Evolution of the impact of the COVID-19 pandemic on heart transplant recipients: Decreasing risk, improving perspective.

BACKGROUND AND METHODS: Heart transplant recipients (HTr) have a higher probability of suffer from severe coronavirus disease-2019 (COVID-19) in comparison to general population, but their risk has changed over the course of the pandemic in relation to various factors. We conducted a prospective study including all HTr at risk of COVID-19 in a tertiary center between February 2020 and October 2022. The aim was to analyze how the prognosis (incidence of pneumonia and mortality) of COVID-19 in HTr has evolved over time, contextualizing variants, vaccination, and other treatments. RESULTS: Of 308 HTr included, 124 got the infection (39.2%). COVID and non-COVID HTr had similar baseline characteristics. COVID-19 patients with pneumonia had a poorer prognosis than those with less severe presentations, with a higher rate of hospitalization (93.3 vs. 14.1%, p < .001) and death (41.0 vs. 1.2%, p < .001). Multivariate analysis identified age ≥60 years (odds ratio [OR] 3.65, 95% confidence interval [CI] 1.16-11.49, p = .027), and chronic kidney disease ≥3a (OR 4.95, 95% CI 1.39-17.54, p = .014) as predictors of pneumonia. Two-dose vaccination (OR 0.20, CI 95% 0.05-0.72, p = .02) and early remdesivir administration (OR 0.17, CI 0.03-0.90, p = .037) were protective factors. Over the course of the pandemic considering three periods in the follow-up (prevaccination February-December 2020, postvaccination January-December 2021, and post early remdesivir indication January-October 2022), we observed a reduction in pneumonia incidence from 62% to 19% (p < .001); and mortality (from 23% to 4%, p < .001). CONCLUSIONS: The prognosis of COVID-19 in HTr has improved over time, likely due to vaccination and early administration of remdesivir.

Axial-equatorial equilibrium in substituted cyclohexanes: a DFT perspective on a small but complex problem.

In Chemistry, complexity is not necessarily associated to large systems, as illustrated by the textbook example of axial-equatorial equilibrium in mono-substituted cyclohexanes. The difficulty in modelling such a simple isomerization is related to the need for reproducing the delicate balance between two forces, with opposite effects, namely the attractive London dispersion and the repulsive steric interactions. Such balance is a stimulating challenge for density-functional approximations and it is systematically explored here by considering 20 mono-substituted cyclohexanes. In comparison to highly accurate CCSD(T) reference calculations, their axial-equatorial equilibrium is studied with a large set of 48 exchange-correlation approximations, spanning from semilocal to hybrid to more recent double hybrid functionals. This dataset, called SAV20 (as Steric A-values for 20 molecules), allows to highlight the difficulties encountered by common and more original DFT approaches, including those corrected for dispersion with empirical potentials, the 6-31G*-ACP model, and our cost-effective PBE-QIDH/DH-SVPD protocol, in modeling these challenging interactions. Interestingly, the performance of the approaches considered in this contribution on the SAV20 dataset does not correlate with that obtained with other more standard datasets, such as S66, IDISP or NC15, thus indicating that SAV20 covers physicochemical features not already considered in previous noncovalent interaction benchmarks.

The Effect of Ultrasound on the Extraction and Functionality of Proteins from Duckweed (Lemna minor).

The inclusion of protein in the regular human diet is important for the prevention of several chronic diseases. In the search for novel alternative protein sources, plant-based proteins are widely explored from a sustainable and ecological point of view. Duckweed (Lemna minor), also known as water lentil, is an aquatic plant with potential applications for human consumption due to its protein content and carbohydrate contents. Among all the conventional and novel protein extraction methods, the utilization of ultrasound has attracted the attention of scientists because of its effects on improving protein extraction and its functionalities. In this work, a Box-Behnken experimental design was proposed to optimize the alkaline extraction of protein from duckweed. In addition, an exploration of the effects of ultrasound on the morphological, structural, and functional properties of the extracted protein was also addressed. The optimal extraction parameters were a pH of 11.5 and an ultrasound amplitude and processing time of 60% and 20 min, respectively. These process conditions doubled the protein content extracted in comparison to the value from the initial duckweed sample. Furthermore, the application of ultrasound during the extraction of protein generated changes in the FTIR spectra, color, and structure of the duckweed protein, which resulted in improvements in its solubility, emulsifying properties, and foaming capacity.

Modulation of the autophagy-lysosomal pathway and endoplasmic reticulum stress by ketone bodies in experimental models of stroke.

