Bias-Free Access to Orbital Angular Momentum in Two-Dimensional Quantum Materials.

The demonstration of a topological band inversion constitutes the most elementary proof of a quantum spin Hall insulator (QSHI). On a fundamental level, such an inverted band gap is intrinsically related to the bulk Berry curvature, a gauge-invariant fingerprint of the wave function's quantum geometric properties in Hilbert space. Intimately tied to orbital angular momentum (OAM), the Berry curvature can be, in principle, extracted from circular dichroism in angle-resolved photoemission spectroscopy (CD-ARPES), were it not for interfering final state photoelectron emission channels that obscure the initial state OAM signature. Here, we outline a full-experimental strategy to avoid such interference artifacts and isolate the clean OAM from the CD-ARPES response. Bench-marking this strategy for the recently discovered atomic monolayer system indenene, we demonstrate its distinct QSHI character and establish CD-ARPES as a scalable bulk probe to experimentally classify the topology of two-dimensional quantum materials with time reversal symmetry.

Optimization of synthetic molecular reporters for a mesenchymal glioblastoma transcriptional program by integer programing.

MOTIVATION: A recent approach to perform genetic tracing of complex biological problems involves the generation of synthetic deoxyribonucleic acid (DNA) probes that specifically mark cells with a phenotype of interest. These synthetic locus control regions (sLCRs), in turn, drive the expression of a reporter gene, such as fluorescent protein. To build functional and specific sLCRs, it is critical to accurately select multiple bona fide cis-regulatory elements from the target cell phenotype cistrome. This selection occurs by maximizing the number and diversity of transcription factors (TFs) within the sLCR, yet the size of the final sLCR should remain limited. RESULTS: In this work, we discuss how optimization, in particular integer programing, can be used to systematically address the construction of a specific sLCR and optimize pre-defined properties of the sLCR. Our presented instance of a linear optimization problem maximizes the activation potential of the sLCR such that its size is limited to a pre-defined length and a minimum number of all TFs deemed sufficiently characteristic for the phenotype of interest is covered. We generated an sLCR to trace the mesenchymal glioblastoma program in patients by solving our corresponding linear program with the software optimizer Gurobi. Considering the binding strength of transcription factor binding sites (TFBSs) with their TFs as a proxy for activation potential, the optimized sLCR scores similarly to an sLCR experimentally validated in vivo, and is smaller in size while having the same coverage of TFBSs. AVAILABILITY AND IMPLEMENTATION: We provide a Python implementation of the presented framework in the Supplementary Material with which an optimal selection of cis-regulatory elements can be calculated once the target set of TFs and their binding strength with their TFBSs is known. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

A simple ion chromatography-mass spectrometry method for amino acid analysis in beer.

The amino acid footprint of different beer samples was analyzed using ion chromatography coupled with electrospray ionization mass spectrometry. A tailor-made polymer-based cation-exchange resin was operated with a mass spectrometry-compatible eluent under isocratic conditions on a standard high-performance liquid chromatography system coupled to a single quadrupole mass spectrometer using formic acid as a volatile eluent ion source. The partially separated peaks of the isomeric pair isoleucine/leucine were processed according to their area response ratio using vertical peak splitting or Gaussian fit. Additionally, the chromatographic resolution of the isomers was optimized with an adjusted, solely aqueous mobile phase from 0.85 to 2.92. Ion suppression in the electrospray ion source was investigated for the derivatization-free method and found to be insignificant (recovery value 100 ± 15%) for 15 out of the 20 analytes. Quantitative results for various beer and mixed-beer beverages were found to be in high agreement with existing methods. Simultaneous photometric detection demonstrated the method's ability to successfully remove most of the interfering matrix compounds.

Ventricular Arrhythmias and Sudden Death in Nonischemic Dilated Cardiomyopathy: Matter of Sex or Scar?

