Optical Force Effects of Rayleigh Particles by Cylindrical Vector Beams.

High-order cylindrical vector beams possess flexible spatial polarization and exhibit new effects and phenomena that can expand the functionality and enhance the capability of optical systems. However, building a general analytical model for highly focused beams with different polarization orders remains a challenge. Here, we elaborately develop the vector theory of high-order cylindrical vector beams in a high numerical aperture focusing system and achieve the vectorial diffraction integrals for describing the tight focusing field with the space-variant distribution of polarization orders within the framework of Richards-Wolf diffraction theory. The analytical formulae include the exact three Cartesian components of electric and magnetic distributions in the tightly focused region. Additionally, utilizing the analytical formulae, we can achieve the gradient force, scattering force, and curl-spin force exerted on Rayleigh particles trapped by high-order cylindrical vector beams. These results are crucial for improving the design and engineering of the tightly focused field by modulating the polarization orders of high-order cylindrical vector beams, particularly for applications such as optical tweezers and optical manipulation. This theoretical analysis also extends to the calculation of complicated optical vortex vector fields and the design of diffractive optical elements with high diffraction efficiency and resolution.

Quantitative evaluation and mechanism analysis of soil chemical factors affecting rice yield in saline-sodic paddy fields.

Salinization and sodication have become an important abiotic stress affecting soil fertility and crop production in the western of the Songnen Plain in Northeast China. And rice cultivation is considered as one of the most effective biological methods to reclaim saline-sodic soils and ensure food security. However, it is difficult to select the optimal measures to regulate rice growth for increasing yield, because the independent and comprehensive influences of the soil limitation factors on rice yield are not quantitatively evaluated. In this study, the hierarchical partitioning (HP) and the structural equation model (SEM) were used to quantitatively evaluate the influences of salinization parameters, salt ion concentrations and soil nutrients to identify the dominant limitation factors and obstacle mechanism for rice yield. The results showed that soil pH was the key index in salinization parameters, [CO32- + HCO3-] was the key index in salt ion concentrations and available nitrogen (AN) was the key index in soil nutrients to impact rice yield, which independent influences reached 53.7 %, 45.4 % (negative) and 53.2 % (positive), respectively. Soil pH was determined by [CO32- + HCO3-], and the negative effect of alkali stress on rice yield mainly caused by [CO32- + HCO3-] was greater than that of salt stress mainly caused by [Na+] in saline-sodic paddy fields. Among the soil chemical factors, soil pH and AN were the most important explanatory variables of rice yield in saline-sodic paddy fields, which standardized total effects were - 0.32 and 0.40, respectively. Furthermore, the AN showed a more significant negative correlation with soil pH and a higher yield-increasing potential in severe saline-sodic soils (9 ≤ pH < 10) than that in moderate saline-sodic soils (8 ≤ pH < 9). Therefore, decreasing [CO32- + HCO3-] and increasing the content of AN are key to improve rice yield in saline-sodic paddy fields.

Decidual macrophage: a reversible role in immunotolerance between mother and fetus during pregnancy.

The tolerance of the semi-allogeneic fetus by the maternal immune system is an eternal topic of reproductive immunology for ensuring a satisfactory outcome. The maternal-fetal interface serves as a direct portal for communication between the fetus and the mother. It is composed of placental villi trophoblast cells, decidual immune cells, and stromal cells. Decidual immune cells engage in maintaining the homeostasis of the maternal-fetal interface microenvironment. Furthermore, growing evidence has shown that decidual macrophages play a crucial role in maternal-fetal tolerance during pregnancy. As the second largest cell population among decidual immune cells, decidual macrophages are divided into two subtypes: classically activated macrophages (M1) and alternatively activated macrophages (M2). M2 polarization is critical for placentation and embryonic development. Cytokines, exosomes, and metabolites regulate the polarization of decidual macrophages, and thereby modulate maternal-fetal immunotolerance. Explore the initial relationship between decidual macrophages polarization and maternal-fetal immunotolerance will help diagnose and treat the relevant pregnancy diseases, reverse the undesirable outcomes of mothers and infants.

