Web-CONEXS: an inroad to theoretical X-ray absorption spectroscopy.

Accurate analysis of the rich information contained within X-ray spectra usually calls for detailed electronic structure theory simulations. However, density functional theory (DFT), time-dependent DFT and many-body perturbation theory calculations increasingly require the use of advanced codes running on high-performance computing (HPC) facilities. Consequently, many researchers who would like to augment their experimental work with such simulations are hampered by the compounding of nontrivial knowledge requirements, specialist training and significant time investment. To this end, we present Web-CONEXS, an intuitive graphical web application for democratizing electronic structure theory simulations. Web-CONEXS generates and submits simulation workflows for theoretical X-ray absorption and X-ray emission spectroscopy to a remote computing cluster. In the present form, Web-CONEXS interfaces with three software packages: ORCA, FDMNES and Quantum ESPRESSO, and an extensive materials database courtesy of the Materials Project API. These software packages have been selected to model diverse materials and properties. Web-CONEXS has been conceived with the novice user in mind; job submission is limited to a subset of simulation parameters. This ensures that much of the simulation complexity is lifted and preliminary theoretical results are generated faster. Web-CONEXS can be leveraged to support beam time proposals and serve as a platform for preliminary analysis of experimental data.

Targeting Catechol-O-Methyltransferase Induces Mitochondrial Dysfunction and Enhances the Efficacy of Radiotherapy in Glioma.

Radiotherapy (RT) is commonly used to try to eliminate any remaining tumor cells following surgical resection of glioma. However, tumor recurrence is prevalent, highlighting the unmet medical need to develop therapeutic strategies to enhance the efficacy of RT in glioma. Focusing on the radiosensitizing potential of currently approved drugs known to cross the blood-brain barrier can facilitate rapid clinical translation. Here, we assessed the role of catechol-o-methyltransferase (COMT), a key enzyme to degrade catecholamines and a drug target for Parkinson's disease, in glioma treatment. Analysis of TCGA data showed significantly higher COMT expression levels in both low-grade glioma and glioblastoma compared to normal brain tissues. Inhibition of COMT by genetic knockout or FDA-approved COMT inhibitors significantly sensitized glioma cells to RT in vitro and in vivo. Mechanistically, COMT inhibition in glioma cells led to mitochondria dysfunction and increased mitochondrial RNA release into the cytoplasm, activating the cellular antiviral double-stranded RNA sensing pathway and type I interferon (IFN) response. Elevated type I IFNs stimulated the phagocytic capacity of microglial cells, enhancing RT efficacy. Given the long-established safety record of the COMT inhibitors, these findings provide a solid rationale to evaluate them in combination with RT in glioma patients.

Melatonin: Evolving Physiological Understanding and Potential Therapeutic Role in Pain Medicine Including Intervertebral Disc Degeneration.

BACKGROUND: Melatonin, one of the most versatile hormones in the body, is well appreciated in managing circadian rhythm and for antioxidant properties. Produced in the pineal gland and within mitochondria, melatonin influences many physiologic processes through receptor mediated and direct effects. OBJECTIVE: The present investigation explores the evolving pharmacologic properties of melatonin, as well as current therapeutic uses in areas where mitigating oxidative stress, inflammation, and cellular senescence. This review also delves into novel therapeutic potential of melatonin and how current research is revealing a wide array of therapeutic promise in pain medicine. STUDY DESIGN: A systematic review of randomized controlled trials (RCTs) and observational studies was performed using various search engines focused on melatonin and its role in pain medicine. METHODS: The available literature on melatonin and pain medicine was reviewed. A comprehensive literature search of multiple databases from 1966 to July 2024, including manual searches of the bibliography of known review articles was performed. Quality assessment of the included studies and best evidence synthesis were incorporated into qualitative and quantitative evidence synthesis. OUTCOME MEASURES: The primary outcome measure was the proportion of patients receiving melatonin with significant relief and functional improvement of greater than 50% of at least 3 months. Duration of relief was categorized as short-term (less than 6 months) and long-term (greater than 6 months). RESULTS: Melatonin can affect intervertebral disc (IVD) health through the enhancement of survival and function of nucleus pulposus cells, primarily through activation of the ERK1/2 signaling pathway. Melatonin also influences the biochemical environment of the IVD by modulating inflammation and oxidative stress, crucial factors in the pathogenesis of disc degeneration. Melatonin has been shown to reduce senescence and promote autophagy within disc cells, vital for clearing out damaged cellular components, preserving cellular function and preventing deterioration associated with aging and degenerative diseases. LIMITATIONS: Despite the availability of multiple studies, the paucity of clinical pain related literature is considered as the major drawback. CONCLUSION: Based on the present systematic review, melatonin plays a critical role in sleep, but evolving studies have demonstrated substantive roles in mitigating degenerative conditions in various tissues, including IVD degeneration. Ongoing studies will better clarify the role of melatonin as a potential therapeutic agent, including the targeted delivery to various body regions.

