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Alternative protein sources with greater nutritional value and a lower environmental footprint have recently attracted interest in the production of meat substitutes. However, it is required that these alternatives mimic the texture and structure of meat. This study investigated varying ratios of textured vegetable proteins (TVP) to Tenebrio molitor larvae (brown mealworm; TM) with the addition of transglutaminase (TG) to determine the quality characteristics of these emulsions. The results demonstrated low protein solubility of the emulsions as TVP content increased. Furthermore, when the proportion of TM was high, the TG-treated emulsion had a low pH. Additionally, when there was a high TM ratio to TVP in the TG treatment, the emulsions demonstrated better thermal stability and water holding capacity. Regarding the rheological properties of the emulsion, both the frequency-dependent storage modulus (G') and loss modulus (G'') increased as the proportion of TVP in the emulsion increased with and without the addition of TG. Differential scanning calorimetry analyses demonstrated two protein denaturation peaks in all treatments, with high peak temperatures for both treatments with a high proportion of TM. The hardness and chewiness of the emulsion were highest in the treatment (T6 and T8) with TG, and the gumminess of the emulsion was greatest when TM only or when equal ratios of TVP and TM were treated with TG, respectively. In conclusion, the addition of TM to TVP with TG improves the overall texture of the protein mixture, making it a suitable meat alternative.

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BACKGROUND: Gut microbiota dysbiosis is closely associated with psychiatric disorders such as depression and anxiety (DA). In our preliminary study, fecal microbiota transplantation from volunteers with psychological stress and subclinical symptoms of depression (Vsd) induced DA-like behaviors in mice. Escherichia fergusonii (Esf) was found to be more abundant in the feces of Vsd compared to healthy volunteers. Therefore, we investigated the effect of Esf on DA-like behavior and neuroinflammation in mice with and without celiac vagotomy. METHODS AND RESULTS: Orally gavaged Esf increased DA-like behaviors, tumor necrosis factor (TNF)-α, and toll-like receptor-4 (TLR4) expression, and NF-κB+Iba1+ and lipopolysaccharide (LPS)+Iba1+ cell populations, while decreasing serotonin, 5-HT1A receptor, and brain-derived neurotrophic factor (BDNF) expression in the hippocampus and prefrontal cortex. However, celiac vagotomy attenuated Esf-induced DA-like behavior and neuroinflammation. Orally gavaged extracellular vesicle (EV) from Vsd feces (vfEV) or Esf culture (esEV) induced DA-like behavior and inflammation in hippocampus, prefrontal cortex and colon. However, celiac vagotomy attenuated vfEV- or esEV-induced DA-like behaviors and inflammation in the brain alone, while vfEV- or esEV-induced blood LPS and TNF-α levels, colonic TNF-α expression and NF-κB-positive cell number, and fecal LPS level were not. Although orally gavaged fluorescence isothiocyanate-labeled esEV was translocated into the blood and hippocampus, celiac vagotomy decreased its translocation into the hippocampus alone. CONCLUSIONS: esEVs may be translocated into the brain via the vagus nerve and bloodstream, subsequently inducing TNF-α expression and suppressing serotonin, its receptor, and BDNF expression through the activation of TLR4-mediated NF-κB signaling, thereby contributing to DA pathogenesis.

Asunto(s)

Depresión , Vesículas Extracelulares , Enfermedades Neuroinflamatorias , Nervio Vago , Animales , Ratones , Nervio Vago/metabolismo , Vesículas Extracelulares/metabolismo , Humanos , Masculino , Enfermedades Neuroinflamatorias/metabolismo , Depresión/metabolismo , Depresión/etiología , Ratones Endogámicos C57BL , Vagotomía

