Multiparametric MRI-based radiomic models for early prediction of response to neoadjuvant systemic therapy in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is often treated with neoadjuvant systemic therapy (NAST). We investigated if radiomic models based on multiparametric Magnetic Resonance Imaging (MRI) obtained early during NAST predict pathologic complete response (pCR). We included 163 patients with stage I-III TNBC with multiparametric MRI at baseline and after 2 (C2) and 4 cycles of NAST. Seventy-eight patients (48%) had pCR, and 85 (52%) had non-pCR. Thirty-six multivariate models combining radiomic features from dynamic contrast-enhanced MRI and diffusion-weighted imaging had an area under the receiver operating characteristics curve (AUC) > 0.7. The top-performing model combined 35 radiomic features of relative difference between C2 and baseline; had an AUC = 0.905 in the training and AUC = 0.802 in the testing set. There was high inter-reader agreement and very similar AUC values of the pCR prediction models for the 2 readers. Our data supports multiparametric MRI-based radiomic models for early prediction of NAST response in TNBC.

A smart hypochlorous acid fluorescent probe enabling Ibuprofen-release for osteoarthritis theranostics.

Background: Osteoarthritis (OA) standing as the most prevalent form of arthritis, closely associates with heightened levels of reactive oxygen species, particularly hypochlorous acid (HOCl). Although there are numerous probes available for detecting HOCl in the OA region, probes with dual functions of diagnostic and therapeutic capabilities are still significantly lacking. While this type of probe can reduce the time gap between diagnosis and treatment, which is clinically needed. Methods: We developed a fluorescent probe (DHU-CBA1) toward HOCl with theranostics functions through the release of methylene blue (MB) and ibuprofen (IBP) in this work. DHU-CBA1 can detect HOCl with high specificity and sensitivity, releasing MB and IBP with an impressive efficiency of ≥ 95% in vitro. Results: DHU-CBA1 exhibits good biosafety, enabling in vivo imaging of endogenous HOCl, along with reducing arthritis scores, improving synovitis and cartilage damage, and maintaining catabolic balance while alleviating senescence in cartilage. Conclusions: This study proposes a novel approach to enhance osteoarthritis therapy by releasing IBP via a smart HOCl-enabled fluorescent probe.

Donor-acceptor bulk-heterojunction sensitizer for efficient solid-state infrared-to-visible photon up-conversion.

Solid-state infrared-to-visible photon up-conversion is important for spectral-tailoring applications. However, existing up-conversion systems not only suffer from low efficiencies and a need for high excitation intensity, but also exhibit a limited selection of materials and complex fabrication processes. Herein, we propose a sensitizer with a bulk-heterojunction structure, comprising both an energy donor and an energy acceptor, for triplet-triplet annihilation up-conversion devices. The up-conversion occurs through charge separation at the donor-acceptor interface, followed by the formation of charge transfer state between the energy donor and annihilator following the spin statistics. The bulk-heterojunction sensitizer ensures efficient charge generation and low charge recombination. Hence, we achieve a highly efficient solid-state up-conversion device with 2.20% efficiency and low excitation intensity (10 mW cm-2) through a one-step solution method. We also demonstrate bright up-conversion devices on highly-flexible large-area substrates. This study introduces a simple and scalable platform strategy for fabricating efficient up-conversion devices.

Modulation of cardiac resident macrophages immunometabolism upon high-fat-diet feeding in mice.

Background: A high-fat diet (HFD) contributes to various metabolic disorders and obesity, which are major contributors to cardiovascular disease. As an essential regulator for heart homeostasis, cardiac resident macrophages may go awry and contribute to cardiac pathophysiology upon HFD. Thus, to better understand how HFD induced cardiac dysfunction, this study intends to explore the transcriptional and functional changes in cardiac resident macrophages of HFD mice. Methods: C57BL/6J female mice that were 6 weeks old were fed with HFD or normal chow diet (NCD) for 16 weeks. After an evaluation of cardiac functions by echocardiography, mouse hearts were harvested and cardiac resident CCR2- macrophages were sorted, followed by Smart sequencing. Bioinformatics analysis including GO, KEGG, and GSEA analyses were employed to elucidate transcriptional and functional changes. Results: Hyperlipidemia and obesity were observed easily upon HFD. The mouse hearts also displayed more severe fibrosis and diastolic dysfunction in HFD mice. Smart sequencing and functional analysis revealed metabolic dysfunctions, especially lipid-related genes and pathways. Besides this, antigen-presentation-related gene such as Ctsf and inflammation, particularly for NF-κB signaling and complement cascades, underwent drastic changes in cardiac resident macrophages. GO cellular compartment analysis was also performed and showed specific organelle enrichment trends of the involved genes. Conclusion: Dysregulated metabolism intertwines with inflammation in cardiac resident macrophages upon HFD feeding in mice, and further research on crosstalk among organelles could shed more light on potential mechanisms.

