Author Correction: Topological quantum chemistry.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Heterogeneity of Benefit from Earlier Time-to-Antibiotics for Sepsis.

Rationale: Shorter time-to-antibiotics improves survival from sepsis, particularly among patients in shock. There may be other subgroups for whom faster antibiotics are particularly beneficial.Objectives: Identify patient characteristics associated with greater benefit from shorter time-to-antibiotics.Methods: Observational cohort study of patients hospitalized with community-onset sepsis at 173 hospitals and treated with antimicrobials within 12 hours. We used three approaches to evaluate heterogeneity of benefit from shorter time-to-antibiotics: 1) conditional average treatment effects of shorter (⩽3 h) versus longer (>3-12 h) time-to-antibiotics on 30-day mortality using multivariable Poisson regression; 2) causal forest to identify characteristics associated with greatest benefit from shorter time-to-antibiotics; and 3) logistic regression with time-to-antibiotics modeled as a spline.Measurements and Main Results: Among 273,255 patients with community-onset sepsis, 131,094 (48.0%) received antibiotics within 3 hours. In Poisson models, shorter time-to-antibiotics was associated with greater absolute mortality reduction among patients with metastatic cancer (5.0% [95% confidence interval; CI: 4.3-5.7] vs. 0.4% [95% CI: 0.2-0.6] for patients without cancer, P < 0.001); patients with shock (7.0% [95% CI: 5.8-8.2%] vs. 2.8% [95% CI: 2.7-3.5%] for patients without shock, P = 0.005); and patients with more acute organ dysfunctions (4.8% [95% CI: 3.9-5.6%] for three or more dysfunctions vs. 0.5% [95% CI: 0.3-0.8] for one dysfunction, P < 0.001). In causal forest, metastatic cancer and shock were associated with greatest benefit from shorter time-to-antibiotics. Spline analysis confirmed differential nonlinear associations of time-to-antibiotics with mortality in patients with metastatic cancer and shock.Conclusions: In patients with community-onset sepsis, the mortality benefit of shorter time-to-antibiotics varied by patient characteristics. These findings suggest that shorter time-to-antibiotics for sepsis is particularly important among patients with cancer and/or shock.

Altermagnetic Routes to Majorana Modes in Zero Net Magnetization.

We propose heterostructures that realize first and second order topological superconductivity with vanishing net magnetization by utilizing altermagnetism. Such platforms may offer a significant improvement over conventional platforms with uniform magnetization since the latter suppresses the superconducting gap. We first introduce a 1D semiconductor-superconductor structure in proximity to an altermagnet that realizes end Majorana zero modes (MZMs) with vanishing net magnetization. Additionally, a coexisting Zeeman term provides a tuning knob to distinguish topological and trivial zero modes. We then propose 2D altermagnetic platforms that can realize chiral Majorana fermions or higher order corner MZMs. Our Letter paves the way toward realizing Majorana boundary states with an alternative source of time-reversal breaking and zero net magnetization.

Quantum Geometry Induced Nonlinear Transport in Altermagnets.

Quantum geometry plays a pivotal role in the second-order response of PT-symmetric antiferromagnets. Here we study the nonlinear response of 2D altermagnets protected by C_{n}T symmetry and show that their leading nonlinear response is third order. Furthermore, we show that the contributions from the quantum metric and Berry curvature enter separately: the longitudinal response for all planar altermagnets only has a contribution from the quantum metric quadrupole (QMQ), while transverse responses in general have contributions from both the Berry curvature quadrupole (BCQ) and QMQ. We show that for the well-known example of d-wave altermagnets the Hall response is dominated by the BCQ. Both longitudinal and transverse responses are strongly dependent on the crystalline anisotropy. While altermagnets are strictly defined in the limit of vanishing spin orbit coupling (SOC), real altermagnets exhibit weak SOC, which is essential to observe this response. Specifically, SOC gaps the spin-group protected nodal line, generating a response peak that is sharpest when SOC is weak. Two Dirac nodes also contribute a divergence to the nonlinear response, whose scaling changes as a function of SOC. Finally, we apply our results to thin films of the 3D altermagnet RuO_{2}. Our work uncovers distinct features of altermagnets in nonlinear transport, providing experimental signatures as well as a guide to disentangling the different components of their quantum geometry.

