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Abstract Endoscopic submucosal dissection (ESD) of fibrotic colorectal lesions is difficult and has a high complication rate. There are only a few reports on the utility of orthodontic rubber band (ORB) traction in reducing the difficulty of this procedure. This study aimed to investigate the risk factors for perforation when applying ORB traction during ESD of fibrotic colorectal lesions. We continuously collected the clinical data of 119 patients with fibrotic colorectal lesions who underwent ESD with ORB and clip traction between January 2019 and January 2024. Possible risk factors for perforation were analyzed. The median ORB-ESD operative time was 40 (IQR 28–62) min, and the en bloc and R0 resection rates were 94.1% and 84.0%, respectively. Perforation occurred in 16 of 119 patients (13.4%). The lesion size, lesion at the right half of the colon or across an intestinal plica, the degree of fibrosis, operation time, and the surgeon’s experience were associated with perforation during ORB-ESD (P

Summary: Constructing electric vehicle charging piles (EVCPs) is crucial for promoting electric vehicle (EV) sales. Yet, empirical evidence on the bidirectional relationship between EV sales and public EVCPs is limited, with most related works relying on simulations. We empirically investigate this relationship using panel vector autoregression (PVAR) across 95 Chinese cities from 2018 to 2022. Results show EVCPs significantly boost EV sales, especially in colder regions. Higher air pollution and purchase subsidies inhibit the promoting impact of EV sales on EVCPs. The propelling effect of EVCPs on EV sales is impaired in higher housing prices regions. A significant and positive bidirectional relationship exists between EVCPs and battery electric vehicles (BEVs) sales exists, but not with plug-in hybrid electric vehicles (PHEVs) present. Our findings have implications for stakeholders, such as the construction of fast charging infrastructure under lower temperatures, and differentiated charging demands of EVs with different powertrains need to be addressed.

Abstract Carbolong complexes are one of the primary types of metallaaromatics, and they include metallapentalynes and metallapentalenes. A series of 7C-10C and 12C-carbolong complexes with planar ligand skeletons respectively containing 7-10 and 12 carbon atoms in their backbones, have been previously reported. Herein, two classes of strained substances, metallabenzyne-fused metallapentalenes and metallabenzene-fused metallapentalynes, were prepared, both representing 11C-carbolong complexes with a planar carbon-chain ligand. Furthermore, the former type is also the carbolong derivatives containing a metallabenzyne skeleton, another primary metallaaromatic framework. Metallabenzyne-fused metallapentalenes show versatile reactivities, and the most interesting one is the metal carbyne bond shift from a 6-membered to a more strained 5-membered ring, affording the above-mentioned metallabenzene-fused metallapentalyne. This work makes carbolong chemistry more complete, and provides a method to achieve metallabenzynes, which is anticipated to concurrently advance the development of these two types of metallaaromatics.

Abstract Transparent conducting oxides, like indium tin oxide, enable lateral charge carrier transport in silicon heterojunction solar cells. However, their deposition can damage the passivation quality in the solar cell. This damage during the sputter deposition is a complex issue that has not been fully understood, particularly in various silicon‐based materials like amorphous silicon, polycrystalline silicon, or nanocrystalline silicon carbide. The degradation in passivation quality observed in, for example, amorphous silicon is not only explainable by UV light degradation. This study explores the origin of this degradation based on the example of hydrogenated nanocrystalline silicon carbide by combining simulations with experimental analyses. It delves into potential sources of damage during the sputtering process and determines that neither primary nor secondary effects from plasma luminescence or electron bombardment are likely contributors to the damage. Similarly, the implantation of ions, as well as the creation of vacancies and ionization of lattice atoms, are also considered improbable causes. It is, however, proposed that the transfer of energy to the crystalline silicon interface via phonons can factor into the degradation of the passivation quality. This transfer might be a plausible explanation for the damage observed in the passivation layers during the sputtering process.

BackgroundCarbapenem-resistant Enterobacterales (CRE) bloodstream infections (BSIs) pose a significant risk to patients with hematologic malignancies, yet the distinct features and outcomes of these infections are not thoroughly understood.MethodsThis retrospective study examined the characteristics and clinical outcomes of patients with Enterobacterales BSIs at the Hematology Department of Fujian Medical University Union Hospital from 2018 to 2022. Whole-genome sequencing was conducted on 45 consecutive CRE BSI isolates during this period.ResultsA total of 301 patients with Enterobacterales BSIs were included, with 65 (21.6%) cases of CRE and 236 (78.4%) cases of carbapenem-susceptible Enterobacterales (CSE). CRE infections accounted for 16.9% to 26.9% of all Enterobacterales BSIs, and carbapenem-resistant Klebsiella pneumoniae (CRKP) was the predominant strain. The most frequent sequence type (ST) and carbapenemase among CRKP were ST11 (68.6%) and blaKPC-2 (80.0%), respectively. Perianal infections, multiple infection foci, and a history of multiple hospitalizations, ICU stays, and prior CRE infections were identified as risk factors for CRE BSIs. Patients in the CRE group experienced significantly higher proportions of infection-related septic shock (43.1% vs. 19.9%, P < 0.0003) and 30-day all-cause mortality (56.9% vs. 24.6%, P < 0.0001) compared to those in the CSE group. Patient’s age and disease subtypes, strain subtypes, and antimicrobial treatment regimens significantly influenced survival in patients with CRE BSIs.ConclusionsCRE BSIs are a frequent complication in patients with hematological malignancies undergoing treatment and are associated with poor survival rates. A comprehensive understanding of risk factors and ongoing surveillance of prevalent strains are essential for the effective management of these infections.

Abstract Background and aims Metformin has been reported to inhibit the occurrence and development of colorectal cancer (CRC) by mediating changes in intestinal flora. Studies have also indicated that the occurence of familial adenomatous polyposis (FAP) may also be associated with changes in the intestinal flora. Therefore, we investigated the efficacy and safety of metformin in treating FAP and the association with intestinal flora. Results Compared with the baseline, the mean number and load of polyps in the areas of nanocarbon labeling and postoperative residuals in the test group were lower than those in the placebo group, while the diversity of intestinal flora species was increased. At the genus level, the relative abundance of g_Ruminococcus in the test group was lower than that at baseline, whereas the relative abundance of g_Lactobacillus was higher. These changes were statistically significant (P

Abstract Interferon-gamma (IFN-γ) signaling is necessary for the proinflammatory activation of macrophages but IFN-γ-independent pathways, for which the initiating stimuli and downstream mechanisms are lesser known, also contribute. Here we identify, by high-content screening, SEPTIN2 (SEPT2) as a negative regulation of IFN-γ-independent macrophage autoactivation. Mechanistically, endoplasmic reticulum (ER) stress induces the expression of SEPT2, which balances the competition between acetylation and ubiquitination of heat shock protein 5 at position Lysine 327, thereby alleviating ER stress and constraining M1-like polarization and proinflammatory cytokine release. Disruption of this negative feedback regulation leads to the accumulation of unfolded proteins, resulting in accelerated M1-like polarization, excessive inflammation and tissue damage. Our study thus uncovers an IFN-γ-independent macrophage proinflammatory autoactivation pathway and suggests that SEPT2 may play a role in the prevention or resolution of inflammation during infection.

