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A simple model based on the Holstein-Peirls-Hubbard Hamiltonian are used to calculate the nonlinear responses at infrared and optical frequencies. The model is applied to a molecular ion radical dimer in order to account for the contribution to the nonlinear responses arising from the intermolecular charge transfer excitations and from their coupling to both intramolecular and intermolecular phonons.

Abstract: The huge signal enhancement that motivates the rapid spreading of surface‐enhanced Raman scattering (SERS) in a wide range of applications is commonly quantified by measuring the enhancement factor (EF). Concerning this important parameter, in this paper, we tackle 2 points: (a) We validate the use of a Macro Raman configuration with line focus to measure the EFs, against the more common Micro Raman one. The validation is carried out by comparing the EFs measured in the 2 configurations with the well‐established methodology, on the same set of commercial substrates. Macro Raman with line focus can be advantageous over the Micro Raman because it can provide a higher signal‐to‐noise ratio at equal laser intensity impinging on the sample (useful in sensing or analytical applications). (b) It is a common practice for practitioners validating an experiment by measuring a commercial compound, acting as a “standard,” whose properties have been already determined in the literature: To our knowledge, an equivalent “standard” does not exist for EF measurements, probably due to the reproducibility and aging issues that prevent them from being identically reproduced in different laboratories. Because the EF is the cross‐section ratio of a test molecule under SERS and normal Raman conditions, if one replaces the SERS substrate and the reference liquid with 2 commercial materials in the EF measurement procedure, this leads to the determination of another cross‐section ratio: We propose then to use the cross‐section ratio of suitable commercial materials for the validation of the instrumental procedure used to measure EFs. [ABSTRACT FROM AUTHOR]

The development and understanding of alternative plasmonic materials are crucial steps for leveraging new plasmonic technologies. Although gold and silver nanostructures have been intensively studied, the promising plasmonic, chemical and physical attributes of rhodium remain poorly investigated. Here, we report the synthesis and plasmonic response of spherical Rh nanoparticles (NPs) with sizes in the 20-40 nm range. Due to the high cohesive energy of this metal, synthesis and experimental investigations of Rh nanospheres in this size range have not been reported; yet, it becomes possible here using a green and one-step laser ablation in liquid method. The localized surface plasmon (LSP) of Rh NPs falls in the ultraviolet spectral range (195-255 nm), but the absorption tail in the visible region increases significantly upon clustering of the nanospheres. The surface binding ability of Rh NPs towards thiolated molecules is equivalent to that of Au and Ag NPs, while their chemical and physical stability at high temperatures and in the presence of strong acids such as aqua regia is superior to those of Au and Ag NPs. The plasmonic features are well described by classical electrodynamics, and the results are comparable to Au and Ag NPs in terms of extinction cross-section and local field enhancement, although blue shifted. This allowed, for instance, their use as an optical nanosensor for the detection of ions of toxic metals in aqueous solution and for the surface enhanced Raman scattering of various compounds under blue light excitation. This study explores the prospects of Rh NPs in the realms of UV and visible plasmonics, while also envisaging a multitude of opportunities for other underexplored applications related to plasmon-enhanced catalysis and chiroplasmonics.

