On the sensitivity of computed partial charges toward basis set and (exchange-)correlation treatment.

Partial charges are a central concept in general chemistry and chemical biology, yet dozens of different computational definitions exist. In prior work [Cho et al., ChemPhysChem 21, 688-696 (2020)], we showed that these can be reduced to at most three 'principal components of ionicity'. The present study addressed the dependence of computed partial charges q on 1-particle basis set and (for WFT methods) n -particle correlation treatment or (for DFT methods) exchange-correlation functional, for several representative partial charge definitions such as QTAIM, Hirshfeld, Hirshfeld-I, HLY (electrostatic), NPA, and GAPT. Our findings show that semi-empirical double hybrids can closely approach the CCSD(T) 'gold standard' for this property. In fact, owing to an error compensation in MP2, CCSD partial charges are further away from CCSD(T) than is MP2. The nonlocal correlation is important, especially when there is a substantial amount of nonlocal exchange. Employing range separation proves to be "mostly" not advantageous, while global hybrids perform optimally for 20%-30% Hartree-Fock exchange across all charge types. Basis set convergence analysis shows that an augmented triple-zeta heavy-aug-cc-pV(T+d)Z basis set or a partially augmented jun-cc-pV(T+d)Z basis set is sufficient for Hirshfeld, Hirshfeld-I, HLY, and GAPT charges. In contrast, QTAIM and NPA display slower basis set convergence. It is noteworthy that for both NPA and QTAIM, HF exhibits markedly slower basis set convergence than the correlation components of MP2 and CCSD. Triples corrections in CCSD(T), denoted as CCSD(T)-CCSD, exhibit even faster basis set convergence.

Exploring the influence of (n - 1)d subvalence correlation and of spin-orbit coupling on chalcogen bonding.

This article presents a comprehensive computational investigation into chalcogen bonding interactions, focusing specifically on elucidating the role of subvalence (n - 1)d and (n - 1)sp correlation. The incorporation of inner-shell (n - 1)d correlation leads to a decrease in interaction energies for chalcogen-bonded systems (at least those studied herein), contradicting the observations regarding halogen bonding documented by Kesharwani et al. in J. Phys. Chem. A, 2018, 122 (8), 2184-2197. The significance of (n - 1)sp subvalence correlation appears to be lower by an order of magnitude. Notably, among the various components of interaction energies computed at the PNO-LCCSD(T) or DF-CCSD levels, we identify the PNO-LMP2 or DF-MP2 component of the (n - 1)d correlation as predominant. Furthermore, we delve into the impact of second-order spin-orbit coupling (SOC2) on these interactions. The SOC2 effects appear to be less significant than the (n - 1)d correlation; however, they remain non-trivial, particularly for Te complexes. For the Se complexes, SOC2 is much less important. Generally, SOC2 stabilizes monomers more than dimers, resulting in reduced binding of the latter. Notably, at equilibrium and stretched geometries, SOC2 and (n - 1)d destabilize the complex; however, at compressed geometries, they exhibit opposing effects, with (n - 1)d becoming stabilizing.

The Importance of Tight f Basis Functions for Heavy p-Block Oxides and Halides: A Parallel With Tight d functions in the Second Row.

It is well-known that both wave function ab initio and DFT calculations on second-row compounds exhibit anomalously slow basis set convergence unless the basis sets are augmented with additional "tight" (high-exponent) d functions, as in the cc-pV(n+d)Z and aug-cc-pV(n+d)Z basis sets. This has been rationalized as being necessary for a better description of the low-lying 3d orbital, which as the oxidation state increases sinks low enough to act as a back-donation acceptor from chalcogen and halogen lone pairs. This prompts the question whether a similar phenomenon exists for the isovalent compounds of the heavy p-block. We show that for the fourth and fifth row, this is the case, but this time for tight f functions enhancing the description of the low-lying 4f and 5f Rydberg orbitals, respectively. In the third-row heavy p block, the 4f orbitals are too far up, while the 4d orbitals are adequately covered by the basis functions already present to describe the 3d subvalence orbitals.

S66x8 noncovalent interactions revisited: new benchmark and performance of composite localized coupled-cluster methods.