AimThe study aims to systematically assess the efficacy and safety of Gegen Qinlian decoction in the treatment of type 2 diabetes mellitus.MethodsWe systematically searched a total of nine databases from the time of creation to 20 March 2023. The quality of the literature was assessed using the risk of bias assessment tool in the Cochrane Handbook. RevMan 5. 3 and Stata 14.0 were applied to conduct meta-analysis.ResultsA total of 17 studies, encompassing 1,476 patients, were included in the study. Gegen Qinlian decoction combined with conventional treatment was found to significantly reduce FBG (MD = −0.69 mmol/L, 95% CI −0.84 to −0.55, p < 0.01; I2 = 67%, p

[Objective] To address the issues of delayed, ineffective communication of information and declining instructions among various stakeholders during metro project construction, it is necessary to improve data integration, storage, and transmission in comprehensive monitoring system through digitalization and intelligent means. A DCCMS (digitalized construction-site comprehensive monitoring system) is established. [Method] Taking the construction of Guangzhou Rail Transit Line 3 East Extension project and the DCCMS for synchronous implementation of general contracting project as the research object, the construction content and overall architecture under metro project general contracting mode are outlined. The types and characteristics of users at construction management level, frontline management level, operation-maintenance management level are elaborated. Targeted designs for communication networks and functional scenes in the perception layer are conducted. The innovation in key technologies such as big data visualization dashboards, graphic engines, and emergency command system knowledge base management is analyzed. [Result & Conclusion] The construction system of DCCMS adopts the concept of ′hierarchical design and management′, which is deployed in Guangzhou Rail Transit Line 3 East Extension project and further improved through engineering practice. Through establishing DCCMS, the effective monitoring of personnel safety, construction safety, equipment safety, and construction process is realized. With research on key technologies, data integration, storage, and transmission in the construction-site comprehensive monitoring system are improved and emergency response is effectively supported. The establishment of a safety-controlled construction environment through digitalized construction-site perception system enables big data-driven decision-making and evaluation, providing reference and promotion for the informatization construction of comprehensive monitoring systems in metro construction projects.

Abstract Background The emergence of carbapenem-resistant Klebsiella pneumoniae (CRKP) attracted extensive attention. Information on CRKP from hospital wastewater (HWW) is limited. The aims of this study were to investigate the genomic characteristics and to evaluate the survivability characteristics of 11 CRKP from HWW in a Chinese teaching hospital in Fujian province. Results A total of 11 CRKP from HWW were recovered in this study. All CRKP from HWW were resistant to most antibiotics. Comparative genetic analysis demonstrated that all CRKP isolates were clustered into the three distinct phylogenetic clades and clade 2 and clade 3 were mixtures of samples collected from both HWW and clinical settings. Varieties of resistance genes, virulence genes and plasmid replicon types were detected in CRKP from HWW. In vitro transfer of bla KPC-2 was successful for 3 bla KPC-2-positive CRKP from HWW with high conjugation frequency. Our study demonstrated that the genetic environments of bla KPC−2 shared core structure with ISKpn27-bla KPC−2-ISKpn6. Group analysis showed that CRKP from HWW had a lower survivability in serum compared to clinical CRKP (p 005). Conclusions We analyzed the genomic and survivability characteristics of CRKP from HWW in a Chinese teaching hospital. These genomes represent a significant addition of genomic data from the genus and could serve as a valuable resource for future genomic studies about CRKP from HWW.

IntroductionDementia is a neurological disorder associated with aging that can cause a loss of cognitive functions, impacting daily life. Alzheimer's disease (AD) is the most common cause of dementia, accounting for 50–70% of cases, while frontotemporal dementia (FTD) affects social skills and personality. Electroencephalography (EEG) provides an effective tool to study the effects of AD on the brain.MethodsIn this study, we propose to use shallow neural networks applied to two sets of features: spectral-temporal and functional connectivity using four methods. We compare three supervised machine learning techniques to the CNN models to classify EEG signals of AD / FTD and control cases. We also evaluate different measures of functional connectivity from common EEG frequency bands considering multiple thresholds.Results and discussionResults showed that the shallow CNN-based models achieved the highest accuracy of 94.54% with AEC in test dataset when considering all connections, outperforming conventional methods and providing potentially an additional early dementia diagnosis tool.

Abstract Background Episiotomy is a surgical solution to relieve perineal stress, resulting in an easily repairable incision, in comparison to the risks of serious vaginal trauma during delivery. The midwife typically adopts such a clinical decision, on experience and subjective judgment. However, the association between perineal stress and episiotomy is poorly characterized. Our aim was to identify a threshold value for perineal stress leading to episiotomy, which eventually may be employed as a clinical tool for assessing whether an episiotomy is required or not. Methods In total, 245 nulliparous women were investigated for perineal stress during non-instrumental vaginal delivery in Ningbo Women & Children’s Hospital. During the second stage of labor, a flexible membrane stress sensor was placed between the fetal head and perineal wall above the anal fissure. Once the entire fetal head pressed against the sensor, real-time perineal stress was measured, and the peak value was recorded. Cases were divided into non-episiotomy group (n = 173) and episiotomy group (n = 72). The correlations between perineal stress and episiotomy was assessed through logistic regression with adjustment for maternal age, estimated birthweight, duration of second stage of labor, maternal body mass index, and presence of analgesia. Midwives were blinded to all stress measurement values. The predictive value of perineal stress on performing episiotomy was evaluated, together with the ideal cut-off perineal stress value for performing episiotomy. A ROC analysis was also performed. Results The episiotomy group had significantly higher levels of perineal stress in comparison to the non-episiotomy group (140.50 ± 16.03 N versus 118.37 ± 19.21 N, p

