A generalizable and easy-to-use COVID-19 stratification model for the next pandemic via immune-phenotyping and machine learning.

Introduction: The coronavirus disease 2019 (COVID-19) pandemic has affected billions of people worldwide, and the lessons learned need to be concluded to get better prepared for the next pandemic. Early identification of high-risk patients is important for appropriate treatment and distribution of medical resources. A generalizable and easy-to-use COVID-19 severity stratification model is vital and may provide references for clinicians. Methods: Three COVID-19 cohorts (one discovery cohort and two validation cohorts) were included. Longitudinal peripheral blood mononuclear cells were collected from the discovery cohort (n = 39, mild = 15, critical = 24). The immune characteristics of COVID-19 and critical COVID-19 were analyzed by comparison with those of healthy volunteers (n = 16) and patients with mild COVID-19 using mass cytometry by time of flight (CyTOF). Subsequently, machine learning models were developed based on immune signatures and the most valuable laboratory parameters that performed well in distinguishing mild from critical cases. Finally, single-cell RNA sequencing data from a published study (n = 43) and electronic health records from a prospective cohort study (n = 840) were used to verify the role of crucial clinical laboratory and immune signature parameters in the stratification of COVID-19 severity. Results: Patients with COVID-19 were determined with disturbed glucose and tryptophan metabolism in two major innate immune clusters. Critical patients were further characterized by significant depletion of classical dendritic cells (cDCs), regulatory T cells (Tregs), and CD4+ central memory T cells (Tcm), along with increased systemic interleukin-6 (IL-6), interleukin-12 (IL-12), and lactate dehydrogenase (LDH). The machine learning models based on the level of cDCs and LDH showed great potential for predicting critical cases. The model performances in severity stratification were validated in two cohorts (AUC = 0.77 and 0.88, respectively) infected with different strains in different periods. The reference limits of cDCs and LDH as biomarkers for predicting critical COVID-19 were 1.2% and 270.5 U/L, respectively. Conclusion: Overall, we developed and validated a generalizable and easy-to-use COVID-19 severity stratification model using machine learning algorithms. The level of cDCs and LDH will assist clinicians in making quick decisions during future pandemics.

Abdominal physical examinations in early stages benefit critically ill patients without primary gastrointestinal diseases: a retrospective cohort study.

Background: Gastrointestinal (GI) function is critical for patients in intensive care units (ICUs). Whether and how much critically ill patients without GI primary diseases benefit from abdominal physical examinations remains unknown. No evidence from big data supports its possible additive value in outcome prediction. Methods: We performed a big data analysis to confirm the value of abdominal physical examinations in ICU patients without GI primary diseases. Patients were selected from the Medical Information Mart for Intensive Care (MIMIC)-IV database and classified into two groups depending on whether they received abdominal palpation and auscultation. The primary outcome was the 28-day mortality. Statistical approaches included Cox regression, propensity score matching, and inverse probability of treatment weighting. Then, the abdominal physical examination group was randomly divided into the training and testing cohorts in an 8:2 ratio. And patients with GI primary diseases were selected as the validation group. Several machine learning algorithms, including Random Forest, Gradient Boosting Decision Tree, Adaboost, Extra Trees, Bagging, and Multi-Layer Perceptron, were used to develop in-hospital mortality predictive models. Results: Abdominal physical examinations were performed in 868 (2.63%) of 33,007 patients without primary GI diseases. A significant benefit in terms of 28-day mortality was observed among the abdominal physical examination group (HR 0.75, 95% CI 0.56-0.99; p = 0.043), and a higher examination frequency was associated with improved outcomes (HR 0.62, 95%CI 0.40-0.98; p = 0.042). Machine learning studies further revealed that abdominal physical examinations were valuable in predicting in-hospital mortality. Considering both model performance and storage space, the Multi-Layer Perceptron model performed the best in predicting mortality (AUC = 0.9548 in the testing set and AUC = 0.9833 in the validation set). Conclusion: Conducting abdominal physical examinations improves outcomes in critically ill patients without GI primary diseases. The results can be used to predict in-hospital mortality using machine learning algorithms.