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AIMS: Primary sclerosing cholangitis (PSC) is a cholestatic liver disease that affects the hepatic bile ducts, leading to hepatic inflammation and fibrosis. PSC can also impact skeletal muscle through the muscle-liver axis, resulting in sarcopenia, a complication characterized by a generalized loss of muscle mass and strength. The underlying mechanisms and therapy of PSC-induced sarcopenia are not well understood, but one potential regulator is the transcription factor forkhead box protein O1 (FOXO1), which is involved in the ubiquitin proteasome system. Thus, the aim of this study is to assess the pharmacological potential of FOXO1 inhibition for treating PSC-induced sarcopenia. MATERIALS AND METHODS: To establish diet-induced PSC model, we provided mice with a 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet for 4 weeks. Mice were intramuscularly injected with AS1842856 (AS), a FOXO1 inhibitor, at a dose of 3.5 mg/kg twice a week for last two weeks. C2C12 myotubes with cholic acid (CA) or deoxycholic acid (DCA) were treated with AS. KEY FINDINGS: We observed a decrease in muscle size and performance in DDC-fed mice with upregulated expression of FOXO1 and E3 ligases such as ATROGIN1 and MuRF1. We found that myotube diameter and MyHC protein level were decreased by CA or DCA in C2C12 myotubes, but treatment of AS reversed these reductions. We observed that intramuscular injection of AS effectively mitigates DDC diet-induced sarcopenia in a rodent PSC model. SIGNIFICANCE: Our study suggests that a FOXO1 inhibitor could be a potential leading therapeutic drug for relieving PSC-induced sarcopenia.

Asunto(s)

Colangitis Esclerosante , Modelos Animales de Enfermedad , Proteína Forkhead Box O1 , Sarcopenia , Transducción de Señal , Animales , Sarcopenia/metabolismo , Sarcopenia/etiología , Sarcopenia/tratamiento farmacológico , Sarcopenia/prevención & control , Sarcopenia/patología , Ratones , Proteína Forkhead Box O1/metabolismo , Colangitis Esclerosante/complicaciones , Colangitis Esclerosante/tratamiento farmacológico , Colangitis Esclerosante/metabolismo , Colangitis Esclerosante/patología , Transducción de Señal/efectos de los fármacos , Masculino , Ratones Endogámicos C57BL , Músculo Esquelético/metabolismo , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/patología , Proteínas Musculares/metabolismo , Proteínas Ligasas SKP Cullina F-box/metabolismo , Proteínas Ligasas SKP Cullina F-box/genética , Ubiquitina-Proteína Ligasas/metabolismo , Proteínas de Motivos Tripartitos/metabolismo , Proteínas de Motivos Tripartitos/genética , Piridinas/farmacología , Quinolonas

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The increasing use of contact lenses, artificial tears, and anti-vascular endothelial growth factor (anti-VEGF) drug injections for age-related macular degeneration has heightened the likelihood of eye exposure to microplastic particles. Extensive research has established that microplastic particles can induce oxidative stress on the ocular surface, resulting in damage. However, the impact of these particles on the retina remains unclear. Therefore, this study investigated whether microplastics/nanoplastics (MPs/NPs) cause retinal damage. In vitro human retinal pigment epithelial (RPE) cells were exposed to polystyrene MPs and NPs for 48 h. Assessment of cell viability using WST-8; evaluation of TNF-α and IL-1ß expression; observation of cell morphology and particle invasion via TEM; measurement of ROS levels using the DCFDA reagent; and western blot analysis of SOD2, FIS1, Drp1, and LC3B expression were conducted. In vivo experiments involved intravitreal injection of MPs/NPs in rats, followed by retinal H&E staining 24 h later and evaluation of TNF-α and IL-1ß expression. Results indicated that exposure to MPs did not significantly alter RPE cell viability, whereas exposure to NPs led to a noticeable decrease. TEM images revealed NPs' penetration into cells, causing increased oxidative stress (SOD2), mitochondrial fission (FIS1, Drp1), and mitochondrial autophagy (LC3B). In vivo experiments demonstrated an increase in inflammatory cells in retinal tissues exposed to NPs, along with elevated levels of TNF-α and IL-1ß. Conclusively, both MPs and NPs impact the retina, with NPs displaying greater toxicity. NPs significantly elevate ROS levels in the retina and induce mitochondrial fission and mitophagy in RPE cells compared to MPs.

