The Landscape of Mouse Meiotic Double-Strand Break Formation, Processing, and Repair.

Heritability and genome stability are shaped by meiotic recombination, which is initiated via hundreds of DNA double-strand breaks (DSBs). The distribution of DSBs throughout the genome is not random, but mechanisms molding this landscape remain poorly understood. Here, we exploit genome-wide maps of mouse DSBs at unprecedented nucleotide resolution to uncover previously invisible spatial features of recombination. At fine scale, we reveal a stereotyped hotspot structure-DSBs occur within narrow zones between methylated nucleosomes-and identify relationships between SPO11, chromatin, and the histone methyltransferase PRDM9. At large scale, DSB formation is suppressed on non-homologous portions of the sex chromosomes via the DSB-responsive kinase ATM, which also shapes the autosomal DSB landscape at multiple size scales. We also provide a genome-wide analysis of exonucleolytic DSB resection lengths and elucidate spatial relationships between DSBs and recombination products. Our results paint a comprehensive picture of features governing successive steps in mammalian meiotic recombination.

A hierarchical combination of factors shapes the genome-wide topography of yeast meiotic recombination initiation.

The nonrandom distribution of meiotic recombination influences patterns of inheritance and genome evolution, but chromosomal features governing this distribution are poorly understood. Formation of the DNA double-strand breaks (DSBs) that initiate recombination results in the accumulation of Spo11 protein covalently bound to small DNA fragments. By sequencing these fragments, we uncover a genome-wide DSB map of unprecedented resolution and sensitivity. We use this map to explore how DSB distribution is influenced by large-scale chromosome structures, chromatin, transcription factors, and local sequence composition. Our analysis offers mechanistic insight into DSB formation and early processing steps, supporting the view that the recombination terrain is molded by combinatorial and hierarchical interaction of factors that work on widely different size scales. This map illuminates the occurrence of DSBs in repetitive DNA elements, repair of which can lead to chromosomal rearrangements. We also discuss implications for evolutionary dynamics of recombination hot spots.

Mechanistic View and Genetic Control of DNA Recombination during Meiosis.

Meiotic recombination is essential for fertility and allelic shuffling. Canonical recombination models fail to capture the observed complexity of meiotic recombinants. Here, by combining genome-wide meiotic heteroduplex DNA patterns with meiotic DNA double-strand break (DSB) sites, we show that part of this complexity results from frequent template switching during synthesis-dependent strand annealing that yields noncrossovers and from branch migration of double Holliday junction (dHJ)-containing intermediates that mainly yield crossovers. This complexity also results from asymmetric positioning of crossover intermediates relative to the initiating DSB and Msh2-independent conversions promoted by the suspected dHJ resolvase Mlh1-3 as well as Exo1 and Sgs1. Finally, we show that dHJ resolution is biased toward cleavage of the pair of strands containing newly synthesized DNA near the junctions and that this bias can be decoupled from the crossover-biased dHJ resolution. These properties are likely conserved in eukaryotes containing ZMM proteins, which includes mammals.

Development and validation of a prognostic score to identify the optimal candidate for preemptive TIPS in patients with cirrhosis and acute variceal bleeding.

BACKGROUND AND AIM: Baveno VII workshop recommends the use of preemptive TIPS (p-TIPS) in patients with cirrhosis and acute variceal bleeding (AVB) at high- risk of treatment failure. However, the criteria defining "high-risk" have low clinical accessibility or include subjective variables. We aimed to develop and externally validate a model for better identification of p-TIPS candidates. APPROACH AND RESULTS: The derivation cohort included 1554 patients with cirrhosis and AVB who were treated with endoscopy plus drug (n = 1264) or p-TIPS (n = 290) from 12 hospitals in China between 2010 and 2017. We first used competing risk regression to develop a score for predicting 6-week and 1-year mortality in patients treated with endoscopy plus drugs, which included age, albumin, bilirubin, international normalized ratio, white blood cell, creatinine, and sodium. The score was internally validated with the bootstrap method, which showed good discrimination (6 wk/1 y concordance-index: 0.766/0.740) and calibration, and outperformed other currently available models. In the second stage, the developed score was combined with treatment and their interaction term to predicate the treatment effect of p-TIPS (mortality risk difference between treatment groups) in the whole derivation cohort. The estimated treatment effect of p-TIPS varied substantially among patients. The prediction model had good discriminative ability (6 wk/1 y c -for-benefit: 0.696/0.665) and was well calibrated. These results were confirmed in the validation dataset of 445 patients with cirrhosis with AVB from 6 hospitals in China between 2017 and 2019 (6-wk/1-y c-for-benefit: 0.675/0.672). CONCLUSIONS: We developed and validated a clinical prediction model that can help to identify individuals who will benefit from p-TIPS, which may guide clinical decision-making.