Advanced multifunctional hydrogels for diabetic foot ulcer healing: Active substances and biological functions.

AIM: Hydrogels with excellent biocompatibility and biodegradability can be used as the desirable dressings for the therapy of diabetic foot ulcer (DFU). This review aimed to summarize the biological functions of hydrogels, combining with the pathogenesis of DFU. METHODS: The studies in the last 10 years were searched and summarized from the online database PubMed using a combination of keywords such as hydrogel and diabetes. The biological functions of hydrogels and their healing mechanism on DFU were elaborated. RESULTS: In this review, hydrogels were classified by their active substances such as drugs, cytokines, photosensitizers, and biomimetic peptide. Based on this, the biological functions of hydrogels were summarized by associating the pathogenesis of DFU, including oxidative stress, chronic inflammation, cell phenotype change, vasculopathy, and infection. This review also pointed out some of the shortcomings of hydrogels in present researches. CONCLUSIONS: Hydrogels were classified into carrier hydrogels and self-functioning hydrogels in this review. Besides, the functions and components of existing hydrogels were clarified to provide assistance for future researches and clinical applications.

Terahertz-triggered ultrafast nonlinear optical activities in two-dimensional centrosymmetric PtSe2.

The nonlinear mechanisms of polarization and optical fields can induce extensive responses in materials. In this study, we report on two kinds of nonlinear mechanisms in the topological semimetal PtSe2 crystal under the excitation of intense terahertz (THz) pulses, which are manipulated by the real and imaginary parts of the nonlinear susceptibility of PtSe2. Regarding the real part, the broken inversion symmetry of PtSe2 is achieved through a THz-electric-field polarization approach, which is characterized by second harmonic generation (SHG) measurements. The transient THz-laser-induced SHG signal occurs within 100 fs and recombines to the equilibrium state within 1 ps, along with a high signal-to-noise ratio (∼51 dB) and a high on/off ratio (∼102). Regarding the imaginary part, a nonlinear absorption change can be generated in the media. We reveal a THz-induced absorption enhancement in PtSe2 via nonlinear transmittance measurements, and the sheet conductivity can be modulated up to 42% by THz electric fields in our experiment. Therefore, the THz-induced ultrafast nonlinear photoresponse reveals the application potential of PtSe2 in photonic and optoelectronic devices in the THz technology.

Continuous tuning of pulse parameters in a soliton fiber laser by adjusting the effect of nonlinear polarization rotation: publisher's note.

This publisher's note contains a correction to Opt. Lett.49, 674 (2024)10.1364/OL.509981.

Characteristics of broadband OPCPA based on DKDP crystals with different deuterations for the SEL-100 PW laser system.

We present the performances of a broadband optical parametric chirped pulse amplification (OPCPA) using partially deuterated potassium dihydrogen phosphate (DKDP) crystals with deuteration levels of 70% and 98%. When pumped by a Nd:glass double frequency laser, the OPCPA system using the 98% deuterated DKDP crystal achieves a broad bandwidth of 189 nm (full width at 1/e2 maximum) from 836 nm to 1025 nm. For the DKDP crystal with length of 43 mm, the pump-to-signal conversion efficiency reaches 28.4% and the compressed pulse duration is 13.7 fs. For a 70% deuterated DKDP crystal with a length of 30 mm, the amplified spectrum ranges from 846-1021 nm, the compressed pulse duration is 15.7 fs, and the conversion efficiency is 25.5%. These results demonstrate the potential of DKDP crystals with higher deuteration as promising nonlinear crystals for use as final amplifiers in 100 Petawatt (PW) laser systems, supporting compression pulse duration shorter than 15 fs.

Continuous tuning of pulse parameters in a soliton fiber laser by adjusting the effect of nonlinear polarization rotation.

