Tet1-mediated 5hmC regulates hippocampal neuroinflammation via wnt signaling as a novel mechanism in obstructive sleep apnoea leads to cognitive deficit.

BACKGROUND: Obstructive sleep apnoea (OSA) is a sleep-disordered breathing characterized by intermittent hypoxia (IH) that may cause cognitive dysfunction. However, the impact of IH on molecular processes involved in cognitive function remains unclear. METHODS: C57BL / 6 J mice were exposed to either normoxia (control) or IH for 6 weeks. DNA hydroxymethylation was quantified by hydroxymethylated DNA immunoprecipitation (hMeDIP) sequencing. ten-eleven translocation 1 (Tet1) was knocked down by lentivirus. Specifically, cognitive function was assessed by behavioral experiments, pathological features were assessed by HE staining, the hippocampal DNA hydroxymethylation was examined by DNA dot blot and immunohistochemical staining, while the Wnt signaling pathway and its downstream effects were studied using qRT-PCR, immunofluorescence staining, and Luminex liquid suspension chip analysis. RESULTS: IH mice showed pathological changes and cognitive dysfunction in the hippocampus. Compared with the control group, IH mice exhibited global DNA hydroxylmethylation in the hippocampus, and the expression of three hydroxylmethylases increased significantly. The Wnt signaling pathway was activated, and the mRNA and 5hmC levels of Wnt3a, Ccnd2, and Prickle2 were significantly up-regulated. Further caused downstream neurogenesis abnormalities and neuroinflammatory activation, manifested as increased expression of IBA1 (a marker of microglia), GFAP (a marker of astrocytes), and DCX (a marker of immature neurons), as well as a range of inflammatory cytokines (e.g. TNFa, IL3, IL9, and IL17A). After Tet1 knocked down, the above indicators return to normal. CONCLUSION: Activation of Wnt signaling pathway by hippocampal Tet1 is associated with cognitive dysfunction induced by IH.

Kelp as a biomonitor of persistent organic pollutants in coastal areas of China: Contamination levels and human health risk.

Kelp, the brown alga distributed in coastal areas all over the world, is also an important medicine food homology product in China. However, the levels and profiles of persistent organic pollutants (POPs) in kelp have not been thoroughly investigated to date. Polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs) and emerging bromine flame retardants (eBFRs) were evaluated in 41 kelp samples from the main kelp producing areas in China. The concentrations of total PCBs, PBDEs and eBFRs were in the range of 0.321-4.24 ng/g dry weight (dw), 0.255-25.5 ng/g dw and 3.00 × 10-3-47.2 ng/g dw in kelp, respectively. The pollutant pattern was dominated by decabromodiphenyl ethane (DBDPE, 13.0 ± 11.7 ng/g dw) followed in decreasing order by BDE-209 (2.74 ± 4.09 ng/g dw), CB-11 (1.32 ± 1.06 ng/g dw). The tested results showed that kelp could reflect the pollution status of PCBs, PBDEs and eBFRs, indicating the suitability of kelp as a biomonitor of these harmful substances. Finally, the data obtained was used to evaluate human non-cancer and cancer risks of PCBs and PBDEs via kelp consumption for Chinese. Though the calculated risk indices were considered acceptable according to the international standards even in the worst scenarios, the POPs levels in kelp should be monitored continuously as a good environmental indicator.

Influenza vaccination features revealed by a single-cell transcriptome atlas.

Emerging and re-emerging viruses like influenza virus pose a continuous global public health threat. Vaccines are one of the most effective public health strategies for controlling infectious diseases. However, little is known about the immunological features of vaccination at the single-cell resolution, including for influenza vaccination. Here, we report the single-cell transcriptome atlas of longitudinally collected peripheral blood mononuclear cells (PBMCs) in individuals immunized with an inactivated influenza vaccine. Overall, vaccination with the influenza vaccine only had a small impact on the composition of peripheral immune cells, but elicited global transcriptional changes in multiple immune cell subsets. In plasma and B cell subsets, transcriptomic changes, which were mostly involved in antibody production as well as B cell activation and differentiation, were observed after influenza vaccinations. In influenza-vaccinated individuals, we found a reduction in multiple biological processes (e.g., interferon response, inflammatory response, HLA-I/II molecules, cellular apoptosis, migration, and cytotoxicity, etc.,) 7 days postvaccination in multiple immune cell subsets. However, 14 days postvaccination, these levels returned to similar levels observed in prevaccination samples. Additionally, we did not observe significant upregulation of pro-inflammatory response genes and key thrombosis-related genes in influenza-vaccinated individuals. Taken together, we report a cell atlas of the peripheral immune response to influenza vaccination and provide a resource for understanding the immunological response mechanisms of influenza vaccination.

