Associations of nirmatrelvir-ritonavir treatment with death and clinical improvement in hospitalized patients with COVID-19 during the Omicron wave in Beijing, China: a multicentre, retrospective cohort study.

BACKGROUND: The effectiveness of nirmatrelvir-ritonavir has mainly been shown in non-hospitalized patients with mild-to-moderate coronavirus disease 2019 (COVID-19). The real-world effectiveness of nirmatrelvir-ritonavir urgently needs to be determined using representative in-hospital patients with COVID-19 during the Omicron wave of the pandemic. METHODS: We performed a multicentre, retrospective study in five Chinese PLA General Hospital medical centers in Beijing, China. Patients hospitalized with COVID-19 from 10 December 2022 to 20 February 2023 were eligible for inclusion. A 1:1 propensity score matching was performed between the nirmatrelvir-ritonavir group and the control group. RESULTS: 1010 recipients of nirmatrelvir-ritonavir and 1010 matched controls were finally analyzed after matching. Compared with matched controls, the nirmatrelvir-ritonavir group had a lower incidence rate of all-cause death (4.6/1000 vs. 6.3/1000 person-days, p = 0.013) and a higher incidence rate of clinical improvement (47.6/1000 vs. 45.8/1000 person-days, p = 0.012). Nirmatrelvir-ritonavir was associated with a 22% lower all-cause mortality and a 14% higher incidence of clinical improvement. Initiation of nirmatrelvir-ritonavir within 5 days after symptom onset was associated with a 50% lower mortality and a 26% higher clinical improvement rate. By contrast, no significant associations were identified among patients receiving nirmatrelvir-ritonavir treatment more than 5 days after symptom onset. Nirmatrelvir-ritonavir was also associated with a 50% increase in survival days and a 12% decrease in days to clinical improvement. CONCLUSION: Among hospitalized patients with COVID-19 during the Omicron wave in Beijing, China, the early initiation of nirmatrelvir-ritonavir was associated with clinical benefits of lowering mortality and improving clinical recovery.

Real-world effectiveness of nirmatrelvir-ritonavir versus azvudine in hospitalized patients with COVID-19 during the omicron wave in Beijing: a multicenter retrospective cohort study.

BACKGROUND AND AIM: Two oral antivirals (Nirmatrelvir- ritonavir and Azvudine) are widely used in China practice during the Omicron wave of the pandemic. However, little evidence regarding the real-world effectiveness of these two oral antivirals in in-hospital patients. We aimed to evaluate the clinical effectiveness of nirmatrelvir-ritonavir versus azvudine among adult hospitalized patients with COVID-19. METHODS: This retrospective cohort study used data from three Chinese PLA General Hospital medical centres. Hospitalized patients with COVID-19 treated with azvudine or nirmatrelvir-ritonavir from Dec 10, 2022, to February 20, 2023, and did not require invasive ventilation support on admission were eligible for inclusion. RESULTS: After exclusions and propensity-score matching, the final analysis included 486 azvudine recipients and 486 nirmatrelvir-ritonavir recipients. By 28 days of initiation of the antivirus treatment, the crude incidence rate of all-cause death was similar in both types of antivirus treatment (nirmatrelvir-ritonavir group 2.8 events 1000 person-days [95% CI, 2.1-3.6] vs azvudine group 3.4 events/1000 person-days [95% CI, 2.6-4.3], P = 0.38). Landmark analysis showed that all-cause death was lower in the nirmatrelvir-ritonavir (3.5%) group than the azvudine (6.8%, P = 0.029) within the initial 10-day admission period, while no significant difference was observed for results between 10 and 28 days follow-up. There was no significant difference between the nirmatrelvir-ritonavir group and the azvudine group in cumulative incidence of the composite disease progression event (8.6% with nirmatrelvir-ritonavir vs. 10.1% with azvudine, HR, 1.22; 95% CI 0.80-1.86, P = 0.43). CONCLUSION: Among patients hospitalized with COVID-19 during the omicron wave in Beijing, similar in-hospital clinical outcomes on 28 days were observed between patients receiving nirmatrelvir-ritonavir and azvudine. However, it is worth noticing that nirmatrelvir-ritonavir appears to hold an advantage over azvudine in reducing early mortality. Further randomized controlled trials are needed to verify the efficacy of those two antivirus medications especially in early treatment.