Molecular modification and biotechnological applications of microbial aspartic proteases.

The growing preference for incorporating microbial aspartic proteases in industries is due to their high catalytic function and high degree of substrate selectivity. These properties, however, are attributable to molecular alterations in their structure and a variety of other characteristics. Molecular tools, functional genomics, and genome editing technologies coupled with other biotechnological approaches have aided in improving the potential of industrially important microbial proteases by addressing some of their major limitations, such as: low catalytic efficiency, low conversion rates, low thermostability, and less enzyme yield. However, the native folding within their full domain is dependent on a surrounding structure which challenges their functionality in substrate conversion, mainly due to their mutual interactions in the context of complex systems. Hence, manipulating their structure and controlling their expression systems could potentially produce enzymes with high selectivity and catalytic functions. The proteins produced by microbial aspartic proteases are industrially capable and far-reaching in regulating certain harmful distinctive industrial processes and the benefits of being eco-friendly. This review provides: an update on current trends and gaps in microbial protease biotechnology, exploring the relevant recombinant strategies and molecular technologies widely used in expression platforms for engineering microbial aspartic proteases, as well as their potential industrial and biotechnological applications.

A Sn-Based Hybrid Ferroelastic Semiconductor with High-Temperature Dielectric Switching.

Organic-inorganic halide hybrids have been extensively developed and used in optoelectronic devices because of their superior performance such as ease of assembly, flexible structural tunability, and excellent optoelectronic properties. Ferroelastic strain might be used to modulate and control photoelectric properties such as photovoltaic voltage, while organic-inorganic hybrid ferroelastic semiconductors remain relatively unexplored. Herein, we successfully design a new Sn-base, lead-free hybrid ferroelastic semiconductor, [TPMA]2[SnCl6] (TPMA = benzyl trimethylammonium). It undergoes a high-temperature -3mF-1-type ferroelastic phase transition at 408 K, and intriguingly, its ferroelastic domains can be simultaneously switched under the stimulation of external heat and stress. The ferroelastic phase transition might be derived from the order-disorder transition of organic cations during heating and cooling. Moreover, [TPMA]2[SnCl6] also demonstrates a high-temperature dielectric switching property around 408 K, which has good stability and reproducibility. With those benefits, [TPMA]2[SnCl6] shows great potential in applications such as energy storage devices, optoelectronic devices, shape memory, intelligent switches, and so on.

A framework for longitudinal latent factor modelling of treatment response in clinical trials with applications to Psoriatic Arthritis and Rheumatoid Arthritis.

OBJECTIVE: Clinical trials involve the collection of a wealth of data, comprising multiple diverse measurements performed at baseline and follow-up visits over the course of a trial. The most common primary analysis is restricted to a single, potentially composite endpoint at one time point. While such an analytical focus promotes simple and replicable conclusions, it does not necessarily fully capture the multi-faceted effects of a drug in a complex disease setting. Therefore, to complement existing approaches, we set out here to design a longitudinal multivariate analytical framework that accepts as input an entire clinical trial database, comprising all measurements, patients, and time points across multiple trials. METHODS: Our framework composes probabilistic principal component analysis with a longitudinal linear mixed effects model, thereby enabling clinical interpretation of multivariate results, while handling data missing at random, and incorporating covariates and covariance structure in a computationally efficient and principled way. RESULTS: We illustrate our approach by applying it to four phase III clinical trials of secukinumab in Psoriatic Arthritis (PsA) and Rheumatoid Arthritis (RA). We identify three clinically plausible latent factors that collectively explain 74.5% of empirical variation in the longitudinal patient database. We estimate longitudinal trajectories of these factors, thereby enabling joint characterisation of disease progression and drug effect. We perform benchmarking experiments demonstrating our method's competitive performance at estimating average treatment effects compared to existing statistical and machine learning methods, and showing that our modular approach leads to relatively computationally efficient model fitting. CONCLUSION: Our multivariate longitudinal framework has the potential to illuminate the properties of existing composite endpoint methods, and to enable the development of novel clinical endpoints that provide enhanced and complementary perspectives on treatment response.