Characterisation of brain microstructural alterations in children with obstructive sleep apnea syndrome using diffusion kurtosis imaging.

Obstructive sleep apnea (OSA) is a common chronic sleep-related breathing disorder in children. Previous studies showed widespread alterations in white matter (WM) in children with OSA mainly by using diffusion tensor imaging (DTI), while diffusional kurtosis imaging (DKI) extended DTI and exhibited improved sensitivity in detecting developmental and pathological changes in neural tissues. Therefore, we conducted whole-brain DTI and DKI analyses and compared the differences in kurtosis and diffusion parameters within the skeleton between 41 children with OSA and 32 healthy children. Between-group differences were evaluated by tract-based spatial statistics (TBSS) analysis (p < 0.05, TFCE corrected), and partial correlations between DKI metrics and sleep parameters were assessed considering age and gender as covariates. Compared with the controls, children with OSA showed significantly decreased kurtosis fractional anisotropy (KFA) mainly in white matter regions with a complex fibre arrangement including the posterior corona radiate (PCR), superior longitudinal fasciculus (SLF), and inferior fronto-occipital fasciculus (IFOF), while decreased FA in white matter regions with a coherent fibre arrangement including the posterior limb of internal capsule (PLIC), anterior thalamic radiation (ATR), and corpus callosum (CC). Notably, the receiver operating characteristic (ROC) curve analysis demonstrated the KFA value in complex tissue regions significantly (p < 0.001) differentiated children with OSA from the controls. In addition, the KFA value in the left PCR, SLF, and IFOF showed significant partial correlations to the sleep parameters for children with OSA. Combining DKI derived kurtosis and diffusion parameters can provide complementary neuroimaging biomarkers for assessing white matter alterations, and reveal pathological changes and monitor disease progression in paediatric OSA.

Serum-integrated omics reveal the host response landscape for severe pediatric community-acquired pneumonia.

OBJECTIVE: Community-acquired pneumonia (CAP) is the primary cause of death for children under five years of age globally. Hence, it is essential to investigate new early biomarkers and potential mechanisms involved in disease severity. METHODS: Proteomics combined with metabolomics was performed to identify biomarkers suitable for early diagnosis of severe CAP. In the training cohort, proteomics and metabolomics were performed on serum samples obtained from 20 severe CAPs (S-CAPs), 15 non-severe CAPs (NS-CAPs) and 15 healthy controls (CONs). In the verification cohort, selected biomarkers and their combinations were validated using ELISA and metabolomics in an independent cohort of 129 subjects. Finally, a combined proteomics and metabolomics analysis was performed to understand the major pathological features and reasons for severity of CAP. RESULTS: The proteomic and metabolic signature was markedly different between S-CAPs, NS-CAPs and CONs. A new serum biomarker panel including 2 proteins [C-reactive protein (CRP), lipopolysaccharide (LBP)] and 3 metabolites [Fasciculol C, PE (14:0/16:1(19Z)), PS (20:0/22:6(4Z, 7Z, 10Z, 13Z, 16Z, 19Z))] was developed to identify CAP and to distinguish severe pneumonia. Pathway analysis of changes revealed activation of the cell death pathway, a dysregulated complement system, coagulation cascade and platelet function, and the inflammatory responses as contributors to tissue damage in children with CAP. Additionally, activation of glycolysis and higher levels of nucleotides led to imbalanced deoxyribonucleotide pools contributing to the development of severe CAP. Finally, dysregulated lipid metabolism was also identified as a potential pathological mechanism for severe progression of CAP. CONCLUSION: The integrated analysis of the proteome and metabolome might open up new ways in diagnosing and uncovering the complexity of severity of CAP.

Aberrant Topological Properties of Brain Functional Network in Children with Obstructive Sleep Apnea Derived from Resting-State fMRI.

