Long-acting growth hormone in the treatment of growth hormone deficiency in children: a systematic literature review and network meta-analysis.

The purpose of this study is to compare the relative efficacy and safety of long-acting growth hormone (LAGH) as a growth hormone replacement therapy in prepubertal children with growth hormone deficiency (GHD). We searched the PubMed, Embase, CNKI, and Wanfang databases from inception to July 2023 and identified eleven relevant studies. PEG-LAGH showed better effect on height velocity (mean difference [MD]: - 0.031, 95% credibility interval [CrI]: - 0.278, 0.215) than somatrogon (MD: 0.105, 95% CrI: - 0.419, 0.636), somapacitan (MD: 0.802, 95% CrI: - 0.451, 2.068) and lonapegsomatropin (MD: 1.335, 95% CrI: - 0.3, 2.989) when compared with daily growth hormone (DGH). Furthermore, in terms of height standard deviation score, PEG-LAGH demonstrated better improvement (MD: - 0.15, 95% CrI: - 1.1, 0.66) than somatrogon (MD: - 0.055, 95% CrI: - 1.3, 0.51) and somapacitan (MD: 0.22, 95% CrI: - 0.91, 1.3). PEG-LAGH (risk ratio [RR]: 1.00, 95% CrI: 0.82, 1.2) reduced the risk of adverse events compared with other LAGH (somatrogon, RR: 1.1, 95% CrI: 0.98, 1.2; somapacitan, RR: 1.1, 95% CrI: 0.96, 1.4; lonapegsomatropin, RR, 1.1, 95% CrI: 0.91, 1.3) and was comparable with DGH. This is the first study to indirectly compare the LAGH thorough a network meta-analysis and provide evidence of the optimal efficacy of various LAGH specifically PEG-LAGH and acceptable safety profile in prepubertal children with GHD.

Variations in proton transfer pathways and energetics on pristine and defect-rich quartz surfaces in water: Insights into the bimodal acidities of quartz.

HYPOTHESIS: Understanding the mechanisms of proton transfer on quartz surfaces in water is critical for a range of processes in geochemical, environmental, and materials sciences. The wide range of surface acidities (>9 pKa units) found on the ubiquitous mineral quartz is caused by the structural variations of surface silanol groups. Molecular scale simulations provide essential tools for elucidating the origin of site-specific surface acidities. SIMULATIONS: We used density-functional tight-binding-based molecular dynamics combined with rare-event metadynamics simulations to probe the mechanisms of deprotonation reactions from ten representative surface silanol groups found on both pristine and defect-rich quartz (101) surfaces with Si vacancies. FINDINGS: The results show that deprotonation is a highly dynamic process where both the surface hydroxyls and bridging oxygen atoms serve as the proton acceptors, in addition to water. Deprotonation of embedded silanols through intrasurface proton transfer exhibited lower pKa values with less H-bond participation and higher energy barriers, suggesting a new mechanism to explain the bimodal acidity observed on quartz surface. Defect sites, recently shown to comprise a significant portion of the quartz (101) surface, diversify the coordination and local H-bonding environments of the surface silanols, changing both the deprotonation pathways and energetics, leading to a wider range of pKa values (2.4 to 11.5) than that observed on pristine quartz surface (10.4 and 12.1).

Self-Supervised Learning Reveals Clinically Relevant Histomorphological Patterns for Therapeutic Strategies in Colon Cancer.

Self-supervised learning (SSL) automates the extraction and interpretation of histopathology features on unannotated hematoxylin-and-eosin-stained whole-slide images (WSIs). We trained an SSL Barlow Twins-encoder on 435 TCGA colon adenocarcinoma WSIs to extract features from small image patches. Leiden community detection then grouped tiles into histomorphological phenotype clusters (HPCs). HPC reproducibility and predictive ability for overall survival was confirmed in an independent clinical trial cohort (N=1213 WSIs). This unbiased atlas resulted in 47 HPCs displaying unique and sharing clinically significant histomorphological traits, highlighting tissue type, quantity, and architecture, especially in the context of tumor stroma. Through in-depth analysis of these HPCs, including immune landscape and gene set enrichment analysis, and association to clinical outcomes, we shed light on the factors influencing survival and responses to treatments like standard adjuvant chemotherapy and experimental therapies. Further exploration of HPCs may unveil new insights and aid decision-making and personalized treatments for colon cancer patients.