Sublattice Structure and Topology in Spontaneously Crystallized Electronic States.

The prediction and realization of the quantum anomalous Hall effect are often intimately connected to honeycomb lattices in which the sublattice degree of freedom plays a central role in the nontrivial topology. Two-dimensional Wigner crystals, on the other hand, form triangular lattices without sublattice degrees of freedom, resulting in a topologically trivial state. Here, we discuss the possibility of spontaneously formed honeycomb-lattice crystals that exhibit the quantum anomalous Hall effect. Starting from a single-band system with nontrivial quantum geometry, we derive the mean-field energy functional of a class of crystal states and express it as a model of sublattice pseudospins in momentum space. We find that nontrivial quantum geometry leads to extra terms in the pseudospin model that break an effective "time-reversal symmetry" and favor a topologically nontrivial pseudospin texture. When the effects of these extra terms dominate over the ferromagnetic exchange coupling between pseudospins, the anomalous Hall crystal state becomes energetically favorable over the trivial Wigner crystal state.

Social Determinants of Health and Risk-Adjusted Sepsis Mortality in the Nationwide Veterans Affairs Healthcare System.

IMPORTANCE: Traditional risk prediction and risk adjustment models have focused on clinical characteristics, but accounting for social determinants of health (SDOH) and complex health conditions could improve understanding of sepsis outcomes and our ability to predict outcomes, treat patients, and assess quality of care. OBJECTIVE: To evaluate the impact of SDOH and health scales in sepsis mortality risk prediction and hospital performance assessment. DESIGN: Observational cohort study. SETTING: One hundred twenty-nine hospitals in the nationwide Veterans Affairs (VA) Healthcare System between 2017 and 2021. PARTICIPANTS: Veterans admitted through emergency departments with community-acquired sepsis. EXPOSURES: Individual- and community-level SDOH (race, housing instability, marital status, Area Deprivation Index [ADI], and rural residence) and two health scales (the Care Assessment Need [CAN] score and Claims-Based Frailty Index [CFI]). MAIN OUTCOMES AND MEASURES: The primary outcome was 90-day mortality from emergency department arrival; secondary outcomes included 30-day mortality and in-hospital mortality. RESULTS: Among 144,889 patients admitted to the hospital with community-acquired sepsis, 139,080 were men (96.0%), median (IQR) age was 71 (64-77) years, and median (IQR) ADI was 60 (38-81). Multivariable regression models had good calibration and discrimination across models that adjusted for different sets of variables (e.g., AUROC, 0.782; Brier score, 1.33; and standardized mortality rate, 1.00). Risk-adjusted hospital performance was similar across all models. Among 129 VA hospitals, three hospitals shifted from the lowest or highest quintile of performance when comparing models that excluded SDOH to models that adjusted for all variables. Models that adjusted for ADI reported odds ratios (CI) of 1.00 (1.00-1.00), indicating that ADI does not significantly predict sepsis mortality in this cohort of patients. CONCLUSION AND RELEVANCE: In patients with community-acquired sepsis, adjusting for community SDOH variables such as ADI did not improve 90-day sepsis mortality predictions in mortality models and did not substantively alter hospital performance within the VA Healthcare System. Understanding the role of SDOH in risk prediction and risk adjustment models is vital because it could prevent hospitals from being negatively evaluated for treating less advantaged patients. However, we found that in VA hospitals, the potential impact of SDOH on 90-day sepsis mortality was minimal.

Atomically Sharp Internal Interface in a Chiral Weyl Semimetal Nanowire.

Internal interfaces in Weyl semimetals (WSMs) are predicted to host distinct topological features that are different from the commonly studied external interfaces (crystal-to-vacuum boundaries). However, the lack of atomically sharp and crystallographically oriented internal interfaces in WSMs makes it difficult to experimentally investigate topological states buried inside the material. Here, we study a unique internal interface known as merohedral twin boundary in chemically synthesized single-crystal nanowires (NWs) of CoSi, a chiral WSM of space group P213 (No. 198). Scanning transmission electron microscopy reveals that this internal interface is a (001) twin plane which connects two enantiomeric counterparts at an atomically sharp interface with inversion twinning. Ab initio calculations show localized internal Fermi arcs at the (001) twin plane that can be clearly distinguished from both external Fermi arcs and bulk states. These merohedrally twinned CoSi NWs provide an ideal platform to explore topological properties associated with internal interfaces in WSMs.