The S66x8 noncovalent interactions benchmark has been re-evaluated at the "sterling silver" level, using explicitly correlated MP2-F12 near the complete basis set limit, CCSD(F12*)/aug-cc-pVTZ-F12, and a (T) correction from conventional CCSD(T)/sano-V{D,T}Z+ calculations. The revised reference values differ by 0.1 kcal mol-1 RMS from the original Hobza benchmark and its revision by Brauer et al., but by only 0.04 kcal mol-1 RMS from the "bronze" level data in Kesharwani et al., Aust. J. Chem., 2018, 71, 238-248. We then used these to assess the performance of localized-orbital coupled cluster approaches with and without counterpoise corrections, such as PNO-LCCSD(T) as implemented in MOLPRO, DLPNO-CCSD(T1) as implemented in ORCA, and LNO-CCSD(T) as implemented in MRCC, for their respective "Normal", "Tight", and "very Tight" settings. We also considered composite approaches combining different basis sets and cutoffs. Furthermore, in order to isolate basis set convergence from domain truncation error, for the aug-cc-pVTZ basis set we compared PNO, DLPNO, and LNO approaches with canonical CCSD(T). We conclude that LNO-CCSD(T) with veryTight criteria performs very well for "raw" (CP-uncorrected), but struggles to reproduce counterpoise-corrected numbers even for veryveryTight criteria: this means that accurate results can be obtained using either extrapolation from basis sets large enough to quench basis set superposition error (BSSE) such as aug-cc-pV{Q,5}Z, or using a composite scheme such as Tight{T,Q} + 1.11[vvTight(T) - Tight(T)]. In contrast, PNO-LCCSD(T) works best with counterpoise, while performance with and without counterpoise is comparable for DLPNO-CCSD(T1). Among more economical methods, the highest accuracies are seen for dRPA75-D3BJ, ωB97M-V, ωB97M(2), revDSD-PBEP86-D4, and DFT(SAPT) with a TDEXX or ATDEXX kernel.

MP2-F12 Basis Set Convergence near the Complete Basis Set Limit: Are h Functions Sufficient?

We have investigated the title question for the W4-08 thermochemical benchmark using l-saturated truncations of a large reference (REF) basis set, as well as for standard F12-optimized basis sets. With the REF basis set, the root-mean-square (RMS) contribution of i functions to the MP2-F12 total atomization energies (TAEs) is about 0.01 kcal/mol, the largest individual contributions being 0.04 kcal/mol for P2 and P4. However, even for these cases, basis set extrapolation from {g,h} basis sets adequately addresses the problem. Using basis sets insufficiently saturated in the spdfgh angular momenta may lead to exaggerated i function contributions. For extrapolation from spdfg and spdfgh basis sets, basis set convergence appears to be quite close to the theoretical asymptotic ∝ L-7 behavior. We hence conclude that h functions are sufficient even for highly demanding F12 applications. With one-parameter extrapolation, spdf and spdfg basis sets are adequate, aug-cc-pV{T,Q}Z-F12 yielding a RMSD = 0.03 kcal/mol. A limited exploration of CCSD(F12*) and CCSD-F12b suggests our conclusions are applicable to higher-level F12 methods as well.

SARS-CoV-2 (COVID-19): What Do We Know About Children? A Systematic Review.

BACKGROUND: Few pediatric cases of coronavirus disease 2019 (COVID-19) have been reported and we know little about the epidemiology in children, although more is known about other coronaviruses. We aimed to understand the infection rate, clinical presentation, clinical outcomes, and transmission dynamics for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in order to inform clinical and public health measures. METHODS: We undertook a rapid systematic review and narrative synthesis of all literature relating to SARS-CoV-2 in pediatric populations. The search terms also included SARS-CoV and MERS-CoV. We searched 3 databases and the COVID-19 resource centers of 11 major journals and publishers. English abstracts of Chinese-language papers were included. Data were extracted and narrative syntheses conducted. RESULTS: Twenty-four studies relating to COVID-19 were included in the review. Children appear to be less affected by COVID-19 than adults by observed rate of cases in large epidemiological studies. Limited data on attack rate indicate that children are just as susceptible to infection. Data on clinical outcomes are scarce but include several reports of asymptomatic infection and a milder course of disease in young children, although radiological abnormalities are noted. Severe cases are not reported in detail and there are few data relating to transmission. CONCLUSIONS: Children appear to have a low observed case rate of COVID-19 but may have rates similar to adults of infection with SARS-CoV-2. This discrepancy may be because children are asymptomatic or too mildly infected to draw medical attention and be tested and counted in observed cases of COVID-19.

Semi-empirical or non-empirical double-hybrid density functionals: which are more robust?

