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The olfactory system is one of the six basic sensory nervous systems. Developing artificial olfactory systems is challenging due to the complexity of chemical information decoding and memory. Conventional chemical sensors can convert chemical signals into electric signals to decode gas information but they lack memory functions. Additional storage and processing units would significantly increase the complexity and power consumption of the devices, especially for portable and wearable devices. Here, an olfactory-inspired in-sensor organic electrochemical transistor (OI-OECT) is proposed, with the integrated functions of chemical information decoding, tunable memory level, and selectivity of vapor sensing. The ion-gel electrolyte endows the OI-OECT with the function of tunable memory levels and a low operating voltage. Typical synaptic behaviors, including inhibitory postsynaptic current and paired-pulse facilitations, are successfully achieved. Importantly, the gas memory level can be effectively modulated by the gate voltages (0 and -1 V), which realized the transformation of volatile and nonvolatile memory. Furthermore, benefiting from the recognition of multiple gases and ability to detect cumulative damage caused by gases, the OI-OECT is demonstrated for early warning system targeting leakage detection of two gases (NH3 and H2S). This work achieves the integrated functions of chemical gas information decode, tunable gas memory level, and selectivity of gas in a single device, which provides a promising pathway for the development of future artificial olfactory systems.
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Gene-editing technology has become a transformative tool for the precise manipulation of biological genomes and holds great significance in the field of animal disease-resistant breeding. Mastitis, a prevalent disease in animal husbandry, imposes a substantial economic burden on the global dairy industry. In this study, a regulatory sequence gene editing breeding strategy for the successful creation of a gene-edited dairy (GED) goats with enhanced mastitis resistance using the ISDra2-TnpB system and dairy goats as the model animal is proposed. This included the targeted integration of an innate inflammatory regulatory sequence (IRS) into the promoter region of the lysozyme (LYZ) gene. Upon Escherichia Coli (E. coli) mammary gland infection, GED goats exhibited increased LYZ expression, showing robust anti-mastitis capabilities, mitigating PANoptosis activation, and alleviating blood-milk-barrier (BMB) damage. Notably, LYZ is highly expressed only in E. coli infection. This study marks the advent of anti-mastitis gene-edited animals with exogenous-free gene expression and demonstrates the feasibility of the gene-editing strategy proposed in this study. In addition, it provides a novel gene-editing blueprint for developing disease-resistant strains, focusing on disease specificity and biosafety while providing a research basis for the widespread application of the ISDra2-TnpB system.
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This study examines managing urban energy systems in the Sichuan Basin, considering natural gas production. An integrated approach assessed the economy, energy, ecology, and technology (EEET) connections. The study identifies systemic issues and significant differences across locations and emphasizes the interdependent nature of economic expansion, energy innovations, and environmental commitment. Findings offer valuable insights for policymakers, providing strategic directions for overcoming barriers to sustainable city and energy advancements, and nurturing resilient urban environments. The EEET framework sheds light on the complex interactions of urban development, enabling officials to focus on areas for improvement. Addressing conflicts can create more cohesive and sustainable urban landscapes, uncovering serious environmental and energy-use issues in cities with dense industrial zones. Decision-makers could prioritize solutions like enforcing pollution controls and encouraging green energy use. Addressing disputes among urban development participants can craft strategies to encourage cooperation, finding win-win outcomes for sustainable city growth.
