Targeted Cyclo[8]pyrrole-Based NIR-II Photoacoustic Tomography Probe for Suppression of Orthotopic Pancreatic Tumor Growth and Intra-abdominal Metastases.

Pancreatic cancer is highly lethal. New diagnostic and treatment modalities are desperately needed. We report here that an expanded porphyrin, cyclo[8]pyrrole (CP), with a high extinction coefficient (89.16 L/g·cm) within the second near-infrared window (NIR-II), may be formulated with an αvß3-specific targeting peptide, cyclic-Arg-Gly-Asp (cRGD), to form cRGD-CP nanoparticles (cRGD-CPNPs) with promising NIR-II photothermal (PT) therapeutic and photoacoustic (PA) imaging properties. Studies with a ring-array PA tomography system, coupled with analysis of control nanoparticles lacking a targeting element (CPNPs), revealed that cRGD conjugation promoted the delivery of the NPs through abnormal vessels around the tumor to the solid tumor core. This proved true in both subcutaneous and orthotopic pancreatic tumor mice models, as confirmed by immunofluorescent studies. In combination with NIR-II laser photoirradiation, the cRGD-CPNPs provided near-baseline tumor growth inhibition through PTT both in vitro and in vivo. Notably, the combination of the present cRGD-CPNPs and photoirradiation was found to inhibit intra-abdominal metastases in an orthotopic pancreatic tumor mouse model. The cRGD-CPNPs also displayed good biosafety profiles, as inferred from PA tomography, blood analyses, and H&E staining. They thus appear promising for use in combined PA imaging and PT therapeutic treatment of pancreatic cancer.

Relief of tumor hypoxia using a nanoenzyme amplifies NIR-II photoacoustic-guided photothermal therapy.

Hypoxia is a critical tumor microenvironment (TME) component. It significantly impacts tumor growth and metastasis and is known to be a major obstacle for cancer therapy. Integrating hypoxia modulation with imaging-based monitoring represents a promising strategy that holds the potential for enhancing tumor theranostics. Herein, a kind of nanoenzyme Prussian blue (PB) is synthesized as a metal-organic framework (MOF) to load the second near-infrared (NIR-II) small molecule dye IR1061, which could catalyze hydrogen peroxide to produce oxygen and provide a photothermal conversion element for photoacoustic imaging (PAI) and photothermal therapy (PTT). To enhance stability and biocompatibility, silica was used as a coating for an integrated nanoplatform (SPI). SPI was found to relieve the hypoxic nature of the TME effectively, thus suppressing tumor cell migration and downregulating the expression of heat shock protein 70 (HSP70), both of which led to an amplified NIR-II PTT effect in vitro and in vivo, guided by the NIR-II PAI. Furthermore, label-free multi-spectral PAI permitted the real-time evaluation of SPI as a putative tumor treatment. A clinical histological analysis confirmed the amplified treatment effect. Hence, SPI combined with PAI could offer a new approach for tumor diagnosing, treating, and monitoring.

Internet Health Resources on Nocturnal Enuresis: A Readability, Quality, and Accuracy Analysis.

INTRODUCTION: Nocturnal enuresis is a common yet quality-of-life-limiting pediatric condition. There is an increasing trend for parents to obtain information on the disease's nature and treatment options via the internet. However, the quality of health-related information on the internet varies greatly and is largely uncontrolled and unregulated. With this study, a readability, quality, and accuracy evaluation of the health information regarding nocturnal enuresis is carried out. MATERIALS AND METHODS: A questionnaire was administered to parents and patients with nocturnal enuresis to determine their use of the internet to research their condition. The most common search terms were determined, and the first 30 websites returned by the most popular search engines were used to assess the quality of information about nocturnal enuresis. Each site was categorized by type and assessed for readability using the Gunning fog score, Simple Measure of Gobbledygook (SMOG) index, and Dale-Chall score; for quality using the DISCERN score; and for accuracy by comparison to the International Children's Continence Society guidelines by three experienced pediatric urologists and nephrologists. RESULTS: A total of 30 websites were assessed and classified into five categories: professional (n = 13), nonprofit (n = 8), commercial (n = 4), government (n = 3), and other (n = 2). The information was considered difficult for the public to comprehend, with mean Gunning fog, SMOG index, and Dale-Chall scores of 12.1 ± 4.3, 14.1 ± 4.3, and 8.1 ± 1.3, respectively. The mean summed DISCERN score was 41 ± 11.6 out of 75. Only seven (23%) websites were considered of good quality (DISCERN score > 50). The mean accuracy score of the websites was 3.2 ± 0.6 out of 5. Commercial websites were of the poorest quality and accuracy. Websites generally scored well in providing their aims and identifying treatment benefits and options, while they lacked references and information regarding treatment risks and mechanisms. CONCLUSION: Online information about nocturnal enuresis exists for parents; however, most websites are of suboptimal quality, readability, and accuracy. Pediatric surgeons should be aware of parents' health-information-seeking behavior and be proactive in guiding parents to identify high-quality resources.