Topological Superconductivity in Doped Magnetic Moiré Semiconductors.

We show that topological superconductivity may emerge upon doping of transition metal dichalcogenide heterobilayers above an integer-filling magnetic state of the topmost valence moiré band. The effective attraction between charge carriers is generated by an electric p-wave Feshbach resonance arising from interlayer excitonic physics and has a tunable strength, which may be large. Together with the low moiré carrier densities reachable by gating, this robust attraction enables access to the long-sought p-wave BEC-BCS transition. The topological protection arises from an emergent time reversal symmetry occurring when the magnetic order and long wavelength magnetic fluctuations do not couple different valleys. The resulting topological superconductor features helical Majorana edge modes, leading to half-integer quantized spin-thermal Hall conductivity and to charge currents induced by circularly polarized light or other time-reversal symmetry-breaking fields.

Topological and Stacked Flat Bands in Bilayer Graphene with a Superlattice Potential.

We show that bilayer graphene in the presence of a 2D superlattice potential provides a highly tunable setup that can realize a variety of flat band phenomena. We focus on two regimes: (i) topological flat bands with nonzero Chern numbers, C, including bands with higher Chern numbers |C|>1 and (ii) an unprecedented phase consisting of a stack of nearly perfect flat bands with C=0. For realistic values of the potential and superlattice periodicity, this stack can span nearly 100 meV, encompassing nearly all of the low-energy spectrum. We further show that in the topological regime, the topological flat band has a favorable band geometry for realizing a fractional Chern insulator (FCI) and use exact diagonalization to show that the FCI is in fact the ground state at 1/3 filling. Our results provide a realistic guide for future experiments to realize a new platform for flat band phenomena.

Topological quantum chemistry.

Since the discovery of topological insulators and semimetals, there has been much research into predicting and experimentally discovering distinct classes of these materials, in which the topology of electronic states leads to robust surface states and electromagnetic responses. This apparent success, however, masks a fundamental shortcoming: topological insulators represent only a few hundred of the 200,000 stoichiometric compounds in material databases. However, it is unclear whether this low number is indicative of the esoteric nature of topological insulators or of a fundamental problem with the current approaches to finding them. Here we propose a complete electronic band theory, which builds on the conventional band theory of electrons, highlighting the link between the topology and local chemical bonding. This theory of topological quantum chemistry provides a description of the universal (across materials), global properties of all possible band structures and (weakly correlated) materials, consisting of a graph-theoretic description of momentum (reciprocal) space and a complementary group-theoretic description in real space. For all 230 crystal symmetry groups, we classify the possible band structures that arise from local atomic orbitals, and show which are topologically non-trivial. Our electronic band theory sheds new light on known topological insulators, and can be used to predict many more.

Exact Landau Level Description of Geometry and Interaction in a Flatband.

Flatbands appear in many condensed matter systems, including the two-dimensional electron gas in a high magnetic field, correlated materials, and moiré heterostructures. They are characterized by intrinsic geometric properties such as the Berry curvature and Fubini-Study metric. The influence of the band geometry on electron-electron interaction is difficult to understand analytically because the geometry is in general nonuniform in momentum space. In this work, we study the topological flatband of Chern number C=1 with a momentum-dependent but positive definite Berry curvature that fluctuates in sync with Fubini-Study metric. We derive an exact correspondence between such ideal flatbands and Landau levels and show that the band geometry fluctuation gives rise to a new type of interaction in the corresponding Landau levels that depends on the center of mass of two particles. We characterize such interactions by generalizing the usual Haldane pseudopotentials. This mapping gives exact zero-energy ground states for short-ranged repulsive generalized pseudopotentials in flatbands, in analogy to fractional quantum Hall systems. Driving the center-of-mass interactions beyond the repulsive regime leads to a dramatic reconstruction of the ground states towards gapless phases. The generalized pseudopotential could be a useful basis for future numerical studies.

The Role of Delocalized Chemical Bonding in Square-Net-Based Topological Semimetals.

