Donor-Acceptor Modulating of Ionic AIE Photosensitizers for Enhanced ROS Generation and NIR-II Emission.

Photosensitizers (PSs) with aggregation-induced emission (AIE) characteristics are competitive candidates for bioimaging and therapeutic applications. However, their short emission wavelength and non-specific organelle targeting hinder their therapeutic effectiveness. Herein, we report a donor-acceptor modulation approach to construct a series of ionic AIE photosensitizers with enhanced photodynamic therapy (PDT) outcomes and fluorescent emission in the second near-infrared (NIR-II) window. By employing dithieno[3,2-b:2',3'-d]pyrrole (DTP) and indolium (In) as the strong donor and acceptor, respectively, the compound DTP-In exhibits a substantial redshift in absorption and fluorescent emission reach to NIR-II region. The reduced energy gap between singlet and triplet states in DTP-In also increases the reactive oxygen species (ROS) generation rate. Further, DTP-In can self-assemble in aqueous solutions, forming positively charged nanoaggregates, which are superior to conventional encapsulated nanoparticles in cellular uptake and mitochondrial targeting. Consequently, DTP-In aggregates show efficient photodynamic ablation of 4T1 cancer cells and outstanding tumor theranostic in vivo under 660 nm laser irradiation. This work highlights the potential of molecular engineering of donor-acceptor AIE PSs with multiple functionalities, thereby facilitating the development of more effective strategies for cancer therapy. This article is protected by copyright. All rights reserved.

Effect of emulsified lipid and saponified lipid on the enzyme desizing of starch and its mechanism.

To enhance the flexibility of starch film adhesion on yarns, sizing lipids (saponified lipid or emulsified lipid) must be added during the sizing process. However, different types of sizing lipids may have diverse combinations with starch to impact enzyme desizing. Therefore, this study investigated the effects of saponified lipid and emulsified lipid commonly used in warp sizing on the hydrolysis of starch. Additionally, the desizing efficiency and chain structure of desizing residues were analyzed. Experimental results demonstrated that the existence of saponified lipid or emulsified lipid led to a reduction in the degree of hydrolysis (1.1 % and 2.6 %, respectively) compared to the original corn starch. Notably, saponified lipid exhibited a relatively strong negative impact. Furthermore, the desizing efficiency decreased after adding emulsified lipid (1.2 %) or saponified lipid (2.9 %). Starch-lipid V-type complexes and physical hindrance could inhibit the enzyme desizing, resulting in a larger wavelength of maximum absorbance for desizing residues, along with higher molecular weight, z-average radius of gyration, and an increased proportion of long chains. The presence of saponified lipid significantly negatively influenced desizing, possibly due to the smaller particle size and propensity for complex formation with starch.

Therapeutic potential of targeting Nrf2 by panobinostat in pituitary neuroendocrine tumors.

We aimed to identify the druggable cell-intrinsic vulnerabilities and target-based drug therapies for PitNETs using the high-throughput drug screening (HTS) and genomic sequencing methods. We examined 9 patient-derived PitNET primary cells in HTS. Based on the screening results, the potential target genes were analyzed with genomic sequencing from a total of 180 PitNETs. We identified and verified one of the most potentially effective drugs, which targeted the Histone deacetylases (HDACs) both in in vitro and in vivo PitNET models. Further RNA sequencing revealed underlying molecular mechanisms following treatment with the representative HDACs inhibitor, Panobinostat. The HTS generated a total of 20,736 single-agent dose responses which were enriched among multiple inhibitors for various oncogenic targets, including HDACs, PI3K, mTOR, and proteasome. Among these drugs, HDAC inhibitors (HDACIs) were, on average, the most potent drug class. Further studies using in vitro, in vivo, and isolated PitNET primary cell models validated HDACIs, especially Panobinostat, as a promising therapeutic agent. Transcriptional surveys revealed substantial alterations to the Nrf2 signaling following Panobinostat treatment. Moreover, Nrf2 is highly expressed in PitNETs. The combination of Panobinostat and Nrf2 inhibitor ML385 had a synergistic effect on PitNET suppression. The current study revealed a class of effective anti-PitNET drugs, HDACIs, based on the HTS and genomic sequencing. One of the representative compounds, Panobinostat, may be a potential drug for PitNET treatment via Nrf2-mediated redox modulation. Combination of Panobinostat and ML385 further enhance the effectiveness for PitNET treatment.