Ischemic stroke is a leading cause of disability worldwide. There is no simple treatment to alleviate ischemic brain injury, as thrombolytic therapy is applicable within a narrow time window. During the last years, the ketogenic diet (KD) and the exogenous administration of the ketone body ß-hydroxybutyrate (BHB) have been proposed as therapeutic tools for acute neurological disorders and both can reduce ischemic brain injury. However, the mechanisms involved are not completely clear. We have previously shown that the D enantiomer of BHB stimulates the autophagic flux in cultured neurons exposed to glucose deprivation (GD) and in the brain of hypoglycemic rats. Here, we have investigated the effect of the systemic administration of D-BHB, followed by its continuous infusion after middle cerebral artery occlusion (MCAO), on the autophagy-lysosomal pathway and the activation of the unfolded protein response (UPR). Results show for the first time that the protective effect of BHB against MCAO injury is enantiomer selective as only D-BHB, the physiologic enantiomer of BHB, significantly reduced brain injury. D-BHB treatment prevented the cleavage of the lysosomal membrane protein LAMP2 and stimulated the autophagic flux in the ischemic core and the penumbra. In addition, D-BHB notably reduced the activation of the PERK/eIF2α/ATF4 pathway of the UPR and inhibited IRE1α phosphorylation. L-BHB showed no significant effect relative to ischemic animals. In cortical cultures under GD, D-BHB prevented LAMP2 cleavage and decreased lysosomal number. It also abated the activation of the PERK/eIF2α/ATF4 pathway, partially sustained protein synthesis, and reduced pIRE1α. In contrast, L-BHB showed no significant effects. Results suggest that protection elicited by D-BHB treatment post-ischemia prevents lysosomal rupture allowing functional autophagy, preventing the loss of proteostasis and UPR activation.

Total neoadjuvant therapy approach for the treatment of locally advanced rectal cancer. Where do we stand?

BACKGROUND: for the management of locally advanced rectal cancer (LARC), initial treatment with neoadjuvant chemoradiotherapy followed by surgery and chemotherapy in selected patients is considered one of the recommended options by the main international clinical guidelines. Nonetheless, the administration of all chemotherapy before definitive treatment (total neoadjuvant therapy or TNT) is an optimal alternative with a growing level of evidence that must be evaluated in multidisciplinary boards. This review summarizes the available data and controversies in this scenario. SUMMARY: we have analyzed the characteristics of the main published studies that assess the use of TNT in patients with LARC, evaluating their inclusion criteria and distinguishing between the employed radiotherapy fractionations, systemic agents, timing, and the implications of these treatments in regard to surgery and long-term oncological results. Our aim is to describe the evidence that supports the use of a specific regime in everyday clinical practice. KEY POINTS: there is solid evidence for the use of TNT in patients with LARC. There is no data indicating the superiority of one specific TNT scheme among all the existing options. International clinical guidelines leave the door open to choose the most adequate treatment based on the clinical and pathological characteristics of each patient. This review shows the different approaches to TNT and assesses the best options based on clinical evidence.

Computational Design of Multiple Resonance-Type BN Molecules for Inverted Singlet and Triplet Excited States.

A computational design of linearly extended multiple resonance (MR)-type BN molecules based on DABNA-1 is proposed herein in the quest to find potential candidates that exhibit a negative singlet-triplet gap (ΔEST) and a large oscillator strength value. The impact of a proper account of the electron correlation in the lowest singlet and triplet excited states is systematically investigated by using double-hybrid functionals within the TD-DFT framework, as well as wavefunction-based methods (EOM-CCSD and SCS-CC2), since this contribution plays an essential role in driving the magnitude of the ΔEST in MR-TADF and inverted singlet-triplet gap compounds. Our results point out a gradual reduction of the ΔEST gap with respect to the increasing sum of the number of B and N atoms, reaching negative ΔEST values for some molecules as a function of their size. The double-hybrid functionals reproduce the gap with only slight deviation compared to available experimental data for DABNA-1, ν-DABNA, and mDBCz and nicely agree with high-level quantum mechanical methods (e.g., EOM-CCSD and SCS-CC2). Larger oscillator strengths are found compared to the azaphenalene-type molecules, also exhibiting the inversion of their singlet and triplet excited states. We hope this study can serve as a motivation for further design of the molecules showing negative ΔEST based on boron- and nitrogen-doped polyaromatic hydrocarbons.