To examine the difference in the topological properties of brain functional network between the children with obstructive sleep apnea (OSA) and healthy controls, and to explore the relationships between these properties and cognitive scores of OSA children. Twenty-four OSA children (6.5 ± 2.8 years, 15 males) and 26 healthy controls (8.0 ± 2.9 years, 11 males) underwent resting-state fMRI (rs-fMRI), based on which brain functional networks were constructed. We compared the global and regional topological properties of the network between OSA children and healthy controls. Partial correlation analysis was performed between topological properties and cognitive scores across OSA children. When comparing the OSA children with the healthy controls, lower full-scale intelligent quotient (FIQ) and verbal intelligent quotient (VIQ) were observed. Additionally, nodal degree centrality decreased in the bilateral anterior cingulate and paracingulate gyrus, but increased in the right middle frontal gyrus, the left fusiform gyrus, and the left supramarginal gyrus. Nodal efficiency decreased in the right precentral gyrus, and the bilateral anterior cingulate and paracingulate gyrus, but increased in the left fusiform gyrus. Nodal betweenness centrality increased in the dorsolateral part of the right superior frontal gyrus, the left fusiform gyrus, and the left supramarginal gyrus. Further, the nodal degree centrality in the left supramarginal gyrus was positively correlated with FIQ. In contrast, none of global topological properties showed difference between those two groups. The outcomes of OSA may impaired the regional topological properties of the brain functional network of OSA children, which may be potential neural mechanism underlying the cognitive declines of these patients.

Distinct effects of typical sludge pretreatment approaches on the antibiotic resistance genes variations, associated bacterial community dynamics and metabolic activities during anaerobic fermentation process.

Anaerobic fermentation is effective for waste activated sludge (WAS) disposal to realize resource generation and pollutants reduction, and various pretreatments were commonly applied to improve the performance. This work mainly investigated the effects of typical WAS pretreatment approaches on the antibiotic resistance genes (ARGs, as emerging contaminants) removal during anaerobic fermentation processes and unveiled the underlying mechanisms. The results indicated that all the pretreatment strategies exhibited evident effects on the overall ARGs removal with the order of Fe2+ activated persulfate (PS/Fe2+) > pH 10 > Ultrasonication > Heat, and showed selective removal tendency for the specific ARGs (namely easily removed (aadA1 and sul1) and persistent ARGs). Mechanistic analysis demonstrated that the pretreatments disrupted the extracellular polymeric substances (EPS) and rose the cell membrane permeability (particularly for PS/Fe2+ and Heat). Then the increased ARGs release benefitted the subsequent reduction of mobile genetic elements (MGEs) and extracellular ARGs (especially for PS/Fe2+ and pH10), resulting the ARGs attenuation. Pretreatments significantly shifted the microbial community structure and the abundances of potential ARGs hosts (i.e., Sulfuritalea, and Denitratisoma). Also, the different pretreatments exhibited distinct effects on the microbial metabolic traits related with ARGs proliferation (i.e., ABC transporters, two-component system and bacterial secretion systems), which also contributed to the ARGs attenuations during WAS fermentation. The partial least-squares path modeling (PLS-PM) analysis indicated that the bacterial community (total effects = 0.968) was key factor determining ARGs fates.

Diagnosis of obstructive sleep apnea in children based on the XGBoost algorithm using nocturnal heart rate and blood oxygen feature.