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We report a systematic Raman spectroscopy investigation of chemical vapor deposited 2D nonlayered Cr2S3, with both linearly and circularly polarized light over a wide temperature range (5-300 K). Temperature-dependent Raman spectra exhibit a good linear relationship between the peak positions of the phonon modes and temperature. Angle-resolved polarized Raman spectra reveal the polarization-dependent optical response of in-plane and out-of-plane phonon modes. Helicity-dependent Raman investigations complete definite assignment of all the phonon modes observed in the Raman spectra of 2D nonlayered Cr2S3 by the optical selection rule based on a Raman tensor. Our work realizes clear phonon mode identification over a wide temperature range for the emerging material 2D Cr2S3, an important representative of nonlayered 2D system with unique properties for optoelectronic and spintronic applications.

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Background: The rapid aging of Korea's population underscores the urgent need for effective programs to enhance the well-being and longevity of the elderly. This study presents preliminary results from the Korean project, examining the impact of cost-effective and accessible exercise programs on functional performance of older people and to determine the long-term maintenance of intervention. Methods: We randomized 90 older adults aged ≥65 years to the walking group (WG), resistance + walking (RWG), or active control (CG) group. We designed a 12-week main intervention (supervised resistance training 2 d/week and individual walking exercise) and a 12-week follow-up through self-directed exercise (same protocol but unsupervised). The participants' mini mental state examination, color-word Stroop test and 5-time sit to stand, timed up & go, handgrip strength, and knee extensor strength tests were assessed at pre, post, as well as follow-up. Results: For the RWG group, significant improvements were found in timed up & go (P < 0.001), and 5-time sit to stand (P < 0.001) compared to CG, with benefits maintained at follow-up. Both RWG and WG showed significant enhancements in knee extensor power (RWG: P < 0.0001; WG: P < 0.001) and flexor power (RWG: P < 0.01; WG: P = 0.018) compared to CG. Although cognitive performance did not show significant group-by-time interactions, RWG exhibited improvements in the Stroop Color and Color-Word tests at follow-up compared to baseline. Conclusion: A resistance training program combined with walking effectively enhanced functional performance in older adults, providing lasting benefits over 12 weeks on physical functions, such as strength and endurance. However, it showed limited benefits on cognitive performance.

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BACKGROUND: COPD primarily impairs expiratory flow due to progressive airflow obstruction and reduced lung elasticity. Increasing evidence underlines the importance of inspiratory flow as a biomarker for selecting inhaler devices and providing ancillary aerodynamic information. RESEARCH QUESTION: Does the longitudinal changes in maximum forced inspiratory flow (FIFmax) influence acute exacerbations and lung function decline in patients with COPD? STUDY DESIGN AND METHODS: This longitudinal study evaluated FIFmax in patients with COPD over a 7-year period from 2004 to 2020. Eligible patients were categorized into 2 groups based on FIFmax trajectory: the increased FIFmax group and the decreased FIFmax group. The study assessed the annual rate of acute exacerbations and the annual decline rate of FEV1. Subgroup analyses were conducted based on treatment status, with a focus on inhaled therapy and inhaler device usage. RESULTS: Among the eligible 956 patients with COPD, 56.5% belonged to the increased FIFmax group. After propensity score matching, the increased FIFmax group experienced lower rates of severe exacerbations (0.16 per year vs 0.25 per year, P = .017) and a slower decline in FEV1 (0 [interquartile range, -51 to 71] mL/y vs -43 [interquartile range, -119 to 6] mL/y; P < .001) compared with the decreased FIFmax group. These associations were particularly prominent in patients using specific inhaler therapies such as dry powder inhalers. INTERPRETATION: This study showed that the longitudinal changes in FIFmax are associated with clinical outcomes in patients with COPD. Patients with increased FIFmax experienced a lower rate of severe exacerbations and a slower decline in lung function. These findings suggest the potential benefits of optimizing inspiratory flow in COPD management, although further studies are needed to confirm these observations due to potential confounding factors.