Total Infectome Characterization of Respiratory Infections during the 2022-23 COVID-19 Outbreak in China Revealed Extensive Coinfections with Links to SARS-CoV-2 Status, Age, and Disease Severity.

Between 7 December 2022 and 28 February 2023, China experienced a new wave of COVID-19 that swept across the entire country and resulted in an increasing amount of respiratory infections and hospitalizations. The purpose of this study is to reveal the intensity and composition of coinfecting microbial agents. In total, 196 inpatients were recruited from The Third People's Hospital of Shenzhen, and 169 respiratory and 73 blood samples were collected for metagenomic next-generation sequencing. The total "Infectome" was characterized and compared across different groups defined by the SARS-CoV-2 detection status, age groups, and severity of disease. Our results revealed a total of 22 species of pathogenic microbes (4 viruses, 13 bacteria, and 5 fungi), and more were discovered in the respiratory tract than in blood. The diversity of the total infectome was highly distinguished between respiratory and blood samples, and it was generally higher in patients that were SARS-CoV-2-positive, older in age, and with more severe disease. At the individual pathogen level, HSV-1 seemed to be the major contributor to these differences observed in the overall comparisons. Collectively, this study reveals the highly complex respiratory infectome and high-intensity coinfection in patients admitted to the hospital during the period of the 2023 COVID-19 pandemic in China.

Comparative analysis of characteristics of antibiotic resistomes between Arctic soils and representative contaminated samples using metagenomic approaches.

Antibiotic resistance is one of the most concerned global health issues. However, comprehensive profiles of antibiotic resistance genes (ARGs) in various environmental settings are still needed to address modern antibiotic resistome. Here, Arctic soils and representative contaminated samples from ARG pollution sources were analyzed using metagenomic approaches. The diversity and abundance of ARGs in Arctic soils were significantly lower than those in contaminated samples (p < 0.01). ARG profiles in Arctic soils were featured with the dominance of vanF, ceoB, and bacA related to multidrug and bacitracin, whereas those from ARG pollution sources were characterized by prevalent resistance to anthropogenic antibiotics such as sulfonamides, tetracyclines, and beta-lactams. Mobile genetic elements (MGEs) were found in all samples, and their abundance and relatedness to ARGs were both lower in Arctic soils than in polluted samples. Significant relationships between bacterial communities and ARGs were observed (p < 0.01). Cultural bacteria in Arctic soils had clinically-concerned resistance to erythromycin, vancomycin, ampicillin, etc., but ARGs relevant to those antibiotics were undetectable in their genomes. Our results suggested that Arctic environment could be an important reservoir of novel ARGs, and antibiotic stresses could cause ARG pollution via horizontal gene transfer and enrichment of resistant bacteria.

PHF6 loss reduces leukemia stem cell activity in an acute myeloid leukemia mouse model.

Acute myeloid leukemia (AML) is a malignant hematologic disease caused by gene mutations and genomic rearrangements in hematologic progenitors. The PHF6 (PHD finger protein 6) gene is highly conserved and located on the X chromosome in humans and mice. We found that PHF6 was highly expressed in AML cells with MLL rearrangement and was related to the shortened survival time of AML patients. In our study, we knocked out the Phf6 gene at different disease stages in the AML mice model. Moreover, we knocked down PHF6 by shRNA in two AML cell lines and examined the cell growth, apoptosis, and cell cycle. We found that PHF6 deletion significantly inhibited the proliferation of leukemic cells and prolonged the survival time of AML mice. Interestingly, the deletion of PHF6 at a later stage of the disease displayed a better anti-leukemia effect. The expressions of genes related to cell differentiation were increased, while genes that inhibit cell differentiation were decreased with PHF6 knockout. It is very important to analyze the maintenance role of PHF6 in AML, which is different from its tumor-suppressing function in T-cell acute lymphoblastic leukemia (T-ALL). Our study showed that inhibiting PHF6 expression may be a potential therapeutic strategy targeting AML patients.

Endothelial Robo4 suppresses endothelial-to-mesenchymal transition induced by irradiation and improves hematopoietic reconstitution.