PURPOSE: Obstructive sleep apnea (OSA) is a serious type of obstructive sleep-disordered breathing (SDB) that can cause a series of adverse effects on children's cardiovascular, growth, cognition, etc. The gold standard for diagnosis is polysomnography (PGS), which is used to assess the prevalence of OSA by obtaining the apnea-hypopnea index (AHI), but this diagnosis method is expensive and needs to be performed in a specialized laboratory, making it difficult to be of benefit to children with suspected OSA on a large scale. Our goal was to use a machine learning method to identify children with OSA of varying severity using data on children's nighttime heart rate and blood oxygen data. METHODS: This study included 3139 children who received diagnostic PSG with suspected OSA. Age, sex, BMI, 3 % oxygen depletion index (ODI), average nighttime heart rate and fastest heart rate were used as predictive features. Data sets were established with AHI ≥ 1, AHI ≥ 5, and AHI ≥ 10 as the diagnostic criteria for mild, moderate and severe OSA, and the samples of each data set were randomly divided into a training set and a test set at a ratio of 8:2. An OSA diagnostic model was established based on the XGBoost algorithm, and the ability of the machine learning model to diagnose OSA children with different severities was evaluated through different classification ability evaluation indicators. As a comparison, traditional classifier Logistic Regression was used to perform the same diagnostic task. The SHAP algorithm was used to evaluate the role of these features in the classification task. RESULTS: We established a diagnostic model of OSA in children based on the XGBoost algorithm. On the test set, the AUCs of the model for diagnosing mild, moderate, and severe OSA were 0.95, 0.88, and 0.88, respectively, and the classification accuracy was 90.45 %, 85.67 %, and 89.81 %, respectively, perform better than Logistic Regression classifiers. ODI is the most important feature in all classification tasks, and a higher fastest heart rate and ODI make the model tend to classify samples as positive. A high BMI value caused the model to tend to classify samples as positive in the mild and moderate classification tasks and as negative in the classification task with severe OSA. CONCLUSION: Using heart rate and blood oxygen data as the main features, a machine learning diagnostic model based on the XGBoost algorithm can accurately identify children with OSA at different severities. This diagnostic modality reduces the number of signals and the complexity of the diagnostic process compared to PSG, which could benefit children with suspected OSA who do not have the opportunity to receive a diagnostic PSG and provide a diagnostic priority reference for children awaiting a diagnostic PSG.

Quantifying the effect of socio-economic-geo drivers on the change of municipal waste disposal in China by an integrated TWFE-PRF-SDM methodology.

Municipal solid waste management and disposal in China have significantly evolved since 2000. Due to China's vast land area and significant socioeconomic and geographic disparities, nationwide waste management strategies need to be further evaluated. This study quantified the effect of social, economic, and geographic drivers on municipal waste disposal activities in 31 provincial-level administrative regions from 2003 to 2020, by establishing a methodology integrated by two-way fixed effects regression model, panel random forest, and spatial Durbin model. The results showed, in the past two decades, socio-economic-geo indicators significantly co-decided the landfill and incineration activities. In particular, the explanatory ability of GDP per capita was above 45%, while land resources and city size also showed great significance. Spatial autocorrelation analysis showed that the relationship between landfill/incineration rates and socio-economic-geo drivers changed notably from unobvious to significant with economic growth. Furthermore, the local economy and land resources displayed more impact than those of the neighboring regions, while sci-tech and education showed clear spatial spillover effects. Chinese government would carefully assess the full-scale promotion policy of incineration plants, landfill is still hold as a reasonable option for regions with specific socio-economic-geo conditions.

Application of the metal ions as potential population biomarkers for wastewater-based epidemiology: estimating tobacco consumption in Southern China.

Wastewater-based epidemiology (WBE) is an objective approach for the estimation of population-level exposure to a wide range of substances, in which the use of a population biomarker (PB) could significantly reduce back-calculation errors. Although some endogenous or exogenous compounds such as cotinine and other hormones have been developed as PBs, more PBs still need to be identified and evaluated. This study aimed to propose a novel method to estimate population parameters from the mass load of metal ion biomarkers in wastewater, and estimate the consumption of tobacco in 24 cities in Southern China using the developed method. Daily wastewater samples were collected from 234 wastewater treatment plants (WWTPs) in 24 cities in Southern China. Atomic absorption spectroscopy (AAS) was applied to determine the concentrations of common health-related metal ions in wastewater, including sodium (Na), potassium (K), magnesium (Mg), calcium (Ca), iron (Fe), and zinc (Zn), and compared them with the daily mass load of cotinine corresponding to catchment populations. The concentrations of cotinine in wastewater samples were measured using liquid chromatography-tandem mass spectrometry. There were clear and strong correlations between the target metal ion equivalent population and census data. The correlation coefficients (R) were RK = 0.78, RNa = 0.66, RCa = 0.81, RMg = 0.77, and RFe = 0.69, at p < 0.01 and R2 > 0.6. Subsequently, the combination of WBE and metal ion PBs was used to estimate tobacco consumption. Daily consumption of nicotine was estimated to be approximately 1.76 ± 1.19 mg/d/capita, equivalent to an average of 13.0 ± 8.75 cigarettes/d being consumed by smokers. The data on tobacco consumption in this study were consistent with those in traditional surveys in Southern China. The metal ion potassium is an appropriate PB for reflecting the real-time population and could be used to evaluate the tobacco consumption in WBE study.