Background: The preplanned interim analysis of the COMMANDS trial showed greater efficacy of luspatercept than epoetin alfa for treating anaemia in erythropoiesis-stimulating agent (ESA)-naive patients with transfusion-dependent, lower-risk myelodysplastic syndromes. In this Article, we report the results of the primary analysis of the trial., Methods: COMMANDS is a phase 3, open-label, randomised, controlled trial conducted at 142 sites in 26 countries. Eligible patients were those aged 18 years or older, with myelodysplastic syndromes of very low risk, low risk, or intermediate risk (as defined by the Revised International Prognostic Scoring System), who were ESA-naive and transfusion dependent, and had a serum erythropoietin concentration of less than 500 U/L. Patients were stratified by baseline red blood cell transfusion burden, serum erythropoietin concentration, and ring sideroblast status, and randomly allocated (1:1) to receive luspatercept (1·0-1·75 mg/kg body weight, subcutaneously, once every 3 weeks) or epoetin alfa (450-1050 IU/kg body weight, subcutaneously, once a week; maximum total dose 80 000 IU) for at least 24 weeks. The primary endpoint was red blood cell transfusion independence lasting at least 12 weeks with a concurrent mean haemoglobin increase of at least 1·5 g/dL (weeks 1-24), evaluated in the intention-to-treat population. The safety population included all patients who received at least one dose of treatment. This trial is registered with ClinicalTrials.gov (NCT03682536; active, not recruiting)., Findings: Between Jan 2, 2019, and Sept 29, 2022, 363 patients were screened and randomly allocated: 182 (50%) to luspatercept and 181 (50%) to epoetin alfa. Median age was 74 years (IQR 69-80), 162 (45%) patients were female, and 201 (55%) were male. 289 (80%) were White, 44 (12%) were Asian, and two (1%) were Black or African American. 23 (6%) were Hispanic or Latino and 311 (86%) were not Hispanic or Latino. Median follow-up for the primary endpoint was 17·2 months (10·4-27·7) for the luspatercept group and 16·9 months (10·1-26·6) for the epoetin alfa group. A significantly greater proportion of patients in the luspatercept group reached the primary endpoint (110 [60%] vs 63 [35%]; common risk difference on response rate 25·4% [95% CI 15·8-35·0]; p<0·0001). Median follow-up for safety analyses was 21·4 months (IQR 14·2-32·4) for the luspatercept group and 20·3 months (12·7-30·9) for the epoetin alfa group. Common grade 3-4 treatment-emergent adverse events occurring among luspatercept recipients (n=182) were hypertension (19 [10%] patients), anaemia (18 [10%]), pneumonia (ten [5%]), syncope (ten [5%]), neutropenia (nine [5%]), thrombocytopenia (eight [4%]), dyspnoea (eight [4%]), and myelodysplastic syndromes (six [3%]); and among epoetin alfa recipients (n=179) were anaemia (14 [8%]), pneumonia (14 [8%]), neutropenia (11 [6%]), myelodysplastic syndromes (ten [6%]), hypertension (eight [4%]), iron overload (seven [4%]), and COVID-19 pneumonia (six [3%]). The most common serious treatment-emergent adverse events in both groups were pneumonia (nine [5%] luspatercept recipients and 13 [7%] epoetin alfa recipients) and COVID-19 (eight [4%] luspatercept recipients and ten [6%] epoetin alfa recipients). One death (due to acute myeloid leukaemia) considered to be luspatercept-related was reported at the interim analysis., Interpretation: Luspatercept represents a new standard of care for ESA-naive patients with transfusion-dependent, lower-risk myelodysplastic syndromes. Significantly more patients had red blood cell transfusion independence and haematological improvement with luspatercept than with epoetin alfa, with benefits observed across patient subgroups., Funding: Celgene and Acceleron Pharma., Competing Interests: Declaration of interests Editorial and medical writing support were funded by Bristol Myers Squibb. MGDP reports receiving honoraria from and advisory or data safety monitoring board fees from Bristol Myers Squibb. GG-M reports receiving consulting fees from Bristol Myers Squibb; research support from AbbVie, Astex, Bristol Myers Squibb, Chordia, Curis, Genentech, Novartis, Rigel Pharmaceuticals, and Zentalis; and honoraria from Astex and Curis. VS reports receiving honoraria from AbbVie, Bristol Myers Squibb, and Novartis; travel support from AbbVie and Jazz Pharmaceuticals; and advisory or data safety monitoring board fees from AbbVie, Bristol Myers Squibb, CTI BioPharma, Curis, Geron, Gilead, Keros, Menarini, Novartis, Servier, and Syros. AMZ reports receiving grant support from AbbVie, Amgen, Astex, Bristol Myers Squibb, Celgene, Geron, Kura, Novartis, Otsuka, Shattuck Labs, and Syros; and consulting fees and honoraria from AbbVie, Agios, Akeso Pharma, ALX Oncology, Amgen, Astellas Pharma, BeiGene, BioCryst, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Chiesi, Daiichi Sankyo, Epizyme, Faron, Genentech, Geron, Gilead, Glycomimetics, Hikma, Janssen, Karyopharma, Keros, Kura, Kyowa Kirin, Lava Therapeutics, Medus, Notable, Novartis, Orum, Otsuka, Pfizer, Regeneron, Rigel Pharmaceuticals, Schrodinger, Servier, Sumitomo Pharma, Syndax, Syros, Taiho, Takeda, Treadwell, Vincerx, and Zentalis. RSK reports receiving grant support from Bristol Myers Squibb; consulting fees from Geron, Janssen, and Sumitomo Pharma; speakers bureau fees from AbbVie, Jazz Pharmaceuticals, Pharma Essentia, Rigel Pharmaceuticals, Servio, and Sobi; and advisory or data safety monitoring board fees from AbbVie, Bristol Myers Squibb, DSI, Jazz Pharmaceuticals, Pharma Essentia, Rigel Pharmaceuticals, Servio, Sobi, and Sumitomo Pharma. JS reports receiving grant support from Amgen Australia, Astex Pharmaceuticals, and Bristol Myers Squibb; consulting fees paid to himself from Astellas Pharma, Mundipharma, Novartis, Otsuka, and Pfizer; speakers bureau fees paid to himself and his institution from Mundipharma and Novartis; support for meeting attendance from AstraZeneca (no payment to healthcare provider); being a named investigator on patent PCT/AU2021/050562 assigned to his institution; trial steering committee fees paid to his institution from Bristol Myers Squibb; and serving an unpaid appointment on the Australasia Leukaemia and Lymphoma Group Scientific Advisory Committee. DV reports receiving consulting fees from Amgen, Astellas Pharma, Bristol Myers Squibb, Jazz Pharmaceuticals, Kite Pharma, Merck Sharp & Dohme, Novartis, Sanofi, and Sobi; honoraria from Agios, Amgen, Astellas Pharma, Bristol Myers Squibb, Gebro, Grifols, Janssen, Jazz Pharmaceuticals, Kite Pharma, Merck Sharp & Dohme, Novartis, Pfizer, Sanofi, and Sobi; travel support from Bristol Myers Squibb, Jazz Pharmaceuticals, Novartis, Sanofi, and Sobi; and advisory or data safety monitoring board fees from Amgen, Bristol Myers Squibb, Grifols, Jazz Pharmaceuticals, Novartis, Servier, and Sobi. AJ reports receiving support for study materials from Bristol Myers Squibb; consulting fees from Bristol Myers Squibb; honoraria from AbbVie, Bristol Myers Squibb, and Novartis; travel support from AbbVie and Novartis; advisory or data safety monitoring board fees from AbbVie, Bristol Myers Squibb, GSK, and Novartis; and a leadership or fiduciary role as the head of the Czech MDS Group. JL, RP, SK, KLK, TP, and YL are employed by and own stock in Bristol Myers Squibb. JZ is employed by Bristol Myers Squibb. VP is employed by and owns stock in Bristol Myers Squibb and owns stock in Merck. SR is employed by, owns stock in, and has received travel support from Bristol Myers Squibb and owns stock in Celgene. AD reports receiving honoraria from Bristol Myers Squibb; travel support from Johnson & Johnson; and advisory or data safety monitoring board fees from Swixx BioPharma. TC reports receiving consulting fees from AbbVie, Agios, BluePrint, Bristol Myers Squibb/Celgene, Jazz Pharmaceuticals, Novartis, and Servier; honoraria from Astellas, Bristol Myers Squibb/Celgene, Incyte, Jazz Pharmaceuticals, Novartis, Servier, and Takeda; travel support from AbbVie, Bristol Myers Squibb/Celgene, Gilead, Novartis, Pfizer, and Servier; and advisory or data safety monitoring board fees from Astellas, Bristol Myers Squibb/Celgene, Incyte, Jazz Pharmaceuticals, Novartis, Servier, and Takeda. PF reports receiving grant support from AbbVie, Agios, Bristol Myers Squibb, and Novartis; and honoraria from AbbVie, Agios, Bristol Myers Squibb, and Novartis. UP reports receiving grant support paid to GWT-TUD, from Amgen and Janssen; grant support, paid to University of Leipzig, from Bristol Myers Squibb, Merck, and Novartis; consulting fees from AbbVie, Bristol Myers Squibb, Curis, Geron, Janssen, and Novartis; honoraria from Bristol Myers Squibb and Novartis; and fees for serving on a steering committee and travel support from Bristol Myers Squibb. All other authors declare no competing interests., (2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Graphyne- and graphdiyne-like model systems have attracted much attention from many structural, theoretical, and synthetic scientists because of their promising electronic, optical, and mechanical properties, which are crucially affected by the presence, abundance and distribution of triple bonds within the nanostructures. In this work, we performed the two-step bottom-up on-surface synthesis of graphyne- and graphdiyne-based molecular wires on the Au(111). We characterized their structural and chemical properties both in situ (UHV conditions) through STM and XPS and ex situ (in air) through Raman spectroscopy. By comparing the results with the well-known growth of poly( p -phenylene) wires (namely the narrowest armchair graphene nanoribbon), we were able to show how to discriminate different numbers of triple bonds within a molecule or a nanowire also containing phenyl rings. Even if the number of triple bonds can be effectively determined from the main features of STM images and confirmed by fitting the C1s peak in XPS spectra, we obtained the most relevant results from ex situ Raman spectroscopy, despite the sub-monolayer amount of molecular wires. The detailed analysis of Raman spectra, combined with density functional theory (DFT) simulations, allowed us to identify the main features related to the presence of isolated (graphyne-like systems) or at least two conjugated triple bonds (graphdiyne-like systems). Moreover, other spectral features can be exploited to understand if the chemical structure of graphyne- and graphdiyne-based nanostructures suffered unwanted reactions. As in the case of sub-monolayer graphene nanoribbons obtained by on-surface synthesis, we demonstrate that Raman spectroscopy can be used for a fast, highly sensitive and non-destructive determination of the properties, the quality and the stability of the graphyine- and graphdiyne-based nanostructures obtained by this highly promising approach.