Principles that predict reactions or properties of materials define the discipline of chemistry. In this work, we derive chemical rules, based on atomic distances and chemical bond character, which predict topological materials in compounds that feature the structural motif of a square-net. Using these rules, we identify over 300 potential new topological materials. We show that simple chemical heuristics can be a powerful tool to characterize topological matter. In contrast to previous database-driven materials' categorization, our approach allows us to identify candidates that are alloys, solid-solutions, or compounds with statistical vacancies. While previous material searches relied on density functional theory, our approach is not limited by this method and could also be used to discover magnetic and statistically disordered topological semimetals.

Partial Lattice Defects in Higher-Order Topological Insulators.

Nonzero weak topological indices are thought to be a necessary condition to bind a single helical mode to lattice dislocations. In this work we show that higher-order topological insulators (HOTIs) can, in fact, host a single helical mode along screw or edge dislocations (including step edges) in the absence of weak topological indices. When this occurs, the helical mode is necessarily bound to a dislocation characterized by a fractional Burgers vector, macroscopically detected by the existence of a stacking fault. The robustness of a helical mode on a partial defect is demonstrated by an adiabatic transformation that restores translation symmetry in the stacking fault. We present two examples of HOTIs, one intrinsic and one extrinsic, that show helical modes at partial dislocations. Since partial defects and stacking faults are commonplace in bulk crystals, the existence of such helical modes can measurably affect the expected conductivity in these materials.

Topology of Disconnected Elementary Band Representations.

Elementary band representations are the fundamental building blocks of atomic limit band structures. They have the defining property that at partial filling they cannot be both gapped and trivial. Here, we give two examples-one each in a symmorphic and a nonsymmorphic space group-of elementary band representations realized with an energy gap. In doing so, we explicitly construct a counterexample to a claim by Michel and Zak that single-valued elementary band representations in nonsymmorphic space groups with time-reversal symmetry are connected. For each example, we construct a topological invariant to explicitly demonstrate that the valence bands are nontrivial. We discover a new topological invariant: a movable but unremovable Dirac cone in the "Wilson Hamiltonian" and a bent-Z_{2} index.

Linking the content to demographic reach of online advertising of electronic nicotine delivery systems.

INTRODUCTION: Recent studies have separately examined the content and demographic reach of the advertising of electronic nicotine delivery systems (ENDS). No study to our knowledge has linked the two in investigating whether racial/ethnic groups are differentially exposed to the comparative messages conveyed in online ENDS advertisements. METHODS: 932 unique ENDS advertisements (6311 total), which were posted on 3435 websites between December, 2009 and October, 2015, were categorized as either comparative or non-comparative with respect to the traditional cigarette. The race/ethnicity of website visitors was obtained from a proprietary source and used in constructing variables for racial/ethnic viewership. The variables for advertising content and website racial/ethnic viewership were then linked yielding a final sample of 551 unique ENDS advertisements (2498 total) on 1206 websites. A two-level hierarchical generalized linear model, used in estimating website racial/ethnic viewership as a predictor of comparative advertising, accounted for the nesting of advertisements (level 1) within 152 ENDS brands (level 2). RESULTS: In contrast to racial/ethnic minorities, a greater proportion of non-Hispanic whites visited websites with ENDS advertisements than the overall proportion of nonHispanic white U.S. Internet users. Yet, it was the advertisements on websites that appealed to Hispanics that had greater odds of comparing ENDS to traditional cigarettes. CONCLUSIONS: The lower exposure to ENDS advertising among racial/ethnic minorities versus non-Hispanic whites is consistent with survey data. Yet, the greater odds of comparative advertising of ENDS on websites that appeal to racial/ethnic minorities (ie, Hispanics) could impact the longterm health of minority smokers. IMPLICATIONS: This study's findings have important implications for the uptake of ENDS among minority smokers. If the comparative advertising yields greater interest and eventual use of ENDS, then minority smokers could either benefit from smoking cessation because they switch to ENDS, or adopt dual tobacco use. The fate of comparative advertising of ENDS versus the traditional cigarette will depend on the Food and Drug Administration enforcement of its deeming rules and the ensuing changes in the ENDS marketplace.

An Essential Role of INI1/hSNF5 Chromatin Remodeling Protein in HIV-1 Posttranscriptional Events and Gag/Gag-Pol Stability.

