A difficulty-aware and task-augmentation method based on meta-learning model for few-shot diabetic retinopathy classification.

Background: Accurate classification techniques are essential for the early diagnosis and treatment of patients with diabetic retinopathy (DR). However, the limited amount of annotated DR data poses a challenge for existing deep-learning models. This article proposes a difficulty-aware and task-augmentation method based on meta-learning (DaTa-ML) model for few-shot DR classification with fundus images. Methods: The difficulty-aware (Da) method operates by dynamically modifying the cross-entropy loss function applied to learning tasks. This methodology has the ability to intelligently down-weight simpler tasks, while simultaneously prioritizing more challenging tasks. These adjustments occur automatically and aim to optimize the learning process. Additionally, the task-augmentation (Ta) method is used to enhance the meta-training process by augmenting the number of tasks through image rotation and improving the feature-extraction capability. To implement the expansion of the meta-training tasks, various task instances can be sampled during the meta-training stage. Ultimately, the proposed Ta method was introduced to optimize the initialization parameters and enhance the meta-generalization performance of the model. The DaTa-ML model showed promising results by effectively addressing the challenges associated with few-shot DR classification. Results: The Asia Pacific Tele-Ophthalmology Society (APTOS) 2019 blindness detection data set was used to evaluate the DaTa-ML model. The results showed that with only 1% of the training data (5-way, 20-shot) and a single update step (training time reduced by 90%), the DaTa-ML model had an accuracy rate of 89.6% on the test data, which is a 1.7% improvement over the transfer-learning method [i.e., residual neural network (ResNet)50 pre-trained on ImageNet], and a 16.8% improvement over scratch-built models (i.e., ResNet50 without pre-trained weights), despite having fewer trainable parameters (the parameters used by the DaTa-ML model are only 0.47% of the ResNet50 parameters). Conclusions: The DaTa-ML model provides a more efficient DR classification solution with little annotated data and has significant advantages over state-of-the-art methods. Thus, it could be used to guide and assist ophthalmologists to determine the severity of DR.

Optimization of the cavity length and pulse characterization based on germanene as a saturable absorber in an Er-doped fiber laser.

In this study, germanene-nanosheets (NSs) were synthesized by liquid-phase exfoliation, followed by an experimental investigation into the nonlinear saturable absorption characteristics and morphological structure of germanene. The germanene-NSs were employed as saturable absorbers, exhibiting saturation intensity and modulation depth values of 22.64M W/c m 2 and 4.48%, respectively. This demonstrated the feasibility of utilizing germanene-NSs passively mode-locked in an erbium-doped fiber laser (EDFL). By optimizing the cavity length, improvements in the output of EDFL characteristics were achieved, resulting in 883 fs pulses with a maximum average output power of 19.74 mW. The aforementioned experimental outcomes underscore the significant potential of germanene in the realms of ultrafast photonics and nonlinear optics.

[Long-term hearing outcomes of children with cochlear implant].

Objective:To investigate the long-term rehabilitation outcomes of children with cochlear implants（CI） and provide constructive guidance for clinical application. Methods:Fifteen children with unilateral CI over 5 years（CI group） were recruited. Ten children with normal hearing were recruited as the healthy control group. The project collected aided sound-field hearing thresholds and speech recognition scores using disyllabic words and C-HINT sentences with and without speech noise for 15 children with unilateral CI. In addition, children's guardians were requested to fill out the Mandarin Parental Perspectives questionnaire（MPP） in order to evaluate the hearing aspects of quality of life. MPP results from the 15 children were then compared with previous responses from 17 unilateral CI children whose overall CI wearing time was one year（CI control group）. Results:The aided pure-tone average（PTA） of the recruited children was below 35 dB HL, all children reached 80% for the speech recognition test in a quiet environment, yet their performance decreased in a noisy environment. Regarding the hearing aspects of the MPP questionnaire results, recruited children demonstrated better results than those from CI control group（P<0.05）. Speech noise had a significant impact on the recognition rate, and the CI group had higher recognition rate scores in the quiet environment than in the noise environment（two-syllable words t=18.81, P<0.001, short sentences t=16.48, P<0.001）. In the comparison of quality of life, in the dimension of "support for children", both the CI group and the CI control group can obtain better benefits, and there is no statistically significant difference between the groups（P>0.05）. The CI group benefited more significantly, and the scores were higher than those of the CI control group（P<0.05）. Conclusion:The long-term hearing outcome of children with CI is adequate for daily communication, but there is still a gap compared with hearing children of the same age, and they still need support from the entire society.

