Bi-directional relativistic electron bunches (at 40° and 150°) are observed exiting from the 500 lines/mm grating target at the SPR conditions. The surface plasmon excited grating target enhances the electron flux and temperature by factor of 6.0 and 3.6, respectively, compared to that of the plane substrate. Particle-in-Cell simulations indicate that fast electrons are emitted in different directions at different stages of the laser interaction, which are related to the resultant surface magnetic field evolution. This study suggests that the SPR mechanism can be used to generate multiple, bright, ultrafast relativistic electron bunches for a variety of applications.

Dopant-induced ignition of helium nanodroplets in intense few-cycle laser pulses.

We demonstrate ultrafast resonant energy absorption of rare-gas doped He nanodroplets from intense few-cycle (~10 fs) laser pulses. We find that less than 10 dopant atoms "ignite" the droplet to generate a nonspherical electronic nanoplasma resulting ultimately in complete ionization and disintegration of all atoms, although the pristine He droplet is transparent for the laser intensities applied. Our calculations at those intensities reveal that the minimal pulse length required for ignition is about 9 fs.

Effect of forkhead box O1 (FOXO1) on beta cell development in the human fetal pancreas.

AIMS/HYPOTHESIS: Recent studies have demonstrated that in adult murine beta cells the forkhead box O1 (FOXO1) transcription factor regulates proliferation and stress resistance. However, the role of FOXO1 during pancreatic development remains largely unknown. The present study aimed to characterise the expression of the FOXO1 transcription factor in the early to mid-gestation human fetal pancreas and to understand its role in islet cell development. METHODS: Human (8-21 week fetal age) pancreases were examined using immunohistological, quantitative RT-PCR and western blotting. Isolated human (18-21 week) fetal islet epithelial cell clusters were treated with insulin or glucose, or transfected with FOXO1 small interfering RNA (siRNA). RESULTS: Nuclear and cytoplasmic FOXO1 were widely produced during human fetal endocrine pancreatic development, co-localising in cells with the transcription factors pancreatic and duodenal homeobox 1 (PDX-1) and neurogenin 3 (NGN3) as well as cytokeratin 19 (CK19), insulin and glucagon. Treatment with exogenous insulin (50 nmol/l) induced the nuclear exclusion of FOXO1 in both cytokeratin 19 (CK19)(+) (p < 0.01) and insulin(+) cells (p < 0.05) in parallel with increased phospho-Akt (p < 0.05) production. siRNA knockdown of FOXO1 significantly increased the number of NGN3(+) (p < 0.01) and NK6 homeobox 1 (NKX6-1)(+) (p < 0.05) cells in parallel with increases in insulin gene expression (p < 0.03) and C-peptide(+) cells (p < 0.05) and reduced levels of hairy and enhancer of split 1 (HES1) (p < 0.01). CONCLUSIONS/INTERPRETATION: Our results indicate that FOXO1 may negatively regulate beta cell differentiation in the human fetal pancreas by controlling critical transcription factors, including NGN3 and NKX6-1. These data suggest that the manipulation of FOXO1 levels may be a useful tool for improving cell-based strategies for the treatment of diabetes.

Direct, absolute, and in situ measurement of fast electron transport via Cherenkov emission.

We present direct measurements of the absolute energy distribution of relativistic electrons generated in intense, femtosecond laser interaction with a solid. Cherenkov emission radiated by these electrons in a novel prism target is spectrally dispersed to obtain yield and energy distribution of electrons simultaneously. A crucial advance is the observation of high density electron current as predicted by particle simulations and its transport as it happens inside the target. In addition, the strong sheath potential present at the rear side of the target is inferred from a comparison of the electron spectra derived from Cherenkov light observation with that from a magnet spectrometer.

On the importance of field driven single particle processes in short pulse absorption of clusters.

Nano-clusters are acclaimed to be very efficient absorbers of intense femto second light due to dominant collective mechanisms. Enhanced near 100% absorption due to collective linear plasma resonance compared to a small fraction of absorption by unclustered gas was an important drive in nano-plasma studies. Contrary to such perception, we show that if the pulse duration is (<100 fs), absorption is same irrespective of whether the systems are condensed to large clusters or not. So long as there are same number of similar ionizable systems in the focal volume, absorption is the same and such absorption can be accounted for by single particle response to the field and collisional ionization of atoms. Short pulse absorption by the single particle response can be comparable to the linear plasma resonance absorption for smaller clusters.

Data Mining by Pluralistic Approach on CRISPR Gene Editing in Plants.

Genome engineering by site-specific nucleases enables reverse genetics and targeted editing of genomes in an efficacious manner. Contemporary revolutionized progress in targeted-genome engineering technologies based on Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-related RNA-guided endonucleases facilitate coherent interrogation of crop genome function. Evolved as an innate component of the adaptive immune response in bacterial and archaeal systems, CRISPR/Cas system is now identified as a versatile molecular tool that ensures specific and targeted genome modification in plants. Applications of this genome redaction tool-kit include somatic genome editing, rectification of genetic disorders or gene therapy, treatment of infectious diseases, generation of animal models, and crop improvement. We review the utilization of these synthetic nucleases as precision, targeted-genome editing platforms with the inherent potential to accentuate basic science "strengths and shortcomings" of gene function, complement plant breeding techniques for crop improvement, and charter a knowledge base for effective use of editing technology for ever-increasing agricultural demands. Furthermore, the emerging importance of Cpf1, Cas9 nickase, C2c2, as well as other innovative candidates that may prove more effective in driving novel applications in crops are also discussed. The mined data has been prepared as a library and opened for public use at www.lipre.org.