Benchmarking DFT Functionals for Excited-State Calculations of Donor-Acceptor TADF Emitters: Insights on the Key Parameters Determining Reverse Inter-System Crossing.

The importance of intermediate triplet states and the nature of excited states has gained interest in recent years for the thermally activated delayed fluorescence (TADF) mechanism. It is widely accepted that simple conversion between charge transfer (CT) triplet and singlet excited states is too crude, and a more complex route involving higher-lying locally excited triplet excited states has to be invoked to witness the magnitude of the rate of reverse inter-system crossing (RISC) rates. The increased complexity has challenged the reliability of computational methods to accurately predict the relative energy between excited states as well as their nature. Here, we compare the results of widely used density functional theory (DFT) functionals, CAM-B3LYP, LC-ωPBE, LC-ω*PBE, LC-ω*HPBE, B3LYP, PBE0, and M06-2X, against a wavefunction-based reference method, Spin-Component Scaling second-order approximate Coupled Cluster (SCS-CC2), in 14 known TADF emitters possessing a diversity of chemical structures. Overall, the use of the Tamm-Dancoff Approximation (TDA) together with CAM-B3LYP, M06-2X, and the two ω-tuned range-separated functionals LC-ω*PBE and LC-ω*HPBE demonstrated the best agreement with SCS-CC2 calculations in predicting the absolute energy of the singlet S1, and triplet T1 and T2 excited states and their energy differences. However, consistently across the series and irrespective of the functional or the use of TDA, the nature of T1 and T2 is not as accurately captured as compared to S1. We also investigated the impact of the optimization of S1 and T1 excited states on ΔEST and the nature of these states for three different functionals (PBE0, CAM-B3LYP, and M06-2X). We observed large changes in ΔEST using CAM-B3LYP and PBE0 functionals associated with a large stabilization of T1 with CAM-B3LYP and a large stabilization of S1 with PBE0, while ΔEST is much less affected considering the M06-2X functional. The nature of the S1 state barely evolves after geometry optimization essentially because this state is CT by nature for the three functionals tested. However, the prediction of the T1 nature is more problematic since these functionals for some compounds interpret the nature of T1 very differently. SCS-CC2 calculations on top of the TDA-DFT optimized geometries lead to a large variation in terms of ΔEST and the excited-state nature depending on the chosen functionals, further stressing the large dependence of the excited-state features on the excited-state geometries. The presented work highlights that despite good agreement of energies, the description of the exact nature of the triplet states should be undertaken with caution.

SOS1-RSX-QIDH: A spin-opposite-scaled range-separated-exchange quadratic-integrand double-hybrid density functional.

We develop and validate the SOS1-RSX-QIDH density functional, a one-parameter spin-opposite-scaled variant of the range-separated-exchange quadratic-integrand double-hybrid (RSX-QIDH) model. By entering into the family of spin-biased double hybrids, this new density functional benefits from an improved computational scaling that rivals with the one of hybrids, still conserving the accuracy of its RSX-QIDH version. As part of the latter family, this density functional is well-adapted to treat molecular systems that are particularly prone to self-interaction errors in their ground and excited states. In particular, we show that the SOS1-RSX-QIDH model is a good compromise to treat ground-state problems dealing with kinetics and has a real added value when applied to the evaluation of the excited-state properties of equilibrium and out-of-equilibrium molecular complexes. Even if spin-biased double hybrids are recognized to strongly underestimate noncovalent interactions, we notice and recommend coupling SOS1-RSX-QIDH with a nonlocal van der Waals potential, a combination that is here proved to compete with the best density-functional approximations currently in use.

Theoretical study of Gibbs free energy and NMR chemical shifts, of the effect of methyl substituents on the isomers of (E)-1-(α,Ꞵ-Dimethylbenzyliden)-2,2-diphenylhydrazine.

A theoretical analysis of free Gibbs Energy and NMR 1H 13C chemical shifts of the effect of introduce methyl groups on diphenyl rings, to produce different isomers of (E)-1-(α,Ꞵ-dimethylbenzylidene)-2,2-diphenylhydrazine, is presented. IR vibrational frequencies, Mulliken charges, molecular electrostatic potential (MEP), Gibbs free energy (G) and 1H- and 13C-NMR chemical shifts were obtained by theoretical calculations. In this analysis it was found that the position of the methyl group affects the values of the 1H- and 13C-NMR chemical shifts and the ∆G and ∆H thermodynamic properties of formation and reaction, these properties vary with the same trend, for the isomers studied. Gibbs free energy calculations show that the theoretical (E)-1-(3,4-Dimethylbenzylidene)-2,2-diphenylhydrazine isomer is the most stable, which explains the success of the experimental synthesis of this compound among the other isomers. For this molecule, the C of the HC=N group is the most nucleophilic and the H is the least acidic. The 1H-NMR chemical shifts of protons show a strong correlation with the C=N distance. It was also observed that methyl affects the ν(C=N) frequencies, the C=N distance increases when the inductive effect of the methyl groups is in the structure.