Congenital lung malformations.

Congenital lung malformations (CLMs) are rare developmental anomalies of the lung, including congenital pulmonary airway malformations (CPAM), bronchopulmonary sequestration, congenital lobar overinflation, bronchogenic cyst and isolated congenital bronchial atresia. CLMs occur in 4 out of 10,000 live births. Postnatal presentation ranges from an asymptomatic infant to respiratory failure. CLMs are typically diagnosed with antenatal ultrasonography and confirmed by chest CT angiography in the first few months of life. Although surgical treatment is the gold standard for symptomatic CLMs, a consensus on asymptomatic cases has not been reached. Resection, either thoracoscopically or through thoracotomy, minimizes the risk of local morbidity, including recurrent infections and pneumothorax, and avoids the risk of malignancies that have been associated with CPAM, bronchopulmonary sequestration and bronchogenic cyst. However, some surgeons suggest expectant management as the incidence of adverse outcomes, including malignancy, remains unknown. In either case, a planned follow-up and a proper transition to adult care are needed. The biological mechanisms through which some CLMs may trigger malignant transformation are under investigation. KRAS has already been confirmed to be somatically mutated in CPAM and other genetic susceptibilities linked to tumour development have been explored. By summarizing current progress in CLM diagnosis, management and molecular understanding we hope to highlight open questions that require urgent attention.

Baseline gut microbiota and metabolome predict durable immunogenicity to SARS-CoV-2 vaccines.

The role of gut microbiota in modulating the durability of COVID-19 vaccine immunity is yet to be characterised. In this cohort study, we collected blood and stool samples of 121 BNT162b2 and 40 CoronaVac vaccinees at baseline, 1 month, and 6 months post vaccination (p.v.). Neutralisation antibody, plasma cytokine and chemokines were measured and associated with the gut microbiota and metabolome composition. A significantly higher level of neutralising antibody (at 6 months p.v.) was found in BNT162b2 vaccinees who had higher relative abundances of Bifidobacterium adolescentis, Bifidobacterium bifidum, and Roseburia faecis as well as higher concentrations of nicotinic acid (Vitamin B) and γ-Aminobutyric acid (P < 0.05) at baseline. CoronaVac vaccinees with high neutralising antibodies at 6 months p.v. had an increased relative abundance of Phocaeicola dorei, a lower relative abundance of Faecalibacterium prausnitzii, and a higher concentration of L-tryptophan (P < 0.05) at baseline. A higher antibody level at 6 months p.v. was also associated with a higher relative abundance of Dorea formicigenerans at 1 month p.v. among CoronaVac vaccinees (Rho = 0.62, p = 0.001, FDR = 0.123). Of the species altered following vaccination, 79.4% and 42.0% in the CoronaVac and BNT162b2 groups, respectively, recovered at 6 months. Specific to CoronaVac vaccinees, both bacteriome and virome diversity depleted following vaccination and did not recover to baseline at 6 months p.v. (FDR < 0.1). In conclusion, this study identified potential microbiota-based adjuvants that may extend the durability of immune responses to SARS-CoV-2 vaccines.

YoloCurvSeg: You only label one noisy skeleton for vessel-style curvilinear structure segmentation.