BACKGROUND: To evaluate the association between sex and ventricular arrhythmias (VA) or sudden death (SD) in nonischemic dilated cardiomyopathy, including analysis of potential confounders. METHODS AND RESULTS: Retrospective cohort study of consecutive patients with DCM referred for cardiac magnetic resonance at 2 tertiary hospitals. The primary combined end point encompassed sustained VA, appropriate implantable cardioverter defibrillator therapies, resuscitated cardiac arrest, and SD. We included 1165 patients with median follow-up of 36 months (interquartile range 20-58 months). The majority of patients (66%) were males. Males and females had similar left ventricular ejection fraction, but the prevalence of late gadolinium enhancement (LGE) at cardiac magnetic resonance was significantly higher among males (48% vs 30%, P < .001). Males had higher cumulative incidence of the primary end point (8% vs 4%, P = .02), and male sex was a significant predictor of the primary end point at univariate analysis (hazard ratio 1.93, P = .02). However, LGE had a major confounding effect in the association between sex and the primary outcome: the hazard ratio of male sex adjusted for LGE was 1.29 (P = .37). LGE+ females had significantly higher cumulative incidence of the primary end point than LGE- males (13% vs 1.8%, P < .001). CONCLUSIONS: In patients with DCM, the prevalence of LGE is significantly higher among males, implying a major confounding effect in the association between male sex and VA or SD. LGE+ females have significantly higher risk than LGE- males. These data do not support the inclusion of sex into risk stratification algorithms for VA or SD in DCM.

Self-bound droplets of a dilute magnetic quantum liquid.

Self-bound many-body systems are formed through a balance of attractive and repulsive forces and occur in many physical scenarios. Liquid droplets are an example of a self-bound system, formed by a balance of the mutual attractive and repulsive forces that derive from different components of the inter-particle potential. It has been suggested that self-bound ensembles of ultracold atoms should exist for atom number densities that are 108 times lower than in a helium droplet, which is formed from a dense quantum liquid. However, such ensembles have been elusive up to now because they require forces other than the usual zero-range contact interaction, which is either attractive or repulsive but never both. On the basis of the recent finding that an unstable bosonic dipolar gas can be stabilized by a repulsive many-body term, it was predicted that three-dimensional self-bound quantum droplets of magnetic atoms should exist. Here we report the observation of such droplets in a trap-free levitation field. We find that this dilute magnetic quantum liquid requires a minimum, critical number of atoms, below which the liquid evaporates into an expanding gas as a result of the quantum pressure of the individual constituents. Consequently, around this critical atom number we observe an interaction-driven phase transition between a gas and a self-bound liquid in the quantum degenerate regime with ultracold atoms. These droplets are the dilute counterpart of strongly correlated self-bound systems such as atomic nuclei and helium droplets.

Observing the Rosensweig instability of a quantum ferrofluid.

Ferrofluids exhibit unusual hydrodynamic effects owing to the magnetic nature of their constituents. As magnetization increases, a classical ferrofluid undergoes a Rosensweig instability and creates self-organized, ordered surface structures or droplet crystals. Quantum ferrofluids such as Bose-Einstein condensates with strong dipolar interactions also display superfluidity. The field of dipolar quantum gases is motivated by the search for new phases of matter that break continuous symmetries. The simultaneous breaking of continuous symmetries such as the phase invariance in a superfluid state and the translational symmetry in a crystal provides the basis for these new states of matter. However, interaction-induced crystallization in a superfluid has not yet been observed. Here we use in situ imaging to directly observe the spontaneous transition from an unstructured superfluid to an ordered arrangement of droplets in an atomic dysprosium Bose-Einstein condensate. By using a Feshbach resonance to control the interparticle interactions, we induce a finite-wavelength instability and observe discrete droplets in a triangular structure, the number of which grows as the number of atoms increases. We find that these structured states are surprisingly long-lived and observe hysteretic behaviour, which is typical for a crystallization process and in close analogy to the Rosensweig instability. Our system exhibits both superfluidity and, as we show here, spontaneous translational symmetry breaking. Although our observations do not probe superfluidity in the structured states, if the droplets establish a common phase via weak links, then our system is a very good candidate for a supersolid ground state.

The effect of 1.5 T cardiac magnetic resonance on human circulating leucocytes.

Aims: Investigators have proposed that cardiovascular magnetic resonance (CMR) should have restrictions similar to those of ionizing imaging techniques. We aimed to investigate the acute effect of 1.5 T CMR on leucocyte DNA integrity, cell counts, and function in vitro, and in a large cohort of patients in vivo. Methods and results: In vitro study: peripheral blood mononuclear cells (PBMCs) were isolated from healthy volunteers, and histone H2AX phosphorylation (γ-H2AX) expression, leucocyte counts, and functional parameters were quantified using flow cytometry under the following conditions: (i) immediately following PBMC isolation, (ii) after standing on the benchside as a temperature and time control, (iii) after a standard CMR scan. In vivo study: blood samples were taken from 64 consecutive consenting patients immediately before and after a standard clinical scan. Samples were analysed for γ-H2AX expression and leucocyte counts. CMR was not associated with a significant change in γ-H2AX expression in vitro or in vivo, although there were significant inter-patient variations. In vitro cell integrity and function did not change with CMR. There was a significant reduction in circulating T cells in vivo following CMR. Conclusion: 1.5 T CMR was not associated with DNA damage in vitro or in vivo. Histone H2AX phosphorylation expression varied markedly between individuals; therefore, small studies using γ-H2AX as a marker of DNA damage should be interpreted with caution. Cardiovascular magnetic resonance was not associated with loss of leucocyte viability or function in vitro. Cardiovascular magnetic resonance was associated with a statistically significant reduction in viable leucocytes in vivo.

