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.

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.

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.

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.

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.

A gated Thomson parabola spectrometer for improved ion and neutral atom measurements in intense laser produced plasmas.

Ions of high energy and high charge are accelerated from compact intense laser produced plasmas and are routinely analysed either by time of flight or Thomson parabola spectrometry. At the highest intensities where ion energies can be substantially large, both these techniques have limitations. Strong electromagnetic pulse noise jeopardises the arrival time measurement, and a bright central spot in the Thomson parabola spectrometer affects the signal to noise ratio of ion traces that approach close to the central spot. We present a gated Thomson parabola spectrometer that addresses these issues and provides an elegant method to improvise ion spectrometry. In addition, we demonstrate that this method provides the ability to detect and measure high energy neutral atoms that are invariably present in most intense laser plasma acceleration experiments.

Compact acceleration of energetic neutral atoms using high intensity laser-solid interaction.

Recent advances in high-intensity laser-produced plasmas have demonstrated their potential as compact charge particle accelerators. Unlike conventional accelerators, transient quasi-static charge separation acceleration fields in laser produced plasmas are highly localized and orders of magnitude larger. Manipulating these ion accelerators, to convert the fast ions to neutral atoms with little change in momentum, transform these to a bright source of MeV atoms. The emittance of the neutral atom beam would be similar to that expected for an ion beam. Since intense laser-produced plasmas have been demonstrated to produce high-brightness-low-emittance beams, it is possible to envisage generation of high-flux, low-emittance, high energy neutral atom beams in length scales of less than a millimeter. Here, we show a scheme where more than 80% of the fast ions are reduced to energetic neutral atoms and demonstrate the feasibility of a high energy neutral atom accelerator that could significantly impact applications in neutral atom lithography and diagnostics.

Transition from Coherent to Stochastic electron heating in ultrashort relativistic laser interaction with structured targets.

Relativistic laser interaction with micro- and nano-scale surface structures enhances energy transfer to solid targets and yields matter in extreme conditions. We report on the comparative study of laser-target interaction mechanisms with wire-structures of different size, revealing a transition from a coherent particle heating to a stochastic plasma heating regime which occurs when migrating from micro-scale to nano-scale wires. Experiments and kinetic simulations show that large gaps between the wires favour the generation of high-energy electrons via laser acceleration into the channels while gaps smaller than the amplitude of electron quivering in the laser field lead to less energetic electrons and multi-keV plasma generation, in agreement with previously published experiments. Plasma filling of nano-sized gaps due to picosecond pedestal typical of ultrashort pulses strongly affects the interaction with this class of targets reducing the laser penetration depth to approximately one hundred nanometers. The two heating regimes appear potentially suitable for laser-driven ion/electron acceleration schemes and warm dense matter investigation respectively.

A source to deliver mesoscopic particles for laser plasma studies.

Intense ultrashort laser produced plasmas are a source for high brightness, short burst of X-rays, electrons, and high energy ions. Laser energy absorption and its disbursement strongly depend on the laser parameters and also on the initial size and shape of the target. The ability to change the shape, size, and material composition of the matter that absorbs light is of paramount importance not only from a fundamental physics point of view but also for potentially developing laser plasma sources tailored for specific applications. The idea of preparing mesoscopic particles of desired size/shape and suspending them in vacuum for laser plasma acceleration is a sparsely explored domain. In the following report we outline the development of a delivery mechanism of microparticles into an effusive jet in vacuum for laser plasma studies. We characterise the device in terms of particle density, particle size distribution, and duration of operation under conditions suitable for laser plasma studies. We also present the first results of x-ray emission from micro crystals of boric acid that extends to 100 keV even under relatively mild intensities of 1016 W/cm2.

N-Chlorosuccinimide-Mediated Oxidative Chlorination of Thiols to Nα -Protected Amino Alkyl Sulfonyl Azides and Their Utility in the Synthesis of Sulfonyl Triazole Acids

An efficient oxidative chlorination of thiols to Nα-protected amino alkyl sulfonyl azides is delineated. The reaction involves in situ generation of sulfonyl chloride employing Nchlorosuccinimide and tetrabutylammonium chloride-water in acetonitrile, followed by the reaction with sodium azide. The protocol is simple, straight forward, mild and high yielding. Amino acids with simple as well as bifunctional side chains were used to obtain Nα-protected amino alkyl sulfonyl azides. Further, sulfonyl azides were utilized to synthesize unnatural amino acids via Cu(OAc)2.H2O/2-amino phenol catalyzed Click reaction with propiolic acid.

N-Chlorosuccinimide-mediated oxidative chlorination of thiols to Nα-protected amino alkyl sulfonyl azides and their utility in the synthesis of sulfonyl triazole acids.

An efficient oxidative chlorination of thiols to Nα-protected amino alkyl sulfonyl azides is delineated. The reaction involves in situ generation of sulfonyl chloride employing N-chlorosuccinimide and tetrabutylammonium chloride-water in acetonitrile, followed by the reaction with sodium azide. The protocol is simple, straight forward, mild and high yielding. Amino acids with simple as well as bifunctional side chains were used to obtain Nα-protected amino alkyl sulfonyl azides. Further, sulfonyl azides were utilized to synthesize unnatural amino acids via Cu(OAc)2.H2O/2-amino phenol catalyzed Click reaction with propiolic acid.

Crystal structure of ethyl 4-(2-fluoro-phen-yl)-6-methyl-2-sulfanyl-idene-1,2,3,4-tetra-hydro-pyrimidine-5-carboxyl-ate.

