Spin splitting of dopant edge state in magnetic zigzag graphene nanoribbons.

Spin-ordered electronic states in hydrogen-terminated zigzag nanographene give rise to magnetic quantum phenomena1,2 that have sparked renewed interest in carbon-based spintronics3,4. Zigzag graphene nanoribbons (ZGNRs)-quasi one-dimensional semiconducting strips of graphene bounded by parallel zigzag edges-host intrinsic electronic edge states that are ferromagnetically ordered along the edges of the ribbon and antiferromagnetically coupled across its width1,2,5. Despite recent advances in the bottom-up synthesis of GNRs featuring symmetry protected topological phases6-8 and even metallic zero mode bands9, the unique magnetic edge structure of ZGNRs has long been obscured from direct observation by a strong hybridization of the zigzag edge states with the surface states of the underlying support10-15. Here, we present a general technique to thermodynamically stabilize and electronically decouple the highly reactive spin-polarized edge states by introducing a superlattice of substitutional N-atom dopants along the edges of a ZGNR. First-principles GW calculations and scanning tunnelling spectroscopy reveal a giant spin splitting of low-lying nitrogen lone-pair flat bands by an exchange field (~850 tesla) induced by the ferromagnetically ordered edge states of ZGNRs. Our findings directly corroborate the nature of the predicted emergent magnetic order in ZGNRs and provide a robust platform for their exploration and functional integration into nanoscale sensing and logic devices15-21.

Recommendations for empowering early career researchers to improve research culture and practice.

Early career researchers (ECRs) are important stakeholders leading efforts to catalyze systemic change in research culture and practice. Here, we summarize the outputs from a virtual unconventional conference (unconference), which brought together 54 invited experts from 20 countries with extensive experience in ECR initiatives designed to improve the culture and practice of science. Together, we drafted 2 sets of recommendations for (1) ECRs directly involved in initiatives or activities to change research culture and practice; and (2) stakeholders who wish to support ECRs in these efforts. Importantly, these points apply to ECRs working to promote change on a systemic level, not only those improving aspects of their own work. In both sets of recommendations, we underline the importance of incentivizing and providing time and resources for systems-level science improvement activities, including ECRs in organizational decision-making processes, and working to dismantle structural barriers to participation for marginalized groups. We further highlight obstacles that ECRs face when working to promote reform, as well as proposed solutions and examples of current best practices. The abstract and recommendations for stakeholders are available in Dutch, German, Greek (abstract only), Italian, Japanese, Polish, Portuguese, Spanish, and Serbian.

Engineering Small HOMO-LUMO Gaps in Polycyclic Aromatic Hydrocarbons with Topologically Protected States.

Topological phases in laterally confined low-dimensional nanographenes have emerged as versatile design tools that can imbue otherwise unremarkable materials with exotic band structures ranging from topological semiconductors and quantum dots to intrinsically metallic bands. The periodic boundary conditions that define the topology of a given lattice have thus far prevented the translation of this technology to the quasi-zero-dimensional (0D) domain of small molecular structures. Here, we describe the synthesis of a polycyclic aromatic hydrocarbon (PAH) featuring two localized zero modes (ZMs) formed by the topological junction interface between a trivial and nontrivial phase within a single molecule. First-principles density functional theory calculations predict a strong hybridization between adjacent ZMs that gives rise to an exceptionally small HOMO-LUMO gap. Scanning tunneling microscopy and spectroscopy corroborate the molecular structure of 9/7/9-double quantum dots and reveal an experimental quasiparticle gap of 0.16 eV, corresponding to a carbon-based small molecule long-wavelength infrared (LWIR) absorber.

Regioselective On-Surface Synthesis of [3]Triangulene Graphene Nanoribbons.