The accurate determination of the local temperature is one of the most important challenges in the field of nanotechnology and nanomedicine. For this purpose, different techniques and materials have been extensively studied in order to identify both the best-performing materials and the techniques with greatest sensitivity. In this study, the Raman technique was exploited for the determination of the local temperature as a non-contact technique and titania nanoparticles (NPs) were tested as nanothermometer Raman active material. Biocompatible titania NPs were synthesized following a combination of sol-gel and solvothermal green synthesis approaches, with the aim of obtaining pure anatase samples. In particular, the optimization of three different synthesis protocols allowed materials to be obtained with well-defined crystallite dimensions and good control over the final morphology and dispersibility. TiO 2 powders were characterized by X-ray diffraction (XRD) analyses and room-temperature Raman measurements, to confirm that the synthesized samples were single-phase anatase titania, and using SEM measurements, which clearly showed the nanometric dimension of the NPs. Stokes and anti-Stokes Raman measurements were collected, with the excitation laser at 514.5 nm (CW Ar/Kr ion laser), in the temperature range of 293-323 K, a range of interest for biological applications. The power of the laser was carefully chosen in order to avoid possible heating due to the laser irradiation. The data support the possibility of evaluating the local temperature and show that TiO 2 NPs possess high sensitivity and low uncertainty in the range of a few degrees as a Raman nanothermometer material.

Noble metal nanoparticles are efficient converters of light into heat but typically cover a limited spectral range or have intense light scattering, resulting in unsuited for broadband thermoplasmonic applications and sunlight-driven heat generation. Here, Au-Ag alloy nanoparticles were deliberately molded with an irregular nanocoral (NC) shape to obtain broadband plasmon absorption from the visible to the near-infrared yet at a lower cost compared to pure Au nanostructures. The Au-Ag NCs are produced through a green and scalable methodology that relies on pulsed laser fragmentation in a liquid, without chemicals or capping molecules, leaving the particles surface free for conjugation with thiolated molecules and enabling full processability and easy inclusion in various matrixes. Numerical calculations showed that panchromism, i.e., the occurrence of a broadband absorption from the visible to the near-infrared region, is due to the special morphology of Au-Ag alloy NCs and consists of a purely absorptive behavior superior to monometallic Au or Ag NCs. The thermoplasmonic properties were assessed by multiwavelength light-to-heat conversion experiments and exploited for the realization of a cellulose-based solar-steam generation device with low-cost, simple design but competitive performances. Overall, here it is shown how laser light can be used to harvest solar light. Besides, the optimized broadband plasmon absorption, the green synthetic procedure, and the other set of positive features for thermoplasmonic applications of Au-Ag NCs will contribute to the development of environmentally friendly devices of practical utility in a sustainable world.