MicroRNA Dysregulation in Early Breast Cancer Diagnosis: A Systematic Review and Meta-Analysis.

Breast cancer continues to be the leading cause of death in women worldwide. Mammography, which is the current gold standard technique used to diagnose it, presents strong limitations in early ages where breast cancer is much more aggressive and fatal. MiRNAs present in numerous body fluids might represent a new line of research in breast cancer biomarkers, especially oncomiRNAs, known to play an important role in the suppression and development of neoplasms. The aim of this systematic review and meta-analysis was to evaluate dysregulated miRNA biomarkers and their diagnostic accuracy in breast cancer. Two independent researchers reviewed the included studies according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. A protocol for this review was registered in PROSPERO with the registration number "CRD42021256338". Observational case-control-based studies analyzing concentrations of microRNAs which have been published within the last 10 years were selected, and the concentrations of miRNAs in women with breast cancer and healthy controls were analyzed. Random-effects meta-analyses of miR-155 were performed on the studies which provided enough data to calculate diagnostic odds ratios. We determined that 34 microRNAs were substantially dysregulated and could be considered biomarkers of breast cancer. Individually, miR-155 provided better diagnostic results than mammography on average. However, when several miRNAs are used to screen, forming a panel, sensitivity and specificity rates improve, and they can be associated with classic biomarkers such us CA-125 or CEA. Based on the results of our meta-analysis, miR-155 might be a promising diagnostic biomarker for this patient population.

Design Strategies for Diradical Boron/Nitrogen Doped Carbon-Based Materials.

New heterocyclic diradicaloids based on boron and nitrogen-doped polycyclic systems with open-shell ground-states are obtained via concomitant structural and quinoidal extensions, thus allowing to merge the best of both design strategies. A combination of experimental characterization and theoretical calculations have helped disclose their electronic structure, as well as rationalize their associated magnetic and photophysical properties, spanning the chemical space of available molecular templates for cutting-edge applications in organic electronics and spintronics.

Progress towards the elimination of hepatitis B in children in Colombia: A novel two-phase study approach.

The World Health Organization (WHO) has established a target to eliminate mother-to-child-transmission (EMTCT) of hepatitis B virus (HBV), defined as a prevalence of hepatitis B surface antigen (HBsAg) of ≤0.1% among children, by 2030. Using nationally representative serosurveys to verify achievement of this target requires large sample sizes and significant resources. We assessed the feasibility of a potentially more efficient two-phase method to verify EMTCT of HBV in Colombia. In the first phase, we conducted a risk assessment to identify municipalities at the highest risk of ongoing HBV transmission. We ranked the 1122 municipalities of Colombia based on the reports of HBV infection in pregnant women per 1000 population. Municipalities with ≥0.3 reports per 1000 persons (equating to the top quartile) were further assessed based on health facility birth rates, coverage with three doses of hepatitis B vaccine (HepB3) and seroprevalence data. Hepatitis B risk was considered to be further increased for municipalities with HepB3 coverage or health facility birth rate <90%. In the second phase, we conducted a multistage household serosurvey of children aged 5-10 years in 36 municipalities with the highest assessed HBV risk. HBsAg was not detected in any of 3203 children tested, yielding a 90% upper confidence bound of <0.1% prevalence. Coverage with HepB3 and hepatitis B birth dose was high at 97.5% and 95.6%, respectively. These results support the conclusion that Colombia has likely achieved EMTCT of HBV.

Double Hybrids and Noncovalent Interactions: How Far Can We Go?