Gemcitabine enhances pharmacokinetic exposure of the major components of Danggui Buxue Decoction in rat via the promotion of intestinal permeability and down-regulation of CYP3A for combination treatment of non-small cell lung cancer.

CONTEXT: Danggui Buxue Decoction (DBD), a traditional Chinese medicine formula, has the potential to enhance the antitumor effect of gemcitabine in non-small cell lung cancer (NSCLC) treatment by increasing gemcitabine's active metabolites. However, whether gemcitabine affects the pharmacokinetics of DBD's major components remains unclear. OBJECTIVE: This study evaluates the herb-drug interaction between DBD's major components and gemcitabine and validates the underlying pharmacokinetic mechanism. MATERIALS AND METHODS: The pharmacokinetics of 3.6 g/kg DBD with and without a single-dose administration of 50 mg/kg gemcitabine was investigated in Sprague-Dawley rats. The effects of gemcitabine on intestinal permeability, hepatic microsomal enzymes in rat tissues, and CYP3A overexpressing HepG2 cells were determined using western blot analysis. RESULTS: The combination of gemcitabine significantly altered the pharmacokinetic profiles of DBD's major components in rats. The Cmax and AUC of calycosin-7-O-ß-d-glucoside notably increased through sodium-glucose transporter 1 (SGLT-1) expression promotion. The AUC of ligustilide and ferulic acid was also significantly elevated with the elimination half-life (t1/2) prolonged by 2.4-fold and 7.8-fold, respectively, by down-regulating hepatic CYP3A, tight junction proteins zonula occludens-1 (ZO-1) and occludin expression. DISCUSSION AND CONCLUSIONS: Gemcitabine could modulate the pharmacokinetics of DBD's major components by increasing intestinal permeability, enhancing transporter expression, and down-regulating CYP3A. These findings provide critical information for clinical research on DBD as an adjuvant for NSCLC with gemcitabine and help make potential dosage adjustments more scientifically and rationally.

Evaluation of the household solid waste mandatory sorting policy in Shanghai: A 1-year public opinion survey.

Sustainable management of household solid waste (HSW) is an essential step in realizing the development of a circular economy (CE). However, for many developing countries, HSW sorting is evolving incrementally, and focusing on the intervention role of policy and the sorting behaviour of residents can help achieve sustainable waste management. This study aims to investigate the main determinants of residents' HSW sorting behaviour and how policy particularly contributes to it. Drawing upon the theory of planned behaviour (TPB) and incorporating experiences, a conceptual framework is tested on a sample of Chinese residents in Shanghai (n = 560, from November to December 2020) using structural equation modelling analysis. The empirical results show that experience and behavioural intention greatly influence HSW sorting behaviour. Moreover, the positive attitude of residents promotes the success of HSW sorting. Subjective norms and perceived behaviour control indirectly affect behavioural intention and behaviour via attitude. The findings of this study provide policymakers with critical factors for the successful implementation of HSW sorting. We also propose policy implications to maintain and improve sorting efficiency from the perspective of residents (education, communication and publicity), neighbourhood committees (degree and efficiency of supervision) and property management companies (good infrastructure, services and processes).

Single-cell transcriptomic atlas reveals distinct immunological responses between COVID-19 vaccine and natural SARS-CoV-2 infection.