Sialic Acid Conjugate-Modified Cationic Liposomal Paclitaxel for Targeted Therapy of Lung Metastasis in Breast Cancer: What a Difference the Cation Content Makes.

Cationic lipids play a pivotal role in developing novel drug delivery systems for diverse biomedical applications, owing to the success of mRNA vaccines against COVID-19 and the Phase III antitumor agent EndoTAG-1. However, the therapeutic potential of these positively charged liposomes is limited by dose-dependent toxicity. While an increased content of cationic lipids in the formulation can enhance the uptake and cytotoxicity toward tumor-associated cells, it is crucial to balance these advantages with the associated toxic side effects. In this work, we synthesized the cationic lipid HC-Y-2 and incorporated it into sialic acid (SA)-modified cationic liposomes loaded with paclitaxel to target tumor-associated immune cells efficiently. The SA-modified cationic liposomes exhibited enhanced binding affinity toward both RAW264.7 cells and 4T1 tumor cells in vitro due to the increased ratios of cationic HC-Y-2 content while effectively inhibiting 4T1 cell lung metastasis in vivo. By leveraging electrostatic forces and ligand-receptor interactions, the SA-modified cationic liposomes specifically target malignant tumor-associated immune cells such as tumor-associated macrophages (TAMs), reduce the proportion of cationic lipids in the formulation, and achieve dual objectives: high cellular uptake and potent antitumor efficacy. These findings highlight the potential advantages of this innovative approach utilizing cationic liposomes.

Exosomal miR-146a-5p derived from human umbilical cord mesenchymal stem cells can alleviate antiphospholipid antibody-induced trophoblast injury and placental dysfunction by regulating the TRAF6/NF-κB axis.

Exosomes originating from human umbilical cord mesenchymal stem cells (hucMSC-exos) have become a novel strategy for treating various diseases owing to their ability to regulate intercellular signal communication. However, the potential of hucMSC-exos to improve placental injury in obstetric antiphospholipid syndrome and its underlying mechanism remain unclear. Our objective was to explore the potential application of hucMSC-exos in the treatment of obstetric antiphospholipid syndrome and elucidate its underlying mechanism. In our study, hucMSC-exos ameliorated the functional impairment of trophoblasts caused by antiphospholipid antibodies in vitro and attenuated placental dysfunction in mice with obstetric antiphospholipid syndrome by delivering miR-146a-5p. Exosomal miR-146a-5p suppressed the expression of tumor necrosis factor receptor-associated factor 6 (TRAF6) and inhibited the activation of NF-κB signaling, leading to the down-regulation of IL-1ß and IL-18 to rescue inflammation and modulation of Cleaved-CASP3, BAX, and BCL2 to inhibit apoptosis in HTR8/SVneo cells and mice placenta. This study identified the potential molecular basis of how hucMSC-exos improved antiphospholipid antibody-induced placental injury and highlighted the functional importance of the miR-146a-5p/TRAF6 axis in the progression of obstetric antiphospholipid syndrome. More importantly, this study provided a fresh outlook on the promising use of hucMSC-exos as a novel and effective treatment approach in obstetric antiphospholipid syndrome.

Preeclampsia impedes foetal kidney development by delivering placenta-derived exosomes to glomerular endothelial cells.

