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Separation of the two mirror images of a chiral molecule, the enantiomers, is a historically complicated problem of major relevance for biological systems. Since chiral molecules are optically active, it has been speculated that strong coupling to circularly polarized fields may be used as a general procedure to unlock enantiospecific reactions. In this work, we focus on how chiral cavities can be used to drive asymmetry in the photochemistry of chiral molecular systems. We first show that strong coupling to circularly polarized fields leads to enantiospecific Rabi splittings, an effect that displays a collective behavior in line with other strong coupling phenomena. Additionally, entanglement with circularly polarized light generates an asymmetry in the enantiomer population of the polaritons, leading to a condensation of the excitation on a preferred molecular configuration. These results confirm that chiral cavities represent a tantalizing opportunity to drive asymmetric photochemistry in enantiomeric mixtures., (Creative Commons Attribution license.)

The fate of thymine upon excitation by ultraviolet radiation has been the subject of intense debate. Today, it is widely believed that its ultrafast excited state gas phase decay stems from a radiationless transition from the bright ππ* state to a dark nπ* state. However, conflicting theoretical predictions have made the experimental data difficult to interpret. Here we simulate the early gas phase ultrafast dynamics in thymine at the highest level of theory to date. This is made possible by performing wavepacket dynamics with a recently developed coupled cluster method. Our simulation confirms an ultrafast ππ* to nπ* transition (τ = 41 ± 14 fs). Furthermore, the predicted oxygen-edge X-ray absorption spectra agree quantitatively with experiment. We also predict an as-yet uncharacterized πσ* channel that leads to hydrogen dissociation at one of the two N-H bonds. Similar behavior has been identified in other heteroaromatic compounds, including adenine, and several authors have speculated that a similar pathway may exist in thymine. However, this was never confirmed theoretically or experimentally. This prediction calls for renewed efforts to experimentally identify or exclude the presence of this channel., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Multilevel coupled cluster theory offers reduced scaling computation of intensive properties in systems that are too large for standard coupled cluster calculations. A significant benefit of the multilevel coupled cluster framework is the possibility of calculating intensive properties that are not tightly localized if an appropriate set of active orbitals is used. Correlated natural transition orbitals (CNTOs) are tailored to describe excitation processes. For multilevel coupled cluster singles and doubles (MLCCSD) and singles and perturbative doubles (MLCC2) calculations, the construction of CNTOs generally becomes the computational bottleneck. Here, we demonstrate how CNTOs can be obtained with O ( N 3 ) operations, eliminating the O ( N 5 ) -scaling steps involved in the original approach. This reduction in scaling moves the bottleneck of MLCC2 and MLCCSD calculations from the active orbital space preparation to the MLCC2 and MLCCSD equations with O ( N 4 ) -scaling.

Analytical gradients of potential energy surfaces play a central role in quantum chemistry, allowing for molecular geometry optimizations and molecular dynamics simulations. In strong coupling conditions, potential energy surfaces can account for strong interactions between matter and the quantized electromagnetic field. In this paper, we derive expressions for the ground state analytical gradients in quantum electrodynamics coupled cluster theory. We also present a Cholesky-based implementation for the coupled cluster singles and doubles model. We report timings to show the performance of the implementation and present optimized geometries to highlight cavity-induced molecular orientation effects in strong coupling conditions.

A comprehensive understanding of electron-photon correlation is essential for describing the reshaping of molecular orbitals in quantum electrodynamics (QED) environments. The strong coupling QED Hartree-Fock (SC-QED-HF) theory tackles these aspects by providing consistent molecular orbitals in the strong coupling regime. The previous implementation, however, has significant convergence issues that limit the applicability. In this work, we introduce two second-order algorithms that significantly reduce the computational requirements, thereby enhancing the modeling of large molecular systems in QED environments. Furthermore, the implementation will enable the development of correlated methods based on a reliable molecular orbital framework as well as multi-level methodologies able to model the inclusion of solvent effects in this kind of complex systems.

Objective: To explore the ability of artificial intelligence (AI) to classify breast cancer by mammographic density in an organized screening program., Materials and Method: We included information about 99,489 examinations from 74,941 women who participated in BreastScreen Norway, 2013-2019. All examinations were analyzed with an AI system that assigned a malignancy risk score (AI score) from 1 (lowest) to 10 (highest) for each examination. Mammographic density was classified into Volpara density grade (VDG), VDG1-4; VDG1 indicated fatty and VDG4 extremely dense breasts. Screen-detected and interval cancers with an AI score of 1-10 were stratified by VDG., Results: We found 10,406 (10.5% of the total) examinations to have an AI risk score of 10, of which 6.7% (704/10,406) was breast cancer. The cancers represented 89.7% (617/688) of the screen-detected and 44.6% (87/195) of the interval cancers. 20.3% (20,178/99,489) of the examinations were classified as VDG1 and 6.1% (6047/99,489) as VDG4. For screen-detected cancers, 84.0% (68/81, 95% CI, 74.1-91.2) had an AI score of 10 for VDG1, 88.9% (328/369, 95% CI, 85.2-91.9) for VDG2, 92.5% (185/200, 95% CI, 87.9-95.7) for VDG3, and 94.7% (36/38, 95% CI, 82.3-99.4) for VDG4. For interval cancers, the percentages with an AI score of 10 were 33.3% (3/9, 95% CI, 7.5-70.1) for VDG1 and 48.0% (12/25, 95% CI, 27.8-68.7) for VDG4., Conclusion: The tested AI system performed well according to cancer detection across all density categories, especially for extremely dense breasts. The highest proportion of screen-detected cancers with an AI score of 10 was observed for women classified as VDG4., Clinical Relevance Statement: Our study demonstrates that AI can correctly classify the majority of screen-detected and about half of the interval breast cancers, regardless of breast density., Key Points: • Mammographic density is important to consider in the evaluation of artificial intelligence in mammographic screening. • Given a threshold representing about 10% of those with the highest malignancy risk score by an AI system, we found an increasing percentage of cancers with increasing mammographic density. • Artificial intelligence risk score and mammographic density combined may help triage examinations to reduce workload for radiologists., (© 2024. The Author(s).)