Endogenous cell wall degrading enzyme LytD is important for the biocontrol activity of Bacillus subtilis.

Autolysins are endogenous cell wall degrading enzymes (CWDEs) in bacteria that remodel the peptidoglycan layer of its own cell wall. In the Bacillus subtilis genome, at least 35 autolysin genes have been identified. However, the study of their roles in bacterial physiology has been hampered by their complexity and functional redundancy. B. subtilis GLB191 is an effective biocontrol strain against grape downy mildew disease, the biocontrol effect of which results from both direct effect against the pathogen and stimulation of the plant defense. In this study, we show that the autolysin N-acetylglucosaminidase LytD, a major autolysin of vegetative growth in B. subtilis, plays an important role in its biocontrol activity against grape downy mildew. Disruption of lytD resulted in reduced suppression of the pathogen Plasmopara viticola and stimulation of the plant defense. LytD is also shown to affect the biofilm formation and colonization of B. subtilis on grape leaves. This is the first report that demonstrates the role of an endogenous CWDE in suppressing plant disease infection of a biological control microorganism. These findings not only expand our knowledge on the biological function of autolysins but also provide a new target to promote the biocontrol activity of B. subtilis.

Synthesis of grafted bromoisobutyryl esterified starch using electron transfer atom transfer radical polymerization method with high-performance adhesion and film properties.

Nowadays, few investigations on the process parameters of grafted starch synthesized using electron transfer atom transfer radical polymerization (ARGET ATRP) and its applications in warp sizing and paper-making are presented. Therefore, this study aimed to survey the appropriate process parameters of bromoisobutyryl esterified starch-g-poly(acrylic acid) (BBES-g-PAA) synthesized by the ARGET ATRP, and also aimed to provide a new biobased BBES-g-PAA adhesive. The appropriate synthesis process parameters were 1.2, 0.32, and 0.6 in the molar ratios of vitamin C, CuBr2, and pentamethyldivinyltriamine to BBES, respectively, at 40 °C for 5 h. The BBES-g-PAA samples with a grafting ratio range of 4.63-14.14 % exhibited bonding forces of 57.8-64.6 N to wool fibers [55.5 N (BBES) and 53.8 N (ATS)], and their films showed breaking elongations of 3.29-3.80 % [2.74 % (BBES) and 2.49 % (ATS)] and tensile strengths of 29.1-25.4 MPa [30.4 MPa (BBES) and 34.7 MPa (ATS)]. Compared with BBES, significantly increased bonding forces and film elongations, and decreased film strengths for the BBES-g-PAA samples with grafting ratios ≥10.54 % were displayed (p < 0.05). The time (100-42 s) taken for the BBES-g-PAA films was significantly shorter than that of ATS (246 s) and BBES (196 s) films (p < 0.05), corresponding to better desizability.

[Moxifloxacin treatment for Mycoplasma hominis meningitis in an extremely preterm infant]. / èŽ«è¥¿æ²™æ˜Ÿæ²»ç–—è¶ æ—©äº§å„¿äººåž‹æ”¯åŽŸä½“è„‘è†œç‚Ž1例.

The patient, a male newborn, was admitted to the hospital 2 hours after birth due to prematurity (gestational age 27+5 weeks) and respiratory distress occurring 2 hours postnatally. After admission, the infant developed fever and elevated C-reactive protein levels. On the fourth day after birth, metagenomic next-generation sequencing of cerebrospinal fluid indicated a positive result for Mycoplasma hominis (9 898 reads). On the eighth day, a retest of cerebrospinal fluid metagenomics confirmed Mycoplasma hominis (56 806 reads). The diagnosis of purulent meningitis caused by Mycoplasma hominis was established, and the antibiotic treatment was switched to moxifloxacin [5 mg/(kg·day)] administered intravenously for a total of 4 weeks. After treatment, the patient's cerebrospinal fluid tests returned to normal, and he was discharged as cured on the 76th day after birth. This article focuses on the diagnosis and treatment of neonatal Mycoplasma hominis purulent meningitis, introducing the multidisciplinary diagnosis and treatment of the condition in extremely preterm infants.