The integration of low-energy states into bottom-up engineered graphene nanoribbons (GNRs) is a robust strategy for realizing materials with tailored electronic band structure for nanoelectronics. Low-energy zero-modes (ZMs) can be introduced into nanographenes (NGs) by creating an imbalance between the two sublattices of graphene. This phenomenon is exemplified by the family of [n]triangulenes (n ∈ N). Here, we demonstrate the synthesis of [3]triangulene-GNRs, a regioregular one-dimensional (1D) chain of [3]triangulenes linked by five-membered rings. Hybridization between ZMs on adjacent [3]triangulenes leads to the emergence of a narrow band gap, Eg,exp ∼ 0.7 eV, and topological end states that are experimentally verified using scanning tunneling spectroscopy. Tight-binding and first-principles density functional theory calculations within the local density approximation corroborate our experimental observations. Our synthetic design takes advantage of a selective on-surface head-to-tail coupling of monomer building blocks enabling the regioselective synthesis of [3]triangulene-GNRs. Detailed ab initio theory provides insights into the mechanism of on-surface radical polymerization, revealing the pivotal role of Au-C bond formation/breakage in driving selectivity.

Topological band engineering of graphene nanoribbons.

Topological insulators are an emerging class of materials that host highly robust in-gap surface or interface states while maintaining an insulating bulk1,2. Most advances in this field have focused on topological insulators and related topological crystalline insulators3 in two dimensions4-6 and three dimensions7-10, but more recent theoretical work has predicted the existence of one-dimensional symmetry-protected topological phases in graphene nanoribbons (GNRs)11. The topological phase of these laterally confined, semiconducting strips of graphene is determined by their width, edge shape and terminating crystallographic unit cell and is characterized by a [Formula: see text] invariant12 (that is, an index of either 0 or 1, indicating two topological classes-similar to quasi-one-dimensional solitonic systems13-16). Interfaces between topologically distinct GNRs characterized by different values of [Formula: see text] are predicted to support half-filled, in-gap localized electronic states that could, in principle, be used as a tool for material engineering11. Here we present the rational design and experimental realization of a topologically engineered GNR superlattice that hosts a one-dimensional array of such states, thus generating otherwise inaccessible electronic structures. This strategy also enables new end states to be engineered directly into the termini of the one-dimensional GNR superlattice. Atomically precise topological GNR superlattices were synthesized from molecular precursors on a gold surface, Au(111), under ultrahigh-vacuum conditions and characterized by low-temperature scanning tunnelling microscopy and spectroscopy. Our experimental results and first-principles calculations reveal that the frontier band structure (the bands bracketing filled and empty states) of these GNR superlattices is defined purely by the coupling between adjacent topological interface states. This manifestation of non-trivial one-dimensional topological phases presents a route to band engineering in one-dimensional materials based on precise control of their electronic topology, and is a promising platform for studies of one-dimensional quantum spin physics.

How Are Age, Gender, and Country Differences Associated With PROMIS Physical Function, Upper Extremity, and Pain Interference Scores?