In this work, we present ab initio cavity quantum electrodynamics (QED) methods which include interactions with a static magnetic field and nuclear spin degrees of freedom using different treatments of the quantum electromagnetic field. We derive explicit expressions for QED-HF magnetizability, nuclear shielding, and spin-spin coupling tensors. We apply this theory to explore the influence of the cavity field on the magnetizability of saturated, unsaturated, and aromatic hydrocarbons, showing the effects of different polarization orientations and coupling strengths. We also examine how the cavity affects aromaticity descriptors, such as the nucleus-independent chemical shift and magnetizability exaltation. We employ these descriptors to study the trimerization reaction of acetylene to benzene. We show how the optical cavity induces modifications in the aromatic character of the transition state leading to variations in the activation energy of the reaction. Our findings shed light on the effects induced by the cavity on magnetic properties, especially in the context of aromatic molecules, providing valuable insights into understanding the interplay between the quantum electromagnetic field and molecules.

Objectives: To compare the location of AI markings on screening mammograms with cancer location on diagnostic mammograms, and to classify interval cancers with high AI score as false negative, minimal sign, or true negative., Methods: In a retrospective study from 2022, we compared the performance of an AI system with independent double reading according to cancer detection. We found 93% (880/949) of the screen-detected cancers, and 40% (122/305) of the interval cancers to have the highest AI risk score (AI score of 10). In this study, four breast radiologists reviewed mammograms from 126 randomly selected screen-detected cancers and all 120 interval cancers with an AI score of 10. The location of the AI marking was stated as correct/not correct in craniocaudal and mediolateral oblique view. Interval cancers with an AI score of 10 were classified as false negative, minimal sign significant/non-specific, or true negative., Results: All screen-detected cancers and 78% (93/120) of the interval cancers with an AI score of 10 were correctly located by the AI system. The AI markings matched in both views for 79% (100/126) of the screen-detected cancers and 22% (26/120) of the interval cancers. For interval cancers with an AI score of 10, 11% (13/120) were correctly located and classified as false negative, 10% (12/120) as minimal sign significant, 26% (31/120) as minimal sign non-specific, and 31% (37/120) as true negative., Conclusion: AI markings corresponded to cancer location for all screen-detected cancers and 78% of the interval cancers with high AI score, indicating a potential for reducing the number of interval cancers. However, it is uncertain whether interval cancers with subtle findings in only one view are actionable for recall in a true screening setting., Clinical Relevance Statement: In this study, AI markings corresponded to the location of the cancer in a high percentage of cases, indicating that the AI system accurately identifies the cancer location in mammograms with a high AI score., Key Points: • All screen-detected and 78% of the interval cancers with high AI risk score (AI score of 10) had AI markings in one or two views corresponding to the location of the cancer on diagnostic images. • Among all 120 interval cancers with an AI score of 10, 21% (25/120) were classified as a false negative or minimal sign significant and had AI markings matching the cancer location, suggesting they may be visible on prior screening. • Most of the correctly located interval cancers matched only in one view, and the majority were classified as either true negative or minimal sign non-specific, indicating low potential for being detected earlier in a real screening setting., (© 2024. The Author(s).)

The development of new methodologies for the selective synthesis of individual enantiomers is still one of the major challenges in synthetic chemistry. Many biomolecules, and also many pharmaceutical compounds, are indeed chiral. While the use of chiral reactants or catalysts has led to substantial progress in the field of asymmetric synthesis, a systematic approach applicable to general reactions has still not been proposed. In this work, we demonstrate that strong coupling to circularly polarized fields can induce asymmetry in otherwise nonselective reactions. Specifically, we show that the field induces stereoselectivity in the early stages of chemical reactions by selecting an energetically preferred direction of approach for the reagents. Although the effects observed thus far are too small to significantly drive asymmetric synthesis, our results provide a proof of principle for field-induced stereoselective mechanisms. These findings lay the groundwork for future research.

Coupled cluster theory is one of the most accurate electronic structure methods for predicting ground and excited state chemistry. However, the presence of numerical artifacts at electronic degeneracies, such as complex energies, has made it difficult to apply the method in nonadiabatic dynamics simulations. While it has already been shown that such numerical artifacts can be fully removed by using similarity constrained coupled cluster (SCC) theory [ J. Phys. Chem. Lett. 2017, 8 (19), 4801-4807], simulating dynamics requires efficient implementations of gradients and nonadiabatic couplings. Here, we present an implementation of nuclear gradients and nonadiabatic derivative couplings at the similarity constrained coupled cluster singles and doubles (SCCSD) level of theory, thereby making possible nonadiabatic dynamics simulations using a coupled cluster theory that provides a correct description of conical intersections between excited states. We present a few numerical examples that show good agreement with literature values and discuss some limitations of the method.