How Precise Are Preinterventional Measurements Using Centerline Analysis Applications? Objective Ground Truth Evaluation Reveals Software-Specific Centerline Characteristics.

PURPOSE: To evaluate different centerline analysis applications using objective ground truth from realistic aortic aneurysm phantoms with precisely defined geometry and centerlines to overcome the lack of unknown true dimensions in previously published in vivo validation studies. METHODS: Three aortic phantoms were created using computer-aided design (CAD) software and a 3-dimensional (3D) printer. Computed tomography angiograms (CTAs) of phantoms and 3 patients were analyzed with 3 clinically approved and 1 research software application. The 3D centerline coordinates, intraluminal diameters, and lengths were validated against CAD ground truth using a dedicated evaluation software platform. RESULTS: The 3D centerline position mean error ranged from 0.7±0.8 to 2.9±2.5 mm between tested applications. All applications calculated centerlines significantly different from ground truth. Diameter mean errors varied from 0.5±1.2 to 1.1±1.0 mm among 3 applications, but exceeded 8.0±11.0 mm with one application due to an unsteady distortion of luminal dimensions along the centerline. All tested commercially available software tools systematically underestimated centerline total lengths by -4.6±0.9 mm to -10.4±4.3 mm (maximum error -14.6 mm). Applications with the highest 3D centerline accuracy yielded the most precise diameter and length measurements. CONCLUSION: One clinically approved application did not provide reproducible centerline-based analysis results, while another approved application showed length errors that might influence stent-graft choice and procedure success. The variety and specific characteristics of endovascular aneurysm repair planning software tools require scientific evaluation and user awareness.

Intraoperative contrast-enhanced cone beam computed tomography to assess technical success during endovascular aneurysm repair.

BACKGROUND: The aim of the study was to analyze the use of contrast-enhanced cone beam computed tomography (ceCBCT) during endovascular aneurysm repair (EVAR) and to compare this imaging modality with standard completion digital subtraction angiography (cDSA) and postoperative computed tomography angiography (CTA) regarding the detection of endograft-associated complications. METHODS: Between September 2012 and April 2015, ceCBCT was used in 98 EVAR patients in addition to cDSA and CTA. Endoleaks, intraluminal thrombus and limb stenoses, contrast agent use, and radiation exposure were recorded for all modalities. RESULTS: cDSA detected 16 (16.3%) endoleaks; ceCBCT, 35 (35.7%) endoleaks; and CTA, 22 (22.4%) endoleaks. All endoleaks identified by cDSA or CTA were also seen on ceCBCT. ceCBCT detected intraluminal thrombus in three patients (none in cDSA or CTA) and previously undetected limb stenoses in three patients. It prompted intraoperative interventions in 7 of 98 patients (7.1%). Replacing cDSA and CTA by ceCBCT would have caused a 39% reduction of in-hospital contrast agent volume in this cohort. CONCLUSIONS: ceCBCT can reliably detect all endograft-associated complications during EVAR. It offers the chance for immediate revision of remediable problems in a relevant proportion of patients and could thus reduce early reintervention rates. ceCBCT can safely replace early follow-up CTA and thereby reduce in-hospital use of contrast media.

Feasibility and accuracy of fusion imaging during thoracic endovascular aortic repair.