BACKGROUND: The interpretation of patient-reported outcomes requires appropriate comparison data. Currently, no patient-specific reference data exist for the Patient-Reported Outcome Measurement Information System (PROMIS) Physical Function (PF), Upper Extremity (UE), and Pain Interference (PI) scales for individuals 50 years and older. QUESTIONS/PURPOSES: (1) Can all PROMIS PF, UE, and PI items be used for valid cross-country comparisons in these domains among the United States, the United Kingdom, and Germany? (2) How are age, gender, and country related to PROMIS PF, PROMIS UE, and PROMIS PI scores? (3) What is the relationship of age, gender, and country across individuals with PROMIS PF, PROMIS UE, and PROMIS PI scores ranging from very low to very high? METHODS: We conducted telephone interviews to collect custom PROMIS PF (22 items), UE (eight items), and PI (eight items) short forms, as well as sociodemographic data (age, gender, work status, and education level), with participants randomly selected from the general population older than 50 years in the United States (n = 900), United Kingdom (n = 905), and Germany (n = 921). We focused on these individuals because of their higher prevalence of surgeries and lower physical functioning. Although response rates varied across countries (14% for the United Kingdom, 22% for Germany, and 12% for the United States), we used existing normative data to ensure demographic alignment with the overall populations of these countries. This helped mitigate potential nonresponder bias and enhance the representativeness and validity of our findings. We investigated differential item functioning to determine whether all items can be used for valid crosscultural comparisons. To answer our second research question, we compared age groups, gender, and countries using median regressions. Using imputation of plausible values and quantile regression, we modeled age-, gender-, and country-specific distributions of PROMIS scores to obtain patient-specific reference values and answer our third research question. RESULTS: All items from the PROMIS PF, UE, and PI measures were valid for across-country comparisons. We found clinically meaningful associations of age, gender, and country with PROMIS PF, UE, and PI scores. With age, PROMIS PF scores decreased (age ß Median = -0.35 [95% CI -0.40 to -0.31]), and PROMIS UE scores followed a similar trend (age ß Median = -0.38 [95% CI -0.45 to -0.32]). This means that a 10-year increase in age corresponded to a decline in approximately 3.5 points for the PROMIS PF score-a value that is approximately the minimum clinically important difference (MCID). Concurrently, we observed a modest increase in PROMIS PI scores with age, reaching half the MCID after 20 years. Women in all countries scored higher than men on the PROMIS PI and 1 MCID lower on the PROMIS PF and UE. Additionally, there were higher T-scores for the United States than for the United Kingdom across all domains. The difference in scores ranged from 1.21 points for the PROMIS PF to a more pronounced 3.83 points for the PROMIS UE. Participants from the United States exhibited up to half an MCID lower T-scores than their German counterparts for the PROMIS PF and PROMIS PI. In individuals with high levels of physical function, with each 10-year increase in age, there could be a decrease of up to 4 points in PROMIS PF scores. Across all levels of upper extremity function, women reported lower PROMIS UE scores than men by an average of 5 points. CONCLUSION: Our study provides age-, gender-, and country-specific reference values for PROMIS PF, UE, and PI scores, which can be used by clinicians, researchers, and healthcare policymakers to better interpret patient-reported outcomes and provide more personalized care. These findings are particularly relevant for those collecting patient-reported outcomes in their clinical routine and researchers conducting multinational studies. We provide an internet application ( www.common-metrics.org/PROMIS_PF_and_PI_Reference_scores.php ) for user-friendly accessibility in order to perform age, gender, and country conversions of PROMIS scores. Population reference values can also serve as comparators to data collected with other PROMIS short forms or computerized adaptive tests. LEVEL OF EVIDENCE: Level II, diagnostic study.

Fermi-Level Engineering of Nitrogen Core-Doped Armchair Graphene Nanoribbons.

Substitutional heteroatom doping of bottom-up engineered 1D graphene nanoribbons (GNRs) is a versatile tool for realizing low-dimensional functional materials for nanoelectronics and sensing. Previous efforts have largely relied on replacing C-H groups lining the edges of GNRs with trigonal planar N atoms. This type of atomically precise doping, however, only results in a modest realignment of the valence band (VB) and conduction band (CB) energies. Here, we report the design, bottom-up synthesis, and spectroscopic characterization of nitrogen core-doped 5-atom-wide armchair GNRs (N2-5-AGNRs) that yield much greater energy-level shifting of the GNR electronic structure. Here, the substitution of C atoms with N atoms along the backbone of the GNR introduces a single surplus π-electron per dopant that populates the electronic states associated with previously unoccupied bands. First-principles DFT-LDA calculations confirm that a sizable shift in Fermi energy (∼1.0 eV) is accompanied by a broad reconfiguration of the band structure, including the opening of a new band gap and the transition from a direct to an indirect semiconducting band gap. Scanning tunneling spectroscopy (STS) lift-off charge transport experiments corroborate the theoretical results and reveal the relationship among substitutional heteroatom doping, Fermi-level shifting, electronic band structure, and topological engineering for this new N-doped GNR.

