RhoB expression associated with chemotherapy response and prognosis in colorectal cancer.

PURPOSE: To examine the role of RhoB expression in relation to chemotherapy response, clinical outcomes and associated signaling pathways in colorectal cancer patients. MATERIALS AND METHODS: The study included 5 colon cancer cell lines, zebrafish embryos and 260 colorectal cancer patients treated with 5-fluorouracil (5-FU) and oxaliplatin (OXL). The methods consisted of CRISPR/Cas9, reactive oxygen species (ROS), caspase-3 activity, autophagy flux, in-silico RNA sequencing and immunohistochemistry. Gene expression analysis and pathway analysis were conducted using RNA-seq data. RESULTS: All cancer lines tested, including SW480, SW480-KO13 (RhoB knockout), SW480-KO55 (RhoB knockout), HCT116 and HCT116-OE (RhoB overexpressed), exhibited cytotoxicity to 5-FU and OXL. RhoB knockout cell lines demonstrated significantly reduced migration compared to the control cell lines. Furthermore, RhoB played a role in caspase-3-dependent apoptosis, regulation of ROS production and autophagic flux. The mRNA sequencing data indicated lower expression levels of oncogenes in RhoB knockout cell lines. The zebrafish model bearing SW480-KO showed a light trend toward tumor regression. RhoB expression by immunohistochemistry in patients was increased from normal mucosa to tumor samples. In patients who received chemotherapy, high RhoB expression was related to worse survival compared to low RhoB expression. Furthermore, the molecular docking analysis revealed that OXL had a higher binding affinity for RhoB than 5-FU, with a binding affinity of -7.8 kcal/mol and HADDOCK predicted molecular interactions between RhoB and caspase 3 protein. Gene-set enrichment analysis supported these findings, showing that enrichment of DNA damage response pathway and p53 signaling in RhoB overexpression treatment group, while the RhoB knockout treatment group exhibited enrichment in the negative regulation pathway of cell migration. CONCLUSION: RhoB was negatively associated with chemotherapy response and survival in colorectal cancers. Therefore, RhoB inhibition may enhance chemotherapeutic responses and patient survival.

The importance of considering competing risks in recurrence analysis of intracranial meningioma.

BACKGROUND: The risk of recurrence is overestimated by the Kaplan-Meier method when competing events, such as death without recurrence, are present. Such overestimation can be avoided by using the Aalen-Johansen method, which is a direct extension of Kaplan-Meier that accounts for competing events. Meningiomas commonly occur in older individuals and have slow-growing properties, thereby warranting competing risk analysis. The extent to which competing events are considered in meningioma literature is unknown, and the consequences of using incorrect methodologies in meningioma recurrence risk analysis have not been investigated. METHODS: We surveyed articles indexed on PubMed since 2020 to assess the usage of competing risk analysis in recent meningioma literature. To compare recurrence risk estimates obtained through Kaplan-Meier and Aalen-Johansen methods, we applied our international database comprising ~ 8,000 patients with a primary meningioma collected from 42 institutions. RESULTS: Of 513 articles, 169 were eligible for full-text screening. There were 6,537 eligible cases from our PERNS database. The discrepancy between the results obtained by Kaplan-Meier and Aalen-Johansen was negligible among low-grade lesions and younger individuals. The discrepancy increased substantially in the patient groups associated with higher rates of competing events (older patients with high-grade lesions). CONCLUSION: The importance of considering competing events in recurrence risk analysis is poorly recognized as only 6% of the studies we surveyed employed Aalen-Johansen analyses. Consequently, most of the previous literature has overestimated the risk of recurrence. The overestimation was negligible for studies involving low-grade lesions in younger individuals; however, overestimation might have been substantial for studies on high-grade lesions.

Risk factors for rebleeding and mortality following prophylactic transarterial embolization for patients with high-risk peptic ulcer bleeding: a single-center retrospective cohort study.