Validation of Scales for Researching Stakeholders' Attitudes Toward Domestic Violence in China.

Domestic violence (DV) is a significant concern within China. Currently, there are few standardized measurement tools to gauge Chinese stakeholders' perceptions and beliefs concerning DV. This research sought to validate tools to be used with such stakeholders. Factor analyses were utilized on cross-sectional, survey data from a purposive sample of 683 Chinese DV professionals working in four institutions in Guangdong. Analyses developed three scales for measuring DV Definitions, DV Attitudes, and DV Policing. The development of these scales is beneficial to advance the already growing research related to DV in China in ways that are relevant to the Chinese context.

Delivery vehicle and route of administration influences self-amplifying RNA biodistribution, expression kinetics, and reactogenicity.

Self-amplifying RNA (saRNA) is a next-generation RNA platform derived from an alphavirus that enables replication in host cytosol, offering a promising shift from traditional messenger RNA (mRNA) therapies by enabling sustained protein production from minimal dosages. The approval of saRNA-based vaccines, such as the ARCT-154 for COVID-19 in Japan, underscores its potential for diverse therapeutic applications, including vaccine development, cancer immunotherapy, and gene therapy. This study investigates the role of delivery vehicle and administration route on saRNA expression kinetics and reactogenicity. Employing ionizable lipid-based nanoparticles (LNPs) and polymeric nanoparticles, we administered saRNA encoding firefly luciferase to BALB/c mice through six routes (intramuscular (IM), intradermal (ID), intraperitoneal (IP), intranasal (IN), intravenous (IV), and subcutaneous (SC)), and observed persistent saRNA expression over a month. Our findings reveal that while LNPs enable broad route applicability and stability, pABOL (poly (cystamine bisacrylamide-co-4-amino-1-butanol)) formulations significantly amplify protein expression via intramuscular delivery. Notably, the disparity between RNA biodistribution and protein expression highlight the nuanced interplay between administration routes, delivery vehicles, and therapeutic outcomes. Additionally, our research unveiled distinct biodistribution profiles and inflammatory responses contingent upon the chosen delivery formulation and route. This research illuminates the intricate dynamics governing saRNA delivery, biodistribution and reactogenicity, offering essential insights for optimizing therapeutic strategies and advancing the clinical and commercial viability of saRNA technologies.

Virtual Pooled Registry-Cancer Linkage System: an improved method for ascertaining cancer diagnoses.

BACKGROUND: The National Cancer Institute funds many large cohort studies that rely on self-reported cancer data requiring medical record validation. This is labor intensive, costly, and prone to underreporting or misreporting of cancer and disparity-related differential response. US population-based central cancer registries identify incident cancer within their catchment area, yielding all malignant neoplasms and benign brain and central nervous system tumors with standardized data fields. This manuscript describes the development, implementation, and features of a system to facilitate linkage between cohort studies and cancer registries and the release of cancer registry data for matched cohort participants. METHODS: The Virtual Pooled Registry-Cancer Linkage System (VPR-CLS) provides an online system to link cohorts with multiple state cancer registries by 1) securely transmitting a study file to registries, 2) providing an optimized linkage algorithm to generate preliminary match counts, and 3) providing a streamlined process and templated forms for submitting and tracking data requests for cohort participants who matched with registries. RESULTS: In 2022, the VPR-CLS launched with 45 registries, covering 95% of the US state populations and Puerto Rico. Registries have linked with 15 studies having 14 273-10.9 million participants. Except in 1 study, linkage sensitivity ranged from 87.0% to 99.9%. Numerous registries have adopted the VPR-CLS templated institutional review board-registry application (n = 39), templated data use agreement (n = 25), and central institutional review board (n = 16). CONCLUSIONS: The VPR-CLS markedly improves ascertainment of cancer outcomes and is the preferred approach for determination of outcomes from cohort studies, postmarketing surveillance, and clinical trials.