The development of non-empirical double-hybrid density functionals (DHDFs) is a very active research area with the number of approaches in this field having increased rapidly. At the same time, there is a lack of published work that provides a fair assessment and comparison between non-empirical and semi-empirical DHDFs on an equal footing. Herein, we close this gap and present a thorough analysis of both classes of DHDFs on the large GMTKN55 benchmark database for general main-group thermochemistry, kinetics, and noncovalent interactions [Goerigk et al., Phys. Chem. Chem. Phys., 2017, 19, 32184-32215]. In total, 115 variations of dispersion-corrected and -uncorrected DHDFs are tested, which will be condensed to an in-depth assessment of 31 methods: 19 non-empirical and 12 semi-empirical DHDFs. As such, our study represents the largest DHDF study ever conducted and can serve as an important benchmark informing method developers and users alike. Our results show that semi-empirical DHDFs are the most robust density functional approximations and more reliable and accurate than non-empirical ones. In fact, some non-empirical approaches are even outperformed by hybrid approaches or even dispersion-corrected and -uncorrected MP2 and SCS-MP2. SOS0-PBE0-2-D3(BJ) is the only exception and the only non-empirical DHDF that we can safely recommend for general applicability. However, it is still outperformed by six semi-empirical DHDFs, of which we would like to particularly recommend the following five: ωB97X-2-D3(BJ), DSD-BLYP-D3(BJ), DSD-PBEP86-D3(BJ), B2NC-PLYP-D3(BJ), and B2GPPLYP-D3(BJ). Our findings seriously question current trends in the field and they highlight that novel strategies have to be found in order to outperform the currently best density functional theory methods on the market. We hope that our study can function as an important cornerstone inspiring such a change of direction in the field.

Evidence for effective interventions to reduce mental-health-related stigma and discrimination.

Stigma and discrimination in relation to mental illnesses have been described as having worse consequences than the conditions themselves. Most medical literature in this area of research has been descriptive and has focused on attitudes towards people with mental illness rather than on interventions to reduce stigma. In this narrative Review, we summarise what is known globally from published systematic reviews and primary data on effective interventions intended to reduce mental-illness-related stigma or discrimination. The main findings emerging from this narrative overview are that: (1) at the population level there is a fairly consistent pattern of short-term benefits for positive attitude change, and some lesser evidence for knowledge improvement; (2) for people with mental illness, some group-level anti-stigma inventions show promise and merit further assessment; (3) for specific target groups, such as students, social-contact-based interventions usually achieve short-term (but less clearly long-term) attitudinal improvements, and less often produce knowledge gains; (4) this is a heterogeneous field of study with few strong study designs with large sample sizes; (5) research from low-income and middle-income countries is conspicuous by its relative absence; (6) caution needs to be exercised in not overgeneralising lessons from one target group to another; (7) there is a clear need for studies with longer-term follow-up to assess whether initial gains are sustained or attenuated, and whether booster doses of the intervention are needed to maintain progress; (8) few studies in any part of the world have focused on either the service user's perspective of stigma and discrimination or on the behaviour domain of behavioural change, either by people with or without mental illness in the complex processes of stigmatisation. We found that social contact is the most effective type of intervention to improve stigma-related knowledge and attitudes in the short term. However, the evidence for longer-term benefit of such social contact to reduce stigma is weak. In view of the magnitude of challenges that result from mental health stigma and discrimination, a concerted effort is needed to fund methodologically strong research that will provide robust evidence to support decisions on investment in interventions to reduce stigma.

Satisfaction with psychiatric in-patient care as rated by patients at discharge from hospitals in 11 countries.

PURPOSE: There is disregard in the scientific literature for the evaluation of psychiatric in-patient care as rated directly by patients. In this context, we aimed to explore satisfaction of people treated in mental health in-patient facilities. The project was a part of the Young Psychiatrist Program by the Association for the Improvement of Mental Health Programmes. METHODS: This is an international multicentre cross-sectional study conducted in 25 hospitals across 11 countries. The research team at each study site approached a consecutive target sample of 30 discharged patients to measure their satisfaction using the five-item study-specific questionnaire. Individual and institution level correlates of 'low satisfaction' were examined by comparisons of binary and multivariate associations in multilevel regression models. RESULTS: A final study sample consisted of 673 participants. Total satisfaction scores were highly skewed towards the upper end of the scale, with a median total score of 44 (interquartile range 38-48) out of 50. After taking clustering into account, the only independent correlates of low satisfaction were schizophrenia diagnosis and low psychiatrist to patient ratio. CONCLUSION: Further studies on patients' satisfaction should additionally pay attention to treatment expectations formed by the previous experience of treatment, service-related knowledge, stigma and patients' disempowerment, and power imbalance.

The importance of psychiatry in public mental health.

There is a lack of consensus over fundamental issues in public mental health in England. A move away from poorly evidenced 'well-being' policy approaches is needed. The authors have developed a more inclusive model using the World Health Organization's approach to public mental health. Public mental health policy makers must acknowledge the importance of psychiatry within the field.