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BACKGROUND: Post-acute sequelae of COVID-19 (PASC) is incurring a huge health and economic burden worldwide. There is currently no effective treatment or recommended drug for PASC. METHODS: This prospective randomized controlled study was conducted in a hospital in China. The effect of intermittent hypoxia exposure (IHE; 5-min hypoxia alternating with 5-min normal air, repeated five times) on dyspnea and fatigue was investigated in patients meeting the NICE definition of PASC. Patients were computationally randomized to receive normoxia exposure (NE) and routine therapy or IHE and routine therapy. Six-minute walk distance (6MWD) and spirometry were tested before and after the interventions; the Borg Dyspnea Scale (Borg) and the modified Medical Research Council Dyspnea Scale (mMRC) were used to assess dyspnea; and the Fatigue Assessment Scale (FAS) and the Chalder Fatigue Scale-11 (CFQ-11) were used to assess fatigue. The study was registered in the Chinese Clinical Trial Registry (ChiCTR2300070565). FINDINGS: Ninety-five participants (33 males and 62 females) were recruited between March 1, 2023 and December 30, 2023. Forty-seven patients in the IHE group received 10.0 (9.0, 15.0) days of IHE, and 48 patients in NE group received 10.0 (8.0, 12.0) days of NE. 6MWD, forced vital capacity (FVC), FVC %pred, forced expiratory volume in 1 s (FEV1), FEV1 %pred, tidal volume (VT), and dyspnea and fatigue scales markedly improved after IHE (p < 0.05), and improvements were greater than in the NE group (all p < 0.05). Furthermore, participants in IHE group had better subjective improvements in dyspnea and fatigue than those in the NE group (p < 0.05). Compared with <10 days of IHE, ≥10 days of IHE had a greater impact on 6MWD, FVC, FEV1, FEV1 %pred, VT, FAS, and CFQ-11. No severe adverse events were reported. INTERPRETATION: IHE improved spirometry and 6MWD and relieved dyspnea and fatigue in PASC patients. Larger prospective studies are now needed to verify these findings.
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Precise diagnostic biomarkers of anticitrullination protein antibody (ACPA)-negative and early-stage RA are still to be improved. We aimed to screen autoantibodies in ACPA-negative patients and evaluated their diagnostic performance. The human genome-wide protein arrays (HuProt arrays) were used to define specific autoantibodies from the sera of 182 RA patients and 261 disease and healthy controls. Statistical analysis was performed with SPSS 17.0. In Phase I study, 51 out of 19,275 recombinant proteins covering the whole human genome were selected. In Phase II validation study, anti-ANAPC15 (anaphase promoting complex subunit 15) exhibited 41.8% sensitivity and 91.5% specificity among total RA patients. There were five autoantibodies increased in ACPA-negative RA, including anti-ANAPC15, anti-LSP1, anti-APBB1, anti-parathymosin, and anti-UBL7. Anti-parathymosin showed the highest prevalence of 46.2% (p = 0.016) in ACPA-negative early stage (<2 years) RA. To further improve the diagnostic efficacy, a prediction model was constructed with 44 autoantibodies. With increased threshold for RA calling, the specificity of the model is 90.8%, while the sensitivity is 66.1% (87.8% in ACPA-positive RA and 23.8% in ACPA-negative RA) in independent testing patients. Therefore, HuProt arrays identified RA-associated autoantibodies that might become possible diagnostic markers, especially in early stage ACPA-negative RA.
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Emerging evidence has demonstrated the profound impact of the gut microbiome on cardiovascular diseases through the production of diverse metabolites. Using an animal model of myocardial ischemia-reperfusion (I/R) injury, we found that the prophylactic administration of a well-known probiotic, Bifidobacterium infantis (B. infantis), exhibited cardioprotective effects in terms of preserving cardiac contractile function and preventing adverse cardiac remodeling following I/R and that these cardioprotective effects were recapitulated by its metabolite inosine. Transcriptomic analysis further revealed that inosine mitigated I/R-induced cardiac inflammation and cell death. Mechanistic investigations elucidated that inosine suppressed the production of pro-inflammatory cytokines and reduced the numbers of dendritic cells and natural killer cells, achieved through the activation of the adenosine A2A receptor (A2AR) that when inhibited abrogated the cardioprotective effects of inosine. Additionally, in vitro studies using C2C12 myoblasts revealed that inosine attenuated cell death by serving as an alternative carbon source for adenosine triphosphate (ATP) generation through the purine salvage pathway when subjected to oxygen-glucose deprivation/reoxygenation that simulated myocardial I/R injury. Likewise, inosine reversed the I/R-induced decrease in ATP levels in mouse hearts. Taken together, our findings indicate that B. infantis or its metabolite inosine exerts cardioprotective effects against I/R by suppressing cardiac inflammation and attenuating cardiac cell death, suggesting prophylactic therapeutic options for acute ischemic cardiac injury.