Introduction Reproductive concerns refer to worries about impaired or lost reproductive ability due to disease or/and treatment. Many young female patients with breast cancer experience reproductive concerns because they still desire to have children at the time of diagnosis. Reproductive concerns can impact patients’ treatment decision-making as well as their psychological health and quality of life. Understanding the situation, contributing factors and health-related consequences of reproductive concerns among patients with breast cancer is essential to minimise their impacts.Methods and analysis A systematic review will be conducted. We will search five English databases (PubMed, Embase, CINAHL, Web of Science and APA PsycInfo) and four Chinese databases (Wang Fang database, VIP, CBM and CNKI) for pertinent studies. Other relevant studies will be identified from the reference lists of included studies. Two reviewers will independently perform study selection, data extraction and quality appraisal. Any discrepancies between the two reviewers will be resolved through consultation and discussion with the senior reviewer. A formal narrative synthesis will be performed to summarise the findings of individual studies. This review aims to improve understanding of the level of reproductive concerns, factors associated with reproductive concerns and health-related consequences of reproductive concerns among patients with breast cancer. The findings can contribute to the development of tailored interventions to alleviate reproductive concerns of patients with breast cancer, enhancing their psychological health and quality of life.Ethics and dissemination Ethical approval is not required for this review, as it will be based on published studies. The findings will be disseminated by publishing in a journal.PROSPERO registration number CRD42022375247.

Objective: Nurses play a crucial role in cancer control. Prior reviews presented the effectiveness of nursing interventions such as tobacco cessation counseling and cervical cancer screening but did not focus on low- and middle-income countries (LMICs). This scoping review addresses a gap in the literature by describing the roles and activities of nurses in cancer prevention and early detection in LMICs. Methods: Following Arksey and O'Malley's scoping review framework, we searched seven databases using subject headings and keywords from 1990 to January 2021 and updated in April 2022. The reference lists of relevant studies were also searched. Two reviewers independently screened the relevance of studies through Rayyan, assessed full text articles, and extracted data using a Google Form. Conflicts were resolved by a third reviewer. Results: A total of 180 studies were included, representing all six World Health Organization regions and 48 LMICs. The largest number of studies were from the African region (n ​= ​72), the Americas (n ​= ​49), and South-East Asia region (n ​= ​29). The main nursing roles featured were patient/community education (n ​= ​113), history taking and cancer risk assessment (n ​= ​63), performing screening exams (n ​= ​136), care coordination (n ​= ​57), and training other healthcare professionals (n ​= ​9). Conclusions: This scoping review provides a comprehensive picture of nurses’ role in cancer prevention and early detection in LMICs, across all six World Health Organization regions. Additional cancer workforce data sources at the country level are needed to fully understand the activities of nurses in cancer prevention. Future research is also needed to measure the impact of nursing educational and other interventions in both primary and secondary cancer prevention.

Objectives The aim of this study was to investigate the level of practice of peripherally inserted central catheter (PICC) maintenance among nurses in Guizhou province, China, and to explore its influencing factors.Design Cross-sectional study.Setting 11 tertiary and 26 secondary hospitals of Guizhou province, China.Participants A total of 832 nurses engaged in clinical work of PICC maintenance participated in the present study.Primary outcome measures PICC maintenance knowledge questionnaire, PICC maintenance attitude questionnaire and PICC maintenance practice questionnaire were administrated online for measuring participants’ knowledge, attitude and practice of PICC maintenance, respectively.Results The mean score of nurses’ practice of PICC maintenance was 79.77±12.13 and 60.8% of participants reported acceptable practices of PICC maintenance. The availability of PICC guidelines (β=0.10, p=0.002), previous training on PICC maintenance (β=0.18, p

Abstract Background The effect of dairy products intake on breast cancer (BC) is highly controversial. This study aims to investigate the relationship between dairy intake and BC incidence. Methods A search was carried out in PubMed, EBSCO, Web of Science, and Cochrane Library databases before January 2021. The primary objective was the risk of BC and intake of dairy products were exposure variables. Results The meta-analysis comprised 36 articles with 1,019,232 participants. Total dairy products have a protective effect on female population (hazard ratio (HR) =0.95, 95% confidence interval (CI) =0.91–0.99, p = 0.019), especially for estrogen receptor-positive (ER+) (HR = 0.79, p = 0.002) and progesterone receptor-positive (PR+) BC (HR = 0.75, p = 0.027). For ER+/PR+ BC, there is a trend of protection, but it has not reached statistical significance (HR = 0.92, p = 0.075). Fermented dairy products can reduce BC risk in postmenopausal population (HR = 0.96, 95%CI = 0.93–0.99, p = 0.021), but have no protective effect on premenopausal population (HR = 0.98, 95%CI = 0.94–1.03, p = 0.52). Non-fermented dairy products have no significant effect on BC occurrence (p > 0.05). High-fat dairy products are harmful to women, without statistical difference (HR = 1.06, 95%CI = 1.00–1.13, p = 0.066). On the contrary, low-fat dairy products can protect the premenopausal population (HR = 0.94, 95%CI = 0.89–1.00, p = 0.048). Conclusion The intake of dairy products can overall reduce BC risk in the female population, but different dairy products have varying effects on different BC subtypes and menopausal status.

Abstract Background After a stroke, 80% of the chronic patients have difficulties to use their paretic upper limb (UL) in activities of daily life (ADL) even after rehabilitation. Virtual reality therapy (VRT) and anodal transcranial direct current stimulation (tDCS) are two innovative methods that have shown independently to positively impact functional recovery of the paretic UL when combined with conventional therapy. The objective of the project will be to evaluate the impact of adding anodal high-definition (HD)-tDCS during an intensive 3-week UL VRT and conventional therapy program on paretic UL function in chronic stroke. Methods The ReArm project is a quadruple-blinded, randomized, sham-controlled, bi-centre, two-arm parallel, and interventional study design. Fifty-eight chronic (> 3 months) stroke patients will be recruited from the Montpellier and Nimes University Hospitals. Patients will follow a standard 3-week in-patient rehabilitation program, which includes 13 days of VRT (Armeo Spring, 1 × 30 min session/day) and conventional therapy (3 × 30 min sessions/day). Twenty-nine patients will receive real stimulation (4x1 anodal HD-tDCS montage, 2 mA, 20 min) to the ipsilesional primary motor cortex during the VRT session and the other 29 patients will receive active sham stimulation (2 mA, 30 s). All outcome measures will be assessed at baseline, at the end of rehabilitation and again 3 months later. The primary outcome measure will be the wolf motor function test. Secondary outcomes will include measures of UL function (Box and Block Test), impairment (Fugl Meyer Upper Extremity), compensation (Proximal Arm Non-Use), ADL (Actimetry, Barthel Index). Other/exploratory outcomes will include pain, fatigue, effort and performance, kinematics, and motor cortical region activation during functional motor tasks. Discussion This will be the first trial to determine the impact of adding HD-tDCS during UL VRT and conventional therapy in chronic stroke patients. We hypothesize that improvements in UL function will be greater and longer-lasting with real stimulation than in those receiving sham. Trial registration The ReArm project was approved by The French Research Ethics Committee, (Comité de Protection des Personnes-CPP SUD-EST II, N°ID-RCB: 2019-A00506-51, http://www.cppsudest2.fr/ ). The ReArm project was registered on ClinicalTrials.gov ( NCT04291573 , 2nd March 2020.