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Soybean alleviates cognitive impairment. In our preparatory experiment, we found that dry-heat (90 °C for 30 min)-processed soybean embryo ethanol extract (hSE) most potently suppressed lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-α expression in BV2 cells among dry-heat-, steaming-, and oil exclusion-processed soybean embryo ethanol extracts (SEs). Heat processing increased the absorbable soyasaponin Bb content of SE. Therefore, we investigated whether hSE and its supplement could mitigate LPS-impaired cognitive function in mice. Among dry-heat-, steaming-, and oil exclusion-processed SEs, hSE mitigated LPS-impaired cognitive function more than parental SE. hSE potently upregulated LPS-suppressed brain-derived neurotropic factor (BDNF) expression in the hippocampus, while LPS-induced TNF-α and IL-1ß expression in the hippocampus and colon were downregulated. Lactobacillus gasseri NK109 additively increased the cognitive function-enhancing activity of hSE in mice with LPS-induced cognitive impairment as follows: the hSE and NK109 mix potently increased cognitive function and hippocampal BDNF expression and BDNF-positive neuron cell numbers and decreased TNF-α expression and NF-κB-positive cell numbers in the hippocampus and colon. These findings suggest that hSE and its supplement may decrease colitis and neuroinflammation by suppressing NF-κB activation and inducing BDNF expression, resulting in the attenuation of cognitive impairment.

Asunto(s)

Factor Neurotrófico Derivado del Encéfalo , Disfunción Cognitiva , Colitis , Suplementos Dietéticos , Glycine max , Hipocampo , Lactobacillus gasseri , Lipopolisacáridos , Extractos Vegetales , Animales , Disfunción Cognitiva/inducido químicamente , Glycine max/química , Lipopolisacáridos/efectos adversos , Ratones , Hipocampo/metabolismo , Hipocampo/efectos de los fármacos , Masculino , Extractos Vegetales/farmacología , Colitis/inducido químicamente , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Calor , Factor de Necrosis Tumoral alfa/metabolismo , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , Colon/metabolismo , FN-kappa B/metabolismo

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Despite various health effects of per- and polyfluoroalkyl substances (PFAS) exposure, the association between PFAS exposure and age-related macular degeneration (AMD) has not been investigated. We aimed to assess associations of PFAS exposure with AMD, using data from 1722 U.S. adults aged 40 years or more participating in the National Health and Nutrition Examination Survey 2005-2008 with complete data on PFAS measurement, AMD diagnosis, and covariates. Serum concentrations of PFAS, including perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorohexane sulfonic acid (PFHxS), and perfluorooctane sulfonic acid (PFOS), were measured. An overall PFAS burden score was calculated using item response theory scoring. Individual PFAS concentration and overall PFAS burden score were categorized into low (reference), medium, and high groups. Diagnosis of AMD was based on retinal image examination. Any AMD was defined as the presence of early or late AMD. Survey-weighted logistic regression adjusted for potential confounders was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for presence of AMD according to PFAS exposure. Overall, 132 (6.5%) individuals were diagnosed as any AMD, including 115 (5.7%) individuals with early AMD. A significant dose-response association was observed between serum PFOS concentration and any AMD (p-trend = 0.03), with a significant OR of 1.99 (95% CI: 1.05, 3.79) for the high group compared to the reference. Overall PFAS burden showed a non-monotonic association with any AMD, with a significant OR of 2.18 (95% CI: 1.18, 4.04) for the medium. Inverted U-shaped associations were observed by restricted cubic spline analyses. Also, early AMD showed similar patterns in PFOS and overall PFAS burden and additionally an inverted U-shape association in PFNA. Our findings suggest that exposure to PFAS estimated by serum PFOS and PFNA as well as overall PFAS burden might be a risk factor for AMD in middle-aged and older population.