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OBJECTIVE: Emerging evidence suggests a higher risk of human papillomavirus-associated subsequent malignant neoplasms (HPV-SMNs) in childhood cancer survivors. However, comprehensive population-based risk estimates for HPV-SMNs are lacking. METHODS: We utilized longitudinal data obtained from the Surveillance, Epidemiology, and End Results program between 1975 and 2018 to establish a cohort comprising childhood cancer individuals who survived for at least 5 years. Standardized incidence ratio (SIR) with corresponding 95â¯% confidence interval (95â¯%CI) was used to evaluate the relative risk of HPV-SMNs. The competing risk regression model was performed to identify risk factors associated with HPV-SMNs. RESULTS: A total of 35,397 childhood cancer survivors were included. Among them, 42 individuals subsequently developed HPV-SMNs (median time from primary cancer, 25 years). HPV-SMN anatomic sites included cervix (N=16), oropharynx (N=15), anus (N=5), vulva\vagina (N=5), and penis (N=1). The 40-year cumulative incidence rate of HPV-SMNs was estimated to be 0.51â¯%. All survivors had a 10-fold increased risk of developing HPV-SMNs compared to individuals of similar age in the general population (SIR 10.1, 95â¯%CI 7.3-13.6). The competing risk regression model indicted that age at diagnosis and the type of primary malignancy could potentially influence the development of HPV-SMNs. Furthermore, multivariable Cox regression analysis confirmed that the presence of HPV-SMNs significantly increased the risk of mortality for survivors (hazard ratio 2.63, 95â¯%CI 1.68-4.14). CONCLUSIONS: Childhood cancer survivors have a significantly elevated risk of developing HPV-SMNs, accompanied by poor survival outcomes. Encouraging HPV vaccination and robust surveillance protocols may improve long-term health outcomes in childhood cancer survivors.
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PURPOSE: This current study attempted to investigate whether one-stitch method (OM) of temporary ileostomy influenced the stoma-related complications after laparoscopic low anterior resection (LLAR). METHODS: We searched for eligible studies in four databases including PubMed, Embase, Cochrane Library, and CNKI from inception to July 20, 2023. Both surgical outcomes and stoma-related complications were compared between the OM group and the traditional method (TM) group. The Newcastle-Ottawa Scale (NOS) was adopted for quality assessment. RevMan 5.4 was conducted for data analyzing. RESULTS: Totally 590 patients from six studies were enrolled in this study (272 patients in the OM group and 318 patients in the TM group). No significant difference was found in baseline information (P > 0.05). Patients in the OM group had shorter operative time in both the primary LLAR surgery (MD = - 17.73, 95%CI = - 25.65 to - 9.80, P < 0.01) and the stoma reversal surgery (MD = - 18.70, 95%CI = - 22.48 to -14.92, P < 0.01) than patients in the TM group. There was no significant difference in intraoperative blood loss of the primary LLAR surgery (MD = - 2.92, 95%CI = - 7.15 to 1.32, P = 0.18). Moreover, patients in the OM group had fewer stoma-related complications than patients in the TM group (OR = 0.55, 95%CI = 0.38 to 0.79, P < 0.01). CONCLUSION: The OM group had shorter operation time in both the primary LLAR surgery and the stoma reversal surgery than the TM group. Moreover, the OM group had less stoma-related complications.