De-escalating aggression in acute inpatient mental health settings: a behaviour change theory-informed, secondary qualitative analysis of staff and patient perspectives.

BACKGROUND: De-escalation is often advocated to reduce harm associated with violence and use of restrictive interventions, but there is insufficient understanding of factors that influence de-escalation behaviour in practice. For the first time, using behaviour change and implementation science methodology, this paper aims to identify the drivers that will enhance de-escalation in acute inpatient and psychiatric intensive care mental health settings. METHODS: Secondary analysis of 46 qualitative interviews with ward staff (n = 20) and patients (n = 26) informed by the Theoretical Domains Framework. RESULTS: Capabilities for de-escalation included knowledge (impact of trauma on memory and self-regulation and the aetiology and experience of voice hearing) and skills (emotional self-regulation, distress validation, reducing social distance, confirming autonomy, setting limits and problem-solving). Opportunities for de-escalation were limited by dysfunctional risk management cultures/ relationships between ward staff and clinical leadership, and a lack of patient involvement in safety maintenance. Motivation to engage in de-escalation was limited by negative emotion associated with moral formulations of patients and internal attributions for behaviour. CONCLUSION: In addition to training that enhances knowledge and skills, interventions to enhance de-escalation should target ward and organisational cultures, as well as making fundamental changes to the social and physical structure of inpatient mental health wards. Psychological interventions targeting negative emotion in staff are needed to increase motivation. This paper provides a new evidence-based framework of indicative changes that will enhance de-escalation in adult acute mental health inpatient and PICU settings.

Epidemiological inference at the threshold of data availability: an influenza A(H1N2)v spillover event in the United Kingdom.

Viruses that infect animals regularly spill over into the human population, but individual events may lead to anything from a single case to a novel pandemic. Rapidly gaining an understanding of a spillover event is critical to calibrating a public health response. We here propose a novel method, using likelihood-free rejection sampling, to evaluate the properties of an outbreak of swine-origin influenza A(H1N2)v in the United Kingdom, detected in November 2023. From the limited data available, we generate historical estimates of the probability that the outbreak had died out in the days following the detection of the first case. Our method suggests that the outbreak could have been said to be over with 95% certainty between 19 and 29 days after the first case was detected, depending upon the probability of a case being detected. We further estimate the number of undetected cases conditional upon the outbreak still being live, the epidemiological parameter R 0, and the date on which the spillover event itself occurred. Our method requires minimal data to be effective. While our calculations were performed after the event, the real-time application of our method has potential value for public health responses to cases of emerging viral infection.

RMCProfile7: reverse Monte Carlo for multiphase systems.

This work introduces a completely rewritten version of the program RMCProfile (version 7), big-box, reverse Monte Carlo modelling software for analysis of total scattering data. The major new feature of RMCProfile7 is the ability to refine multiple phases simultaneously, which is relevant for many current research areas such as energy materials, catalysis and engineering. Other new features include improved support for molecular potentials and rigid-body refinements, as well as multiple different data sets. An empirical resolution correction and calculation of the pair distribution function as a back-Fourier transform are now also available. RMCProfile7 is freely available for download at https://rmcprofile.ornl.gov/.

Leveraging real-world data to predict cancer cachexia stage, quality of life, and survival in a racially and ethnically diverse multi-institutional cohort of treatment-naïve patients with pancreatic ductal adenocarcinoma.