Engineering Robust Metallic Zero-Mode States in Olympicene Graphene Nanoribbons.

Metallic graphene nanoribbons (GNRs) represent a critical component in the toolbox of low-dimensional functional materials technology serving as 1D interconnects capable of both electronic and quantum information transport. The structural constraints imposed by on-surface bottom-up GNR synthesis protocols along with the limited control over orientation and sequence of asymmetric monomer building blocks during the radical step-growth polymerization have plagued the design and assembly of metallic GNRs. Here, we report the regioregular synthesis of GNRs hosting robust metallic states by embedding a symmetric zero-mode (ZM) superlattice along the backbone of a GNR. Tight-binding electronic structure models predict a strong nearest-neighbor electron hopping interaction between adjacent ZM states, resulting in a dispersive metallic band. First-principles density functional theory-local density approximation calculations confirm this prediction, and the robust, metallic ZM band of olympicene GNRs is experimentally corroborated by scanning tunneling spectroscopy.

External validation of a shortened screening tool using individual participant data meta-analysis: A case study of the Patient Health Questionnaire-Dep-4.

Shortened versions of self-reported questionnaires may be used to reduce respondent burden. When shortened screening tools are used, it is desirable to maintain equivalent diagnostic accuracy to full-length forms. This manuscript presents a case study that illustrates how external data and individual participant data meta-analysis can be used to assess the equivalence in diagnostic accuracy between a shortened and full-length form. This case study compares the Patient Health Questionnaire-9 (PHQ-9) and a 4-item shortened version (PHQ-Dep-4) that was previously developed using optimal test assembly methods. Using a large database of 75 primary studies (34,698 participants, 3,392 major depression cases), we evaluated whether the PHQ-Dep-4 cutoff of ≥ 4 maintained equivalent diagnostic accuracy to a PHQ-9 cutoff of ≥ 10. Using this external validation dataset, a PHQ-Dep-4 cutoff of ≥ 4 maximized the sum of sensitivity and specificity, with a sensitivity of 0.88 (95% CI 0.81, 0.93), 0.68 (95% CI 0.56, 0.78), and 0.80 (95% CI 0.73, 0.85) for the semi-structured, fully structured, and MINI reference standard categories, respectively, and a specificity of 0.79 (95% CI 0.74, 0.83), 0.85 (95% CI 0.78, 0.90), and 0.83 (95% CI 0.80, 0.86) for the semi-structured, fully structured, and MINI reference standard categories, respectively. While equivalence with a PHQ-9 cutoff of ≥ 10 was not established, we found the sensitivity of the PHQ-Dep-4 to be non-inferior to that of the PHQ-9, and the specificity of the PHQ-Dep-4 to be marginally smaller than the PHQ-9.

Scale agreement, ceiling and floor effects, construct validity, and relative efficiency of the PROPr and EQ-5D-3L in low back pain patients.