BACKGROUND: Foetal renal dysplasia is still the main cause of adult renal disease. Placenta-derived exosomes are an important communication tool, and they may play an important role in placental (both foetal and maternal) function. We hypothesize that in women with preeclampsia, foetal renal dysplasia is impeded by delivering placenta-derived exosomes to glomerular endothelial cells. METHODS: In the present study, we established a PE trophoblast oxidative stress model to isolate exosomes from supernatants by ultracentrifugation (NO-exo and H/R-exo) and collected normal and PE umbilical cord blood plasma to isolate exosomes by ultracentrifugation combined with sucrose density gradient centrifugation (N-exo and PE-exo), then we investigated their effects on foetal kidney development by in vitro, ex vivo and in vivo models. RESULTS: The PE trophoblast oxidative stress model was established successfully. After that, in in vitro studies, we found that H/R-exo and PE-exo could adversely affect glomerular endothelial cell proliferation, tubular formation, migration, and barrier functions. In ex vivo studies, H/R-exo and PE-exo both inhibited the growth and branch formation of kidney explants, along with the decrease of VE-cadherin and Occludin. In in vivo studies, we also found that H/R-exo and PE-exo could result in renal dysplasia, reduced glomerular number, and reduced barrier function in foetal mice. CONCLUSIONS: In conclusion, we demonstrated that PE placenta-derived exosomes could lead to foetal renal dysplasia by delivering placenta-derived exosomes to foetal glomerular endothelial cells, which provides a novel understanding of the pathogenesis of foetal renal dysplasia. Video Abstract.

Longitudinal wastewater surveillance of four key pathogens during an unprecedented large-scale COVID-19 outbreak in China facilitated a novel strategy for addressing public health priorities-A proof of concept study.

Wastewater-based epidemiology (WBE) is a promising tool for monitoring the spread of SARS-CoV-2 and other pathogens, providing a novel public health strategy to combat disease. In this study, we first analysed nationwide reports of infectious diseases and selected Salmonella, norovirus, and influenza A virus (IAV) as prioritized targets apart from SARS-CoV-2 for wastewater surveillance. Next, the decay rates of Salmonella, norovirus, and IAV in wastewater at various temperatures were established to obtain corrected pathogen concentrations in sewage. We then monitored the concentrations of these pathogens in wastewater treatment plant (WWTP) influents in three cities, establishing a prediction model to estimate the number of infected individuals based on the mass balance between total viral load in sewage and individual viral shedding. From October 2022 to March 2023, we conducted multipathogen wastewater surveillance (MPWS) in a WWTP serving one million people in Xi'an City, monitoring the concentration dynamics of SARS-CoV-2, Salmonella, norovirus, and IAV in sewage. The infection peaks of each pathogen were different, with Salmonella cases and sewage concentration declining from October to December 2022 and only occasionally detected thereafter. The SARS-CoV-2 concentration rapidly increased from December 5th, peaked on December 26th, and then quickly decreased until the end of the study. Norovirus and IAV were detected in wastewater from January to March 2023, peaking in February and March, respectively. We used the prediction models to estimate the rate of SARS-CoV-2 infection in Xi'an city, with nearly 90 % of the population infected in urban regions. There was no significant difference between the predicted and actual number of hospital admissions for IAV. We also accurately predicted the number of norovirus cases relative to the reported cases. Our findings highlight the importance of wastewater surveillance in addressing public health priorities, underscoring the need for a novel workflow that links the prediction results of populations with public health interventions and allocation of medical resources at the community level. This approach would prevent medical resource panic squeezes, reduce the severity and mortality of patients, and enhance overall public health outcomes.

Aging effects on residential biomass burning emissions under quasi-real atmospheric conditions.

Emissions from biomass burning (BB) vastly contribute to the atmospheric trace gases and particles, which affect air quality and human health. After emission, the chemical evolution changes the mass and composition of organic aerosol (OA) in the diluted and aged plume. In this study, we used a quasi-real atmospheric smog chamber system to conduct aging experiments and investigated the multiphase oxidation of primary organic aerosol (POA) and the formation of secondary organic aerosols (SOA) in residential biomass burning plumes. We found that the emissions in the gas and particle phases were interlinked during the plume evolution. During photochemical aging, more oxidized OA was produced, and SOA formation increased by a factor of 2 due to functionalization reactions of gaseous precursors such as furans, phenols, and carbonyls. On the other hand, dark aging resulted in a lower OA mass enhancement by a factor of 1.2, with weaker oxidation from gaseous reactions. Dark aging experiments resulted in the generation of substantial quantities of nitrogen-containing organic compounds in both gas and particulate phases, while photochemical aging led to a notable increase in the concentration of gaseous carboxylic acids. Our observations show that the properties of SOA are influenced by exposure to sunlight radiation and oxidants such as OH or NO3 radicals. These results reflect the aging process of BB plumes in real-world atmospheric conditions and highlight the importance of considering various aging mechanisms.