Subject(s)
Ileostomy , Laparoscopy , Postoperative Complications , Rectal Neoplasms , Humans , Ileostomy/adverse effects , Ileostomy/methods , Laparoscopy/adverse effects , Laparoscopy/methods , Rectal Neoplasms/surgery , Postoperative Complications/etiology , Surgical Stomas/adverse effects , Operative Time , Female , MaleABSTRACT
Introduction: Breeding rice with drought tolerance for harsh environments is crucial for agricultural sustainability. Understanding the genetic underpinnings of drought tolerance is vital for developing resilient rice varieties. Genome-wide association studies (GWAS) have emerged as pivotal tools in unravelling the complex genetic architecture of traits like drought tolerance, capitalizing on the natural genetic diversity within rice germplasm collections. Methods: In this study, a comprehensive panel of 210 rice varieties was phenotyped over ten days in controlled conditions, subjected to simulated drought stress using 20% PEG 6000 in petri dishes. Throughout the stress period, crucial traits such as germination percentage (GP), germination rate index (GRI), mean germination time (MGT), and seedling percentage (SP) were meticulously monitored. Results: The GWAS analysis uncovered a total of 38 QTLs associated with drought tolerance traits, including novel loci like qMGT-5.2, qSP-3, qSP7.2, and qGP-5.2. Additionally, RNA-seq analysis identified ten genes with significant expression differences under drought stress conditions. Notably, haplotype analysis pinpointed elite haplotypes in specific genes linked to heightened drought tolerance. Discussion: Overall, this study underscores the importance of GWAS in validating known genes while unearthing novel loci to enrich the genetic resources for enhancing drought tolerance in rice breeding programs.
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It has been over 4 years since the coronavirus disease 2019 outbreak, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). As an effective response to coronavirus disease 2019, the SARS-CoV-2 vaccines have been widely used around the world. However, couples who are planning to conceive naturally or by assisted reproductive technology (ART) are concerned about the impact of SARS-CoV-2 vaccines on pregnancy and offspring safety. Furthermore, in the initial stage of the epidemic, opinions among physicians and healthcare providers on whether ART patients should be immunized are divided due to the lack of data regarding the impact of the SARS-CoV-2 vaccine on ART. This is not the first, nor will it be the last time humans confront pandemics. It is time to summarize the experience about the effect of the SARS-CoV-2 vaccine on the outcomes of ART, which can provide a reference for the future. This paper reviewed relevant research, and significant adverse effects of the SARS-CoV-2 vaccine on the outcome of ART have not been observed. Considering the increased risk of serious complications in pregnant women infected with SARS-CoV-2, timely vaccination may be a wiser choice.
Subject(s)
COVID-19 Vaccines , COVID-19 , Reproductive Techniques, Assisted , Humans , COVID-19 Vaccines/adverse effects , COVID-19 Vaccines/administration & dosage , Pregnancy , Female , COVID-19/prevention & control , SARS-CoV-2/immunology , Pregnancy Complications, Infectious/prevention & control , Vaccination/adverse effectsABSTRACT
Background: This study investigated factors influencing discrepancies between fractional flow reserve (FFR) and resting full-cycle ratio (RFR) in the functional assessment of coronary artery stenosis in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS). Methods: We included 320 diseased vessels from 253 consecutive patients with NSTE-ACS. Vessels were categorized into four groups based on FFR ≤ 0.80 and RFR ≤ 0.89 thresholds: group 1 concordant negative (RFR-/FFR-), group 2 positive RFR and negative FFR (RFR+/FFR-), group 3 negative RFR and positive FFR (RFR-/FFR+), and group 4 concordant positive (RFR+/FFR+). Univariate and multivariate logistic regression analyses were conducted to identify predictors of diagnostic discrepancy between FFR and RFR. Results: Of the 320 diseased vessels, 182 (56.9%) were in group 1 (RFR-/FFR-), 33 (10.3%) in group 2 (RFR+/FFR-), 31 (9.7%) in group 3 (RFR-/FFR+), and 74 (23.1%) in group 4 (RFR+/FFR+). The concordance between FFR and RFR was 80.0%. Notably, left anterior descending artery (LAD) lesions exhibited significantly lower consistency compared to non-LAD lesions (p = 0.001), with distinct differences in FFR and RFR values between these groups (p < 0.001). The presence of a LAD lesion emerged as an independent predictor of diagnostic inconsistency between positive RFR and negative FFR measurements (p = 0.001). Conclusions: LAD involvement independently predicts diagnostic discrepancies between FFR and RFR in evaluating functional coronary artery stenosis in NSTE-ACS patients.
