Association of body roundness index with diabetes and prediabetes in US adults from NHANES 2007-2018: a cross-sectional study.

OBJECTIVE: The present study examined the ability of the body roundness index (BRI) to predict the incidence of diabetes and prediabetes among adults in the USA. METHOD: The study enrolled 11,980 adults aged ≥ 20 years from the National Health and Nutrition Examination Survey (NHANES). Logistic regression served as the primary method for analyzing the relevant link between BRI and the incidence of diabetes and prediabetes, including univariate analysis, multivariate regression analysis, smooth curve fitting analysis, and subgroup analysis. What's more, receiver operating characteristic (ROC) analysis was applied to confirm the predictive values of BRI for diabetes and prediabetes. RESULTS: Each unit higher than BRI was associated with a 17% increased risk of diabetes and prediabetes after covariate adjustments (OR: 1.17, 95% CI: 1.07-1.27). Those with BRI in the high scores (Q4) possessed an increased likelihood of having diabetes and prediabetes than individuals in the reference group (OR: 1.83, 95% CI: 1.29-2.58). A smooth curve fitting analysis revealed a non-linear trend. The results across all population subgroups were uniform to those of the total population. The ROC curve indicated that the BRI was the best predictor of diabetes and prediabetes among other anthropometric indices. CONCLUSIONS: Diabetes and prediabetes occurrence rates and BRI have a positive and non-linear relationship in American adults. The BRI indices could function as predictive markers for diabetes and prediabetes.

ISG15 accelerates acute kidney injury and the subsequent AKI-to-CKD transition by promoting TGFßR1 ISGylation.

Rationale: Acute kidney injury (AKI) has substantial rates of mortality and morbidity, coupled with an absence of efficacious treatment options. AKI commonly transits into chronic kidney disease (CKD) and ultimately culminates in end-stage renal failure. The interferon-stimulated gene 15 (ISG15) level was upregulated in the kidneys of mice injured by ischemia-reperfusion injury (IRI), cisplatin, or unilateral ureteral obstruction (UUO), however, its role in AKI development and subsequent AKI-to-CKD transition remains unknown. Methods: Isg15 knockout (Isg15 KO) mice challenged with bilateral or unilateral IRI, cisplatin, or UUO were used to investigate its role in AKI. We established cellular models with overexpression or knockout of ISG15 and subjected them to hypoxia-reoxygenation, cisplatin, or transforming growth factor- ß1 (TGF-ß1) stimulation. Renal RNA-seq data obtained from AKI models sourced from public databases and our studies, were utilized to examine the expression profiles of ISG15 and its associated genes. Additionally, published single cell RNA-seq data from human kidney allograft biopsies and mouse IRI model were analyzed to investigate the expression patterns of ISG15 and the type I TGF-ß receptor (TGFßR1). Western blotting, qPCR, co-immunoprecipitation, and immunohistochemical staining assays were performed to validate our findings. Results: Alleviated pathological injury and renal function were observed in Isg15 KO mice with IRI-, cisplatin-, or UUO-induced AKI and the following AKI-to-CKD transition. In hypoxia-reoxygenation, cisplatin or TGF-ß1 treated HK-2 cells, knockout ISG15 reduced stimulus-induced cell fibrosis, while overexpression of ISG15 with modification capacity exacerbated cell fibrosis. Immunoprecipitation assays demonstrated that ISG15 promoted ISGylation of TGFßR1, and inhibited its ubiquitination. Moreover, knockout of TGFßR1 blocked ISG15's fibrosis-exacerbating effect in HK-2 cells, while overexpression of TGFßR1 abolished the renal protective effect of ISG15 knockout during IRI-induced kidney injury. Conclusions: ISG15 plays an important role in the development of AKI and subsequent AKI-to-CKD transition by promoting TGFßR1 ISGylation.

BI1 Activates Autophagy and Mediates TDP43 to Regulate ALS Pathogenesis.