Bone marrow ablation is routinely performed before hematopoietic stem cell transplantation (HSCT). Hematopoietic stem and progenitor cells (HSPCs) require a stable bone marrow microenvironment to expand and refill the peripheral blood cell pool after ablation. Roundabout guidance receptor 4 (Robo4) is a transmembrane protein exclusive to endothelial cells and is vital in preserving vascular integrity. Hence, the hypothesis is that Robo4 maintains the integrity of bone marrow endothelial cells following radiotherapy. We created an endothelial cell injury model with γ-radiation before Robo4 gene manipulation using lentiviral-mediated RNAi and gene overexpression techniques. We demonstrate that Robo4 and specific mesenchymal proteins (Fibronectin, Vimentin, αSma, and S100A4) are upregulated in endothelial cells exposed to irradiation (IR). We found that Robo4 depletion increases the expression of endoglin (CD105), an auxiliary receptor for the transforming growth factor (TGF-ß) family of proteins, and promotes endothelial-to-mesenchymal transition (End-MT) through activation of both the canonical (Smad) and non-canonical (AKT/NF-κB) signaling pathways to facilitate Snail1 activation and its nuclear translocation. Endothelial Robo4 overexpression stimulates the expression of immunoglobulin-like adhesion molecules (ICAM-1 and VCAM-1) and alleviates irradiation-induced End-MT. Our coculture model showed that transcriptional downregulation of endothelial Robo4 reduces HSPC proliferation and increases HSC quiescence and apoptosis. However, Robo4 overexpression mitigated the damaged endothelium's suppressive effects on HSC proliferation and differentiation. These findings indicate that by controlling End-MT, Robo4 preserves microvascular integrity after radiation preconditioning, protects endothelial function, and lessens the inhibitory effect of damaged endothelium on hematopoietic reconstitution.

Pericytes contribute to pulmonary vascular remodeling via HIF2α signaling.

Vascular remodeling is the process of structural alteration and cell rearrangement of blood vessels in response to injury and is the cause of many of the world's most afflicted cardiovascular conditions, including pulmonary arterial hypertension (PAH). Many studies have focused on the effects of vascular endothelial cells and smooth muscle cells (SMCs) during vascular remodeling, but pericytes, an indispensable cell population residing largely in capillaries, are ignored in this maladaptive process. Here, we report that hypoxia-inducible factor 2α (HIF2α) expression is increased in the lung tissues of PAH patients, and HIF2α overexpressed pericytes result in greater contractility and an impaired endothelial-pericyte interaction. Using single-cell RNAseq and hypoxia-induced pulmonary hypertension (PH) models, we show that HIF2α is a major molecular regulator for the transformation of pericytes into SMC-like cells. Pericyte-selective HIF2α overexpression in mice exacerbates PH and right ventricular hypertrophy. Temporal cellular lineage tracing shows that HIF2α overexpressing reporter NG2+ cells (pericyte-selective) relocate from capillaries to arterioles and co-express SMA. This novel insight into the crucial role of NG2+ pericytes in pulmonary vascular remodeling via HIF2α signaling suggests a potential drug target for PH.

Mutational signature dynamics indicate SARS-CoV-2's evolutionary capacity is driven by host antiviral molecules.

The COVID-19 pandemic has been characterised by sequential variant-specific waves shaped by viral, individual human and population factors. SARS-CoV-2 variants are defined by their unique combinations of mutations and there has been a clear adaptation to more efficient human infection since the emergence of this new human coronavirus in late 2019. Here, we use machine learning models to identify shared signatures, i.e., common underlying mutational processes and link these to the subset of mutations that define the variants of concern (VOCs). First, we examined the global SARS-CoV-2 genomes and associated metadata to determine how viral properties and public health measures have influenced the magnitude of waves, as measured by the number of infection cases, in different geographic locations using regression models. This analysis showed that, as expected, both public health measures and virus properties were associated with the waves of regional SARS-CoV-2 reported infection numbers and this impact varies geographically. We attribute this to intrinsic differences such as vaccine coverage, testing and sequencing capacity and the effectiveness of government stringency. To assess underlying evolutionary change, we used non-negative matrix factorisation and observed three distinct mutational signatures, unique in their substitution patterns and exposures from the SARS-CoV-2 genomes. Signatures 1, 2 and 3 were biased to C→T, T→C/A→G and G→T point mutations. We hypothesise assignments of these mutational signatures to the host antiviral molecules APOBEC, ADAR and ROS respectively. We observe a shift amidst the pandemic in relative mutational signature activity from predominantly Signature 1 changes to an increasingly high proportion of changes consistent with Signature 2. This could represent changes in how the virus and the host immune response interact and indicates how SARS-CoV-2 may continue to generate variation in the future. Linkage of the detected mutational signatures to the VOC-defining amino acids substitutions indicates the majority of SARS-CoV-2's evolutionary capacity is likely to be associated with the action of host antiviral molecules rather than virus replication errors.