This paper reports on the fabrication and characterization of a plasmonic/sol-gel sensor for the detection of aromatic molecules. The sol-gel film was engineered using polysilsesquioxanes groups to capture the analyte, through π-π interaction, and to concentrate it close to the plasmonic surface, where Raman amplification occurs. Xylene was chosen as an analyte to test the sensor. It belongs to the general class of volatile organic compounds and can be found in water or in the atmosphere as pollutants released from a variety of processes; its detection with SERS is typically challenging, due to its low affinity toward metallic surfaces. The identification of xylene was verified in comparison with that of other aromatic molecules, such as benzene and toluene. Investigations were carried out on solutions of xylene in cyclohexane, using concentrations in the range from 0 to 800 mM, to evaluate the limit of detection (LOD) of about 40 mM.

Nonequilibrium nanoalloys are metastable solids obtained at the nanoscale under nonequilibrium conditions that allow the study of kinetically frozen atoms and the discovery of new physical and chemical properties. However, the stabilization of metastable phases in the nanometric size regime is challenging and the synthetic route should be easy and sustainable, for the nonequilibrium nanoalloys to be practically available. Here we report on the one-step laser ablation synthesis in solution (LASiS) of nonequilibrium Au-Co alloy nanoparticles (NPs) and their characterization on ensembles and at the single nanoparticle level. The NPs are obtained as a polycrystalline solid solution stable in air and water, although surface cobalt atoms undergo oxidation to Co(II). Since gold is a renowned plasmonic material and metallic cobalt is ferromagnetic at room temperature, these properties are both found in the NPs. Besides, surface conjugation with thiolated molecules is possible and it was exploited to obtain colloidally stable solutions in water. Taking advantage of these features, an array of magnetic-plasmonic dots was obtained and used for surface-enhanced Raman scattering experiments. Overall, this study confirms that LASiS is an effective method for the formation of kinetically stable nonequilibrium nanoalloys and shows that Au-Co alloy NPs are appealing magnetically responsive plasmonic building blocks for several nanotechnological applications., (© 2021 Wiley-VCH GmbH.)

The determination of local temperature at the nanoscale is a key point to govern physical, chemical and biological processes, strongly influenced by temperature. Since a wide range of applications, from nanomedicine to nano- or micro-electronics, requires a precise determination of the local temperature, significant efforts have to be devoted to nanothermometry. The identification of efficient materials and the implementation of detection techniques are still a hot topic in nanothermometry. Many strategies have been already investigated and applied to real cases, but there is an urgent need to develop new protocols allowing for accurate and sensitive temperature determination. The focus of this work is the investigation of efficient optical thermometers, with potential applications in the biological field. Among the different optical techniques, Raman spectroscopy is currently emerging as a very interesting tool. Its main advantages rely on the possibility of carrying out non-destructive and non-contact measurements with high spatial resolution, reaching even the nanoscale. Temperature variations can be determined by following the changes in intensity, frequency position and width of one or more bands. Concerning the materials, Titanium dioxide has been chosen as Raman active material because of its intense cross-section and its biocompatibility, as already demonstrated in literature. Raman measurements have been performed on commercial anatase powder, with a crystallite dimension of hundreds of nm, using 488.0, 514.5, 568.2 and 647.1 nm excitation lines of the CW Ar + /Kr + ion laser. The laser beam was focalized through a microscope on the sample, kept at defined temperature using a temperature controller, and the temperature was varied in the range of 283-323 K. The Stokes and anti-Stokes scattered light was analyzed through a triple monochromator and detected by a liquid nitrogen-cooled CCD camera. Raw data have been analyzed with Matlab, and Raman spectrum parameters-such as area, intensity, frequency position and width of the peak-have been calculated using a Lorentz fitting curve. Results obtained, calculating the anti-Stokes/Stokes area ratio, demonstrate that the Raman modes of anatase, in particular the E g one at 143 cm -1 , are excellent candidates for the local temperature detection in the visible range.

