Multifactor assessment of ovarian cancer reveals immunologically interpretable molecular subtypes with distinct prognoses.

Background: Ovarian cancer (OC) is a highly heterogeneous and malignant gynecological cancer, thereby leading to poor clinical outcomes. The study aims to identify and characterize clinically relevant subtypes in OC and develop a diagnostic model that can precisely stratify OC patients, providing more diagnostic clues for OC patients to access focused therapeutic and preventative strategies. Methods: Gene expression datasets of OC were retrieved from TCGA and GEO databases. To evaluate immune cell infiltration, the ESTIMATE algorithm was applied. A univariate Cox analysis and the two-sided log-rank test were used to screen OC risk factors. We adopted the ConsensusClusterPlus algorithm to determine OC subtypes. Enrichment analysis based on KEGG and GO was performed to determine enriched pathways of signature genes for each subtype. The machine learning algorithm, support vector machine (SVM) was used to select the feature gene and develop a diagnostic model. A ROC curve was depicted to evaluate the model performance. Results: A total of 1,273 survival-related genes (SRGs) were firstly determined and used to clarify OC samples into different subtypes based on their different molecular pattern. SRGs were successfully stratified in OC patients into three robust subtypes, designated S-I (Immunoreactive and DNA Damage repair), S-II (Mixed), and S-III (Proliferative and Invasive). S-I had more favorable OS and DFS, whereas S-III had the worst prognosis and was enriched with OC patients at advanced stages. Meanwhile, comprehensive functional analysis highlighted differences in biological pathways: genes associated with immune function and DNA damage repair including CXCL9, CXCL10, CXCL11, APEX, APEX2, and RBX1 were enriched in S-I; S-II combined multiple gene signatures including genes associated with metabolism and transcription; and the gene signature of S-III was extensively involved in pathways reflecting malignancies, including many core kinases and transcription factors involved in cancer such as CDK6, ERBB2, JAK1, DAPK1, FOXO1, and RXRA. The SVM model showed superior diagnostic performance with AUC values of 0.922 and 0.901, respectively. Furthermore, a new dataset of the independent cohort could be automatically analyzed by this innovative pipeline and yield similar results. Conclusion: This study exploited an innovative approach to construct previously unexplored robust subtypes significantly related to different clinical and molecular features for OC and a diagnostic model using SVM to aid in clinical diagnosis and treatment. This investigation also illustrated the importance of targeting innate immune suppression together with DNA damage in OC, offering novel insights for further experimental exploration and clinical trial.

An experimental study for quantitative assessment of fatty infiltration and blood flow perfusion in quadriceps muscle of rats using IDEAL-IQ and BOLD-MRI for early diagnosis of sarcopenia.

BACKGROUND: Severe sarcopenia may result in severe disability. Early diagnosis is currently the key to enhancing the treatment of sarcopenia, and there is an urgent need for a highly sensitive and dependable tool to evaluate the course of early sarcopenia in clinical practice. This study aims to investigate longitudinally the early diagnosability of magnetic resonance imaging (MRI)-based fat infiltration and blood flow perfusion technology in sarcopenia progression. METHODS: 48 Sprague-Dawley rats were randomly assigned into six groups that were based on different periods of dexamethasone (DEX) injection (0, 2, 4, 6, 8, 10 days). Multimodal MRI was scanned to assess muscle mass. Grip strength and swimming exhaustion time of rats were measured to assess muscle strength and function. Immunofluorescence staining for CD31 was employed to assess skeletal muscle capillary formation, and western blot was used to detect vascular endothelial growth factor-A (VEGF-A) and muscle ring finger-1 (MuRF-1) protein expression. Subsequently, we analyzed the correlation between imaging and histopathologic parameters. A receiver operating characteristic (ROC) analysis was conducted to assess the effectiveness of quantitative MRI parameters for discriminating diagnosis in both pre- and post-modeling of DEX-induced sarcopenic rats. RESULTS: Significant differences were found in PDFF, R2* and T2 values on day 2 of DEX-induction compared to the control group, occurring prior to the MRI-CSA values and limb grip strength on day 6 of induction and swimming exhaustion time on day 8 of induction. There is a strong correlation between MRI-CSA with HE-CSA values (r = 0.67; p < 0.001), oil red O (ORO) area with PDFF (r = 0.67; p < 0.001), microvascular density (MVD) (r = -0.79; p < 0.001) and VEGF-A (r = -0.73; p < 0.001) with R2*, MuRF-1 with MRI-CSA (r = -0.82; p < 0.001). The AUC of PDFF, R2*, and T2 values used for modeling evaluation are 0.81, 0.93, and 0.98, respectively. CONCLUSION: Imaging parameters PDFF, R2*, and T2 can be used to sensitively evaluate early pathological changes in sarcopenia. The successful construction of a sarcopenia rat model can be assessed when PDFF exceeds 1.25, R2* exceeds 53.85, and T2 exceeds 33.88.