Direct thrombin inhibitors fail to reverse the negative effects of heparin on lung growth and function after murine left pneumonectomy.

Neonates with congenital diaphragmatic hernia (CDH) frequently require cardiopulmonary bypass and systemic anticoagulation. We previously demonstrated that even subtherapeutic heparin impairs lung growth and function in a murine model of compensatory lung growth (CLG). The direct thrombin inhibitors (DTIs) bivalirudin and argatroban preserved growth in this model. Although DTIs are increasingly used for systemic anticoagulation clinically, patients with CDH may still receive heparin. In this experiment, lung endothelial cell proliferation was assessed following treatment with heparin-alone or mixed with increasing concentrations of bivalirudin or argatroban. The effects of subtherapeutic heparin with or without DTIs in the CLG model were also investigated. C57BL/6J mice underwent left pneumonectomy and subcutaneous implantation of osmotic pumps. Pumps were preloaded with normal saline, bivalirudin, or argatroban; treated animals received daily intraperitoneal low-dose heparin. In vitro, heparin-alone decreased endothelial cell proliferation and increased apoptosis. The effect of heparin on proliferation, but not apoptosis, was reversed by the addition of bivalirudin and argatroban. In vivo, low-dose heparin decreased lung volume compared with saline-treated controls. All three groups that received heparin demonstrated decreased lung function on pulmonary function testing and impaired exercise performance on treadmill tolerance testing. These findings correlated with decreases in alveolarization, vascularization, angiogenic signaling, and gene expression in the heparin-exposed groups. Together, these data suggest that bivalirudin and argatroban fail to reverse the inhibitory effects of subtherapeutic heparin on lung growth and function. Clinical studies on the impact of low-dose heparin with DTIs on CDH outcomes are warranted.NEW & NOTEWORTHY Infants with pulmonary hypoplasia frequently require cardiopulmonary bypass and systemic anticoagulation. We investigate the effects of simultaneous exposure to heparin and direct thrombin inhibitors (DTIs) on lung growth and pulmonary function in a murine model of compensatory lung growth (CGL). Our data suggest that DTIs fail to reverse the inhibitory effects of subtherapeutic heparin on lung growth and function. Clinical studies on the impact of heparin with DTIs on clinical outcomes are thus warranted.

Reaction Layer Formation on MgO in the Presence of Humidity.

Mineralization by MgO is an attractive potential strategy for direct air capture (DAC) of CO2 due to its tendency to form carbonate phases upon exposure to water and CO2. Hydration of MgO during this process is typically assumed to not be rate limiting, even at ambient temperatures. However, surface passivation by hydrated phases likely reduces the CO2 capture capacity. Here, we examine the initial hydration reactions that occur on MgO(100) surfaces to determine whether they could potentially impact CO2 uptake. We first used atomic force microscopy (AFM) to explore changes in reaction layers in water (pH = 6 and 12) and MgO-saturated solution (pH = 11) and found the reaction layers on MgO are heterogeneous and nonuniform. To determine how relative humidity (R.H.) affects reactivity, we reacted samples at room temperature in nominally dry N2 (∼11-12% R.H.) for up to 12 h, in humid (>95% R.H.) N2 for 5, 10, and 15 min, and in air at 33 and 75% R.H. for 8 days. X-ray reflectivity and electron microscopy analysis of the samples reveal that hydrated phases form rapidly upon exposure to humid air, but the growth of the hydrated reaction layer slows after its initial formation. Reaction layer thickness is strongly correlated with R.H., with denser reaction layers forming in 75% R.H. compared with 33% R.H. or nominally dry N2. The reaction layers are likely amorphous or poorly crystalline based on grazing incidence X-ray diffraction measurements. After exposure to 75% R.H. in air for 8 days, the reaction layer increases in density as compared to the sample reacted in humid N2 for 5-15 min. This may represent an initial step toward the crystallization of the reaction layer. Overall, high R.H. favors the formation of a hydrated, disordered layer on MgO. Based on our results, DAC in a location with a higher R.H. will be favorable, but growth may slow significantly from initial rates even on short timescales, presumably due to surface passivation.