Duplex Real-Time Fluorescent Quantitative PCR Assays for the Detection of Toxigenic Microcystis Genotypes Based on SNP/InDel Variation in mcy Gene Cluster.

In this study, the toxigenic characteristics of 14 strains of Microcystis were analyzed, and single nucleotide polymorphism (SNP) and insertion/deletion (InDel) loci in microcystin synthetase (mcy) gene clusters were screened. Based on SNP and InDel loci associated with the toxigenic characteristics, primers and TaqMan or Cycling fluorescent probes were designed to develop duplex real-time fluorescent quantitative PCR (FQ-PCR) assays. After evaluating specificity and sensitivity, these assays were applied to detect the toxigenic Microcystis genotypes in a shrimp pond where Microcystis blooms occurred. The results showed a total of 2155 SNP loci and 66 InDel loci were obtained, of which 12 SNP loci and 5 InDel loci were associated with the toxigenic characteristics. Three duplex real-time FQ-PCR assays were developed, each of which could quantify two genotypes of toxigenic Microcystis. These FQ-PCR assays were highly specific, and two Cycling assays were more sensitive than TaqMan assay. In the shrimp pond, six genotypes of toxigenic Microcystis were detected using the developed FQ-PCR assays, indicating that above genotyping assays have the potential for quantitative analysis of the toxigenic Microcystis genotypes in natural water.

Co-Creating a Synchronous Tele-Education Program With Community-Dwelling Older Adults Using a Participatory Approach: A Mixed-Methods Study.

There is a pressing need to include older individuals in health education and uncover their specific needs. Leveraging the advantages of digitized health education, this study employed a participatory approach to engage community-dwelling older adults in co-creating a synchronous tele-education program, with dementia as the focus due to its rising prevalence and associated stigma in Singapore. Our findings demonstrate the preliminary effectiveness and feasibility of tele-education. Participants' feedback and recommendations provided valuable insights and could guide the future development of a comprehensive tele-education program. Participants' satisfaction with the co-design workshops also indicates the potential of involving older generations in the design process of user-centered digital health interventions in online environments. Moving forward, the study advocates collaboration among health institutes, government and social agencies, and community organizations, alongside systematic evaluation of the long-term impacts of tele-education, with the aim of improving health outcomes and reducing health inequalities among the older population.

Frontiers and hotspots in comorbid epilepsy and depression: a bibliometric analysis from 2003 to 2023.

Background: Epilepsy ranks among the most common neurological disorders worldwide, frequently accompanied by depression as a prominent comorbidity. This study employs bibliometric analysis to reveal the research of comorbid epilepsy and depression over the past two decades, aiming to explore trends and contribute insights to ongoing investigations. Methods: We conducted a comprehensive search on the Web of Science Core Collection database and downloaded relevant publications on comorbid epilepsy and depression published from 2003 to 2023. VOSviewer and CiteSpace were mainly used to analyze the authors, institutions, countries, publishing journals, reference co-citation patterns, keyword co-occurrence, keyword clustering, and other aspects to construct a knowledge atlas. Results: A total of 5,586 publications related to comorbid epilepsy and depression were retrieved, with a general upward trend despite slight fluctuations in annual publications. Publications originated from 121 countries and 636 institutions, with a predominant focus on clinical research. The United States led in productivity (1,529 articles), while Melbourne University emerged as the most productive institution (135 articles). EPILEPSY & BEHAVIOR was the journal with the highest publication output (1,189 articles) and citation count. Keyword analysis highlighted emerging trends, including "recognitive impairment" and "mental health," indicating potential future research hotspots and trends. Conclusion: This study is one of the first to perform a bibliometric analysis of the 20-year scientific output of comorbid epilepsy and depression. While research has trended upwards, ambiguity in pathogenesis and the absence of standardized diagnostic guidelines remain concerning. Our analysis offers valuable guidance for researchers, informing that this might be a strong area for future collaborations.

Stretchable Sweat Lactate Sensor with Dual-Signal Read-outs.