Simulations of photochemical reaction dynamics have been a challenge to the theoretical chemistry community for some time. In an effort to determine the predictive character of current approaches, we predict the results of an upcoming ultrafast diffraction experiment on the photodynamics of cyclobutanone after excitation to the lowest lying Rydberg state (S2). A picosecond of nonadiabatic dynamics is described with ab initio multiple spawning. We use both time dependent density functional theory (TDDFT) and equation-of-motion coupled cluster singles and doubles (EOM-CCSD) theory for the underlying electronic structure theory. We find that the lifetime of the S2 state is more than a picosecond (with both TDDFT and EOM-CCSD). The predicted ultrafast electron diffraction spectrum exhibits numerous structural features, but weak time dependence over the course of the simulations., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

Objective: Irregular attendance in breast cancer screening has been associated with higher breast cancer mortality compared to regular attendance. Early performance measures of a screening program following regular versus irregular screening attendance have been less studied. We aimed to investigate early performance measures following regular versus irregular screening attendance., Methods: We used information from 3,302,396 screening examinations from the Cancer Registry of Norway. Examinations were classified as regular or irregular. Regular was defined as an examination 2 years ± 6 months after the prior examination, and irregular examination >2 years and 6 months after prior examination. Performance measures included recall, biopsy, screen-detected and interval cancer, positive predictive values, and histopathological tumor characteristics., Results: Recall rate was 2.4% (72,429/3,070,068) for regular and 3.5% (8217/232,328) for irregular examinations. The biopsy rate was 1.0% (29,197/3,070,068) for regular and 1.7% (3825/232,328) for irregular examinations, while the rate of screen-detected cancers 0.51% (15,664/3,070,068) versus 0.86% (2003/232,328), respectively. The adjusted odds ratio was 1.53 (95% CI: 1.49-1.56) for recall, 1.73 (95% CI: 1.68-1.80) for biopsy, and 1.68 (95% CI: 1.60-1.76) for screen-detected cancer after irregular examinations compared to regular examinations. The proportion of lymph node-positive tumors was 20.1% (2553/12,719) for regular and 25.6% (426/1662) for irregular examinations., Conclusion: Irregular attendance was linked to higher rates of recall, needle biopsies, and cancer detection. Cancers detected after irregular examinations had less favorable histopathological tumor characteristics compared to cancers detected after regular examinations. Women should be encouraged to attend screening when invited to avoid delays in diagnosis., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The X-ray absorption spectra of aqueous ammonia and ammonium are computed using a combination of coupled cluster singles and doubles (CCSD) with different quantum mechanical and molecular mechanical embedding schemes. Specifically, we compare frozen Hartree-Fock (HF) density embedding, polarizable embedding (PE), and polarizable density embedding (PDE). Integrating CCSD with frozen HF density embedding is possible within the CC-in-HF framework, which circumvents the conventional system-size limitations of standard coupled cluster methods. We reveal similarities between PDE and frozen HF density descriptions, while PE spectra differ significantly. By including approximate triple excitations, we also investigate the effect of improving the electronic structure theory. The spectra computed using this approach show an improved intensity ratio compared to CCSD-in-HF. Charge transfer analysis of the excitations shows the local character of the pre-edge and main-edge, while the post-edge is formed by excitations delocalized over the first solvation shell and beyond.

We present a novel three-layer approach based on multilevel density functional theory (MLDFT) and polarizable molecular mechanics to simulate the electronic excitations of chemical systems embedded in an external environment within the time-dependent DFT formalism. In our method, the electronic structure of a target system, the chromophore, is determined in the field of an embedded inactive layer, which is treated as frozen. Long-range interactions are described by employing the polarizable fluctuating charge (FQ) force field. The resulting MLDFT/FQ thus accurately describes both electrostatics (and polarization) and non-electrostatic target-environment interactions. The robustness and reliability of the approach are demonstrated by comparing our results with experimental data reported for various organic molecules in solution.

X-ray absorption (XA) spectroscopy is an essential experimental tool to investigate the local structure of liquid water. Interpretation of the experiment poses a significant challenge and requires a quantitative theoretical description. High-quality theoretical XA spectra require reliable molecular dynamics simulations and accurate electronic structure calculations. Here, we present the first successful application of coupled cluster theory to model the XA spectrum of liquid water. We overcome the computational limitations on system size by employing a multilevel coupled cluster framework for large molecular systems. Excellent agreement with the experimental spectrum is achieved by including triple excitations in the wave function and using molecular structures from state-of-the-art path-integral molecular dynamics. We demonstrate that an accurate description of the electronic structure within the first solvation shell is sufficient to successfully model the XA spectrum of liquid water within the multilevel framework. Furthermore, we present a rigorous charge transfer analysis of the XA spectrum, which is reliable due to the accuracy and robustness of the electronic structure methodology. This analysis aligns with previous studies regarding the character of the prominent features of the XA spectrum of liquid water., (© 2024. The Author(s).)

Intermolecular (Coulombic) interactions are pivotal for aggregation, solvation, and crystallization. We demonstrate that the collective strong coupling of several molecules to a single optical mode results in notable changes in the molecular excitations around a single perturbed molecule, thus representing an impurity in an otherwise ordered system. A competition between short-range coulombic and long-range photonic correlations inverts the local transition density in a polaritonic state, suggesting notable changes in the polarizability of the solvation shell. Our results provide an alternative perspective on recent work in polaritonic chemistry and pave the way for the rigorous treatment of cooperative effects in aggregation, solvation, and crystallization.

We present state-of-the-art calculations of the core-ionization spectrum of water. Despite significant progress in procedures developed to mitigate various experimental complications and uncertainties, the experimental determination of ionization energies of solvated species involves several non-trivial steps such as assessing the effect of the surface potential, electrolytes, and finite escape depths of photoelectrons. This provides a motivation to obtain robust theoretical values of the intrinsic bulk ionization energy and the corresponding solvent-induced shift. Here we develop theoretical protocols based on coupled-cluster theory and electrostatic embedding. Our value of the intrinsic solvent-induced shift of the 1s O ionization energy of water is -1.79 eV. The computed absolute position and the width of the 1s O peak in photoelectron spectrum of water are 538.47 eV and 1.44 eV, respectively, agreeing well with the best experimental values.

The core-level electron excitation and ionization spectra of glycolaldehyde have been investigated by photoabsorption and photoemission spectroscopy at both carbon and oxygen K -edges; the valence ionization spectra were also recorded by photoelectron spectroscopy in the UV-vis region. The spectra are interpreted by means of ab initio calculations based on the equation-of-motion coupled cluster singles and doubles (EOM-CCSD) and coupled cluster singles, doubles, and perturbative are in good agreement with the experimental results, and many of the observed features are assigned. The photoabsorption spectra are not only dominated by transitions from core-level orbitals to unoccupied π and σ orbitals but also show structures due to Rydberg transitions.