We demonstrate that through inserting a short length of highly birefringent small-core photonic crystal fiber (Hi-Bi SC-PCF) into a soliton fiber laser, the nonlinear polarization rotation effect in this laser can be manipulated, leading to continuous tuning of the output pulse parameters. In experiments, we observed that by adjusting the polarization state of light launched into the Hi-Bi SC-PCF and varying the cavity attenuation, the laser spectral width can be continuously tuned from ∼7.1 to ∼1.7 nm, corresponding to a pulse-width-tuning range from ∼350 fs to ∼1.56 ps. During the parameter tuning, the output pulses strictly follow the soliton area theory, giving an almost constant time-bandwidth-product of ∼0.31. This soliton fiber laser, being capable of continuous parameter tuning, could be applied as the seed source in ultrafast laser systems and may find some applications in nonlinear-optics and soliton-dynamics experiments.

Stable, intense supercontinuum light generation at 1 kHz by electric field assisted femtosecond laser filamentation in air.

Supercontinuum (SC) light source has advanced ultrafast laser spectroscopy in condensed matter science, biology, physics, and chemistry. Compared to the frequently used photonic crystal fibers and bulk materials, femtosecond laser filamentation in gases is damage-immune for supercontinuum generation. A bottleneck problem is the strong jitters from filament induced self-heating at kHz repetition rate level. We demonstrated stable kHz supercontinuum generation directly in air with multiple mJ level pulse energy. This was achieved by applying an external DC electric field to the air plasma filament. Beam pointing jitters of the 1 kHz air filament induced SC light were reduced by more than 2 fold. The stabilized high repetition rate laser filament offers the opportunity for stable intense SC generation and its applications in air.

Blood Urea Nitrogen-to-Albumin Ratio May Predict Mortality in Patients with Traumatic Brain Injury from the MIMIC Database: A Retrospective Study.

Traumatic brain injury (TBI), a major global health burden, disrupts the neurological system due to accidents and other incidents. While the Glasgow coma scale (GCS) gauges neurological function, it falls short as the sole predictor of overall mortality in TBI patients. This highlights the need for comprehensive outcome prediction, considering not just neurological but also systemic factors. Existing approaches relying on newly developed biomolecules face challenges in clinical implementation. Therefore, we investigated the potential of readily available clinical indicators, like the blood urea nitrogen-to-albumin ratio (BAR), for improved mortality prediction in TBI. In this study, we investigated the significance of the BAR in predicting all-cause mortality in TBI patients. In terms of research methodologies, we gave preference to machine learning methods due to their exceptional performance in clinical support in recent years. Initially, we obtained data on TBI patients from the Medical Information Mart for Intensive Care database. A total of 2602 patients were included, of whom 2260 survived and 342 died in hospital. Subsequently, we performed data cleaning and utilized machine learning techniques to develop prediction models. We employed a ten-fold cross-validation method to obtain models with enhanced accuracy and area under the curve (AUC) (Light Gradient Boost Classifier accuracy, 0.905 ± 0.016, and AUC, 0.888; Extreme Gradient Boost Classifier accuracy, 0.903 ± 0.016, and AUC, 0.895; Gradient Boost Classifier accuracy, 0.898 ± 0.021, and AUC, 0.872). Simultaneously, we derived the importance ranking of the variable BAR among the included variables (in Light Gradient Boost Classifier, the BAR ranked fourth; in Extreme Gradient Boost Classifier, the BAR ranked sixth; in Gradient Boost Classifier, the BAR ranked fifth). To further evaluate the clinical utility of BAR, we divided patients into three groups based on their BAR values: Group 1 (BAR < 4.9 mg/g), Group 2 (BAR ≥ 4.9 and ≤10.5 mg/g), and Group 3 (BAR ≥ 10.5 mg/g). This stratification revealed significant differences in mortality across all time points: in-hospital mortality (7.61% vs. 15.16% vs. 31.63%), as well as one-month (8.51% vs. 17.46% vs. 36.39%), three-month (9.55% vs. 20.14% vs. 41.84%), and one-year mortality (11.57% vs. 23.76% vs. 46.60%). Building on this observation, we employed the Cox proportional hazards regression model to assess the impact of BAR segmentation on survival. Compared to Group 1, Groups 2 and 3 had significantly higher hazard ratios (95% confidence interval (CI)) for one-month mortality: 1.77 (1.37-2.30) and 3.17 (2.17-4.62), respectively. To further underscore the clinical potential of BAR as a standalone measure, we compared its performance to established clinical scores, like sequential organ failure assessment (SOFA), GCS, and acute physiology score III(APS-III), using receiver operator characteristic curve (ROC) analysis. Notably, the AUC values (95%CI) of the BAR were 0.67 (0.64-0.70), 0.68 (0.65-0.70), and 0.68 (0.65-0.70) for one-month mortality, three-month mortality, and one-year mortality. The AUC value of the SOFA did not significantly differ from that of the BAR. In conclusion, the BAR is a highly influential factor in predicting mortality in TBI patients and should be given careful consideration in future TBI prediction research. The blood urea nitrogen-to-albumin ratio may predict mortality in TBI patients.