Amyotrophic lateral sclerosis (ALS) is the most prevalent motor neuron disease in adults. Currently, there are no known drugs or clinical approaches that have demonstrated efficacy in treating ALS. Mitochondrial function and autophagy have been identified as crucial mechanisms in the development of ALS. While Bax inhibitor 1 (BI1) has been implicated in neurodegenerative diseases, its exact mechanism remains unknown. This study investigates the therapeutic impact of BI1 overexpression on ALS both in vivo and in vitro, revealing its ability to mitigate SOD1G93A-induced apoptosis, nuclear damage, mitochondrial dysfunction, and axonal degeneration of motor neurons. At the same time, BI1 prolongs onset time and lifespan of ALS mice, improves motor function, and alleviates neuronal damage, muscle damage, neuromuscular junction damage among other aspects. The findings indicate that BI1 can inhibit pathological TDP43 morphology and initially stimulate autophagy through interaction with TDP43. This study establishes a solid theoretical foundation for understanding the regulation of autophagy by BI1 and TDP43 while shedding light on the pathogenesis of ALS through their interaction - offering new concepts and targets for clinical implementation and drug development.

Rate-Distortion-Perception Optimized Neural Speech Transmission System for High-Fidelity Semantic Communications.

We consider the problem of learned speech transmission. Existing methods have exploited joint source-channel coding (JSCC) to encode speech directly to transmitted symbols to improve the robustness over noisy channels. However, the fundamental limit of these methods is the failure of identification of content diversity across speech frames, leading to inefficient transmission. In this paper, we propose a novel neural speech transmission framework named NST. It can be optimized for superior rate-distortion-perception (RDP) performance toward the goal of high-fidelity semantic communication. Particularly, a learned entropy model assesses latent speech features to quantify the semantic content complexity, which facilitates the adaptive transmission rate allocation. NST enables a seamless integration of the source content with channel state information through variable-length joint source-channel coding, which maximizes the coding gain. Furthermore, we present a streaming variant of NST, which adopts causal coding based on sliding windows. Experimental results verify that NST outperforms existing speech transmission methods including separation-based and JSCC solutions in terms of RDP performance. Streaming NST achieves low-latency transmission with a slight quality degradation, which is tailored for real-time speech communication.

Phase Separation of Chromatin Structure-related Biomolecules: A Driving Force for Epigenetic Regulations.

Intracellularly, membrane-less organelles are formed by spontaneous fusion and fission of macro-molecules in a process called phase separation, which plays an essential role in cellular activities. In certain disease states, such as cancers and neurodegenerative diseases, aberrant phase separations take place and participate in disease progression. Chromatin structure-related proteins, based on their characteristics and upon external stimuli, phase separate to exert functions like genome assembly, transcription regulation, and signal transduction. Moreover, many chromatin structure-related proteins, such as histones, histone-modifying enzymes, DNA-modifying enzymes, and DNA methylation binding proteins, are involved in epigenetic regulations through phase separation. This review introduces phase separation and how phase separation affects epigenetics with a focus on chromatin structure-related molecules.

Zeolitic imidazolate framework-90 loaded with methylprednisolone sodium succinate effectively reduces hypertrophic scar in vivo.

Hypertrophic scar (HS) is characterized by an abnormal fibroblast-myofibroblast transformation; non-apoptosis of fibroblasts; and redundant expression of TGF-ß1, VEGF, α-SMA, and collagen I/III. An HS affects patients' physical and psychological quality of life, leading to joint dysfunction and skin cancer. However, there is currently no satisfactory drug to treat this disorder. In this study, we constructed methylprednisolone sodium succinate (MPSS) encapsulated ZIF-90 (MPSS@ZIF-90) for the effective treatment of an HS. The encapsulation of MPSS in ZIF-90 can achieve the controllable drug release of MPSS and prolong its effective treatment time. MPSS@ZIF-90 enhanced the apoptosis of human hypertrophic scar fibroblasts and downregulated the overexpression of TGF-ß1, VEGF, α-SMA, and collagen I/III both in vitro and in vivo. The instant injection of MPSS@ZIF-90 effectively intervened with the formation of the HS after 28 days. On the contrary, MPSS@ZIF-90 greatly reduced the HS with two injections and 14 days of treatment after the HS was formed. This work provides evidence of effective intervention in the formation of an HS and the therapeutic effectiveness of MPSS@ZIF-90 with short treatment periods in vivo. It suggests that MPSS@ZIF-90 can be used as a biomedical option in the treatment of skin wounds and may reveal the potential molecular basis for promising future antifibrotic agents against scarring.