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The operating lifetime of quantum-dot light-emitting diodes (QLED) is a bottleneck for commercial display applications. To enhance the operational stability of QLEDs, we developed a robust solution-processed highly conductive hole-transport-layer (HTL) structure, which enables a thick HTL structure to mitigate the electric field. An alternating doping strategy, which involves multiple alternating stacks of N4,N4'-di(naphthalen-1-yl)-N4,N4'-bis(4-vinylphenyl)biphenyl-4,4'-diamine and phosphomolybdic acid layers, could provide significantly improved conductivity; more specifically, the 90 nm-thick alternatingly doped HTL exhibited higher conductivity than the 45 nm-thick undoped HTL. Therefore, when applied to a QLED, the increase in the thickness of the alternatingly doped HTL increased device reliability. As a result, the lifetime of the QLED with a thick, alternatingly doped HTL was 48-fold higher than that of the QLED with a thin undoped HTL. This alternating doping strategy provides a new paradigm for increasing the stability of solution-based optoelectronic devices in addition to QLEDs.

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Although previous studies have suggested that meteorological factors and air pollutants can cause dry eye disease (DED), few clinical cohort studies have determined the individual and combined effects of these factors on DED. We investigated the effects of meteorological factors (humidity and temperature) and air pollutants [particles with a diameter ≤ 2.5 µ m (PM2.5), ozone (O3), nitrogen dioxide (NO2), and carbon monoxide (CO)] on DED. A retrospective cohort study was conducted on 53 DED patients. DED was evaluated by Symptom Assessment in Dry Eye (SANDE), tear secretion, tear film break-up time (TBUT), ocular staining score (OSS), and tear osmolarity. To explore the individual, non-linear, and joint associations between meteorological factors, air pollutants, and DED parameters, we used generalized linear mixed model (GLMM) and Bayesian kernel machine regression (BKMR). After adjusting for all covariates, lower relative humidity or temperature was associated with a higher SANDE (p < 0.05). Higher PM2.5, O3, and NO2 levels were associated with higher SANDE and tear osmolarity (p < 0.05). Higher O3 levels were associated with lower tear secretion and TBUT, whereas higher NO2 levels were associated with higher OSS (p < 0.05). BKMR analyses indicated that a mixture of meteorological factors and air pollutants was significantly associated with increased SANDE, OSS, tear osmolarity, and decreased tear secretion.

Asunto(s)

Contaminantes Atmosféricos , Síndromes de Ojo Seco , Humanos , Estudios Retrospectivos , Masculino , Femenino , Síndromes de Ojo Seco/etiología , Síndromes de Ojo Seco/epidemiología , Persona de Mediana Edad , Contaminantes Atmosféricos/efectos adversos , Contaminantes Atmosféricos/análisis , Anciano , Material Particulado/efectos adversos , Material Particulado/análisis , Adulto , Lágrimas/metabolismo , Dióxido de Nitrógeno/análisis , Dióxido de Nitrógeno/efectos adversos , Humedad/efectos adversos , Conceptos Meteorológicos , Ozono/efectos adversos , Ozono/análisis , Temperatura

RESUMEN

STUDY OBJECTIVES: The demand for cost-effective and accessible alternatives to polysomnography (PSG), the conventional diagnostic method for obstructive sleep apnea (OSA), has surged. In this study, we have developed and validated a deep learning model for detecting apnea-hypopnea events using radar data. METHODS: We conducted a single-center prospective cohort study, dividing participants with suspected sleep-disordered breathing into development and temporally independent test sets. Utilizing a hybrid CNN-Transformer architecture, we performed 5-fold cross-validation on the development set to develop and subsequently validate the model. Evaluation metrics included sensitivity for event detection, mean absolute error (MAE), intraclass correlation coefficient (ICC), and Pearson correlation coefficient (r) for apnea-hypopnea index (AHI) estimation. Linearly weighted kappa statistics (κ) assessed OSA severity. RESULTS: The development set comprised 54 participants (July 2021-May 2022), while the test set included 35 participants (June 2022-June 2023). In the test set, our model achieved an event detection sensitivity of 67.2% (95% CI: 65.8%, 68.5%) and demonstrated a MAE of 7.54 (95% CI: 5.36, 9.72), indicating good agreement (ICC = 0.889 [95% CI: 0.792, 0.942]) and a strong correlation (r = 0.892 [95% CI: 0.795, 0.945]) with the ground truth for AHI estimation. Furthermore, OSA severity estimation showed substantial agreement (κ = 0.780 [95% CI: 0.658, 0.903]). CONCLUSIONS: Our study highlights radar sensors and advanced AI models' potential to improve OSA diagnosis, paving the path for future radar-based diagnostic models in sleep medicine research.