To control the ongoing coronavirus disease-2019 (COVID-19) pandemic, CoronaVac (Sinovac), an inactivated vaccine, has been granted emergency use authorization by many countries. However, the underlying mechanisms of the inactivated COVID-19 vaccine-induced immune response remain unclear, and little is known about its features compared to (Severe acute respiratory syndrome coronavirus 2) SARS-CoV-2 infection. Here, we implemented single-cell RNA sequencing (scRNA-seq) to profile longitudinally collected PBMCs (peripheral blood mononuclear cells) in six individuals immunized with CoronaVac and compared these to the profiles of COVID-19 infected patients from a Single Cell Consortium. Both inactivated vaccines and SARS-CoV-2 infection altered the proportion of different immune cell types, caused B cell activation and differentiation, and induced the expression of genes associated with antibody production in the plasma. The inactivated vaccine and SARS-COV-2 infection also caused alterations in peripheral immune activity such as interferon response, inflammatory cytokine expression, innate immune cell apoptosis and migration, effector T cell exhaustion and cytotoxicity, however, the magnitude of change was greater in COVID-19 patients, especially those with severe disease, than in immunized individuals. Further analyses revealed a distinct peripheral immune cell phenotype associated with CoronaVac immunization (HLA class II upregulation and IL21R upregulation in naïve B cells) versus SARS-CoV-2 infection (HLA class II downregulation and IL21R downregulation in naïve B cells from severe disease individuals). There were also differences in the expression of important genes associated with proinflammatory cytokines and thrombosis. In conclusion, this study provides a single-cell atlas of the systemic immune response to CoronaVac immunization and revealed distinct immune responses between inactivated vaccines and SARS-CoV-2 infection.

SymMap database and TMNP algorithm reveal Huanggui Tongqiao granules for Allergic rhinitis through IFN-mediated neuroimmuno-modulation.

Allergic rhinitis (AR) is a series of reactions to allergen mediated by immunoglobulin E (IgE) and is one of the most common allergic diseases that affects children. Traditional Chinese Medicine, due to its diverse regulatory functions, may offer new strategies for AR therapy. Huanggui Tongqiao Granules (HTG) is a Chinese formula consisting of twelve herbs and has long been prescribed for patients with AR. The aim of this study is to determine the possible targets and action mechanisms of HTG for the AR treatment. SymMap database and TMNP algorithm were employed to show that interferon-gamma (IFN-gamma), acting as a molecular link between immunity and neural circuits, is the involved key target. The enrichment of immune and virus-related signaling pathways indicated the neuroimmunomodulatory potential of HTG. Then, AR mouse model was established by ovalbumin (OVA) challenge and was used to verify the therapeutic effects of HTG in vivo. HTG significantly relieved AR symptoms and nasal mucosal inflammation, reduced OVA-specific IgE levels and balanced IFN-gamma/IL-4 ratio. Moreover, transcriptional profile based on clinical data presented that blood cell-specific IFN-gamma co-expressed gene module (BIM) was underexpressed in AR patients, further validating the potential of IFN-gamma as target for AR. Collectively, these findings suggest that HTG could be a promising candidate drug for AR.

Pattern of anatomic disorder and surgical management of anorectal prolapse in anorectal malformation.

AIM: Due to the paucity of data and controversy regarding the etiology and surgical approach for managing anorectal prolapse (ARP) after anorectoplasty, we sought to investigate the underlying anatomic disorder and the surgical outcome in managing this challenging complication. METHODS: We performed a retrospective study on 83 patients with ARP related to anorectal malformations (ARM). Logistic regression analyses were performed to detect the risk factors for the ARP severity. Surgical procedures were stratified according to identified anatomical abnormalities and surgical outcomes were analyzed. RESULTS: 50 patients (62.7%) had high-type ARM. The original anorectoplasty had a higher rate of ARP in laparoscopic-assisted anorectoplasty (n = 49, 59.0%) versus posterior sagittal anorectoplasty (n = 11, 13.3%). ARP was associated with rectal fat hyperplasia (67.5%), dilated muscular tunnel (79.5%), longitudinal muscle (LM) discontinuity (16.9%), rectal dilation (22.9%), mislocated anus (7.2%), and excessive mobile mesorectum (3.6%). Based on the ARP severity, the patients were divided into a severe group (Group 1, n = 38) and a moderate group (Group 2, n = 45). Binary logistic regression analysis showed that hyperplasia rectal fat (OR 4.55, 95% CI 1.16-17.84), rectal dilation (OR 4.21, 95% CI 1.05-16.94), and high-type ARM (OR 2.90, 95% CI 1.14-7.39) were independent risk factors for the development of severe ARP. Complications after stratified surgical repair included wound infection in six patients (7.2%), anal stenosis in one patient (1.2%), and ARP recurrence in two patients (2.4%). Twenty-six patients without colostomy before prolapse repair were followed up for 2 to 12 years. All the patients maintained voluntary bowel movements. Following ARP repair, there was an overall higher rate of no soiling or grade 1 soiling (88.5 vs. 65.4%), but 3 of 12 patients with grade 2 constipation were upgraded to grade 3. CONCLUSION: Our study shows that ARM-related anorectal prolapse is associated with excessive rectum, hyperplasia of rectal fat, mobile mesorectum, loose muscular tunnel, LM discontinuity, and anal mislocation. Surgical repair with techniques stratified according to the patients' underlying risk factors is effective to prevent recurrence and improve the soiling continence.