Absence of CD4 or CD8 lymphocytes changes infiltration of inflammatory cells and profiles of cytokine expression in skin wounds, but does not impair healing.

The involvement of lymphocytes in skin wound healing has not been studied extensively. This study shows that CD4 and CD8 cells are present in significant numbers in skin wounds with peak levels at days 5-10 and 7-10, respectively. Both subsets expressed inflammatory and/or regulatory cytokines. To examine the function of CD4 and CD8 lymphocytes in tissue repair, wound healing was examined in mice deficient for either CD4 or CD8 cells. Wounds in CD4 deficient mice exhibited an initial delayed infiltration of CD8 cells followed by a relative increase in CD8 cells at day 10 and thereafter. Wounds in CD4 deficient mice also displayed up-regulated expression of IL1ß, IL-6, IL-17, IFN-γ, CXCL-1 and down-regulated expression of IL-4 as compared to wild-type mice. In contrast, wounds in CD8 deficient mice showed significantly decreased infiltration of CD4+ cells, neutrophils, and macrophages along with down-regulated expression of IL1ß, IL-6, TNF-α, CXCL-1, CCL-2 and up-regulated expression of IL-4 as compared to wild-type mice. Despite these significant changes in cytokine expression and inflammatory cell infiltrate, the rate of wound closure, wound breaking strength, collagen content and angiogenesis in either CD4 or CD8 deficiency showed no significant difference from that of wild-type mice. The results suggest that, despite being present and involved in wound inflammation, neither CD4+ nor CD8+ cells play critical roles in the healing process of skin wounds. Further studies are needed to investigate whether these cells might play critical roles in wounds that experience stress such as ischemia or infection.

Purinergic receptor P2X7: a novel target for anti-inflammatory therapy.

Purinergic receptors, also known as purinoceptors, are ligand gated membrane ion channels involved in many cellular functions. Among all identified purinergic receptors, P2X7 subform is unique since it induces the caspase activity, cytokine secretion, and apoptosis. The distribution of P2X7 receptors, and the need of high concentration of ATP required to activate this receptor exhibited its ability to function as 'danger' sensor associated with tissue inflammation and damage. Further, the modulation of other signalling pathways associated with P2X7 has also been proposed to play an important role in the control of macrophage functions and inflammatory responses, especially towards lipopolysaccharides. Experimentally, researchers have also observed the decreased severity of inflammatory responses in P2X7 receptor expressing gene (P2RX7) knockout (KO) phenotypes. Therefore, newly developed potent antagonists of P2X7 receptor would serve as novel therapeutic agents to combat various inflammatory conditions. In this review article, we tried to explore various aspects of P2X7 receptors including therapeutic potential, and recent discoveries and developments of P2X7 receptor antagonists.

Impact of the "Like Minds, Like Mine" anti-stigma and discrimination campaign in New Zealand on anticipated and experienced discrimination.

OBJECTIVE: The "Like Minds, Like Mine" anti-stigma and discrimination programme has been running in New Zealand since 1997. We aimed to investigate the nature and degree of anticipated and experienced discrimination reported by people with mental illness, and their views on whether the campaign was contributing to reductions in stigma and discrimination. METHODS: Questionnaires were sent to randomly selected people who were representative of those who had recently used mental health services in New Zealand. The measure used was the modified Discrimination and Stigma Scale (DISC-12), adding questions on the effect of "Like Minds, Like Mine", and also assessing overall changes in discrimination in the previous 5 years. RESULTS: A total of 1135 participants completed the questionnaire. This included 225 Ma-ori, 196 Pacific, and 152 Asian persons. Over half of all participants reported improvement in discrimination over the previous 5 years, and 48% thought that the "Like Minds Like Mine" programme had assisted in reducing discrimination "moderately" or "a lot". Nevertheless, a clear majority (89%) reported experiencing at least "a little" unfair treatment in the previous 12 months due to their mental health problems. The primary source of both positive and negative discrimination was the family. Many (57%) participants had concealed or hidden their mental health problems from others, and 33% had stopped themselves from applying for work because they anticipated discrimination. CONCLUSIONS: Family, friendship, and social life were the most common areas of discrimination reported by the participants; however, many believed the overall level of discrimination had reduced over the previous 5 years. Overall, these results characterize the nature of stigma and discrimination anticipated and experienced by people with mental health problems and indicate modest but clear and positive recent progress in their reduction.

Insights from degradation studies of alpha mangostin from Garcinia mangostana: key findings.