The accurate evaluation of weak noncovalent interactions in large, that is those containing up to thousand atoms, molecular systems represents a difficult challenge for any quantum chemical method. Indeed, some approximations are often introduced to render affordable these calculations. Here, we consider the PBE-QIDH/DH-SVPD protocol, combining a nonempirical double hybrid functional (PBE-QIDH) with a small basis set (DH-SVPD) tailored for noncovalent interactions with a double aim: (i) explore the robustness and accuracy of this protocol with respect to other Density Functional Approximations; (ii) illustrate how its performances are affected by the computational parameters underlying the calculation of the exact exchange and the Coulomb contribution, as well as the perturbative term. To this end, we consider three data sets, namely S66, L7, and CiM13, incorporating molecules of increasing size. On the bright side, our results suggest that the PBE-QIDH/DH-SVPD protocol is particularly accurate for large systems such as those contained in the CiM13 set (up to more than 1000 atoms and 14 000 basis functions), for which the DLPNO approximation leads to a significant speed-up for the evaluation of the perturbative correlation term. However, our analysis also points out the limit of this statistical exercise, when the quality of the reference data cannot be easily assessed, due to the size of the molecular complexes involved, and when the number of molecules is limited.

Tackling an accurate description of molecular reactivity with double-hybrid density functionals.

In this Communication, we assess a panel of 18 double-hybrid density functionals for the modeling of the thermochemical and kinetic properties of an extended dataset of 449 organic chemistry reactions belonging to the BH9 database. We show that most of DHs provide a statistically robust performance to model barrier height and reaction energies in reaching the "chemical accuracy." In particular, we show that nonempirical DHs, such as PBE0-DH and PBE-QIDH, or minimally parameterized alternatives, such as ωB2PLYP and B2K-PLYP, succeed to accurately model both properties in a balanced fashion. We demonstrate, however, that parameterized approaches, such as ωB97X-2 or DSD-like DHs, are more biased to only one of both properties.

Assessing challenging intra- and inter-molecular charge-transfer excitations energies with double-hybrid density functionals.

We investigate the performance of a set of recently introduced range-separated double-hybrid functionals, namely ωB2-PLYP, ωB2GP-PLYP, RSX-0DH, and RSX-QIDH models for hard-to-calculate excitation energies. We compare with the parent (B2-PLYP, B2GP-PLYP, PBE0-DH, and PBE-QIDH) and other (DSD-PBEP86) double-hybrid models as well as with some of the most widely employed hybrid functionals (B3LYP, PBE0, M06-2X, and ωB97X). For this purpose, we select a number of medium-sized intra- and inter-molecular charge-transfer excitations, which are known to be challenging to calculate using time-dependent density-functional theory (TD-DFT) and for which accurate reference values are available. We assess whether the high accuracy shown by the newest double-hybrid models is also confirmed for those cases too. We find that asymptotically corrected double-hybrid models yield a superior performance, especially for the inter-molecular charge-transfer excitation energies, as compared to standard double-hybrid models. Overall, the PBE-QIDH and its corresponding range-separated RSX-QIDH functional are recommended for general-purpose TD-DFT applications, depending on whether long-range effects are expected to play a significant role.

Beyond Chemical Accuracy for Alkane Thermochemistry: The DHthermo Approach.

The so-called protobranching phenomenon, that is the greater stability of branched alkanes with respect to their linear isomers, represents an interesting challenge for approaches based on density functional theory (DFT), since it requires a balanced description of several electronic effects, including (intramolecular) dispersion forces. Here, we investigate this problem using a protocol recently developed based on double-hybrid functionals and a small basis set, DH-SVPD, suited for noncovalent interactions. The energies of bond separation reactions (BSR), defined on the basis of an isodesmic principle, are taken as reference properties for the evaluation of 15 DFT approaches. The obtained results show that error lower than the so-called "chemical accuracy" (<1.0 kcal/mol) can be obtained by the proposed protocol on both relative reaction energies and enthalpies. These results are then verified on the standard BSR36 data set and support the proposition of our computational protocol, named DHthermo, where any DH functional, such as PBE-QIDH or B2PLYP, provides accurate results when coupled to an empirical dispersion correction and the DH-SVPD basis set. This protocol not only gives subchemical accuracy on the thermochemistry of alkanes but it is extremely easy to use with common quantum-chemistry codes.

How to adapt sexual and reproductive health services to the needs and circumstances of trans people- a qualitative study in Colombia.