Chemical and photochemical reactivity, as well as supramolecular organization and several other molecular properties, can be modified by strong interactions between light and matter. Theoretical studies of these phenomena require the separation of the Schrödinger equation into different degrees of freedom as in the Born-Oppenheimer approximation. In this paper, we analyze the electron-photon Hamiltonian within the cavity Born-Oppenheimer approximation (CBOA), where the electronic problem is solved for fixed nuclear positions and photonic parameters. In particular, we focus on intermolecular interactions in representative dimer complexes. The CBOA potential energy surfaces are compared with those obtained using a polaritonic approach, where the photonic and electronic degrees of freedom are treated at the same level. This allows us to assess the role of electron-photon correlation and the accuracy of CBOA., (© 2023 Author(s). Published under an exclusive license by AIP Publishing.)

We extend the multilevel coupled cluster framework with triplet excitation energies at the singles and perturbative doubles (MLCC2) and singles and doubles (MLCCSD) levels of theory. In multilevel coupled cluster theory, we partition the orbitals and restrict the higher-order excitations in the cluster operator to a set of active orbitals. With an appropriate choice of these orbitals, the multilevel approach can give significant computational savings while maintaining the high accuracy of standard coupled cluster theory. In this work, we generated active orbitals from approximate correlated natural transition orbitals (CNTOs). The CNTOs form a compact orbital space specifically tailored to describe the triplet excited states of interest. We compare the performance of MLCCSD and MLCC2, in terms of cost and accuracy, to those of their standard coupled cluster counterparts (CC2 and CCSD) and finally show proof-of-concept calculations of the singlet-triplet gaps of molecules that are of interest for their potential use in organic light-emitting diodes.

Time-dependent equation-of-motion coupled cluster (TD-EOM-CC) is used to simulate impulsive stimulated X-ray Raman scattering (ISXRS) of ultrashort laser pulses by neon, carbon monoxide, pyrrole, and p -aminophenol. The TD-EOM-CC equations are expressed in the basis of field-free EOM-CC states, where the calculation of the core-excited states is simplified through the use of the core-valence separation (CVS) approximation. The transfer of electronic population from the ground state to the core- and valence-excited states is calculated for different numbers of included core- and valence-excited states, as well as for electric field pulses with different polarizations and carrier frequencies. The results indicate that Gaussian pulses can transfer significant electronic populations to the valence states through the Raman process. The sensitivity of this population transfer to the model parameters is analyzed. The time-dependent electronic density for p -aminophenol is also showcased, supporting the interpretation that ISXRS involves localized core excitations and can be used to rapidly generate valence wavepackets.

Intermolecular van der Waals interactions are central to chemical and physical phenomena ranging from biomolecule binding to soft-matter phase transitions. In this work, we demonstrate that strong light-matter coupling can be used to control the thermodynamic properties of many-molecule systems. Our analyses reveal orientation dependent single molecule energies and interaction energies for van der Waals molecules. For example, we find intermolecular interactions that depend on the distance between the molecules R as R -3 and R 0 . Moreover, we employ ab initio cavity quantum electrodynamics calculations to develop machine-learning-based interaction potentials for molecules inside optical cavities. By simulating systems ranging from 12 H 2 to 144 H 2 molecules, we observe varying degrees of orientational order because of cavity-modified interactions, and we explain how quantum nuclear effects, light-matter coupling strengths, number of cavity modes, molecular anisotropies, and system size all impact the extent of orientational order.

Background Few studies have evaluated the role of artificial intelligence (AI) in prior screening mammography. Purpose To examine AI risk scores assigned to screening mammography in women who were later diagnosed with breast cancer. Materials and Methods Image data and screening information of examinations performed from January 2004 to December 2019 as part of BreastScreen Norway were used in this retrospective study. Prior screening examinations from women who were later diagnosed with cancer were assigned an AI risk score by a commercially available AI system (scores of 1-7, low risk of malignancy; 8-9, intermediate risk; and 10, high risk of malignancy). Mammographic features of the cancers based on the AI score were also assessed. The association between AI score and mammographic features was tested with a bivariate test. Results A total of 2787 prior screening examinations from 1602 women (mean age, 59 years ± 5.1 [SD]) with screen-detected ( n = 1016) or interval ( n = 586) cancers showed an AI risk score of 10 for 389 (38.3%) and 231 (39.4%) cancers, respectively, on the mammograms in the screening round prior to diagnosis. Among the screen-detected cancers with AI scores available two screening rounds (4 years) before diagnosis, 23.0% (122 of 531) had a score of 10. Mammographic features were associated with AI score for invasive screen-detected cancers ( P < .001). Density with calcifications was registered for 13.6% (43 of 317) of screen-detected cases with a score of 10 and 4.6% (15 of 322) for those with a score of 1-7. Conclusion More than one in three cases of screen-detected and interval cancers had the highest AI risk score at prior screening, suggesting that the use of AI in mammography screening may lead to earlier detection of breast cancers. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Mehta in this issue.