Overall and patient-specific comparative effectiveness of dimethyl fumarate versus teriflunomide: A novel approach to precision medicine applied to the German NeuroTrans Data Multiple Sclerosis Registry.

Background: Multiple sclerosis (MS) comparative effectiveness research needs to go beyond average treatment effects (ATEs) and post-host subgroup analyses. Objective: This retrospective study assessed overall and patient-specific effects of dimethyl fumarate (DMF) versus teriflunomide (TERI) in patients with relapsing-remitting MS. Methods: A novel precision medicine (PM) scoring approach leverages advanced machine learning methods and adjusts for imbalances in baseline characteristics between patients receiving different treatments. Using the German NeuroTransData registry, we implemented and internally validated different scoring systems to distinguish patient-specific effects of DMF relative to TERI based on annualized relapse rates, time to first relapse, and time to confirmed disease progression. Results: Among 2791 patients, there was superior ATE of DMF versus TERI for the two relapse-related endpoints (p = 0.037 and 0.018). Low to moderate signals of treatment effect heterogeneity were detected according to individualized scores. A MS patient subgroup was identified for whom DMF was more effective than TERI (p = 0.013): older (45 versus 38 years), longer MS duration (110 versus 50 months), not newly diagnosed (74% versus 40%), and no prior glatiramer acetate usage (35% versus 5%). Conclusion: The implemented approach can disentangle prognostic differences from treatment effect heterogeneity and provide unbiased patient-specific profiling of comparative effectiveness based on real-world data.

Assessing the utility of magnetic resonance imaging-based "SuStaIn" disease subtyping for precision medicine in relapsing-remitting and secondary progressive multiple sclerosis.

BACKGROUND: Patient stratification and individualized treatment decisions based on multiple sclerosis (MS) clinical phenotypes are arbitrary. Subtype and Staging Inference (SuStaIn), a published machine learning algorithm, was developed to identify data-driven disease subtypes with distinct temporal progression patterns using brain magnetic resonance imaging; its clinical utility has not been assessed. The objective of this study was to explore the prognostic capability of SuStaIn subtyping and whether it is a useful personalized predictor of treatment effects of natalizumab and dimethyl fumarate. METHODS: Subtypes were available from the trained SuStaIn model for 3 phase 3 clinical trials in relapsing-remitting and secondary progressive MS. Regression models were used to determine whether baseline SuStaIn subtypes could predict on-study clinical and radiological disease activity and progression. Differences in treatment responses relative to placebo between subtypes were determined using interaction terms between treatment and subtype. RESULTS: Natalizumab and dimethyl fumarate reduced inflammatory disease activity in all SuStaIn subtypes (all p < 0.001). SuStaIn MS subtyping alone did not discriminate responder heterogeneity based on new lesion formation and disease progression (p > 0.05 across subtypes). CONCLUSION: SuStaIn subtypes correlated with disease severity and functional impairment at baseline but were not predictive of disability progression and could not discriminate treatment response heterogeneity.

Glial fibrillary acidic protein and multiple sclerosis progression independent of acute inflammation.