BACKGROUND: The PROMIS Preference score (PROPr) is a new health state utility (HSU) score that aims to comprehensively incorporate the biopsychosocial model of health and apply favorable psychometric properties from the descriptive PROMIS system to HSU measurements. However, minimal evidence concerning comparisons to the EQ-5D-3L and the PROPr's capability to differentiate clinical severity are available. Therefore, the aim of this study was to compare the PROPr to the EQ-5D-3L in terms of scale agreement, ceiling/floor effects, distribution, construct validity, discriminatory power, and relative efficiency (RE) in terms of the Oswestry Disability Index (ODI) for patients with low back pain (LBP). METHODS: We used intra-class correlation coefficients (ICC) and Bland-Altman plots to compare the PROPr and EQ-5D-3L with regared to scale agreement in a cross-sectional routine sample of LBP patients. For distribution, we used the Pearson's coefficient for skewness and for ceiling/floor effects, a 15%-top/bottom threshold. For convergent validity, we used Pearson's correlation coefficients. For known-groups validity, we applied a linear regression with interaction terms (predictors sex, age, and ODI level) and an analysis of variance (ANOVA). For discriminatory power, we calculated the effect size (ES) using Cohen's d and the ratio of the area under the receiver-operating characteristics curves (AUROC-ratio = AUROCPROPr/AUROCEQ-5D-3L). RE was measured using the ratio of F-values (RE = FPROPr/FEQ-5D-3L). RESULTS: Of 218 LBP patients, 50.0% were female and the mean age was 61.8 years. The mean PROPr (0.20, 95%CI: 0.18; 0.22) and EQ-5D-3L scores (0.55, 95%CI: 0.51; 0.58) showed low agreement (d = 0.35, p < 0.001; ICC 0.27, 95%CI: -0.09; 0.59). The PROPr's distribution was positively skewed, whereas the EQ-5D-3L's was negative. Neither tool showed ceiling/floor effects, but all EQ-5D-3L dimensions did. Pearson correlation was r = 0.66 (95%CI: 0.58; 0.73). Differences were invariant to sex and age but not to ODI severity: ESEQ-5D-3L > ESPROPr and RE < 1 in higher ODI severity; ESEQ-5D-3L < ESPROPr and RE > 1 in lower ODI severity. AUROC-ratios did not show significant differences in terms of ODI severity. CONCLUSIONS: All PROPr and EQ-5D-3L biopsychosocial dimensions of health showed impairment in LPB patients. The capability of EQ-5D-3L and PROPr to differentiate ODI levels depends on ODI severity. Joint application of both tools may provide additional information.

Measuring individual true change with PROMIS using IRT-based plausible values.

AIMS: A primary advantage of IRT-based patient-reported outcome measures such as PROMIS short forms and computer-adaptive tests is that each estimate of the latent trait comes with a standard error. Such measurement error needs to be acknowledged, in particular when monitoring individual patients over time. In this study, we use plausible values to account for measurement error and analyze the probability of true within-individual change. METHODS: We use a longitudinal, observational study of stable and exacerbated COPD patients (N = 185), providing PROMIS Physical Function and Fatigue T-scores over 3 months. At each measurement, we imputed 1000 plausible values from the scores' posterior distribution. These were then used to calculate probability of true change using a pre-specified threshold such as minimally important difference supported by the literature, or [Formula: see text] > 0. We demonstrate assessment of change in individuals and in groups, across different measures (Short Forms and CATs), and at various levels of confidence. RESULTS: Using plausible value imputation and with 95% certainty, 47.5% of participants in the exacerbated group reported less fatigue, compared with 26.5% of participants in the stable group. Comparison of Short Forms and CATs suggests that CATs have better ability to detect change compared to short forms. We also illustrate this method using an individual's probability of change at different time points. CONCLUSION: Plausible values offer a flexible way to include measurement error in analysis of individuals and on sample level. Assessment of probability of true change can complement existing distribution-based approaches and facilitates interpretation of improvement or decline.

Are OMERACT recommendations followed in clinical trials on fibromyalgia? A systematic review of patient-reported outcomes and their measures.

PURPOSE: Patient-Reported Outcomes (PROs) and its measures (PROMs) are key to outcome assessment in Fibromyalgia (FM) trials. The aim of this review was to investigate which domains and instruments were assessed in recent FM trials and to compare them to recommendations by the Outcome Measures in Rheumatology (OMERACT) initiative. In addition, we investigated the overlap with a generic health assessment approach, i.e. eight domains suggested by the Patient-Reported Outcome Measurement Information System® (PROMIS®). METHODS: In compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic literature search in scientific databases including PubMed, PsycInfo, and Embase was conducted to identify studies that assessed at least two dimensions of health-related quality of life (HRQoL) from 2015 to June 2022. Non-randomized and randomized controlled trials were included in the analysis. We extracted PROs and PROMs used in each study. RESULTS: From 1845 identified records, 107 records out of 105 studies met the inclusion criteria. Studies investigated 50 PROs using 126 different PROMs. Most frequently assessed domains were pain, depression, fatigue, and anxiety (> 95% of the studies). The disease-specific FIQ was the most frequently applied PROM (82%). Overall, only 9% of the studies covered all domains deemed mandatory by OMERACT. Very few studies covered all eight generic health domains suggested by PROMIS. CONCLUSION: The majority of trials covered most OMERACT domains or generic PROMIS health domains. There was, however, great variability in the instruments used to assess the domains, which points at a limited degree of standardization in the field.

