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Abstract Background Echinocandins belong to the fourth generation of antifungals, and there are no systematic studies on their risk in coagulation dysfunction; this study will predict the risk of coagulation dysfunction of echinocandins using the US Food and Drug Administration Adverse Event Reporting System (FAERS) database. Method Data from January 2004 to March 2024 were obtained from FAERS. We examined the clinical characteristics of the coagulation dysfunction events and conducted disproportionality analysis by using reporting odds ratios (ROR) to compare echinocandins with the full database. Results There were 313 reports of coagulation dysfunction related to echinocandins as the primary suspect (PS) drug. The median time to incident for coagulation dysfunction was 3 (interquartile range [IQR] 1–9) days. Compared to triazoles and polyenes, echinocandins have a stronger signal (ROR 3.18, 95%CI 2.81–3.51, p

Abstract Presbycusis, or age-related hearing loss, affects both elderly humans and dogs, significantly impairing their social interactions and cognition. In humans, presbycusis involves changes in peripheral and central auditory systems, with central changes potentially occurring independently. While peripheral presbycusis in dogs is well-documented, research on central changes remains limited. Diffusion tensor imaging (DTI) is a useful tool for detecting and quantifying cerebral white matter abnormalities. This study used DTI to explore the central auditory pathway of senior dogs, aiming to enhance our understanding of canine presbycusis. Dogs beyond 75% of their expected lifespan were recruited and screened with brainstem auditory evoked response testing to select dogs without severe peripheral hearing loss. Sixteen dogs meeting the criteria were scanned using a 3 T magnetic resonance scanner. Tract-based spatial statistics was used to analyze the central auditory pathways. A significant negative correlation between fractional lifespan and fractional anisotropy was found in the acoustic radiation, suggesting age-related white matter changes in the central auditory system. These changes, observed in dogs without severe peripheral hearing loss, may contribute to central presbycusis development.

Abstract Objective To provide evidence for choosing surgical or nonsurgical treatment for epilepsy in patients with unilateral multilobar and hemispheric polymicrogyria (PMG). Methods We searched published studies until September 2022 related to unilateral multilobar and hemispheric PMG and included patients who were followed up at the Pediatric Epilepsy Centre of Peking University First Hospital in the past 10 years. We summarized the clinical characteristics and compared the long‐term outcomes after surgical or nonsurgical (anti‐seizure medications, ASMs) treatment. Results A total of 70 patients (49 surgical, 21 non‐surgical) with unilateral multilobar and hemispheric PMG were included. The median age at epilepsy onset was 2.5 years (1.0–4.1). The most common seizure types were focal and atypical absence seizures. In the whole cohort, 87.3% had hemiparesis and 67.1% had electrical status epilepticus during slow sleep (ESES). There were significant differences in age at epilepsy onset, extent of lesion, and EEG interictal discharges between the two groups. At the last follow‐up (median 14.1 years), the rates of seizure‐freedom (81.6% vs. 57.1%, p = 0.032) and ASM discontinuation (44.4% vs. 6.3%, p = 0.006) were higher in the surgical group than in the nonsurgical group. Patients in the surgical group had a higher rate of seizure‐freedom with complete resection/disconnection than with subtotal resection (87.5% vs. 55.6%, p = 0.078), but with no statistically significant difference. In the nonsurgical group, more extensive lesions were associated with worse seizure outcomes. Cognition improved postoperatively in 90% of surgical patients. Significance In patients with unilateral multilobar and hemispheric PMG, the age of seizure onset, the extent of the lesion and EEG features can help determine whether surgery should be performed early. Additionally, surgery could be more favorable for achieving seizure freedom and cognitive improvement sooner. Plain Language Summary We aim to summarize clinical characteristics and compare the long‐term outcomes after surgical and nonsurgical (ASM) treatment to provide a basis for treatment decisions for patients with unilateral multilobar and hemispheric polymicrogyria (PMG)‐related epilepsy. We found that patients with unilateral hemispheric and multilobar PMG had significantly higher rates of seizure freedom and ASM discontinuation with surgical treatment than with nonsurgical treatment. In the surgical group, seizure outcomes were better in patients treated with complete resection/disconnection than in those treated with subtotal resection, but the difference was not statistically significant.

Abstract The spectral content of macroscopic neural activity evolves throughout development, yet how this maturation relates to underlying brain network formation and dynamics remains unknown. Here, we assess the developmental maturation of electroencephalogram spectra via Bayesian model inversion of the spectral graph model, a parsimonious whole-brain model of spatiospectral neural activity derived from linearized neural field models coupled by the structural connectome. Simulation-based inference was used to estimate age-varying spectral graph model parameter posterior distributions from electroencephalogram spectra spanning the developmental period. This model-fitting approach accurately captures observed developmental electroencephalogram spectral maturation via a neurobiologically consistent progression of key neural parameters: long-range coupling, axonal conduction speed, and excitatory:inhibitory balance. These results suggest that the spectral maturation of macroscopic neural activity observed during typical development is supported by age-dependent functional adaptations in localized neural dynamics and their long-range coupling across the macroscopic structural network.

Abstract The study of brain differences across Eastern and Western populations provides vital insights for understanding potential cultural and genetic influences on cognition and mental health. Diffusion MRI (dMRI) tractography is an important tool in assessing white matter (WM) connectivity and brain tissue microstructure across different populations. However, a comprehensive investigation into WM fiber tracts between Eastern and Western populations is challenged due to the lack of a cross-population WM atlas and the large site-specific variability of dMRI data. This study presents a dMRI tractography atlas, namely the East-West WM Atlas, for concurrent WM mapping between Eastern and Western populations and creates a large, harmonized dMRI dataset (n=306) based on the Human Connectome Project and the Chinese Human Connectome Project. The curated WM atlas, as well as subject-specific data including the harmonized dMRI data, the whole brain tractography data, and parcellated WM fiber tracts and their diffusion measures, are publicly released. This resource is a valuable addition to facilitating the exploration of brain commonalities and differences across diverse cultural backgrounds.

AIM: To compare and analyse the diagnostic efficacy of the College of Optometrists Vision Development Quality of Life Questionnaire (COVD-QOL) and the Convergence Insufficiency Symptom Survey (CISS) in detecting convergence insufficiency and to compare their diagnostic value in clinical applications. METHODS: Using the diagnostic test method, 62 adult patients with convergence insufficiency (age: 24.74±3.75y) and 62 normal participants (age: 23.61±3.13y) who visited the Optometry Clinic of West China Hospital of Sichuan University from April 2021 to January 2023 were included. All subjects completed the CISS and COVD-QOL. Statistical analysis of the sensitivity and specificity of the CISS and COVD-QOL and comparison and joint experimental analysis of their diagnostic efficacy were performed. RESULTS: The sensitivity of the CISS and COVD-QOL for convergence insufficiency was 64.5% and 71.0%, respectively, while the specificity was 96.8% and 67.7%, respectively. Compared to the CISS alone, the combination of the CISS and COVD-QOL demonstrated lower sensitivity and specificity. The areas under the receiver operating characteristic curve of CISS, COVD-QOL and CISS combined with COVD-QOL were 0.806, 0.694 and 0.782, respectively. CONCLUSION: Considering the low sensitivity of the CISS and the low specificity of the COVD-QOL, it is recommended to supplement these questionnaires with other screening tests for the detection of convergence insufficiency.