Purpose: To explore Norwegian breast radiologists' expectations of adding artificial intelligence (AI) in the interpretation procedure of screening mammograms., Methods: All breast radiologists involved in interpretation of screening mammograms in BreastScreen Norway during 2021 and 2022 (n = 98) were invited to take part in this anonymous cross-sectional survey about use of AI in mammographic screening. The questionnaire included background information of the respondents, their expectations, considerations of biases, and ethical and social implications of implementing AI in screen reading. Data was collected digitally and analyzed using descriptive statistics., Results: The response rate was 61% (60/98), and 67% (40/60) of the respondents were women. Sixty percent (36/60) reported ≥10 years' experience in screen reading, while 82% (49/60) reported no or limited experience with AI in health care. Eighty-two percent of the respondents were positive to explore AI in the interpretation procedure in mammographic screening. When used as decision support, 68% (41/60) expected AI to increase the radiologists' sensitivity for cancer detection. As potential challenges, 55% (33/60) reported lack of trust in the AI system and 45% (27/60) reported discrepancy between radiologists and AI systems as possible challenges. The risk of automation bias was considered high among 47% (28/60). Reduced time spent reading mammograms was rated as a potential benefit by 70% (42/60)., Conclusion: The radiologists reported positive expectations of AI in the interpretation procedure of screening mammograms. Efforts to minimize the risk of automation bias and increase trust in the AI systems are important before and during future implementation of the tool., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

We present a novel framework for spin-adapted coupled cluster theory. The approach exploits the entanglement of an open-shell molecule with electrons in a non-interacting bath. Together, the molecule and the bath form a closed-shell system, and electron correlation can be included using the standard spin-adapted closed-shell coupled cluster formalism. A projection operator, which enforces conditions on the electrons in the bath, is used to obtain the desired state of the molecule. This entanglement coupled cluster theory is outlined, and proof-of-concept calculations for doublet states are reported. The approach is further extendable to open-shell systems with other values of the total spin., (© 2023 Author(s). Published under an exclusive license by AIP Publishing.)

Strong coupling between molecules and quantized fields has emerged as an effective methodology to engineer molecular properties. New hybrid states are formed when molecules interact with quantized fields. Since the properties of these states can be modulated by fine-tuning the field features, an exciting and new side of chemistry can be explored. In particular, significant modifications of the molecular properties can be achieved in plasmonic nanocavities, where the field quantization volume is reduced to subnanometric volumes, thus leading to intriguing applications such as single-molecule imaging and high-resolution spectroscopy. In this work, we focus on phenomena where the simultaneous effects of multiple plasmonic modes are critical. We propose a theoretical methodology to account for many plasmonic modes simultaneously while retaining computational feasibility. Our approach is conceptually simple and allows us to accurately account for the multimode effects and rationalize the nature of the interaction between multiple plasmonic excitations and molecules.

Objectives: To compare results of selected performance measures in mammographic screening for an artificial intelligence (AI) system versus independent double reading by radiologists., Methods: In this retrospective study, we analyzed data from 949 screen-detected breast cancers, 305 interval cancers, and 13,646 negative examinations performed in BreastScreen Norway during the period from 2010 to 2018. An AI system scored the examinations from 1 to 10, based on the risk of malignancy. Results from the AI system were compared to screening results after independent double reading. AI score 10 was set as the threshold. The results were stratified by mammographic density., Results: A total of 92.7% of the screen-detected and 40.0% of the interval cancers had an AI score of 10. Among women with a negative screening outcome, 9.1% had an AI score of 10. For women with the highest breast density, the AI system scored 100% of the screen-detected cancers and 48.6% of the interval cancers with an AI score of 10, which resulted in a sensitivity of 80.9% for women with the highest breast density for the AI system, compared to 62.8% for independent double reading. For women with screen-detected cancers who had prior mammograms available, 41.9% had an AI score of 10 at the prior screening round., Conclusions: The high proportion of cancers with an AI score of 10 indicates a promising performance of the AI system, particularly for women with dense breasts. Results on prior mammograms with AI score 10 illustrate the potential for earlier detection of breast cancers by using AI in screen-reading., Key Points: • The AI system scored 93% of the screen-detected cancers and 40% of the interval cancers with AI score 10. • The AI system scored all screen-detected cancers and almost 50% of interval cancers among women with the highest breast density with AI score 10. • About 40% of the screen-detected cancers had an AI score of 10 on the prior mammograms, indicating a potential for earlier detection by using AI in screen-reading., (© 2023. The Author(s).)

We present an efficient implementation of analytical non-adiabatic derivative coupling elements for the coupled cluster singles and doubles model. The derivative coupling elements are evaluated in a biorthonormal formulation in which the nuclear derivative acts on the right electronic state, where this state is biorthonormal with respect to the set of left states. This stands in contrast to earlier implementations based on normalized states and a gradient formula for the derivative coupling. As an illustration of the implementation, we determine a minimum energy conical intersection between the nπ* and ππ* states in the nucleobase thymine., (© 2023 Author(s). Published under an exclusive license by AIP Publishing.)

We present a novel multiscale approach to study the electronic structure of open shell molecular systems embedded in an external environment. The method is based on the coupling of multilevel Hartree-Fock (MLHF) and Density Functional Theory (MLDFT), suitably extended to the unrestricted formalism, to Molecular Mechanics (MM) force fields (FF). Within the ML region, the system is divided into active and inactive parts, thus describing the most relevant interactions (electrostatic, polarization, and Pauli repulsion) at the quantum level. The surrounding MM part, which is formulated in terms of nonpolarizable or polarizable FFs, permits a physically consistent treatment of long-range electrostatics and polarization effects. The approach is extended to the calculation of hyperfine coupling constants and applied to selected nitroxyl radicals in an aqueous solution.

We present a computational study of static and dynamic linear polarizabilities in solution. We use different theoretical approaches to describe solvent effects, ranging from quantum mechanics/molecular mechanics (QM/MM) to quantum embedding approaches. In particular, we consider non-polarizable and polarizable QM/MM methods, the latter based on the fluctuating charge (FQ) force field. In addition, we use a quantum embedding method defined in the context of multilevel Hartree-Fock (MLHF), where the system is divided into active and inactive regions, and combine it with a third layer described by means of the FQ model. The multiscale approaches are then used as reference wave functions for equation-of-motion coupled cluster (EOM-CC) response properties, allowing for the account of electron correlation. The developed models are applied to the calculation of linear response properties of two organic moieties-namely, para -nitroaniline and benzonitrile-in non-aqueous solvents-1,4-dioxane, acetonitrile, and tetrahydrofuran. The computed polarizabilities are then discussed in terms of the physico-chemical solute-solvent interactions described by each method (electrostatic, polarization and Pauli repulsion), and finally compared with the available experimental references.