PROMIS-29 and EORTC QLQ-C30: an empirical investigation towards a common conception of health.

PURPOSE: The assessment of health-related quality of life (HRQOL) measured via patient-reported outcomes (PROs) is a key component in clinical trials and increasingly used in clinical routine worldwide. Two PRO measures (PROMs) that share the same definition of health and report outcomes on a comparable T-metric anchored to general population samples are the PROMIS-29 and the EORTC QLQ-C30. In this study, we investigate the empirical agreement of these underlying concepts. METHODS: We collected PROMIS-29 and EORTC QLQ-C30 data from 1,478 female patients at a breast cancer outpatient centre. We calculated descriptive statistics and correlations between the subscales of both instruments. We performed exploratory (EFA) and confirmatory factor analysis (CFA) in randomly split subsamples in order to assess the underlying psychometric structure of both instruments. RESULTS: The cohort (mean age = 47.4, ± 14.49) reported comparable mean HRQOL scores between the corresponding subscales of both instruments similar to general population reference values. Correlation between the corresponding subscales of both instruments ranged between 0.59 (Social Role) and 0.78 (Physical Functioning). Both an exploratory and a theoretically driven confirmatory factor analysis provided further support for conceptual agreement of the scales. CONCLUSION: EORTC QLQ-C30 and PROMIS-29 showed similar scores and satisfactory agreement in conceptional and statistical analysis. This suggests that the underlying conceptualization of health is reasonably close. Hence, the development of score transformation algorithms or calibration of both instruments on common scales could prospectively increase the comparability of clinical and research PRO data collected with either instrument.

Measuring PROMIS pain interference in German patients with chronic conditions: calibration, validation, and cross-cultural use of item parameters.

PURPOSE: To calibrate the item parameters of the German PROMIS® Pain interference (PROMIS PI) items using an item-response theory (IRT) model and investigate psychometric properties of the item bank. METHODS: Forty items of the PROMIS PI item bank were collected in a convenience sample of 660 patients, which were recruited during inpatient rheumatological treatment or outpatient psychosomatic medicine visits in Germany. Unidimensionality, monotonicity, and local independence were tested as required for IRT analyses. Unidimensionality was examined using confirmatory factor analyses (CFA) and exploratory factor analysis (EFA). Unidimensional and bifactor graded-response IRT models were fitted to the data. Bifactor indices were used to investigate whether multidimensionality would lead to biased scores. To evaluate convergent and discriminant validity, the item bank was correlated with legacy pain instruments. Potential differential item functioning (DIF) was examined for gender, age, and subsample. To investigate whether U.S. item parameters may be used to derive T-scores in German patients, T-scores based on previously published U.S. and newly estimated German item parameters were compared with each other after adjusting for sample specific differences. RESULTS: All items were sufficiently unidimensional, locally independent, and monotonic. Whereas the fit of the unidimensional IRT model was not acceptable, a bifactor IRT model demonstrated acceptable fit. Explained common variance and Omega hierarchical suggested that using the unidimensional model would not lead to biased scores. One item demonstrated DIF between subsamples. High correlations with legacy pain instruments supported construct validity of the item bank. T-scores based on U.S. and German item parameters were similar suggesting that U.S. parameters could be used in German samples. CONCLUSION: The German PROMIS PI item bank proved to be a clinically valid and precise instrument for assessing pain interference in patients with chronic conditions.