Introduction: Despite improvements in the treatment of advanced non-small cell lung cancer (NSCLC), certain patient populations remain underrepresented in clinical trials. Many patients have benefited from platinum doublets, including nab -paclitaxel-based regimens, but there are patients with comorbidities who particularly require careful balancing of efficacy and safety. Clinical trial data are limited for patients who are elderly or have renal impairment, diabetes, or impaired performance status., Methods: To better understand outcomes in these patient populations, we performed a pooled analysis using data from the ABOUND clinical trial program (ABOUND.SQM, ABOUND.PS2, ABOUND.70+) and the key phase III trial of nab -paclitaxel/carboplatin in advanced NSCLC. The populations included in this pooled analysis consisted of elderly patients (≥ 70 years) and patients with renal impairment (eGFR < 60 ml/min/1.73 m 2 ), diabetes, or poor performance status (ECOG PS 2)., Results: Median progression-free survival (PFS) ranged from 4.1 months in patients with ECOG PS 2 (95% CI, 2.04-5.09 months) to 7.7 months in patients with diabetes (95% CI, 5.88-10.12 months). PFS for elderly patients and patients with renal impairment was 6.9 months each (95% CI, 6.01-7.98 months and 4.47-9.79 months, respectively). Median overall survival (OS) was 18.2 months (95% CI, 10.94-28.22 months), 17.4 months (95% CI, 14.59-20.14 months), and 16.1 months (95% CI, 14.09-18.50 months) in patients with renal impairment, patients with diabetes, and elderly patients, respectively. Patients with ECOG PS 2 exhibited the shortest median OS: 5.6 months (95% CI, 3.98-11.37 months). Overall response rates were 56.9%, 54.6%, 45.9%, and 29.4% in patients with diabetes, elderly patients, patients with renal impairment, and patients with ECOG PS 2, respectively. Most treatment-related adverse events were hematologic. The most common grade 3/4 hematologic adverse events in patients with renal impairment, elderly patients, patients with diabetes, and patients with poor performance status included neutropenia, anemia, and thrombocytopenia., Conclusions: Although survival data in patients with ECOG PS 2 were notably inferior to the other cohorts, our findings are consistent with those previously reported in the population-specific studies of the ABOUND trials and lend additional support for the use of nab -paclitaxel-based regimens in historically understudied and vulnerable populations., Competing Interests: CJL: Consultant/advisory fees, Celgene Corporation; other consulting fees: AstraZeneca, Bristol Myers Squibb, Genentech/Roche, Novartis, Pfizer, Takeda, Hospira, Merck, Boehringer Ingelheim. AG: Honoraria for Advisory Board, AstraZeneca; other fees, ICON Plc, CRO. CG: Advisory Board and Speakers’ Bureau member, MSD, Bristol Myers Squibb, Roche, AstraZeneca. DM: Advisory/Consultant, AbbVie, Bristol Myers Squibb, PharmaMar, Takeda. DS: Consulting or advisory role and research funding, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Celgene Corporation, Genentech/Roche, Lilly, Novartis, Pfizer; research funding, Merck, University of Texas Southwestern Medical Center—Simmons Cancer Center. MT: Grants, Celgene Corporation, Bristol Myers Squibb, Roche, AstraZeneca; consulting fees, Celgene Corporation, AbbVie, Bristol Myers Squibb, Boehringer Ingelheim, Lilly, MSD, Novartis, Roche. JW: Grants, Celgene Corporation; consulting fees, Celgene Corporation. RP: Employment, Bristol Myers Squibb. RB: Employment, Bristol Myers Squibb. MW: Consulting fees, Bristol Myers Squibb. TJO: Employment, Bristol Myers Squibb. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declare that this study received funding from Celgene, a wholly owned subsidiary of Bristol Myers Squibb. The funder had the following involvement with the study: study design, data collection and data analysis., (Copyright © 2021 Langer, Gajra, Gridelli, Konduri, Morgensztern, Spigel, Talbot, Thomas, Weiss, Pilot, Bhore, Wolfsteiner, Ong and Socinski.)

We tested the hypothesis that reduced-salt versions of four "better-for-you" dishes enhanced with monosodium glutamate (MSG) through a "Salt Flip" in an amount that still substantially reduced total sodium matched the consumer acceptance of normal-salt versions. Three versions each-standard recipe with normal salt, reduced salt, and reduced salt with MSG, of four dishes-roasted vegetables (RV), quinoa bowl (QB), savory yogurt dip (SD), and pork cauliflower fried rice (CR) were evaluated by 163 consumers for overall liking and liking of appearance, flavor, and texture/mouthfeel on the nine-point hedonic scale, preference, adequacy of flavor, saltiness, and aftertaste on just-about-right (JAR) scales, likeliness to order, and sensory characteristics by check-all-that-apply. For each dish, the MSG recipe was liked the same (or significantly more for SD, P < 0.05) than the standard recipe, and better than the reduced salt recipe for QB and CR. The same was true of likeliness to order. MSG recipes of QB and SD were significantly preferred to the standard recipes, with no difference for RV and CR. MSG recipes were consistently described as "delicious," "flavorful," and "balanced." Penalty-lift analysis showed that "delicious," "flavorful," "balanced," "fresh," and "savory"; and "bland," "rancid," and "bitter," were positive and negative drivers of liking, respectively. Two of three uncovered preference clusters, accounting for 68% of consumers, consistently liked MSG recipes, and the same or more so than standard recipes. We conclude that MSG can successfully be used to mitigate salt and sodium reduction without compromising consumer acceptance of better-for-you foods. PRACTICAL APPLICATION: The Salt Flip offers a promising dietary sodium reduction strategy through the addition of monosodium glutamate (MSG) to reduced-salt, savory, better-for-you foods that does not compromise consumer acceptance of their sensory profile., (© 2020 The Authors. Journal of Food Science published by Wiley Periodicals LLC on behalf of Institute of Food Technologists.)

Surface-enhanced Raman scattering (SERS) has become a powerful tool in chemical, material and life sciences, owing to its intrinsic features (i.e., fingerprint recognition capabilities and high sensitivity) and to the technological advancements that have lowered the cost of the instruments and improved their sensitivity and user-friendliness. We provide an overview of the most significant aspects of SERS. First, the phenomena at the basis of the SERS amplification are described. Then, the measurement of the enhancement and the key factors that determine it (the materials, the hot spots, and the analyte-surface distance) are discussed. A section is dedicated to the analysis of the relevant factors for the choice of the excitation wavelength in a SERS experiment. Several types of substrates and fabrication methods are illustrated, along with some examples of the coupling of SERS with separation and capturing techniques. Finally, a representative selection of applications in the biomedical field, with direct and indirect protocols, is provided. We intentionally avoided using a highly technical language and, whenever possible, intuitive explanations of the involved phenomena are provided, in order to make this review suitable to scientists with different degrees of specialization in this field., Competing Interests: The authors declare no conflicts of interest.