INI1/hSNF5/SMARCB1/BAF47 is an HIV-specific integrase (IN)-binding protein that influences HIV-1 transcription and particle production. INI1 binds to SAP18 (Sin3a-associated protein, 18 kDa), and both INI1 and SAP18 are incorporated into HIV-1 virions. To determine the significance of INI1 and the INI1-SAP18 interaction during HIV-1 replication, we isolated a panel of SAP18-interaction-defective (SID)-INI1 mutants using a yeast reverse two-hybrid screen. The SID-INI1 mutants, which retained the ability to bind to IN, cMYC, and INI1 but were impaired for binding to SAP18, were tested for their effects on HIV-1 particle production. SID-INI1 dramatically reduced the intracellular Gag/Gag-Pol protein levels and, in addition, decreased viral particle production. The SID-INI1-mediated effects were less dramatic in trans complementation assays using IN deletion mutant viruses with Vpr-reverse transcriptase (RT)-IN. SID-INI1 did not inhibit long-terminal-repeat (LTR)-mediated transcription, but it marginally decreased the steady-state gag RNA levels, suggesting a posttranscriptional effect. Pulse-chase analysis indicated that in SID-INI1-expressing cells, the pr55Gag levels decreased rapidly. RNA interference analysis indicated that small hairpin RNA (shRNA)-mediated knockdown of INI1 reduced the intracellular Gag/Gag-Pol levels and further inhibited HIV-1 particle production. These results suggest that SID-INI1 mutants inhibit multiple stages of posttranscriptional events of HIV-1 replication, including intracellular Gag/Gag-Pol RNA and protein levels, which in turn inhibits assembly and particle production. Interfering INI1 leads to a decrease in particle production and Gag/Gag-Pol protein levels. Understanding the role of INI1 and SAP18 in HIV-1 replication is likely to provide novel insight into the stability of Gag/Gag-Pol, which may lead to the development of novel therapeutic strategies to inhibit HIV-1 late events. IMPORTANCE: Significant gaps exist in our current understanding of the mechanisms and host factors that influence HIV-1 posttranscriptional events, including gag RNA levels, Gag/Gag-Pol protein levels, assembly, and particle production. Our previous studies suggested that the IN-binding host factor INI1 plays a role in HIV-1 assembly. An ectopically expressed minimal IN-binding domain of INI1, S6, potently and selectively inhibited HIV-1 Gag/Gag-Pol trafficking and particle production. However, whether or not endogenous INI1 and its interacting partners, such as SAP18, are required for late events was unknown. Here, we report that endogenous INI1 and its interaction with SAP18 are necessary to maintain intracellular levels of Gag/Gag-Pol and for particle production. Interfering INI1 or the INI1-SAP18 interaction leads to the impairment of these processes, suggesting a novel strategy for inhibiting posttranscriptional events of HIV-1 replication.

Emergent flat band and topological Kondo semimetal driven by orbital-selective correlations.

Flat electronic bands are expected to show proportionally enhanced electron correlations, which may generate a plethora of novel quantum phases and unusual low-energy excitations. They are increasingly being pursued in d-electron-based systems with crystalline lattices that feature destructive electronic interference, where they are often topological. Such flat bands, though, are generically located far away from the Fermi energy, which limits their capacity to partake in the low-energy physics. Here we show that electron correlations produce emergent flat bands that are pinned to the Fermi energy. We demonstrate this effect within a Hubbard model, in the regime described by Wannier orbitals where an effective Kondo description arises through orbital-selective Mott correlations. Moreover, the correlation effect cooperates with symmetry constraints to produce a topological Kondo semimetal. Our results motivate a novel design principle for Weyl Kondo semimetals in a new setting, viz. d-electron-based materials on suitable crystal lattices, and uncover interconnections among seemingly disparate systems that may inspire fresh understandings and realizations of correlated topological effects in quantum materials and beyond.

Convergent Validity Between the Motor Domain of PediaTracTM and Ages and Stages in Term and Preterm Infants at 2, 4, 6, and 9 Months of Age.