An In Vitro Assessment Method for Chemotherapy-Induced Peripheral Neurotoxicity Caused by Anti-Cancer Drugs Based on Electrical Measurement of Impedance Value and Spontaneous Activity.

Chemotherapy-induced peripheral neurotoxicity (CIPN) is a major adverse event of anti-cancer drugs, which still lack standardized measurement and treatment methods. In the present study, we attempted to evaluate neuronal dysfunctions in cultured rodent primary peripheral neurons using a microelectrode array system. After exposure to typical anti-cancer drugs (i.e., paclitaxel, vincristine, oxaliplatin, and bortezomib), we successfully detected neurotoxicity in dorsal root ganglia neurons by measuring electrical activities, including impedance value and spontaneous activity. The impedance value decreased significantly for all compounds, even at low concentrations, which indicated cell loss and/or neurite degeneration. The spontaneous activity was also suppressed after exposure, which suggested neurotoxicity again. However, an acute response was observed for paclitaxel and bortezomib before toxicity, which showed different mechanisms based on compounds. Therefore, MEA measurement of impedance value could provide a simple assessment method for CIPN, combined with neuronal morphological changes.

Development of an In Vitro Assessment Method for Chemotherapy-Induced Peripheral Neuropathy (CIPN) by Integrating a Microphysiological System (MPS) with Morphological Deep Learning of Soma and Axonal Images.

Several anticancer drugs used in cancer therapy induce chemotherapy-induced peripheral neuropathy (CIPN), leading to dose reduction or therapy cessation. Consequently, there is a demand for an in vitro assessment method to predict CIPN and mechanisms of action (MoA) in drug candidate compounds. In this study, a method assessing the toxic effects of anticancer drugs on soma and axons using deep learning image analysis is developed, culturing primary rat dorsal root ganglion neurons with a microphysiological system (MPS) that separates soma from neural processes and training two artificial intelligence (AI) models on soma and axonal area images. Exposing the control compound DMSO, negative compound sucrose, and known CIPN-causing drugs (paclitaxel, vincristine, oxaliplatin, suramin, bortezomib) for 24 h, results show the somatic area-learning AI detected significant cytotoxicity for paclitaxel (* p < 0.05) and oxaliplatin (* p < 0.05). In addition, axonal area-learning AI detected significant axonopathy with paclitaxel (* p < 0.05) and vincristine (* p < 0.05). Combining these models, we detected significant toxicity in all CIPN-causing drugs (** p < 0.01) and could classify anticancer drugs based on their different MoA on neurons, suggesting that the combination of MPS-based culture segregating soma and axonal areas and AI image analysis of each area provides an effective evaluation method to predict CIPN from low concentrations and infer the MoA.

Protocol of a multicenter, single-blind, randomized, parallel controlled trial evaluating the effect of microbiological rapid on-site evaluation (M-ROSE) guiding anti-infection treatment in patients with severe hospital-acquired pneumonia.

INTRODUCTION: The mortality rate of hospitalized patients with severe hospital-acquired pneumonia (SHAP) remains high. Empirical broad-spectrum antibiotic coverage and the misuse of high-grade antibiotics could lead to the emergence of multi-drug and even pandrug-resistant bacteria. In addition to metagenomic next-generation sequencing (mNGS), microbiological rapid on-site evaluation (M-ROSE) might be a useful technique to identify the pathogens in the early stage; however, the effect of M-ROSE guiding anti-infection treatment on prognostic outcomes of SHAP patients is still unclear. METHODS/DESIGN: This is a multicenter, single-blind, prospective, randomized controlled trial to evaluate the effect of M-ROSE guiding anti-infection treatment in SHAP patients, which will provide new strategies for the prevention and control of clinical multi-drug resistance bacteria. A total of 166 patients with SHAP, aged 18 years and over, will be recruited from seven centers in Beijing and randomly assigned to the intervention group (M-ROSE combined with mNGS) or the control group (mNGS only) in a 1:1 ratio using the central randomization system. Patients in the intervention group will accept M-ROSE and mNGS analysis, and the control group will accept mNGS analysis. Individualized anti-infective treatment and routine treatment will be selected according to the analysis results. The primary outcome is the ICU outcome (mortality). The safety of the intervention measures will be evaluated during the entire trial period. This trial will be the first randomized controlled trial to evaluate the effect of M-ROSE guiding treatment on mortality in patients with SHAP and may change the prevalence of multi-drug resistant bacteria. ETHICS AND DISSEMINATION: This trial adheres to the Declaration of Helsinki and guidelines of Good Clinical Practice. Signed informed consent will be obtained from all participants. The trial has been approved by the Chinese PLA General Hospital (Approval Number: 20220322001). TRIAL REGISTRATION: ClinicalTrials.gov NCT05300776. Registered on 25 March 2022.