BACKGROUND: To investigate factors associated with risk for rebleeding and 30-day mortality following prophylactic transarterial embolization in patients with high-risk peptic ulcer bleeding. METHODS: We retrospectively reviewed medical records and included all patients who had undergone prophylactic embolization of the gastroduodenal artery at Rigshospitalet, Denmark, following an endoscopy-verified and treated peptic Sulcer bleeding, from 2016 to 2021. Data were collected from electronic health records and imaging from the embolization procedures. Primary outcomes were rebleeding and 30-day mortality. We performed logistical regression analyses for both outcomes with possible risk factors. Risk factors included: active bleeding; visible hemoclips; Rockall-score; anatomical variants; standardized embolization procedure; and number of endoscopies prior to embolization. RESULTS: We included 176 patients. Rebleeding occurred in 25% following embolization and 30-day mortality was 15%. Not undergoing a standardized embolization procedure increased the odds of both rebleeding (odds ratio 3.029, 95% confidence interval (CI) 1.395-6.579) and 30-day overall mortality by 3.262 (1.252-8.497). More than one endoscopy was associated with increased odds of rebleeding (odds ratio 2.369, 95% CI 1.088-5.158). High Rockall-score increased the odds of 30-day mortality (odds ratio 2.587, 95% CI 1.243-5.386). Active bleeding, visible hemoclips, and anatomical variants did not affect risk of rebleeding or 30-day mortality. Reasons for deviation from standard embolization procedure were anatomical variations, targeted treatment without embolizing the gastroduodenal artery, and technical failure. CONCLUSIONS: Deviation from the standard embolization procedure increased the risk of rebleeding and 30-day mortality, more than one endoscopy prior to embolization was associated with higher odds of rebleeding, and a high Rockall-score increased the risk of 30-day mortality. We suggest that patients with these risk factors are monitored closely following embolization. Early detection of rebleeding may allow for proper and early re-intervention.

Understanding early deaths after major emergency abdominal surgery: An observational study of 754 patients.

BACKGROUND: Major emergency abdominal surgery is associated with severe postoperative complications and high short- and long-term mortality. Despite recent advancements in standardizing multidisciplinary care bundles, a subgroup of patients continues to face a heightened risk of short-term mortality. This study aimed to identify and describe the high-risk surgical patients and risk factors for short-term postoperative mortality. METHODS: In this study, we included all patients undergoing major emergency abdominal surgery over 2 years and collected data on demographics, intraoperative variables, and short-term outcomes. The primary outcome measure was short-term mortality and secondary outcome measures were pre, intra, and postoperative risk factors for premature death. Multivariable binary regression analysis was performed to determine possible risk factors for short-term mortality. RESULTS: Short-term mortality within 14 days of surgery in this cohort of 754 consecutive patients was 8%. Multivariable analysis identified various independent risk factors for short-term mortality throughout different phases of patient care. These factors included advanced age, preoperative history of myocardial infarction or ischemic heart disease, chronic obstructive pulmonary disease, liver cirrhosis, chronic kidney disease, and vascular bowel ischemia or perforation of the stomach or duodenum during the primary surgery. CONCLUSION: Patients at high risk of early mortality following major emergency abdominal surgery exhibited distinct perioperative risk factors. This study underscores the importance of clinicians identifying and managing these factors in high-risk patients to ensure optimal care.

A recursive cell multipole method for atomistic electrodynamics models.

For large plasmonic nanoparticles, retardation effects become important once their length becomes comparable to the wavelength of light. However, most models do not incorporate retardation effects due to the high computational cost of solving for the optical properties of large atomistic electrodynamics systems. In this work, we derive and implement a recursive fast multipole method (FMM) in Cartesian coordinates that includes retardation effects. In this method, higher-order electrodynamic interaction tensors used for the FMM are calculated recursively, thus greatly reducing the implementation complexity of the model. This method allows for solving of the optical properties of large atomistic nanoparticles with controlled accuracy; in practice, taking the expansion to the fifth order provides a good balance of accuracy and computational time. Finally, we study the effects retardation has on the near- and far-field properties of large plasmonic nanoparticles with over a million atoms using this method. We specifically focus on nanorods and their dimers, which are known to generate highly confined fields in their junctions. In the future, this method can be applied to simulations in which accurate near-field properties are required, such as surface-enhanced Raman scattering.