[Correlation analysis of pediatric otitis media with effusion and learning difficulty].

Objective:To investigate the impact of otitis media with effusion（OME） on school-age children regarding their intelligence level and academic performance, providing guidance for clinical diagnosis and treatment. Methods:A total of 34 school-age children with OME were recruited. Children and their guardians were asked to complete the WISC-R intelligence tests and self-designed questionnaires. Comprehensive otologic and audiologic examinations were also performed. Children were grouped according to the extent of hearing loss and the overall duration of illness, and then correlations with the intelligence tests and questionnaires were analyzed. Results:Single factor analysis and multiple linear regression analysis revealed intelligence level and academic performance of children were correlated with their pure tune threshold and duration of illness（P<0.05）, while there was no significant difference among the factors within each group（P>0.05）. Conclusion:As a common condition in school-age children, OME can adversely affect the hearing and speech of children, and even affect intellectual development and learning ability. Therefore, children should be diagnosed and treated promptly to minimize the impact of hearing loss and other related symptoms on their learning and life.

Third-order harmonic mode-locked and Q-switched Er-doped fiber laser based on a Cr2Ge2Te6 saturable absorber.

This paper reports the generation of fundamental solitons and third-order solitons in an erbium-doped fiber laser (EDFL) by a Cr2Ge2Te6-polyvinyl alcohol (CGT-PVA) saturable absorber (SA). Stable fundamental solitons at 1559.09 nm at a repetition frequency of 5.1 MHz were detected, and third-order solitons with a maximum output power of 6.807 mW and narrowest monopulse duration of 615.2 fs were obtained under a repetition frequency of 15.3 MHz by changing pump power. To the best of our knowledge, it is the first time to achieve a Q-switched pulse with a minimum pulse duration of 2.2 µs and maximum single pulse energy of 12.11 nJ in EDFL based on CGT-PVA SA after reducing the cavity length. Its repetition rate monotonically increased from 18.8 kHz to 61.8 kHz with a tuning range of about 43 kHz. The experimental results sufficiently demonstrate that CGT has enormous potential as an ultrafast photonics device.

Influence of cochlear implants on hearing-related quality of life: results from Chinese children with cochlear implants entering mainstream education.

OBJECTIVES: This study aimed to 1) assess the hearing-related Quality of Life (QoL) of children with cochlear implants (CIs) in China and 2) investigate the impact of CI in children and of the socio-demographic backgrounds of their guardians on the hearing-related QoL of children with CIs in the Chinese mainstream education system. METHODS: This study used the Mandarin Children with Cochlear Implants: Parental Perspectives questionnaire (MPP), which assessed the communication capability, auditory perception, self-independence, level of happiness with family, social interaction, academic performance, outcome assessment for CI, and level of family support in children with CIs. Both univariate and multiple linear regression analyses were performed to identify the relationship of CI in children and the socio-demographic backgrounds of their guardians with hearing-related QoL in children with CI. RESULT: A total of 124 responses were collected, and they indicated satisfaction and improvement across all aspects of the MPP Questionnaire. Statistical analysis revealed that an earlier age of cochlear implantation (≤3 years old) could improve the communication capabilities, self-independence, social interaction performance, and academic performance of children with CIs. In addition, children with CI from the urban regions demonstrated better social interaction performance than that by those from the rural regions of China. CONCLUSION: CIs can improve hearing-related QoL in children with pre-lingual or congenital hearing loss entering the mainstream education system in China. This study showed that early age of cochlear implantation was critical for successful long-term auditory development and academic achievement in children with CIs in China. Therefore, healthcare professionals and educators in China should advocate for CI for children with severe congenital or pre-lingual hearing loss.

Silenced microRNA-222 suppresses inflammatory response in gestational diabetes mellitus mice by promoting CXCR4.