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Fast, accurate, real-time measurement of gas concentration is an important task for preventing coal mining disasters. In order to develop an accurate monitoring method for methane gas concentration at different locations in a mine environment, a non-source optical fiber sensor for multi-point methane detection has been developed in this paper. A 16-channel fiber splitter and a multi-channel time-sharing acquisition module are employed within the sensor, enabling simultaneous detection of methane gas at 16 points by a host. Furthermore, the methane sensors are connected to the monitoring host via an all-optical method, achieving non-source and long-range detection of methane. To assess the performance of the methane gas sensor, experiments were conducted to evaluate its detection range, response time, and stability. The results indicated that the average detection error was approximately 1.84% across the full range, and the response time did not exceed 10 s. The minimum detection limit of the sensor, as determined by the 1σ criteria, was obtained as 58.42 ppm. Additionally, the concentrations of methane gas measured at varying distances (1 km, 2 km, 5 km) were found to be essentially consistent over an extended period. These results suggest that the development of this non-source optical fiber sensor holds significant potential for providing a method for mine environment, multi-point online methane gas detection.
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Objectives: The objective of this study is to investigate the indirect causalities between gut microbiota and sleep disorders. Methods: In stage 1, we utilized 196 gut microbiota as the exposure factor and conducted a two-sample univariable Mendelian randomization (MR) analysis on five sleep disorders: insomnia, excessive daytime sleepiness (EDS), sleep-wake rhythm disorders (SWRD), obstructive sleep apnea (OSA), and isolated REM sleep behavior disorder (iRBD). In stage 2, we validated the MR findings by comparing fecal microbiota abundance between patients and healthy controls through 16S rDNA sequencing. In stage 3, we explored the indirect pathways by which the microbiota affects sleep, using 205 gut microbiota metabolic pathways and 9 common risk factors for sleep disorders as candidate mediators in a network MR analysis. Results: In stage 1, the univariable MR analysis identified 14 microbiota potentially influencing five different sleep disorders. In stage 2, the results from our observational study validated four of these associations. In stage 3, the network MR analysis revealed that the Negativicutes class and Selenomonadales order might worsen insomnia by increasing pain [mediation: 12.43% (95% CI: 0.47, 24.39%)]. Oxalobacter could raise EDS by disrupting adenosine reuptake [25.39% (1.84, 48.95%)]. Allisonella may elevate OSA risk via obesity promotion [36.88% (17.23, 56.54%)], while the Eubacterium xylanophilum group may lower OSA risk by decreasing smoking behavior [7.70% (0.66, 14.74%)]. Conclusion: Triangulation of evidence from the MR and observational study revealed indirect causal relationships between the microbiota and sleep disorders, offering fresh perspectives on how gut microbiota modulate sleep.
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AlGaN-based light-emitting diodes (LEDs) operating in the deep-ultraviolet (DUV) spectral range (210-280 nm) have demonstrated potential applications in physical sterilization. However, the poor external quantum efficiency (EQE) hinders further advances in the emission performance of AlGaN-based DUV LEDs. Here, we demonstrate the performance of 270-nm AlGaN-based DUV LEDs beyond the state-of-the-art by exploiting the innovative combination of bandgap engineering and device craft. By adopting tailored multiple quantum wells (MQWs), a reflective Al reflector, a low-optical-loss tunneling junction (TJ) and a dielectric SiO2 insertion structure (IS-SiO2), outstanding light output powers (LOPs) of 140.1 mW are achieved in our DUV LEDs at 850 mA. The EQEs of our DUV LEDs are 4.5 times greater than those of their conventional counterparts. This comprehensive approach overcomes the major difficulties commonly faced in the pursuit of high-performance AlGaN-based DUV LEDs, such as strong quantum-confined Stark effect (QCSE), severe optical absorption in the p-electrode/ohmic contact layer and poor transverse magnetic (TM)-polarized light extraction. Furthermore, the on-wafer electroluminescence characterization validated the scalability of our DUV LEDs to larger production scales. Our work is promising for the development of highly efficient AlGaN-based DUV LEDs.