BACKGROUND: The clinical relevance of serum glial fibrillary acidic protein (sGFAP) concentration as a biomarker of MS disability progression independent of acute inflammation has yet to be quantified. OBJECTIVE: To test whether baseline values and longitudinal changes in sGFAP concentration are associated with disability progression without detectable relapse of magnetic resonance imaging (MRI) inflammatory activity in participants with secondary-progressive multiple sclerosis (SPMS). METHODS: We retrospectively analyzed longitudinal sGFAP concentration and clinical outcome data from the Phase 3 ASCEND trial of participants with SPMS, with no detectable relapse or MRI signs of inflammatory activity at baseline nor during the study (n = 264). Serum neurofilament (sNfL), sGFAP, T2 lesion volume, Expanded Disability Status Scale (EDSS), Timed 25-Foot Walk (T25FW), 9-Hole Peg Test (9HPT), and composite confirmed disability progression (CDP) were measured. Linear and logistic regressions and generalized estimating equations were used in the prognostic and dynamic analyses. RESULTS: We found a significant cross-sectional association between baseline sGFAP and sNfL concentrations and T2 lesion volume. No or weak correlations between sGFAP concentration and changes in EDSS, T25FW, and 9HPT, or CDP were observed. CONCLUSION: Without inflammatory activity, changes in sGFAP concentration in participants with SPMS were neither associated with current nor predictive of future disability progression.

Real-World Safety and Effectiveness After 5 Years of Dimethyl Fumarate Treatment in Black and Hispanic Patients with Multiple Sclerosis in ESTEEM.

INTRODUCTION: Multiple sclerosis (MS) clinical trials have included low numbers of patients from racial and ethnic minority populations; therefore, it is uncertain whether differences exist in response to disease-modifying therapies. We evaluated the real-world safety and effectiveness of dimethyl fumarate (DMF) treatment over 5 years in four patient cohorts: Black, non-Black, Hispanic, and non-Hispanic people with relapsing-remitting MS. METHODS: ESTEEM is an ongoing, 5-year, multinational, prospective study evaluating the long-term safety and effectiveness of DMF in people with MS. The analysis included patients newly prescribed DMF in routine practice at 393 sites globally. RESULTS: Overall, 5251 patients were analyzed (220 Black, 5031 non-Black; 105 Hispanic, 5146 non-Hispanic). Median (min-max) months of follow-up was 32 (0-72) for Black, 29 (1-77) for Hispanic, and 41 (0-85) for both the non-Black and non-Hispanic populations. In total, 39 (18%) Black and 29 (28%) Hispanic patients reported adverse events leading to treatment discontinuation versus 1126 (22%) non-Black and 1136 (22%) non-Hispanic patients; gastrointestinal disorders were the most common in all subgroups. Median lymphocyte counts decreased by 37% in Black, 40% in non-Black, 10% in Hispanic, and 39% in non-Hispanic patients in the first year, then remained stable and above the lower limit of normal in most patients. Annualized relapse rates (ARRs) (95% confidence intervals) up to 5 years were 0.054 (0.038-0.078) for Black, 0.077 (0.072-0.081) for non-Black, 0.069 (0.043-0.112) for Hispanic, and 0.076 (0.072-0.081) for non-Hispanic populations, representing reductions of 91-92% compared with ARR 12 months before study entry (all p < 0.0001). CONCLUSION: The safety profile of DMF in these subgroups was consistent with the overall ESTEEM population. Relapse rates remained low in Black and Hispanic patients, and consistent with non-Black and non-Hispanic patients. These data demonstrate a comparable real-world treatment benefit of DMF in Black and Hispanic patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02047097.

The role of photorespiration in plant immunity.

To defend themselves in the face of biotic stresses, plants employ a sophisticated immune system that requires the coordination of other biological and metabolic pathways. Photorespiration, a byproduct pathway of oxygenic photosynthesis that spans multiple cellular compartments and links primary metabolisms, plays important roles in defense responses. Hydrogen peroxide, whose homeostasis is strongly impacted by photorespiration, is a crucial signaling molecule in plant immunity. Photorespiratory metabolites, interaction between photorespiration and defense hormone biosynthesis, and other mechanisms, are also implicated. An improved understanding of the relationship between plant immunity and photorespiration may provide a much-needed knowledge basis for crop engineering to maximize photosynthesis without negative tradeoffs in plant immunity, especially because the photorespiratory pathway has become a major target for genetic engineering with the goal to increase photosynthetic efficiency.