The title compound, C14H15FN2O2S, crystallizes with two mol-ecules in the asymmetric unit. In each mol-ecule, the pyrimidine ring adopts a sofa conformation with the sp (3)-hybridized C atom forming the flap and the fluoro-substituted ring in an axial position. In the crystal, mol-ecules are linked via N-H⋯S hydrogen bonds, forming chains of R 2 (2)(8) rings along [100]. In one independent mol-ecule, an intra-molecular C-H⋯O hydrogen bond is observed.

Crystal structure of ethyl 5-acetyl-2-{[(di-methyl-amino)-methyl-idene]amino}-4-methyl-thio-phene-3-carboxyl-ate.

In the title thio-phene derivative, C13H18N2O3S, the dihedral angles between the thio-phene ring and the [(di-methyl-amino)-methyl-idene]amino side chain (r.m.s. deviation = 0.009 Å) and the -CO2 ester group are 3.01 (16) and 59.9 (3)°, respectively. In the crystal, inversion dimers linked by pairs of C-H⋯O hydrogen bonds generate R 2 (2)(16) loops. The dimers are linked by another weak C-H⋯O inter-action, forming chains along [001]. In addition, weak C-H⋯π inter-actions are observed, which link the chains into (001) layers.

Crystal structure of 2-acetyl-5-(3,4-di-meth-oxy-phen-yl)-6-eth-oxy-carbonyl-3,7-dimethyl-5H-thia-zolo[3,2-a]pyrimidin-8-ium chloride.

The title mol-ecular salt, C21H25N2O5S(+)·Cl(-), crystallizes with two ion pairs in the asymmetric unit. The cations have similar conformations (r.m.s. overlay fit = 0.40 Å), with one of them showing disorder of the terminal methyl group of the ester in a 0.72 (2):0.28 (2) ratio. In the first cation, the 3,4-dimeth-oxy-substituted phenyl ring subtends a dihedral angle of 88.38 (7)° with the pyrimidine ring and 6.79 (8)° with the thia-zole ring. The equivalent data for the second cation are 89.97 (3) and 6.42 (7)°, respectively. The pyrimidine ring adopts a sofa conformation in each cation. In the crystal, the components are linked by N-H⋯Cl hydrogen bonds, generating isolated ion pairs. The ion pairs are are linked by C-H⋯O inter-actions, generating a three-dimensional network. In addition, a weak C-H⋯π inter-action is observed.

Crystal structure of methyl 4-(2-fluoro-phenyl)-6-methyl-2-sulfanylidene-1,2,3,4-tetra-hydro-pyrimidine-5-carb-oxy-late.

In the title compound, C13H13FN2O2S, the pyrimidine ring adopts a twist-boat conformation with the MeCN and methine-C atoms displaced by 0.0938 (6) and 0.2739 (3) Å, respectively, from the mean plane through the other four atoms of the ring. The 2-fluoro-benzene ring is positioned axially and forms a dihedral angle of 89.13 (4)° with the mean plane through the pyrimidine ring. The crystal structure features N-H⋯O, N-H⋯S and C-H⋯O hydrogen bonds that link mol-ecules into supra-molecular chains along the b axis. These chains are linked into a layer parallel to (10-1) by C-H⋯π inter-actions; layers stack with no specific inter-actions between them.

Crystal structure of ethyl 2-acetyl-3,7-dimethyl-5-(thio-phen-2-yl)-5H-thia-zolo[3,2-a]pyrimidine-6-carboxyl-ate.

In the title compound, C17H18N2O3S2, the pyrimidine ring adopts a shallow sofa conformation, with the C atom bearing the axially-oriented thio-phene ring as the flap [deviation = 0.439 (3) Å]. The plane of the thio-phene ring lies almost normal to the pyrimidine ring, making a dihedral angle of 79.36 (19)°. In the crystal, pairs of very weak C-H⋯O hydrogen bonds link the mol-ecules related by twofold rotation axes, forming R 2 (2)(18) rings, which are in turn linked by another C-H⋯O inter-action, forming chains of rings along [010]. In addition, weak C-H⋯π(thio-phene) inter-actions link the chains into layers parallel to [001] and π-π inter-actions with a centroid-centroid distance of 3.772 (10) Šconnect these layers into a three-dimensional network.

Preferential enhancement of laser-driven carbon ion acceleration from optimized nanostructured surfaces.

High-intensity ultrashort laser pulses focused on metal targets readily generate hot dense plasmas which accelerate ions efficiently and can pave way to compact table-top accelerators. Laser-driven ion acceleration studies predominantly focus on protons, which experience the maximum acceleration owing to their highest charge-to-mass ratio. The possibility of tailoring such schemes for the preferential acceleration of a particular ion species is very much desired but has hardly been explored. Here, we present an experimental demonstration of how the nanostructuring of a copper target can be optimized for enhanced carbon ion acceleration over protons or Cu-ions. Specifically, a thin (≈ 0.25 µm) layer of 25-30 nm diameter Cu nanoparticles, sputter-deposited on a polished Cu-substrate, enhances the carbon ion energy by about 10-fold at a laser intensity of 1.2 × 10(18) W/cm(2). However, particles smaller than 20 nm have an adverse effect on the ion acceleration. Particle-in-cell simulations provide definite pointers regarding the size of nanoparticles necessary for maximizing the ion acceleration. The inherent contrast of the laser pulse is found to play an important role in the species selective ion acceleration.

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.