OBJECTIVE: To evaluate accuracy and feasibility of fusion imaging during thoracic endovascular aortic repair (TEVAR). METHODS: From January 2013 to January 2015 fusion imaging was used in 18 TEVAR procedures. Patients were prospectively enrolled for the survey and informed consent was obtained. Planning of the procedure and computed tomography (CT) angiography (CTA) segmentation with determination of all relevant surgical landmarks that should be displayed on fusion imaging was done using the preoperative CTA data. The registration was done with an intraoperative noncontrast-enhanced cone beam CT and CTA (three-dimensional [3D]-3D registration; n = 15) or with two fluoroscopic images in anteroposterior and lateral projection and the CTA (two-dimensional-3D registration; n = 3). An intraoperative digital subtraction angiography was performed to adjust fusion imaging and to allow accuracy measurement. RESULTS: Fusion imaging was possible in all included patients. The median dose for noncontrast-enhanced cone beam CT imaging was 28.6 Gy/cm(2) (range, 17.9-43.3) and 0.46 Gy cm(2) for two fluoroscopic images in the two-dimensional-3D group. Full accuracy was achieved in two cases (11%), with a median deviation of 11.7 mm (range, 0.0-37.2). Manual realignment was possible in all cases. CONCLUSIONS: This early experience shows that fusion imaging is feasible in TEVAR procedures using different registration methods. However, it shows a significant deviation in thoracic procedures because of different sources of error, making confirmation of fusion overlay with a digital subtraction angiography necessary in any case.

Observation of Quantum Droplets in a Strongly Dipolar Bose Gas.

Quantum fluctuations are the origin of genuine quantum many-body effects, and can be neglected in classical mean-field phenomena. Here, we report on the observation of stable quantum droplets containing ∼800 atoms that are expected to collapse at the mean-field level due to the essentially attractive interaction. By systematic measurements on individual droplets we demonstrate quantitatively that quantum fluctuations mechanically stabilize them against the mean-field collapse. We observe in addition the interference of several droplets indicating that this stable many-body state is phase coherent.

Fusion Imaging to Support Endovascular Aneurysm Repair Using 3D-3D Registration.

PURPOSE: To evaluate the feasibility and accuracy of fusion imaging (FI) during endovascular aneurysm repair (EVAR). METHODS: FI was performed in 101 consecutive EVAR patients (median age 72 years; 93 men) using automatic registration of the preoperative computed tomography angiography (CTA) with an intraoperative noncontrast cone beam CT (nCBCT; 3D-3D registration). Operative landmarks defined on the CTA were then overlaid in 3 dimensions on fluoroscopy images. Accuracy was measured as the deviation of the position of the lowest renal artery between the FI and angiography. Factors potentially influencing accuracy (α angle, ß angle, anesthesia, tortuosity index, neck calcification, neck length, CTA slice thickness, and conventional or sac sealing stent-graft) were analyzed in a multivariate linear regression model. RESULTS: Median procedure time for nCBCT was 3 minutes (range 2-20), with 4 minutes (range 0.4-15) for registration. An automatic registration tool was used successfully in 90 (89%) patients. Median craniocaudal deviation of the FI was 3 mm (range 0-15). Full accuracy (<1-mm deviation) was seen in 23 (23%) patients, 1- to 3-mm deviation in 23 (23%), 4- to 5-mm deviation in 22 (22%), and >5-mm deviation in 33 (33%). Caudal deviation potentially resulting in renal coverage was seen in 9 (9%). Lateral plus craniocaudal deviation was a median 5.8 mm (range 0-22). The position of the lowest renal artery compared to the FI was left and cranial in 62 (61%). Aneurysm morphology (ß angle, p=0.04), CTA slice thickness (p=0.02), and the use of 2 stiff guidewires in endovascular aneurysm sealing (p=0.01) influenced the overlay accuracy. CONCLUSION: Fusion imaging can be integrated into a daily workflow adding little to the procedure time. Craniocaudal accuracy (<5 mm) was achieved in 68% of cases, allowing optimal C-arm and angiographic catheter positioning or cannulation of target vessels in most patients. However, the accuracy of FI does not allow a noncontrast EVAR procedure without confirmation of FI overlay by a minimal contrast injection or vessel cannulation.

The Value of Cardiovascular Magnetic Resonance in Heart Transplant Patients.

Heart transplant patients present a unique set of anatomical and pathophysiological considerations. Patients often present non-specifically, requiring a low index for further investigation. Accurate assessment with standard imaging modalities can be difficult, and cardiovascular magnetic resonance (CMR) is becoming an increasingly useful modality in the assessment of heart transplant patients. This review describes the anatomy of the transplanted heart and typical CMR appearances and discusses the role of CMR in heart transplant disease.

Cardiovascular magnetic resonance validation of fractional changes in annulo-apical angles and tricuspid annular plane systolic excursion for rapid assessment of right ventricular systolic function.