Exploring global research status and trends in anti-obesity effects of traditional Chinese medicine through intestinal microbiota: a bibliometric study.

Background: The intestinal microbiota (IM) has been found to contribute to metabolic disorders that lead to excessive fat accumulation, systemic and chronic low-grade inflammation, and insulin resistance in the host. Current research highlights a pivotal interaction between IM and traditional Chinese medicine (TCM) in mitigating obesity-related diseases. Undeniably, IM stands as a central focus in TCM research aimed at preventing and treating obesity. Therefore, tracing the progress and trends in this field can offer valuable references and insights for future studies. Methods: On June 17, 2023, we conducted a literature search on the topic of "IM and obesity in TCM" spanning the period from 2009 to 2023. We extracted the primary information of the publications, which includes complete records and reference citations, from the Science Citation Index Expanded (SCI-E) within the Web of Science Core Collection (WoSCC). To visualize and analyze the literature, we utilized CiteSpace and VOSviewer for bibliometric analysis. Results: During the past fifteen years, a rapid increase in the number of publications has been observed. The cooperative networks demonstrate China, Beijing University of Chinese Medicine, and Food & Function as the most active countries, organizations, and journals in this field, respectively. Liu Bin has contributed the most publications. A paper by Xu Jia, published in 2014, holds the highest Local Citation Score (LCS). Analyses of keyword co-occurrence and reference co-citation indicate that the research hotspots of IM and obesity in TCM are primarily focused on the metabolic benefits driven by endogenous functional metabolic molecules generated by TCM regulation of IM. Other focal points include the mechanism by which TCM regulates IM to restore the intestinal mucosal barrier This is a provisional file, not the final typeset article, and manages the gut-organ axis, the metabolic advantages of acupuncture's regulation of IM, and the process by which Chinese medicine small molecules transform IM. Conclusion: This research offers a comprehensive understanding of the current status, hotspots, and trends in global TCM research. Additionally, it provides a comprehensive summary and exploration of the latest advancements in this field, thereby emphasizing the essence of TCM more effectively.

Clinical efficacy of LED golden light combined with acyclovir in the treatment of herpes zoster: a single-center prospective study.

This study aimed to explore the safety and clinical efficacy of light emitting diode (LED) golden light combined with acyclovir in treating herpes zoster (HZ). According to the random number table, 54 inpatients with HZ were divided into control group, golden-light group, and red-light group, with 18 cases in each group. The control group received acyclovir intravenous drip, while the patients in the red-light group received acyclovir intravenous drip and red-light LED phototherapy, and the golden-light group received acyclovir intravenous drip and golden-light LED phototherapy. Primary assessments included herpes stopping time, incrustation time, decrustation time, pain visual analog scale scores (VAS), and incidence of postherpetic neuralgia (PHN) on the 30th and 90th days. Golden-light group and red-light group showed a shorter herpes stopping time, incrustation time, and decrustation time (P < 0.05) compared to the control group (P < 0.05), while the golden-light group showed a shorter incrustation time and decrustation time than the red light group (all P < 0.05). After treatment VAS scores, the golden-light group showed a significant improvement compared to the control group. The golden-light group showed a better PHN incidence than the control group at 30 days follow-up. Compared with the comprehensive curative effect, the total effective rates of the golden-light group, red-light group, and control group were 88.89%, 77.78%, and 72.22%, respectively, and the efficacy of the golden-light group was better than that of the control group and red-light group. Golden light combined with acyclovir can shorten the course of HZ, relieve pain, and reduce the occurrence of PHN, and the effect is better than that of the red-light group and the control group.