Research on the pre-pulses caused by post-pulses in the optical parametric chirped-pulse amplifier.

Pre-pulses caused by the post-pulses in the optical parametric chirped-pulse amplifier were comprehensively studied for the first time, including the underlying mechanism for the delay-shift of pre-pulses, the intensity variation of pre-pulses affected by the initial delay of post-pulses and the pump energy, and also the nonlinear beat noise. The simulation and measurement confirmed that the high-order dispersion of the pulse stretcher was the main cause for the delay-shift of pre-pulses, which should be similar with the chirped-pulse amplifiers. The intensity of pre-pulses would decrease significantly as the initial delay of post-pulses increased, but would increase with the growth of pump energy. Moreover, the temporal position of the nonlinear beat noise in the experiment was successfully predicted by our simulation. This work could help us better understand the pre-pulses in OPCPA and provide helpful guidance for designing high-contrast laser systems.

Experimental studies on the core-structure dependence of backward Brillouin gain in solid-core photonic crystal fibers.

Stimulated Brillouin scattering (SBS) in solid-core photonic crystal fibers (PCFs) differs significantly from that in standard optical fibers due to the tight confinement of both optical and acoustic fields in their µm-sized fiber cores, as resultantly evident in their Brillouin gain spectra. Despite many theoretical studies based on either simplified models or numerical simulations, the structural dependency of Brillouin gain spectra in small-core PCFs has not been characterized comprehensively using PCFs with elaborated parameter controls. In this work we report a comprehensive characterization on the core-structure dependences of backward SBS effects in solid-core PCFs that are drawn with systematically varied core-diameter, revealing several key trends of the fiber Brillouin spectrum in terms of its gain magnitude, Brillouin shift and multi-peak structure, which have not been reported in detail previously. Our work provides some practical guidance on PCF design for potential applications like Brillouin fiber lasers and Brillouin fiber sensing.

Tellurium-Doped 0D Organic-Inorganic Hybrid Lead-Free Perovskite for X-ray Imaging.

The application of X-ray imaging in military, industrial flaw detection, and medical examination is inseparable from the wide application of scintillator materials. In order to substitute for lead, lower costs, and reduce self-absorption, organic-inorganic hybrid lead-free perovskite scintillators are emerging as a new option. In this work, novel (TEA)2Zr1-xTexCl6 perovskite microcrystals (MCs) were successfully synthesized by a hydrothermal method, with Te4+ doping, which leads to yellow triplet-state self-trapped excitons emission. The emission peak of (TEA)2Zr1-xTexCl6 located at 605 nm under X-ray excitation, which was applied to X-ray imaging, shows a clear wiring structure inside the USB connector. The detection limit (DL) of 820 nGyair/s for (TEA)2Zr0.9Te0.1Cl6 is well below the dose rate corresponding to a standard medical X-ray diagnosis is 5.5 µGyair/s. This work opens up a new path for organic-inorganic hybrid lead-free scintillators.