Introduction: Cancer-associated cachexia (CC) is a progressive syndrome characterized by unintentional weight loss, muscle atrophy, fatigue, and poor outcomes that affects most patients with pancreatic ductal adenocarcinoma (PDAC). The ability to identify and classify CC stage along its continuum early in the disease process is challenging but critical for management. Objectives: The main objective of this study was to determine the prevalence of CC stage overall and by sex and race and ethnicity among treatment-naïve PDAC cases using clinical, nutritional, and functional criteria. Secondary objectives included identifying the prevalence and predictors of higher symptom burden, supportive care needs, and quality of life (QoL), and examining their influence on overall survival (OS). Materials and methods: A population-based multi-institutional prospective cohort study of patients with PDAC was conducted between 2018 and 2021 by the Florida Pancreas Collaborative. Leveraging patient-reported data and laboratory values, participants were classified at baseline into four stages [non-cachexia (NCa), pre-cachexia (PCa), cachexia (Ca), and refractory cachexia (RCa)]. Multivariate regression, Kaplan Meier analyses, and Cox regression were conducted to evaluate associations. Results: CC stage was estimated for 309 PDAC cases (156 females, 153 males). The overall prevalence of NCa, PCa, Ca, and RCa was 12.9%, 24.6%, 54.1%, and 8.4%, respectively. CC prevalence across all CC stages was highest for males and racial and ethnic minorities. Criteria differentiated NCa cases from other groups, but did not distinguish PCa from Ca. The most frequently reported symptoms included weight loss, fatigue, pain, anxiety, and depression, with pain significantly worsening over time. The greatest supportive care needs included emotional and physical domains. Males, Black people, and those with RCa had the worst OS. Conclusions: Using clinical, nutritional, and functional criteria, nearly one-quarter of the PDAC cases in our diverse, multi-institutional cohort had PCa and 62.5% had Ca or RCa at the time of diagnosis. The PCa estimate is higher than that reported in prior studies. We recommend these criteria be used to aid in CC classification, monitoring, and management of all incident PDAC cases. Findings also highlight the recommendation for continued emotional support, assistance in alleviating pain, and supportive care needs throughout the PDAC treatment journey.

Do Prophylactic Postoperative Antibiotics Prevent Sacral Neuromodulation Infections?

IMPORTANCE: There are no definitive guidelines for use of postoperative antibiotics after sacral neuromodulation (SNM) leading to practice pattern variation among health care professionals. OBJECTIVES: The objectives of this study were to determine if additional antibiotics beyond preoperative intravenous antibiotics and surgical preparation decrease postoperative infections and to determine if additional antibiotics are associated with other postoperative complications. STUDY DESIGN: This was a single-center, retrospective cohort study of all SNM procedures from 2014 to 2023 performed by 12 surgeons. Cohorts were stratified between patients who received preoperative antibiotics only (OnlyPreAbx) and patients who received both preoperative antibiotics and postoperative antibiotics (PrePostAbx) after either insertion of tined lead and/or after insertion of a neurostimulator. RESULTS: There were 212 patients included in this study: 70 (33.0%) in the OnlyPreAbx group and 142 (67.0%) in the PrePostAbx group. Of patients receiving postoperative antibiotics, 76 (53.5%) received cephalexin, 49 (34.5%) received sulfamethoxazole-trimethoprim, and 17 (12.0%) received alternative antibiotics. Six patients overall (2.8%) experienced infections after SNM. There was no difference in the rates of infection between groups (4 [1.9%] PrePostAbx vs 2 [0.9%] OnlyPreAbx, P = 0.99). Of the 4 patients with postoperative infections in the PrePostAbx group, 2 had cellulitis requiring antibiotics and 2 required full explantation. Of the 2 patients with postoperative infections in the OnlyPreAbx group, both patients required explantation. In a subanalysis comparing infected and noninfected patients, infected patients (n = 6) had higher rates of hypertension (n = 6, 100%; P = 0.02) and diabetes mellitus (n = 3, 50%; P = 0.05). CONCLUSIONS: Additional postoperative antibiotics did not decrease infection rates in patients undergoing SNM. Similar comparative analyses should be performed with larger sample sizes.

Assessing Surgeons' Attitude to Teaching Intra-Corporeal Anastomosis.

Introduction: There is a controversy in minimally invasive colorectal procedures regarding choosing optimal technique between intra-corporeal (ICA) and extra-corporeal anastomosis (ECA). Previous studies recognize the short-term benefits in right hemicolectomy with intra-corporeal approach; however, ICA can result in increased operative difficulty. The aim of this study is to understand attitudes towards teaching ICA in colorectal procedures and how this varies between subspeciality training. Methods: Active members of General Surgeons Australia were contacted through email to participate in a voluntary, unincentivized survey. Demographic details were collected and participants were asked to rate agreement for simulation-based training for increasing adoption of ICA through a Likert scale and when preferences for teaching ICA. Descriptive statistics were completed to describe frequencies and ordinal regression was completed to determine factors for Likert scale question. Results: There were 43 respondents and most participants recognized that ECA was easier to teach trainees and should be taught first. 53.5% of respondents recognized that simulation-based training would assist the adoption of ICA. Surgeons who routinely close bowel or enteric defects intra-corporeally are 354% more likely to show an interest in simulation-based training for adopting ICA, however, surgeons who are not involved in teaching trainees did not show an interest in simulation-based training. Conclusion: There is significant agreement that ECA forms the basis to learn ICA and simulation-based training would assist with the uptake of ICA. However, a multimodal approach, including expanding training avenues and providing financial incentives, would be necessary to enhance the adoption of ICA in colorectal surgery.