PURPOSE: To evaluate the use of right ventricular (RV) annulo-apical angle (AA) changes acquired by magnetic resonance imaging (MRI), alongside tricuspid annular plane systolic excursion (TAPSE), for its association with RV systolic function. MATERIALS AND METHODS: Thirty patients with varying RV dysfunction and 10 normal controls were enrolled and scanned after obtaining written consent. Systolic change in AAs, alpha (α), beta (ß), and theta (θ), subtended by a triangle connecting the septal and lateral extent of the tricuspid valve annulus and RV apex, and TAPSE were measured. Spearman rank correlations of parameters with RV ejection fraction (RVEF) were performed. Receiver operating characteristic (ROC) analysis was used to determine accuracy of these surrogate markers for detecting abnormal RVEF. RESULTS: Correlations with RVEF included: TAPSE (r = 0.74 P < 0.001), fractional systolic changes in α angle (0.64, P < 0.001), ß angle (-0.39, P < 0.05), and θ angle (-0.77, P < 0.001). The best markers for RVEF <50% were fractional θ angle change ≥ -25.5% (eg, -24%) (sensitivity of 97% and specificity of 91%), and TAPSE ≤1.87 cm (sensitivity of 100% and specificity of 82%). Intra- and inter-observer agreement was excellent, with intraclass correlation coefficients for fractional θ angle change (intra = 0.96, inter = 0.94) and TAPSE (intra = 0.98, inter = 0.87). CONCLUSION: Fractional θ angle change is a useful semiquantitative parameter associated with the presence and severity of RV systolic dysfunction, with high observer agreement.

Multiparametric cardiovascular magnetic resonance surveillance of acute cardiac allograft rejection and characterisation of transplantation-associated myocardial injury: a pilot study.

BACKGROUND: Serial surveillance endomyocardial biopsies are performed in patients who have recently undergone heart transplantation in order to detect acute cardiac allograft rejection (ACAR) before symptoms occur, however the biopsy process is associated with a number of limitations. This study aimed to prospectively and longitudinally evaluate the performance of multiparametric cardiovascular magnetic resonance (CMR) for detecting and monitoring ACAR in the early phase post-transplant, and characterize graft recovery following transplantation. METHODS: All patients receiving a heart transplant at a single UK centre over a period of 25 months were approached within one month of transplantation. Multiparametric CMR was prospectively performed on the same day as biopsy on four separate occasions (6 weeks, 10 weeks, 15 weeks and 20 weeks post-transplant). CMR included assessment of global and regional ventricular function, myocardial tissue characterization (T1 mapping, T2 mapping, extracellular volume, LGE) and pixel-wise absolute myocardial blood flow quantification. CMR parameters were compared with biopsy findings. As is standard, grade 2R or higher ACAR was considered significant. RESULTS: 88 CMR-matched biopsies were performed in 22 patients. Eight (9%) biopsies in 5 patients demonstrated significant ACAR. Significant ACAR was associated with a reduction in circumferential strain (-12.7±2.5% vs. -13.7±3.6%, p=0.047) but there was considerable overlap between groups. Whilst trends were observed between ACAR and proposed CMR markers of oedema, particularly after adjusting for primary graft dysfunction, differences were not significant. Significant improvements were seen in markers of graft structure and contractility, oedema and microvascular function over the period studied, although few parameters normalised. CONCLUSIONS: This study provides novel insight into the myocardial injury associated with transplantation, and its recovery, however multiparametric CMR was not able to accurately detect ACAR during the early phase post-transplantation.

Voxel-wise quantification of myocardial blood flow with cardiovascular magnetic resonance: effect of variations in methodology and validation with positron emission tomography.

BACKGROUND: Quantitative assessment of myocardial blood flow (MBF) from cardiovascular magnetic resonance (CMR) perfusion images appears to offer advantages over qualitative assessment. Currently however, clinical translation is lacking, at least in part due to considerable disparity in quantification methodology. The aim of this study was to evaluate the effect of common methodological differences in CMR voxel-wise measurement of MBF, using position emission tomography (PET) as external validation. METHODS: Eighteen subjects, including 9 with significant coronary artery disease (CAD) and 9 healthy volunteers prospectively underwent perfusion CMR. Comparison was made between MBF quantified using: 1. Calculated contrast agent concentration curves (to correct for signal saturation) versus raw signal intensity curves; 2. Mid-ventricular versus basal-ventricular short-axis arterial input function (AIF) extraction; 3. Three different deconvolution approaches; Fermi function parameterization, truncated singular value decomposition (TSVD) and first-order Tikhonov regularization with b-splines. CAD patients also prospectively underwent rubidium-82 PET (median interval 7 days). RESULTS: MBF was significantly higher when calculated using signal intensity compared to contrast agent concentration curves, and when the AIF was extracted from mid- compared to basal-ventricular images. MBF did not differ significantly between Fermi and Tikhonov, or between Fermi and TVSD deconvolution methods although there was a small difference between TSVD and Tikhonov (0.06 mL/min/g). Agreement between all deconvolution methods was high. MBF derived using each CMR deconvolution method showed a significant linear relationship (p<0.001) with PET-derived MBF however each method underestimated MBF compared to PET (by 0.19 to 0.35 mL/min/g). CONCLUSIONS: Variations in more complex methodological factors such as deconvolution method have no greater effect on estimated MBF than simple factors such as AIF location and observer variability. Standardization of the quantification process will aid comparison between studies and may help CMR MBF quantification enter clinical use.