Silkworm pupae protein co-degradation by magnetic nanoparticles immobilized proteinase K and Mucor circinelloides aspartic protease for further utilization of sericulture by-products.

Silkworm pupae, by-product of sericulture industry, is massively discarded. The degradation rate of silkworm pupae protein is critical to further employment, which reduces the impact of waste on the environment. Herein, magnetic Janus mesoporous silica nanoparticles immobilized proteinase K mutant T206M and Mucor circinelloides aspartic protease were employed in the co-degradation. The thermostability of T206M improved by enhancing structural rigidity (t1/2 by 30 min and T50 by 5 °C), prompting the degradation efficiency. At 65 °C and pH 7, degradation rate reached the highest of 61.7%, which improved by 26% compared with single free protease degradation. Besides, the immobilized protease is easy to separate and reuse, which maintains 50% activity after 10 recycles. Therefore, immobilized protease co-degradation was first applied to the development and utilization of silkworm pupae resulting in the release of promising antioxidant properties and reduces the environmental impact by utilizing a natural and renewable resource.

Quantitative evaluation of disc degeneration using dual-energy CT: advantages of R-VH, D-VH values and the IVNCa + CT model.

OBJECTIVE: To evaluate the correlation between dual-energy CT (DECT) virtual calcium free (VNCA), CT attenuation, the ratio and difference of VNCA to CT attenuation, and Pfirrmann grading of lumbar disc degeneration. METHODS: A retrospective analysis on 135 intervertebral discs from 30 patients who underwent DECT and MR. Discs was graded using the Pfirrmann system. ROIs on the sagittal plane assessed HU value, VNCA value, Rho value, Z value, R-VH value, and D-VH value. Correlation, grade differences, and multivariate regression models were assessed. Diagnostic performance and cut-off values were determined using AUC. RESULTS: VNCA (r = 0.589, P < 0.001), R-VH (r = 0.622, P < 0.001), and D-VH (r = 0.613, P < 0.001) moderately correlated with Pfirrmann grading. HU (r = 0.388, P < 0.001), Rho (r = 0.142, P = 0.102), and Z (r = -0.125, P = 0.153) showed a weak correlation. R-VH, D-VH, and VNCA had significantly higher correlation than HU. Statistically significant differences were observed in P values of VNCA, HU, R-VH, and D-VH in relative groups (P < 0.05), but not in Rho and Z values (P > 0.05). R-VH and D-VH had significant differences between Pfirrmann grades 1 and 2, and grades 2 and 3 (early stage) (P < 0.05). AUC readings of R-VH and D-VH (≥2, ≥3, ≥4) were higher. The multivariate model IVNCa + CT had the highest AUC. CONCLUSION: The new quantitative indices R-VH value and D-VH value of DECT have advantages over VNCA value and HU value in evaluating early-stage disc degeneration (≥2 grades, ≥3 grades). The multivariate model IVNCa + CT has the best AUC values for evaluating disc degeneration at all stages.

Structure-Based Design of Novel Thiazolone[3,2-a]pyrimidine Derivatives as Potent RNase H Inhibitors for HIV Therapy.

Ribonuclease H (RNase H) was identified as an important target for HIV therapy. Currently, no RNase H inhibitors have reached clinical status. Herein, a series of novel thiazolone[3,2-a]pyrimidine-containing RNase H inhibitors were developed, based on the hit compound 10i, identified from screening our in-house compound library. Some of these derivatives exhibited low micromolar inhibitory activity. Among them, compound 12b was identified as the most potent inhibitor of RNase H (IC50 = 2.98 µM). The experiment of magnesium ion coordination was performed to verify that this ligand could coordinate with magnesium ions, indicating its binding ability to the catalytic site of RNase H. Docking studies revealed the main interactions of this ligand with RNase H. A quantitative structure activity relationship (QSAR) was also conducted to disclose several predictive mathematic models. A molecular dynamics simulation was also conducted to determine the stability of the complex. Taken together, thiazolone[3,2-a]pyrimidine can be regarded as a potential scaffold for the further development of RNase H inhibitors.

Inflammatory cytokines mediating the effect of oral lichen planus on oral cavity cancer risk: a univariable and multivariable mendelian randomization study.