Tendon injury is one of the most serious orthopedic diseases often leading to disability of patients. Major shortages of tendon healing are due to its multiple comorbidities, uncertainty of therapeutic efficacy and insufficient of angiogenesis. With a deeper understanding of angiogenic mechanism of tendon healing, we investigated an innovative microneedle patch loaded with platelet derived growth factor (PDGF) to achieve a constant systemic administration of PDGF to enhance topical tendon healing. Rat achilles tendon injury model was performed as in vivo animal models. Histological staining showed an enhancement of tendon healing quality, especially angiogenesis. Biomechanical studies demonstrated an increase of tendon stiffness, maximum load and maximum stress with treatment of PDGF-loaded microneedles. Furthermore, MAPK/p38/Cyclin D1 pathway and angiogenesis were found to play an important role in tendon healing process by using a biological high throughput RNA-sequence method and bioinformatic analysis. The high throughput RNA-seq tendon healing results were confirmed by histochemical staining and western blot. These results suggest the novel therapeutic potential of PDGF-loaded microneedle patch in tendon surgery.

Due to the lack of fault data in the daily work of rotating machinery components, existing data-driven fault diagnosis procedures cannot accurately diagnose fault classes and are difficult to apply to most components. At the same time, the complex and variable working conditions of components pose a challenge to the feature extraction capability of the models. Therefore, a transferable pipeline is constructed to solve the fault diagnosis of multiple components in the presence of imbalanced data. Firstly, synchrosqueezed wavelet transforms (SWT) are improved to highlight the time-frequency feature of the signal and reduce the time-frequency differences between different signals. Secondly, we proposed a novel hierarchical window transformer model that obeys a dynamic seesaw (HWT-SS), which compensates for imbalanced samples while fully extracting key features of the samples. Finally, a transfer diagnosis between components provides a new approach to solving fault diagnosis with imbalanced data among multiple components. The comparison with the benchmark models in four datasets proves that the proposed model has the advantages of strong feature extraction capability and low influence from imbalanced data. The transfer tests between datasets and the visual interpretation of the model prove that the transfer diagnosis between components can further improve the diagnostic capability of the model for extremely imbalanced data.

Using vibration signals for bearing fault diagnosis can generally achieve good diagnostic results. However, it is not suitable for practical industrial applications due to the restricted installation and high cost of vibration sensors. Therefore, the easily obtainable motor current signal (MCS) has received widespread attention in recent years. Meanwhile, traditional fault diagnosis methods cannot meet the diagnostic accuracy requirements because of the low signal-to-noise ratio (SNR) of the MCS. Committed to achieving bearing fault diagnosis through MCS, a rolling bearing fault diagnosis method, ISCV-ViT, based on the MCS and the Vision Transformer (ViT) model, is proposed. In particular, a signal processing method based on the instantaneous square current value (ISCV) is proposed to process the MCS directly obtained through a frequency converter into time-domain images. Then, the ViT model is applied for bearing fault diagnosis. Finally, experimental verification is carried out based on the public bearing dataset of Paderborn University (PU) and the bearing dataset of Shenzhen Technology University (SZTU). The analysis of the experimental results demonstrates that the average accuracy of the ISCV-ViT for the two datasets is up to 96.60% and 94.87%, respectively.

The lack of labeled data and variable working conditions brings challenges to the application of intelligent fault diagnosis. Given this, extracting labeled information and learning distribution-invariant representation provides a feasible and promising way. Enlightened by metric learning and semi-supervised architecture, a triplet-guided path-interaction ladder network (Tri-CLAN) is proposed based on the aspects of algorithm structure and feature space. An encoder–decoder structure with path interaction is built to utilize the unlabeled data with fewer parameters, and the network structure is simplified by CNN and an element additive combination activation function. Metric learning is introduced to the feature space of the established algorithm structure, which enables the mining of hard samples from extremely limited labeled data and the learning of working condition-independent representations. The generalization and applicability of Tri-CLAN are proved by experiments, and the contribution of the algorithm structure and the metric learning in the feature space are discussed.

The elastic thickness of the lithosphere (Te) is a key parameter used to describe the strength of the lithosphere. It is usually estimated by a spectral analysis between gravity and topography. In previous research on the estimation of Te, altimetry data were used on both the gravity data and topography data, which could lead to deviations. The study described in this paper analyzed the effects of using gravity anomalies derived from different data sources on the estimation of Te. Taking the western Pacific region as an example, this study analyzed the impact of the repeated presence of altimetry satellite data on the calculation of the effective elastic thickness and found that if gravity anomalies and topography model both contain altimetry satellite data, they systematically overestimate effective elasticity. For a uniform area, the difference in Te can reach up to 30%. For a Te distribution, the difference can reach up to about 16%. After eliminating this effect, the effective elastic thickness of the western Pacific region was found to be 10 km, and the statistical results of the effective elastic thickness distribution showed that the effective elastic thickness of the lithosphere in most areas of the western Pacific is about 12 km. The paper shows the importance of choosing the appropriate gravity model in evaluating the elastic thickness of lithosphere in the oceans. A figure of Te at seamounts with loading ages demonstrates that Te in the western Pacific is generally distributed within the 100–300 °C isotherm depth and does not increase with loading age.

N6‐methyladenosine (m6A) has emerged as the most prevalent post‐transcriptional modification on mRNA that contributes prominently to tumorigenesis. However, the specific function of m6A methyltransferase methyltransferase‐like 3 (METTL3) in colorectal cancer (CRC) remains elusive. Herein, we explored the biological function of METTL3 in CRC progression. Clinically, METTL3 was frequently upregulated in CRC tissues, cell lines, and plasma samples and its high expression predicted poor prognosis of CRC patients. Functionally, knockdown of METTL3 significantly repressed CRC cell proliferation and migration in vitro, while its overexpression accelerated CRC tumor formation and metastasis both in vitro and in vivo. Mechanistically, METTL3 epigenetically repressed YPEL5 in an m6A‐YTHDF2‐dependent manner by targeting the m6A site in the coding sequence region of the YPEL5 transcript. Moreover, overexpression of YPEL5 significantly reduced CCNB1 and PCNA expression. Collectively, we identified the pivotal role of METTL3‐catalyzed m6A modification in CRC tumorigenesis, wherein it facilitates CRC tumor growth and metastasis through suppressing YPEL5 expression in an m6A‐YTHDF2‐dependent manner, suggesting a promising strategy for the diagnosis and therapy of CRC.