Interfacial Synthesis of an Ultrathin Two-Dimensional Polymer Film via [2 + 2] Photocycloaddition.

A carbon-carbon-linked, ultrathin, two-dimensional (2D) polymer film was prepared at the air/water interface through photochemically triggered [2 + 2] cycloaddition. The preorganization of the monomers on the water surface and the subsequent photo-polymerization led to the successful preparation of the ultrathin 2D polymer film. The obtained film is continuous, free standing, and has a large area (over 50 µm2). Transmission electron microscopy (TEM) and atomic force microscopy (AFM) give clear evidence of the ultrathin film morphology. Raman spectroscopy and X-ray photoelectron spectroscopy (XPS) indicate successful photo-induced [2 + 2] polymerization.

Molecular docking and molecular dynamics simulation study the mechanism of progesterone in the treatment of spinal cord injury.

PURPOSE: Spinal cord injury can lead to incomplete or complete loss of voluntary movement and sensory function, leading to serious complications. Numerous studies have shown that progesterone exhibits strong therapeutic potential for spinal cord injury. However, the mechanism by which progesterone treats spinal cord injury remains unclear. Therefore, this article explores the mechanism of progesterone in the treatment of spinal cord injury by means of molecular docking and molecular dynamics simulation. METHODS: We used bioinformatics to screen active pharmaceutical ingredients and potential targets, and molecular docking and molecular dynamics were used to validate and analysis by the supercomputer platform. RESULTS: Progesterone had 3606 gene targets, spinal cord injury had 6560 gene targets, the intersection gene targets were 2355. GO and KEGG analysis showed that the abundant pathways involved multiple pathways related to cell metabolism and inflammation. Molecular docking showed that progesterone played a role in treating spinal cord injury by acting on BDNF, AR, NGF and TNF. Molecular dynamics was used to prove and analyzed the binding stability of active ingredients and protein targets, and AR/Progesterone combination has the strongest binding energy. CONCLUSION: Progesterone promotes recovery from spinal cord injury by promoting axonal regeneration, remyelination, neuronal survival and reducing inflammation.

Exploring the mechanism of action of licorice in the treatment of COVID-19 through bioinformatics analysis and molecular dynamics simulation.

Purpose: The rapid worldwide spread of Corona Virus Disease 2019 (COVID-19) has become not only a global challenge, but also a lack of effective clinical treatments. Studies have shown that licorice can significantly improve clinical symptoms such as fever, dry cough and shortness of breath in COVID-19 patients with no significant adverse effects. However, there is still a lack of in-depth analysis of the specific active ingredients of licorice in the treatment of COVID-19 and its mechanism of action. Therefore, we used molecular docking and molecular dynamics to explore the mechanism of action of licorice in the treatment of COVID-19. Methods: We used bioinformatics to screen active pharmaceutical ingredients and potential targets, the disease-core gene target-drug network was established and molecular docking was used for verification. Molecular dynamics simulations were carried out to verify that active ingredients were stably combined with protein targets. The supercomputer platform was used to measure and analyze stability of protein targets at the residue level, solvent accessible surface area, number of hydrogen bonds, radius of gyration and binding free energy. Results: Licorice had 255 gene targets, COVID-19 had 4,628 gene targets, the intersection gene targets were 101. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene ontology (GO) analysis showed that licorice played an important role mainly through the signaling pathways of inflammatory factors and oxidative stress. Molecular docking showed that Glycyrol, Phaseol and Glyasperin F in licorice may playe a role in treating COVID-19 by acting on STAT3, IL2RA, MMP1, and CXCL8. Molecular dynamics were used to demonstrate and analyze the binding stability of active ingredients to protein targets. Conclusion: This study found that Phaseol in licorice may reduce inflammatory cell activation and inflammatory response by inhibiting the activation of CXCL8 and IL2RA; Glycyrol may regulate cell proliferation and survival by acting on STAT3. Glyasperin F may regulate cell growth by inhibiting the activation of MMP1, thus reducing tissue damage and cell death caused by excessive inflammatory response and promoting the growth of new tissues. Therefore, licorice is proposed as an effective candidate for the treatment of COVID-19 through STAT3, IL2RA, MMP1, and CXCL8.