Weakly-supervised learning (WSL) has been proposed to alleviate the conflict between data annotation cost and model performance through employing sparsely-grained (i.e., point-, box-, scribble-wise) supervision and has shown promising performance, particularly in the image segmentation field. However, it is still a very challenging task due to the limited supervision, especially when only a small number of labeled samples are available. Additionally, almost all existing WSL segmentation methods are designed for star-convex structures which are very different from curvilinear structures such as vessels and nerves. In this paper, we propose a novel sparsely annotated segmentation framework for curvilinear structures, named YoloCurvSeg. A very essential component of YoloCurvSeg is image synthesis. Specifically, a background generator delivers image backgrounds that closely match the real distributions through inpainting dilated skeletons. The extracted backgrounds are then combined with randomly emulated curves generated by a Space Colonization Algorithm-based foreground generator and through a multilayer patch-wise contrastive learning synthesizer. In this way, a synthetic dataset with both images and curve segmentation labels is obtained, at the cost of only one or a few noisy skeleton annotations. Finally, a segmenter is trained with the generated dataset and possibly an unlabeled dataset. The proposed YoloCurvSeg is evaluated on four publicly available datasets (OCTA500, CORN, DRIVE and CHASEDB1) and the results show that YoloCurvSeg outperforms state-of-the-art WSL segmentation methods by large margins. With only one noisy skeleton annotation (respectively 0.14%, 0.03%, 1.40%, and 0.65% of the full annotation), YoloCurvSeg achieves more than 97% of the fully-supervised performance on each dataset. Code and datasets will be released at https://github.com/llmir/YoloCurvSeg.

Restoring the imaging quality of circular transducer array-based PACT using synthetic aperture focusing technique integrated with 2nd-derivative-based back projection scheme.

Circular-array-based photoacoustic computed tomography (CA-PACT) is a promising imaging tool owing to its broad acoustic detection coverage and fidelity. However, CA-PACT suffers from poor image quality outside the focal zone along both elevational and lateral dimensions. To address this challenge, we proposed a novel reconstruction strategy by integrating the synthetic aperture focusing technique (SAFT) with the 2nd derivative-based back projection (2nd D-BP) algorithm to restore the image quality outside the focal zone along both the elevational and lateral axes. The proposed solution is a two-phase reconstruction scheme. In the first phase, with the assistance of an acoustic lens, we designed a circular array-based SAFT algorithm to restore the resolution and SNR along the elevational axis. The acoustic lens pushes the boundary of the upper limit of the SAFT scheme to achieve enhanced elevational resolution. In the second phase, we proposed a 2nd D-BP scheme to improve the lateral resolution and suppress noises in 3D imaging results. The 2nd D-BP strategy enhances the image quality along the lateral dimension by up-converting the high spatial frequencies of the object's absorption pattern. We validated the effectiveness of the proposed strategy using both phantoms and in vivo human experiments. The experimental results demonstrated superior image quality (7-fold enhancement in elevational resolution, 3-fold enhancement in lateral resolution, and an 11-dB increase in SNR). This strategy provides a new paradigm in the PACT system as it significantly enhances the spatial resolution and imaging contrast in both the elevational and lateral dimensions while maintaining a large focal zone.

Handheld photoacoustic imaging of indocyanine green clearance for real-time quantitative evaluation of liver reserve function.

Preoperative assessment of liver function reserve (LFR) is essential for determining the extent of liver resection and predicting the prognosis of patients with liver disease. In this paper, we present a real-time, handheld photoacoustic imaging (PAI) system-based noninvasive approach for rapid LFR assessment. A linear-array ultrasound transducer was sealed in a housing filled with water; its front end was covered with a plastic wrap. This PAI system was first implemented on phantoms to confirm that the photoacoustic (PA) intensity of indocyanine green (ICG) in blood reflects the concentration of ICG in blood. In vivo studies on normal rabbits and rabbits with liver fibrosis were carried out by recording the dynamic PA signal of ICG in their jugular veins. By analyzing the PA intensity-time curve, a clear difference was identified in the pharmacokinetic behavior of ICG between the two groups. In normal rabbits, the mean ICG clearance rate obtained by PAI at 15 min after administration (PAI-R15) was below 21.6%, whereas in rabbits with liver fibrosis, PAI-R15 exceeded 62.0% because of poor liver metabolism. The effectiveness of the proposed method was further validated by the conventional ICG clearance test and pathological examination. Our findings suggest that PAI is a rapid, noninvasive, and convenient method for LFR assessment and has immense potential for assisting clinicians in diagnosing and managing patients with liver disease.

Obesity in children and adolescents: Overview of the diagnosis and management.

Childhood obesity is one of the biggest public health challenges globally. It is associated with various adverse health consequences throughout life. Prevention and early intervention represent the most reasonable and cost-effective approaches. Considerable progress has been achieved in the management of obesity in children and adolescents; yet, implementation in the real world remains a challenge. This article aimed to present an overview of the diagnosis and management of obesity in children and adolescents.

Feature issue introduction: ultrafast optical imaging.