Anchoring Bi2S3 quantum dots on flower-like TiO2 nanostructures to boost photoredox coupling of H2 evolution and oxidative organic transformation.

The rational integration of semiconductor quantum dots (QDs) with anatase TiO2 nanostructures is a promising strategy to develop efficient photocatalysts. Herein, Bi2S3QD/TiO2 photocatalyst was constructed by controllably depositing Bi2S3 QDs on flower-like TiO2 nanostructures and used for the photocatalytic redox-coupling reaction of H2 evolution and oxidative transformation of benzyl alcohol. The abundant amino groups in TiO2 nanostructures served as the anchoring sites for uniform growth of Bi2S3 QDs. The anchoring of Bi2S3 QDs onto TiO2 nanostructures not only enhanced the photoabsorption ability and the photogenerated charge separation efficiency but also afforded powerful photogenerated charge carriers and abundant active sites for the photocatalytic reaction. As a result, the Bi2S3QD/TiO2 photocatalyst exhibited a favorable performance in the redox-coupling reaction, providing the high production rates of H2 up to 4.75 mmol·gcat-1·h-1 and benzaldehyde up to 6.12 mmol·gcat-1·h-1, respectively, as well as an excellent stability in the long-term photocatalytic reaction. Meanwhile, a trace amount of water in the reaction system could act as a promoter to accelerate the photocatalytic redox-coupling reaction. The photocatalytic mechanism following S-scheme heterojunction was proposed according to the systematic characterizations and experimental results. This work offers some insight into the rational construction of efficient and cost-effective photocatalysts for the conversion of solar to chemical energy.

Large-Area Field Potential Imaging Having Single Neuron Resolution Using 236 880 Electrodes CMOS-MEA Technology.

The electrophysiological technology having a high spatiotemporal resolution at the single-cell level and noninvasive measurements of large areas provide insights on underlying neuronal function. Here, a complementary metal-oxide semiconductor (CMOS)-microelectrode array (MEA) is used that uses 236 880 electrodes each with an electrode size of 11.22 × 11.22 µm and 236 880 covering a wide area of 5.5 × 5.9 mm in presenting a detailed and single-cell-level neural activity analysis platform for brain slices, human iPS cell-derived cortical networks, peripheral neurons, and human brain organoids. Propagation pattern characteristics between brain regions changes the synaptic propagation into compounds based on single-cell time-series patterns, classification based on single DRG neuron firing patterns and compound responses, axonal conduction characteristics and changes to anticancer drugs, and network activities and transition to compounds in brain organoids are extracted. This detailed analysis of neural activity at the single-cell level using the CMOS-MEA provides a new understanding of the basic mechanisms of brain circuits in vitro and ex vivo, on human neurological diseases for drug discovery, and compound toxicity assessment.

Revealing EXPH5 as a potential diagnostic gene biomarker of the late stage of COPD based on machine learning analysis.