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Medial elbow pain is a common musculoskeletal problem among individuals engaging in repetitive activities. Medial epicondylitis is the predominant cause of this pain. However, other potential causes must be considered as part of the differential diagnosis. This article discusses several etiologies of medial elbow pain, including medial epicondylitis, ulnar neuropathy, snapping triceps syndrome, ulnar collateral ligament injury, medial antebrachial cutaneous neuropathy, and diseases of the elbow joint, with an emphasis on ultrasound (US) findings. Awareness of possible diagnoses and their US features can assist radiologists in establishing a comprehensive diagnosis for medial elbow pain.

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Combining cryoablation and immunotherapy presents a promising approach to revert immunosuppressive responses to solid tumors. However, challenges such as postablated residual tumors and insufficient immune activity contribute to recurrence after cryo-immunotherapy. Herein, we investigated metallic supra-structured cryo-nanocatalyst (MSCN), which features numerous ice nucleation sites and interspace loading of therapeutic agents. MSCN elevates the freezing point and enhances ice nucleation, facilitating effective ice formation during cryotreatment. MSCN-loaded tumor cells showed a 2-fold increase in cryo-cytotoxicity and undergo osmotic-related cell damage, primarily necroptosis rather than other regulated cell death mechanisms. In prostate cancer models, RNA sequencing reveals that MSCN-cryoablation promoted antitumor inflammatory pathways, including necroptosis, compared to cryoablation alone. Additionally, following programmed death-ligand 1 (PD-L1) upregulation postcryoablation, synergistic effects with PD-L1 blockade were confirmed. Given the interspace of MSCN for aPD-L1 loading, we compared the intratumoral delivery of PD-L1 blockade against systemic injection. Enhanced necrosis and necroptosis from MSCN-cryoablation and PD-L1 blockade effectively eradicated tumors and triggered antitumor and memory immune responses locally and systemically. Lastly, a spatial landscape of tumor-infiltrating immune cells was analyzed to gain insight into heterogeneous tumor responses, leading to the limitations of conventional focal ablation techniques. Our findings highlight the potential of advanced cryo-immunotherapy using cryo-nanocatalysis to promote ice formation and necroptosis, stimulating antitumor immunogenic responses.

Asunto(s)

Antígeno B7-H1 , Inmunoterapia , Necroptosis , Necroptosis/efectos de los fármacos , Ratones , Animales , Humanos , Masculino , Antígeno B7-H1/antagonistas & inhibidores , Antígeno B7-H1/metabolismo , Criocirugía , Línea Celular Tumoral , Inhibidores de Puntos de Control Inmunológico/farmacología , Inhibidores de Puntos de Control Inmunológico/química , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/terapia , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/inmunología

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Public health systems reported low mortality from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in East Asia, in low-income countries, and for children during the first year of the SARS-CoV-2 pandemic. These reports led commentators to suggest that cross-reactive immunity from prior exposure to other pathogens reduced fatality risk. Resolution of initial infection waves also contributed to speculation that herd immunity prevented further waves prior to vaccination. Serology instead implied that immunity was too limited to achieve herd immunity and that there was little impact from cross-reactive protection. Paediatric deaths exceeded those from influenza, with higher age-specific fatality risk in lower-income nations and similar fatality risk in East Asia compared with demographically similar regions. Neither pre-outbreak exposure to related pathogens nor immunity induced by initial infection waves are necessarily a reliable response to future pathogen outbreaks. Preparedness for future pathogen outbreaks should instead focus on strategies such as voluntary behavioural changes, nonpharmaceutical interventions, and vaccination.

