Atomically thin two-dimensional (2D) metals may be key ingredients in next-generation quantum and optoelectronic devices. However, 2D metals must be stabilized against environmental degradation and ...integrated into heterostructure devices at the wafer scale. The high-energy interface between silicon carbide and epitaxial graphene provides an intriguing framework for stabilizing a diverse range of 2D metals. Here we demonstrate large-area, environmentally stable, single-crystal 2D gallium, indium and tin that are stabilized at the interface of epitaxial graphene and silicon carbide. The 2D metals are covalently bonded to SiC below but present a non-bonded interface to the graphene overlayer; that is, they are 'half van der Waals' metals with strong internal gradients in bonding character. These non-centrosymmetric 2D metals offer compelling opportunities for superconducting devices, topological phenomena and advanced optoelectronic properties. For example, the reported 2D Ga is a superconductor that combines six strongly coupled Ga-derived electron pockets with a large nearly free-electron Fermi surface that closely approaches the Dirac points of the graphene overlayer.
Invadosomes are protrusive and mechanosensitive actin devices critical for cell migration, invasion, and extracellular matrix remodeling. The dynamic, proteolytic, and protrusive natures of ...invadosomes have made these structures fascinating and attracted many scientists to develop new technologies for their analysis. With these exciting methodologies, many biochemical and biophysical properties of invadosomes have been well characterized and appreciated, and those discoveries elegantly explained the biological and pathological effects of invadosomes in human health and diseases. In this review, we focus on these commonly used or newly developed methods for invadosome analysis and effort to reason some discrepancies among those assays. Finally, we explore the opposite regulatory mechanisms among invadosomes and focal adhesions, another actin‐rich adhesive structures, and speculate a potential rule for their switch.
Over the past decades, technologies aiming to probe the properties of subcellular structures have been developed and incorporated into the field of invadosome research. With the help of these technologies, scientists are now able to gain a deeper understanding of invadosomes and raise exciting unanswered questions. In this review, Lin et al. summarize the current knowledge on invadosomes, as well as commonly used and newly developed methods for invadosome analysis.
Several randomized controlled trials and real‐world cohort studies have demonstrated the efficacies of nirmatrelvir plus ritonavir (NMV‐r) and molnupiravir (MOV) in at‐risk patients with COVID‐19; ...however, the effectiveness of antisevere acute respiratory syndrome‐coronavirus 2 treatments on older patients (≥65 years) remains unclear. This retrospective cohort study aimed to assess the clinical effectiveness of the oral antiviral agents, MOV and NMV‐r, in older patients (≥65 years) infected with severe acute respiratory syndrome‐coronavirus 2. Nonhospitalized older patients with COVID‐19 between January 1, 2022, and December 31, 2022, were recruited from the TriNetX Research Network. Propensity score matching (PSM) was used to match patients who received either NMV‐r or MOV treatment with those who did not receive any oral antiviral agents. Hazard ratios (HRs) for composite all‐cause hospitalization or death during the 30‐day follow‐up period were calculated. PSM revealed two cohorts with 28 824 patients each having balanced baseline characteristics. The antiviral group was associated with significantly lower risk of the primary composite outcome of all‐cause hospitalization or death than the control group (241 vs. 801; HR, 0.307; 95% confidence interval (CI), 0.27–0.36) during the follow‐up period. For the secondary outcome, the antiviral group had a significantly lower risk of all‐cause hospitalization (288 vs. 725; HR, 0.322; 95% CI, 0.28–0.37) and mortality (16 vs. 94; HR, 0.176; 95% CI, 0.10–0.30) than the control group. Moreover, the reduced risk of all‐cause hospitalization or death remained consistent in patients receiving NMV‐r (HR, 0.279; 95% CI, 0.24–0.33) and MOV (HR, 0.279; 95% CI, 0.21–0.38). Our results revealed that NMV‐r and MOV decreased the all‐cause hospitalization and death rates among older patients with COVID‐19, supporting the use of antivirals in this vulnerable population.
