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Journal of Chemical Theory and... Jul 2023Fast and accurate estimation of electronic coupling matrix elements between molecules is essential for the simulation of charge transfer phenomena in chemistry,...
Fast and accurate estimation of electronic coupling matrix elements between molecules is essential for the simulation of charge transfer phenomena in chemistry, materials science, and biology. Here we investigate neural-network-based coupling estimators combined with different protocols for sampling reference data (random, farthest point, and query by committee) and compare their performance to the physics-based analytic overlap method (AOM), introduced previously. We find that neural network approaches can give smaller errors than AOM, in particular smaller maximum errors, while they require an order of magnitude more reference data than AOM, typically one hundred to several hundred training points, down from several thousand required in previous ML works. A Δ-ML approach taking AOM as a baseline is found to give the best overall performance at a relatively small computational overhead of about a factor of 2. Highly flexible π-conjugated organic molecules like non-fullerene acceptors are found to be a particularly challenging case for ML because of the varying (de)localization of the frontier orbitals for different intramolecular geometries sampled along molecular dynamics trajectories. Here the local symmetry functions used in ML are insufficient, and long-range descriptors are expected to give improved performance.
PubMed: 37345885
DOI: 10.1021/acs.jctc.3c00184 -
Journal of Chemical Theory and... Jul 2023F. Gygi recently suggested an analytic, norm-conserving, regularized nuclear potential to enable all-electron plane-wave calculations [Gygi 2023, 19, 1300-1309.]. This...
F. Gygi recently suggested an analytic, norm-conserving, regularized nuclear potential to enable all-electron plane-wave calculations [Gygi 2023, 19, 1300-1309.]. This potential () is determined by inverting the Schrödinger equation for the wave function Ansatz ϕ() = exp[-()]/√π with () = erf() + exp(-), where and are parameters. Gygi fixes by demanding ϕ to be normalized, with the value () depending on the strength of the regularization controlled by . We begin this work by re-examining the determination of () and find that the original 10-decimal tabulations of Gygi are only correct to 5 decimals, leading to normalization errors in the order of 10. In contrast, we show that a simple 100-point radial quadrature scheme not only ensures at least 10 correct decimals of but also leads to machine-precision level satisfaction of the normalization condition. Moreover, we extend Gygi's plane-wave study by examining the accuracy of () with high-precision finite element calculations with Hartree-Fock and LDA, GGA, and meta-GGA functionals on first- to fifth-period atoms. We find that although the convergence of the total energy appears slow in the regularization parameter , orbital energies and shapes are indeed reproduced accurately by the regularized potential even with relatively small values of , as compared to results obtained with a point nucleus. The accuracy of the potential is furthermore studied with - excitation energies of Sc-Cu as well as ionization potentials of He-Kr, which are found to converge to sub-meV precision with = 4. The findings of this work are in full support of Gygi's contribution, indicating that all-electron plane-wave calculations can be accurately performed with the regularized nuclear potential.
PubMed: 37354116
DOI: 10.1021/acs.jctc.3c00530 -
Science Advances Apr 2024The formation of protein precursors, due to the condensation of atomic carbon under the low-temperature conditions of the molecular phases of the interstellar medium,...
The formation of protein precursors, due to the condensation of atomic carbon under the low-temperature conditions of the molecular phases of the interstellar medium, opens alternative pathways for the origin of life. We perform peptide synthesis under conditions prevailing in space and provide a comprehensive analytic characterization of its products. The application of C allowed us to confirm the suggested pathway of peptide formation that proceeds due to the polymerization of aminoketene molecules that are formed in the C + CO + NH reaction. Here, we address the question of how the efficiency of peptide production is modified by the presence of water molecules. We demonstrate that although water slightly reduces the efficiency of polymerization of aminoketene, it does not prevent the formation of peptides.
Topics: Extraterrestrial Environment; Water; Peptides
PubMed: 38630826
DOI: 10.1126/sciadv.adj7179 -
Journal of Exposure Science &... Nov 2023Toenails are a promising matrix for chronic metal exposure assessment, but there are currently no standard methods for collection and analysis. Questions remain about...