Signalling switches maintain intercellular communication in the vascular endothelium.

BACKGROUND AND PURPOSE: The single layer of cells lining all blood vessels, the endothelium, is a sophisticated signal co-ordination centre that controls a wide range of vascular functions including the regulation of blood pressure and blood flow. To co-ordinate activities, communication among cells is required for tissue level responses to emerge. While a significant form of communication occurs by the propagation of signals between cells, the mechanism of propagation in the intact endothelium is unresolved. EXPERIMENTAL APPROACH: Precision signal generation and targeted cellular manipulation was used in conjunction with high spatiotemporal mesoscale Ca2+ imaging in the endothelium of intact blood vessels. KEY RESULTS: Multiple mechanisms maintain communication so that Ca2+ wave propagation occurs irrespective of the status of connectivity among cells. Between adjoining cells, regenerative IP3-induced IP3 production transmits Ca2+ signals and explains the propagated vasodilation that underlies the increased blood flow accompanying tissue activity. The inositide is itself sufficient to evoke regenerative phospholipase C-dependent Ca2+ waves across coupled cells. None of gap junctions, Ca2+ diffusion or the release of extracellular messengers is required to support this type of intercellular Ca2+ signalling. In contrast, when discontinuities exist between cells, ATP released as a diffusible extracellular messenger transmits Ca2+ signals across the discontinuity and drives propagated vasodilation. CONCLUSION AND IMPLICATIONS: These results show that signalling switches underlie endothelial cell-to-cell signal transmission and reveal how communication is maintained in the face of endothelial damage. The findings provide a new framework for understanding wave propagation and cell signalling in the endothelium.

Intramolecular Hydrogen Bonds Assisted Construction of Planar Tricyclic Structures for Insensitive and Highly Thermostable Energetic Materials.

Safety is fundamental for the practical development and application of energetic materials. Three tricyclic energetic compounds, namely, 1,3-di(1H-tetrazol-5-yl)-1H-1,2,4-triazol-5-amine (ATDT), 5'-nitro-3-(1H-tetrazol-5-yl)-2'H-[1,3'-bi(1,2,4-triazol)]-5-amine (ATNT), and 1-(3,4-dinitro-1H-pyrazol-5-yl)-3-(1H-tetrazol-5-yl)-1H-1,2,4-triazol-5-amine (ATDNP), were effectively synthesized through a simple two-step synthetic route. The introduction of intramolecular hydrogen bonds resulted in excellent molecular planarity for the three new compounds. Additionally, they exhibit regular crystal packing, leading to numerous intermolecular hydrogen bonds and π-π interactions. Benefiting from planar tricyclic structural features, ATDT, ATNT, and ATDNP are insensitive (IS > 60 J, FS = 360 N) when exposed to external stimuli. Furthermore, ATNT (Td = 361.1 °C) and ATDNP (Td = 317.0 °C) exhibit high decomposition temperatures and satisfying detonation performance. The intermolecular hydrogen bonding that produced this planar tricyclic molecular structure serves as a model for the creation of innovative multiple heterocycle energetic materials with excellent stability.

The CuSCN layer between BiVO4 and NiFeOx for facilitating photogenerated carrier transfer and water oxidation kinetics.

Modification of oxygen evolution co-catalyst (OEC) on the surface of bismuth vanadate (BiVO4) can effectively improve the kinetics of water oxidation, but it is still limited by the small hole extraction driving force at the BiVO4/OEC interface. Modulating the BiVO4/OEC interface with a hole transfer layer (HTL) is expected to facilitate hole transport from BiVO4 to the OEC surface. Herein, a copper(I) thiocyanate (CuSCN) HTL is inserted between BiVO4 and NiFeOx OEC to create BiVO4/CuSCN/NiFeOx photoanode, resulting in a significant enhancement of photoelectrochemical (PEC) water splitting performance. From electrochemical analyses and density functional theory (DFT) simulations, the markedly enhanced PEC performance is attributed to the insertion of CuSCN as an HTL, which promotes the extraction of holes from BiVO4 surface and boosts the water oxidation kinetics. The optimal photoanode achieves a photocurrent density of 5.6 mA cm-2 at 1.23 V versus the reversible hydrogen electrode (vs. RHE) and an impressive charge separation efficiency of 96.2 %. This work offers valuable insights into the development of advanced photoanodes for solar energy conversion and emphasizes the importance of selecting an appropriate HTL to mitigate recombination at the BiVO4/OEC interface.