This study assessed the clinical efficacy of nirmatrelvir plus ritonavir (NMV‐r) in treating patients with coronavirus disease‐2019 (COVID‐19) and substance use disorders (SUDs). This study included ...two cohorts: the first examined patients with SUDs, with and without a prescription for NMV‐r, while the second compared patients prescribed with NMV‐r, with and without a diagnosis of SUDs. SUDs were defined using ICD‐10 codes, related to SUDs, including alcohol, cannabis, cocaine, opioid, and tobacco use disorders (TUD). Patients with underlying SUDs and COVID‐19 were identified using the TriNetX network. We used 1:1 propensity score matching to create balanced groups. The primary outcome of interest was the composite outcome of all‐cause hospitalization or death within 30 days. Propensity score matching yielded two matched groups of 10 601 patients each. The results showed that the use of NMV‐r was associated with a lower risk of hospitalization or death, 30 days after COVID‐19 diagnosis (hazard ratio (HR), 0.640; 95% confidence interval (CI): 0.543–0.754), as well as a lower risk of all‐cause hospitalization (HR, 0.699; 95% CI: 0.592–0.826) and all‐cause death (HR, 0.084; 95% CI: 0.026–0.273). However, patients with SUDs had a higher risk of hospitalized or death within 30 days of COVID‐19 diagnosis than those without SUDs, even with the use of NMV‐r (HR, 1.783; 95% CI: 1.399–2.271). The study also found that patients with SUDs had a higher prevalence of comorbidities and adverse socioeconomic determinants of health than those without SUDs. Subgroup analysis showed that the benefits of NMV‐r were consistent across most subgroups with different characteristics, including age (patients aged ≥60 years HR, 0.507; 95% CI: 0.402–0.640), sex (women HR, 0.636; 95% CI: 0.517–0.783 and men HR, 0.480; 95% CI: 0.373–0.618), vaccine status (vaccinated <2 doses HR, 0.514; 95% CI: 0.435–0.608), SUD subtypes (alcohol use disorder HR, 0.711; 95% CI: 0.511– 0.988, TUD HR, 0.666; 95% CI: 0.555–0.800) and Omicron wave (HR, 0.624; 95% CI: 0.536–0.726). Our findings indicate that NMV‐r could reduce all‐cause hospitalization and death in the treatment of COVID‐19 among patients with SUDs and support the use of NMV‐r for treating patients with SUDs and COVID‐19.
Although a novel oral antiviral agent can improve short‐term COVID‐19 outcomes, its effects on the long‐term outcomes, namely the risk of major adverse cardiovascular events (MACEs), remains unknown. ...This retrospective cohort study used the TriNetX research network to identify nonhospitalized adult patients with COVID‐19 between March 1, 2020, and January 1, 2022. A propensity score matching method was used to form two matched cohorts with and without receiving nirmatrelvir–ritonavir (NMV‐r) or molnupiravir. The primary outcome was the incidence of MACEs within a 30‐day to 1‐year period following a diagnosis of COVID‐19. Two cohorts of each 80 888 patients with balanced baseline characteristics were formed using propensity score matching. During the follow‐up period, 976 patients in the study group and 1609 patients in the control group developed MACE. Overall, the study group had a significantly lower risk of MACE than the control group (hazard ratio HR, 0.683; 95% confidence interval: 0.630–0.739). The significantly lower HRs of overall MACEs were consistently observed in most subgroup analyses (age: >41–≤64 years: 0.60 0.52–0.89; age: ≥65 years: 0.68 0.62–0.76; women: 0.63 0.57–0.71; men: 0.62 0.55–0.70; vaccinated: 0.74 0.63–0.88; unvaccinated: 0.66 0.60–0.73; NMV‐r; 0.65 0.59–0.71; and molnupiravir: 0.75 0.61–0.92). In conclusion, novel oral antiviral agents, namely NMV‐r and molnupiravir, were effective in reducing long‐term MACEs among nonhospitalized patients with COVID‐19, particularly when treated with NMV‐r or in patients aged ≥40 years. These findings suggest the potential role of novel antiviral agents as a preventive measure to reduce further adverse cardiovascular outcomes.
The aim of this study was to investigate the clinical efficacy of a combination of nirmatrelvir and ritonavir (NMV‐r) for treating COVID‐19 in patients with diabetes mellitus (DM). This retrospective ...cohort study used the TriNetX research network to identify adult diabetic patients with COVID‐19 between January 1, 2020, and December 31, 2022. Propensity score matching was used to match patients who received NMV‐r (NMV‐r group) with those who did not receive NMV‐r (control group). The primary outcome was all‐cause hospitalization or death during the 30‐day follow‐up period. Two cohorts comprising 13 822 patients with balanced baseline characteristics were created using propensity score matching. During the follow‐up period, the NMV‐r group had a lower risk of all‐cause hospitalization or death than the control group (1.4% n = 193 vs. 3.1% n = 434; hazard ratio HR, 0.497; 95% confidence interval CI, 0.420–0.589). Compared with the control group, the NMV‐r group also had a lower risk of all‐cause hospitalization (HR, 0.606; 95% CI, 0.508–0.723) and all‐cause mortality (HR, 0.076; 95% CI, 0.033–0.175). This lower risk was consistently observed in almost all subgroup analyses, which examined sex (male: 0.520 0.401–0.675; female: 0.586 0.465–0.739), age (age 18–64 years: 0.767 0.601–0.980; ≥65 years: 0.394 0.308–0.505), level of HbA1c (<7.5%: 0.490 0.401–0.599; ≥7.5%: 0.655 0.441–0.972), unvaccinated (0.466 0.362–0.599), type 1 DM (0.453 0.286–0.718) and type 2 DM (0.430 0.361–0.511). NMV‐r can help reduce the risk of all‐cause hospitalization or death in nonhospitalized patients with DM and COVID‐19.