This feature issue of Optics Express collects 20 articles that report the most recent progress of ultrafast optical imaging. This review provides a summary of these articles that cover the spectrum of ultrafast optical imaging, from new technologies to applications.

Large-scale fabrication of an ultrathin broadband absorber using quasi-random dielectric Mie resonators.

Ultrathin broadband absorber maintaining a near-uniform low reflectivity over a broadband wavelength is essential for many optical applications, such as light harvesting and nanoscale imaging. Recently, there has been considerable interest in employing arrays of high-index dielectric Mie resonators on surfaces to trap light and reduce the reflectivity. For such Mie-resonant metasurfaces, however, antireflection properties featuring both a flat low reflectance curve and a wide bandwidth are hard to be satisfied simultaneously, and an efficient large-scale nanofabrication technique rarely exists. Here, we present a high-throughput laser interference induced quasi-random patterning (LIIQP) technique to fabricate quasi-random Mie resonators in large scale. Mie resonators with feature sizes down to sub-100 nm have been fabricated using a 1064 nm laser source. Each Mie resonator concentrates light at its shape-dependent resonant frequency, and all such resonators are arranged quasi-randomly to provide both rich (with broadband Fourier components) and strong (with large intensities) Fourier spectra. Specifically, a near-uniform broadband reflectivity over 400-1100 nm spectrum region has been confined below 3% by fabricating a large-scale ultrathin (around 400 nm) absorber. Our concept and high-throughput fabrication technique allows the rapid production of quasi-random dielectric Mie-resonant metasurfaces in a controllable way, which can be used in various promising applications including thin-film solar cells, display, and imaging.

An optofluidic platform for interrogating chemosensory behavior and brainwide neural representation in larval zebrafish.

Studying chemosensory processing desires precise chemical cue presentation, behavioral response monitoring, and large-scale neuronal activity recording. Here we present Fish-on-Chips, a set of optofluidic tools for highly-controlled chemical delivery while simultaneously imaging behavioral outputs and whole-brain neuronal activities at cellular resolution in larval zebrafish. These include a fluidics-based swimming arena and an integrated microfluidics-light sheet fluorescence microscopy (µfluidics-LSFM) system, both of which utilize laminar fluid flows to achieve spatiotemporally precise chemical cue presentation. To demonstrate the strengths of the platform, we used the navigation arena to reveal binasal input-dependent behavioral strategies that larval zebrafish adopt to evade cadaverine, a death-associated odor. The µfluidics-LSFM system enables sequential presentation of odor stimuli to individual or both nasal cavities separated by only ~100 µm. This allowed us to uncover brainwide neural representations of cadaverine sensing and binasal input summation in the vertebrate model. Fish-on-Chips is readily generalizable and will empower the investigation of neural coding in the chemical senses.

Observation of modulation instability Kerr frequency combs in a fiber Fabry-Pérot resonator.

We report the experimental observation of a modulation instability induced Kerr frequency comb in an all fiber Fabry-Pérot resonator. We fully characterized, in intensity and phase, the frequency comb using a commercial 10 MHz resolution heterodyne detection system to reveal more than 125 comb teeth within each of the modulation instability sidelobes. Moreover, we were able to reveal the fine temporal structure in phase and intensity of the output Turing patterns. The experimental results are generally in good agreement with numerical simulations.

Quantized spiral-phase-modulation based deep learning for real-time defocusing distance prediction.

Whole slide imaging (WSI) has become an essential tool in pathological diagnosis, owing to its convenience on remote and collaborative review. However, how to bring the sample at the optimal position in the axial direction and image without defocusing artefacts is still a challenge, as traditional methods are either not universal or time-consuming. Until recently, deep learning has been shown to be effective in the autofocusing task in predicting defocusing distance. Here, we apply quantized spiral phase modulation on the Fourier domain of the captured images before feeding them into a light-weight neural network. It can significantly reduce the average predicting error to be lower than any previous work on an open dataset. Also, the high predicting speed strongly supports it can be applied on an edge device for real-time tasks with limited computational source and memory footprint.

Dynamics of dissipative soliton molecules in a dual-wavelength ultrafast fiber laser.