Global, regional, and national burden of neonatal sepsis and other neonatal infections, 1990-2019: findings from the Global Burden of Disease Study 2019.

To provide an overview of the global, regional, and national incidence and mortality of neonatal sepsis and other neonatal infections (NS) and their change trends from 1990 to 2019, based on the data from the 2019 Global Burden of Disease study. This was a retrospective demographic analysis based on aggregated data. Annual incident cases, deaths, age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR) and their percentage changes of NS during 1990-2019 were collected from the 2019 Global Burden of Disease study. Globally, the incident cases of NS increased by 12.79% (from 5.59 million in 1990 to 6.31 million in 2019), and the deaths decreased by 12.93% (from 0.26 million in 1990 to 0.23 million in 2019). In the globe, the ASIR of NS per 100,000 population increased by 14.35% (from 85.21 in 1990 to 97.43 in 2019), and the ASMR decreased by 11.91% (from 3.97 in 1990 to 3.5 in 2019). CONCLUSION: Increasing trends in incidence and decreasing trends in mortality of NS were observed worldwide from 1990 to 2019. More robust epidemiological research and effective health strategies are urgently needed to reduce the disease burden of neonatal sepsis worldwide. WHAT IS KNOWN: • Neonatal sepsis has significant impacts on neonatal health, but estimates on the global burden and trends of neonatal sepsis are scarce and existing findings vary considerably. WHAT IS NEW: • Globally, there were 6.31 million incident cases of neonatal sepsis and 0.23 million deaths due to neonatal sepsis. • Increasing trends in incidence and decreasing trends in mortality of neonatal sepsis were observed worldwide from 1990 to 2019, with the highest absolute burden in sub-Saharan Africa and Asia.

Comprehensive assessment of dissolved organic matter processing in the Amazon River and its major tributaries revealed by positive and negative electrospray mass spectrometry and NMR spectroscopy.

Rivers are natural biogeochemical systems shaping the fates of dissolved organic matter (DOM) from leaving soils to reaching the oceans. This study focuses on Amazon basin DOM processing employing negative and positive electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (ESI[±] FT-ICR MS) and nuclear magnetic resonance spectroscopy (NMR) to reveal effects of major processes on the compositional space and structural characteristics of black, white and clear water systems. These include non-conservative mixing at the confluences of (1) Solimões and the Negro River, (2) the Amazon River and the Madeira River, and (3) in-stream processing of Amazon River DOM between the Madeira River and the Tapajós River. The Negro River (black water) supplies more highly oxygenated and high molecular weight compounds, whereas the Solimões and Madeira Rivers (white water) contribute more CHNO and CHOS molecules to the Amazon River main stem. Aliphatic CHO and abundant CHNO compounds prevail in Tapajos River DOM (clear water), likely originating from primary production. Sorption onto particles and heterotrophic microbial degradation are probably the principal mechanisms for the observed changes in DOM composition in the Amazon River and its tributaries.

Assessment of the oral health literacy and oral health behaviors among nurses in China: a cross-sectional study.