Chronic obstructive pulmonary disease is a kind of chronic lung disease characterized by persistent air flow obstruction, which was the third leading cause of death in China. The incidence of COPD is steadily and increasing and has been a globally sever disease. Accordingly, it is urgently needed to explore how to diagnose and treat COPD timely. This study aims to find key genes to diagnose COPD as soon as possible to avoid COPD processing and analyze immune cell infiltration between COPD early stage and late stage. Two GEO datasets were merged as the merge data for analyses. 157 DEGs were used for GSEA analysis to find the pathway between COPD early stage and late stage. Above all, gene EXPH5 stood out from the screen as the most likely candidate diagnosis biomarker of COPD indicating the late-stage by least LASSO and SVM-RFE. ROC curves of EXPH5 were applied to represent the discriminatory ability through the area under the curve which is the gold standard to evaluate the accuracy of diagnosis and survival rate. The CIBERSORT algorithm was used to assess the distribution of tissue-infiltrating immune cells between two COPD stages. The diagnosis biomarker, gene EXPH5 had a positive correlation with NK cells resting; mast cell resting, eosinophils, and negative correlation with T cell gamma delta, macrophages M1, which underscore the role of gene and immune cell infiltration. To make results more reliable, we further analyzed the gene EXPH5 expression in single-cell transcriptome data and showed again that EXPH5 genes significantly downregulated in the late stage of COPD especially in the main lung cell types AT1 and AT2. In a word, our study identified genes EXPH5 as a marker gene, which adds to the knowledge for clinical diagnosis and pharmaceutical design of COPD.

Multiband tunable exciton-induced transparencies: Exploiting both strong and intermediate coupling in a nanocube-hexagonal-nanoplate heterodimer J-aggregates hybrid.

Understanding and mastering the light-light and light-matter interactions in coupled structures have become significant subjects, as they provide versatile tools for manipulating light in both classical and quantum regimes. Mimicking quantum interference effects in pure photonic nanostructures, from weak Fano dip to intense electromagnetically induced transparency, usually requires strong asymmetries in complex geometries and larger interactions between resonances, i.e., in the intermediate coupling regime. Here, we numerically demonstrate a simple and chemically feasible plasmonic nanocube-hexagonal-nanoplate heterodimer with a strong, tunable self-induced transparency window created by the intermediate coupling between the near-degenerate dark and bright hybridized modes. Further assisted by the strong coupling introduced by the J-aggregate excitons covering the heterodimer, three evident exciton-induced transparency windows were observed. These multiband transparencies in a single-particle-level subwavelength configuration, could on one hand enrich the toolbox of multi-frequency light filtering, slowing and switching beyond the diffraction limit, and on the other hand, work as a fundamental testbed for investigating multiscale light-matter interactions at the nanoscale.

A functional neuron maturation device provides convenient application on microelectrode array for neural network measurement.

BACKGROUND: Microelectrode array (MEA) systems are valuable for in vitro assessment of neurotoxicity and drug efficiency. However, several difficulties such as protracted functional maturation and high experimental costs hinder the use of MEA analysis requiring human induced pluripotent stem cells (hiPSCs). Neural network functional parameters are also needed for in vitro to in vivo extrapolation. METHODS: In the present study, we produced a cost effective nanofiber culture platform, the SCAD device, for long-term culture of hiPSC-derived neurons and primary peripheral neurons. The notable advantage of SCAD device is convenient application on multiple MEA systems for neuron functional analysis. RESULTS: We showed that the SCAD device could promote functional maturation of cultured hiPSC-derived neurons, and neurons responded appropriately to convulsant agents. Furthermore, we successfully analyzed parameters for in vitro to in vivo extrapolation, i.e., low-frequency components and synaptic propagation velocity of the signal, potentially reflecting neural network functions from neurons cultured on SCAD device. Finally, we measured the axonal conduction velocity of peripheral neurons. CONCLUSIONS: Neurons cultured on SCAD devices might constitute a reliable in vitro platform to investigate neuron functions, drug efficacy and toxicity, and neuropathological mechanisms by MEA.

Chiral Third-Harmonic Metasurface for Multiplexed Holograms.

Chiral nonlinear metasurfaces could natively synergize nonlinear wavefront manipulation and circular dichroism, offering enhanced capacity for multifunctional and multiplexed nonlinear metasurfaces. However, it is still quite challenging to simultaneously enable strong chiral response, precise wavefront control, high nonlinear conversion efficiency, and independent functions on spins and chirality. Here, we propose and experimentally demonstrate multiplexed third-harmonic (TH) holograms with four channels based on a chiral Au-ZnO hybrid metasurface. Specifically, the left- and right-handed circularly polarized (LCP and RCP) components of the TH holographic images can be designed independently under the excitation of an LCP (or RCP) fundamental beam. In addition, the TH conversion efficiency is measured to be as large as 10-5, which is 8.6 times stronger than that of a bare ZnO film with the same thickness. Thus, our work provides a promising platform for realizing efficient and multifunctional nonlinear nanodevices.