This study examined the bidirectional impact of Chinese agricultural subsidy policies on agricultural efficiency and farmers' income. It employed panel data from 2004 to 2020 across 31 Chinese provinces, and the three-stage least squares method was used for simultaneous estimation. Different regions and farmer types were analysed separately. The findings revealed a significant bidirectional impact of the agricultural subsidy policy on agricultural efficiency and farmers' income, signifying a strong positive feedback loop. Varied types and levels of subsidy policies differently impacted regions and farmer categories, showcasing diverse outcomes and adaptive responses to subsidy policies. The ratio of total subsidy to GDP (SUBGDP) positively impacted production efficiency and per capita disposable income. This result suggests that the subsidy policy helped enhance agricultural production efficiency and increased farmers' income levels. Conversely, the ratio of various subsidies to the total subsidy manifested different directions and degrees of impact on production efficiency and per capita disposable income, suggesting areas where the subsidy policy framework can be optimised. In addition to presenting a theoretical discussion on agricultural subsidy policies, this study provides theoretical insights and policy recommendations for the formulation and implementation of an optimal agricultural subsidy policy.

ABSTRACTEfficiently querying multiple spatial datasets is a challenging task in geoscience. The majority of spatial processing techniques use minimum bounding box (MBB) to approximate neighbouring spatial objects and and place them adjacent in the spatial index. However, due to the existence of redundant space in MBB of these methods, this problem can significantly reduce the query efficiency. In this paper, we propose a novel two-stage adaptive method of clipping the bounding box in spatial query, called IB-CBB (Intersection Based Clipped Bounding Boxes). The first stage employs a clipped bounding box, which records the redundant spatial spaces within the bounding box of the spatial index by calculating the clip points. As a result, the computational complexity of indexed child nodes in the query process is reduced. The second stage optimizes the above query algorithm by judging the intersection of the query box and the MBB of index node, significantly reducing the query time. Experiments demonstrate that IB-CBB outperforms the baseline method in terms of reducing the computational time.

Abstract Background The purpose of this study was to analyze myopic regression after corneal refractive surgery (CRS) in civilian pilots and to explore the factors that may cause long-term myopic regression. Methods We included civilian pilots who had undergone CRS to correct their myopia and who had at least 5 years of follow-up. We collected retrospective data and completed eye examinations and a questionnaire to assess their eye habits. Results A total of 236 eyes were evaluated in this study. 211 eyes had Intrastromal ablations (167 eyes had laser in situ keratomileusis, LASIK, 44 eyes had small incision lenticule extraction, SMILE) and 25 eyes had subepithelial ablations (15 eyes had laser epithelial keratomileusis, LASEK and 10 eyes had photorefractive keratectomy, PRK). The mean preoperative spherical equivalent (SE) was − 2.92 ± 1.11 D (range from − 1.00 to -5.00 D). A total of 56 eyes (23.6%) suffered from myopic regression after CRS. Comparisons of individual and eye characteristics between the regression and non-regression groups revealed statistically significant differences in age, cumulative flight time, postoperative SE (at 6 months and current), uncorrected visual acuity (UCVA), accommodative amplitude (AA), positive relative accommodation (PRA), postoperative period, types of CRS and eye habits. Generalized propensity score weighting (GPSW) was used to balance the distribution of covariates among different age levels, types of CRS, cumulative flying time, postoperative period and continuous near-work time. The results of GPS weighted logistic regression demonstrated that the associations between age and myopic regression, types of CRS and myopic regression, continuous near-work time and myopic regression were significant. Cumulative flying time and myopic regression, postoperative period and myopic regression were no significant. Specifically, the odds ratio (OR) for age was 1.151 (P = 0.022), and the OR for type of CRS was 2.769 (P 45 min and poor accommodative function may be related factors in this specific population.

Abstract The human cerebellum is engaged in a broad array of tasks related to motor coordination, cognition, language, attention, memory, and emotional regulation. A detailed cerebellar atlas can facilitate the investigation of the structural and functional organization of the cerebellum. However, existing cerebellar atlases are typically limited to a single imaging modality with insufficient characterization of tissue properties. Here, we introduce a multifaceted cerebellar atlas based on high-resolution multimodal MRI, facilitating the understanding of the neurodevelopment and neurodegeneration of the cerebellum based on cortical morphology, tissue microstructure, and intra-cerebellar and cerebello-cerebral connectivity.

Abstract The binding of peroxisome proliferator‐activated receptor γ (PPARγ) to the orphan nuclear receptor Nur77 facilitates the ubiquitination and degradation of Nur77, and leads to aberrant fatty acid uptake for breast cancer progression. Because of its crucial role in clinical prognosis, the interaction between Nur77 and PPARγ is an attractive target for anti‐breast‐cancer therapy. However, developing an inhibitor of the Nur77‐PPARγ interaction poses a technical challenge due to the absence of the crystal structure of PPARγ and its corresponding interactive model with Nur77. Here, ST‐CY14, a stapled peptide, is identified as a potent modulator of Nur77 with a KD value of 3.247 × 10−8 M by in silico analysis, rational design, and structural modification. ST‐CY14 effectively increases Nur77 protein levels by blocking the Nur77‐PPARγ interaction, thereby inhibiting lipid metabolism in breast tumor cells. Notably, ST‐CY14 significantly suppresses breast cancer growth and bone metastasis in mice. The findings demonstrate the feasibility of exploiting directly Nur77‐PPARγ interaction in breast cancer, and generate what to the best knowledge is the first direct inhibitor of the Nur77‐PPARγ interaction available for impeding fatty acid uptake and therapeutic development.

Summary: The tumor-associated mucin MUC1 is overexpressed in almost all types of epithelial tumor tissues, making it an attractive target antigen for cancer immunotherapy. Here we present a protocol to prepare MUC1 glycopeptide vaccines and to evaluate immunization effects in mice. We describe steps for synthesizing glycopeptide antigen and conjugating it with carrier protein to make vaccine candidates. We then detail procedures for mice immunization, antibody response evaluation, and cellular immune response.For complete details on the use and execution of this protocol, please refer to Cai et al.1,2 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Abstract Diffusion MRI (dMRI) is a safe and noninvasive technique that provides insight into the microarchitecture of brain tissue. Relaxation-diffusion MRI (rdMRI) is an extension of traditional dMRI that captures diffusion imaging data at multiple TEs to detect tissue heterogeneity between relaxation and diffusivity. rdMRI has great potential in neurosurgical research including brain tumor grading and treatment response evaluation. However, the lack of available data has limited the exploration of rdMRI in clinical settings. To address this, we are sharing a high-quality rdMRI dataset from 18 neurosurgical patients with different types of lesions, as well as two healthy individuals as controls. The rdMRI data was acquired using 7 TEs, where at each TE multi-shell dMRI with high spatial and angular resolutions is obtained at each TE. Each rdMRI scan underwent thorough artifact and distortion corrections using a specially designed processing pipeline. The dataset’s quality was assessed using standard practices, including quality control and assurance. This resource is a valuable addition to neurosurgical studies, and all data are openly accessible.