PURPOSE: Oral health is important for general health; nurses are expected to possess good oral health awareness and work together for public oral health promotion. The purpose of this study is to investigate oral health literacy (OHL)and oral health behaviors of nurses, and explore the association between oral health literacy with demographic variables and oral health behaviors. METHODS: A cross-sectional study in a tertiary hospital was conducted using a short-form Health Literacy in Dentistry-14 (HeLD-14) and a 16-items oral health behaviors questionnaire. Information about the subjects' demographic details including age, gender, place of residence, marital status, marital status, education level, monthly household income, working experience, etc. were collected. Independent sample t- test, One- way ANOVA, and multivariable regression were used to identify the association of oral health literacy with demographic variables and oral health behaviors. RESULTS: A total number of 317 nursing nurses participated in the survey, with a mean OHL score of 36.72, SD10.531, 21.8% were categorized as good, 34.1% medium and 44.2% poor oral health literacy; monthly household income, self-rated oral health, brushing time, use of fluoride toothpaste, and regular oral examination were signficantly associated with OHL scores. CONCLUSION: The overall oral health literacy of the nurse population is at a moderate to low level. These findings may help to map and design an oral health education intervention to improve oral health literacy amongst nurses, especially nurses with low monthly household income and poor self-assessed oral health status. Nursing administrators and nursing educators should pay more attention to the oral health status of the nurse population.

Accessibility of essential anticancer medicines for children in the Sichuan Province of China.

Background: Compared with high-income countries, the survival rate of childhood cancer is lower in low- and middle-income countries. Access to essential anticancer medicines is an indispensable component of pediatric cancer treatment, which is still a big challenge in low- and middle-income countries. Objective: To assess the accessibility of essential anticancer medicines for children in public hospitals in the Sichuan Province of China. Methods: Based on the data of the Sichuan Province Drug Use Monitoring Platform in 2020, a retrospective study was conducted to investigate the original brands and generics of 34 anticancer and three supportive essential medicines for children (a total of 97 specific strengths) in Sichuan Province. The availability, price, and affordability of surveyed medicines were evaluated in all 152 tertiary public hospitals (120 general hospitals, 31 children's hospitals, and one cancer hospital) that could diagnose and treat cancer for children. Results: The average availability of generics and original brands was 18.5% and 2.6%, respectively. In regions with different gross domestic product (GDP) per capita levels, the average availability was similar, but the city with lower GDP per capita levels had fewer tertiary public hospitals. The prices of most original brands were higher than the lowest-priced generics, and the median price ratios of 31 lowest-priced generics and 16 original brands were 0.744 (P25~P75, 0.446~2.791) and 2.908 (1.719~6.465). After paying medical insurance for medicines, the affordability of essential anticancer medicines was improved. The monthly medicine cost did not exceed 10% of the monthly household income for 78.9% (30/38) of the lowest-priced generics and 50.0% (8/16) of the original brands. Conclusion: The availability of lowest-priced generics was higher than original brands in public hospitals, but the availability of both was low, which was similar to previous studies in low- and middle-income countries. About half of the lowest-priced generics and 87.5% of the original brands cost more than 1.5 times the International Reference Price. Although the National Basic Medical Insurance greatly improved the affordability of essential anticancer medicines for children, higher subsidies for essential medicines for cancer treatment to limit catastrophic health expenditures are still recommended.

Changes in physical activity after joining a bikeshare program: a cohort of new bikeshare users.

BACKGROUND: There are hundreds of bikeshare programs worldwide, yet few health-related evaluations have been conducted. We enrolled a cohort of new bikeshare members in Philadelphia (Pennsylvania, USA) to assess whether within-person moderate and vigorous physical activity (MVPA) increased with higher use of the program and whether effects differed for vulnerable sub-groups. METHODS: During 2015-2018, 1031 new members completed baseline and one-year follow-up online surveys regarding their personal characteristics and past 7-day MVPA minutes per week (minutes per week with- and without walking). Participants were linked to their bikeshare trips to objectively assess program use. Negative binomial (for continuous outcomes) and multinomial (for categorical outcomes) regression adjusted for person characteristics (socio-demographics, health), weather, biking-infrastructure, and baseline biking. RESULTS: Participant median age was 30, 25% were of Black or Latino race/ethnicity, and 30% were socioeconomically disadvantaged. By follow-up, personal bike ownership increased and 75% used bikeshare, although most used it infrequently. Per 10 day change in past year (PY) bikeshare use, non-walking MVPA min/wk increased 3% (roughly 6 min/wk, P < 0.014). More days of bikeshare was also associated with change from inactive to more active (odds ratio for ≥ 15 days in PY vs. no bikeshare use 1.80, CI 1.05-3.09, P < 0.03). Results were consistent across vulnerable sub-groups. In general, impacts on MVPA were similar when exposure was personal bike or bikeshare. CONCLUSIONS: Bikeshare facilitated increases in cycling, slightly increased non-walking MVPA, and showed potential for activating inactive adults; however, for larger program impact, members will need to use it more frequently.