Factors Influencing the Sample Adequacy of Ultrasound-Guided Fine-Needle Aspiration from Solid Thyroid Nodules for Liquid-Based Cytology: A Demographic, Sonographic, and Technical Perspective.

Background and Objectives: To identify factors that influence the sample adequacy of solid thyroid nodules based on ultrasound-guided fine-needle aspiration (FNA) with subsequent liquid-based cytology. Materials and Methods: We retrospectively reviewed 855 patients who underwent ultrasound-guided FNA at our hospital between July 2019 and July 2020. The final analysis included 801 solid thyroid nodules in 801 patients. After reviewing the demographic data, ultrasonic features, and FNA technique-related factors, we defined 14 potential variables. For cytological results, the Bethesda categories II−VI were defined as adequate sample results. Univariate and multivariate analyses were performed to identify factors that influenced sample adequacy. Results: The adequate sample rate was 87.1%. The univariate analysis showed that four factors were related to adequate sampling in patients with thyroid FNA. These factors included age (p < 0.001), nodule orientation (p = 0.0232), calcification (p = 0.0034), and operator experience (p = 0.0286). After the multivariate analysis, five independent factors were identified to improve the diagnostic results of FNA for solid thyroid nodules: (1) the presence of Hashimoto's thyroiditis (odds ratio (OR) = 1.810; 95% confidence interval (CI): 1.076−3.045; p = 0.0254), (2) a taller-than-wide orientation (OR = 2.038; 95% CI: 1.260−3.296; p = 0.0037), (3) the presence of calcification (OR = 1.767; 95% CI: 1.115−2.799; p = 0.0153), (4) four needle passes to obtain material (OR = 1.750; 95% CI: 1.094−2.799; p = 0.0196), and (5) an experienced operator (OR = 0.561; 95% CI: 0.319−0.987; p = 0.0451). Conclusions: A taller-than-wide orientation, the presence of calcification, and the presence of Hashimoto's thyroiditis were found to affect the sample adequacy of ultrasound-guided FNA with liquid-based cytology. The sample adequacy could be improved when FNA is performed with four needle passes by experienced doctors.

MicroRNA-206 down-regulated human umbilical cord mesenchymal stem cells alleviate cognitive decline in D-galactose-induced aging mice.

BACKGROUND: Non-pathological cognitive decline is a neurodegenerative condition associated with brain aging owing to epigenetic changes, telomere shortening, stem cells exhaustion, or altered differentiation. Human umbilical cord mesenchymal stem cells (hUCMSCs) have shown excellent therapeutic prospects on the hallmarks of aging. In this study, we aimed to elucidate the role of hUCMSCs with down-regulated miRNA-206 (hUCMSCs anti-miR-206) on cognitive decline and the underlying mechanism. METHODS: After daily subcutaneous injection of D-gal (500 mg/kg/d) for 8 weeks, 17-week-old male C57BL/6 J mice were stem cells transplanted by lateral ventricular localization injection. During the 10-day rest period, were tested the behavioral experiments applied to cognitive behavior in the hippocampus. And then, the mice were sacrificed for sampling to complete the molecular and morphological experiments. RESULTS: Our behavioral experiments of open field test (OFT), new object recognition test (NOR), and Y-maze revealed that D-galactose (D-gal)-induced aging mice treated with hUCMSCs anti-miR-206 had no obvious spontaneous activity disorder and had recovery in learning and spatial memory ability compared with the PBS-treated group. The hUCMSCs anti-miR-206 reconstituted neuronal physiological function in the hippocampal regions of the aging mice with an increase of Nissl bodies and the overexpression of Egr-1, BDNF, and PSD-95. CONCLUSION: This study first reports that hUCMSCs anti-miR-206 could provide a novel stem cell-based antiaging therapeutic approach.

Transcription factor EB-mediated mesenchymal stem cell therapy induces autophagy and alleviates spinocerebellar ataxia type 3 defects in neuronal cells model.