Associations between sex, systemic iron and inflammatory status and subcortical brain iron.

Brain iron increases in several neurodegenerative diseases are associated with disease progression. However, the causes of increased brain iron remain unclear. This study investigates relationships between subcortical iron, systemic iron and inflammatory status. Brain magnetic resonance imaging (MRI) scans and blood plasma samples were collected from cognitively healthy females (n = 176, mean age = 61.4 ± 4.5 years, age range = 28-72 years) and males (n = 152, mean age = 62.0 ± 5.1 years, age range = 32-74 years). Regional brain iron was quantified using quantitative susceptibility mapping. To assess systemic iron, haematocrit, ferritin and soluble transferrin receptor were measured, and total body iron index was calculated. To assess systemic inflammation, C-reactive protein (CRP), neutrophil:lymphocyte ratio (NLR), macrophage colony-stimulating factor 1 (MCSF), interleukin 6 (IL6) and interleukin 1ß (IL1ß) were measured. We demonstrated that iron levels in the right hippocampus were higher in males compared with females, while iron in the right caudate was higher in females compared with males. There were no significant associations observed between subcortical iron levels and blood markers of iron and inflammatory status indicating that such blood measures are not markers of brain iron. These results suggest that brain iron may be regulated independently of blood iron and so directly targeting global iron change in the treatment of neurodegenerative disease may have differential impacts on blood and brain iron.

Molecular mechanisms and environmental adaptations of flagellar loss and biofilm growth of Rhodanobacter under environmental stress.

Biofilms aid bacterial adhesion to surfaces via direct and indirect mechanisms, and formation of biofilms is considered as an important strategy for adaptation and survival in sub-optimal environmental conditions. However, the molecular underpinnings of biofilm formation in subsurface sediment/groundwater ecosystems where microorganisms often experience fluctuations in nutrient input, pH, nitrate or metal concentrations is underexplored. We examined biofilm formation under different nutrient, pH, metal, and nitrate regimes of 16 Rhodanobacter strains isolated from subsurface groundwater wells spanning diverse pH (3.5 to 5) and nitrate levels (13.7 to 146 mM). Eight Rhodanobacter strains demonstrated significant biofilm growth under low pH, suggesting adaptation to survive and grow at low pH. Biofilms intensified under aluminum stress, particularly in strains possessing fewer genetic traits associated with biofilm formation warranting further investigation. Through RB-TnSeq, proteomics, use of specific mutants and transmission electron microscopy analysis, we discovered flagellar loss under aluminum stress, indicating a potential relationship between motility, metal tolerance, and biofilm growth. Comparative genomic analyses revealed absence of flagella and chemotaxis genes, and presence of putative Type VI secretion system in the high biofilm-forming strain FW021-MT20. This study identifies genetic determinants associated with biofilm growth in a predominant environmental genus, Rhodanobacter, under metal stress and identifies traits aiding survival and adaptation to contaminated subsurface environments.

Does Severity of Donor Acute Kidney Injury Influence Outcomes Following Kidney Transplantation?

INTRODUCTION: The study purpose was to review retrospectively our single-center experience transplanting kidneys from deceased donors (DD) with acute kidney injury (AKI) according to terminal serum creatinine (tSCr) level. METHODS: AKI kidneys were defined by a doubling of the DD's admission SCr and a tSCr ≥ 2.0 mg/dL. RESULTS: From 1/07 to 11/21, we transplanted 236 AKI DD kidneys, including 100 with a tSCr ≥ 3.0 mg/dL (high SCr AKI group, mean tSCr 4.2 mg/dL), and the remaining 136 from DDs with a tSCr of 2.0-2.99 mg/dL (lower SCr AKI group, mean tSCr 2.4 mg/dL). These two AKI groups were compared to 996 concurrent control patients receiving DD kidneys with a tSCr < 1.0 mg/dL. Mean follow-up was 69 months. Delayed graft function (DGF) rates were 51% versus 46% versus 29% (p < 0.0001), and 5-year patient and death-censored kidney graft survival rates were 96.8% versus 83.5% versus 82.2% (p = 0.002) and 86.7% versus 77.8% versus 78.8% (p = 0.18) in the high tSCr AKI versus lower tSCr AKI versus control groups, respectively. CONCLUSIONS: Despite a higher incidence of DGF, patients receiving kidneys from DDs with tSCr levels ≥3.0 mg/dL have acceptable medium-term outcomes compared to either AKI DDs with a lower tSCr or DDs with a tSCr < 1.0 mg/dL.