Innovations in wearable sweat sensors hold great promise to provide deeper insights into molecular level health information non-invasively. Lactate, a key metabolite present in sweat, holds immense significance in assessing physiological conditions and performance in sports physiology and health sensing. This paper presents the development and characterization of stretchable electrodes with ultrahigh active surface area of 648% for lactate sensing. The as-printed stretchable electrodes were functionalized with an electron transfer layer comprising of Toluidine Blue O and multi-walled carbon nanotubes (MWCNTs), and an enzymatic layer consisting of lactate dehydrogenase with ß-Nicotinamide adenine dinucleotide as the cofactor for lactate selectivity. This sensor achieves a dual-signal read-out in which both electrochemical and fluorescence signals were obtained during lactate detection, demonstrating promising sensor performance in terms of sensitivity and reliability. We demonstrate the robustness of the dual-signal sensor under simulated conditions of physical deformation and shifted excitation. Under these compromised conditions, the performance of the stretchable electrodes remained largely unaffected, showcasing their potential for robust and adaptable sensing platforms in wearable health monitoring applications.

High Hydrostatic Pressure Exacerbates Bladder Fibrosis through Activating Piezo1.

OBJECTIVE: Bladder outlet obstruction (BOO) results in significant fibrosis in the chronic stage and elevated bladder pressure. Piezo1 is a type of mechanosensitive (MS) channel that directly responds to mechanical stimuli. To identify new targets for intervention in the treatment of BOO-induced fibrosis, this study investigated the impact of high hydrostatic pressure (HHP) on Piezo1 activity and the progression of bladder fibrosis. METHODS: Immunofluorescence staining was conducted to assess the protein abundance of Piezo1 in fibroblasts from obstructed rat bladders. Bladder fibroblasts were cultured under normal atmospheric conditions (0 cmH2O) or exposed to HHP (50 cmH2O or 100 cmH2O). Agonists or inhibitors of Piezo1, YAP1, and ROCK1 were used to determine the underlying mechanism. RESULTS: The Piezo1 protein levels in fibroblasts from the obstructed bladder exhibited an elevation compared to the control group. HHP significantly promoted the expression of various pro-fibrotic factors and induced proliferation of fibroblasts. Additionally, the protein expression levels of Piezo1, YAP1, ROCK1 were elevated, and calcium influx was increased as the pressure increased. These effects were attenuated by the Piezo1 inhibitor Dooku1. The Piezo1 activator Yoda1 induced the expression of pro-fibrotic factors and the proliferation of fibroblasts, and elevated the protein levels of YAP1 and ROCK1 under normal atmospheric conditions in vitro. However, these effects could be partially inhibited by YAP1 or ROCK inhibitors. CONCLUSION: The study suggests that HHP may exacerbate bladder fibrosis through activating Piezo1.

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OBJECTIVES: To investigate the risk factors for bronchopulmonary dysplasia (BPD) in twin preterm infants with a gestational age of <34 weeks, and to provide a basis for early identification of BPD in twin preterm infants in clinical practice. METHODS: A retrospective analysis was performed for the twin preterm infants with a gestational age of <34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020. According to their conditions, they were divided into group A (both twins had BPD), group B (only one twin had BPD), and group C (neither twin had BPD). The risk factors for BPD in twin preterm infants were analyzed. Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins. RESULTS: A total of 904 pairs of twins with a gestational age of <34 weeks were included in this study. The multivariate logistic regression analysis showed that compared with group C, birth weight discordance of >25% between the twins was an independent risk factor for BPD in one of the twins (OR=3.370, 95%CI: 1.500-7.568, P<0.05), and high gestational age at birth was a protective factor against BPD (P<0.05). The conditional logistic regression analysis of group B showed that small-for-gestational-age (SGA) birth was an independent risk factor for BPD in individual twins (OR=5.017, 95%CI: 1.040-24.190, P<0.05). CONCLUSIONS: The development of BPD in twin preterm infants is associated with gestational age, birth weight discordance between the twins, and SGA birth.

Effect of Mn2+ Doping on the Photoluminescence of Hybrid One-Dimensional Lead Halide Post-Perovskites.