Abstract A design approach is presented based on insights into power division among modes for a dual‐band filtering power divider using a single multimode resonator. The relationship between the energy of the input port under different modes and the corresponding external quality factor (Qe) is analysed. Then, the power distribution among the in‐band modes and between output ports can be all expressed by Qe. Therefore, the synthesis of a coupling matrix to achieve independent power distribution in the two bands is simplified. For further verification, a quad‐mode dielectric resonator with independently controllable modes is designed. Based on this, dual‐band filtering power dividers with equal and unequal power split ratios (1:1 in the lower band and 2:1 in the higher band) are simulated and implemented. The simulation and measurement agree, proving the correctness of the approach.

Background and purposeThe treatment of aneurysms located in the posterior and distal anterior circulations remains a challenge. Leo stents with a flow diversion (FD) effect may be a potential option, which needs to be clearly studied.MethodsFrom January 2016 to October 2021, 133 patients with 145 aneurysms in the posterior and distal anterior circulations, treated with Leo stents, were retrospectively analyzed in three neurosurgical centers. Data on demographic information, aneurysm characteristics, procedural outcomes, postoperative course, and aneurysm occlusion were retrospectively analyzed.ResultsAfter immediate surgery, 90 aneurysms (60.1%) were in complete occlusion [Raymond-Ray Occlusion Class (RROC) 1 and O'Kelly Marotta (OKM) grade D], 29 aneurysms (20%) in good occlusion (RROC 2 and OKM grade C), 17.9% in incomplete occlusion (RROC 3a or OKM grade B), and no aneurysms in invalid occlusion (RROC 3b and OKM grade A). A total of 112 patients with 117 aneurysms received angiographic follow-up (mean 11.4 months), and the degree of occlusion showed a significant improvement (Z = 3.900, p < 0.001). The complete occlusion rate increased to 84.6% (99/117), while good and incomplete occlusion decreased to 6.8% (8/117) and 8.6% (10/117), respectively. A total of 14 cases (10.5%) presented narrowing of the parent artery, and nine cases (6.8%) had injured side branches. Cerebral hemorrhage occurred in four patients (3.0%), and symptomatic ischemic infarction occurred in six patients (4.5%). The final permanent morbidity (mCS ≥3) and mortality were 2.8% (3/133) and 0.8% (1/133), respectively. For 82 aneurysms treated by stent-assisted with coiling (SAC), large-sized, ruptured aneurysms (χ2 = 7.767, p = 0.005) occurred. For 63 aneurysms treated by LEO stent monotherapy (LSM), multiple aneurysms, fusiform aneurysms (χ2 = 18.958, p < 0.01), and/or small-sized aneurysms (Z = −2.692, p = 0.007) occurred.ConclusionsLeo stents are safe and effective for aneurysms located in the posterior and distal anterior circulations. The overall degree of occlusion improved during a follow-up because of the FD effect of Leo stents. Aneurysms in these areas should be treated with personalized measures.

Abstract Background IgA nephropathy(IgAN)) is the common pathological type of glomerular diseases. The role of gut microbiota in mediating “gut-IgA nephropathy” has not received sufficient attention in the previous studies. The purpose of this study was to investigate the changes of fecal short-chain fatty acids(SCFAs), a metabolite of the intestinal microbiota, in patients with IgAN and its correlation with intestinal flora and clinical indicators, and to further investigate the role of the gut-renal axis in IgAN. Methods There were 29 patients with IgAN and 29 normal control subjects recruited from January 2018 to May 2018. The fresh feces were collected. The fecal SCFAs were measured by gas chromatography/mass spectrometry and gut microbiota was analysed by16S rDNA sequences, followed by estimation of α- and β-diversity. Correlation analysis was performed using the spearman’s correlation test between SCFAs and gut microbiota. Results The levels of acetic acid, propionic acid, butyric acid, isobutyric acid and caproic acid in the IgAN patients were significantly reduced compared with control group(P

Single image super-resolution (SISR) aims to recover a high-resolution image from a single low-resolution image. In recent years, SISR methods based on deep convolutional neural networks have achieved remarkable success, and some methods further improve the performance of the SISR model by introducing nonlocal attention into the model. However, most SISR methods that introduce nonlocal attention focus on more complex attention mechanisms and only use fixed functions for measurement when exploring image similarity. In addition, the model penalizes the algorithm in terms of loss when the output predicted by the model does not match the target data, even if this output is a potentially valid solution. To this end, we propose learnable nonlocal contrastive attention (LNLCA), which flexibly aggregates image features while maintaining linear computational complexity. Then, we introduce the adaptive target generator (ATG) model to address the problem of the single model training mode. Based on LNLCA, we construct a learnable nonlocal contrastive network (LNLCN). The experimental results demonstrate the effectiveness of the algorithm, which produces reconstructed images with more natural texture details.

Cancer cachexia is characterized by weight loss, anorexia, asthenia, and anemia among cancer patients and can lead to their decreased physical function, poor quality of life, and reduced survival. Progestins have been reported to have beneficial effects on appetite improvement in patients with cancer; however, serious complications have been reported as a result of their use. Traditional Chinese medicine (TCM) is a complementary and alternative system of medicine that may be effective in treating cancer cachexia. This review aims to identify existing evidence on the efficacy and safety of traditional Chinese herbs and common TCM technologies in treating cancer cachexia. We searched six databases – the Cochrane Library, PubMed, EMBASE, CINAHL, China National Knowledge Infrastructure, and Wan Fang Database, using medical subject headings and free text. The search was performed in January 2021, and the reference lists of relevant articles were also searched. A total of 4685 citations were identified, and 20 studies were included. The results showed that traditional Chinese herbs can improve appetite, weight, biomarkers, the Karnofsky performance status, cachexia-related symptoms, and quality of life in patients with cancer cachexia. Some traditional Chinese herbs may have superiority in curative effects and safety, compared with progestins. Interestingly, acupuncture can improve appetite, nausea, constipation, and quality of life among patients with cancer cachexia but cannot increase body weight. However, high-quality evidence regarding the effect of TCM technologies in treating cancer cachexia is limited. It would be beneficial to explore the use of moxibustion and other TCM technologies in future studies.