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OBJECTIVE: We analyzed the predictive value of dynamic changes in neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) in recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) treated with immune checkpoint inhibitors (ICIs). STUDY DESIGN: A total of 104 patients with R/M HNSCC treated with ICIs during August 2018 to June 2023 were included. Dynamic changes were defined as the difference between NLR and PLR on day 1 of cycles 1 and 2. RESULTS: Patients with increased NLR or PLR had an independently increased risk of disease progression at the first response evaluation (odds ratio [OR] 5.26, P = .005; OR 2.29, P = .042), disease progression (hazard ratio [HR] 2.29, P = .003; HR 1.68, P = .027), and death (HR 1.86, P = .027; HR 1.68, P = .037). Furthermore, patients with a decrease in NLR showed longer progression-free survival, with HRs of 0.36 (P < .001) for those with low pre-ICI NLR and 0.52 (P = .041) for those with high pre-ICI NLR, compared to those with increased NLR. CONCLUSIONS: Increased NLR or PLR was associated with adverse outcomes after ICI treatment in patients with R/M HNSCC.

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Biodegradable radioactive microspheres labeled with positron emitters hold significant promise for diagnostic and therapeutic applications in cancers and other diseases, including arthritis. The alginate-based polymeric microspheres offer advantages such as biocompatibility, biodegradability, and improved stability, making them suitable for clinical applications. In this study, we developed novel positron emission tomography (PET) microspheres using alginate biopolymer radiolabeled with gallium-68 (68Ga) through a straightforward conjugation reaction. Polyethylenimine (PEI)-decorated calcium alginate microspheres (PEI-CAMSs) were fabricated and further modified using azadibenzocyclooctyne-N-hydroxysuccinimide ester (ADIBO-NHS). Subsequently, azide-functionalized NOTA chelator (N3-NOTA) was labeled with [68Ga]Ga to obtain [68Ga]Ga-NOTA-N3, which was then reacted with the surface-modified PEI-CAMSs using strain-promoted alkyne-azide cycloaddition (SPAAC) reaction to develop [68Ga]Ga-NOTA-PEI-CAMSs, a novel PET microsphere. The radiolabeling efficiency and radiochemical stability of [68Ga]Ga-NOTA-PEI-CAMSs were determined using the radio-instant thin-layer chromatography-silica gel (radio-ITLC-SG) method. The in vivo PET images were also acquired to study the in vivo stability of the radiolabeled microspheres in normal mice. The radiolabeling efficiency of [68Ga]Ga-NOTA-PEI-CAMSs was over 99%, and the microspheres exhibited high stability (92%) in human blood serum. PET images demonstrated the stability and biodistribution of the microspheres in mice for up to 2 h post injection. This study highlights the potential of biodegradable PET microspheres for preoperative imaging and targeted radionuclide therapy. Overall, the straightforward synthesis method and efficient radiolabeling technique provide a promising platform for the development of theranostic microspheres using other radionuclides such as 90Y, 177Lu, 188Re, and 64Cu.

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Background: Aspirin is a representative non-steroidal anti-inflammatory drug (NSAIDs) and has been commonly used for the treatment of tendinopathy in clinical practice. In this study, we aimed to evaluate the biomechanical and histological healing effects of aspirin on the healing of the tendon-to-bone interface after rotator cuff tear repair. Methods: A total of 20 male Sprague-Dawley rats were randomly divided into two groups of 10 rats each. Group-C performed repaironly, and group-aspirin treated with aspirin after tendon repair. Group-aspirin rat were intraperitoneally injected with aspirin at 10 mg/kg every 24 h for 7 days. Eight weeks after surgery, the left shoulder of each rat was used for histological analysis and the right shoulder for biomechanical analysis. Results: In the biomechanical analysis, there was no significant difference in load-to-failure (group-C: 0.61 ± 0.32 N, group-aspirin: 0.74 ± 0.91 N; p = .697) and ultimate stress (group-C: 0.05 ± 0.01 MPa, group-aspirin: 0.29 ± 0.43 MPa; p = .095). For the elongation (group-C: 222.62 ± 57.98%, group-aspirin: 194.75 ± 75.16%; p = .028), group-aspirin confirmed a lower elongation level than group-C. In the histological evaluation, the Bonar score confirmed significant differences in collagen fiber density (group-C: 1.60 ± 0.52, group-aspirin: 2.60 ± 0.52, p = .001) and vascularity (group-C: 1.00 ± 0.47, group-aspirin: 2.20 ± 0.63, p = .001) between the groups. Conclusions: Aspirin injection after rotator cuff tear repair may enhance the healing effect during the early remodeling phase of tendon healing.