BACKGROUND: While observational studies and experimental data suggest a link between oral lichen planus (OLP) and oral cavity cancer (OCC), the causal relationship and the role of inflammatory cytokines remain unclear. METHODS: This study employed a univariable and multivariable Mendelian Randomization (MR) analysis to investigate the causal relationship between OLP and the risk of OCC. Additionally, the potential role of inflammatory cytokines in modulating this association was explored. Instrumental variables were derived from genetic variants associated with OLP (n = 377,277) identified in Finngen R9 datasets, with 41 inflammatory cytokines as potential mediators, and OCC (n = 4,151) as the outcome variable. Analytical methods including Inverse Variance Weighted (IVW), Weighted Median, MR-Egger, and MR-PRESSO were utilized to assess the causal links among OLP, inflammatory cytokines, and OCC risk. Multivariable MR (MVMR) was then applied to quantify the mediating effects of these cytokines in the relationship between OLP and increased OCC risk. RESULTS: MR analysis provided strong evidence of a causal relationship between OLP (OR = 1.417, 95% CI = 1.167-1.721, p < 0.001) and the risk of OCC. Furthermore, two inflammatory cytokines significantly influenced by OLP, IL-13 (OR = 1.088, 95% CI: 1.007-1.175, P = 0.032) and IL-9 (OR = 1.085, 95% CI: 1.005-1.171, P = 0.037), were identified. Subsequent analysis revealed a significant causal association only between IL-13 (OR = 1.408, 95% CI: 1.147-1.727, P = 0.001) and higher OCC risk, establishing it as a potential mediator. Further, MVMR analysis indicated that IL-13 (OR = 1.437, 95% CI = 1.139-1.815, P = 0.002) mediated the relationship between OLP and OCC, accounting for 8.13% of the mediation. CONCLUSION: This study not only elucidates the potential causal relationship between OLP and the risk of OCC but also highlights the pivotal mediating role of IL-13 in this association.

Secukinumab in enthesitis-related arthritis and juvenile psoriatic arthritis: a randomised, double-blind, placebo-controlled, treatment withdrawal, phase 3 trial.

BACKGROUND: Treatment options in patients with enthesitis-related arthritis (ERA) and juvenile psoriatic arthritis (JPsA) are currently limited. This trial aimed to demonstrate the efficacy and safety of secukinumab in patients with active ERA and JPsA with inadequate response to conventional therapy. METHODS: In this randomised, double-blind, placebo-controlled, treatment-withdrawal, phase 3 trial, biologic-naïve patients (aged 2 to <18 years) with active disease were treated with open-label subcutaneous secukinumab (75/150 mg in patients <50/≥50 kg) in treatment period (TP) 1 up to week 12, and juvenile idiopathic arthritis (JIA) American College of Rheumatology 30 responders at week 12 were randomised 1:1 to secukinumab or placebo up to 100 weeks. Patients who flared in TP2 immediately entered open-label secukinumab TP3 that lasted up to week 104. Primary endpoint was time to disease flare in TP2. RESULTS: A total of 86 patients (median age, 14 years) entered open-label secukinumab in TP1. In TP2, responders (ERA, 44/52; JPsA, 31/34) received secukinumab or placebo. The study met its primary end point and demonstrated a statistically significant longer time to disease flare in TP2 for ERA and JPsA with secukinumab versus placebo (27% vs 55%, HR, 0.28; 95% CI 0.13 to 0.63; p<0.001). Exposure-adjusted incidence rates (per 100 patient-years (PY), 95% CI) for total patients were 290.7/100 PY (230.2 to 362.3) for adverse events and 8.2/100 PY (4.1 to 14.6) for serious adverse events in the overall JIA population. CONCLUSIONS: Secukinumab demonstrated significantly longer time to disease flare than placebo in children with ERA and JPsA with a consistent safety profile with the adult indications of psoriatic arthritis and axial spondyloarthritis. TRIAL REGISTRATION NUMBER: NCT03031782.

CXCL10 is a prognostic marker for pancreatic adenocarcinoma and tumor microenvironment remodeling.