Modeling the near-field effect on molecular excited states using the discrete interaction model/quantum mechanical method.

Strong light-matter interactions significantly modify the optical properties of molecules in the vicinity of plasmonic metal nanoparticles. Since the dimension of the plasmonic cavity approaches that of the molecules, it is critical to explicitly describe the nanoparticle junctions. In this work, we use the discrete interaction model/quantum mechanical (DIM/QM) method to model the coupling between the plasmonic near-field and molecular excited states. DIM/QM is a combined electrodynamics/quantum mechanical model that uses an atomistic description of the nanoparticle. We extend the DIM/QM method to include the local field effects in the sum-over-state formalism of time-dependent density functional theory. As a test of the method, we study the interactions between small organic chromophores and metal nanoparticles. In particular, we examine how the inclusion of multiple electronic transitions and intermolecular interactions modify the coupling between molecules and nanoparticles. Using the sum-over-state formalism of DIM/QM, we show that two-state models break down when the plasmon excitation is detuned from the molecular excitations. To gain further insight, we compare the simple coupled-dipole model (CDM) with the DIM/QM model. We find that CDM works well for simple systems but fails when going beyond the single molecule or single nanoparticle cases. We also find that the coupling depends strongly on the site of the nanoparticle in which the chromophore couples to. Our work suggests the importance of explicitly describing the cavity to capture the atomistic level local field environment in which the molecule strongly couples to.

Non-communicable diseases, digital education and considerations for the Indian context - a scoping review.

INTRODUCTION: The increasing ageing of the population with growth in NCD burden in India has put unprecedented pressure on India's health care systems. Shortage of skilled human resources in health, particularly of specialists equipped to treat NCDs, is one of the major challenges faced in India. Keeping in view the shortage of healthcare professionals and the guidelines in NEP 2020, there is an urgent need for more health professionals who have received training in the diagnosis, prevention, and treatment of NCDs. This paper conducts a scoping review and aims to collate the existing evidence on the use of digital education of health professionals within NCD topics. METHODS: We searched four databases (Web of Science, PubMed, EBSCO Education Research Complete, and PsycINFO) using a three-element search string with terms related to digital education, health professions, and terms related to NCD. The inclusion criteria covered the studies to be empirical and NCD-related with the target population as health professionals rather than patients. Data was extracted from 28 included studies that reported on empirical research into digital education related to non-communicable diseases in health professionals in India. Data were analysed thematically. RESULTS: The target groups were mostly in-service health professionals, but a considerable number of studies also included pre-service students of medicine (n = 6) and nursing (n = 6). The majority of the studies included imparted online learning as self-study, while some imparted blended learning and online learning with the instructor. While a majority of the studies included were experimental or observational, randomized control trials and evaluations were also part of our study. DISCUSSION: Digital HPE related to NCDs has proven to be beneficial for learners, and simultaneously, offers an effective way to bypass geographical barriers. Despite these positive attributes, digital HPE faces many challenges for its successful implementation in the Indian context. Owing to the multi-lingual and diverse health professional ecosystem in India, there is a need for strong evidence and guidelines based on prior research in the Indian context.

Accuracy of FAST in detecting intraabdominal bleeding in major trauma with pelvic and/or acetabular fractures: a retrospective cohort study.