In the last two decades, plasmon resonance in gold nanoparticles (Au NPs) has been the subject of intense research efforts. Plasmon physics is intriguing and its precise modelling proved to be challenging. In fact, plasmons are highly responsive to a multitude of factors, either intrinsic to the Au NPs or from the environment, and recently the need emerged for the correction of standard electromagnetic approaches with quantum effects. Applications related to plasmon absorption and scattering in Au NPs are impressively numerous, ranging from sensing to photothermal effects to cell imaging. Also, plasmon-enhanced phenomena are highly interesting for multiple purposes, including, for instance, Raman spectroscopy of nearby analytes, catalysis, or sunlight energy conversion. In addition, plasmon excitation is involved in a series of advanced physical processes such as non-linear optics, optical trapping, magneto-plasmonics, and optical activity. Here, we provide the general overview of the field and the background for appropriate modelling of the physical phenomena. Then, we report on the current state of the art and most recent applications of plasmon resonance in Au NPs.

Purpose: To examine outcomes in a phase 3 trial of nab-paclitaxel plus carboplatin (nab-P/C) versus solvent-based paclitaxel plus carboplatin (sb-P/C) in a subset of patients with advanced non-small-cell lung cancer (NSCLC) and diabetes., Patients and Methods: Patients with stage IIIB/IV NSCLC received nab-P 100 mg/m 2 on days 1, 8, and 15 or sb-P 200 mg/m 2 on day 1, both with C at an area under the curve of 6 mg·min/mL on day 1 every 3 weeks. Overall response rate (ORR) and progression-free survival (PFS) were determined by blinded, independent, centralized review. P values were based on chi-square test for ORR and log-rank test for overall survival (OS) and PFS., Results: Of the 1052 randomized patients in the phase 3 trial, 61 had diabetes according to prespecified terms (nab-P/C, 31; sb-P/C, 30). ORR for nab-P/C versus sb-P/C in this subset was 52% versus 27% (relative risk ratio, 1.935; P = .046), median PFS was 10.9 versus 4.9 months (hazard ratio, 0.420; P = .016), and median OS was 17.5 versus 11.1 months (hazard ratio, 0.550; P = .057). Treatment differences in PFS remained significant (P ≤ .036) after adjusting for histology, region, stage, race, and age and also remained significant in OS for histology (P = .039). Patients with diabetes experienced lower rates of grade 3 or higher neutropenia and peripheral neuropathy and higher rates of thrombocytopenia and anemia with nab-P/C versus sb-P/C., Conclusion: nab-P/C demonstrated improved efficacy and manageable tolerability in patients with advanced NSCLC and diabetes., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Educational brochures are an important tool for communicating risk to health-care professionals. It is important to evaluate the impact of any risk minimization tool to understand the effectiveness of the strategy. The objective of this study was to assess the effectiveness (i.e., respondents' awareness and understanding of the communication) of a targeted educational brochure distributed to health-care professionals (HCPs) as a risk minimization strategy for the communication of new rare and important adverse events (AEs)., Methods: A prospective, non-interventional, online survey was performed following distribution of a specifically designed brochure highlighting new and important adverse events to a targeted HCP population, consisting of known users of the target medicine, as represented by a commercial database. Predefined multiple-choice survey questions assessed overall HCP awareness of the brochure and understanding and retention of information in those HCPs who reported receiving the brochure., Results: The educational brochure was sent to a total of 565 HCPs; 121 (21.4%) responded to the survey. The majority of respondents (95.0%) had previously prescribed or dispensed the target medicine. In all, 88 (72.7%) respondents said they had received the educational brochure, of whom 95.5% stated they had at least scanned the main points. More participants who had received the brochure (86.4% to 96.6%) answered the five individual survey questions correctly compared with those who did not (51.5% to 97.0%); this was significant for four out of five questions (P ≤ 0.005). Significantly more HCPs who received the brochure achieved the predefined pass rate (at least four of five questions answered correctly) compared with HCPs who did not receive the brochure (93.2% vs 57.6%, respectively; P = 0.000003)., Conclusions: Distribution of targeted educational brochures may be an effective risk minimization strategy to raise HCP awareness of new rare and important AEs; educational brochures may also be an effective channel for sharing information on how these AEs can be best managed and on the importance and means of reporting AEs., Funding: Celgene Pty Ltd, Melbourne, Australia.