Abstract Jaw cysts commonly affect the oral and maxillofacial region, involving adjacent tooth roots. The management of these teeth, particularly regarding root canal therapy and apicoectomy, lacks consensus. This study introduces a novel treatment concept and refined surgical approach to preserve pulp viability in teeth involved in jaw cysts. The objective was to investigate the effectiveness and potential benefits of this approach over a 36-month follow-up period. A conservative management approach prioritized vitality preservation, reserving root canal treatment and apicectomy for cases with post-operative discomfort. A comprehensive follow-up of 108 involved teeth from 36 jaw cyst cases treated with the modified method was conducted. Clinical observation, X-ray imaging, cone-beam computed tomography (CBCT), and pulp vitality testing assessed changes in cyst size, tooth color, pulp vitality, root structure, and surrounding alveolar bone. After 36 months, our modified surgical approach successfully preserved tooth vitality in 84 involved teeth. Adverse symptoms in 19 teeth, such as redness, swelling, fistula, and pain, resolved with postoperative root canal therapy. Follow-up was lost for five teeth in two cases. No cyst recurrences were observed, and in 34 cases, the bone cavity gradually disappeared, restoring normal bone density during long-term follow-up. Our modified surgical method effectively preserves tooth vitality in jaw cysts. This innovative approach has the potential to improve the management of teeth involved in jaw cysts.

T cell infiltration and proliferation in tumor tissues are the main factors that significantly affect the therapeutic outcomes of cancer immunotherapy. Emerging evidence has shown that interferon-gamma (IFNγ) could enhance CXCL9 secretion from macrophages to recruit T cells, but Siglec15 expressed on TAMs can attenuate T cell proliferation. Therefore, targeted regulation of macrophage function could be a promising strategy to enhance cancer immunotherapy via concurrently promoting the infiltration and proliferation of T cells in tumor tissues. We herein developed reduction-responsive nanoparticles (NPs) made with poly (disulfide amide) (PDSA) and lipid-poly (ethylene glycol) (lipid-PEG) for systemic delivery of Siglec15 siRNA (siSiglec15) and IFNγ for enhanced cancer immunotherapy. After intravenous administration, these cargo-loaded could highly accumulate in the tumor tissues and be efficiently internalized by tumor-associated macrophages (TAMs). With the highly concentrated glutathione (GSH) in the cytoplasm to destroy the nanostructure, the loaded IFNγ and siSiglec15 could be rapidly released, which could respectively repolarize macrophage phenotype to enhance CXCL9 secretion for T cell infiltration and silence Siglec15 expression to promote T cell proliferation, leading to significant inhibition of hepatocellular carcinoma (HCC) growth when combining with the immune checkpoint inhibitor. The strategy developed herein could be used as an effective tool to enhance cancer immunotherapy.

Organochlorine pesticides are chlorinated hydrocarbon compounds. The production and use of organochlorine pesticides have been restricted around the world because they are persistent and toxic and able to undergo long-range transport and bioaccumulate. It is necessary to develop efficient techniques for eliminating organochlorine pesticides from environmental media, and we also need to better understand how these techniques operate. Understanding how organochlorine herbicides behave in various environmental settings is very crucial. We looked on the photodegradation of endosulfan (endosulfan I and II) and hexachlorobenzene (HCB), two common organochlorine insecticides. Tests were conducted with pesticides at different concentrations, dissolved in various organic solvents, and exposed to light at different wavelengths. Density Functional Theory (DFT) was employed to study solvent effects. Degradation kinetics followed first-order models. The pesticides dissolved in various organic solvents showed a decrease in their degradation rates in the following order: toluene > acetone > n-hexane. It was discovered that there was a good chance the Cl atoms on the benzene ring in HCB would be eliminated through nucleophilic processes. It was discovered that endosulfan breaks preferentially at the SO double bond. The findings will aid in the development of strategies for successfully eliminating organochlorine pesticides from environmental media by aiding in the prediction and assessment of the photochemical behaviors of the pesticides under various environmental circumstances.

Abstract Background Toosendanin (TSN) exhibits potent antitumor activity against various tumor cell lines. However, its efficacy against oral squamous cell carcinoma (OSCC) remains unknown. Here, we investigated the effects of TSN on OSCC cells in vitro and verified them in vivo using a patient-derived xenograft (PDX) model. Methods The effect of TSN on OSCC cells was investigated by cytotoxicity assays and flow cytometry. The expression of proteins was detected by western blotting. An OSCC PDX model was constructed to further investigate the role of TSN in regulating the function of OSCC. Results The cell viability of CAL27 and HN6 cells decreased as the concentration of TSN increased within the experimental range. Compared with controls, TSN at lower doses inhibited cell proliferation and induced apoptosis through S-phase cell cycle arrest. TSN inhibited OSCC cell proliferation by downregulating the STAT3 pathway through the inhibition of STAT3 phosphorylation. After successful construction of the OSCC PDX model with high pathological homology to the primary tumor and treatment with an intraperitoneal injection of TSN, we showed that TSN significantly reduced the tumor size of the PDX model mice without obvious toxicity. Conclusions Both in vitro and in vivo, TSN significantly inhibits the proliferation and promoted apoptosis of OSCC cells. Furthermore, TSN demonstrates potent inhibition of STAT3 phosphorylation, indicating its potential as a promising therapeutic agent for OSCC. Therefore, TSN holds great promise as a viable drug candidate for the treatment of OSCC.

Abstract. Background:. Changes in white matter (WM) underlie the neurocognitive damages induced by a human immunodeficiency virus (HIV) infection. This study aimed to examine using a bundle-associated fixel-based analysis (FBA) pipeline for investigating the microstructural and macrostructural alterations in the WM of the brain of HIV patients. Methods:. This study collected 93 HIV infected patients and 45 age/education/handedness matched healthy controls (HCs) at the Beijing Youan Hospital between January 1, 2016 and December 30, 2016.All HIV patients underwent neurocognitive evaluation and laboratory testing followed by magnetic resonance imaging (MRI) scanning. In order to detect the bundle-wise WM abnormalities accurately, a specific WM bundle template with 56 tracts of interest was firstly generated by an automated fiber clustering method using a subset of subjects. Fixel-based analysis was used to investigate bundle-wise differences between HIV patients and HCs in three perspectives: fiber density (FD), fiber cross-section (FC), and fiber density and cross-section (FDC). The between-group differences were detected by a two-sample t-test with the false discovery rate (FDR) correction (P

Abstract Objective Mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE) is a new and rare histopathological entity of cortical developmental malformations. The clinical characteristics of MOGHE remain challenging. Methods Children with histologically confirmed MOGHE were retrospectively studied. The clinical findings, electroclinical and imaging features, and postoperative outcomes were analyzed, and previously published studies were reviewed up to June 2022. Results Thirty‐seven children were included in our cohort. Clinical characteristics included early onset in infancy (94.6% before 3 years), multiple seizure types, and moderate or severe delay. Epileptic spasm is the most common seizure type and initial manifestation. The lesions were mainly multilobar (59.5% multiple lobes and 8.1% hemispheres), and predominance in the frontal lobe was observed. The interictal EEG pattern was circumscribed or widespread. The prominent MRI characteristics were cortical thickening, cortical/subcortical hyperintense T2/FLAIR signal, and blurring at the GM and WM transition. Among the 21 children followed up for more than 1 year after surgery, 76.2% were seizure‐free. Preoperative interictal circumscribed discharges and larger resections were significantly associated with a good postoperative outcome. The clinical features of 113 patients in the reviewed studies were similar to those we reported, but the lesions were mainly unilobar (73.5%) and Engel I was achieved in only 54.2% after surgery. Significance Distinct clinical characteristics in MOGHE, especially age at onset, epileptic spasm, and age‐related MRI characteristics, can help in early diagnosis. Preoperative interictal discharge and surgical strategy may be predictors of postoperative outcomes.