PURPOSE: The Focused Assessment with Sonography for Trauma (FAST) is a tool to rapidly detect intraabdominal and intrapericardial fluid with point-of-care ultrasound. Previous studies have questioned the role of FAST in patients with pelvic fractures. The aim of the present study was to assess the accuracy of FAST to detect clinically significant intraabdominal hemorrhage in patients with pelvic fractures. METHODS: We included all consecutive patients with pelvic and/or acetabular fractures treated our Level 1 trauma center from 2009-2020. We registered patient and fracture characteristics, FAST investigations and CT descriptions, explorative laparotomy findings, and transfusion needs. We compared FAST to CT and laparotomy findings, and calculated true positive and negative findings, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). RESULTS: We included 389 patients. FAST had a sensitivity of 75%, a specificity of 98%, a PPV of 84%, and a NPV of 96% for clinically significant intraabdominal bleeding. Patients with retroperitoneal hematomas were at increased risk for laparotomy both because of True-negative FAST and False-positive FAST. CONCLUSION: FAST is accurate to identify clinically significant intraabdominal blood in patients with severe pelvic fractures and should be a standard asset in these patients. Retroperitoneal hematomas challenge the FAST interpretation and thus the decision making when applying FAST in patients with pelvic fractures.

Visualization of human T lymphocyte-mediated eradication of cancer cells in vivo.

Lymphocyte-based immunotherapy has emerged as a breakthrough in cancer therapy for both hematologic and solid malignancies. In a subpopulation of cancer patients, this powerful therapeutic modality converts malignancy to clinically manageable disease. However, the T cell- and chimeric antigen receptor T (CAR-T) cell-mediated antimetastatic activity, especially their impacts on microscopic metastatic lesions, has not yet been investigated. Here we report a living zebrafish model that allows us to visualize the metastatic cancer cell killing effect by tumor- infiltrating lymphocytes (TILs) and CAR-T cells in vivo at the single-cell level. In a freshly isolated primary human melanoma, specific TILs effectively eliminated metastatic cancer cells in the living body. This potent metastasis-eradicating effect was validated using a human lymphoma model with CAR-T cells. Furthermore, cancer-associated fibroblasts protected metastatic cancer cells from T cell-mediated killing. Our data provide an in vivo platform to validate antimetastatic effects by human T cell-mediated immunotherapy. This unique technology may serve as a precision medicine platform for assessing anticancer effects of cellular immunotherapy in vivo before administration to human cancer patients.

Digital education for health professionals in India: a scoping review of the research.

BACKGROUND: The World Health Organization (WHO) predicts a global shortfall of 18 million health workers by 2030, particularly in low- and middle-income countries like India. The country faces challenges such as inadequate numbers of health professionals, poor quality of personnel, and outdated teaching styles. Digital education may address some of these issues, but there is limited research on what approaches work best in the Indian context. This paper conducts a scoping review of published empirical research related to digital health professions education in India to understand strengths, weaknesses, gaps, and future research opportunities. METHODS: We searched four databases using a three-element search string with terms related to digital education, health professions, and India. Data was extracted from 36 included studies that reported on empirical research into digital educational innovations in the formal health professions education system of India. Data were analysed thematically. RESULTS: Most study rationales related to challenges facing the Indian health care system, rather than a wish to better understand phenomena related to teaching and learning. Similarly, most studies can be described as general evaluations of digital educational innovations, rather than educational research per se. They mostly explored questions related to student perception and intervention effectiveness, typically in the form of quantitative analysis of survey data or pre- and post-test results. CONCLUSIONS: The analysis revealed valuable insights into India-specific needs and challenges. The Indian health professions education system's size and unique challenges present opportunities for more nuanced, context-specific investigations and contributions to the wider digital education field. This, however, would require a broadening of methodological approaches, in particular rigorous qualitative designs, and a focus on addressing research-worthy educational phenomena.

Leakage of stomal effluent outside the baseplate leads to rise in product usage and health professional interactions.

BACKGROUND: Leakage of stomal effluent outside the baseplate that soils clothes or bedsheets is a common problem for many people with a stoma and significantly impacts their quality of life. AIM: To understand behavioural changes for people experiencing faecal leakage outside the baseplate regarding the usage of pouching systems, supporting products and interactions with health professionals. METHODS: Retrospective, self-reported questionnaire. FINDINGS: Respondents on average experienced 1.1 incidents of faecal leakage outside the baseplate per fortnight. In periods with issues of leakage, 21% of respondents had been in contact with health professionals, 40% increased their use of pouching systems, 25% increased their use of existing supporting products, and 21% included additional supporting products to their change routine. The increased use of healthcare resources was estimated to cost £32.47 in the 3 weeks following a leakage incident. CONCLUSION: Incidents of leakage outside the baseplate lead to increased use of healthcare resources.