PurposeTo establish an easy and widely applicable prognostic prediction model for uveal melanoma (UM) based on a Chinese population.Patients and MethodsA total of 295 consecutive cases treated at the Eye & ENT Hospital of Fudan University were included as the primary cohort, and 256 cases were included in the validation cohorts from two external Caucasian databases. Clinicopathological data were collected retrospectively, and nomogram models were formulated based on multivariable analysis. The concordance index (C-index), AUC (area under the Receiver Operating Characteristic, ROC curve), and Brier score were calculated and compared.ResultsBased on the training cohort, a nomogram model was established with five relevant variables: age, tumor size, ciliary body involvement, non-spindle cell type and extra-scleral extension. The C-index was 0.737, the 3- and 5-year AUCs were 0.767 and 0.742, and the Brier scores for 3- and 5-year survival were 0.082 and 0.129, respectively, which showed superior prediction compared to that of the Tumor, Node and Metastasis staging system. The model also displayed good discrimination and calibration in the external validation cohorts. By risk stratification, patients could be divided into low- and high-risk groups, and the overall survival curves displayed significant differences in the training and validation cohorts.ConclusionOur nomogram model was simple and accurate at predicting the overall survival of patients with UM. It was established based on Asian patients and proved suitable for Caucasian patients; thus, it has a wide range of potential applications, especially for patients living in less medically developed countries and regions.

BackgroundDifferential diagnosis of patients with suspected infections is particularly difficult, but necessary for prompt diagnosis and rational use of antibiotics. A substantial proportion of these patients have non-infectious diseases that include malignant tumors. This study aimed to explore the clinical value of metagenomic next-generation sequencing (mNGS) for tumor detection in patients with suspected infections.MethodsA multicenter, prospective case study involving patients diagnosed with suspected infections was conducted in four hospitals in Shanghai, China between July 2019 and January 2020. Based upon mNGS technologies and chromosomal copy number variation (CNV) analysis on abundant human genome, a new procedure named Onco-mNGS was established to simultaneously detect pathogens and malignant tumors in all of the collected samples from patients.ResultsOf 140 patients screened by Onco-mNGS testing, 115 patients were diagnosed with infections; 17 had obvious abnormal CNV signals indicating malignant tumors that were confirmed clinically. The positive percent agreement and negative percent agreement of mNGS testing compared to clinical diagnosis was 53.0% (61/115) and 60% (15/25), vs. 20.9% (24/115) and 96.0% (24/25), respectively, for conventional microbiological testing (both P

The arc-shaped tectonic belt, located in the northeastern margin of the Tibetan Plateau, is one of the leading edges of the plateau’s outward growth and uplift expansion, with a large number of active faults and frequent seismic activity. Researchers have carried out numerous studies on active faults in this region, and a wealth of reliable basic data has been accumulated. However, integrating multidisciplinary data to establish a 3D geometrical structure model that is concerned about seismogenic tectonics and can be tested, has become the key to restricting the regional seismic hazard evaluation. Based on a series of published active tectonic research, we analyze in detail the surface and deep coupling relationships of the major active faults in this region and establish three sets of 3D fault structure models, which are built respectively by active fault mapping and dip angles (the V1 model), 7 magnetotelluric profiles and 7 auxiliary profiles (the V2 model), and multi-source data (the V3 model) and continuously close to the real geological facts. From the model perspective, it is suggested that the controversial Haiyuan fault is a crustal-scale left-slip fault and the shape of the Liupanshan fault reflects the absorption of the left-slip component of the Haiyuan fault. Comparing the same fault plane of these three models, we find that the V3 model is more consistent with geological facts, showing that by assisting the multi-source data 3D geological modeling technique we can establish a 3D geological model closest to the real regional structure. Finally, combining the V3 model, the fault segmentation, and the empirical formulas of the moment magnitude-rupture parameters, we segment the faults and calculate the potential moment magnitudes of the major active faults in the study region. The faults with relatively higher seismic hazards are the Liupanshan fault, the southeastern segment of the Xiangshan-Tianjingshan fault, the westernmost segment of the Haiyuan fault, and the West Qinling fault, of which the estimated potential moment magnitudes are generally more than 7.0. Our study provides a referenced 3D geological model for exploring the deep structures of the region, regional geological research, and earthquake disaster prevention.

Abstract In this paper, we deduce the generalized q-difference equations for general Al-Salam–Carlitz polynomials and generalize Arjika’s recent results (Arjika in J. Differ. Equ. Appl. 26:987–999, 2020). In addition, we obtain transformational identities by the method of q-difference equation. Moreover, we deduce U ( n + 1 ) $U(n+1)$ type generating functions and Ramanujan’s integrals involving general Al-Salam–Carlitz polynomials by q-difference equation.

Heart failure (HF) is the common consequences of various cardiovascular diseases, often leading to severe cardiac output deficits with a high morbidity and mortality. In recent years, light emitting diodes-based therapy (LEDT) has been widely used in multiple cardiac diseases, while its modulatory effects on cardiac function with HF still remain unclear. Therefore, the objective of this study was to investigate the effects of LED-Red irradiation on cardiac function in mice with HF and to reveal its mechanisms. In this study, we constructed a mouse model of HF. We found that LED-Red (630 nm) was an effective wavelength for the treatment of HF. Meanwhile, the application of LED-Red therapy to treat HF mice improved cardiac function, ameliorate heart morphology, reduced pulmonary edema, as well as inhibited collagen deposition. Moreover, LED-Red therapy attenuated the extent of perivascular fibrosis. Besides, LED-Red irradiation promoted calcium transients in cardiomyocytes as well as upregulated ATP synthesis, which may have positive implications for contractile function in mice with HF. Collectively, we identified that LED-Red exerts beneficial effects on cardiac function in HF mice possibly by promoting the synthesis of ATP.

Objective: This study aims to comprehensively analyze the influence of spontaneous tumor rupture on the prognosis of hepatocellular carcinoma patients following hepatic resection.Methods: We systematically searched four online electronic databases, including PubMed, Embase, Web of Science, and Cochrane Library, for eligible studies published from inception to March 2021. The main endpoints were overall survival (OS) and disease-free survival (DFS).Results: This meta-analysis included 21 observational articles with 57,241 cases. The results revealed that spontaneous tumor rupture was associated with worse OS (hazard ratio (HR), 1.65; 95% confidence interval (CI), 1.33–2.05) and DFS (HR, 1.42; 95% CI, 1.12–1.80) in resectable hepatocellular carcinoma patients. This phenomenon was observed in most subgroups, which were classified by recorded survival time, age, country, alpha-fetoprotein (AFP) concentration, liver cirrhosis, and microvascular invasion. However, in subgroups of macrovascular invasion positive, spontaneous tumor rupture was not a risk factor for OS (HR, 1.55; 95% CI, 0.99–2.42) and DFS (HR, 1.23; 95% CI, 0.91–1.65) in hepatocellular carcinoma patients after hepatectomy. For macrovascular invasion negative, compared with non-ruptured hepatocellular carcinoma patients, ruptured hepatocellular carcinoma patients exhibited worse prognosis for OS (HR, 1.55; 95% CI, 0.99–2.42) and DFS (HR, 1.23; 95% CI, 0.91–1.65) following hepatectomy.Conclusions: Spontaneous tumor rupture was a prognostic risk factor for hepatocellular carcinoma patients after hepatic resection. However, in macrovascular invasion patients, spontaneous tumor rupture was not a prognostic risk factor.