Access to medicines for children in China.

Access to essential medicines for children is a big challenge, particularly in low-income and middle-income countries. In China, the average availability of essential medicines for children is 1.6%-46.5%. The availability of generics was generally higher than original brands in public hospitals and the prices of generics were relatively lower and more reasonable (generics: availability, 27.3%-46.5%, prices, 0.52-4.28 times the international reference prices; original brands: 1.6%-33.0%, 2.59-11.38 times the international reference prices). In terms of affordability of medicines for children, generics were more affordable than original brands and tablets/capsules were more affordable than injections. Most commonly used anti-infective medicines (such as amoxicillin capsule, azithromycin tablet, cefuroxime tablet) and antipyretics (such as ibuprofen suspension) were relatively affordable. Six commonly used medicines in paediatrics, including amoxicillin/clavulanic acid, beclomethasone, cefazolin, ceftazidime, ceftriaxone, cyclosporine were unaffordable. Since August 2011, China has successively issued several policies to ensure the accessibility of medicines for children, covering research and development, production, procurement and prices of medicines. The accessibility of medicines for children has been partially improved, but still needs continuous improvement.

How a Virus Circumvents Energy Barriers to Form Symmetric Shells.

Previous self-assembly experiments on a model icosahedral plant virus have shown that, under physiological conditions, capsid proteins initially bind to the genome through an en masse mechanism and form nucleoprotein complexes in a disordered state, which raises the question as to how virions are assembled into a highly ordered structure in the host cell. Using small-angle X-ray scattering, we find out that a disorder-order transition occurs under physiological conditions upon an increase in capsid protein concentrations. Our cryo-transmission electron microscopy reveals closed spherical shells containing in vitro transcribed viral RNA even at pH 7.5, in marked contrast with the previous observations. We use Monte Carlo simulations to explain this disorder-order transition and find that, as the shell grows, the structures of disordered intermediates in which the distribution of pentamers does not belong to the icosahedral subgroups become energetically so unfavorable that the caps can easily dissociate and reassemble, overcoming the energy barriers for the formation of perfect icosahedral shells. In addition, we monitor the growth of capsids under the condition that the nucleation and growth is the dominant pathway and show that the key for the disorder-order transition in both en masse and nucleation and growth pathways lies in the strength of elastic energy compared to the other forces in the system including protein-protein interactions and the chemical potential of free subunits. Our findings explain, at least in part, why perfect virions with icosahedral order form under different conditions including physiological ones.

A SWAT-based optimization tool for obtaining cost-effective strategies for agricultural conservation practice implementation at watershed scales.

To address the harmful algal blooms problem in Lake Erie, one solution is to determine the most cost-effective strategies for implementing agricultural best management practices (BMPs) in the Maumee River watershed. An optimization tool, which combines multi-objective optimization algorithms, SWAT (Soil and Water Assessment Tool), and a computational efficient framework, was created to optimally identify agricultural BMPs at watershed scales. The optimization tool was demonstrated in the Matson Ditch watershed, an agricultural watershed in the Maumee River basin considering critical areas (25% of the watershed with the greatest pollutant loadings per area) and the entire watershed. The initial implementation of BMPs with low expenditures greatly reduced pollutant loadings; beyond certain levels of pollutant reductions, additional expenditures resulted in less significant reductions in pollutant loadings. Compared to optimization for the entire watershed, optimization in critical areas can greatly reduce computational time and obtain similar optimization results for initial reductions in pollutant loadings, which were 10% for Dissolved Reactive Phosphorus (DRP) and 38% for Total Phosphorus (TP); however, for greater reductions in pollutant loadings, critical area optimization was less cost-effective. With the target of simultaneously reducing March-July DRP/TP losses by 40%, the optimized scenario that reduced DRP losses by 40% was found to reduce 51.1% of TP; however, the optimized scenario that reduced TP losses by 40% can only decrease 11.3% of DRP. The optimization tool can help stakeholders identify optimal types, quantities, and spatial locations of BMPs that can maximize reductions in pollutant loadings with the lowest BMP costs.