BACKGROUND: The tumor microenvironment (TME) plays a crucial role in the progression of pancreatic adenocarcinoma (PAAD). However, challenges remain regarding the role played by TME associated genes in the prognosis of PAAD. METHODS: The scores of tumor infiltrating immune cells (TICs), the immune and stroma scores of 182 PAAD patients in the Cancer Genome Atlas (TCGA) database were determined using CIBERSORT and ESTIMATE calculations. The final genes were identified by protein-protein interaction (PPI) networks and univariate Cox regression of differentially expressed genes. Finally, the correlation between gene expression and TCGA and clinical characteristics of patients in local hospital database was discussed. Gene set enrichment analysis (GSEA), the association between CXCL10 expression and TICs components were conducted. RESULTS: In TCGA database and local hospital data, CXCL10 expression was correlated with the survival rate and TNM classification of patients with PAAD. Immune-related activities were enriched in the CXCL10 high expression group, while metabolic pathways were enriched in the CXCL10 low expression group. The expression of CXCL10 correlated with the proportion of TICs. CXCL10 expression was correlated with the proportion of TICs. CONCLUSION: CXCL10 is a potential prognostic marker for PAAD and provide additional insights into the treatment of PAAD based on TME transformation. However, more independent experimentation with the CXCL10 is need.

Stigmasterol Protects Against Steatohepatitis Induced by High-Fat and High-Cholesterol Diet in Mice by Enhancing the Alternative Bile Acid Synthesis Pathway.

BACKGROUND: Hepatic cholesterol accumulation is a significant risk factor in the progression of nonalcoholic fatty liver disease (NAFLD) to steatohepatitis. However, the precise mechanism by which stigmasterol (STG) mitigates this process remains unclear. OBJECTIVES: This study aimed to investigate the potential mechanism underlying the protective effect of STG in mice with NAFLD progressing to steatohepatitis while being fed a high-fat and high-cholesterol (HFHC) diet. METHODS: Male C57BL/6 mice were fed an HFHC diet for 16 wk to establish the NAFLD model. Subsequently, the mice received STG or a vehicle via oral gavage while continuing the HFHC diet for an additional 10 wk. The study evaluated hepatic lipid deposition and inflammation as well as the expression of key rate-limiting enzymes involved in the bile acid (BA) synthesis pathways. BAs in the colonic contents were quantified using ultra-performance liquid chromatography-tandem mass spectrometry. RESULTS: Compared with the vehicle control group, STG significantly reduced hepatic cholesterol accumulation (P < 0.01) and suppressed the gene expression of NLRP3 inflammasome and interleukin-18 (P < 0.05) in the livers of HFHC diet-fed mice. The total fecal BA content in the STG group was nearly double that of the vehicle control group. Additionally, the administration of STG increased the concentrations of representative hydrophilic BAs in the colonic contents (P < 0.05) along with the upregulation of gene and protein expression of CYP7B1 (P < 0.01). Furthermore, STG enhanced the α-diversity of the gut microbiota and partially reversed the alterations in the relative abundance of the gut microbiota induced by the HFHC diet. CONCLUSIONS: STG mitigates steatohepatitis by enhancing the alternative pathway for BA synthesis.

Antibiotic resistance and resistance mechanism of Corynebacterium kroppenstedtii isolated from patients with mastadenitis.

To investigate the antibiotic resistance and resistance mechanism of Corynebacterium kroppenstedtii (C. kroppenstedtii) isolated from patients with mastadenitis. Ninety C. kroppenstedtii clinical isolates were obtained from clinical specimens in 2018-2019. Species identification was performed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Antimicrobial susceptibility testing was performed by the broth microdilution method. The resistance genes were detected using PCR and DNA sequencing. The results of antimicrobial susceptibility testing indicated that the resistance rates of C. kroppenstedtii to erythromycin and clindamycin, ciprofloxacin, tetracycline, and trimethoprim-sulfamethoxazole were 88.9%, 88.9%, 67.8%, 62.2%, and 46.6%, respectively. None of the C. kroppenstedtii isolates was resistant to rifampicin, linezolid, vancomycin, or gentamicin. The gene of erm(X) was detected in all clindamycin and erythromycin-resistant strains. The gene of sul(1) and tet(W) were detected among all trimethoprim sulfamethoxazole-resistant strains and tetracycline-resistant strains, respectively. Furthermore, 1 or 2 amino acid mutations (mainly single mutation) were observed in the gyrA gene among ciprofloxacin-resistant strains.

A Practical Model for Predicting Esophageal Variceal Rebleeding in Patients with Hepatitis B-Associated Cirrhosis.