Glomerulus morphology on renal pathology images provides valuable diagnosis and outcome prediction information. To provide better care, an efficient, standardized, and scalable method is urgently ...needed to optimize the time-consuming and labor-intensive interpretation process by renal pathologists. This paper proposes a deep convolutional neural network (CNN)-based approach to automatically detect and classify glomeruli with different stains in renal pathology images. In the glomerulus detection stage, this paper proposes a flattened Xception with a feature pyramid network (FX-FPN). The FX-FPN is employed as a backbone in the framework of faster region-based CNN to improve glomerulus detection performance. In the classification stage, this paper considers classifications of five glomerulus morphologies using a flattened Xception classifier. To endow the classifier with higher discriminability, this paper proposes a generative data augmentation approach for patch-based glomerulus morphology augmentation. New glomerulus patches of different morphologies are generated for data augmentation through the cycle-consistent generative adversarial network (CycleGAN). The single detection model shows the F1 score up to 0.9524 in H&E and PAS stains. The classification result shows that the average sensitivity and specificity are 0.7077 and 0.9316, respectively, by using the flattened Xception with the original training data. The sensitivity and specificity increase to 0.7623 and 0.9443, respectively, by using the generative data augmentation. Comparisons with different deep CNN models show the effectiveness and superiority of the proposed approach.
•Collection of renal pathological images with annotations of glomerulus classes.•A flattened Xception with feature pyramid network (FX-FPN) for glomerulus detection.•Generative glomerulus morphology augmentation to improve classification performance.•A two-stage detection and classification framework with performance evaluation.
Abstract
This study was aimed at investigating the risk of cytomegalovirus (CMV) disease among coronavirus disease 2019 (COVID‐19) survivors. In this retrospective cohort study, we used the TriNetX ...research network to identify adults with and without COVID‐19 between January 1, 2022 and December 31, 2022. Propensity score matching was used to match the patients with and without COVID‐19. The primary outcome was the risk of CMV disease during the 90‐day follow‐up period. Two matched cohorts comprising 2 501 634 patients with balanced baseline characteristics were created using propensity score matching. During the follow‐up period, patients with COVID‐19 had a higher risk of CMV disease than those without COVID‐19 (hazard ratio HR, 2.55; 95% confidence interval: 2.01–3.23). The higher risk of CMV disease in the COVID‐19 cohort compared with that of the non‐COVID‐19 cohort remained unchanged in the subgroup analyses by sex (men: HR, 1.85 1.38–2.47; women: HR, 2.31 1.63–3.27), age (18–64 years: HR, 2.21 1.71–2.85; ≥65 years: HR, 1.97 1.20–3.25), obesity (HR, 1.54 1.04–2.30), diabetes mellitus (HR, 1.50 1.08–2.08), cancer (HR, 3.10 1.95–4.92), glucocorticoid use (HR, 3.14 2.45–4.02), transplantation (HR, 1.38 1.08–1.77), and unvaccinated status (HR, 2.37 1.82–3.08). In conclusion, COVID‐19 can increase the risk of CMV disease. Clinicians should be aware of the risk of CMV disease in patients with COVID‐19.
This systematic review and meta-analysis aimed to investigate the clinical efficacy and safety of systemic corticosteroids in the treatment of patients with severe community-acquired pneumonia ...(sCAP).
A comprehensive search was conducted using the Medline, Embase, ClinicalTrials.gov, and Scopus databases for articles published until April 24, 2023. Only randomized controlled trials (RCTs) that assessed the clinical efficacy and safety of adjunctive corticosteroids for treating sCAP were included. The primary outcome was the 30-day all-cause mortality.
A total of severe RCTs involving 1689 patients were included in this study. Overall, the study group had a lower mortality rate at day 30 than the control group (risk ratio RR, 0.61; 95% CI 0.44 to 0.85; p < 0.01) with low heterogeneity (I
= 0%, p = 0.42). Compared to the control group, the study group had a lower risk of the requirement of mechanical ventilation (RR 0.57; 95% CI 0.45 to 0.73; p < 0.001), shorter length of intensive care unit (MD - 0.8; 95% CI - 1.4 to - 0.1; p = 0.02), and hospital stay (MD - 1.1; 95% CI - 2.0 to - 0.1; p = 0.04). Finally, no significant difference was observed between the study and the control groups in terms of gastrointestinal tract bleeding (RR 1.03; 95% CI 0.49 to 2.18; p = 0.93), healthcare-associated infection (RR 0.89; 95% CI 0.60 to 1.32; p = 0.56), and acute kidney injury (RR 0.68; 95% CI 0.21 to 2.26; p = 0.53).
In patients with sCAP, adjunctive corticosteroids can provide survival benefits and improve clinical outcomes without increasing adverse events. However, because the pooled evidence remains inconclusive, further studies are required.
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