Human action recognition based on optical and infrared video data is greatly affected by the environment, and feature extraction in traditional machine learning classification methods is complex; therefore, this paper proposes a method for human action recognition using Frequency Modulated Continuous Wave (FMCW) radar based on an asymmetric convolutional residual network. First, the radar echo data are analyzed and processed to extract the micro-Doppler time domain spectrograms of different actions. Second, a strategy combining asymmetric convolution and the Mish activation function is adopted in the residual block of the ResNet18 network to address the limitations of linear and nonlinear transformations in the residual block for micro-Doppler spectrum recognition. This approach aims to enhance the network’s ability to learn features effectively. Finally, the Improved Convolutional Block Attention Module (ICBAM) is integrated into the residual block to enhance the model’s attention and comprehension of input data. The experimental results demonstrate that the proposed method achieves a high accuracy of 98.28% in action recognition and classification within complex scenes, surpassing classic deep learning approaches. Moreover, this method significantly improves the recognition accuracy for actions with similar micro-Doppler features and demonstrates excellent anti-noise recognition performance.

The galvanic dissolved oxygen sensor finds widespread applications in multiple critical fields due to its high precision and excellent stability. As its core sensing components, the oxygen-permeable membrane, electrode, and electrolyte significantly impact the sensor’s performance. To systematically investigate the comprehensive effects of these core sensing components on the performance of galvanic dissolved oxygen sensors, this study selected six types of oxygen-permeable membranes made from two materials (Perfluoroalkoxy Polymer (PFA) and Fluorinated Ethylene Propylene Copolymer (FEP)) with three thicknesses (0.015 mm, 0.03 mm, and 0.05 mm). Additionally, five concentrations of KCl electrolyte were configured, and four different proportions of lead–tin alloy electrodes were chosen. Single-factor and crossover experiments were conducted using the OxyGuard dissolved oxygen sensor as the experimental platform. The experimental results indicate that under the same membrane thickness conditions, PFA membranes provide a higher output voltage compared to FEP membranes. Moreover, the oxygen permeability of FEP membranes is more significantly affected by temperature. Furthermore, the oxygen permeability of the membrane is inversely proportional to its thickness; the thinner the membrane, the better the oxygen permeability, resulting in a corresponding increase in sensor output voltage. When the membrane thickness is reduced from 0.05 mm to 0.015 mm, the sensor output voltage for PFA and FEP membranes increases by 86% and 74.91%, respectively. However, this study also observed that excessively thin membranes might compromise measurement accuracy. In a saturated, dissolved oxygen environment, the sensor output voltage corresponding to the six oxygen-permeable membranes used in the experiment exhibits a highly linear inverse relationship with temperature (correlation coefficient ≥ 98%). Meanwhile, the lead–tin ratio of the electrode and electrolyte concentration have a relatively minor impact on the sensor output voltage, demonstrating good stability at different temperatures (coefficient of variation ≤ 0.78%). In terms of response time, it is directly proportional to the thickness of the oxygen-permeable membrane, especially for PFA membranes. When the thickness increases from 0.015 mm to 0.05 mm, the response time extends by up to 2033.33%. In contrast, the electrode material and electrolyte concentration have a less significant effect on response time. To further validate the practical value of the experimental results, the best-performing combination of core sensing components from the experiments was selected to construct a new dissolved oxygen sensor. A performance comparison test was conducted between this new sensor and the OxyGuard dissolved oxygen sensor. The results showed that both sensors had the same response time (49 s). However, in an anaerobic environment, the OxyGuard sensor demonstrated slightly higher accuracy by 2.44%. This study not only provides a deep analysis of the combined effects of oxygen-permeable membranes, electrodes, and electrolytes on the performance of galvanic dissolved oxygen sensors but also offers scientific evidence and practical guidance for optimizing sensor design.

Abstract The tumor‐associated glycoprotein Mucin 1 (MUC1) is aberrantly glycosylated on cancer cells and is considered a promising target for antitumor vaccines. The weak immunogenicity and low sequence homology of mouse mucins and human MUC1 are the main obstacles for the development of vaccines. Herein, a self‐adjuvanted strategy combining toll‐like receptor 2 lipopeptide ligands and T‐cell epitopes and the multivalent effect were used to amplify the immune response and evade the unpredictable immunogenicity, generating two self‐adjuvanted three‐component MUC1 vaccines (mono‐ and trivalent MUC1 vaccines). To simulate the aberrantly glycosylated MUC1 glycoprotein, the MUC1 tandem repeat peptide was bounded with Tn antigens at T9, S15, and T16, and served as B‐cell epitopes. Results showed that both vaccines elicited a robust antibody response in wild‐type mice compared with a weaker response in MUC1 transgenic mice. The trivalent vaccine did not elevate the antibody response level compared with the monovalent vaccine; however, a more delayed tumor growth and prolonged survival time was realized in wild‐type and transgenic mouse models treated with the trivalent vaccine. These results indicate that the self‐adjuvanted three‐component MUC1 vaccines, especially the trivalent vaccine, can trigger robust antitumor effects regardless of sequence homology, and, therefore, show promise for clinical translation.

From 2013 to 2019, a series of air pollution control actions significantly reduced PM2.5 pollution in China. Control actions included changes in activity levels, structural adjustment (SA) policy, energy and material saving (EMS) policy, and end-of-pipe (EOP) control in several sources, which have not been systematically studied in previous studies. Here, we integrate an emission inventory, a chemical transport model, a health impact assessment model, and a scenario analysis to quantify the contribution of each control action across a range of major emission sources to the changes in PM2.5 concentrations and associated mortality in China from 2013 to 2019. Assuming equal toxicity of PM2.5 from all the sources, we estimate that PM2.5-related mortality decreased from 2.52 (95 % confidence interval, 2.13–2.88) to 1.94 (1.62–2.24) million deaths. Anthropogenic emission reductions and declining baseline incidence rates significantly contributed to health benefits, but population aging partially offset their impact. Among the major sources, controls on power plants and industrial boilers were responsible for the highest reduction in PM2.5-related mortality (∼80 %), followed by industrial processes (∼40 %), residential combustion (∼40 %), and transportation (∼30 %). However, considering the potentially higher relative risks of power plant PM2.5, the adverse effects avoided by their control could be ∼2.4 times the current estimation. Our power plant sensitivity analyses indicate that future estimates of source-specific PM2.5 health effects should incorporate variations in individual source PM2.5 effect coefficients when available. As for the control actions, while activity levels increased for most sources, SA policy significantly reduced the emissions in residential combustion and industrial boilers, and EOP control dominated the contribution in health benefits in most sources except residential combustion. Considering the emission reduction potential by source and control actions in 2019, our results suggest that promoting clean energy in residential combustion and enforcing more stringent EOP control in the iron and steel industry should be prioritized in the future.