Background: Variceal rebleeding is a significant and potentially life-threatening complication of cirrhosis. Unfortunately, currently, there is no reliable method for stratifying high-risk patients. Liver stiffness measurements (LSM) have been shown to have a predictive value in identifying complications associated with portal hypertension, including first-time bleeding. However, there is a lack of evidence to confirm that LSM is reliable in predicting variceal rebleeding. The objective of our study was to evaluate the ability of generating a extreme gradient boosting (XGBoost) algorithm model to improve the prediction of variceal rebleeding. Methods: This retrospective analysis examined a cohort of 284 patients with hepatitis B-related cirrhosis. XGBoost models were developed using laboratory data, LSM, and imaging data to predict the risk of rebleeding in the patients. In addition, we compared the XGBoost models with traditional logistic regression (LR) models. We evaluated and compared the two models using the area under the receiver operating characteristic curve (AUROC) and other model performance parameters. Lastly, we validated the models using nomograms and decision curve analysis (DCA). Results: During a median follow-up of 66.6 weeks, 72 patients experienced rebleeding, including 21 (7.39%) and 61 (21.48%) patients who rebleed within 6 weeks and 1 year, respectively. In brief, the AUC of the LR models in predicting rebleeding at 6 weeks and 1 year was 0.828 (0.759-0.897) and 0.799 (0.738-0.860), respectively. In contrast, the accuracy of the XGBoost model in predicting rebleeding at 6 weeks and 1 year was 0.985 (0.907-0.731) and 0.931 (0.806-0.935), respectively. LSM and high-density lipoprotein (HDL) levels differed significantly between the rebleeding and nonrebleeding groups, with LSM being a reliable predictor in those models. The XGBoost models outperformed the LR models in predicting rebleeding within 6 weeks and 1 year, as demonstrated by the ROC and DCA curves. Conclusion: The XGBoost algorithm model can achieve higher accuracy than the LR model in predicting rebleeding, making it a clinically beneficial tool. This implies that the XGBoost model is better suited for predicting the risk of esophageal variceal rebleeding in patients.

Prevalence of and factors associated with alexithymia among patients with chronic obstructive pulmonary disease in China: a cross-sectional study.

BACKGROUND: Alexithymia is a common psychological disorder. However, few studies have investigated its prevalence and predictors in patients with chronic obstructive pulmonary disease (COPD). Therefore, we aimed to determine the prevalence and predictors of alexithymia in Chinese patients. METHODS: This cross-sectional study included 842 COPD patients to assess the prevalence and predictors of alexithymia using the 20-item Toronto Alexithymia Scale (TAS-20). We used the Hospital Anxiety and Depression Scale (HADS) to assess anxiety and depression, the modified British Medical Research Council dyspnea Rating Scale (mMRC) to assess dyspnea, St. George's Respiratory Questionnaire (SGRQ) to assess quality of life, and the age-adjusted Charlson comorbidity index (ACCI) to assess comorbidities. Alexithymia-related predictors were identified using univariate and multivariate logistic regression analyses. RESULTS: The prevalence of alexithymia in COPD patients was 23.6% (199/842). Multivariate analysis showed that age [odds ratio (OR) 0.886; 95% confidence interval (CI) 0.794-0.998], body mass index (OR 0.879; 95% CI 0.781-0.989), HADS-anxiety (OR 1.238; 95% CI 1.097-1.396), HADS-depression (OR 1.178; 95% CI 1.034-1.340), mMRC (OR 1.297; 95% CI 1.274-1.320), SGRQ (OR 1.627; 95% CI 1.401-1.890), ACCI (OR 1.165; 95% CI 1.051-1.280), and GOLD grade (OR 1.296; 95% CI 1.256-1.337) were independent predictors for alexithymia in patients with COPD. CONCLUSIONS: The prevalence of alexithymia was high in Chinese COPD patients. Anxiety, depression, dyspnea, quality of life, comorbidities, and disease severity are independent risk factors, and age and BMI are predictive factors for alexithymia in COPD patients.

Parent-reported Barriers and Parental Beliefs Associated with Intentions to Obtain HPV Vaccination for Children in a Primary care Patient Population in Minnesota, USA.