Analysis and Accuracy Improvement of UWB-TDoA-Based Indoor Positioning System.

Positioning systems are used in a wide range of applications which require determining the position of an object in space, such as locating and tracking assets, people and goods; assisting navigation systems; and mapping. Indoor Positioning Systems (IPSs) are used where satellite and other outdoor positioning technologies lack precision or fail. Ultra-WideBand (UWB) technology is especially suitable for an IPS, as it operates under high data transfer rates over short distances and at low power densities, although signals tend to be disrupted by various objects. This paper presents a comprehensive study of the precision, failure, and accuracy of 2D IPSs based on UWB technology and a pseudo-range multilateration algorithm using Time Difference of Arrival (TDoA) signals. As a case study, the positioning of a 4×4m2 area, four anchors (transceivers), and one tag (receiver) are considered using bitcraze's Loco Positioning System. A Cramér-Rao Lower Bound analysis identifies the convex hull of the anchors as the region with highest precision, taking into account the anisotropic radiation pattern of the anchors' antennas as opposed to ideal signal distributions, while bifurcation envelopes containing the anchors are defined to bound the regions in which the IPS is predicted to fail. This allows the formulation of a so-called flyable area, defined as the intersection between the convex hull and the region outside the bifurcation envelopes. Finally, the static bias is measured after applying a built-in Extended Kalman Filter (EKF) and mapped using a Radial Basis Function Network (RBFN). A debiasing filter is then developed to improve the accuracy. Findings and developments are experimentally validated, with the IPS observed to fail near the anchors, precision around ±3cm, and accuracy improved by about 15cm for static and 5cm for dynamic measurements, on average.

Tim-3 is a potential regulator that inhibits monocyte inflammation in response to intermittent hypoxia in children with obstructive sleep apnea syndrome.

The mechanism of the characteristic intermittent hypoxia (IH) of obstructive sleep apnea syndrome (OSAS) on monocyte remain unclear. Our study found that OSAS children had a significantly upregulated expression in circulating proinflammatory cytokines IL-6 and IL-12, and endothelial injury markers VEGF and ICAM1. Association analysis revealed that the plasma TNFα, IL-1ß, IL-6, IL-10 and IL-12 concentration were negatively associated with the minimal SpO2, a negative index for disease severity. OSAS monocytes presented an inflammatory phenotype with higher mRNA levels of inflammatory cytokines. Importantly, we noted a significant decrease in T-cell immunoglobulin and mucin domain (Tim)-3 expression in OSAS monocytes with the increase of the plasma proinflammatory cytokines. In vitro assay demonstrated that IH induced THP-1 cell overactivation via NF-κB dependent pathway was inhibited by the Tim-3 signal. Our results indicated that activation of monocyte inflammatory responses is closely related to OSAS-induced IH, and negatively mediated by a Tim-3 signaling pathway.

A population-based analysis of clinical features and lymph node dissection in head and neck malignant neurogenic tumors.