Impact of high-performance HPV testing to improve cervical cancer screening in China: A prospective population-based multicenter cohort study.

OBJECTIVES: The aim of the study was to evaluate the clinical performance of HBRT-H14, a real-time PCR-based assay that separates human papillomavirus (HPV) 16 and HPV18 from 12 other high-risk (HR) HPV types, in population according to Chinese guideline. METHODS: 9829 eligible women aged 21-64 years from Henan, Shanxi and Guangdong provinces were performed by HBRT-H14 testing and liquid-based cytology (LBC) screening at baseline and followed up for three-year. The sensitivity, specificity, positive predictive value (absolute risk), and negative predictive value of LBC diagnosis and HPV testing were calculated for cervical intraepithelial neoplasia grade 2 or worse (CIN2+) Lesions. RESULTS: At baseline, 80 (0.81%) participants were diagnosed with CIN2+. HR-HPV with reflex LBC had a significantly higher sensitivity (78/80, 97.50% [95% CI: 91.34-99.31%] vs. 62/80, 77.50% [67.21-85.27%], PMcNemar<0.001), and a slightly lower specificity (8528/9749, 87.48% [86.80-88.12%] vs. 8900/9749, 91.29% [90.72-91.83%], PMcNemar<0.001) than LBC with reflex HR-HPV for CIN2+. 7832 (79.6%) participants completed 3-year follow-up and 172 (2.20%) participants were cumulatively diagnosed with CIN2+. Compared with LBC with reflex HR-HPV, HR-HPV with reflex LBC significantly increased the sensitivity (161/172, 93.60% [88.91-96.39%] vs. 87/172, 50.58% [43.18-57.96%], PMcNemar<0.001), but marginally decreased the specificity (6776/7660, 88.46% [87.72-89.16%] vs. 6933/7660, 90.51% [89.83-91.15], PMcNemar<0.001). In addition, the absolute three-year risk of CIN2+ in HPV16/18-positive individuals was as high as 33% (80/238), while the risk in the HPV-negative population was only 0.16% (11/6787), much lower than those in the negative for intraepithelial lesion or malignancy (NILM) population (1.21%, 85/7018). Moreover, similar results were found in women ≥ 30 years old. CONCLUSIONS: The study has indicated that HBRT-14 has a reliable clinical performance for use in cervical screening. The validated HPV test would improve the quality of population screening.

Engineering Modular DNA Reaction Networks for Signal Processing.

Diversified molecular information-processing methods have significant implications for nanoscale manipulation and control, monitoring and disease diagnosis of organisms, and direct intervention in biological activities. However, as an effective approach for implementing multifunctional molecular information processing, DNA reaction networks (DRNs) with numerous functionally specialized molecular structures have challenged them on scale and modular design, leading to increased network complexity, further causing problems such as signal leakage, attenuation, and cross-talk in network reactions. Our study developed a strategy for performing various signal-processing tasks through engineering modular DRNs composed of simple molecular structures. This strategy is based on a universal core unit with signal selection capability, and a timeadjustable signal self-resetting module is achieved by combing the core unit and self-resetting unit, which improves the time controllability of modular DRNs. In addition, multi-input and -output signal crosscatalytic and continuously adjustable signal delay modules were realized by combining core and threshold units, providing a flexible, precise method for modular DRNs to process the signal. The strategy simplifies the design of DRNs, helps generate design ideas for largescale integrated DRNs with multiple functions, and provides prospects in biocomputing, gene regulation, and biosensing.

Quantitative measurement of acute myocardial infarction cardiac biomarkers by "All-in-One" immune microfluidic chip for early diagnosis of myocardial infarction.