Optical solitons, particle-like excitations ubiquitous in many fields, can bind to form soliton molecules with striking molecule-like interactions. However, the exotic soliton interactions in soliton molecules are still largely unexplored in dual-wavelength mode-locked fiber lasers. Here, we reveal the dynamics of dissipative soliton molecules with periodic solitons collision in a dual-wavelength ultrafast fiber laser. The soliton molecules with a central wavelength of 1532.8 nm and 1561 nm exhibit conspicuously different evolution characteristics attributed to the difference in gain spectral intensity and trapped potential. The long-wavelength soliton molecule swiftly recovers to the initial state after collision, while the short-wavelength soliton molecule has a remarkable variation in temporal separation and operation state. Moreover, the multiple intensive repulsion and attraction in soliton molecule with energy transfer between leading and trailing solitons, and the formation of triplet soliton molecule in short-wavelength with multiple switching have also been observed. The different oscillating solutions coexisting in dual-wavelength soliton molecules involving oscillating and sliding phase evolution confirm the multistability of the dissipative system. These findings shed new insights into the dynamics of soliton molecules and solitons collision in nonlinear systems.

890-nm-excited SHG and fluorescence imaging enabled by an all-fiber mode-locked laser.

We demonstrate second-harmonic generation (SHG) microscopy excited by the ∼890-nm light frequency-doubled from a 137-fs, 19.4-MHz, and 300-mW all-fiber mode-locked laser centered at 1780 nm. The mode-locking at the 1.7-µm window is realized by controlling the emission peak of the gain fiber, and uses the dispersion management technique to broaden the optical spectrum up to 30 nm. The spectrum is maintained during the amplification and the pulse is compressed by single-mode fibers. The SHG imaging performance is showcased on a mouse skull, leg, and tail. Two-photon fluorescence imaging is also demonstrated on C. elegans labeled with green and red fluorescent proteins. The frequency-doubled all-fiber laser system provides a compact and efficient tool for SHG and fluorescence microscopy.

Long-term follow-up of biliary atresia using liver transient elastography.

OBJECTIVE: Liver transient elastography (TE) using FibroScan® has gained popularity as a non-invasive technique to assess hepatic fibrosis by measuring liver stiffness. This study focused on biliary atresia patients post Kasai operation for more than 10 years to prospectively correlate the hepatic fibrosis score to the biochemical changes of liver fibrosis and clinical development of portal hypertensive complications. METHODS: TE was performed in 37 patients who had biliary atresia post Kasai operation done at median age of 60 days. Biochemical indices of liver fibrosis including aspartate aminotransferase/platelet ratio index (APRI) and Fibrosis-4 (FIB-4) score based on age, platelet count, alanine aminotransferase and aspartate aminotransferase level were calculated at the time of TE. Platelet count, spleen size, varices, ascites and hepatic encephalopathy were evaluated as clinical markers of portal hypertension. RESULTS: There were 22 female and 15 male with TE done at median age of 17.0 years. Median FibroScan® fibrosis score was 11.4. Fibrosis score of 6.8 kilopascal (kPa) was taken as the upper reference limit of normal. Nine patients (24%) had normal fibrosis score. Score above or equal to 6.8 kPa was significantly associated with lower platelet level (p = 0.001), higher INR (p = 0.043), higher APRI (p = 0.021), higher FIB-4 score (p = 0.013), and larger splenic diameter (p = 0.004). Higher FibroScan® fibrosis score was also significantly associated with portal hypertensive complications (p = 0.001). CONCLUSIONS: The FibroScan® fibrosis score correlated well with the biochemical changes of liver fibrosis and development of portal hypertensive complications clinically. Screening of portal hypertensive complications such as varices is recommended for patients with raised fibrosis score upon long-term follow-up. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Dynamics of breathing dissipative soliton pairs in a bidirectional ultrafast fiber laser.

The breathing dissipative soliton as a dynamic solution to many nonlinear systems has induced substantial interest in nonlinear photonics and ultrafast laser science. However, the exotic breathing multi-soliton dynamics are still largely unexplored in the bidirectional fiber laser compared to the unidirectional laser. Here, we reveal nonequilibrium dynamics of a breathing soliton pair (BSP) with energy transfer in a bidirectional laser; in particular, the dissociation and annihilation of the BSP was triggered by control over intra-cavity polarization. Optical rogue waves were detected simultaneously, and the collision of breathers significantly increased the intensity of rogue waves, which is characteristic of the bidirectional laser. Further, the buildup dynamics of the BSP with nanosecond pulse separation and a breathing soliton molecule were observed. Multiple single soliton explosions and transient pulse splitting are distinct features of soliton molecule buildup compared to the soliton pair. These findings shed new insights into the multiple breather dynamics of nonlinear systems.