Abstract This paper presents the design, fabrication, and characterization of a middle-infrared (MIR) linear variable optical filter (LVOF) and thermopile detectors that will be used in a miniaturized mixed gas detector for CH4/CO2/CO measurement. The LVOF was designed as a tapered-cavity Fabry-Pérot optical filter, which can transform the MIR continuous spectrum into multiple narrow band-pass spectra with peak wavelength in linear variation. Multi-layer dielectric structures were used to fabricate the Bragg reflectors on the both sides of tapered cavity as well as the antireflective film combined with the function of out-of-band rejection. The uncooled thermopile detectors were designed and fabricated as a multiple-thermocouple suspension structure using micro-electro-mechanical system technology. Experimentally, the LVOF exhibits a mean full-width-at-half-maximum of 400 nm and mean peak transmittance of 70% at the wavelength range of 2.3~5 μm. The thermopile detectors exhibit a responsivity of 146 μV/°C at the condition of room temperature. It is demonstrated that the detectors can achieve the quantification and identification of CH4/CO2/CO mixed gas.

Abstract In this work, three-dimensional (3D) CoMoSe4 nanosheet arrays on network fibers of a carbon cloth denoted as CoMoSe4@C converted directly from CoMoO4 nanosheet arrays prepared by a hydrothermal process followed by the plasma-assisted selenization at a low temperature of 450 °C as an anode for sodium-ion battery (SIB) were demonstrated for the first time. With the plasma-assisted treatment on the selenization process, oxygen (O) atoms can be replaced by selenium (Se) atoms without the degradation on morphology at a low selenization temperature of 450 °C. Owing to the high specific surface area from the well-defined 3D structure, high electron conductivity, and bi-metal electrochemical activity, the superior performance with a large sodium-ion storage of 475 mA h g−1 under 0.5–3 V potential range at 0.1 A g−1 was accomplished by using this CoMoSe4@C as the electrode. Additionally, the capacity retention was well maintained over 80 % from the second cycle, exhibiting a satisfied capacity of 301 mA h g−1 even after 50 cycles. The work delivered a new approach to prepare a binary transition metallic selenide and definitely enriches the possibilities for promising anode materials in SIBs with high performances.

BackgroundThis is a study aimed at exploring the relationship between pretreatment overweight/obesity, adipose tissue distribution, and long-term prognosis of gastric cancer.MethodsA total of 607 gastric cancer patients were involved in the retrospective cohort study. Overweight/obese patients were defined as body mass index (BMI) greater than 25 kg/m2, and adipose tissue distribution parameters, including visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and VAT/SAT ratio were measured at the level of the third lumbar vertebra using computerized tomography images within 15 days before the surgery. Multiple Cox regression models were applied to evaluate the association between overweight/obesity and disease-specific survival (DSS) of gastric cancer, and covariates including age, gender, T stage, N stage, and chemotherapy were adjusted. Furthermore, multiple Cox regression models were performed to evaluate the association between adipose tissue distribution parameters and DSS of gastric cancer; except for covariates mentioned above, overweight/obesity was adjusted additionally.ResultsOverweight/obesity was a predictive factor (HR = 0.61, 95% CI: 0.37–0.99) for the prognosis of gastric cancer. After additionally adjusting for overweight/obesity, high SAT percentage was an independent protective factor (HR = 0.59, 95% CI: 0.36–0.96), while high VAT percentage (HR = 1.68, 95% CI: 1.06–2.68) and high VAT/SAT ratio (HR = 1.99, 95% CI: 1.19–3.34) were independent risk factors for DSS of gastric cancer. Compared with other patients (overweight/obesity with low VAT/SAT ratio group, non-overweight/obesity or high VAT/SAT ratio group), patients in the non-overweight/obesity with high VAT/SAT ratio group had a worse prognosis (HR = 1.89, 95% CI: 1.28–2.77).ConclusionThese results suggest that overweight/obesity is a predictive factor for the prognosis of gastric cancer. The VAT/SAT ratio could be used as a promising prognostic factor for gastric cancer. Therefore, in preoperative evaluation of gastric cancer patients, attention should be paid not only to BMI but also to adipose tissue distribution.

BackgroundPrevious studies have shown that the all-cause mortality and non-colorectal cancer mortality of patients with fecal occult blood test (FOBT) positivity are significantly increased, implying that FOBT results may have more prognostic value.MethodsRetrospective analysis was performed for gastric cancer (GC) patients who underwent R0 gastrectomy from July 2007 to July 2014 at our hospital. Propensity score matching (PSM) was used to reduce confounding bias and a computerized technique for the nearest available score matching without replacement was applied. The cumulative survival rate was calculated using the Kaplan-Meier method and a log-rank test. Cox proportional hazards regression and logistic regression was used to determine the independent prognostic factors associated with survival and postoperative complications, respectively. The expression level of tumor-associated macrophages (TAMs) and proinflammatory cytokines (TNF-α, IL-6) were evaluated by immunohistochemical (IHC).ResultsA total of 3,003 patients were included and 246 patients (8.2%) were in preoperative FOBT positive status. There was no significant difference in demographic data between preoperative FOBT positive and negative group after a 1:4 PSM. The overall postoperative complications, major complications, and anastomotic leakage were significantly higher in the preoperative FOBT-positive group than in the preoperative FOBT-negative group. Moreover, preoperative FOBT-positivity was an independent risk factor for 5-year overall survival (OS) (HR: 1.32, p = 0.005). For stage II/III patients, the postoperative adjuvant chemotherapy (PAC) benefit was found in preoperative FOBT-negative group (5-year OS: 49.9 vs. 36.8%, p = 0.001), whereas the PAC benefit was lost in preoperative FOBT-positive groups (5-year OS: 40.8 vs. 37.7% p = 0.896). Finally, IHC found that preoperative FOBT-positivity in patients was significantly associated with higher TAMs infiltration and higher expression of IL-6 and TNF-α in tumor tissues than in the preoperative FOBT-negative group.ConclusionAs a simple and low-cost method, preoperative FOBT results can predict both complications and survival after R0 gastrectomy for GC. More importantly, stage II/III GC patients with FOBT-positive seem not benefit from PAC alone. Further exploration is warranted.