Bak interacts with AKT and is involved in TNFα/CHX-induced apoptosis.

Bak is important for TNFα/CHX-induced neuronal death, but the precise molecular mechanism remains unclear. At the same time, TNFα/CHX concomitantly activates the phosphorylation of the MAPK and PI3K/AKT kinases. This study for the first time clarified the association between the MAPK and AKT under the TNFα/CHX stimulation upon addition of different kinase inhibitors to show whether Bak is associated with the kinase activation. The bioinformatics software HDOCK predicted the interaction between Bak and AKT. The addition of TNFα/CHX was proposed to destroy the complex, such that the dissociated Bak would exert a proapoptosis effect AKT can influence the inhibition of cell apoptosis. There was no cell death upon inducing TNFα/CHX for 3 h. AKT was less obvious with apoptosis but in the Bak knockout cells, the anti-apoptotic effect of AKT was very obvious. This study, therefore, provides the theoretical basis for the molecular mechanism of apoptosis induced by TNFα/CHX, providing a new target and direction for studying drug resistance.

Mechanism of a new photosensitizer (TBZPy) in the treatment of high-risk human papillomavirus-related diseases.

BACKGROUND: High-risk human papillomavirus infection is closely related to the development of several diseases, including cervical cancer and condyloma acuminatum. We recently designed a new photosensitizer, 1-triphenylaminebenzo[c][1,2,5]thiadiazole-4-yl)styryl)-1-methylpyridin-1-ium iodide salt (TBZPy), which shows good photodynamic properties. In this study, we explored the mechanism of action of the TBZPy photosensitizer and its potential application in the treatment of high-risk human papillomavirus-related diseases. METHODS: HeLa cells (infected by the high-risk human papillomavirus strain HPV18) were treated with TBZPy-photodynamic therapy (PDT). Cell viability, production of reactive oxygen species, apoptosis, and mitochondrial membrane depolarization were evaluated using cell counting kit-8, immunofluorescence, and flow cytometry assays, respectively. Expression levels of the anti-apoptotic proteins Bcl-2 and Bcl-XL; pro-apoptotic proteins Bax, cytochrome C, cleaved caspase 3, and cleaved caspase 9; and the mitochondrial stress protein heat shock protein 60 were examined by western blotting. RESULTS: TBZPy-PDT inhibited the viability and promoted reactive oxygen species production, lactate dehydrogenase release, and apoptosis of HeLa cells in vitro. TBZPy-PDT also promoted the loss of mitochondrial membrane potential, downregulated the expression of anti-apoptotic proteins, and upregulated the expression of pro-apoptotic proteins. Moreover, TBZPy-PDT downregulated the expression of the human papillomavirus E6 and E7 proteins. CONCLUSION: Our study demonstrates the effectiveness of TBZPy-PDT against human papillomavirus-related diseases. These findings provide a foundation for using this novel photosensitizer to treat diseases associated with high-risk human papillomavirus infection.

Multiomics Analysis Reveals the Prognostic Non-tumor Cell Landscape in Glioblastoma Niches.