Acute myocardial infarction (AMI) is a life-threatening condition with a narrow treatment window, necessitating rapid and accurate diagnostic methods. We present an "all-in-one" convenient and rapid immunoassay system that combines microfluidic technology with a colloidal gold immunoassay. A degassing-driven chip replaces a bulky external pump, resulting in a user-friendly and easy-to-operate immunoassay system. The chip comprises four units: an inlet reservoir, an immunoreaction channel, a waste pool, and an immunocomplex collection chamber, allowing single-channel flow for rapid and accurate AMI biomarker detection. In this study, we focused on cardiac troponin I (cTnI). With a minimal sample of just 4 µL and a total detection time of under 3 min, the chip enabled a quantitative visual analysis of cTnI concentration within a range of 0.5 âˆ¼ 60.0 ng mL-1. This all-in-one integrated microfluidic chip with colloidal gold immunoassay offers a promising solution for rapid AMI diagnosis. The system's portability, small sample requirement, and quantitative visual detection capabilities make it a valuable tool for AMI diagnostics.

Numerical simulation study on the evolution law of mechanical properties of different metamorphic coals after heat treatment.

In order to study the effect of temperature on the structure and mechanical properties of coal with different metamorphic degree. Three coal samples with varying degrees of metamorphism were chosen for analysis. The discrete element software PFC2D is used to simulate the heat treatment and compression of coal. The findings indicate that during the heating process, low-order coal exhibits noticeable thermal cracks at an early stage, while thermal crack development in middle-order coal is concentrated in the later stages. In contrast, high-order coal demonstrates a more stable macroscopic structure. The strength and stiffness of low rank coal show the lowest value and decrease significantly within 135 °C. However, the strength and stiffness of medium rank coal decrease significantly after 135 °C. The changes of mechanical properties and damage modes of coal caused by thermal damage are often ignored, which may lead to the deviation of design and research results from the actual situation. Therefore, this study is of great significance to the prevention and control of coal mine disasters.

[Analysis of Influencing Factors of Complications for CT-guided 
Percutaneous Lung Biopsy].

BACKGROUND: Computed tomography guided percutaneous lung biopsy (CT-PLB) is a widely used method for the diagnosis of lung lesions. However, it is invasive, and the most common complications are pneumothorax and pulmonary hemorrhage, which can be life-threatening in severe cases. Therefore, the aim of this study is to analyze the independent risk factors affecting the occurrence of different complications of CT-PLB, so as to reduce the incidence of complications. METHODS: The 605 patients with complete clinical data who underwent CT-PLB in our hospital from May 2018 to December 2019 were retrospectively analyzed. According to the location of the lesions, they were divided into subpleural group and non-subpleural group. The patients were divided into pneumothorax group, pulmonary hemorrhage group, pneumothorax with pulmonary hemorrhage group and non-pneumothorax/pulmonary hemorrhage group according to the complications. The risk factors affecting the incidence of different complications and the independent risk factors of each complication were analyzed. RESULTS: The incidence of pneumothorax was 34.1%, the incidence of pulmonary hemorrhage was 28.1%, and the incidence of pneumothorax complicated with pulmonary hemorrhage was 10.8% (63 cases). The independent risk factor affecting the incidence of subpleural pneumothorax was lesion size (P=0.002). The independent risk factors affecting the occurrence of pneumothorax in the non-subpleural group were plain scan CT value (P=0.035), length of needle through lung tissue (P=0.003), and thickness of needle through chest wall (P=0.020). Independent risk factors affecting the occurrence of pulmonary hemorrhage in the non-subpleural group were length of needle through lung tissue (P<0.001), △CT value of needle travel area (P=0.001), lesion size (P=0.034) and body position (P=0.014). The independent risk factors affecting the co-occurrence of pneumothorax and pulmonary hemorrhage were the length of needle through lung tissue (P<0.001) and the △CT value of needle travel area (P<0.001). CONCLUSIONS: CT-PLB is a safe and effective diagnostic method, which of high diagnostic value for lung lesions. Selecting the appropriate puncture program can reduce complications such as pneumothorax and pulmonary hemorrhage, and improve diagnosis and treatment efficiency.

The PKA-CREB1 axis regulates coronavirus proliferation by viral helicase nsp13 association.