BACKGROUND: People living a trans-life require access to equitable healthcare services, policies and research that address their needs. However, trans people have experienced different forms of violence, discrimination, stigma, and unfair access barriers when dealing with healthcare providers. Therefore, adapting sexual and reproductive health services with the purpose of providing more equitable, inclusive and discrimination-free healthcare services is an urgent need. The article presents an example of how operative research can be used in order to adjust sexual and reproductive healthcare services to trans people's needs, identities and circumstances. METHODS: This is a qualitative study written from a constructivist perspective, and it is based on the voices and experiences of trans people in four major cities in Colombia. The research used a combination of focus groups of discussion (n = 6) and in-depth interviews with trans people (n = 13) in Barranquilla, Bogota, Cali and Medellin. This research had two specific objectives: i) identifying the main sexual and reproductive health needs of people living a trans-life; and ii) generating new evidence in order to guide the adaptation of sexual and reproductive health services centered to trans people's needs, identities, and circumstances. Qualitative data codification and analysis was using NVivo. RESULTS: Once access barriers to sexual and reproductive health services, unmet sexual and reproductive health needs were identified, the research helped define strategies to adapt sexual and reproductive health services to the needs, identities, and circumstances of people living a trans-life in Colombia. Amongst the main barriers found were healthcare costs, lack of insurance, stigmatization, discrimination and abuse by health care providers. Perhaps among the most notable sexual and reproductive health needs presented were trans-specific services such as sensitive assistance for the transition process, endocrinology appointments, and sex reaffirmation surgeries. CONCLUSIONS: The evidence obtained from this research allowed Profamilia, a Colombian healthcare provider, to adapt the sexual and reproductive health services it provides to people living a trans-life in Colombia. Furthermore, it was possible for Profamilia to design and implement an inclusive sexual and reproductive health program that specifically addresses trans people's needs, identities, and circumstances.

Mapping analysis to predict EQ-5D-5 L utility values based on the Oxford Hip Score (OHS) and Oxford Knee Score (OKS) questionnaires in the Spanish population suffering from lower limb osteoarthritis.

BACKGROUND: The EQ-5D-5 L is a quality-of-life questionnaire based on individuals' preferences that is widely employed for cost-effectiveness analysis. Given the current demand for mapping algorithms to directly assign "utilities", this study aimed to generate different mapping models for predicting EQ-5D-5 L utility values based on scores of the Oxford Hip Score (OHS) and Oxford Knee Score (OKS) questionnaires provided by patients suffering from hip and knee osteoarthritis (OA), respectively, and to assess the predictive capability of these functions. METHODS: This was a prospective, observational study. Following the criteria of the American Rheumatism Association, 361 patients with hip OA and 397 with knee OA from three regions in Spain were included. Health-related quality of life (HRQoL) was assessed through the EQ-5D-5 L general questionnaire and the OHS and OKS specifically for lower limb OA. Based on the scores on the OHS and OKS questionnaires, EQ-5D-5 L utilities were estimated using 4 models: ordinary least squares (OLS), Tobit, generalized linear model (GLM), and beta regression (Breg). The models were validated on the same patients after 6 months: the mean absolute error (MAE) and mean squared error (MSE) with their 95% confidence intervals (CI), mean values of standard errors (SE), intraclass correlation coefficients (ICC), and Bland-Altman plots were obtained. RESULTS: The lowest MAEs were obtained using GLM and Breg models, with values of 0.1103 (0.0993-0.1214) and 0.1229 (0.1102-0.1335) for hip OA, and values of 0.1127 (0.1014-0.1239) and 0.1141 (0.1031-0.1251) for knee OA. MSE values were also lower using GLM and Breg. ICCs between predicted and observed values were around or over the 0.8 cut-off point. Bland-Altman plots showed an acceptable correlation, but precision was lower for subjects with worse HRQoL, which was also evident when comparing MAEs of the bottom and top halves of the utilities scale. Predictive equations for utilities based on OHS/OKS scores were proposed. CONCLUSIONS: The OHS and OKS scores allow for estimating EQ-5D-5 L utility indexes for patients with hip and knee OA, respectively, with adequate validity and precision. GLM and Breg produce the best predictions. The predictive power of proposed equations is more consistent for subjects in better health condition.

Investigating the (Poly)Radicaloid Nature of Real-World Organic Compounds with DFT-Based Methods.

Recent advances in the synthesis of stable organic (open-shell) polyradicaloids have opened their application as active compounds for emerging technologies. These systems typically exhibit small energy differences between states with different spin multiplicities, which are intrinsically difficult to calculate by theoretical methods. We thus apply here some DFT-based variants (FT-DFT, SF-DFT, and SF-TDDFT) on a test set of large and real-world molecules, as test systems for which such energy differences are experimentally available, also comparing systematically with RAS-SF results to infer if shortcomings of previous DFT applications are corrected. Additionally, we explore the spin-spin contribution to the ZFS tensor, of high interest for EPR spectroscopy, and derive the spatial extent of the corresponding (photoexcited) triplet state.