A multidisciplinary perspective on the complex interactions between sleep, circadian, and metabolic disruption in cancer patients.

Sleep is a basic need that is frequently set aside in modern societies. This leads to profound but complex physiological maladaptations in the body commonly referred to as circadian disruption, which recently has been characterized as a carcinogenic factor and reason for poor treatment outcomes, shortened survival, and reduced quality of life in cancer patients. As sleep and circadian physiology in cancer patients spans several disciplines including nursing science, neurology, oncology, molecular biology and medical technology, there is a lack of comprehensive and integrated approaches to deal with this serious and growing issue and at best a fractionated understanding of only part of the problem among researchers within each of these segments. Here, we take a multidisciplinary approach to comprehensively review the diagnosis and impact of sleep and circadian disruption in cancer patients. We discuss recent discoveries on molecular regulation of the circadian clock in healthy and malignant cells, the neurological and endocrine pathways controlling sleep and circadian rhythmicity, and their inputs to and outputs from the organism. The benefits and drawbacks of the various technologies, devices, and instruments used to assess sleep and circadian function, as well as the known consequences of sleep disruption and how sleep can be corrected in cancer patients, will be analyzed. We will throughout the review highlight the extensive crosstalk between sleep, circadian rhythms, and metabolic pathways involved in malignancy and identify current knowledge gaps and barriers for addressing the issue of sleep and circadian disruption in cancer patients. By addressing these issues, we hope to provide a foundation for further research as well as better and more effective care for the patients in the future.

Implementation of TERT promoter mutations improve prognostication of the WHO classification in meningioma.

TERT promoter mutations have been associated with increased risk of recurrence in meningioma cohorts, thus a potential biomarker for aggressive phenotypes. A main purpose of refining tumour classification is better predictions on the patient level. We compiled data from previous published cohorts to investigate patient-level predictions of recurrence based on TERTp-mut status. Implementation of TERTp-mut into the WHO grading led to better patient prognostication by improved prediction of recurrence. Our results support implementation of TERTp-mut into diagnostics and classification of meningiomas.

Understanding chemical enhancements of surface-enhanced Raman scattering using a Raman bond model for extended systems.

In this work, we extend a previously developed Raman bond model to periodic slab systems for interpreting chemical enhancements of surface-enhanced Raman scattering (SERS). The Raman bond model interprets chemical enhancements as interatomic charge flow modulations termed Raman bonds. Here, we show that the Raman bond model offers a unified interpretation of chemical enhancements for localized and periodic systems. As a demonstration of the Raman bond model, we study model systems consisting of CO and pyridine molecules on Ag clusters and slabs. We find that for both localized and periodic systems, the dominant Raman bonds are distributed near the molecule-metal interface and, therefore, the chemical enhancements are determined by a common Raman bond pattern. The effects of surface coverage, thickness, and roughness on the chemical enhancements have been studied, which shows that decreasing surface coverage or creating surface roughness increases chemical enhancements. In both of these cases, the inter-fragment charge flow connectivity is improved due to more dynamic polarization at the interface. The chemical enhancement is shown to scale with the inter-fragment charge flow to the fourth power. Since the inter-fragment charge flow is determined by the charge transfer excitation energy, the Raman bond model is connected to the transition-based analysis of chemical enhancements. We also show that the SERS spectra of localized and periodic systems normalized by inter-fragment charge flows can be unified. In summary, the Raman bond model offers a unique framework for understanding SERS spectra in terms of Raman bond distributions and offers a connection between localized and periodic model systems of SERS studies.

Somatostatin analogues in treatment-refractory meningioma: a systematic review with meta-analysis of individual patient data.

