Inverse design of optical pulse shapes for time-varying photonics.

Recent advancements in materials and metamaterials with strong, time-varying, nonlinear optical responses have spurred a surge of interest in time-varying photonics. This opens the door to novel optical phenomena including reciprocity breaking, frequency translation, and amplification that can be further optimized by improving the light-matter interaction. Although there has been recent interest in applying topology-based inverse design to this problem, we propose a novel approach in this article. We introduce a method for the inverse design of optical pulse shapes to enhance their interaction with time-varying media. We validate our objective-first approach by maximizing the transmittance of optical pulses of equal intensity through time-varying media. Through this approach, we achieve large, broadband enhancements in pulse energy transmission, including gain, without altering the incident pulse energy. As a final test, we maximize pulse transmission through thin films of indium tin oxide, a time-varying medium when strongly pumped in its ENZ band. Our work presents a new degree of freedom for the exploration, application, and design of time-varying systems and we hope it inspires further research in this direction.

Decoding the role of macrophages in periodontitis and type 2 diabetes using single-cell RNA-sequencing.

Macrophages are resident myeloid cells in the gingival tissue which control homeostasis and play a pivotal role in orchestrating the immune response in periodontitis. Cell heterogeneity and functional phenotypes of macrophage subpopulations in periodontitis remain elusive. Here, we isolated gingival tissue from periodontitis-affected and healthy sites of patients with and without type 2 diabetes mellitus (T2DM). We then used single-cell RNA-sequencing (scRNA-seq) to define the heterogeneity of tissue-resident macrophages in gingival tissue in health vs. periodontitis. scRNA-seq demonstrated an unforeseen gene expression heterogeneity among macrophages in periodontitis and showed transcriptional and signaling heterogeneity of identified subsets in an independent cohort of patients with periodontitis and T2DM. Our bioinformatic inferences indicated divergent expression profiles in macrophages driven by transcriptional regulators CIITA, RELA, RFX5, and RUNX2. Macrophages in periodontitis expressed both pro-inflammatory and anti-inflammatory markers and their polarization was not mutually exclusive. The majority of macrophages in periodontitis expressed the monocyte lineage marker CD14, indicating their bone marrow lineage. We also found high expression and activation of RELA, a subunit of the NF-κB transcription factor complex, in gingival macrophages of periodontitis patients with T2DM. Our data suggested that heterogeneity and hyperinflammatory activation of macrophages may be relevant to the pathogenesis and outcomes of periodontitis, and may be further augmented in patients with T2DM.

SP140 inhibits STAT1 signaling, induces IFN-γ in tumor-associated macrophages, and is a predictive biomarker of immunotherapy response.

BACKGROUND: Understanding the role and potential therapeutic targeting of tumor-associated macrophages (TAMs) is crucial to developing new biomarkers and therapeutic strategies for cancer immunotherapies. The epigenetic reader SP140 has emerged as a master regulator of macrophage transcriptional programs; however, its role in the signaling of TAMs and response to immunotherapy has not been investigated. METHODS: We evaluated the correlation between SP140 expression in head and neck squamous cell carcinoma (HNSCC) TAMs and clinical outcomes. We also used complementary bioinformatics and experimental approaches to study the association of SP140 expression with tumor mutation burden, patient survival, immunogenic signature of tumors, and signaling of TAMs. SP140 overexpression or knockdown was implemented to identify the role of SP140 in downstream signaling and production of inflammatory cytokine and chemokines. Chromatin immunoprecipitation and analysis of assay of transposase accessible chromatin sequencing data were used to demonstrate the direct binding of SP140 on the promoters of STAT1. Finally, correlation of SP140 with immune cell infiltrates and response to immune-checkpoint blockade in independent cohorts of HNSCC, metastatic melanoma, and melanoma was assessed. RESULTS: We found that SP140 is highly expressed in TAMs across many cancer types, including HNSCCs. Interestingly, higher expression of SP140 in the tumors was associated with higher tumor mutation burden, improved survival, and a favorable response to immunotherapy. Tumors with high SP140 expression showed enrichment of inflammatory response and interferon-gamma (IFN-γ) pathways in both pan-cancer analysis and HNSCC-specific analysis. Mechanistically, SP140 negatively regulates transcription and phosphorylation of STAT1 and induces IFN-γ signaling. Activating SP140 in macrophages and TAMs induced the proinflammatory macrophage phenotype, increased the antitumor activity of macrophages, and increased the production of IFN-γ and antitumor cytokines and chemokines including interleukin-12 and CXCL10. SP140 expression provided higher sensitivity and specificity to predict antiprogrammed cell death protein 1 immunotherapy response compared with programmed death-ligand 1 in HNSCCs and lung cancer. In metastatic melanoma, higher levels of SP140 were associated with a durable response to immunotherapy, higher immune score estimates, high infiltrations of CD8+ T cells, and inflammatory TAMs. CONCLUSIONS: Our findings suggest that SP140 could serve as both a therapeutic target and a biomarker to identify immunotherapy responders.

Hyperpolarizability of Plasmonic Meta-Atoms in Metasurfaces.