OBJECTIVE: Gestational diabetes mellitus (GDM) is induced by multiple factors, and the microRNAs (miRNAs) are well-known to be implicated in GDM progression. We aimed to explore the functional mechanisms of miR-222 in the inflammatory response in GDM by mediating C-X-C chemokine receptor type 4 (CXCR4) and NLRP3 inflammasomes. METHODS: GDM models were established by intraperitoneal injection of streptozocin, and the levels of miR-222 and CXCR4 in GDM patients' placenta tissues as well as GDM mice' placenta and pancreatic tissues were determined. The GDM mice were treated with miR-222 Antagomir/Agomir or overexpressed CXCR4 to evaluate the apoptosis and pathological changes in tissues, and the levels of blood glucose, insulin, biochemical indices, inflammatory factors and inflammasome-related proteins. Importantly, the target relation between miR-222 and CXCR4 was verified. RESULTS: MiR-222 was increased while CXCR4 was decreased in GDM patients and mice. The down-regulated miR-222 and up-regulated CXCR4 could promote insulin sensitivity and insulin level, while inhibit apoptosis, inflammation and glucagon level in GDM mice. Moreover, CXCR4 was targeted by miR-222. CONCLUSION: We demonstrated that the silenced miR-222 could suppress inflammatory response in GDM mice by promoting CXCR4 and inactivating NLRP3 inflammasomes, which may contribute to GDM treatment.

Underwater Superoleophobic Surface Based on Silica Hierarchical Cylinder Arrays with a Low Aspect Ratio.

A superantiwetting surface based on low-aspect-ratio hierarchical cylinder arrays (HCAs) was successfully obtained on a silica substrate by colloidal lithography with photolithography. Colloidal lithography is a technique involving transfer of a pattern to a substrate by etching or exposure to a radiation source through a mask composed of a packed colloidal crystal, while photolithography is utilized by which a pattern is transferred photographically to a photoresist-coated substrate, and the substrate is subsequently etched. The surface provides an alternative approach to apply aligned micro-nano integrated structures with a relatively low aspect ratio in superantiwetting. The obtained HCAs successfully integrated micro- and nanoscale structures into one system, and the physical structure of the HCAs can be tuned by modulating the fabrication approach. Using a postmodification process, the underwater-oil wetting behavior of cylinder-array based surfaces can be easily modulated from the superoleophobic state (an oil contact angle (OCA) of 161°) to oleophilic state (an OCA of 19°). Moreover, the underwater-oil wettability can be reversibly transformed from the superoleophobic state (an OCA of approximately 153°) into the oleophilic state (an OCA of approximately 31°) by grafting stimuli-responsive polymer (PNIPAAm) brushes onto this specific hierarchical structure. Due to the temperature-responsive property, modifying the surface with PNIPAAm provides a possibility to control the oil wettability (repellent or sticky) by temperature, which will benefit the use of HCAs in oil-water separation and other application fields.

Large-scale Au nanoparticle cluster arrays with tunable particle numbers evolved from colloidal lithography.

The assembly of metal nanoparticles (NPs) can regulate their plasmon resonance properties to pursue the best properties for applications. However, the controllable assembly of large-scale metal NP cluster arrays remains a significant challenge. This paper presents a novel strategy to prepare large-scale Au NP cluster arrays based on colloidal lithography and template-guided self-assembly technique. The NPs arrays are fabricated by introducing Au NPs onto the quaternized poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) brush templates via electrostatic interaction. The number of Au NPs in cluster can be arbitrarily tuned by changing the surface area of the polymer templates created by colloidal lithography, which resulted in tunable plasmonic properties. The prepared Au NP cluster arrays were used for surface enhanced Raman scattering (SERS) and the SERS properties of the Au NP cluster arrays were studied.

Nanomaterial-Based Organelles Protect Normal Cells against Chemotherapy-Induced Cytotoxicity.