Background: A man in his fifties, originally from a Middle Eastern country, presented with left-sided otalgia and neck pain which worsened over several months. He had pre-existing hypertension, diabetes mellitus type 2 and end stage renal disease requiring dialysis., Case Presentation: His presenting complaints started whilst on a long stay in his country of origin. Symptoms progressively worsened over the coming months while he underwent extensive medical examinations and investigations. This revealed opacifications in the mastoid cavities, raised inflammatory markers, and finally a CT scan revealed osteolytic lesions in his cervical spine. The lesions continued to progress, and his clinical condition deteriorated to the point that he required surgery. Culture was obtained through perioperative biopsies and showed growth of Aspergillus flavus., Interpretation: The patient had initially received topical treatment for an assumed infectious external otitis. Later culture from his outer ear also showed growth of A. flavus, the same pathogen that was found in a biopsy from his cervical spine. He was diagnosed with cervical mycotic osteomyelitis, probably secondary to a chronic external otitis. Long term antimycotic therapy and three neurosurgical operations were required to treat the patient.

We present an efficient implementation of the equation of motion oscillator strengths for the closed-shell multilevel coupled cluster singles and doubles with perturbative triples method (MLCC3) in the electronic structure program e T . The orbital space is split into an active part treated with CC3 and an inactive part computed at the coupled cluster singles and doubles (CCSD) level of theory. Asymptotically, the CC3 contribution scales as O ( n V n v 3 n o 3 ) floating-point operations, where n V is the total number of virtual orbitals while n v and n o are the number of active virtual and occupied orbitals, respectively. The CC3 contribution, thus, only scales linearly with the full system size and can become negligible compared to the cost of CCSD. We demonstrate the capabilities of our implementation by calculating the ultraviolet-visible spectrum of azobenzene and a core excited state of betaine 30 with more than 1000 molecular orbitals.

We introduce the concept of fragment localized molecular orbitals (FLMOs), which are Hartree-Fock molecular orbitals localized in specific fragments constituting a molecular system. In physical terms, we minimize the local electronic energies of the different fragments, at the cost of maximizing the repulsion between them. To showcase the approach, we rationalize the main interactions occurring in large biological systems in terms of interactions between the fragments of the system. In particular, we study an anticancer drug intercalated within DNA and retinal in anabaena sensory rhodopsin as prototypes of molecular systems embedded in biological matrixes. Finally, the FLMOs are exploited to rationalize the formation of two oligomers, prototypes of amyloid diseases, such as Parkinson and Alzheimer.

We present a trust-region optimization of the Edmiston-Ruedenberg orbital localization function. The approach is used to localize both the occupied and the virtual orbitals and is the first demonstration of general virtual orbital localization using the Edmiston-Ruedenberg localization function. In the Edmiston-Ruedenberg approach, the sum of the orbital self-repulsion energies is maximized to obtain the localized orbitals. The Cholesky decomposition reduces the cost of transforming the electron repulsion integrals, and the overall scaling of our implementation is O ( N 4 ) . The optimization is performed with all quantities in the molecular orbital basis, and the localization of the occupied orbitals is often less expensive than the corresponding self-consistent field (SCF) optimization. Furthermore, the occupied orbital localization scales linearly with the basis set. For the virtual space, the cost is significantly higher than the SCF optimization. The orbital spreads of the resulting virtual Edmiston-Ruedenberg orbitals are larger than for other, less expensive, orbital localization functions. This indicates that other localization procedures are more suitable for applications such as local post-Hartree-Fock calculations.

We present an efficient implementation of ground and excited state coupled cluster singles and doubles (CCSD) gradients based on Cholesky-decomposed electron repulsion integrals. Cholesky decomposition and density fitting are both inner projection methods, and, thus, similar implementation schemes can be applied for both methods. One well-known advantage of inner projection methods, which we exploit in our implementation, is that one can avoid storing large V 3 O and V 4 arrays by instead considering three-index intermediates. Furthermore, our implementation does not require the formation and storage of Cholesky vector derivatives. The new implementation is shown to perform well, with less than 10% of the time spent calculating the gradients in geometry optimizations. Furthermore, the computational time per optimization cycle is significantly lower compared to other implementations based on an inner projection method. We showcase the capabilities of the implementation by optimizing the geometry of the retinal molecule (C 20 H 28 O) at the CCSD/aug-cc-pVDZ level of theory.

The ionization of molecular systems is important in many chemical processes, such as electron transfer and hot electron injection. Strong coupling between molecules and quantized fields (e.g., inside optical cavities) represents a new promising way to modify molecular properties in a non-invasive way. Recently, strong light-matter coupling has shown the potential to significantly improve the rates of hot electron driven processes, for instance, in water splitting. In this paper, we demonstrate that inside an optical cavity, the residual interaction between an outgoing free electron and the vacuum field is significant. We further show that since the quantized field is also interacting with the ionized molecule, the free electron and the molecular system are correlated. We develop a theoretical framework to account for the field induced correlation and show that the interaction between the free electron and the field, free electron-field interaction, has sizable effects on the ionization potential of typical organic molecules.

The computation of Dyson orbitals and corresponding ionization energies has been implemented within the equation of motion coupled cluster singles, doubles and perturbative triples (EOM-CC3) method. Coupled to an accurate description of the electronic continuum via a time-dependent density functional approach using a multicentric B-spline basis, this yields highly accurate photoionization dynamical parameters (cross-sections, branching ratios, asymmetry parameters and dichroic coefficients) for primary (1h) states as well as satellite states of (2h1p) character. Illustrative results are presented for the molecular systems H 2 O, H 2 S, CS, CS 2 and ( S )-propylene oxide (a.k.a. methyloxirane).