Plasmonic metasurfaces are promising as enablers of nanoscale nonlinear optics and flat nonlinear optical components. Nonlinear optical responses of such metasurfaces are determined by the nonlinear optical properties of individual plasmonic meta-atoms. Unfortunately, no simple methods exist to determine the nonlinear optical properties (hyperpolarizabilities) of the meta-atoms hindering the design of nonlinear metasurfaces. Here, we develop the equivalent RLC circuit (resistor, inductor, capacitor) model of such meta-atoms to estimate their second-order nonlinear optical properties, that is, the first-order hyperpolarizability in the optical spectral range. In parallel, we extract from second-harmonic generation experiments the first-order hyperpolarizabilities of individual meta-atoms consisting of asymmetrically shaped (elongated) plasmonic nanoprisms, verified with detailed calculations using both nonlinear hydrodynamic-FDTD and nonlinear scattering theory. All three approaches, analytical, experimental, and computational, yield results that agree very well. Our empirical RLC model can thus be used as a simple tool to enable an efficient design of nonlinear plasmonic metasurfaces.

Clinical outcomes in patients admitted to hospital with cervical spine fractures or with hip fractures.

Patients admitted with a cervical fracture are twice as likely to die within 30 days of injury than those with a hip fracture. However, guidelines for the management of cervical fractures are less available than for hip fractures. We hypothesise that outcomes may differ between these types of fractures. We analysed 1359 patients (406 men, 953 women) with mean age of 83.8 years (standard deviation = 8.7) admitted to a National Health Service hospital in 2013-2019 with a cervical (7.5%) or hip fracture (92.5%) of similar age. The association of cervical fracture (hip fracture as reference), hospital length of stay (LOS), co-morbidities, age and sex with outcomes (acute delirium, new pressure ulcer, and discharge to residential/nursing care) was assessed by stepwise multivariate logistic regression. Acute delirium without history of dementia was increased with cervical fractures: odds ratio (OR) = 2.4, 95% confidence interval (CI) = 1.3-4.7, age ≥ 80 years: OR = 3.5 (95% CI = 1.9-6.4), history of stroke: OR = 1.8 (95% CI = 1.0-3.1) and ischaemic heart disease: OR = 1.9 (95% CI = 1.1-3.6); pressure ulcers was increased with cervical fractures: OR = 10.9 (95% CI = 5.3-22.7), LOS of 2-3 weeks: OR = 3.0 (95% CI = 1.2-7.5) and LOS of ≥ 3 weeks: OR = 4.9, 95% CI = 2.2-11.0; and discharge to residential/nursing care was increased with cervical fractures: OR = 3.2 (95% CI = 1.4-7.0), LOS of ≥ 3 weeks: OR = 4.4 (95% CI = 2.5-7.6), dementia: OR = 2.7 (95% CI = 1.6-4.7), Parkinson's disease: OR = 3.4 (95% CI = 1.3-8.8), and age ≥ 80 years: OR = 2.7 (95% CI = 1.3-5.6). In conclusion, compared with hip fracture, cervical fracture is more likely to associate with acute delirium and pressure ulcers, and for discharge to residency of high level of care, independent of established risk factors.

Plasmonic colours predicted by deep learning.

Picosecond laser pulses have been used as a surface colouring technique for noble metals, where the colours result from plasmonic resonances in the metallic nanoparticles created and redeposited on the surface by ablation and deposition processes. This technology provides two datasets which we use to train artificial neural networks, data from the experiment itself (laser parameters vs. colours) and data from the corresponding numerical simulations (geometric parameters vs. colours). We apply deep learning to predict the colour in both cases. We also propose a method for the solution of the inverse problem - wherein the geometric parameters and the laser parameters are predicted from colour - using an iterative multivariable inverse design method.

Utility of cocaine drug screens to predict safe delivery of general anesthesia for elective surgical patients.

Cocaine has been associated with acute hemodynamic changes, causing anesthesia providers to be concerned about adverse hemodynamic events during general anesthesia. We sought to determine if there were differences in the prevalence of adverse hemodynamic events, and if hemodynamic instability could be predicted in cocaine-positive patients undergoing general anesthesia for elective surgery. A retrospective cohort study was conducted in 300 (150 cocaine-positive, 150 cocaine-negative) consecutive adults with similar general anesthesia plans who were hemodynamically normal at baseline. Subjects were excluded if they were not alert at baseline, or if they required more than 1 surgical procedure. Slightly more than 50% of subjects were female, but cocaine-positive subjects were significantly more likely to be male (chi2 = 5.9; P = .02). Baseline systolic pressure (P = .001; mean difference, 6.5 mm Hg; 95% confidence interval [CI], 2.7-70.2), mean arterial pressure (P = .04; mean difference, 2.9 mm Hg; 95% CI, 1.0-5.7), and heart rate (P = .02; mean difference, 3.3/min; 95% CI, 0.46-6.2) were significantly higher, but not clinically important in the cocaine-positive cohort. Our study demonstrates that use of drug screen results alone is insufficient to predict the safe administration of general anesthesia in patients undergoing elective surgeries.