[Effect of bleaching combined with Er:YAG or Nd:YAG laser on shear bond strength and microleakage of resin restoration].

PURPOSE: To evaluate the effects of bleaching combined with Er:YAG laser or Nd:YAG laser on bond strength and microleakage of resin fillings on enamel surface. METHODS: Sixty-four pieces of enamel specimens prepared from isolated teeth were randomly divided into 4 groups(n=16): control group, simple bleaching group, bleaching combined with Er: YAG laser group and bleaching combined with Nd:YAG laser group. Then the shear bond strength and the depth of microleakage were tested, and the fracture mode of the specimen was observed under microscope. SPSS 26.0 software package was used for statistical analysis. RESULTS: After bleaching simply, the bond strength of the restoration was significantly decreased, and the marginal microleakage was significantly increased(P＜0.05). There was no significant difference in shear bond strength and microleakage depth between the group bleaching combined with Er: YAG laser and control group(P＞0.05). The shear bond strength after bleaching combined with Nd:YAG laser was significantly reduced (P＜0.05), but there was no significant difference in the depth of microleakage compared with unbleached microleakage(P＞0.05). Bonding interface fracture was the main fracture mode for all groups. CONCLUSIONS: Compared to traditional bleaching, bleaching combined with laser has certain clinical advantages due to its less influence on bond strength and microleakage of resin fillings.

Modulating Electronic Structure and Atomic Insights into the Novel Hierarchically Porous PdCuFe Trimetallic Alloy Aerogel for Efficient Oxygen Reduction.

The high cost of noble Pd/Pt required for the oxygen reduction reaction (ORR) in the cathode restricts the wide applications of fuel cells. In this study, the synthesis of a novel Pd3 CuFe0.5 aerogel electrocatalyst is successfully demonstrated using self-assembly and lyophilization techniques, employing a mild reducing agent. The resulting aerogel electrocatalyst exhibits a distinctive 3D network structure, possessing a substantial BET-specific surface area of 75.19 m2  g-1 . It is worth noting that the optimized Pd3 CuFe0.5 aerogel demonstrates exceptional ORR performance with a high half-wave potential of 0.92 V versus RHE, a significant limiting current density of 7.6 mA cm-2 , and the excellent electrocatalytic stability, superior to the reported noble metal electrocatalysts, with the ORR activity decays only 4.9% after 16 000 s. In addition, the Pd3 CuFe0.5 aerogel electrocatalyst shows superior cycling stability for ≈120 h at a charge/discharge current density of 10 mA cm-2 , indicating its promising application in fuel cells. Furthermore, the resulting composite aerogel possesses excellent hydrogen evolution reaction and ethanol oxidation reaction activity. The density functional theory calculations show that the partial oxidation of Pd3 CuFe0.5 aerogel leads to a negative shift of the d-band center, which energetically optimizes the binding strength of *O intermediates, therefore accelerating the ORR activity.

An electronic voting scheme based on homomorphic encryption and decentralization.

Compared with paper-based voting, electronic voting not only has advantages in storage and transmission, but also can solve the security problems that exist in traditional voting. However, in practice, most electronic voting faces the risk of voting failure due to malicious voting by voters or ballot tampering by attackers. To solve this problem, this article proposes an electronic voting scheme based on homomorphic encryption and decentralization, which uses the Paillier homomorphic encryption method to ensure that the voting results are not leaked until the election is over. In addition, the scheme applies signatures and two layers of encryption to the ballots. First, the ballot is homomorphically encrypted using the homomorphic public key; then, the voter uses the private key to sign the ballot; and finally, the ballot is encrypted using the public key of the counting center. By signing the ballots and encrypting them in two layers, the security of the ballots in the transmission process and the establishment of the decentralized scheme are guaranteed. The security analysis shows that the proposed scheme can guarantee the completeness, verifiability, anonymity, and uniqueness of the electronic voting scheme. The performance analysis shows that the computational efficiency of the proposed scheme is improved by about 66.7% compared with the Fan et al. scheme (https://doi.org/10.1016/j.future.2019.10.016).