The present study emphasises the necessity of substantiating the stability of plant-derived bioactive compounds for their therapeutic effectiveness in pharmaceutical production. The limelight is on alpha-mangostin (AM), a xanthone from Garcinia mangostana L., renowned for its diverse biological properties. Acid exposure during a forced degradation study on AM resulted in degraded alpha-mangostin (DAM) formation, with structural modifications of the two prenyl groups at C2 and C8 positions as determined by NMR and HRMS analysis. Other conditions (temperature, humidity, photolytic, oxidative, and alkaline) showed a minimal impact on AM. DAM, although showed antibacterial activity at concentration higher than AM (MIC values for AM: 0.39-1.56 µg/mL; DAM: >25 µg/mL), it exhibited potential for binding with Glucosyltransferase-SI from Streptococcus mutans and human Acetylcholinesterase in molecular docking simulations, comparable to AM. This suggests, the importance of prenyl group at C2 and C8 positions for AM's potent antibacterial activity and the decreased activity of DAM is due to lack of the prenyl groups.

Evaluation of a dedicated pharmacist staffing model in the medical intensive care unit.

PURPOSE: Published studies have shown that pharmacists on medical rounds reduce the incidence of preventable adverse drug events (ADEs). However, the impact of a dedicated pharmacist who provides consistent patient care in a critical care unit remains to be evaluated. OBJECTIVE: To determine the impact of a pharmacist who is permanently assigned to the medical intensive care unit (MICU) on the incidence of preventable ADEs, drug charges, and length of stay (LOS) in the MICU. DESIGN: A randomized, experimental versus historical control group design was used. Preventable ADEs were identified and validated by 2 pharmacists and a critical care physician. Information about MICU drug charges and LOS were obtained from the hospital administrative database. RESULTS: The intervention group had fewer occurrences of ADEs (10 ADEs/1,000 patient days) when compared to the control group (28 ADEs/1,000 patient days) at a significance level of .03. No significant differences were found between the 2 groups in MICU drug charges and LOS. The vast majority of the 596 documented recommended interventions (99%) were accepted by the medical team. Nutrition monitoring, medication indicated but not prescribed, and dosage modification were the top 3 problems identified by the pharmacist. CONCLUSION: The addition of a dedicated critical care pharmacist to the MICU medical team improves the safe use of medication. The services of a dedicated critical care pharmacist should be expanded to include weekend hours to ensure the benefits of improved medication safety.

Explicitly Correlated Double-Hybrid DFT: A Comprehensive Analysis of the Basis Set Convergence on the GMTKN55 Database.

Double-hybrid density functional theory (DHDFT) offers a pathway to accuracy approaching composite wavefunction approaches such as G4 theory. However, the Görling-Levy second-order perturbation theory (GLPT2) term causes them to partially inherit the slow ∝L-3 (with L the maximum angular momentum) basis set convergence of correlated wavefunction methods. This could potentially be remedied by introducing F12 explicit correlation: we investigate the basis set convergence of both DHDFT and DHDFT-F12 (where GLPT2 is replaced by GLPT2-F12) for the large and chemically diverse general main-group thermochemistry, kinetics, and noncovalent interactions (GMTKN55) benchmark suite. The B2GP-PLYP-D3(BJ) and revDSD-PBEP86-D4 DHDFs are investigated as test cases, together with orbital basis sets as large as aug-cc-pV5Z and F12 basis sets as large as cc-pVQZ-F12. We show that F12 greatly accelerates basis set convergence of DHDFs, to the point that even the modest cc-pVDZ-F12 basis set is closer to the basis set limit than cc-pV(Q+d)Z or def2-QZVPPD in orbital-based approaches, and in fact comparable in quality to cc-pV(5+d)Z. Somewhat surprisingly, aug-cc-pVDZ-F12 is not required even for the anionic subsets. In conclusion, DHDF-F12/VDZ-F12 eliminates concerns about basis set convergence in both the development and applications of double-hybrid functionals. Mass storage and I/O bottlenecks for larger systems can be circumvented by localized pair natural orbital approximations, which also exhibit much gentler system size scaling.

Reduced-Scaling Double Hybrid Density Functional Theory with Rapid Basis Set Convergence through Localized Pair Natural Orbital F12.

Following earlier work [Mehta, N.; Martin, J. M. L. J. Chem. Theory Comput.2022, 10.1021/acs.jctc.2c00426] that showed how the slow basis set convergence of the double hybrid density functional theory can be obviated by the use of F12 explicit correlation in the GLPT2 step (second order Görling-Levy perturbation theory), we demonstrate here for the very large and chemically diverse GMTKN55 benchmark suite that the CPU time scaling of this step can be reduced (asymptotically linearized) using the localized pair natural orbital (PNO-L) approximation at negligible cost in accuracy.