BACKGROUND
Toenails are a promising matrix for chronic metal exposure assessment, but there are currently no standard methods for collection and analysis. Questions remain about sample mass requirements and the extent to which metals measured in this matrix are representative of chronic body burden.
OBJECTIVE
This study proposes a method to maximize sample conservation for toenail metals analysis using inductively coupled plasma mass spectrometry (ICP-MS). We demonstrate the reliability of an ~25 mg toenail sample (typically 1-2 clippings) for metals analysis and evaluate the intra-individual variability of multiple metals in this matrix over time in men from the Gulf Long-term Follow-up (GuLF) Study.
METHODS
Toenail samples from 123 GuLF Study participants were collected at two visits 3 years apart and analyzed for 18 elements using ICP-MS. Participants with samples exceeding 200 mg at the first visit (n = 29) were selected for triplicate sub-sample analysis. Kendall's coefficient of concordance (W) was used to assess sub-sample reliability and Spearman's correlation coefficients (ρ) were used to evaluate fluctuations in elemental concentrations over time.
RESULTS
Results were not reported for Cd, Co, Mo, Sb, and V (detected in <60% of the samples). There was strong agreement among triplicate samples (Kendall's W: 0.72 (Cu)-0.90 (Cu)) across all elements evaluated, moderate correlations of elemental concentrations (Spearman's ρ: 0.21-0.42) over 3 years for As, Ca, Cr, Fe, Pb, Mn, and Zn, and strong correlations (>0.50) for Se, Cu, and Hg.
IMPACT STATEMENT
This toenail reliability study found that a low-mass (~25 mg) toenail sample (1-2 clippings) is suitable for the determination of most elements using ICP-MS and helps to increase the analytical capacity of limited toenail biospecimens collected in cohort studies. The results highlight differences in the suitability of toenails for chronic metal exposure assessment by element and underscore the need to consider intra-person variability, especially when comparing results across studies. We also provide recommendations for analytical standardization and the partitioning of the total collected toenail sample into multiple analytic sub-samples for future studies using toenail biospecimen for multiple assays.
Topics: Male; Humans; Nails; Reproducibility of Results; Metals; Mercury; Biomarkers; Trace Elements
PubMed: 37296232
DOI: 10.1038/s41370-023-00560-y -
The Journal of Headache and Pain Mar 2024The burden and disability associated with headaches are conceptualized and measured differently at patients' and populations' levels. At the patients' level, through... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The burden and disability associated with headaches are conceptualized and measured differently at patients' and populations' levels. At the patients' level, through patient-reported outcome measures (PROMs); at population level, through disability weights (DW) and years lived with a disability (YLDs) developed by the Global Burden of Disease Study (GBD). DW are 0-1 coefficients that address health loss and have been defined through lay descriptions. With this literature review, we aimed to provide a comprehensive analysis of disability in headache disorders, and to present a coefficient referring to patients' disability which might inform future GBD definitions of DW for headache disorders.
METHODS
We searched SCOPUS and PubMed for papers published between 2015 and 2023 addressing disability in headache disorders. The selected manuscript included a reference to headache frequency and at least one PROM. A meta-analytic approach was carried out to address relevant differences for the most commonly used PROMs (by headache type, tertiles of medication intake, tertiles of females' percentage in the sample, and age). We developed a 0-1 coefficient based on the MIDAS, on the HIT-6, and on MIDAS + HIT-6 which was intended to promote future DW iterations by the GBD consortium.
RESULTS
A total of 366 studies, 596 sub-samples, and more than 133,000 single patients were available, mostly referred to cases with migraine. Almost all PROMs showed the ability to differentiate disability severity across conditions and tertiles of medication intake. The indexes we developed can be used to inform future iterations of DW, in particular considering their ability to differentiate across age and tertiles of medication intake.