Development of wound dressings with antimicrobial activity and promotion of sustained wound healing to reduce the use of antibiotics in infected wounds is important. In this study, we developed a thermosensitive ABA triblock copolymer poly {(N-isopropyl acrylamide)–co-[(6-((3-(6-amino-purin-9-yl)propanoyl)oxy)hexyl acrylates)]-b-PEO-b-Poly (N-isopropyl acrylamide)–co-{[(6-((3-(6-amino-purin-9-yl)propanoyl)oxy)hexyl acrylates)]} as matrix and participating nitric oxide (NO) donor (N,N'-dis-sec-butyl-N,N'-dinitroso-1,4-phenylenediamine, BNN6) loaded SiO2@PDA nanoparticles composed of hydrogel dressings (Gel-APB) for efficient antimicrobial and sustainable treatment of wounds. Thanks to the presence of poly (N-isopropyl acrylamide) (PNIPAM) and unique ABA triblock structure, the NAONA copolymer would self-assemble into temperature-sensitive injectable hydrogel with excellent dermal adaptation to dynamic wounds. Meanwhile, the biobase adenine endowed the hydrogel dressing with self-healing ability. Under 808 nm wavelength irradiation, the hydrogel was able to elevate to a mild temperature (∼48 °C) and release NO on demand, which efficiently kills E. coli and S. aureus, realizing highly efficient and mild photothermal antimicrobial therapy (PTAT). In addition, full-thickness skin wound modeling demonstrated that Gel-APB hydrogel dressing accelerated tissue regeneration, angiogenesis, and collagen deposition in S. aureus infected wounds in vivo, achieving rapid wound healing. Thus, Gel-APB is a multifunctional hydrogel dressing with excellent antimicrobial activity and has considerable potential for application in infected skin wound healing.

Intervertebral disc degeneration (IDD) is the main cause of low back pain (LBP), which significantly impacts global wellbeing and contributes to global productivity declines. Conventional treatment approaches, encompassing conservative and surgical interventions, merely serve to postpone the advancement of IDD without offering a fundamental reversal. Consequently, there is an urgent demand for an effective approach to prevent the progression of IDD. Recent investigations focusing on the treatment of IDD utilizing diverse bioactive substances integrated within various biomaterials have exhibited promising outcomes. Various bioactive substances, encompassing conventional small molecule drugs, small molecule nucleic acids, and cell therapies, exhibit distinct capacities for repairing IDD. Additionally, various biological material delivery systems, such as nano micelles, microspheres, and hydrogels, possess diverse biological and release characteristics. Consequently, these diverse materials and drugs hold promise for advancing the treatment of IDD. This article aims to provide a concise overview of the IDD process and investigate the research advancements in biomaterials and bioactive substances for IDD treatment, delving into their mechanisms.

Chronic diabetic wounds seriously threaten human health due to their intractable nature in a complex pathological microenvironment that contains oxidative stress, persistent inflammatory status, hypoxia and bacterial infections, of which oxidative damage contributing the most. Applied materials that can mimic the natural intracellular antioxidant defense system are perceived to have huge therapeutic potential. Herein, we present a novel strategy to prepare a versatile nanocomposite hydrogel by incorporating the nanoenzyme (manganese dioxide (MnO2)) and nonenzymatic antioxidant components (polydopamine (PDA)) in a dynamic hydrogel network composed of thioctic acid and tannic acid (TA). The prepared hydrogel exhibited outstanding adhesive and injectable properties, making it adapt perfectly to wounds with different shapes and depths. More importantly, encapsulation of PDA@MnO2 nanoparticles (NPs) conferred the hydrogel with superior antioxidant performance to effectively scavenge multiple types of reactive nitrogen and oxygen species (RNOS) and reduce the inflammatory response by regulating macrophage polarization. Meanwhile, the hydrogel showed high-performance catalyzing ability to transfer hydrogen peroxide (H2O2) into oxygen (O2), which could further alleviate hypoxic wound environment. Moreover, the nanocomposite hydrogel exhibited excellent near-infrared (NIR) photothermal antibacterial effect. Collectively, our findings indicate that the synthesized nanocomposite hydrogel shows potential for use in a clinical setting to treat diabetic wounds.

A 34-year-old man was admitted to the hospital presenting repeatedly urinary urgency for 3 years and yellow-green lithotripsy foreign body in urine for 1 month. Initially, he was diagnosed with a giant bladder calculi. After a cystoscopy exam and a lithotripsy for bladder calculi, Appendiceal vesical fistula was finally diagnosed and treated with a laparoscopic surgery. We report a rare case of appendiceal vesical fistula，first presenting as giant bladder calculi，and successfully treated with minimal invasive surgery We report this case and reviewed literature to improve the understanding of this disease and reduce misdiagnosis and missed diagnosis.

Abstract Researchers have widely acknowledged the therapeutic value of epilepsy surgery for drug-resistant epilepsy. Nonetheless, there is a substantial gap in the surgical treatment for appropriate candidates owing to several factors, particularly in the population of young children. To standardize the protocols of preoperative evaluation and surgery of young children for epilepsy surgery, the China Association Against Epilepsy has appointed an expert task force to standardize the protocols of preoperative evaluation and surgery in pediatric epilepsy patients. It adopted the modified Delphi method and performed two rounds of surveys through an anonymous inquiry among 75 experts from four subgroups including pediatric neurologists, epileptologists, pediatric epilepsy surgeons, and functional neurosurgeons. The survey contents contained: (1) the participants, comprising children aged ≤ 6 years; (2) adopted DRE definition proposed by the International League Against Epilepsy in 2010; and (3) investigated epilepsy surgery, principally referring to curative epilepsy surgeries. The neuromodulation therapies were excluded because of the differences in treatment mechanisms from the above-mentioned surgeries. According to the Delphi process, a consensus was achieved for most aspects by incorporating two rounds of surveys including preoperative assessment, surgical strategies and techniques, and perioperative and long-term postoperative management, despite controversial opinions on certain items. We hope the results of this consensus will improve the level of surgical treatment and management of intractable epilepsy in young children.

Urea is an essential fertilizer needed to meet the global demand for food. Currently, its production rate by reaction of carbon dioxide with ammonia is slow and the energy demand is high. Here we discuss strategies to overcome these challenges.

Objectives: To investigate the health-related quality of life (HRQL) of long-term survivors of inoperable esophageal squamous cell carcinoma (ESCC) treated with definitive radiation therapy, the real-world trends in the use of advanced radiation techniques, and their impact on the survival outcomes of ESCC patients. Methods: In this multicenter retrospective observational study, the medical records related to demographics and treatment of ESCC patients who were treated with definitive radiation therapy at 14 provincial hospitals in China from 1 January 2015 to 31 December 2016 were analyzed. A HRQL questionnaire was completed by survivors and collected by doctors at the final follow-up. The difference in quality of life between patients with or without recurrence was compared using the Wilcoxon–Mann–Whitney test. Overall survival (OS) was estimated using the Kaplan–Meier method and the group differences were assessed by unstratified log-rank test. The Cox proportional hazards model with Efron's method of tie handling was used to calculate the risk factors for OS. Results: The data of a total of 3,308 patients were collected for this study, 248 were excluded because of missing data, and a final of 3,060 patients were included in the analysis. Most patients (2,901; 94.8%) received intensity-modulated radiotherapy (IMRT)/volumetric-modulated arc therapy (VMAT)/tomotherapy (TOMO). The 5-year OS rate was 30%. Patients who received either two-dimensional radiotherapy (2DRT; HR, 2.43 [95% CI, 1.70–3.47]; P 80% patients did not experience weight loss. Nearly 80% patients found life very enjoyable or were fairly enjoying life. Conclusions: This large, multicenter retrospective study on ESCC patients who received definitive radiation therapy found that most ESCC survivors are satisfied with their quality of life. Most patients received advanced radiation technology. Patients who received either 2DRT or 3DRT had a significantly increased risk of death compared to those who received advanced radiation technology.