Delay-shift and asymmetric broadening of pre-pulses by post-pulses in a petawatt laser facility.

The temporal contrast of high-peak-power lasers is usually limited by pre-pulses, which are generally produced by post-pulses due to the nonlinearity of the active medium. The reason for the conversion between pre-pulse and post-pulse is now well known, but the mechanisms for the delay-shift and asymmetric broadening of the newly generated pre-pulse are not yet clear. In this work, a novel, to the best of our knowledge, numerical model combining the nonlinear Schrödinger equation and the Frantz-Nodvik equation is proposed to investigate the underlying mechanisms for the "distortion" of the pre-pulse. Numerical results show that the gain characteristics of Ti:sapphire amplifiers can only make a minor change on the temporal profile of the pre-pulse, but the high-order dispersion is the main cause for the delay-shift and asymmetric broadening of the pre-pulse, and the effects are more significant for the initial post-pulse with a relatively larger delay.

Beam smoothing by introducing spatial dispersion for high-peak-power laser pulse compression.

Post-compression can effectively further improve the peak power of laser pulses by shortening the pulse duration. Which has been investigated in various ranges of energy and central wavelength. However, the spatial intensity profile of high-peak-power laser pulses is generally inhomogeneous due to pump lasers, imperfect optical components, and dust in the optical layout. In post-compression, the B-integral is proportional to intensity, and wavefront distortions are induced in the spectral broadening stage, leading to a decrease in focusing intensity. Moreover, the beam intensity may be strongly modulated and beam inhomogeneity will be intensified in this process, causing damage to optical components and limiting the achievement of high peak power enhancement. In this study, to address these challenges, the laser pulse is first smoothed by introducing spatial dispersion using prism pairs or asymmetric four-grating compressors, and then the smoothed pulse is used for post-compression. The simulation results indicate that this method can effectively remove hot spots from laser pulses and maintain high peak power enhancement in post-compression.

Water-Resistant Subwavelength Perovskite Lasing from Transparent Silica-Based Nanocavity.

Great research efforts are devoted to exploring the miniaturization of chip-scale coherent light sources possessing excellent lasing performance. Despite the indispensable role in Si photonics, SiO2 is generally considered not contributing to the starting up and operation of integrated lasers. Here, this work demonstrates an extraordinary-performance subwavelength-scale perovskite vertical cavity laser with all-transparent SiO2 cavity, whose cavity is ultra-simple and composed of only two parallel SiO2 plates. By introducing a ligand-assisted thermally co-evaporation strategy, highly luminescent perovskite film with high reproducibility and excellent optical gain is grown directly on SiO2 . Benefitting from their high-refractive-index contrast, low-threshold, high-quality factor, and single-mode lasing is achieved in subwavelength range of ≈120 nm, and verified by long-range coherence distance (115.6 µm) and high linear polarization degree (82%). More importantly, the subwavelength perovskite laser device could operate in water for 20 days without any observable degradation, exhibiting ultra-stable water-resistant performance. These findings would provide a simple but robust and reliable strategy for the miniaturized on-chip lasers compatible with Si photonics.

Research on the biological mechanism and potential application of CEMIP.

Cell migration-inducing protein (CEMIP), also known as KIAA1199 and hyaluronan-binding protein involved in hyaluronan depolymerization, is a new member of the hyaluronidase family that degrades hyaluronic acid (HA) and remodels the extracellular matrix. In recent years, some studies have reported that CEMIP can promote the proliferation, invasion, and adhesion of various tumor cells and can play an important role in bacterial infection and arthritis. This review focuses on the pathological mechanism of CEMIP in a variety of diseases and expounds the function of CEMIP from the aspects of inhibiting cell apoptosis, promoting HA degradation, inducing inflammatory responses and related phosphorylation, adjusting cellular microenvironment, and regulating tissue fibrosis. The diagnosis and treatment strategies targeting CEMIP are also summarized. The various functions of CEMIP show its great potential application value.