Chemotherapy-induced cytotoxicity in normal cells and organs triggers undesired lesions. Although targeted delivery is used extensively, more than half of the chemotherapy dose still concentrates in normal tissues, especially in the liver. Enabling normal cells or organs to defend against cytotoxicity represents an alternative method for improving chemotherapy. Herein, rationally designed nanomaterials are used as artificial organelles to remove unexpected cytotoxicity in normal cells. Nanocomposites of gold-oligonucleotides (Au-ODN) can capture intracytoplasmic doxorubicin (DOX), a standard chemotherapy drug, blocking the drug's access into the cell nucleus. Cells with implanted Au-ODN are more robust since their viability is maintained during DOX treatment. In vivo experiments confirm that the Au-ODN nanomaterials selectively concentrate in hepatocytes and eliminate DOX-induced hepatotoxicity, increasing the cell's capacity to resist the threatening chemotherapeutic milieu. The finding suggests that introducing functional materials as biological devices into living systems may be a new strategy for improving the regulation of cell fate in more complex conditions and for manufacturing super cells.

Biomineralization State of Viruses and Their Biological Potential.

In nature, viruses can realize self-mineralization under metal-ion-abundant conditions. Interestingly, the mineralized state is a transition state of the virus when the host is not available. Mammalian viruses that share the similar chemical properties also stand a chance of transformation into a mineralized state. In this review, we focus on the possibility of mammalian viruses to undergo mineralization under a physiological environment and the development of biomineralized-based virus engineering. We will introduce the effect of biomineralization on the physiochemical or biological properties of viruses and we will discuss the relationship between mineral composition and biological potentials. The new biological prospects of mineralized-state viruses, including bypassing biological barriers, protection, and virus-host recognition, will provide new insight for the biosecurity and prevention of viral infection. With respect to vaccines, the mineralized state can modulate the immune recognition, change the immunization route, and elevate the vaccine efficacy. Together, these findings of the mineralized state of the virus may lead to a new understanding of virus biology, application, and prevention.

Long-term Effect of Biomineralized Insulin Nanoparticles on Type 2 Diabetes Treatment.

Intracellular insulin may exhibit a long-term effect in regulating protein synthesis, DNA synthesis, and gene transcription. However, the intracellular delivery of insulin is a great challenge. Here, we describe how a simple biomineralization modification of insulin can transport it into intact cells on a large scale, leading to a long-term therapeutic effect on diabetes mellitus. Using insulin-resistant HepG2 cell and diabetic KKAy mice as models, in vitro and in vivo assessments have demonstrated that biomineralized insulin nanoparticles can trigger glucose metabolism, and this improvement extends after the treatment. The potential exists to improve the current treatment of type 2 diabetes mellitus through biomineralized modifications of insulin. This study provides a new paradigm of biomimetic nanotechnology for biomedical applications.

Prognostic value of mid-regional pro-adrenomedullin (MR-proADM) in patients with community-acquired pneumonia: a systematic review and meta-analysis.

BACKGROUND: The early identification of patients at risk of dying from community-acquired pneumonia (CAP) is critical for their treatment and for defining hospital resource consumption. Mid-regional pro-adrenomedullin (MR-proADM) has been extensively investigated for its prognostic value in CAP. However, the results are conflicting. The purpose of the present meta-analysis was to explore the diagnostic accuracy of MR-proADM for predicting mortality in patients suffering from CAP, particularly emergency department (ED) patients. METHOD: We systematically searched the PubMed, Embase, Web of Knowledge and Cochrane databases. Studies were included if a 2 × 2 contingency table could be constructed based on both the MR-proADM level and the complications or mortality of patients diagnosed with CAP. The prognostic accuracy of MR-proADM in CAP was assessed using the bivariate meta-analysis model. We used the Q-test and I (2) index to evaluate heterogeneity. RESULTS: MR-proADM displayed moderate diagnostic accuracy for predicting complications in CAP, with an overall area under the SROC curve (AUC) of 0.74 (95 % CI: 0.70-0.78). Eight studies with a total of 4119 patients in the emergency department (ED) were included. An elevated MR-proADM level was associated with increased risk of death from CAP (RR 6.16, 95 % CI 4.71-8.06); the I (2) value was 0.0 %, and a fixed-effects model was used to pool RR. The pooled sensitivity and specificity were 0.74 (95 % CI: 0.67-0.79) and 0.73 (95 % CI: 0.70-0.77), respectively. The positive likelihood ratio (PLR) and negative likelihood ratio (NLR) were 2.8 (95 % CI, 2.3-3.3) and 0.36 (95 % CI, 0.29-0.45), respectively. In addition, the diagnostic odds ratio (DOR) was 8 (95 % CI, 5-11), and the overall area under the SROC curve was 0.76 (95 % CI, 0.72-0.80). CONCLUSIONS: Our study has demonstrated that MR-proADM is predictive of increased complications and higher mortality rates in patients suffering from CAP. Future studies are warranted to determine the prognostic accuracy of MR-proADM in conjunction with severity scores or other biomarkers and to determine an optimal cut-off level.