Gestational Diabetes Mellitus Impedes Fetal Lung Development Through Exosome-Dependent Crosstalk Between Trophoblasts and Lung Epithelial Cells.

Background: Fetal lung underdevelopment (FLUD) is associated with neonatal and childhood severe respiratory diseases, among which gestational diabetes mellitus (GDM) play crucial roles as revealed by recent prevalence studies, yet mechanism underlying GDM-induced FLUD, especially the role of trophoblasts, is not all known. Methods: From the perspective of trophoblast-derived exosomes, we established in vitro, ex vivo, in vivo and GDM trophoblast models. Utilizing placenta-derived exosomes (NUB-exos and GDMUB-exos) isolated from normal and GDM umbilical cord blood plasma and trophoblast-derived exosomes (NC-exos and HG-exos) isolated from HTR8/SVneo trophoblasts medium with/without high glucose treatment, we examined their effects on fetal lung development and biological functions. Results: We found that, compared with the NUB-exos group, the exosome concentration increased in GDMUB-exos group, and the content of exosomes also changed evidenced by 61 dysregulated miRNAs. After applying these exosomes to A549 alveolar type II epithelial cells, the proliferation and biological functions were suppressed while the proportion of apoptotic cells was increased as compared to the control. In ex vivo studies, we found that GDMUB-exos showed significant suppression on the growth of the fetal lung explants, where the number of terminal buds and the area of explant surface decreased and shrank. Besides, the expression of Fgf10, Vegfa, Flt-1, Kdr and surfactant proteins A, B, C, and D was downregulated in GDMUB-exos group, whilst Sox9 was upregulated. For in vivo studies, we found significant suppression of fetal lung development in GDMUB-exos group. Importantly, we found consistent alterations when we used NC-exos and HG-exos, suggesting a dominant role of trophoblasts in placenta-derived exosome-induced FLUD. Conclusion: In conclusion, GDM can adversely affect trophoblasts and alter exosome contents, causing crosstalk disorder between trophoblasts and fetal lung epithelial cells and finally leading to FLUD. Findings of this study will shine insight into the theoretical explanation for the pathogenesis of FLUD.

Contrasting Near-Surface Ozone Pollution in Wet and Dry Year over China.

The near-surface ozone concentration was evaluated in two typical years with contrasting climatic impacts over the China region induced by El Niño-Southern Oscillation, which had either dry conditions (drought) with intense solar radiation and higher temperatures or wet conditions with opposite meteorological conditions. Surface ozone was observed to aggravate notably by 30% over Northern China in summer and by 50% over Eastern China in autumn in the dry year compared to the wet year. The ozone aggravation was found to be mainly ascribed to the reduced precipitation (relative humidity), enhanced solar radiation and increased temperature rather than primary emission (indicated by carbon monoxide). The health impacts showed the mortality attributable to ozone sharply increased by ~55% in Guangdong while the number of cases dying from ozone-related respiratory diseases per 100,000 population at risk was elevated by ~41% and ~17% for Guangdong (in the Pearl River Delta) and Jiangsu (in the Yangtze River Delta) province (two regions that have been reported to be highly influenced by surface ozone in China), respectively, in the dry year relative to the wet year, indicative of the significant adverse health effects of ozone aggravation. These results highlight the essential contribution of climate anomalies to surface ozone pollution. Efforts to suppress ozone aggravation can be beneficial to public health if extreme drought is predicted, and reasonable policy is implemented.

Single-timepoint low-dimensional characterization and classification of acute versus chronic multiple sclerosis lesions using machine learning.

Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease characterized by the appearance of focal lesions across the central nervous system. The discrimination of acute from chronic MS lesions may yield novel biomarkers of inflammatory disease activity which may support patient management in the clinical setting and provide endpoints in clinical trials. On a single timepoint and in the absence of a prior reference scan, existing methods for acute lesion detection rely on the segmentation of hyperintense foci on post-gadolinium T1-weighted magnetic resonance imaging (MRI), which may underestimate recent acute lesion activity. In this paper, we aim to improve the sensitivity of acute MS lesion detection in the single-timepoint setting, by developing a novel machine learning approach for the automatic detection of acute MS lesions, using single-timepoint conventional non-contrast T1- and T2-weighted brain MRI. The MRI input data are supplemented via the use of a convolutional neural network generating "lesion-free" reconstructions from original "lesion-present" scans using image inpainting. A multi-objective statistical ranking module evaluates the relevance of textural radiomic features from the core and periphery of lesion sites, compared within "lesion-free" versus "lesion-present" image pairs. Then, an ensemble classifier is optimized through a recursive loop seeking consensus both in the feature space (via a greedy feature-pruning approach) and in the classifier space (via model selection repeated after each pruning operation). This leads to the identification of a compact textural signature characterizing lesion phenotype. On the patch-level task of acute versus chronic MS lesion classification, our method achieves a balanced accuracy in the range of 74.3-74.6% on fully external validation cohorts.

Connecting the Light Absorption of Atmospheric Organic Aerosols with Oxidation State and Polarity.

The light-absorbing organic aerosol (OA) constitutes an important fraction of absorbing components, counteracting major cooling effect of aerosols to climate. The mechanisms in linking the complex and changeable chemistry of OA with its absorbing properties remain to be elucidated. Here, by using solvent extraction, ambient OA from an urban environment was fractionated according to polarity, which was further nebulized and online characterized with compositions and absorbing properties. Water extracted high-polar compounds with a significantly higher oxygen to carbon ratio (O/C) than methanol extracts. A transition O/C of about 0.6 was found, below and above which the enhancement and reduction of OA absorptivity were observed with increasing O/C, occurring on the less polar and high polar compounds, respectively. In particular, the co-increase of nitrogen and oxygen elements suggests the important role of nitrogen-containing functional groups in enhancing the absorptivity of the less polar compounds (e.g., forming nitrogen-containing aromatics), while further oxidation (O/C > 0.6) on high-polar compounds likely led to fragmentation and bleaching chromophores. The results here may reconcile the previous observations about darkening or whitening chromophores of brown carbon, and the parametrization of O/C has the potential to link the changing chemistry of OA with its polarity and absorbing properties.

Overall and patient-level comparative effectiveness of dimethyl fumarate and fingolimod: A precision medicine application to the Observatoire Français de la Sclérose en Plaques registry.

Background: Comparing real-world effectiveness and tolerability of therapies for relapsing-remitting multiple sclerosis is increasingly important, though average treatment effects fail to capture possible treatment effect heterogeneity. With the clinical course of the disease being highly heterogeneous across patients, precision medicine methods enable treatment response heterogeneity investigations. Objective: To compare real-world effectiveness and discontinuation profiles between dimethyl fumarate and fingolimod while investigating treatment effect heterogeneity with precision medicine methods. Methods: Adults initiating dimethyl fumarate or fingolimod as a second-line therapy were selected from a French registry. The primary outcome was annualized relapse rate at 12 months. Seven secondary outcomes relative to discontinuation and disease progression were considered. A precision medicine framework was used to characterize treatment effect heterogeneity. Results: Annualized relapse rates at 12 months were similar for dimethyl fumarate and fingolimod. The odd of treatment persistence was 47% lower for patients treated with dimethyl fumarate relative to those treated with fingolimod (odds ratio: 0.53, 95% confidence interval: 0.39, 0.70). None of the five precision medicine scoring approaches identified treatment heterogeneity. Conclusion: These findings substantiated the similar effectiveness and different discontinuation profiles for dimethyl fumarate and fingolimod as a second-line therapy for relapsing-remitting multiple sclerosis, with no significant effect heterogeneity observed.

Three-dimensional macroscopical quantification of plaque accumulation on implant-supported fixed complete dental prostheses surfaces: A methodological pilot study.