Abstract Human mobility restriction policies have been widely used to contain the coronavirus disease-19 (COVID-19). However, a critical question is how these policies affect individuals’ behavioral and psychological well-being during and after confinement periods. Here, we analyze China’s five most stringent city-level lockdowns in 2021, treating them as natural experiments that allow for examining behavioral changes in millions of people through smartphone application use. We made three fundamental observations. First, the use of physical and economic activity-related apps experienced a steep decline, yet apps that provide daily necessities maintained normal usage. Second, apps that fulfilled lower-level human needs, such as working, socializing, information seeking, and entertainment, saw an immediate and substantial increase in screen time. Those that satisfied higher-level needs, such as education, only attracted delayed attention. Third, human behaviors demonstrated resilience as most routines resumed after the lockdowns were lifted. Nonetheless, long-term lifestyle changes were observed, as significant numbers of people chose to continue working and learning online, becoming “digital residents.” This study also demonstrates the capability of smartphone screen time analytics in the study of human behaviors.

Abstract This systematic review and meta‐analysis aimed to evaluate the efficacy of vigabatrin (VGB) in treating infantile epileptic spasms syndrome (IESS). Databases of PubMed, Embase, Web of Science, MEDLINE, and Cochrane Library were systematically searched. All the relevant randomized controlled trials (RCTs) and observational studies (OSs) of VGB for IESS were included and analyzed separately. The primary outcome was the cessation of epileptic spasms (ES). Five RCTs and nine OSs compared the efficacy of VGB vs hormonal monotherapy for IESS. Meta‐analysis of the five RCTs showed that hormonal monotherapy was significantly better than VGB monotherapy (OR = 0.37, 95% CI = 0.20‐0.67) for patients with new‐onset IESS. Meta‐analysis of the nine OSs agrees with the result from RCTs (OR = 0.61, 95% CI = 0.43‐0.85). VGB was more effective in patients with TSC than in those with other etiologies (five OSs, OR = 5.59, 95% CI = 2.17‐14.41). There was no significant difference in the efficiency of VGB combined with hormonal therapy vs hormonal monotherapy for IESS (two RCTs, OR = 0.75, 95% CI = 0.09‐6.45). Hormonal monotherapy is better than VGB monotherapy for non‐TSC‐associated IESS. But for patients with IESS due to TSC, VGB is the first choice. VGB combined with hormone therapy does not definitely increase ES control rates compared with that of hormonal monotherapy.

The COVID-19 pandemic continues to impact daily life worldwide. It would be helpful and valuable if we could obtain valid information from the COVID-19 pandemic sequential data itself for characterizing the pandemic. Here, we aim to demonstrate that it is feasible to analyze the patterns of the pandemic using a time-series clustering approach. In this work, we use dynamic time warping distance and hierarchical clustering to cluster time series of daily new cases and deaths from different countries into four patterns. It is found that geographic factors have a large but not decisive influence on the pattern of pandemic development. Moreover, the age structure of the population may also influence the formation of cluster patterns. Our proven valid method may provide a different but very useful perspective for other scholars and researchers.

The spatial spread of COVID-19 during early 2020 in China was primarily driven by outbound travelers leaving the epicenter, Wuhan, Hubei province. Existing studies focus on the influence of aggregated out-bound population flows originating from Wuhan; however, the impacts of different modes of transportation and the network structure of transportation systems on the early spread of COVID-19 in China are not well understood. Here, we assess the roles of the road, railway, and air transportation networks in driving the spatial spread of COVID-19 in China. We find that the short-range spread within Hubei province was dominated by ground traffic, notably, the railway transportation. In contrast, long-range spread to cities in other provinces was mediated by multiple factors, including a higher risk of case importation associated with air transportation and a larger outbreak size in hub cities located at the center of transportation networks. We further show that, although the dissemination of SARS-CoV-2 across countries and continents is determined by the worldwide air transportation network, the early geographic dispersal of COVID-19 within China is better predicted by the railway traffic. Given the recent emergence of multiple more transmissible variants of SARS-CoV-2, our findings can support a better assessment of the spread risk of those variants and improve future pandemic preparedness and responses.

Disruptions in the inter-regional connective correlation within the brain are believed to contribute to memory impairment. To detect these corresponding correlation networks in Alzheimer’s disease (AD), we conducted three types of inter-regional correlation analysis, including structural covariance, functional connectivity and group-level independent component analysis (group-ICA). The analyzed data were obtained from the Alzheimer’s Disease Neuroimaging Initiative, comprising 52 cognitively normal (CN) participants without subjective memory concerns, 52 individuals with late mild cognitive impairment (LMCI) and 52 patients with AD. We firstly performed vertex-wise cortical thickness analysis to identify brain regions with cortical thinning in AD and LMCI patients using structural MRI data. These regions served as seeds to construct both structural covariance networks and functional connectivity networks for each subject. Additionally, group-ICA was performed on the functional data to identify intrinsic brain networks at the cohort level. Through a comparison of the structural covariance and functional connectivity networks with ICA networks, we identified several inter-regional correlation networks that consistently exhibited abnormal connectivity patterns among AD and LMCI patients. Our findings suggest that reduced inter-regional connectivity is predominantly observed within a subnetwork of the default mode network, which includes the posterior cingulate and precuneus regions, in both AD and LMCI patients. This disruption of connectivity between key nodes within the default mode network provides evidence supporting the hypothesis that impairments in brain networks may contribute to memory deficits in AD and LMCI.

Abstract Pseudo‐random number generators (PRNGs) are the cornerstone of various fields including computer science, cryptography, and scientific simulation. To generate high‐quality and unpredictable pseudo‐random sequences, many works draw attention to the use of chaos theory and dynamical systems. However, most of them focus on continuous or low‐dimensional chaotic systems with strong temporal correlations or insufficient nonlinear dynamics. Thus, in this study, a new PRNG based on a four‐dimensional discrete system is proposed to solve the aforementioned flaws. The PRNG has been implemented on Xilinx Artix‐7 xc7a100tfgg484‐2, which can generate pseudo‐random sequences at a high speed of 12811.53 Mb/s without additional post‐processing. All these sequences have successfully passed the NIST SP800.22 standard test. Both throughput and randomness quality of the proposed PRNG outperform the state‐of‐the‐art.

Fluorescence images enhancement is important as it can provide more information for medical diagnosis. In this work, we design three simple yet useful filters based on the combinations of mathematical functions, which are proved to be effective in strengthening the images acquired from the fluorescence microscope. Using these filters, detailed objects can be found in the dark sections of the fluorescence images. In addition, these filters can be used to enhance the low-light image, which provide satisfactory visual information and marginal profile for the blurred objects in the image. Moreover, these filters have been used to enhance the image with high degradation by the Gaussian noise, where clear edge profile can be extracted. Finally, we have shown that these filters can be utilized for the image compression. Compression ratio can be obtained to be 0.9688. This study shows the making of the filters with dual functions for the image enhancement and the image compression. Our designed filters are showing the potentials in the field of biomedical imaging and pattern identification.