BACKGROUND: The influence of lymph node dissection (LND) on survival in patients with head and neck neurogenic tumors remains unclear. We aimed to determine the effect of LND on the outcomes of patients with head and neck neurogenic tumors. METHODS: Data of patients with surgically treated head and neck neurogenic tumors were identified from the Surveillance, Epidemiology, and End Results (SEER) database (1975-2016) to investigate the relationship between LND and clinical outcomes by survival analysis. Subgroup analysis was performed in IVa and IVb group. RESULTS: In total, 662 head and neck neurogenic tumor patients (median age: 49.0 [0-91.0] years) met the inclusion criteria, of whom 13.1% were in the IVa group and 86.9% were in the IVb group. The median follow-up time was 76.0 months (range: 6.0-336.0 months), and the 5-year and 10-year overall survival was 82.4% (95% CI, 0.79-0.85) and 69.0% (95% CI, 0.64-0.73). Cox regression analysis revealed older age (P < .001), advanced stage (P = .037), African American race (P = .002), diagnosis before 2004 (P < .001), and chemotherapy administration (P < .001) to be independent negative predictors of overall survival. Kaplan-Meier analysis demonstrated that LND was not a predictor of clinical nodal negativity (cN0) in either IVa or IVb patients. CONCLUSIONS: In head and neck neurogenic patients, LND may not impact the outcome of cN0 in either IVa or IVb group. These data can be recommended in guiding surgical plan and future studies.

MRI in Children With Pyriform Sinus Fistula.

BACKGROUND: A variety of imaging modalities have been described for the diagnosis of congenital pyriform sinus fistula (CPSF). To date, there have been few MRI reports. PURPOSE: To evaluate MRI findings of CPSF and interobserver reliability. STUDY TYPE: Retrospective. POPULATION: In all, 115 patients aged 23 days to 15.4 years at operation. FIELD STRENGTH/SEQUENCE: 3.0T/axial T1 -weighted image (T1 WI)-SPIR, axial T2 WI, axial T2 WI-STIR, coronal T2 WI-SPIR, diffusion-weighted imaging (DWI), axial and coronal gadolinium-enhanced T1 WI-SPIR. ASSESSMENT: For each patient, the medical records, including demographics, clinical manifestations, and MRI findings were reviewed. All the MRI studies were interpreted by three radiologists independently. STATISTICAL TEST: Kendall's W test was made to determine the interobserver reliability of three reviewers for MRI findings. RESULTS: CPSF occurred on the left side in 104 (90.4%) patients and on the right side in 11 (9.6%) patients. The male-to-female ratio was 59:56. The age at first episode varied from birth to 12.3 years. There was one neonate patient, who presented with a unilocular cystic mass in the left neck. A tunnel-like lesion between the pyriform fossa and the upper pole of the thyroid gland, T2 high signal behind the cricothyroid joint, thyroid gland involvement, deep neck abscesses or masses were noted in 46 (40%), 93 (80.9%), 96 (83.5%), and 36 (31.3%) patients, respectively. There was excellent interobserver reliability for all the MRI findings, ranging from 0.84 to 1.00. DATA CONCLUSION: The sinus tract presenting with a tunnel-like lesion goes behind the cricothyroid joint in most cases. For patients presenting with acute suppurative thyroiditis (AST) or neck infection with thyroid gland involvement, the presence of T2 high signal behind the cricothyroid joint highly suggests the diagnosis of CPSF. MRI is a reliable method for the diagnosis of CPSF. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY STAGE: 2.

LAMP-CRISPR-Cas12-based diagnostic platform for detection of Mycobacterium tuberculosis complex using real-time fluorescence or lateral flow test.

A CRISPR-based nucleic acid detection platform, termed LACD (loop-mediated isothermal amplification coupled with CRISPR-Cas12a-mediated diagnostic) has been developed. In the LACD system, the core primer used in conventional LAMP (forward inner primer or backward inner primer) was engineered to contain a PAM (protospacer adjacent motif) site (TTTT) at the linker region. As a result, the LAMP amplicons contained a specific PAM site for CRISPR-Cas12a recognition. At the CRISPR-mediated detection stage, the resulting LAMP products can activate the corresponding CRISPR-Cas12a effector upon the formation of the CRISPR-Cas12a/gRNA/target DNA complex. The single-strand DNA (ssDNA) reporter molecules are then rapidly cleaved due to the CRISPR-Cas12a's trans-enzyme activity. The ssDNA degradation can then be visualized on a lateral flow biosensor or measured  by a real-time fluorescence instrument. Our LACD assay allows any target sequence to be detected (even targets which do not contain any PAM sites) as long as they met the design requirement for LAMP. The feasibility of the LACD methodology for nucleic acid detection was validated on the Mycobacterium tuberculosis complex (MTC). This proof-of-concept assay can be reconfigured to detect a variety of target sequences by redesigning the engineered LAMP primers.