Broad-spectrum antibiotics disrupt homeostatic efferocytosis.

The clearance of apoptotic cells, termed efferocytosis, is essential for tissue homeostasis and prevention of autoimmunity1. Although past studies have elucidated local molecular signals that regulate homeostatic efferocytosis in a tissue2,3, whether signals arising distally also regulate homeostatic efferocytosis remains elusive. Here, we show that large peritoneal macrophage (LPM) display impairs efferocytosis in broad-spectrum antibiotics (ABX)-treated, vancomycin-treated and germ-free mice in vivo, all of which have a depleted gut microbiota. Mechanistically, the microbiota-derived short-chain fatty acid butyrate directly boosts efferocytosis efficiency and capacity in mouse and human macrophages, and rescues ABX-induced LPM efferocytosis defects in vivo. Bulk messenger RNA sequencing of butyrate-treated macrophages in vitro and single-cell messenger RNA sequencing of LPMs isolated from ABX-treated and butyrate-rescued mice reveals regulation of efferocytosis-supportive transcriptional programmes. Specifically, we find that the efferocytosis receptor T cell immunoglobulin and mucin domain containing 4 (TIM-4, Timd4) is downregulated in LPMs of ABX-treated mice but rescued by oral butyrate. We show that TIM-4 is required for the butyrate-induced enhancement of LPM efferocytosis capacity and that LPM efferocytosis is impaired beyond withdrawal of ABX. ABX-treated mice exhibit significantly worse disease in a mouse model of lupus. Our results demonstrate that homeostatic efferocytosis relies on distal metabolic signals and suggest that defective homeostatic efferocytosis may explain the link between ABX use and inflammatory disease4-7.

Quantifying near-symmetric molecular distortion using symmetry-coordinate structural decomposition.

We imagine molecules to be perfect, but rigidified units can be designed to bend from their ideal shape, discarding their symmetric elements as they progress through vibrations and larger, more permanent distortions. The shape of molecules is either simulated or measured by crystallography and strongly affects chemical properties but, beyond an image or tabulation of atom-to-atom distances, little is often discussed of the accessed conformation. We have simplified the process of shape quantification across multiple molecular types with a new web-accessible program - SCSD - through which a molecular subunit possessing near-symmetry can be dissected into symmetry coordinates with ease. This parameterization allows a common set of numbers for comparing and understanding molecular shape, and is a simple method for database analysis; this program is available at https://www.kingsbury.id.au/scsd.

Understanding the Solid-State Structure of Riboflavin through a Multitechnique Approach.

Crystalline riboflavin (vitamin B2) performs an important biological role as an optically functional material in the tapetum lucidum of certain animals, notably lemurs and cats. The tapetum lucidum is a reflecting layer behind the retina, which serves to enhance photon capture and vision in low-light settings. Motivated by the aim of rationalizing its biological role, and given that the structure of biogenic solid-state riboflavin remains unknown, we have used a range of experimental and computational techniques to determine the solid-state structure of synthetic riboflavin. Our multitechnique approach included microcrystal XRD, powder XRD, three-dimensional electron diffraction (3D-ED), high-resolution solid-state 13C NMR spectroscopy, and dispersion-augmented density functional theory (DFT-D) calculations. Although an independent report of the crystal structure of riboflavin was published recently, our structural investigations reported herein provide a different interpretation of the intermolecular hydrogen-bonding arrangement in this material, supported by all the experimental and computational approaches utilized in our study. We also discuss, more generally, potential pitfalls that may arise in applying DFT-D geometry optimization as a bridging step between structure solution and Rietveld refinement in the structure determination of hydrogen-bonded materials from powder XRD data. Finally, we report experimental and computational values for the refractive index of riboflavin, with implications for its optical function.