Comparing breath hold versus free breathing irradiation for left-sided breast radiotherapy by PlanIQ™.

BACKGROUND: Breast cancer is the most widespread cancer in women and young women worldwide. Moving towards customised radiotherapy, balancing the use of the available technology with the best treatment modality may not be an easy task in the daily routine. This study aims to evaluate the effectiveness of introducing IQ-feasibility into clinical practice to support the decision of free-breathing (FB) versus breath-hold (BH) left-sided breast irradiations, in order to optimise the technology available and the effectiveness of the treatment. METHODS: Thirty-five patients who received 3D radiotherapy treatment of the left breast in deep-inspiration BH were included in this retrospective study. Computed tomography scans in FB and BH were acquired for each patient; targets contoured in both imaging datasets by an experienced radiation oncologist, and organs at risk delineated using automatic segmentation software were exported to PlanIQ™ (Sun Nuclear Corp.) to generate feasibility dose volume histogram (FDVHs). The dosimetric parameter of BH versus FB FDVH, and BH clinical dataset versus BH FDVH were compared. RESULTS: A total of 30 patients out of 35 patients analysed, presented for the BH treatments a significant reduction (p < 0.05) in the heart mean dose ([Formula: see text]), volume receiving 5 Gy ([Formula: see text]) and 20 Gy ([Formula: see text]), of 35.7%, 54.5%, and 2.1%, respectively; for the left lung, a lower reduction was registered and significant only for [Formula: see text] (21.4%, p = 0.046). For the remaining five patients, the FDVH cut-off points of heart and lung were superimposable with differences of less than 1%. Heart and left lung dosimetric parameters of the BH clinical plans are located in the difficult zone of the FDVH and differ significantly (p < 0.05) from the corresponding parameters of the FDVH curves delimiting this buffer area between the impossible and feasible zones, respectively. CONCLUSION: The use of PlanIQTM as a decision-support tool for the FB versus BH treatment delivery modality allows customisation of the treatment technique using the most appropriate technology for each patient enabling accurate management of available technologies.

[Characteristics and Ecological Risk Assessment of Pharmaceutical Active Compounds in Guangdong Province].

Pharmaceutically active compounds(PhACs) have become a class of new pollutants in the environment after extensive production and use of PhACs in China. To investigate the pollution characteristics of PhACs in Guangdong Province, raw sewage was collected from 186 sewage treatment plants in 21 cities, including 178 townships and administrative districts in Guangdong Province. The pollution levels of ten typical PhACs in influent water of sewage treatment plants were analyzed using automatic solid phase extraction and high performance liquid chromatography-triple quadrupole mass spectrometry. The spatial distribution characteristics of PhACs in Guangdong Province were fully revealed, and the potential ecological risks of PhACs were evaluated. The results showed that PhACs were detected in all wastewater plants, and the mass concentration of PhACs ranged from 21.00 to 9558.25 ng·L-1. Metoprolo, acetaminophen, bezafibrate, and caffeine were the main pollutants. In terms of spatial distribution, the average mass concentration of ΣPhACs in various regions of Guangdong Province was in the following order:Pearl River Delta>North Guangdong>East Guangdong≈West Guangdong. When the mass concentration of ΣPhACs was over 2500 ng·L-1 in the influent water of sewage treatment plants, the concentration of PhACs in effluent was estimated according to the sewage disposal technology. The ecological risk of PhACs was carried out based on the effluent. The results revealed that the ecological risk of PhACs was low in Guangdong Province, and the risk of bezafibrate was moderate in the cities of Shaoguan, Jiangmen, and Shenzhen. The highest ecological risk of ΣPhACs was located in Shaoguan.

Characteristics of the pulmonary microbiota in patients with mild and severe pulmonary infection.