A comprehensive characterization of non-tumor cells in the niches of primary glioblastoma is not fully established yet. This study aims to present an overview of non-malignant cells in the complex microenvironment of glioblastoma with detailed characterizations of their prognostic effects. We curate 540 gene signatures covering a total of 64 non-tumor cell types. Cell type-specific expression patterns are interrogated by normalized enrichment score across four large gene expression profiling cohorts of glioblastoma with a total number of 967 cases. The glioblastoma multiforms (GBMs) in each cohort are hierarchically clustered into negative or positive immune response classes with significantly different overall survival. Our results show that astrocytes, macrophages, monocytes, NKTs, and MSC are risk factors, while CD8 T cells, CD8 naive T cells, and plasma cells are protective factors. Moreover, we find that the immune system and organogenesis are uniformly enriched in negative immune response clusters, in contrast to the enrichment of nervous system in positive immune response clusters. Mesenchymal differentiation is also observed in the negative immune response clusters. High enrichment status of macrophages in negative immune response clusters is independently validated by analyzing scRNA-seq data from eight high-grade gliomas, revealing that negative immune response samples comprised 46.63 to 55.12% of macrophages, whereas positive immune response samples comprised only 1.70 to 8.12%, with IHC staining of samples from six short-term and six long-term survivors of GBMs confirming the results.

Stability of Intraocular Lens With Different Haptic Design: A Swept-Source Optical Coherence Tomography Study.

Purpose: To investigate the stability of intraocular lens (IOLs) with different haptics by swept-source anterior-segment optical coherence tomography (AS-OCT). Methods: Sixty-eight eyes from 55 patients received the implantation of Rayner 920H (Closed C-loop Group), Zeiss 509M (Plate Group) or Lenstec SOFTEC HD (C-loop Group) IOLs. The tilt and decentration of IOLs were evaluated using AS-OCT at least 1 month postoperatively. Results: Mean decentration and tilt of IOLs were 0.18 ± 0.12 mm (range 0.02 to 0.59 mm) and 5.63 ± 1.65° (range 2.2 to 9.6°) respectively. Decentration was significantly smaller in the plate haptic group (0.12 ± 0.06 mm) as compared to the C-loop group (0.22 ± 0.13 mm, P = 0.02). The tilt of IOL was also significantly smaller in the plate haptic group (4.96 ± 0.89°) as compared to the C-loop group (6.28 ± 1.83°, P = 0.01). There was marginal difference between the Closed C-loop group (5.52 ± 1.74°) and C-loop group (6.28 ± 1.83°, P = 0.07). Conclusions: The Plate-haptic IOLs should have better stability for the decentration and tilt than the C-loop design IOLs.

Origin and Characterization of Extracellular Vesicles Present in the Spider Venom of Ornithoctonus hainana.

Extracellular vesicles (EVs), including exosomes and microvesicles, are membranous vesicles released from nearly all cellular types. They contain various bioactive molecules, and their molecular composition varies depending on their cellular origin. As research into venomous animals has progressed, EVs have been discovered in the venom of snakes and parasitic wasps. Although vesicle secretion in spider venom glands has been observed, these secretory vesicles' origin and biological properties are unknown. In this study, the origin of the EVs from Ornithoctonus hainana venom was observed using transmission electron microscopy (TEM). The Ornithoctonus hainana venom extracellular vesicles (HN-EVs) were isolated and purified by density gradient centrifugation. HN-EVs possess classic membranous vesicles with a size distribution ranging from 50 to 150 nm and express the arthropod EV marker Tsp29Fb. The LC-MS/MS analysis identified a total of 150 proteins, which were divided into three groups according to their potential function: conservative vesicle transport-related proteins, virulence-related proteins, and other proteins of unknown function. Functionally, HN-EVs have hyaluronidase activity and inhibit the proliferation of human umbilical vein endothelial cells (HUVECs) by affecting the cytoskeleton and cell cycle. Overall, this study investigates the biological characteristics of HN-EVs for the first time and sheds new light on the envenomation process of spider venom.

A Versatile and Robust Platform for the Scalable Manufacture of Biomimetic Nanovaccines.