Defects in ataxin-3 proteins and CAG repeat expansions in its coding gene ATXN3 cause Spinocerebellar Ataxia Type 3 (SCA3) or Machado-Joseph disease (MJD) polyglutamine neurodegenerative disease. The mutant proteins aggregate as inclusion bodies in cells and compete with wild-type ataxin-3, which leads to neuronal dysfunction or death and impairs Beclin1-mediated autophagy. It has been reported that Mesenchymal stem cells (MSCs) can reliably treat several neurodegenerative diseases. Herein, we used a Transcription Factor EB (TFEB) nuclear translocation-mediated MSCs co-culture approach to reconstitute autophagy and lysosomal biogenesis, and reduce SCA3-like behaviors in induced pluripotent stem cells (iPSCs)-derived neuron cells models. Our iPSCs model showed enhanced expression of autophagy proteins, attenuated the expression and toxic effects of mutant ataxin-3 on neurons, and alleviated the effects of ataxin-3 on autophagy. Therefore, MSCs are associated with autophagy-inducing therapy and compared to animal models, our MSCs co-culture could be used as a novel and potential therapeutic approach to study SCA3 disease and other neurodegenerative diseases.

Synthesis of Fe3O4@CdS@CQDs ternary core-shell heterostructures as a magnetically recoverable photocatalyst for selective alcohol oxidation coupled with H2O2 production.

Photocatalytic aerobic oxidation of aromatic alcohols to corresponding aldehydes coupled with producing hydrogen peroxide (H2O2) represents one of the most efficient strategies for converting solar energy into chemical energy. In this work, a magnetically recoverable photocatalyst of Fe3O4@CdS@CQDs ternary core-shell heterostructures is elaborately fabricated through the hydrothermal growth of CdS on Fe3O4 nanospheres with in-situ incorporation of carbon quantum dots (CQDs) and used for selective alcohol oxidation coupled with H2O2 production. The Fe3O4@CdS@CQDs photocatalyst possess distinct advantages of full solar spectral absorption, efficient charge separation, and high stability. The Fe3O4-nanosphere cores not only endow photocatalyst with the characteristics of magnetic recovery but also form Fe3O4@CdS Z-scheme heterojunction to prevent CdS from photocorrosion. The in-situ modified CQDs act as charge mediators to accelerate the photogenerated electron-hole separation and afford active sites to facilitate H2O2 production. As a result, the Fe3O4@CdS@CQDs photocatalyst exhibits excellent performance in selectively converting benzyl alcohol to benzaldehyde accompanied with H2O2 production. The generation rates of benzaldehyde and H2O2 reach up to 57.22 and 27.06 mmol·gCdS-1·h-1, respectively. This work highlights a rational construction of magnetic heterostructure photocatalyst and its application in the photo-redox coupling reactions.

Giant optical anisotropy of WS2flakes in the visible region characterized by Au substrate assisted near-field optical microscopy.

Transition metal dichalcogenides (TMD) have attracted considerable attention in the field of photonic integrated circuits due to their giant optical anisotropy. However, on account of their inherent loss in the visible region and the difficulty of measuring high refractive index materials, near-field characterizations of the optical anisotropy of TMD in the visible region have inherent experimental difficulties. In this work, we present a systematical characterization of the optical anisotropy in tungsten disulfide (WS2) flakes by using scattering-type scanning near-field optical microscopy (s-SNOM) excited at 671 nm. Transverse-electric and transverse-magnetic (TM) waveguide modes can be excited in WS2flakes with suitable thickness, respectively. With the assistance of the Au substrate, the contrast of the near-field fringes is enhanced in comparison with the SiO2substrate. By combining waveguide mode near-field imaging and theoretical calculations, the in-plane and out-of-plane refractive indexes of WS2are determined to be 4.96 and 3.01, respectively, indicating a high birefringence value up to 1.95. This work offers experimental evidence for the potential application of WS2in optoelectronic integrated circuits in the visible region.

Pulmonary Embolism at Extreme High Altitude: A Study of Seven Cases.