The primary aim of this study was to evaluate the convergent validity of the Motor domain (MOT) of PediaTracTM v3.0, an online developmental tracking instrument based on caregiver reports, with fine and gross motor domains (ASQ-FM and ASQ-GM) of the Ages and Stages Questionnaire (ASQ-3) in infants between 2- and 9 months of age. Participants were caregivers of 571 infants born term or preterm (gestational age <37 weeks) enrolled in a multi-site psychometric study of PediaTracTM. Findings revealed significant correlations between MOT and ASQ-3 scores at 2, 4, 6, and 9 months across time periods, term-preterm status, and biological sex. A significantly higher percentage of infants born preterm, compared with those born at term, was identified as a moderate or high risk on both the ASQ-3 and PediaTrac. Future investigations are warranted to further examine the psychometric properties of the MOT domain, including sensitivity, specificity, and positive and negative predictive value.

Targeted delivery of interferon-α to hepatitis B virus-infected cells using T-cell receptor-like antibodies.

UNLABELLED: During antiviral therapy, specific delivery of interferon-α (IFNα) to infected cells may increase its antiviral efficacy, trigger a localized immune reaction, and reduce the side effects caused by systemic administration. Two T-cell receptor-like antibodies (TCR-L) able to selectively bind hepatitis B virus (HBV)-infected hepatocytes of chronic hepatitis B patients and recognize core (HBc18-27) and surface (HBs183-91) HBV epitopes associated with different human leukocyte antigen (HLA)-A*02 alleles (A*02:01, A*02:02, A*02:07, A*02:11) were generated. Each antibody was genetically linked to two IFNα molecules to produce TCR-L/IFNα fusion proteins. We demonstrate that the fusion proteins triggered an IFNα response preferentially on the hepatocytes presenting the correct HBV-peptide HLA-complex and that the mechanism of the targeted IFNα response was dependent on the specific binding of the fusion proteins to the HLA/HBV peptide complexes through the TCR-like variable regions of the antibodies. CONCLUSION: TCR-L antibodies can be used to target cytokines to HBV-infected hepatocytes in vitro. Fusion of IFNα to TCR-L decreased the intrinsic biological activity of IFNα but preserved the overall specificity of the protein for the cognate HBV peptide/HLA complexes. This induction of an effective IFNα response selectively in HBV-infected cells might have a therapeutic advantage in comparison to the currently used native or pegylated IFNα.

Blood count derangements after sepsis and association with post-hospital outcomes.

Rationale: Predicting long-term outcomes in sepsis survivors remains a difficult task. Persistent inflammation post-sepsis is associated with increased risk for rehospitalization and death. As surrogate markers of inflammation, complete blood count parameters measured at hospital discharge may have prognostic value for sepsis survivors. Objective: To determine the incremental value of complete blood count parameters over clinical characteristics for predicting 90-day outcomes in sepsis survivors. Methods: Electronic health record data was used to identify sepsis hospitalizations at United States Veterans Affairs hospitals with live discharge and relevant laboratory data (2013 to 2018). We measured the association of eight complete blood count parameters with 90-day outcomes (mortality, rehospitalization, cause-specific rehospitalizations) using multivariable logistic regression models. Measurements and main results: We identified 155,988 eligible hospitalizations for sepsis. Anemia (93.6%, N=142,162) and lymphopenia (28.1%, N=29,365) were the most common blood count abnormalities at discharge. In multivariable models, all parameters were associated with the primary outcome of 90-day mortality or rehospitalization and improved model discrimination above clinical characteristics alone (likelihood ratio test, p<0.02 for all). A model including all eight parameters significantly improved discrimination (AUROC, 0.6929 v. 0.6756) and reduced calibration error for the primary outcome. Hemoglobin had the greatest prognostic separation with a 1.5 fold increased incidence of the primary outcome in the lowest quintile (7.2-8.9 g/dL) versus highest quintile (12.70-15.80 g/dL). Hemoglobin and neutrophil lymphocyte ratio provided the most added value in predicting the primary outcome and 90-day mortality alone, respectively. Absolute lymphocyte count added little value in predicting 90-day outcomes. Conclusions: The incorporation of discharge complete blood count parameters into prognostic scoring systems could improve prediction of 90-day outcomes. Hemoglobin had the greatest prognostic value for the primary composite outcome of 90-day rehospitalization or mortality. Absolute lymphocyte count provided little added value in multivariable model comparisons, including for infection- or sepsis-related rehospitalization.