Background: Lung infection is a global health problem associated with high morbidity and mortality and increasing rates of hospitalization. The correlation between pulmonary microecology and infection severity remains unclear. Therefore, the purpose of this study was to investigate the differences in lung microecology and potential biomarkers in patients with mild and severe pulmonary infection. Method: Patients with pulmonary infection or suspected infection were divided into the mild group (140 cases) and the severe group (80 cases) according to pneomonia severity index (PSI) scores. Here, we used metagenomic next-generation sequencing (mNGS) to detect DNA mainly from bronchoalveolar lavage fluid (BALF) collected from patients to analyze changes in the lung microbiome of patients with different disease severity. Result: We used the mNGS to analyze the pulmonary microecological composition in patients with pulmonary infection. The results of alpha diversity and beta diversity analysis showed that the microbial composition between mild and severe groups was similar on the whole. The dominant bacteria were Acinetobacter, Bacillus, Mycobacterium, Staphylococcus, and Prevotella, among others. Linear discriminant analysis effect size (LEfSe) results showed that there were significant differences in virus composition between the mild and severe patients, especially Simplexvirus and Cytomegalovirus, which were prominent in the severe group. The random forest model screened 14 kinds of pulmonary infection-related pathogens including Corynebacterium, Mycobacterium, Streptococcus, Klebsiella, and Acinetobacter. In addition, it was found that Rothia was negatively correlated with Acinetobacter, Mycobacterium, Bacillus, Enterococcus, and Klebsiella in the mild group through co-occurrence network, while no significant correlation was found in the severe group. Conclusion: Here, we describe the composition and diversity of the pulmonary microbiome in patients with pulmonary infection. A significant increase in viral replication was found in the severe group, as well as a significant difference in microbial interactions between patients with mild and severe lung infections, particularly the association between the common pathogenic bacteria and Rothia. This suggests that both pathogen co-viral infection and microbial interactions may influence the course of disease. Of course, more research is needed to further explore the specific mechanisms by which microbial interactions influence disease severity.

Which method delivers greater signal-to-noise ratio: Structural equation modelling or regression analysis with weighted composites?

Observational data typically contain measurement errors. Covariance-based structural equation modelling (CB-SEM) is capable of modelling measurement errors and yields consistent parameter estimates. In contrast, methods of regression analysis using weighted composites as well as a partial least squares approach to SEM facilitate the prediction and diagnosis of individuals/participants. But regression analysis with weighted composites has been known to yield attenuated regression coefficients when predictors contain errors. Contrary to the common belief that CB-SEM is the preferred method for the analysis of observational data, this article shows that regression analysis via weighted composites yields parameter estimates with much smaller standard errors, and thus corresponds to greater values of the signal-to-noise ratio (SNR). In particular, the SNR for the regression coefficient via the least squares (LS) method with equally weighted composites is mathematically greater than that by CB-SEM if the items for each factor are parallel, even when the SEM model is correctly specified and estimated by an efficient method. Analytical, numerical and empirical results also show that LS regression using weighted composites performs as well as or better than the normal maximum likelihood method for CB-SEM under many conditions even when the population distribution is multivariate normal. Results also show that the LS regression coefficients become more efficient when considering the sampling errors in the weights of composites than those that are conditional on weights.

A pneumonectomy model to study flow-induced pulmonary hypertension and compensatory lung growth.

In newborns, developmental disorders such as congenital diaphragmatic hernia (CDH) and specific types of congenital heart disease (CHD) can lead to defective alveolarization, pulmonary hypoplasia, and pulmonary arterial hypertension (PAH). Therapeutic options for these patients are limited, emphasizing the need for new animal models representative of disease conditions. In most adult mammals, compensatory lung growth (CLG) occurs after pneumonectomy; however, the underlying relationship between CLG and flow-induced pulmonary hypertension (PH) is not fully understood. We propose a murine model that involves the simultaneous removal of the left lung and right caval lobe (extended pneumonectomy), which results in reduced CLG and exacerbated reproducible PH. Extended pneumonectomy in mice is a promising animal model to study the cellular response and molecular mechanisms contributing to flow-induced PH, with the potential to identify new treatments for patients with CDH or PAH-CHD.