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AIM: To construct a novel liposomal drug delivery system co-modified with SP94 and BR2 ligands, encapsulating both the bitter ginseng derivative B21 and doxorubicin (DOX), to achieve superior anti-tumour efficacy and reduced toxic side effects. METHODS: Liposomes were prepared using an organic phase reaction method, with B21 encapsulated in the lipid phase and DOX in the aqueous phase. The liposomes were further modified with SP94 and BR2 peptides. The characterisations, cytotoxicity, and in vitro targeting effects were assessed through various methods including ultraviolet spectrophotometry, high-performance liquid chromatography, nano-size analysis, ultrafiltration centrifugation, dialysis, transmission electron microscopy, flow cytometry, Methylthiazolyldiphenyl-tetrazolium bromide assay, confocal laser scanning microscopy, transwell assay, and tumorsphere assay. RESULTS: SP94/BR2-B21/DOX-LP liposomes were spherical with an average diameter of 120.87 ± 1.00 nm, a polydispersity index (PDI) of 0.223 ± 0.006, and a surface charge of -23.1 ± 1.27 mV. The encapsulation efficiencies for B21 and DOX were greater than 85% and 97% (mg/mg), respectively. The results indicated that SP94/BR2-B21/DOX-LP exhibited enhanced targeting and cytotoxicity compared to single-ligand modified and unmodified liposomes, with the combined encapsulation of B21 and DOX showing synergistic anti-hepatocarcinogenic effects. CONCLUSION: SP94/BR2-B21/DOX-LP liposomes represent a promising targeted drug delivery system for hepatocellular carcinoma, offering improved membrane penetration, enhanced therapeutic efficacy, and reduced systemic toxicity.
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BACKGROUND: Pulsed field ablation (PFA) is a novel, myocardial-selective, non-thermal ablation modality used to target cardiac arrhythmias. Although prompt EGM signal disappearance is observed immediately after PFA application in the pulmonary veins, whether this finding results in adequate transmural lesions is unknown. STUDY AIM: If application repetition and catheter-tissue contact impact on lesion formation during PFA. METHODS: A circular loop PFA catheter was used to deliver repeated energy applications with various levels of contact-force. A benchtop vegetal potato model and a beating heart ventricular myocardial model were utilized to evaluate the impact of application repetition, contact force, and catheter repositioning on contiguity and lesion depth. Lesion development occurred over 18 hours in the vegetal model and over 6 hours in the porcine model. RESULTS: Lesion formation was found to be dependent on application repetition and contact. In porcine ventricles, single and multiple stacked applications led to a lesion depth of 3.5 ± 0.7 mm and 4.4 ± 1.3 mm, respectively (p =0.002). Furthermore, the greater the catheter-tissue contact, the more contiguous and deeper the lesions in the vegetal model (1.0±0.9 mm with no contact Vs. 5.4±1.4 mm with 30 g of force; p=.0001). CONCLUSION: PFA delivered via a circular catheter showed that both repetition and catheter contact led independently to deeper lesion formation. These findings indicate that endpoints for effective PFA ablation are more related to PFA biophysics than mere EGM attenuation.