Treatment-refractory meningiomas have a dismal prognosis and limited treatment options. Meningiomas express high-densities of somatostatin receptors (SSTR), thus potentially susceptible to antitumorigenic effects of somatostatin analogues (SSA). Evidence for SSA in meningiomas is scarce, and it is unclear if published literature would either (1) support wider use of SSA, if (2) more evidence is desirable, or if (3) available evidence is sufficient to discard SSA. We addressed the need for more evidence with a systematic review and meta-analysis. We performed an individual patient data (IPD) meta-analysis. Main outcomes were toxicity, best radiological response, progression-free survival, and overall survival. We applied multivariable logistic regression models to estimate the effect of SSA on the probability of obtaining radiological disease control. The predictive performance was evaluated using area under the curve and Brier scores. We included 16 studies and compiled IPD from 8/9 of all previous cohorts. Quality of evidence was overall ranked "very low." Stable disease was reported in 58% of patients as best radiological response. Per 100 mg increase in total SSA dosage, the odds ratios for obtaining radiological disease control was 1.42 (1.11 to 1.81, P = 0.005) and 1.44 (1.00 to 2.08, P = 0.05) for patients treated with SSA as monodrug therapy vs SSA in combination with everolimus, respectively. Low quality of evidence impeded exact quantification of treatment efficacy, and the association between response and treatment may represent reverse causality. Yet, the SSA treatment was well tolerated, and beneficial effect cannot be disqualified. A prospective trial without bias from inconsistent study designs is warranted to assess SSA therapy for well-defined meningioma subgroups.

Pharmacological restoration of visual function in a zebrafish model of von-Hippel Lindau disease.

Von Hippel-Lindau (VHL) syndrome is a rare, autosomal dominant disorder, characterised by hypervascularised tumour formation in multiple organ systems. Vision loss associated with retinal capillary hemangioblastomas remains one of the earliest complications of VHL disease. The mortality of Vhl-/- mice in utero restricted modelling of VHL disease in this mammalian model. Zebrafish harbouring a recessive germline mutation in the vhl gene represent a viable, alternative vertebrate model to investigate associated ocular loss-of-function phenotypes. Previous studies reported neovascularisation of the brain, eye and trunk together with oedema in the vhl-/- zebrafish eye. In this study, we demonstrate vhl-/- zebrafish almost entirely lack visual function. Furthermore, hyaloid vasculature networks in the vhl-/- eye are improperly formed and this phenotype is concomitant with development of an ectopic intraretinal vasculature. Sunitinib malate, a multi tyrosine kinase inhibitor, market authorised for cancer, reversed the ocular behavioural and morphological phenotypes observed in vhl-/- zebrafish. We conclude that the zebrafish vhl gene contributes to an endogenous molecular barrier that prevents development of intraretinal vasculature, and that pharmacological intervention with sunitinib can improve visual function and hyaloid vessel patterning while reducing abnormally formed ectopic intraretinal vessels in vhl-/- zebrafish.

Synchronized tissue-scale vasculogenesis and ubiquitous lateral sprouting underlie the unique architecture of the choriocapillaris.

The choriocapillaris is an exceptionally high density, two-dimensional, sheet-like capillary network, characterized by the highest exchange rate of nutrients for waste products per area in the organism. These unique morphological and physiological features are critical for supporting the extreme metabolic requirements of the outer retina needed for vision. The developmental mechanisms and processes responsible for generating this unique vascular network remain, however, poorly understood. Here we take advantage of the zebrafish as a model organism for gaining novel insights into the cellular dynamics and molecular signaling mechanisms involved in the development of the choriocapillaris. We show for the first time that zebrafish have a choriocapillaris highly similar to that in mammals, and that it is initially formed by a novel process of synchronized vasculogenesis occurring simultaneously across the entire outer retina. This initial vascular network expands by un-inhibited sprouting angiogenesis whereby all endothelial cells adopt tip-cell characteristics, a process which is sustained throughout embryonic and early post-natal development, even after the choriocapillaris becomes perfused. Ubiquitous sprouting was maintained by continuous VEGF-VEGFR2 signaling in endothelial cells delaying maturation until immediately before stages where vision becomes important for survival, leading to the unparalleled high density and lobular structure of this vasculature. Sprouting was throughout development limited to two dimensions by Bruch's membrane and the sclera at the anterior and posterior surfaces respectively. These novel cellular and molecular mechanisms underlying choriocapillaris development were recapitulated in mice. In conclusion, our findings reveal novel mechanisms underlying the development of the choriocapillaris during zebrafish and mouse development. These results may explain the uniquely high density and sheet-like organization of this vasculature.