Background: In a phase III trial in patients with metastatic pancreatic cancer (MPC), nab-paclitaxel plus gemcitabine (nab-P/Gem) demonstrated greater efficacy but higher rates of peripheral neuropathy (PN) versus Gem. This exploratory analysis aimed to characterise the frequency, duration, and severity of PN with nab-P/Gem in the MPACT study., Patients and Methods: Patients with previously untreated MPC received nab-P/Gem or Gem. PN was evaluated using a broad-spectrum group of Standardised Medical Dictionary for Regulatory Activities Queries (SMQ) and graded by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 3.0. A case report form was completed by physicians on day 1 of each cycle (also graded by NCI CTCAE version 3.0)., Results: In the nab-P/Gem arm, 227/421 patients (54%) experienced any-grade PN and 70 (17%) experienced grade III PN. No grade IV PN was reported. Most early-onset PN events were grade I, and treatment-related grade III PN occurred in 7% of patients who received up to three cycles of nab-P. Of those who developed grade III PN with nab-P/Gem treatment, 30 (43%) improved to grade ≤ I (median time to improvement = 29 days) and 31 (44%) resumed therapy. Development of PN was associated with efficacy; median overall survival in patients with grade III versus 0 PN was 14.9 versus 5.9 months (hazard ratio, 0.33; P < .0001)., Conclusions: nab-P/Gem was associated with grade III PN in a small percentage of patients. PN development was associated with longer treatment duration and improved survival. Grade III PN was reversible to grade ≤ I in many patients (median ≈ 1 month) NCT00844649., (Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Gold nanoparticles with efficient plasmon absorption in the visible and near infrared (NIR) regions, biocompatibility and easy surface functionalization are of interest for photothermal applications. Herein we describe the synthesis and photothermal properties of gold "nanocorals" (AuNC) obtained by laser irradiation of Au nanospheres (AuNS) dispersed in liquid solution. AuNC are formed in two stages: by photofragmentation of AuNS, followed by spontaneous unidirectional assembly of gold nanocrystals. The whole procedure is performed without chemicals or templating compounds, hence the AuNC can be coated with thiolated molecules in one step. We show that AuNC coated with thiolated polymers are easily dispersed in an aqueous environment or in organic solvents and can be included in polymeric matrixes to yield a plasmonic nanocomposite. AuNC dispersions exhibit flat broadband plasmon absorption ranging from the visible to the NIR and unitary light-to-heat conversion. Besides, in vitro biocompatibility experiments assessed the absence of cytotoxic effects even at a dose as high as 100 μg mL(-1). These safe-by-designed AuNC are promising for use in various applications such as photothermal cancer therapy, light-triggered drug release, antimicrobial substrates, optical tomography, obscurant materials and optical coatings.

Romidepsin is a histone deacetylase inhibitor approved by the FDA for the treatment of patients with cutaneous or peripheral T-cell lymphoma who have received prior systemic therapy. The objective of this analysis was to evaluate the potential QTc effects of romidepsin. Patients with advanced malignancy received 4-h infusions of 14 mg/m(2) romidepsin on days 1, 8, and 15 of a 28-day cycle. In cycle 2, a subset of patients received 1-h infusions of 8-12 mg/m(2) romidepsin. Patients were administered antiemetics before each romidepsin dose and electrolyte supplementation as needed. Electrocardiogram readings were performed prior to antiemetic administration, prior to romidepsin administration, and at specified time points over the subsequent 24 h. Romidepsin exposure and heart rate were also assessed. In the electrocardiogram-evaluable population, 26 patients received romidepsin at 14 mg/m(2) over 4 h. The maximum mean increases from the preantiemetic baseline for QTcF and heart rate were 10.1 msec (upper 90% CI, 14.5 msec) and 18.2 beats per minute, respectively. No patient in this study had an absolute QTcF value >450 msec and only one patient had an increase from the preantiemetic baseline of >60 msec. There was a mild reduction in the PR interval and no meaningful changes in the QRS interval. Despite the use of QT-prolonging antiemetics, treatment with romidepsin did not markedly prolong the QTc interval through 24 h. Increases in calculated QTc may have been exaggerated as a consequence of transient increases in heart rate., (© 2015 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

The amplification of Raman signals of the heteroaromatic cation 1-(N-methylpyrid-4-yl)-2-(N-methylpyrrol-2-yl)ethylene ( PEP+ )) bound to Au nanorods (NRs) was investigated at different excitation wavelengths to study the effect of the laser resonance with the absorption band of the PEP+ moiety and with the two plasmon oscillation modes of the NR. Two different PEP+ derivatives, differing in the length of the alkyl chain bearing the anchoring group, were used as target molecules. Raman spectra obtained exciting at 514 or at 785 nm (i.e., exciting the transverse or the longitudinal plasmon band) present a higher intensity than that at 488 nm suggesting a higher Raman amplification when the laser excitation wavelength is resonant with one of the two plasmon modes. Moreover, considering results of Discrete Dipole Approximation (DDA) calculations of the local field generated at the NR surface when either the transverse or the longitudinal plasmon modes are excited, we deduced that the resonance condition of the 514-nm laser excitation with the absorption band of the dye strongly contributes to the amplification of the Raman signal.

The linear and nonlinear optical properties of a Donor-Acceptor-Donor system have been investigated by using a two-electron three-point-site model system. Some basic features of electron correlations are included in the model by means of a bi-electronic density matrix. The polarizabilities and second hyperpolarizabilities have been computed with a modified version of the Collective Electronic Oscillators (CEO) method which allowed us to include the electron-phonon coupling. Both singly- and doubly-excited states are taken into account in the computation of (hyper-)polarizabilities. The effects of electron-phonon coupling on the two-photon absorption and on the third harmonic generation in the infrared region are discussed.

The replicase protein of Potato virus X (PVX), type species of the genus Potexvirus, was selected to identify regions essential for replication and subgenomic RNA synthesis. Replicase amino acid (aa) sequence alignment of 16 Potexvirus species resulted in the detection of overall sequence homology of 34.4-65.4%. Two regions of consensus with a high proportion of conserved aa (1-411 and 617-1437 according to PVX) were separated by a hyper-variable linker region. Pentapeptide scanning (PS) mutagenesis in a PVX full-length clone expressing green fluorescent protein (GFP) was carried out. For 69 selected PS-mutants where insertions were spread randomly over the replicase ORF the position of the insertion was determined. The replication activity was evaluated by GFP expression from subgenomic viral RNA of PVX replicase mutants. Only one functional PS-mutant was detected in the N-terminal 430 aa, containing the conserved methyltransferase domain of the protein. In the linker region from aa 430-595, nine mutations were discovered which did not induce significant effects on the replicase replication ability. The part of the protein including helicase and polymerase domains was highly intolerant for the PS insertion as demonstrated by 24 independent more or less uniformly spread mutants.