Although organic-inorganic hybrid one-dimensional (1D) lead halide postperovskites (LHPPs) have been reported to show white luminescence and tunable photoluminescence quantum yield (PLQY), their structure-property relationships are not fully understood. Here, we used Mn2+ to test the doping effect on the luminescence of two 1D-LHPPs compounds, namely, {TETA[Pb2Br6]}n 1 and {TETA[Pb2Cl6]}n 2, where TETA = triethylenetetrammonium. We found the pristine compounds show yellowish (551 nm) and bluish (447 nm) emission for 1 and 2, respectively, nanosecond excitation lifetimes (4.17 ns for 1 and 2.29 ns for 2) and low PLQYs (4.65 and 3.57% for 1 and 2, respectively). By fine-doping the Mn2+ ions to ca. 8% the PLQYs for 1 and 2 are maximized to 24 and 25% for 1 and 2, respectively. Upon the increasing Mn2+ dopant, the emission wavelengths can also vary gradually from 551 to 615 nm and from 447 to 660 nm for 1 and 2, respectively, covering almost the whole visible-light range, and the excitation lifetimes are enhanced to microseconds (0.77 µs for 1 and 0.39 µs for 2), owing to the more spin-forbidden d-d transition (4T1-6A1) component from the Mn2+ ions present in the photoluminescence spectra. Moreover, these Mn2+-doped 1D-LHPPs demonstrate high structural and optical stability in humid and high-temperature environments. Hence, such doped materials can be fabricated into a UV-pumped white light-emitting diode, rendering the potential application for solid-state lighting and display systems.

Genetic variations associated with telomere length predict the risk of recurrence of non-oropharyngeal head and neck squamous cell carcinoma.

Genetic factors underlying lymphocyte telomere length (LTL) may provide insights into genomic stability and integrity, with direct links to susceptibility to cancer recurrence. Polymorphisms in telomere-associated genes are strongly associated with LTL and cancer risk, while few large studies have explored the associations between LTL-related polymorphisms and recurrence risk of non-oropharyngeal head and neck squamous cell carcinoma (non-OPHNSCC). Totally 1403 non-OPHNSCC patients were recruited and genotyped for 16 LTL-related polymorphisms identified by genome-wide association studies. Univariate and multivariate analyzes were performed to evaluate associations between the polymorphisms and non-OPHNSCC recurrence risk. Patients carrying rs755017 GA/GG, rs2487999 TC/TT, rs2736108 TC/TT, or rs6772228 AT/AA genotypes exhibited shorter DFS than those with the rs755017 AA, rs2487999 CC, rs2736108 CC, or s6772228 TT genotypes, respectively (all log-rank p < 0.05). Multivariable analysis confirmed an increased risk of recurrence for patients carrying rs755017 GA/GG, rs2487999 TC/TT, rs2736108 TC/TT, or rs6772228 AT/AA genotypes (adjusted hazard ratio [aHR]: 1.66, 95% confidence interval [CI]: 1.32-2.07; aHR: 1.77, 95% CI: 1.41-2.23; aHR: 1.56, 95% CI: 1.22-1.99; aHR: 1.52, 95% CI: 1.20-1.93, respectively). Further stratified analysis revealed stronger associations between these genotypes and recurrence risk in ever-smokers and patients undergoing chemoradiotherapy. The similar but particularly pronounced results were observed for the combined risk genotypes of the four significant polymorphisms. This is the first large study on non-OPHNSCC patients showing that LTL-related polymorphisms may modify risk of non-OPHNSCC recurrence individually and jointly, particularly when analyzed in the context of smoking status and personized treatment. Larger studies are needed to validate these results.

C-reactive protein is a predictor for lower-extremity deep venous thrombosis in patients with primary intracerebral hemorrhage.

OBJECTIVE: Our study aimed to determine whether there exists an association between low-grade systemic inflammation, as measured by serum C-reactive protein (CRP), and the risk of lower-extremity deep venous thrombosis (LEDVT) in patients with primary intracerebral hemorrhage (ICH). METHODS: This observational study was retrospectively conducted on patients with primary ICH who were presented to two tertiary medical centers between January 2021 and August 2022. The primary outcome was detecting LEDVT occurrence within 14 days from the onset of the acute ICH episode. Weighted logistic regression and restricted cubic spline models were employed to estimate the association between CRP and LEDVT following 1:1 propensity score matching (PSM). RESULTS: Of the 538 patients with primary ICH who met the inclusion criteria, 76 (14.13%) experienced LEDVT. Based on the cut-off levels of CRP measured upon admission from the receiver operating characteristic (ROC) curve, patients with primary ICH were categorized into two groups: (i) CRP < 1.59 mg/L and (ii) CRP ≥ 1.59 mg/L. After 1:1 PSM, the LEDVT events occurred in 24.6% of patients with CRP ≥ 1.59 mg/L and 4.1% of patients with CRP < 1.59 mg/L (P < 0.001). ROC curve revealed the area under the ROC curve of 0.717 [95% confidence interval (CI) 0.669-0.761, P < 0.001] for CRP to predict LEDVT with a sensitivity of 85.71% and specificity of 56.29%. After adjusting for all confounding variables, the occurrence of LEDVT in ICH patients with higher CRP levels (≥ 1.59 mg/L) was 10.8 times higher compared to those with lower CRP levels (95% CI 4.5-25.8, P < 0.001). A nonlinear association was observed between CRP and an increased risk of LEDVT in the fully adjusted model (P for overall < 0.001, P for nonlinear = 0.001). The subgroup results indicated a consistent positive link between CRP and LEDVT events following primary ICH. CONCLUSIONS: Higher initial CRP levels (CRP as a dichotomized variable) in patients with primary ICH are significantly associated with an increased risk of LEDVT and may help identify high-risk patients with LEDVT. Clinicians should be vigilant to enable early and effective intervention in patients at high risk of LEDVT.