Monitoring Reaction Intermediates in Plasma-Driven SO2, NO, and NO2 Remediation Chemistry Using In Situ SERS Spectroscopy.

In situ surface-enhanced Raman scattering (SERS) spectroscopy is used to identify the key reaction intermediates during the plasma-based removal of NO and SO2 under dry and wet conditions on Ag nanoparticles. Density functional theory (DFT) calculations are used to confirm the experimental observations by calculating the vibrational modes of the surface-bound intermediate species. Here, we provide spectroscopic evidence that the wet plasma increases the SO2 and the NOx removal through the formation of highly reactive OH radicals, driving the reactions to H2SO4 and HNO3, respectively. We observed the formation of SO3 and SO4 species in the SO2 wet-plasma-driven remediation, while in the dry plasma, we only identified SO3 adsorbed on the Ag surface. During the removal of NO in the dry and wet plasma, both NO2 and NO3 species were observed on the Ag surface; however, the concentration of NO3 species was enhanced under wet-plasma conditions. By closing the loop between the experimental and DFT-calculated spectra, we identified not only the adsorbed species associated with each peak in the SERS spectra but also their orientation and adsorption site, providing a detailed atomistic picture of the chemical reaction pathway and surface interaction chemistry.

A discrete interaction model/quantum mechanical method for simulating surface-enhanced Raman spectroscopy in solution.

Since surface-enhanced Raman scattering (SERS) is of considerable interest for sensing applications in aqueous solution, the role that solvent plays in the spectroscopy must be understood. However, these efforts are hindered due to a lack of simulation approaches for modeling solvent effects in SERS. In this work, we present an atomistic electrodynamics-quantum mechanical method to simulate SERS in aqueous solution based on the discrete interaction model/quantum mechanical method. This method combines an atomistic electrodynamics model of the nanoparticle with a time-dependent density functional theory description of the molecule and a polarizable embedding method for the solvent. The explicit treatment of solvent molecules and nanoparticles results in a large number of polarizable dipoles that need to be considered. To reduce the computational cost, a simple cut-off based approach has been implemented to limit the number of dipoles that need to be treated without sacrificing accuracy. As a test of this method, we have studied how solvent affects the SERS of pyridine in the junction between two nanoparticles in aqueous solution. We find that the solvent leads to an enhanced SERS due to an increased local field at the position of the pyridine. We further demonstrate the importance of both image field and local field effects in determining the enhancements and the spectral signatures. Our results show the importance of describing the local environment due to the solvent molecules when modeling SERS.

Surface-enhanced hyper-Raman scattering of Rhodamine 6G isotopologues: Assignment of lower vibrational frequencies.

We report a comprehensive experimental and theoretical study of the lower-wavenumber vibrational modes in the surface-enhanced hyper-Raman scattering (SEHRS) of Rhodamine 6G (R6G) and its isotopologue R6G-d4. Measurements acquired on-resonance with two different electronic states, S1 and S2, are compared to the time-dependent density functional theory computations of the resonance hyper-Raman spectra and electrodynamics-quantum mechanical computations of the SEHRS spectra on-resonance with S1 and S2. After accounting for surface orientation, we find excellent agreement between experiment and theory for both R6G and its isotopologue. We then present a detailed analysis of the complex vibronic coupling effects in R6G and the importance of surface orientation for characterizing the system. This combination of theory and experiment allows, for the first time, an unambiguous assignment of lower-wavenumber vibrational modes of R6G and its isotopologue R6G-d4.