Summary: The lack of systems to automatically extract epidemiological fields from open-access COVID-19 cases restricts the timeliness of formulating prevention measures. Here we present a protocol for using CCIE, a COVID-19 Cases Information Extraction system based on the pre-trained language model.1 We describe steps for preparing supervised training data and executing python scripts for named entity recognition and text category classification. We then detail the use of machine evaluation and manual validation to illustrate the effectiveness of CCIE.For complete details on the use and execution of this protocol, please refer to Wang et al.2 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Abstract With the increasing severity of the malignant tumors situation worldwide, the impacts of climate on them are receiving increasing attention. In this study, for the first time, all-malignant tumors were used as the dependent variable and absolute humidity (AH) was innovatively introduced into the independent variable to investigate the relationship between all-malignant tumors and meteorological factors. A total of 42,188 cases of malignant tumor deaths and meteorological factors in Wuhu City were collected over a 7-year (2014–2020) period. The analysis method combines distributed lagged nonlinear modeling (DLNM) as well as generalized additive modeling (GAM), with prior pre-analysis using structural equation modeling (SEM). The results showed that AH, temperature mean (T mean) and diurnal temperature range (DTR) all increased the malignant tumors mortality risk. Exposure to low and exceedingly low AH increases the malignant tumors mortality risk with maximum RR values of 1.008 (95% CI: 1.001, 1.015, lag 3) and 1.016 (95% CI: 1.001, 1.032, lag 1), respectively. In addition, low and exceedingly low T mean exposures also increased the risk of malignant tumors mortality, the maximum RR was 1.020 (95% CI: 1.006, 1.034) for low T mean and 1.035 (95% CI: 1.014, 1.058) for exceedingly low T mean. As for DTR, all four levels (exceedingly low, low, high, exceedingly high, from low to high) of exposure increased the risk of death from malignant tumors, from exceedingly low to exceedingly high maximum RR values of 1.018 (95% CI: 1.004, 1.032), 1.011 (95% CI: 1.005, 1.017), 1.006 (95% CI: 1.001, 1.012) and 1.019 (95% CI: 1.007, 1.031), respectively. The results of the stratified analysis suggested that female appear to be more sensitive to humidity, while male require additional attention to reduce exposure to high level of DTR.

Amblyopia is the most common cause of vision loss in children and can persist into adulthood in the absence of effective intervention. Previous clinical and neuroimaging studies have suggested that the neural mechanisms underlying strabismic amblyopia and anisometropic amblyopia may be different. Therefore, we performed a systematic review of magnetic resonance imaging studies investigating brain alterations in patients with these two subtypes of amblyopia; this study is registered with PROSPERO (registration ID: CRD42022349191). We searched three online databases (PubMed, EMBASE, and Web of Science) from inception to April 1, 2022; 39 studies with 633 patients (324 patients with anisometropic amblyopia and 309 patients with strabismic amblyopia) and 580 healthy controls met the inclusion criteria (e.g., case-control designed, peer-reviewed articles) and were included in this review. These studies highlighted that both strabismic amblyopia and anisometropic amblyopia patients showed reduced activation and distorted topological cortical activated maps in the striate and extrastriate cortices during task-based functional magnetic resonance imaging with spatial-frequency stimulus and retinotopic representations, respectively; these may have arisen from abnormal visual experiences. Compensations for amblyopia that are reflected in enhanced spontaneous brain function have been reported in the early visual cortices in the resting state, as well as reduced functional connectivity in the dorsal pathway and structural connections in the ventral pathway in both anisometropic amblyopia and strabismic amblyopia patients. The shared dysfunction of anisometropic amblyopia and strabismic amblyopia patients, relative to controls, is also characterized by reduced spontaneous brain activity in the oculomotor cortex, mainly involving the frontal and parietal eye fields and the cerebellum; this may underlie the neural mechanisms of fixation instability and anomalous saccades in amblyopia. With regards to specific alterations of the two forms of amblyopia, anisometropic amblyopia patients suffer more microstructural impairments in the precortical pathway than strabismic amblyopia patients, as reflected by diffusion tensor imaging, and more significant dysfunction and structural loss in the ventral pathway. Strabismic amblyopia patients experience more attenuation of activation in the extrastriate cortex than in the striate cortex when compared to anisometropic amblyopia patients. Finally, brain structural magnetic resonance imaging alterations tend to be lateralized in the adult anisometropic amblyopia patients, and the patterns of brain alterations are more limited in amblyopic adults than in children. In conclusion, magnetic resonance imaging studies provide important insights into the brain alterations underlying the pathophysiology of amblyopia and demonstrate common and specific alterations in anisometropic amblyopia and strabismic amblyopia patients; these alterations may improve our understanding of the neural mechanisms underlying amblyopia.

Objective Cervical spondylosis is often accompanied by tinnitus. Up to now, there is a lack of large samples and prospective studies to investigate the effect of anterior cervical decompression and fusion (ACDF) on tinnitus associate with cervical spondylosis. To this end, we performed a prospective cohort study to assess the effectiveness of ACDF on the relief of tinnitus. Methods This was a multicenter, prospective, cohort clinical study. Between August 2017 and August 2018, 174 patients with cervical spondylosis accompanied by tinnitus were enrolled, with a follow‐up of 12 months. Among the 174 patients, 142 received anterior cervical surgery (surgery group) and 32 received conservative treatment (conservative group). The primary end point was the mean change in scores on the tinnitus functional index (TFI). The secondary end points included tinnitus loudness, modified Japanese orthopaedic association scores (mJOA) for spinal cord function, and visual analogue scale (VAS) for neck pain. All the above indexes were measured before treatments and at 1, 3, 6, and 12 months after treatments. One‐way analysis of variance and paired samples t‐test was adopted for statistical analysis. Results The TFI score was reduced immediately after cervical decompression surgery (from 54.7 ± 15.6 to 32.3 ± 12.5, P

Highlights Research progress on inorganic perovskites quantum dots is reviewed from three aspects: physical properties, synthesis approaches, and electronic applications. Inorganic perovskite quantum dots have been exploited as either the active layers or the additives in high-performance transistors and memories. Challenges and outlook on future advancement of perovskites quantum dots-based electronics are elaborated.

Endosulfan and hexachlorobenzene (HCB) were previously widely used organochlorine pesticides. Much attention has been paid to trends in human exposure to endosulfan and HCB and to the transport and distribution of endosulfan and HCB within the body. We determined endosulfan I, endosulfan II, and HCB concentrations in serum samples collected from the general population of Wuxi in Jiangsu Province (China) between 2012 and 2016. The endosulfan concentrations varied little throughout the study period, but the HCB concentrations increased. The HCB concentrations were significantly higher in serum from overweight people and smokers than in serum from normal weight people (p = 0.028) and non-smokers (p = 0.011), respectively. HCB binds to human serum albumin (HSA) and can form halogen bonds to CYS-461 and ARG-484 at site II (subdomain IIIA). Fatty acids and nicotine increase the affinity between HCB and HSA, explaining the higher HCB concentrations in serum from overweight people and smokers than normal weight people and non-smokers, respectively.