Hierarchical-Multiplex DNA Patterns Mediated by Polymer Brush Nanocone Arrays That Possess Potential Application for Specific DNA Sensing.

This paper provides a facile and cost-efficient method to prepare single-strand DNA (ssDNA) nanocone arrays and hierarchical DNA patterns that were mediated by poly(2-hydroxyethyl methacrylate) (PHEMA) brush. The PHEMA brush nanocone arrays with different morphology and period were fabricated via colloidal lithography. The hierarchical structure was prepared through the combination of colloidal lithography and traditional photolithography. The DNA patterns were easily achieved via grafting the amino group modified ssDNA onto the side chain of polymer brush, and the anchored DNA maintained their reactivity. The as-prepared ssDNA nanocone arrays can be applied for target DNA sensing with the detection limit reaching 1.65 nM. Besides, with the help of introducing microfluidic ideology, the hierarchical-multiplex DNA patterns on the same substrate could be easily achieved with each kind of pattern possessing one kind of ssDNA, which are promising surfaces for the preparation of rapid, visible, and multiplex DNA sensors.

Overcoming multiple drug resistance by spatial-temporal synchronization of epirubicin and pooled siRNAs.

One-pot solution mineralization can encapsulate epirubicin (EPI) and pooled siRNAs (Pgp and Bcl-2 siRNAs) in calcium phosphate (CaP). The resulting EPI-RNA-CaP nanocomplexes can achieve a spatial-temporal synchronous effect to full-scale overcome sophisticated multiple drug resistance (MDR) by simultaneous inhibitions of drug efflux and intracellular anti-apoptotic defense to maximize the therapeutic efficacy.

Bioinspired polyethylene terephthalate nanocone arrays with underwater superoleophobicity and anti-bioadhesion properties.

This paper presents a facile method to fabricate bioinspired polyethylene terephthalate (PET) nanocone arrays via colloidal lithography. The aspect ratio (AR) of the nanocones can be finely modulated ranging from 1 to 6 by regulating the etching time. The samples with the AR value of 6 can present underwater superoleophobicity with the underwater oil contact angle (OCA) of 171.8°. The as-prepared PET nanocone arrays perform anti-bioadhesion behavior, which inhibits the formation of the actin cytoskeleton when it used as the substrate for cell culture. Moreover, the oil wettability is temperature controlled after modifying the PET nanocone arrays with PNIPAAm film, and the oil wettability of the functionalized nanocone arrays can be transformed from the superoleophobic state with OCA about 151° to the oleophilic state with OCA about 25° reversibly. Due to the high-throughput, parallel fabrication and cost-efficiency of this method, it will be favourable for researchers to introduce oleophobic properties to various substrate and device surfaces. Due to the superoleophobicity and simple functionalizing properties, the PET nanocone arrays are very promising surfaces for anti-adhesion, self-cleaning and have potential applications in material, medical, and biological fields.

Nano regulation of cisplatin chemotherapeutic behaviors by biomineralization controls.

Controllable biomineralization modification of cisplatin can alter the drug biodistribution with extended circulation time in blood. These changes increase passive tumor target and decrease non-specific accumulation significantly, which can improve chemotherapeutic effect with minimum side effects.

Overcoming cisplatin resistance in chemotherapy by biomineralization.

Nano-solidified intermedias (NSI) of cisplatin were prepared via biomineralization and applied to reverse the drug resistance of cancers in vitro and in vivo by an alternative internalization pathway.