Republished: Cardiac MRI of patients with implanted electrical cardiac devices.

Implantable pulse generators and defibrillators have traditionally been considered contraindications to MRI. However, recent data have challenged this paradigm and demonstrated that patients with newer generation devices can safely undergo MRI, including cardiac MRI, provided basic precautions are taken. Indeed, the introduction of MRI conditional systems has led to a conceptual shift in clinical decision making-'can this patient undergo MRI safely?' is being superseded by 'should this patient be implanted with an MRI conditional device?'. This review outlines the risks associated with MRI in patients with implanted cardiac devices, and discusses practical measures to minimise risks and facilitate safe and diagnostic scanning.

Predictive value of a comprehensive atrial assessment with cardiac magnetic resonance in non-ischemic cardiomyopathy: keep it simple.

Cardiac magnetic resonance (CMR) can provide a multi-parametric evaluation of left atrial (LA) size and function. A complete CMR-based LA assessment might improve the risk stratification of patients with non-ischemic dilated cardiomyopathy (DCM). We performed a comprehensive CMR-based evaluation of LA size and function, in order to assess the prognostic impact of specific LA parameters in DCM. Secondary analysis of a prospective registry (UHSM-CMR study, NCT02326324) including 648 consecutive patients with DCM and CMR evaluation of LA area and LA length. Of these, 456 had complete LA assessment covering reservoir, conduit and booster pump function and including LA reservoir strain evaluated with feature tracking. The heart failure (HF) endpoint included HF hospitalizations, HF death and heart transplant. The arrhythmic endpoint included ventricular arrhythmias (VA) (sustained or treated by implantable defibrillator) and sudden death (SD). At median follow-up of 23 months, 34 patients reached the HF endpoint; in a multivariable model including NYHA class and LVEF, LA length had incremental predictive value. LA length ≥ 69 mm was the best cut-off to predict HF events (adjusted HR 2.3, p = 0.03). Among the 456 patients with comprehensive LA assessment, only LA length was independently associated with the HF endpoint after adjusting for LVEF and NYHA class. By contrast, no LA parameter independently predicted the arrhythmic risk. In DCM patients, LA length is an independent predictor of HF events, showing stronger association than other more complex parameters of LA function. No atrial parameter predicts the risk of VA and SD.

Logical design of synthetic cis-regulatory DNA for genetic tracing of cell identities and state changes.

Descriptive data are rapidly expanding in biomedical research. Instead, functional validation methods with sufficient complexity remain underdeveloped. Transcriptional reporters allow experimental characterization and manipulation of developmental and disease cell states, but their design lacks flexibility. Here, we report logical design of synthetic cis-regulatory DNA (LSD), a computational framework leveraging phenotypic biomarkers and trans-regulatory networks as input to design reporters marking the activity of selected cellular states and pathways. LSD uses bulk or single-cell biomarkers and a reference genome or custom cis-regulatory DNA datasets with user-defined boundary regions. By benchmarking validated reporters, we integrate LSD with a computational ranking of phenotypic specificity of putative cis-regulatory DNA. Experimentally, LSD-designed reporters targeting a wide range of cell states are functional without minimal promoters. Applied to broadly expressed genes from human and mouse tissues, LSD generates functional housekeeper-like sLCRs compatible with size constraints of AAV vectors for gene therapy applications. A mesenchymal glioblastoma reporter designed by LSD outperforms previously validated ones and canonical cell surface markers. In genome-scale CRISPRa screens, LSD facilitates the discovery of known and novel bona fide cell-state drivers. Thus, LSD captures core principles of cis-regulation and is broadly applicable to studying complex cell states and mechanisms of transcriptional regulation.