CONCLUSIONS
Our review provides reference values for the most commonly used PROMS and a data-driven coefficient whose main added value is its ability to differentiate across tertiles of age and medication intake which underlie on one side the increased burden due to aging (it is likely connected to the increased impact of common comorbidities), and by the other side the increased burden due to medication consumption, which can be considered as a proxy for headache severity. Both elements should be considered when describing disability of headache disorders at population levels.
Topics: Female; Humans; Global Burden of Disease; Headache; Headache Disorders; Migraine Disorders; Aging
PubMed: 38433202
DOI: 10.1186/s10194-024-01735-0 -
Communications Biology Apr 2024Trace elements are important for human health but may exert toxic or adverse effects. Mechanisms of uptake, distribution, metabolism, and excretion are partly under...
Trace elements are important for human health but may exert toxic or adverse effects. Mechanisms of uptake, distribution, metabolism, and excretion are partly under genetic control but have not yet been extensively mapped. Here we report a comprehensive multi-element genome-wide association study of 57 essential and non-essential trace elements. We perform genome-wide association meta-analyses of 14 trace elements in up to 6564 Scandinavian whole blood samples, and genome-wide association studies of 43 trace elements in up to 2819 samples measured only in the Trøndelag Health Study (HUNT). We identify 11 novel genetic loci associated with blood concentrations of arsenic, cadmium, manganese, selenium, and zinc in genome-wide association meta-analyses. In HUNT, several genome-wide significant loci are also indicated for other trace elements. Using two-sample Mendelian randomization, we find several indications of weak to moderate effects on health outcomes, the most precise being a weak harmful effect of increased zinc on prostate cancer. However, independent validation is needed. Our current understanding of trace element-associated genetic variants may help establish consequences of trace elements on human health.
Topics: Male; Humans; Trace Elements; Genome-Wide Association Study; Zinc; Selenium; Manganese
PubMed: 38594418
DOI: 10.1038/s42003-024-06101-z -
European Journal of Pharmaceutical... Aug 2024Bioequivalence determinations for locally acting dermatology drug products rely on assessing product sameness thru physicochemical composition and structure comparison,...
Bioequivalence determinations for locally acting dermatology drug products rely on assessing product sameness thru physicochemical composition and structure comparison, comparing the concentration of the active ingredient at the putative site of action, or comparing the clinical performance of the test (would-be generic) and reference products. Topical product action on cutaneous disease may be confounded by the action of excipients and are also subject to the inherent variability of how product may interact with the skin, including thermodynamic factors such as evaporation, spreadability, and interaction with the local environment such as heat and light and skin moisture.
Topics: Humans; Administration, Cutaneous; Dermatologic Agents; Excipients; Skin; Skin Diseases; Therapeutic Equivalency
PubMed: 38797441
DOI: 10.1016/j.ejps.2024.106815 -
Medicina Oral, Patologia Oral Y Cirugia... Sep 2023A new classification for periodontitis has been adopted in clinical practice. However, there are still discussions regarding this new classification and difficulties in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
A new classification for periodontitis has been adopted in clinical practice. However, there are still discussions regarding this new classification and difficulties in its adoption, both by professionals and researchers. Thus, this study aimed to evaluate which salivary biomarkers are present in periodontitis, following the new classification of periodontal diseases through meta-analysis.
MATERIAL AND METHODS
A literature search was carried out in the scientific databases: PubMed, Scielo and Google scholar to select studies. The selection of studies was followed by two authors upon reading of the title, abstract and full text. The necessary data were collected and statistical analyses were performed using the Review Manager statistical software version 5.4, with calculation of Mean Difference, heterogeneity (I²) and funnel plot with P < 0.05.
RESULTS
After following the selection criteria, 9 articles were selected for comparison. The studies address the presence of biomarkers in the saliva of patients with periodontitis and their possible use in the monitoring and diagnosis of the disease. For the meta-analytic comparison, a sample size of 1,983 individuals was used. Statistical analyses showed that nitric oxide, IL-6, IL-1B and osteoprotegerin are substances that are significantly present in patients with periodontitis (P < 0.05).