Ionic Solvent-Assisted MAPbBr3 Perovskite Film for Two-Photon Pumped Single-Mode Laser.

Miniaturized coherent light sources on the nanoscale are highly desired for on-chip photonics integration. However, when approaching the diffraction limit, the sub-wavelength-scale all-dielectric lasers are difficult to realize due to the trade-off between lasing performance and physical size. Especially for a thin-film laser, usually an externally complex cavity is required to provide the necessary optical feedback. Herein, we successfully shrink the MAPbBr3 perovskite thin-film laser to sub-wavelength scale (300 nm) with simplified cavity design using only an ultraviolet glue layer and a quartz glass. The morphology quality and the gain properties of the film are enhanced by introducing ionic liquid. Consequently, the stable and low-threshold single-mode laser with a highly linear polarization degree of 78.6% and a narrow line width of 0.35 nm is achieved under two-photon excitation. The excellent single-mode laser with sub-wavelength scale and ultrasimplified structure could provide a facile and versatile platform for future integrated optoelectronic devices.

Intense ultraviolet-visible-infrared full-spectrum laser.

A high-brightness ultrabroadband supercontinuum white laser is desirable for various fields of modern science. Here, we present an intense ultraviolet-visible-infrared full-spectrum femtosecond laser source (with 300-5000 nm 25 dB bandwidth) with 0.54 mJ per pulse. The laser is obtained by sending a 3.9 µm, 3.3 mJ mid-infrared pump pulse into a cascaded architecture of gas-filled hollow-core fiber, a bare lithium niobate crystal plate, and a specially designed chirped periodically poled lithium niobate crystal, under the synergic action of second and third order nonlinearities such as high harmonic generation and self-phase modulation. This full-spectrum femtosecond laser source can provide a revolutionary tool for optical spectroscopy and find potential applications in physics, chemistry, biology, material science, industrial processing, and environment monitoring.

[A new target of precision medicine in sepsis: gut microbiome modified tryptophan metabolism].

Sepsis is a life-threatening organ dysfunction caused by dysregulated host responses to infection. Despite significant advances in anti-infective, immunomodulatory, and organ function support technologies, the precise and targeted management of sepsis remains a challenge due to its high heterogeneity. Studies have identified disturbed tryptophan (TRP) metabolism as a common mechanism in multiple diseases, which is involved in both immune regulation and the development of multi-organ damages. The rise of research on intestinal microflora has further highlighted the critical role of microflora-regulated TRP metabolism in pathogen-host interactions and the "cross-talk" among multi-organs, making it a potential key target for precision medicine in sepsis. This article reviews TRP metabolism, the regulation of TRP metabolism by the intestinal microflora, and the characteristics of TRP metabolism in sepsis, providing clues for further clinical targeting of TRP metabolism for precision medicine in sepsis.

Ultra-broad bandwidth low-dispersion mirror with smooth dispersion and high laser damage resistance.

Low-dispersion mirrors (LDMs), which require a broad bandwidth, low dispersion, and high damage threshold, are essential optics in ultra-intense and ultra-short laser devices. Bragg mirrors and chirped LDMs do not satisfy these requirements simultaneously. We propose a novel LDM (NLDM) based on the hump-like structure and quarter wavelength optical thickness (QWOT) structure to achieve a broad bandwidth, smooth dispersion, and high robustness. The spectral and dispersion characteristics of the two structures compensate for each other, which makes up for the deficiency that the dispersion bandwidth of the sinusoidal modulation structure cannot be broadened. Based on this structure, the LDM can achieve a design bandwidth of 240 nm and support the transmission of sub-11-fs pulses. The accuracy of the NLDM is experimentally evaluated. The structure shows the potential for broad-spectrum laser damage performance due to the low electric field intensity. The NLDM improves the mirror performance and paves the way for a new generation of ultra-intense and ultra-short laser devices.