The 16 kDa cysteine-rich protein (16K) of tobacco rattle virus (TRV) is known to partially suppress RNA silencing in Drosophila cells. In this study, we show that 16K suppresses RNA silencing in green fluorescent protein (GFP)-transgenic Nicotiana benthamiana plants using an Agrobacterium-mediated transient assay. 16K slightly reduced the accumulation of short interfering RNAs (siRNA) of GFP, suggesting that the protein may interfere with the initiation and/or maintenance of RNA silencing. Deletion of either the N- or C-terminal part of 16K indicated that the entire 16K open reading frame (ORF) is necessary for its silencing suppression function. Pentapeptide insertion scanning mutagenesis (PSM) revealed that only two short regions of 16K tolerated five extra amino acid insertions without considerable reduction in its silencing suppression function. The tolerant regions coincide with sequence variability between tobravirus cysteine-rich proteins, indicating a strong functional and/or structural conservation of TRV 16K. Confocal laser scanning microscopy of transiently expressed 16K fusions to red fluorescent protein (RFP) revealed a predominant cytoplasmic localization and, in addition, a nuclear localization. In contrast, fusions of RFP with the N-terminal region of 16K localized exclusively to the cytoplasm, whereas fusions between RFP and the C-terminal region of 16K displayed an exclusive nuclear localization. Further analysis of 16K-derived peptide fusions demonstrated that the 16K C-terminal region contained at least two functional bipartite nuclear localization signals which were independently capable of nuclear targeting.

Imatinib has now been in use for almost 10 years. Despite this cumulative experience, little is known about its effects on pregnancy; as a result, there are few published data to facilitate the counseling of women who conceive while taking imatinib. The results we now present provide information which may be of use in such circumstances. Of 180 women exposed to imatinib during pregnancy, outcome data are available for 125 (69%). Of those with known outcomes, 50% delivered normal infants and 28% underwent elective terminations, 3 following the identification of abnormalities. There were a total of 12 infants in whom abnormalities were identified, 3 of which had strikingly similar complex malformations that are clearly a cause for concern. It appears that although most pregnancies exposed to imatinib are likely to have a successful outcome, there remains a risk that exposure may result in serious fetal malformations.

The excited state dynamics of two generations perylenediimide chromophores substituted in the bay area with dendritic branches bearing triphenylamine units as well as those of the respective reference compounds are investigated. Using single photon timing and multi-pulse femtosecond transient absorption experiments a direct proof of a reversible charge transfer occurring from the peripheral triphenylamine to the electron acceptor perylenediimide core is revealed. Femtosecond pump-dump-probe experiments provide evidence for the ground state dynamics by populating excited vibronic levels. It is found by the means of both techniques that the rotational isomerization of the dendritic branches occurs on a time scale that ranges up to 1 ns. This time scale of the isomerization depends on the size of the dendritic arms and is similar both in the ground and excited state.

Helper component proteinase (HC-Pro) of Plum pox virus is a multifunctional potyvirus protein that has been examined intensively. In addition to its involvement in aphid transmission, genome amplification and long-distance movement, it is also one of the better-studied plant virus suppressors of RNA silencing. The first systematic analysis using pentapeptide-insertion scanning mutagenesis of the silencing suppression function of a potyvirus HC-Pro is presented here. Sixty-three in-frame insertion mutants, each containing five extra amino acids inserted randomly within the HC-Pro protein, were analysed for their ability to suppress transgene-induced RNA silencing using Agrobacterium infiltration in transgenic Nicotiana benthamiana plants expressing green fluorescent protein. A functional map was obtained, consisting of clearly defined regions with different classes of silencing-suppression activity (wild-type, restricted and disabled). This map confirmed that the N-terminal part of the protein, which is indispensable for aphid transmission, is dispensable for silencing suppression and supports the involvement of the central region in silencing suppression, in addition to its role in maintenance of genome amplification and synergism with other viruses. Moreover, evidence is provided that the C-terminal part of the protein, previously known to be necessary mainly for proteolytic activity, also participates in silencing suppression. Pentapeptide-insertion scanning mutagenesis has been shown to be a fast and powerful tool to functionally characterize plant virus proteins.

Based on femtosecond time-resolved spectroscopy and single photon timing experiments, intramolecular photoinduced charge transfer has been investigated in two systems containing a peryleneimide chromophore (P) and thiophene (T) groups. The first compound bearing a single thiophene ring (PT1) is used as model and shows a behavior similar to P, studied previously, while in the compound with two thiophene rings attached (PT2) electron transfer from the thiophene donor to the peryleneimide acceptor is observed in benzonitrile. Femtosecond fluorescence upconversion and femtosecond transient absorption experiments in benzonitrile indicate that this ion-pair state formation occurs in 19 ps. This ion-pair state then decays with two time constants of 1400 and 820 ps, probably corresponding to different conformations of the thiophene rings.

We evaluated sympathetic nervous system function in a patient with primary orthostatic hypotension. Plasma catecholamine levels--except for dopamine levels--and urinary catecholamine excretion were decreased, alpha-adrenoreceptor responsiveness to noradrenaline and beta-adrenoreceptor responsiveness to isoproterenol were increased according to increased beta-2-adrenoreceptor density on intact polymorphonuclear leukocytes. Alpha-2-adrenoreceptor density on intact platelets and adrenaline-induced platelet aggregation in vitro, however, were unchanged. We evolved a therapeutic regimen with fludrocortisone, propranolol, and dihydroergotamine that allowed the patient to resume nearly a regular degree of mobility.