CONCLUSIONS
IL-6, nitric oxide, IL-1B, TNF-α and osteoprotegerin are among the most present biomarkers in patients with periodontitis, and may be used in the future as a monitoring of periodontal disease. The present study also revealed that there was no statistically significant difference in the concentration of these biomarkers for clinical distinction from periodontitis.
Topics: Humans; Osteoprotegerin; Nitric Oxide; Interleukin-6; Periodontitis; Biomarkers; Saliva; Chronic Periodontitis
PubMed: 37026605
DOI: 10.4317/medoral.25876 -
Journal of Chemical Theory and... Oct 2023The developments of the open-source OpenMolcas chemistry software environment since spring 2020 are described, with a focus on novel functionalities accessible in the...
The developments of the open-source OpenMolcas chemistry software environment since spring 2020 are described, with a focus on novel functionalities accessible in the stable branch of the package or via interfaces with other packages. These developments span a wide range of topics in computational chemistry and are presented in thematic sections: electronic structure theory, electronic spectroscopy simulations, analytic gradients and molecular structure optimizations, ab initio molecular dynamics, and other new features. This report offers an overview of the chemical phenomena and processes OpenMolcas can address, while showing that OpenMolcas is an attractive platform for state-of-the-art atomistic computer simulations.
PubMed: 37216210
DOI: 10.1021/acs.jctc.3c00182 -
Journal of Veterinary Internal Medicine 2023Cytosine arabinoside (Ara-C) is a nucleoside analog prodrug utilized for immunomodulatory effects mediated by its active metabolite Ara-CTP. Optimal dosing protocols for...
BACKGROUND
Cytosine arabinoside (Ara-C) is a nucleoside analog prodrug utilized for immunomodulatory effects mediated by its active metabolite Ara-CTP. Optimal dosing protocols for immunomodulation in dogs have not been defined. Cytarabine ocfosfate (CO) is a lipophilic prodrug of Ara-C that can be administered PO and provides prolonged serum concentrations of Ara-C.
OBJECTIVES
Provide pharmacokinetic data for orally administered CO and determine accumulation and functional consequences of Ara-CTP within peripheral blood leukocytes.
ANIMALS
Three healthy female hound dogs and 1 healthy male Beagle.
METHODS
Prospective study. Dogs received 200 mg/m of CO PO q24h for 7 doses. Serum and cerebrospinal fluid (CSF) CO and Ara-C concentrations were measured by liquid chromatography-tandem mass spectroscopy (LC-MS/MS). Complete blood counts, flow cytometry, and leukocyte activation assays were done up to 21 days. Incorporation of Ara-CTP within leukocyte DNA was determined by LC-MS/MS.
RESULTS
Maximum serum concentration (C ) for Ara-C was 456.1-724.0 ng/mL (1.88-2.98 μM) and terminal half-life was 23.3 to 29.4 hours. Cerebrospinal fluid: serum Ara-C ratios ranged from 0.54 to 1.2. Peripheral blood lymphocyte concentrations remained within the reference range, but proliferation rates poststimulation were decreased at 6 days. Incorporation of Ara-CTP was not saturated and remained >25% of peak concentration at 13 days.
CONCLUSIONS AND CLINICAL IMPORTANCE
Oral CO may produce prolonged serum Ara-C half-lives at concentrations sufficient to induce functional changes in peripheral leukocytes and is associated with prolonged retention of DNA-incorporated Ara-CTP. Application of functional and active metabolite assessment is feasible and may provide more relevant data to determine optimal dosing regimens for Ara-C-based treatments.
Topics: Female; Male; Dogs; Animals; Arabinofuranosylcytosine Triphosphate; Chromatography, Liquid; Prodrugs; Prospective Studies; Tandem Mass Spectrometry; Leukocytes; Biomarkers; Cytarabine; DNA
PubMed: 37670479
DOI: 10.1111/jvim.16842