Coupling between molecules and vacuum photon fields inside an optical cavity has proven to be an effective way to engineer molecular properties, in particular reactivity. To ease the rationalization of cavity induced effects we introduce an ab initio method leading to the first fully consistent molecular orbital theory for quantum electrodynamics environments. Our framework is non-perturbative and explains modifications of the electronic structure due to the interaction with the photon field. In this work, we show that the newly developed orbital theory can be used to predict cavity induced modifications of molecular reactivity and pinpoint classes of systems with significant cavity effects. We also investigate electronic cavity-induced modifications of reaction mechanisms in vibrational strong coupling regimes., (© 2022. The Author(s).)

We study the excited state absorption (ESA) properties of the four DNA bases (thymine, cytosine, adenine, and guanine) by different single reference quantum mechanical methods, namely, equation of motion coupled cluster singles and doubles (EOM-CCSD), singles, doubles and perturbative triples (EOM-CC3), and time-dependent density functional theory (TD-DFT), with the long-range corrected CAM-B3LYP functional. Preliminary results at the Tamm-Dancoff (TDA) CAM-B3LYP level using the maximum overlap method (MOM) are reported for thymine. In the gas phase, the three methods predict similar One Photon Absorption (OPA) spectra, which are consistent with the experimental results and with the most accurate computational studies available in the literature. The ESA spectra are then computed for the ππ* states (one for pyrimidine, two for purines) associated with the lowest-energy absorption band, and for the close-lying nπ* state. The EOM-CC3, EOM-CCSD and CAM-B3LYP methods provide similar ESA spectral patterns, which are also in qualitative agreement with literature RASPT2 results. Once validated in the gas phase, TD-CAM-B3LYP has been used to compute the ESA in chloroform, including solvent effects by the polarizable continuum model (PCM). The predicted OPA and ESA spectra in chloroform are very similar to those in the gas phase, most of the bands shifting by less than 0.1 eV, with a small increase of the intensities and a moderate destabilization of the nπ* state. Finally, ESA spectra have been computed from the minima of the lowest energy ππ* state, and found in line with the available experimental transient absorption spectra of the nucleosides in solution, providing further validation of our computational approach.

In this article we use MP2 and CCSD(T) calculations for the A24 and S66 data sets to explore how midbond functions can be used to generate cost effective counterpoise corrected supramolecular interaction energies of noncovalent complexes. We use the A24 data set to show that the primary role of midbond functions is not to approach the complete basis set limit, but rather to ensure a balanced description of the molecules and the interaction region (unrelated to the basis set superposition error). The need for balance is a consequence of using atom centered basis sets. In the complete basis set limit, the error will disappear, but reaching the complete basis set limit is not feasible beyond small systems. For S66 we investigate the need for increasing the number of midbond centers. Results show that adding a second midbond center increases the accuracy, but the effect is secondary to changing the atom centered basis set. Further, by comparing calculations using the 3s3p2d1f1g midbond set with using aug-cc-pVDZ and aug-cc-pVTZ as midbond sets, we see that the requirements for the midbond set to be effective, is not just that it contains diffuse functions, but also that high angular momentum functions are included. By comparing two approaches for placing midbond centers we show that results are not particularly sensitive to placement as long as the placement is reasonable., (© 2021 The Authors. Journal of Computational Chemistry published by Wiley Periodicals LLC.)

We introduce a new algorithm for the construction of the two-electron contributions to the Fock matrix in multilevel Hartree-Fock (MLHF) theory. In MLHF, the density of an active molecular region is optimized, while the density of an inactive region is fixed. The MLHF equations are solved in a reduced molecular orbital (MO) basis localized to the active region. The locality of the MOs can be exploited to reduce the computational cost of the Fock matrix: the cost related to the inactive density becomes linear scaling, while the iterative cost related to the active density is independent of the system size. We demonstrate the performance of this new algorithm on a variety of systems, including amino acid chains, water clusters, and solvated systems.

Time-resolved near-edge X-ray absorption fine structure (TR-NEXAFS) spectroscopy is a powerful technique for studying photochemical reaction dynamics with femtosecond time resolution. In order to avoid ambiguity in TR-NEXAFS spectra from nonadiabatic dynamics simulations, core- and valence-excited states must be evaluated on equal footing and those valence states must also define the potential energy surfaces used in the nonadiabatic dynamics simulation. In this work, we demonstrate that hole-hole Tamm-Dancoff-approximated density functional theory (hh-TDA) is capable of directly simulating TR-NEXAFS spectroscopies. We apply hh-TDA to the excited-state dynamics of acrolein. We identify two pre-edge features in the oxygen K-edge TR-NEXAFS spectrum associated with the S 2 (ππ*) and S 1 (nπ*) excited states. We show that these features can be used to follow the internal conversion dynamics between the lowest three electronic states of acrolein. Due to the low, O(N 2 ) apparent computational complexity of hh-TDA and our GPU-accelerated implementation, this method is promising for the simulation of pre-edge features in TR-NEXAFS spectra of large molecules and molecules in the condensed phase.

Plasmonic nanocavities enable the confinement of molecules and electromagnetic fields within nanometric volumes. As a consequence, the molecules experience a remarkably strong interaction with the electromagnetic field to such an extent that the quantum states of the system become hybrids between light and matter: polaritons. Here, we present a nonperturbative method to simulate the emerging properties of such polaritons: it combines a high-level quantum chemical description of the molecule with a quantized description of the localized surface plasmons in the nanocavity. We apply the method to molecules of realistic complexity in a typical plasmonic nanocavity, featuring also a subnanometric asperity (picocavity). Our results disclose the effects of the mutual polarization and correlation of plasmons and molecular excitations, disregarded so far. They also quantify to what extent the molecular charge density can be manipulated by nanocavities and stand as benchmarks to guide the development of methods for molecular polaritonics.