Estimating structural connectivity from diffusion-weighted magnetic resonance imaging is a challenging task, partly due to the presence of false-positive connections and the misestimation of connection weights. Building on previous efforts, the MICCAI-CDMRI Diffusion-Simulated Connectivity (DiSCo) challenge was carried out to evaluate state-of-the-art connectivity methods using novel large-scale numerical phantoms. The diffusion signal for the phantoms was obtained from Monte Carlo simulations. The results of the challenge suggest that methods selected by the 14 teams participating in the challenge can provide high correlations between estimated and ground-truth connectivity weights, in complex numerical environments. Additionally, the methods used by the participating teams were able to accurately identify the binary connectivity of the numerical dataset. However, specific false positive and false negative connections were consistently estimated across all methods. Although the challenge dataset doesn’t capture the complexity of a real brain, it provided unique data with known macrostructure and microstructure ground-truth properties to facilitate the development of connectivity estimation methods.

Abstract Image enhancement is important given that it can be used to highlight the area of interest in the images. This article designs four filters via special function for realizing image enhancement. Firstly, a filter based on the exponential function is designed. When the value of the progression is even, the edge feature can be extracted. When the value of the progression is odd, sharp contrast can be obtained. Secondly, a filter is built using hyperbolic cosine and its inverse function, where a printmaking feature can be extracted. Thirdly, a filter is made via a hyperbolic secant function and its inverse. It can lead to the extraction of image edge. When the progression value is increasing, marginal effect can be found and the brightness is decreasing. Ripple morphology can be found. Fourthly, a filter is constructed through a hyperbolic sine function and its inverse, where marginal features can be extracted. Furthermore, these filters are useful for extracting the marginal features even when a high noise density of 0.9 is added to the original images. They are useful for highlighting the images acquired from near infrared imaging.

BackgroundPrevious observational studies have reported the striking association between ankylosing spondylitis (AS) and psoriasis, but the causal relationship between the two diseases remains unclear.MethodsTwo-sample Mendelian randomization (MR) analysis with methods of inverse-variance weighted, MR-Egger regression, weighted median, and weighted mode was conducted to evaluate the bidirectional causal associations between AS and psoriasis. Effective single-nucleotide polymorphisms (SNPs) from genome-wide association studies (GWAS) were selected as instrumental variables (IVs). Sensitivity analyses were also applied to verify whether heterogeneity and pleiotropy can bias the results.ResultWe found positive causal effects of genetically increased AS risk on psoriasis (IVW: OR = 1.009, 95% CI = 1.005–1.012, p = 8.07E-07). Comparable outcomes were acquired by MR-Egger regression, weighted median, and weighted mode approaches. Nevertheless, we did not find significant causal effects of psoriasis on AS (IVW: OR = 1.183, 95% CI = 0.137–10.199, p = 0.879). The sensitivity analyses showed that the horizontal pleiotropy was unlikely to skew the causality. The leave-one-out analysis demonstrated that no single SNP can drive the MR estimates. No evidence of heterogeneity was found between the selected IVs.ConclusionOur findings provide evidence that AS has positive causal effects on the risk of psoriasis in the European population.

Abstract Background Drug-resistant epilepsy is one of the most important features of cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder. The ketogenic diet (KD) may be effective for patients with CDKL5-related epilepsy, but there is little high-quality evidence to confirm the efficacy. This meta-analysis investigated the efficacy and safety of KD in CDKL5-related epilepsy. Methods The PubMed, Embase, Web of Science, Cochrane Library, WanFang, CNKI and VIP databases were searched for relevant studies published up to January 1, 2022. Two reviewers independently screened the literature according to inclusion and exclusion criteria and evaluated the bias risk of the included studies. Meta-analysis was performed using Review Manager 5.3 software. Results A total of 12 retrospective studies involving 193 patients met the inclusion criteria. Meta-analysis revealed that the definite responder rate to KD in the treatment of CDKL5-related epilepsy was 18.0% [95% CI (0.07, 0.67)], with no statistical heterogeneity among studies (I2 = 0%, P = 0.45). The clinical responder rate was 50.5% [95% CI (0.75, 1.39)], and there was no statistical heterogeneity among all studies (I2 = 46%, P = 0.05). Subgroup analysis showed that there was no significant difference in the clinical responder rate between the two groups with seizure onset age before and after 1 month (P = 0.14). Only one study mentioned adverse reactions, and the incidence of adverse reactions was 78.3% (18/23). Constipation and vomiting were the main manifestations, implying a high incidence of gastrointestinal adverse reactions. Conclusions The definite responder rate to KD in CDKL5-related epilepsy was 18%, and the gastrointestinal adverse reactions were probably common in these patients. All the studies included in the meta-analysis were retrospective, and most of them had small sample sizes. Additional high-quality studies are needed to confirm the efficacy and tolerance of KD in CDKL5-related epilepsy.

Objectives Autoimmune diseases are a kind of chronic diseases for which the immune system loses tolerance to autoantigens. This meta-analysis’ purpose is to determine whether there exists a correlation between IL-23R polymorphism and common autoimmune diseases like ankylosing spondylitis (AS) and rheumatoid arthritis (RA). Methods We searched the relevant literatures up to September 2021 and used different effect models for meta-analysis. 95% confidence interval (95% CI) and odds ratio (OR) were used to determine the relationship between rs10889677 (A/C) polymorphism and AS as well as RA. Finally, to promote the reliability of results, the trial sequential analysis (TSA) has also been applied and we searched the data related to autoimmune diseases (AS, RA) on genome-wide association studies (GWAS). Results Generally, 31 studies were included. Rs10889677 (A/C) was significantly correlated with the susceptibility to AS and RA among the general individuals (p

Abstract Background The "Law on Doctors of the People's Republic of China," which was officially implemented on March 1, 2022, emphasizes the requirements for rational drug use and the necessity for appropriate management of off-label drug use. The safety and ethical considerations related to off-label drug use are different in children than in adults. There is so far no management guideline for pediatric off-label use of drugs in China, and the applicability of foreign guidelines is limited. Establishing a localized evidence-based management guideline for pediatric off-label use of drugs to support the national legislation and clinical practice is of critical importance. Methods We established a guideline working group, including experts from a broad range of disciplines and developed recommendations following the guidance of the World Health Organization Handbook and the Chinese Medical Association. The following themes were identified by questionnaires and expert interviews to be of great concern in the management of off-label drug use in children: general principles and characteristics of management of pediatric off-label drug use; establishment of expert committees; evidence evaluation; risk–benefit assessment; informed consent; monitoring and assessment of the risk; and monitoring and patient education. Two rounds of Delphi surveys were organized to determine the final recommendations of this guideline. We graded the recommendations based on the body of evidence, referring to the evaluation tool of the Evidence-based management (EBMgt) and the Oxford Center for Evidence-Based Medicine: Level of Evidence (March 2009). Results We developed the first guideline for the management of pediatric off-label use of drugs in China. Conclusions The guideline is to offer guidance for pediatricians, pharmacists, medical managers, policymakers, and primary care physicians on how to manage off-label drug use in pediatrics and to provide recommendations for Chinese healthcare policy in the future.