Human papillomavirus (HPV) vaccine uptake among adolescents remains suboptimal in the US. The COVID-19 pandemic posed new challenges to increase HPV vaccination rates. To characterize parent-reported barriers to obtain HPV vaccination for their children and to identify psychosocial factors associated with parents' intention to vaccinate their children for HPV, we administered parent surveys between April 2020 and January 2022 during a randomized pragmatic trial assessing the impact of evidence-based implementation strategies on HPV vaccination rates for adolescent patients at six Mayo Clinic primary care practices in Southeast Minnesota. A total of 342 surveys were completed (response rate 34.1%). Analyses were focused on parents of unvaccinated children (n = 133). The survey assessed the main reason the child did not receive the HPV vaccine, parental beliefs about the vaccine, and the parent's intention to vaccinate the child for HPV in the next 12 months. Frequently reported awareness and access barriers to HPV vaccination included not knowing the child was due (17.8%) and COVID-19 related delay (11.6%). Frequently reported attitudinal barriers include the belief that the child was too young for the vaccine (17.8%) and that the vaccine is not proven to be safe (16.3%). Injunctive social norm (Adjusted-OR = 3.15, 95%CI: 1.94, 5.41) and perceived harm beliefs (Adjusted-OR = 0.58, 95%CI: 0.35, 0.94) about the HPV vaccine were positively and negatively associated with HPV vaccination intention, respectively. Our findings suggest that continued efforts to overcome parental awareness, access, and attitudinal barriers to HPV vaccination are needed and underscore the importance of utilizing evidence-based health system-level interventions.

Characterizing Mechanical Properties of Layered Engineered Wood Using Guided Waves and Genetic Algorithm.

This study develops a framework for determining the material parameters of layered engineered wood in a nondestructive manner. The motivation lies in enhancing nondestructive evaluation (NDE) and quality assurance (QA) for engineered wood or mass timber, promising construction materials for sustainable and resilient civil structures. The study employs static compression tests, guided wave measurements, and a genetic algorithm (GA) to solve the inverse problem of determining the mechanical properties of a laminated veneer lumber (LVL) bar. Miniature LVL samples are subjected to compression tests to derive the elastic moduli and Poisson's ratios. Due to the intrinsic heterogeneity, the destructive compression tests yield large coefficients of variances ranging from 2.5 to 73.2%. Dispersion relations are obtained from spatial-temporal sampling of dynamic responses of the LVL bar. The GA pinpoints optimal mechanical properties by updating orthotropic elastic constants of the LVL material, and thereby dispersion curves, in a COMSOL simulation in accordance with experimental dispersion relations. The proposed framework can support estimation accuracy with errors less than 10% for most elastic constants. Focusing on vertical flexural modes, the estimated elastic constants generally resemble reference values from compression tests. This is the first study that evaluates the feasibility of using guided waves and multi-variable optimization to gauge the mechanical traits of LVL and establishes the foundation for further advances in the study of layered engineered wood structures.

Lead dissociation and redistribution properties of actual contaminated farmland soil after long-term EKAPR treatment.

Electrokinetic-assisted phytoremediation (EKAPR) is a potential technology much affected by the metal species and accessibility to plant roots. In this study, Pb-contaminated red soil was remediated with Sedum plumbizincicola to investigate the changes in soil pH, available nutrients, dissociation and redistribution of Pb under a long-term periodic reversal direct-current electric field. This approach could effectively activate soil P, K, organic matter (OM) and Pb, without significant soil acidification; the effect was positively correlated with applied voltage. Soil Pb can be continuously dissociated, migrated, and tended to accumulate in the middle region. The maximum Pb removal rate in the anodic section of the EKAPR system was 21.4%, and the aggregation rate in middle regions was 14.4%, higher than the available Pb content of the original soil. The Pb desorption in aqueous solution increased significantly with increasing voltage, irrespective of the solution pH. At a voltage of 20 V, the Pb cumulative desorption content reached 91.1 mg kg-1 (pH = 7), which was 2.7 times than that without electric field (33.2 mg kg-1). Compared to original soil (2.80 mg kg-1) and the control (14.54 mg kg-1), the available Pb in the anode section of EKAPR system (20.66 mg kg-1) increased by 637.9% and 42.1%, respectively. These results indicated that except for the indirect influence of soil pH changes, electrodynamics can directly promote the bioavailability and dissociation of Pb at the soil-water interface. This finding provides a new perspective for further studies on the mechanism of Pb speciation evolution and accumulation changes using EKAPR.