Asunto(s)

Antiinflamatorios no Esteroideos , Aspirina , Modelos Animales de Enfermedad , Ratas Sprague-Dawley , Lesiones del Manguito de los Rotadores , Animales , Aspirina/farmacología , Aspirina/administración & dosificación , Lesiones del Manguito de los Rotadores/tratamiento farmacológico , Lesiones del Manguito de los Rotadores/patología , Masculino , Ratas , Antiinflamatorios no Esteroideos/farmacología , Antiinflamatorios no Esteroideos/administración & dosificación , Fenómenos Biomecánicos , Cicatrización de Heridas/efectos de los fármacos

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With the gradual miniaturization of electronic devices and the increasing interest in wearable devices, flexible microelectronics is being actively studied. Owing to the limitations of existing battery systems corresponding to miniaturization, there is a need for flexible alternative power sources. Accordingly, energy harvesting from surrounding environmental systems using fluorinated polymers with piezoelectric properties has received significant attention. Among them, polyvinylidene fluoride (PVDF) and PVDF co-polymers have been researched as representative organo-piezoelectric materials because of their excellent piezoelectric properties, mechanical flexibility, thermal stability, and light weight. Electrospinning is an effective method for fabricating nanofibrous meshes with superior surface-to-volume ratios from polymer solutions. During electrospinning, the polymer solution is subjected to mechanical stretching and in situ poling, corresponding to an external strong electric field. Consequently, the fraction of the piezoelectric ß-phase in PVDF can be improved by the electrospinning process, and enhanced harvesting output can be realized. An overview of electrospun piezoelectric fibrous meshes composed of PVDF or PVDF co-polymers to be utilized is presented, and the recent progress in enhancement methods for harvesting output, such as fiber alignment, doping with various nanofillers, and coaxial fibers, is discussed. Additionally, other applications of these meshes as sensors are reviewed.

RESUMEN

Magnetic resonance imaging (MRI) can extract the tissue conductivity values from in vivo data using the so-called phase-based magnetic resonance electrical properties tomography (MR-EPT). However, this procedure suffers from noise amplification caused by the use of the Laplacian operator. To counter this issue, we propose a novel preprocessing denoiser for magnetic resonance transceive phase images, operating in an unsupervised manner. Inspired by the deep image prior approach, we apply the random initialization of a convolutional neural network, which enforces an implicit regularization. Additionally, we introduce Stein's unbiased risk estimator, which is the unbiased estimator of the mean square error for optimizing the network without the need for label images. This modification not only tackles the overfitting problem inherent in the deep image prior approach but also operates within a purely unsupervised framework. In addition, instead of using phase images, we use real and imaginary images, which aligns with the theoretical model of the risk estimator. Our generative model needs neither the preparation of training datasets nor prior training procedure, and it maintains adaptability across various resolutions and signal-to-noise ratio levels. In testing. our method significantly diminished residual error remaining in phase maps, quantitatively as well as qualitatively, for both phantom and simulated brain data. Furthermore, it outperformed other denoising methods in reducing noise amplification and boundary error. When applied to healthy volunteer and patient data, the proposed method revealed reduced error in the reconstructed conductivity maps, with conductivity values aligning well with established literature values. To the best of our knowledge, this is the first blind approach using a purely unsupervised denoising framework that can implement a 2D phase-based MR-EPT reconstruction algorithm. The source code is available at https://github.com/Yonsei-MILab/Implicit-Regularization-forMREPT-with-SURE.