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Deep-ultraviolet (UV) birefringent materials are urgently needed to facilitate light polarization in deep-UV lithography. Maximizing anisotropy by regulating the alignment of functional modules is essential for improving the linear optical performance of birefringent materials. In this work, we proposed a strategy to design deep-UV birefringent materials that achieve functional module ordering via weak interactions. Following this strategy, four compounds CN4H7SO3CF3, CN4H7SO3CH3, C(NH2)3SO3CH3, and C(NH2)3SO3CF3 were identified as high-performance candidates for deep-UV birefringent materials. The millimeter-sized crystals of CN4H7SO3CF3, CN4H7SO3CH3, and C(NH2)3SO3CH3 were grown, and the transmittance spectra show that their cutoff edges are below 200 nm. CN4H7SO3CF3 exhibits the largest birefringence (0.149 @ 546 nm, 0.395 @ 200 nm) in the deep-UV region among reported sulfates and sulfate derivatives. It reveals that the hydrogen bond can modulate the module ordering of the heteroleptic tetrahedra and planar π-conjugated cations, thus greatly enhancing the birefringence. Our study not only discovers new deep-UV birefringent materials but also provides an upgraded strategy for optimizing optical anisotropy to achieve efficient birefringence.
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Background: Kawasaki disease (KD) has been considered as the most common required pediatric cardiovascular diseases among the world. However, the molecular mechanisms of KD were not fully underlined, leading to a confused situation in disease management and providing precious prognosis prediction. The disorders of gut microbiome had been identified among several cardiovascular diseases and inflammation conditions. Therefore, it is urgent to elucidate the characteristics of gut microbiome in KD and demonstrate its potential role in regulating intravenous immunoglobulin (IVIG) resistance and coronary artery injuries. Methods: A total of 96 KD children and 62 controls were enrolled in the study. One hundred forty fecal samples had been harvested from KD patients, including individuals before or after IVIG treatment, with or without early coronary artery lesions and IVIG resistance. Fecal samples had been collected before and after IVIG administration and stored at -80°C. Then, metagenomic analysis had been done using Illumina NovaSeq 6000 platform. After that, the different strains and functional differences among comparisons were identified. Results: First, significant changes had been observed between KD and their controls. We found that the decrease of Akkermansia muciniphila, Faecalibacterium prausnitzii, Bacteroides uniformis, and Bacteroides ovatus and the increase of pathogenic bacteria Finegoldia magna, Abiotrophia defectiva, and Anaerococcus prevotii perhaps closely related to the incidence of KD. Then, metagenomic and responding functional analysis demonstrated that short-chain fatty acid pathways and related strains were associated with different outcomes of therapeutic efficacies. Among them, the reduction of Bacteroides thetaiotaomicron, the enrichment of Enterococcus faecalis and antibiotic resistance genes had been found to be involved in IVIG resistance of KD. Moreover, our data also revealed several potential pathogenetic microbiome of that KD patients with coronary artery lesions. Conclusion: These results strongly proved that distinct changes in the gut microbiome of KD and the dysfunction of gut microbiomes should be responsible for the pathogenesis of KD and significantly impact the prognosis of KD.
Subject(s)
Feces , Gastrointestinal Microbiome , Metagenomics , Mucocutaneous Lymph Node Syndrome , Humans , Mucocutaneous Lymph Node Syndrome/microbiology , Mucocutaneous Lymph Node Syndrome/immunology , Gastrointestinal Microbiome/genetics , Male , Metagenomics/methods , Female , Child, Preschool , Infant , Feces/microbiology , Immunoglobulins, Intravenous/therapeutic use , Metagenome , Child , Bacteria/classification , Bacteria/genetics , Bacteria/isolation & purification , Case-Control StudiesABSTRACT