Magnetic Interactions in Substitutional Core-Doped Graphene Nanoribbons.

The design of a spin imbalance within the crystallographic unit cell of bottom-up engineered 1D graphene nanoribbons (GNRs) gives rise to nonzero magnetic moments within each cell. Here, we demonstrate the bottom-up assembly and spectroscopic characterization of a one-dimensional Kondo spin chain formed by a chevron-type GNR (cGNR) physisorbed on Au(111). Substitutional nitrogen core doping introduces a pair of low-lying occupied states per monomer within the semiconducting gap of cGNRs. Charging resulting from the interaction with the gold substrate quenches one electronic state for each monomer, leaving behind a 1D chain of radical cations commensurate with the unit cell of the ribbon. Scanning tunneling microscopy (STM) and spectroscopy (STS) reveal the signature of a Kondo resonance emerging from the interaction of S = 1/2 spin centers in each monomer core with itinerant electrons in the Au substrate. STM tip lift-off experiments locally reduce the effective screening of the unpaired radical cation being lifted, revealing a robust exchange coupling between neighboring spin centers. First-principles DFT-LSDA calculations support the presence of magnetic moments in the core of this GNR when it is placed on Au.

Olefin Metathesis in Confinement: Towards Covalent Organic Framework Scaffolds for Increased Macrocyclization Selectivity.

Covalent organic frameworks (COFs) offer vast structural and chemical diversity enabling a wide and growing range of applications. While COFs are well-established as heterogeneous catalysts, so far, their high and ordered porosity has scarcely been utilized to its full potential when it comes to spatially confined reactions in COF pores to alter the outcome of reactions. Here, we present a highly porous and crystalline, large-pore COF as catalytic support in α,ω-diene ring-closing metathesis reactions, leading to increased macrocyclization selectivity. COF pore-wall modification by immobilization of a Grubbs-Hoveyda-type catalyst via a mild silylation reaction provides a molecularly precise heterogeneous olefin metathesis catalyst. An increased macro(mono)cyclization (MMC) selectivity over oligomerization (O) for the heterogeneous COF-catalyst (MMC:O=1.35) of up to 51 % compared to the homogeneous catalyst (MMC:O=0.90) was observed along with a substrate-size dependency in selectivity, pointing to diffusion limitations induced by the pore confinement.

Immune signature of multiple sclerosis-associated depression.

Multiple neurobiological pathways have been implicated in the pathobiology of major depressive disorder (MDD). The identification of reliable biological substrates across the entire MDD spectrum, however, is hampered by a vast heterogeneity in the clinical presentation, presumably as a consequence of heterogeneous pathobiology. One way to overcome this limitation could be to explore disease subtypes based on biological similarity such as "inflammatory depression". As such a subtype may be particularly enriched in depressed patients with an underlying inflammatory condition, multiple sclerosis (MS) could provide an informative disease context for this approach. Few studies have explored immune markers of MS-associated depression and replications are missing. To address this, we analyzed data from two independent case-control studies on immune signatures of MS-associated depression, conducted at two different academic MS centers (overall sample size of n = 132). Using a stepwise data-driven approach, we identified CD4+CCR7lowTCM cell frequencies as a robust correlate of depression in MS. This signature was associated with core symptoms of depression and depression severity (but not MS severity per se) and linked to neuroinflammation as determined by magnetic resonance imaging (MRI). Furthermore, exploratory analyses of T cell polarization revealed this was largely driven by cells with a TH1-like phenotype. Our findings suggest (neuro)immune pathways linked to affective symptoms of autoimmune disorders such as MS, with potential relevance for the understanding of "inflammatory" subtypes of depression.

Exact replication: Foundation of science or game of chance?