STATEMENT OF PROBLEM: Area calculation is the primary method for quantitatively analyzing accumulated plaque on the intaglio surfaces of implant-supported fixed complete dental prostheses (IFCDPs). However, the classic calculation method for stained dental plaque is based on two-dimensional (2D) photographs, which could mislead the three-dimensional (3D) representation of an object's actual morphology, especially when a surface is not flat. PURPOSE: This pilot in vitro study, used for methodological purposes, evaluated the repeatability and precision of a 3D area calculation method to analyze simulated accumulated biofilm on the intaglio surfaces of an IFCDP. MATERIAL AND METHODS: The titanium framework of an IFCDP with a smooth intaglio surface was prepared with 8 milled sites and scanned by microcomputed tomography. Out of these, 4 sites were cubic (set sides lengths=1, 2, 3, and 4 mm), and 4 sites were hemispherical (set diameters=1, 2, 3, and 4 mm). A green-colored aerosol was sprayed onto the carved-out intaglio sites. The framework intaglio surface was 3D-scanned (n=10) and 2D-photographed (n=10) at 10 different photo angles. Two raters twice measured the 3D and 2D data from the carved-out sites' green-colored area one week apart. Intraobserver repeatability and interobserver reliability were evaluated with an independent t test. The deviation between the measurements and the microtomography values was calculated. Pearson's correlation coefficient (r) evaluated the repeatability of multiple measurements. A standard level of significance was set at α=.05. RESULTS: The differences between the 2D photographs and the microtomography values were statistically significant (P<.001), whereas the differences between the 3D scans and the microtomography values were not significant (P=.063). The overall differences between the microtomography values and the 3D measurements were smaller (2.15 ±2.30 mm2 vs. 18.91 ±22.78 mm2, P=.055) than the differences between the microtomography values and the 2D measurements. The percentage differences between the microtomography values and the 3D measurements were significantly smaller (10.41 ±8.33% vs. 65.66 ±19.22%, P<.001) than the microtomography differences values with the 2D measurements. The measurement differences between the microtomography value and the 3D measured hemispherical site data were significantly smaller than the measurement differences between the microtomography values and the 3D measured cubical site data (P=.026). The 2D method had "poor" repeatability among the 10 different shot angles (r=0.391, P<.001), whereas the 3D method had "good" repeatability among the 10 scans (r=0.999, P<.001). CONCLUSIONS: An irregular intaglio surface of an IFCDP could accurately and repeatedly be recorded and analyzed by a 3D area calculation method. This color-matching assessment of the topological environment is expected to be adopted in future studies.

Predicting risk-adjusted incidence rates of methicillin-resistant Staphylococcus Aureus and Pseudomonas Aeruginosa in cystic fibrosis programs in the United States.

BACKGROUND: Healthcare-associated transmission of methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa occurs for people with cystic fibrosis (CF), but CF programs lack a process to monitor incidence rates (IRs). We assessed predictors of incident infections and created a model to determine risk-adjusted IRs for CF programs. METHODS: Using the CF Foundation Patient Registry data for all patients from 2012 to 2015, coefficients for variables that predicted IRs were estimated. Hazard functions were then used to predict IRs of MRSA and P. aeruginosa for CF programs based on their patient and program characteristics. Predicted IRs were compared with observed IRs over multiple time intervals. RESULTS: Multiple patient and program characteristics were identified as predictors of observed IRs. Our model's predicted IRs closely aligned with observed IRs for most CF programs. Alarm values (defined as observed IR > 95% confidence interval of predicted IR) were found at 5.9%, 5.9%, 6.0% (adult, pediatric, affiliate) of programs for MRSA and 3.0%, 1.7%, 0.0% (adult, pediatric, affiliate) of programs for P. aeruginosa. CONCLUSIONS: We found patient and program characteristics that predicted MRSA and P. aeruginosa IRs. Our model accurately predicted risk-adjusted IRs of MRSA and P. aeruginosa. CF programs could use our model to monitor their IRs and potentially improve infection prevention and control.