Reciprocal regulation of T follicular helper cells and dendritic cells drives colitis development.

The immunological mechanisms underlying chronic colitis are poorly understood. T follicular helper (TFH) cells are critical in helping B cells during germinal center reactions. In a T cell transfer colitis model, a lymphoid structure composed of mature dendritic cells (DCs) and TFH cells was found within T cell zones of colonic lymphoid follicles. TFH cells were required for mature DC accumulation, the formation of DC-T cell clusters and colitis development. Moreover, DCs promoted TFH cell differentiation, contributing to colitis development. A lineage-tracing analysis showed that, following migration to the lamina propria, TFH cells transdifferentiated into long-lived pathogenic TH1 cells, promoting colitis development. Our findings have therefore demonstrated the reciprocal regulation of TFH cells and DCs in colonic lymphoid follicles, which is critical in chronic colitis pathogenesis.

Parametric Control via the Algebraic Expression of Lotus-Type Pore Shapes in Metals.

Lotus-type porous metals, characterized by low densities, large surface areas, and directional properties, are contemporarily utilized as lightweight, catalytic, and energy-damping materials; heat sinks; etc. In this study, the effects of dimensionless working parameters on the morphology of lotus-type pores in metals during unidirectional solidification were extensively investigated via general algebraic expressions. The independent dimensionless parameters include metallurgical, transport, and geometrical parameters such as Sieverts' law constant, a partition coefficient, the solidification rate, a mass transfer coefficient, the imposed mole fraction of a solute gas, the total pressure at the top free surface, hydrostatic pressure, a solute transport parameter, inter-pore spacing, and initial contact angle. This model accounts for transient gas pressure in the pore, affected by the solute transfer, gas, capillary, and hydrostatic pressures, and Sieverts' laws at the bubble cap and top free surface. Solute transport across the cap accounts for solute convection at the cap and the amount of solute rejected by the solidification front into the pore. The shape of lotus-type pores can be described using a proposed fifth-degree polynomial approximation, which captures the major portions between the initial contact angle and the maximum radius at a contact angle of 90 degrees, obtained by conserving the total solute content in the system. The proposed polynomial approximation, along with its working parameters, offers profound insights into the formation and shape of lotus-type pores in metals. It systematically provides deep insights into mechanisms that may not be easily revealed with experimental studies. The prediction of a lotus-type pore shape is thus algebraically achieved in good agreement with the available experimental data and previous analytical results.

Stretchable ionic-electronic bilayer hydrogel electronics enable in situ detection of solid-state epidermal biomarkers.

Continuous and in situ detection of biomarkers in biofluids (for example, sweat) can provide critical health data but is limited by biofluid accessibility. Here we report a sensor design that enables in situ detection of solid-state biomarkers ubiquitously present on human skin. We deploy an ionic-electronic bilayer hydrogel to facilitate the sequential dissolution, diffusion and electrochemical reaction of solid-state analytes. We demonstrate continuous monitoring of water-soluble analytes (for example, solid lactate) and water-insoluble analytes (for example, solid cholesterol) with ultralow detection limits of 0.51 and 0.26 nmol cm-2, respectively. Additionally, the bilayer hydrogel electrochemical interface reduces motion artefacts by a factor of three compared with conventional liquid-sensing electrochemical interfaces. In a clinical study, solid-state epidermal biomarkers measured by our stretchable wearable sensors showed a high correlation with biomarkers in human blood and dynamically correlated with physiological activities. These results present routes to universal platforms for biomarker monitoring without the need for biofluid acquisition.