The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed a worldwide threat in the past 3 years. Although it has been widely and intensively investigated, the mechanism underlying the coronavirus-host interaction requires further elucidation, which may contribute to the development of new antiviral strategies. Here, we demonstrated that the host cAMP-responsive element-binding protein (CREB1) interacts with the non-structural protein 13 (nsp13) of SARS-CoV-2, a conserved helicase for coronavirus replication, both in cells and in lung tissues subjected to SARS-CoV-2 infection. The ATPase and helicase activity of viral nsp13 were shown to be potentiated by CREB1 association, as well as by Protein kinase A (PKA)-mediated CREB1 activation. SARS-CoV-2 replication is significantly suppressed by PKA Cα, cAMP-activated protein kinase catalytic subunit alpha (PRKACA), and CREB1 knockdown or inhibition. Consistently, the CREB1 inhibitor 666-15 has shown significant antiviral effects against both the WIV04 strain and the Omicron strain of the SARS-CoV-2. Our findings indicate that the PKA-CREB1 signaling axis may serve as a novel therapeutic target against coronavirus infection. IMPORTANCE: In this study, we provide solid evidence that host transcription factor cAMP-responsive element-binding protein (CREB1) interacts directly with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) helicase non-structural protein 13 (nsp13) and potentiate its ATPase and helicase activity. And by live SARS-CoV-2 virus infection, the inhibition of CREB1 dramatically impairs SARS-CoV-2 replication in vivo. Notably, the IC50 of CREB1 inhibitor 666-15 is comparable to that of remdesivir. These results may extend to all highly pathogenic coronaviruses due to the conserved nsp13 sequences in the virus.

Adaptive Relation-Aware Network for zero-shot classification.

Supervised learning-based image classification in computer vision relies on visual samples containing a large amount of labeled information. Considering that it is labor-intensive to collect and label images and construct datasets manually, Zero-Shot Learning (ZSL) achieves knowledge transfer from seen categories to unseen categories by mining auxiliary information, which reduces the dependence on labeled image samples and is one of the current research hotspots in computer vision. However, most ZSL methods fail to properly measure the relationships between classes, or do not consider the differences and similarities between classes at all. In this paper, we propose Adaptive Relation-Aware Network (ARAN), a novel ZSL approach that incorporates the improved triplet loss from deep metric learning into a VAE-based generative model, which helps to model inter-class and intra-class relationships for different classes in ZSL datasets and generate an arbitrary amount of high-quality visual features containing more discriminative information. Moreover, we validate the effectiveness and superior performance of our ARAN through experimental evaluations under ZSL and more practical GZSL settings on three popular datasets AWA2, CUB, and SUN.

Clinical characteristics and management of pediatric egg-induced anaphylaxis: A cross-sectional study.

BACKGROUND: Egg is the third most common food allergy in children; however, data on pediatric egg-induced anaphylaxis are sparse. OBJECTIVE: To describe the clinical characteristics, management, and outcomes of pediatric egg-induced anaphylaxis. METHODS: Children presenting with anaphylaxis were recruited from 13 emergency departments as part of the Cross-Canada Anaphylaxis Registry, from which data on anaphylaxis triggered by egg were extracted. Multivariate logistic regression was used to determine factors associated with prehospital epinephrine autoinjector (EAI) use and to compare anaphylaxis triggered by egg with other triggers of food-induced anaphylaxis (FIA). RESULTS: We recruited 302 children with egg-induced anaphylaxis. The mean age was 2.6 years (SD = 3.6), and 55.3% were male. Only 39.4% had previously been diagnosed with an egg allergy. Prehospital EAI use was 32.1%, but this was not significantly lower than in other triggers of FIA (P = .26). Only 1.4% of patients required hospital admission. Relative to other triggers of FIA, patients with egg-induced anaphylaxis were significantly younger (P < .001) and exhibited more vomiting (P = .0053) and less throat tightness (P = .0015) and angioedema (P < .001). CONCLUSION: To the best of our knowledge, this is the largest published cohort of pediatric egg-induced anaphylaxis. In this cohort, prehospital EAI use was very low. In addition, we identified certain symptoms that distinguish egg-induced from other triggers of FIA. Taken together, high suspicion is crucial in identifying egg-induced anaphylaxis, given the younger patient demographic and frequent lack of FIA history.

Differences in excess mortality by recipient sex after heart transplant: An individual patient data meta-analysis.