In this article, we use two extensively studied systems, a retinal model system and azobenzene, to explore the use of coupled cluster models for describing ground and singlet excited state potential energy surfaces of photoswitchable systems. While not being suitable for describing nuclear dynamics of photoisomerization, coupled cluster models have useful attributes, such as the inclusion of dynamical correlation, their black box nature, and the systematic improvement offered by truncation level. Results for the studied systems show that when triple excitations (here through the CC3 model) are included, ground and excited state potential energy surfaces for isomerization paths may reliably be generated, also for states of doubly excited character. For ground state equilibrium cis- and trans-azobenzene, the molecular geometry and basis set is seen to significantly impact the vertical excitation energies for the two lowest excited states. Efficient implementations of coupled cluster models can therefore constitute valuable tools for investigating photoswitchable systems and can be used for preliminary black box studies to gather information before more complicated excited state dynamics approaches are pursued., (© 2021 The Authors. Journal of Computational Chemistry published by Wiley Periodicals LLC.)

We present the first investigation of excited state dynamics by resonant Auger-Meitner spectroscopy (also known as resonant Auger spectroscopy) using the nucleobase thymine as an example. Thymine is photoexcited in the UV and probed with X-ray photon energies at and below the oxygen K-edge. After initial photoexcitation to a ππ* excited state, thymine is known to undergo internal conversion to an nπ* excited state with a strong resonance at the oxygen K-edge, red-shifted from the ground state π* resonances of thymine (see our previous study Wolf, et al., Nat. Commun., 2017, 8, 29). We resolve and compare the Auger-Meitner electron spectra associated both with the excited state and ground state resonances, and distinguish participator and spectator decay contributions. Furthermore, we observe simultaneously with the decay of the nπ* state signatures the appearance of additional resonant Auger-Meitner contributions at photon energies between the nπ* state and the ground state resonances. We assign these contributions to population transfer from the nπ* state to a ππ* triplet state via intersystem crossing on the picosecond timescale based on simulations of the X-ray absorption spectra in the vibrationally hot triplet state. Moreover, we identify signatures from the initially excited ππ* singlet state which we have not observed in our previous study.

We report a production-level implementation of the equation-of-motion (EOM) coupled-cluster (CC) method with double electron-attaching (DEA) EOM operators of 2p and 3p1h types, EOM-DEA-CCSD. This ansatz, suitable for treating electronic structure patterns that can be described as two-electrons-in-many orbitals, represents a useful addition to the EOM-CC family of methods. We analyze the performance of EOM-DEA-CCSD for energy differences and molecular properties. By considering reduced quantities, such as state and transition one-particle density matrices, we compare EOM-DEA-CCSD wave functions with wave functions computed by other EOM-CCSD methods. The benchmarks illustrate that EOM-DEA-CCSD is capable of treating diradicals, bond-breaking, and some types of conical intersections.

We present a computational study of the one-photon and excited-state absorption (ESA) from the two lowest energy excited states of uracil in the gas phase: an nπ* dark state ( 1n ) and the lowest energy bright ππ* state ( 1π ). The predictions of six different linear response electronic structure methods, namely, TD-CAM-B3LYP, EOM-CCSD, EOM-CC3, ADC(2), ADC(2)-x, and ADC(3) are critically compared. In general, the spectral shapes predicted by TD-CAM-B3LYP, EOM-CCSD, EOM-CC3, and ADC(3) are fairly similar, though the quality of TD-CAM-B3LYP slightly deteriorates in the high-energy region. By computing the spectra at some key structures on different potential energy surfaces (PES), that is, the Franck-Condon point, the 1n minimum, and structures representative of different regions of the 1π PES, we obtain important insights into the shift of the ESA spectra, following the motion of the wavepacket on the excited-state PES. Though 1π has larger ESA than 1n , some spectral regions are dominated by these latter signals. Aside from its methodological interest, we thus obtain interesting indications to interpret transient absorption spectra to disentangle the photoactivated dynamics of nucleobases.

Intermolecular bonds are weak compared to covalent bonds, but they are strong enough to influence the properties of large molecular systems. In this work, we investigate how strong light-matter coupling inside an optical cavity can modify intermolecular forces and illustrate the varying necessity of correlation in their description. The electromagnetic field inside the cavity can modulate the ground state properties of weakly bound complexes. Tuning the field polarization and cavity frequency, the interactions can be stabilized or destabilized, and electron densities, dipole moments, and polarizabilities can be altered. We demonstrate that electron-photon correlation is fundamental to describe intermolecular interactions in strong light-matter coupling. This work proposes optical cavities as a novel tool to manipulate and control ground state properties, solvent effects, and intermolecular interactions for molecules and materials.

We investigate the coupling of different quantum-embedding approaches with a third molecular-mechanics layer, which can be either polarizable or non-polarizable. In particular, such a coupling is discussed for the multilevel families of methods, in which the system is divided into an active and an inactive orbital space. The computational cost of the resulting three-layer approaches is reduced by treating the long-range interactions at the classical level. The developed methods are tested by the calculation of excitation energies of molecular systems in aqueous solution, for which an atomistic description of the environment is crucial to correctly reproduce the specific solute-solvent interactions, such as hydrogen bonding. In particular, we present the results obtained for three different moieties - acrolein, pyridine and para-nitroaniline - showing that an almost perfect agreement with experimental data can be achieved when the relevant physico-chemical interactions are included in the modeling of the condensed phase.

Following recent developments in multilevel embedding methods, we introduce a novel density matrix-based multilevel approach within the framework of density functional theory (DFT). In this multilevel DFT, the system is partitioned in an active and an inactive fragment, and all interactions are retained between the two parts. The decomposition of the total system is performed upon the density matrix. The orthogonality between the two parts is maintained by solving the Kohn-Sham equations in the MO basis for the active part only, while keeping the inactive density matrix frozen. This results in the reduction of computational cost. We outline the theory and implementation and discuss the differences and similarities with state-of-the-art DFT embedding methods. We present applications to aqueous solutions of methyloxirane and glycidol.