BACKGROUND: Recent advancements in artificial intelligence (AI) and large language models (LLMs) have shown potential in medical fields, including dermatology. With the introduction of image analysis capabilities in LLMs, their application in dermatological diagnostics has garnered significant interest. These capabilities are enabled by the integration of computer vision techniques into the underlying architecture of LLMs. OBJECTIVE: This study aimed to compare the diagnostic performance of Claude 3 Opus and ChatGPT with GPT-4 in analyzing dermoscopic images for melanoma detection, providing insights into their strengths and limitations. METHODS: We randomly selected 100 histopathology-confirmed dermoscopic images (50 malignant, 50 benign) from the International Skin Imaging Collaboration (ISIC) archive using a computer-generated randomization process. The ISIC archive was chosen due to its comprehensive and well-annotated collection of dermoscopic images, ensuring a diverse and representative sample. Images were included if they were dermoscopic images of melanocytic lesions with histopathologically confirmed diagnoses. Each model was given the same prompt, instructing it to provide the top 3 differential diagnoses for each image, ranked by likelihood. Primary diagnosis accuracy, accuracy of the top 3 differential diagnoses, and malignancy discrimination ability were assessed. The McNemar test was chosen to compare the diagnostic performance of the 2 models, as it is suitable for analyzing paired nominal data. RESULTS: In the primary diagnosis, Claude 3 Opus achieved 54.9% sensitivity (95% CI 44.08%-65.37%), 57.14% specificity (95% CI 46.31%-67.46%), and 56% accuracy (95% CI 46.22%-65.42%), while ChatGPT demonstrated 56.86% sensitivity (95% CI 45.99%-67.21%), 38.78% specificity (95% CI 28.77%-49.59%), and 48% accuracy (95% CI 38.37%-57.75%). The McNemar test showed no significant difference between the 2 models (P=.17). For the top 3 differential diagnoses, Claude 3 Opus and ChatGPT included the correct diagnosis in 76% (95% CI 66.33%-83.77%) and 78% (95% CI 68.46%-85.45%) of cases, respectively. The McNemar test showed no significant difference (P=.56). In malignancy discrimination, Claude 3 Opus outperformed ChatGPT with 47.06% sensitivity, 81.63% specificity, and 64% accuracy, compared to 45.1%, 42.86%, and 44%, respectively. The McNemar test showed a significant difference (P<.001). Claude 3 Opus had an odds ratio of 3.951 (95% CI 1.685-9.263) in discriminating malignancy, while ChatGPT-4 had an odds ratio of 0.616 (95% CI 0.297-1.278). CONCLUSIONS: Our study highlights the potential of LLMs in assisting dermatologists but also reveals their limitations. Both models made errors in diagnosing melanoma and benign lesions. These findings underscore the need for developing robust, transparent, and clinically validated AI models through collaborative efforts between AI researchers, dermatologists, and other health care professionals. While AI can provide valuable insights, it cannot yet replace the expertise of trained clinicians.
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Objectives: The emergency response to the COVID-19 pandemic may disrupt hospital management activities of antimicrobial resistance (AMR). This study aimed to determine the changing AMR trend over the period in China when stringent COVID-19 response measures were implemented. Methods: This retrospective study was conducted in a designated hospital for COVID-19 patients in Guangzhou, China from April 2018 to September 2021. The prevalence of 13 antimicrobial-resistant bacteria was compared before and after the COVID-19 responses through Chi-square tests. Interrupted time series (ITS) models on the weekly prevalence of AMR were established to determine the changing trend. Controlled ITS models were performed to compare the differences between subgroups. Results: A total of 10,134 isolates over 1,265 days were collected. And antimicrobial-resistant strains presented in 38.6% of the testing isolates. The weekly AMR prevalence decreased by 0.29 percentage point (95% CI [0.05-0.80]) after antimicrobial stewardship (AMS) policy, despite an increase in the prevalence of penicillin-resistant Streptococcus pneumoniae (from 0/43 to 15/43, p < 0.001), carbapenem-resistant Escherichia coli (from 20/1254 to 41/1184, p = 0.005), and carbapenem-resistant Klebsiella pneumoniae (from 93/889 to 114/828, p = 0.042). And the changing trend did not vary by gender (male vs. female), age (<65 vs. ≥65 years), service setting (outpatient vs. inpatient), care unit (ICU vs. non-ICU), the primary site of infection (Lung vs. others), and Gram type of bacteria (positive vs. negative). Conclusion: The response to COVID-19 did not lead to an increase in overall AMR; however, it appears that management strategy on the prudent use of antimicrobials likely contributed to a sizable long-term drop. The frequency of several multidrug-resistant bacteria continues to increase after the COVID-19 epidemic. It is crucial to continue to monitor AMR when COVID-19 cases have surged in China after the relaxation of restriction measures.