Biomimetic strategies are useful for designing potent vaccines. Decorating a nanoparticulate adjuvant with cell membrane fragments as the antigen-presenting source exemplifies, such as a promising strategy. For translation, a standardizable, consistent, and scalable approach for coating nanoadjuvant with the cell membrane is important. Here a turbulent mixing and self-assembly method called flash nanocomplexation (FNC) for producing cell membrane-coated nanovaccines in a scalable manner is demonstrated. The broad applicability of this FNC technique compared with bulk-sonication by using ten different core materials and multiple cell membrane types is shown. FNC-produced biomimetic nanoparticles have promising colloidal stability and narrow particle polydispersity, indicating an equal or more homogeneous coating compared to the bulk-sonication method. The potency of a nanovaccine comprised of B16-F10 cancer cell membrane decorating mesoporous silica nanoparticles loaded with the adjuvant CpG is then demonstrated. The FNC-fabricated nanovaccines when combined with anti-CTLA-4 show potency in lymph node targeting, DC antigen presentation, and T cell immune activation, leading to prophylactic and therapeutic efficacy in a melanoma mouse model. This study advances the design of a biomimetic nanovaccine enabled by a robust and versatile nanomanufacturing technique.

neoDL: a novel neoantigen intrinsic feature-based deep learning model identifies IDH wild-type glioblastomas with the longest survival.

BACKGROUND: Neoantigen based personalized immune therapies achieve promising results in melanoma and lung cancer, but few neoantigen based models perform well in IDH wild-type GBM, and the association between neoantigen intrinsic features and prognosis remain unclear in IDH wild-type GBM. We presented a novel neoantigen intrinsic feature-based deep learning model (neoDL) to stratify IDH wild-type GBMs into subgroups with different survivals. RESULTS: We first derived intrinsic features for each neoantigen associated with survival, followed by applying neoDL in TCGA data cohort(AUC = 0.988, p value < 0.0001). Leave one out cross validation (LOOCV) in TCGA demonstrated that neoDL successfully classified IDH wild-type GBMs into different prognostic subgroups, which was further validated in an independent data cohort from Asian population. Long-term survival IDH wild-type GBMs identified by neoDL were found characterized by 12 protective neoantigen intrinsic features and enriched in development and cell cycle. CONCLUSIONS: The model can be therapeutically exploited to identify IDH wild-type GBM with good prognosis who will most likely benefit from neoantigen based personalized immunetherapy. Furthermore, the prognostic intrinsic features of the neoantigens inferred from this study can be used for identifying neoantigens with high potentials of immunogenicity.

Development, manufacturing, and preliminary validation of a reusable half-face respirator during the COVID-19 pandemic.

INTRODUCTION: The COVID-19 pandemic has led to widespread shortages of N95 respirators and other personal protective equipment (PPE). An effective, reusable, locally-manufactured respirator can mitigate this problem. We describe the development, manufacture, and preliminary testing of an open-hardware-licensed device, the "simple silicone mask" (SSM). METHODS: A multidisciplinary team developed a reusable silicone half facepiece respirator over 9 prototype iterations. The manufacturing process consisted of 3D printing and silicone casting. Prototypes were assessed for comfort and breathability. Filtration was assessed by user seal checks and quantitative fit-testing according to CSA Z94.4-18. RESULTS: The respirator originally included a cartridge for holding filter material; this was modified to connect to standard heat-moisture exchange (HME) filters (N95 or greater) after the cartridge showed poor filtration performance due to flow acceleration around the filter edges, which was exacerbated by high filter resistance. All 8 HME-based iterations provided an adequate seal by user seal checks and achieved a pass rate of 87.5% (N = 8) on quantitative testing, with all failures occurring in the first iteration. The overall median fit-factor was 1662 (100 = pass). Estimated unit cost for a production run of 1000 using distributed manufacturing techniques is CAD $15 in materials and 20 minutes of labor. CONCLUSION: Small-scale manufacturing of an effective, reusable N95 respirator during a pandemic is feasible and cost-effective. Required quantities of reusables are more predictable and less vulnerable to supply chain disruption than disposables. With further evaluation, such devices may be an alternative to disposable respirators during public health emergencies. The respirator described above is an investigational device and requires further evaluation and regulatory requirements before clinical deployment. The authors and affiliates do not endorse the use of this device at present.