BACKGROUND: Identification of differences in mortality risk between female and male heart transplant recipients may prompt sex-specific management strategies. Because worldwide, males of all ages have higher absolute mortality rates than females, we aimed to compare the excess risk of mortality (risk above the general population) in female vs male heart transplant recipients. METHODS: We used relative survival models conducted separately in SRTR and CTS cohorts from 1988-2019, and subsequently combined using 2-stage individual patient data meta-analysis, to compare the excess risk of mortality in female vs male first heart transplant recipients, accounting for the modifying effects of donor sex and recipient current age. RESULTS: We analyzed 108,918 patients. When the donor was male, female recipients 0-12 years (Relative excess risk (RER) 1.13, 95% CI 1.00-1.26), 13-44 years (RER 1.17, 95% CI 1.10-1.25), and ≥45 years (RER 1.14, 95% CI 1.02-1.27) showed higher excess mortality risks than male recipients of the same age. When the donor was female, only female recipients 13-44 years showed higher excess risks of mortality than males (RER 1.09, 95% CI 1.00-1.20), though not significantly (p = 0.05). CONCLUSIONS: In the setting of a male donor, female recipients of all ages had significantly higher excess mortality than males. When the donor was female, female recipients of reproductive age had higher excess risks of mortality than male recipients of the same age, though this was not statistically significant. Further investigation is required to determine the reasons underlying these differences.

Multi-step validation of a deep learning-based system with visual explanations for optical diagnosis of polyps with advanced features.

Artificial intelligence (AI) has been found to assist in optical differentiation of hyperplastic and adenomatous colorectal polyps. We investigated whether AI can improve the accuracy of endoscopists' optical diagnosis of polyps with advanced features. We introduced our AI system distinguishing polyps with advanced features with more than 0.870 of accuracy in the internal and external validation datasets. All 19 endoscopists with different levels showed significantly lower diagnostic accuracy (0.410-0.580) than the AI. Prospective randomized controlled study involving 120 endoscopists into optical diagnosis of polyps with advanced features with or without AI demonstration identified that AI improved endoscopists' proportion of polyps with advanced features correctly sent for histological examination (0.960 versus 0.840, p < 0.001), and the proportion of polyps without advanced features resected and discarded (0.490 versus 0.380, p = 0.007). We thus developed an AI technique that significantly increases the accuracy of colorectal polyps with advanced features.

Variability of ambient air ammonia in urban Europe (Finland, France, Italy, Spain, and the UK).

This study addressed the scarcity of NH3 measurements in urban Europe and the diverse monitoring protocols, hindering direct data comparison. Sixty-nine datasets from Finland, France, Italy, Spain, and the UK across various site types, including industrial (IND, 8), traffic (TR, 12), urban (UB, 22), suburban (SUB, 12), and regional background (RB, 15), are analyzed to this study. Among these, 26 sites provided 5, or more, years of data for time series analysis. Despite varied protocols, necessitating future harmonization, the average NH3 concentration across sites reached 8.0 ± 8.9 µg/m3. Excluding farming/agricultural hotspots (FAHs), IND and TR sites had the highest concentrations (4.7 ± 3.2 and 4.5 ± 1.0 µg/m3), followed by UB, SUB, and RB sites (3.3 ± 1.5, 2.7 ± 1.3, and 1.0 ± 0.3 µg/m3, respectively) indicating that industrial, traffic, and other urban sources were primary contributors to NH3 outside FAH regions. When referring exclusively to the FAHs, concentrations ranged from 10.0 ± 2.3 to 15.6 ± 17.2 µg/m3, with the highest concentrations being reached in RB sites close to the farming and agricultural sources, and that, on average for FAHs there is a decreasing NH3 concentration gradient towards the city. Time trends showed that over half of the sites (18/26) observed statistically significant trends. Approximately 50 % of UB and TR sites showed a decreasing trend, while 30 % an increasing one. Meta-analysis revealed a small insignificant decreasing trend for non-FAH RB sites. In FAHs, there was a significant upward trend at a rate of 3.51[0.45,6.57]%/yr. Seasonal patterns of NH3 concentrations varied, with urban areas experiencing fluctuations influenced by surrounding emissions, particularly in FAHs. Diel variation showed differing patterns at urban monitoring sites, all with higher daytime concentrations, but with variations in peak times depending on major emission sources and meteorological patterns. These results offer valuable insights into the spatio-temporal patterns of gas-phase NH3 concentrations in urban Europe, contributing to future efforts in benchmarking NH3 pollution control in urban areas.