The need for replication of initial results has been rediscovered only recently in many fields of research. In preclinical biomedical research, it is common practice to conduct exact replications with the same sample sizes as those used in the initial experiments. Such replication attempts, however, have lower probability of replication than is generally appreciated. Indeed, in the common scenario of an effect just reaching statistical significance, the statistical power of the replication experiment assuming the same effect size is approximately 50%-in essence, a coin toss. Accordingly, we use the provocative analogy of "replicating" a neuroprotective drug animal study with a coin flip to highlight the need for larger sample sizes in replication experiments. Additionally, we provide detailed background for the probability of obtaining a significant p value in a replication experiment and discuss the variability of p values as well as pitfalls of simple binary significance testing in both initial preclinical experiments and replication studies with small sample sizes. We conclude that power analysis for determining the sample size for a replication study is obligatory within the currently dominant hypothesis testing framework. Moreover, publications should include effect size point estimates and corresponding measures of precision, e.g., confidence intervals, to allow readers to assess the magnitude and direction of reported effects and to potentially combine the results of initial and replication study later through Bayesian or meta-analytic approaches.

Comparison of the PROMIS Preference Score (PROPr) and EQ-5D-5L Index Value in General Population Samples in the United Kingdom, France, and Germany.

OBJECTIVES: The Patient-Reported Outcome Measurement Information System (PROMIS) Preference score (PROPr) can be used to assess health state utility (HSU) and estimate quality-adjusted life-years in cost-effectiveness analyses. It is based on item response theory and promises to overcome limitations of existing HSU scores such as ceiling effects. The PROPr contains 7 PROMIS domains: cognitive abilities, depression, fatigue, pain, physical function, sleep disturbance, and ability to participate in social roles and activities. We aimed to compare the PROPr with the 5-level EQ-5D (EQ-5D-5L) in terms of psychometric properties using data from 3 countries. METHODS: We collected PROMIS-29 profile and EQ-5D-5L data from 3 general population samples (United Kingdom = 1509, France = 1501, Germany = 1502). Given that cognition is not assessed by the PROMIS-29, it was predicted by the recommended linear regression model. We compared the convergent validity, known-groups construct validity, and ceiling and floor effects of the PROPr and EQ-5D-5L. RESULTS: The mean PROPr (0.48, 0.53, 0.48; P<.01) and EQ-5D-5L scores (0.82, 0.85, 0.83; P<.01) showed significant differences of similar magnitudes (d = 0.34; d = 0.32; d = 0.35; P<.01) across all samples. The differences were invariant to sex, income, occupation, education, and most conditions but not for age. The Pearson correlation coefficients between both scores were r = 0.74, r = 0.69, and r = 0.72. PROPr's ceiling and floor effects both were minor to moderate. The EQ-5D-5L's ceiling (floor) effects were major (negligible). CONCLUSIONS: Both the EQ-5D-5L and the PROPr assessed by the PROMIS-29 show high validity. The PROPr yields considerably lower HSU values than the EQ-5D-5L. Consequences for quality-adjusted life-year measurements should be investigated in future research.

Gas-phase synthesis of racemic helicenes and their potential role in the enantiomeric enrichment of sugars and amino acids in meteorites.

The molecular origins of homochirality on Earth is not understood well, particularly how enantiomerically enriched molecules of astrobiological significance like sugars and amino acids might have been synthesized on icy grains in space preceding their delivery to Earth. Polycyclic aromatic hydrocarbons (PAHs) identified in carbonaceous chondrites could have been processed in molecular clouds by circularly polarized light prior to the depletion of enantiomerically enriched helicenes onto carbonaceous grains resulting in chiral islands. However, the fundamental low temperature reaction mechanisms leading to racemic helicenes are still unknown. Here, by exploiting synchrotron based molecular beam photoionization mass spectrometry combined with electronic structure calculations, we provide compelling testimony on barrierless, low temperature pathways leading to racemates of [5] and [6]helicene. Astrochemical modeling advocates that gas-phase reactions in molecular clouds lead to racemates of helicenes suggesting a pathway for future astronomical observation and providing a fundamental understanding for the origin of homochirality on early Earth.