Wu, Jialin, Xiaobo Han, Haiwen Ke, Li Wang, Kun Wang, Jianli Zhang, Jun Tang, Wei Yan, Guangjun Wang, and Peng Jiang. Pulmonary embolism at extreme high altitude: A study of seven cases. High Alt Med Biol. 23:209-214, 2022. Background: The incidence of venous thromboembolism (VTE) is high in high-altitude (HA) areas. We analyzed cases of pulmonary embolism (PE) in extreme HA areas to explore the epidemiological characteristics and risk factors of PE in these regions. Methods: Seven cases of PE occurring in an extreme HA region were prospectively collected at an HA (3,800 m) hospital from May to November 2020. All patients resided 5,000 m above sea level and were diagnosed with PE using computed tomography pulmonary angiography. Results: Seven patients (24 ± 3.6 years old) had symptom onset at a mean altitude of 5,200 ± 200 m, and the duration spent at HA ranged from 8 to 210 days (99.29 ± 77.31 days). Cough, expectoration, chest tightness, fever, shortness of breath, and chest pain were the most common symptoms. Six of the seven patients were initially diagnosed with pulmonary inflammation, and four were diagnosed with high-altitude pulmonary edema using computed tomography or X-ray. Most patients presented with an increased concentration of inflammatory cells and high initial D-dimer levels. Conclusions: In this study, a retrospective analysis of PE case data in extreme HA areas suggested that PE was underdiagnosed owing to misdiagnosis or masking by HA-associated disease.

Relationships of persistent depressive symptoms with subsequent lung function trajectory and respiratory disease mortality.

BACKGROUND: Little is known about the longitudinal association between persistent depressive symptoms and future lung health in the general population. METHOD: 4860 middle-aged and older participants with repeated measurements of depressive symptoms at wave 1 (2002-2003) and wave 2 (2004-2005) and at least two measurements of lung function (waves 2-6, 2004-2013) from the English Longitudinal Study of Ageing, were included in this study. The Center for Epidemiologic Studies Depression Scale (CESD) was used to evaluate depressive symptoms. Participants who had depressive symptoms in both waves 1 and 2 were considered to have persistent depressive symptoms. Linear mixed models were applied to assess longitudinal associations. Cox regression models were fitted to analyze respiratory disease mortality. RESULTS: During an 8-year follow-up, we found that women with persistent depressive symptoms suffered accelerated declines in forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), percentage of the FEV1 predicted, percentage of the FVC predicted, and peak expiratory flow, compared with women without depressive symptoms at baseline. Likewise, an elevated risk of respiratory disease mortality (HR: 6.02, 95% CI: 2.30 to 15.79) was observed in women with persistent depressive symptoms compared with women without depressive symptoms. We also observed a dose-response relationship between cumulative depressive symptom scores and subsequent lung health outcomes in women. However, no such association was observed in men. CONCLUSION: Long-term depressive symptoms might predict an accelerated decline of lung function and higher mortality from respiratory disease among women but not among men over an 8-year follow-up. Further studies are needed to verify our findings.

Mechanistic insights of CRISPR/Cas nucleases for programmable targeting and early-stage diagnosis: A review.

Conventional and routine diagnostics such as polymerase chain reaction (PCR) and serological tests are less sensitive, costly, and require sample pretreatment procedures. CRISPR/Cas systems that inherently assist bacteria and archaea in destroying invading phage genetic materials via an RNA-mediated interference strategy have been reconstituted in vitro and harnessed for nucleic and non-nucleic acid diagnostics. CRISPR/Cas-based diagnostics (CRISPR-Dx) are cost-effective, possess excellent sensitivity (attomolar) and specificity (single base distinction), exhibit fast turnaround response, and support nucleic acid extraction-free workflow. However, CRISPR-Dx still needs to address various challenges to translate the laboratory work into end-user tailored solutions. In this perspective, we review the relevant progress of CRISPR/Cas systems-based diagnostics, focusing on the comprehensive customization and applications of leading and trending CRISPR/Cas systems as platform technologies for fluorescence, colorimetric, and electrical signal detection. The impact of the CRISPR game-changing technology on the COVID-19 pandemic is highlighted. We also demonstrate the role of CRISPR/Cas systems for carryover contamination prevention. The advancements in signal amplification strategies using engineered crRNAs, novel reporters, nanoparticles, artificial genetic circuits, microfluidics, and smartphones are also covered. Furthermore, we critically discuss the translation of CRISPR-Dx's basic research into end-user diagnostics for commercialization success in the near future. Finally, we discuss the complex challenges and alternative solutions to harness the CRISPR/Cas potential in detail.