To realize the accurate performance test under high-speed operation and the long-term stable reliability test of the motorized spindle, a reliability test rig (RTR) which can simulate the cutting force in the actual machining process is presented. Firstly, a reasonable prototype integrating dynamic force loading devices and torque loading devices is designed and established based on the load analysis of the spindle, and a complete and explicit control strategy of the reliability loading test is designed. Secondly, the effects of misalignment of the diaphragm coupling caused by assembling are analyzed, and experiments are conducted to test the axis orbit of the motorized spindle. The experimental results illustrate that the axis orbit can identify the occurrence of misalignment, which ensures timely adjustment of misalignment and the accurate performance test under high-speed operation. Lastly, a damper is added in the mechanical structure of the electrohydraulic servo loading system (EHSLS), and the comparison of Bode maps before and after optimization is analyzed by the Nyquist criterion. After the optimization, the gain and phase margin of the Bode diagram are 12.9 dB and 57.2°, respectively, which are both within the stable range and validate the improvements on the ability of long-term reliability tests of the motorized spindle. The presented RTR is able to simulate the actual cutting force and provides an efficient loading approach to guarantee the accuracy and stability of motorized spindle tests.

Surface integrity is the permanent pursuit of industries for decades, and microstructure is a key factor controlling physical and mechanical properties of machined surfaces. During machining, a complicated non-uniform distribution of deformation fields will be applied to machined surfaces, as a result, microstructure evolution will be significantly influenced. In this study, a coupled finite element (FE) and cellular automata (CA) approach is used to characterize and predict microstructure evolution during high-speed machining oxygen-free high-conductivity (OFHC) copper, where a unique material model is presented to describe both constitutive behaviors and microstructure evolution, and a mixed mechanism of continuous dynamic recrystallization (cDRX) and discontinuous dynamic recrystallization (dDRX) is adopted to show grain refinement and grain growth procedure under gradient distributed fields of strains, strain rates and temperatures in machined surfaces. A similar gradient distribution of grain sizes is obtained through both simulation and experimental results, which validates the predictive model and presents an in-depth understanding of microstructure evolution process during surface formation, and it shows the primary factors influencing the grain size distribution in sub-surface are cDRX-induced grain refinement and dDRX-induced grain growth. Moreover, the gradient distribution of microstructures in refined sub-surfaces could be used to explain mechanisms of sub-surface damage in the future.

In order to better implement maintenance strategies according to equipment levels, this paper proposes a method based on the grey correlation interval Analytic hierarchy process(AHP)-Entropy method to divide the importance of production system equipment. First, a three-level importance evaluation index system for the production system equipment is established considering the characteristics of the production system in five aspects of operating rate, reliability, maintainability, economy and detectability. Next, the interval number is combined with the AHP and the Entropy method to obtain the interval AHP and the interval Entropy method, and the two methods are combined into an interval AHP-Entropy method to determine the combined weight of each evaluation index. Combined with the evaluated equipment, the grey correlation comprehensive evaluation analysis is performed, the grey correlation degree is calculated and ranked, and the equipment is finally divided by the ABC classification method. Finally, the method is applied to the equipment division of the actual production system. Compared with the interval AHP and interval Entropy method, the evaluation difference rates are reduced by 20% and 15%, respectively, which verifies the effectiveness of the method and provides an accurate and scientific method for equipment division.

Objectives The present study aimed to assess the level of knowledge on peripherally inserted central catheter (PICC) maintenance among nurses in China and to analyse the related factors influencing this variable.Design A cross-sectional survey.Setting Ninety-one hospitals at three different levels in Hunan Province, China: county hospitals, municipal hospitals and provincial hospitals.Participants A total of 4110 registered nurses engaged in clinical work related to intravenous infusion.Primary and secondary outcome measures Nurses’ knowledge of PICC maintenance was measured by the score of an anonymous, self-reported questionnaire.Results The mean score of PICC maintenance among 4110 nurses was 72.86±14.86. 83.5% of the participants exhibited a score of 60 or above, and 34.1% of them exhibited a good grade with a score of 80 or above. The difference in the correct rate among different dimensions was statistically significant (H=17.721, p

Producing well-defined polymer compositions and structures facilitates their use in many different applications. Here the authors show the synthesis of well-defined asymmetric double-brushes by a one-pot concurrent atom transfer radical polymerization and Cu-catalyzed Click reaction.

Asthma is a dynamic disease, in which lung mechanical and inflammatory processes interact in a complex manner, often resulting in exaggerated physiological, in particular, inflammatory responses to exogenous triggers. We hypothesize that this may be explained by respiratory disease-related systems instability and loss of adaptability to changing environmental conditions, manifested in highly fluctuating biomarkers and symptoms. Using time series of inflammatory (eosinophils, neutrophils, FeNO), clinical and lung function biomarkers (PEF, FVC,FEV1), we estimated this loss of adaptive capacity (AC) during an experimental rhinovirus infection in 24 healthy and asthmatic human volunteers. Loss of AC was estimated by comparing similarities between pre- and post-challenge time series. Unlike healthy participants, the asthmatic’s post-viral-challenge state resembled more other rhinovirus-infected asthmatics than their own pre-viral-challenge state (hypergeometric-test: p=0.029). This reveals loss of AC and supports the concept that in asthma, biological processes underlying inflammatory and physiological responses are unstable, contributing to loss of control.

[This corrects the article DOI: 10.1371/journal.pone.0129206.].

Acute respiratory tract infections (ARI) in infancy have been implicated in the development of chronic respiratory disease, but the complex interplay between viruses, bacteria and host is not completely understood. We aimed to prospectively determine whether nasal microbiota changes occur between the onset of the first symptomatic ARI in the first year of life and 3 weeks later, and to explore possible associations with the duration of respiratory symptoms, as well as with host, environmental and viral factors. Nasal microbiota of 167 infants were determined at both time-points by 16S ribosomal RNA-encoding gene PCR amplification and subsequent pyrosequencing. Infants were clustered based on their nasal microbiota using hierarchical clustering methods at both time-points. We identified five dominant infant clusters with distinct microbiota at the onset of ARI but only three clusters after 3 weeks. In these three clusters, symptom persistence was overrepresented in the Streptococcaceae-dominated cluster and underrepresented in the cluster dominated by “Others” (p

Children with frequent respiratory symptoms in infancy have an increased risk for later wheezing, but the association with symptom dynamics is unknown. We developed an observer-independent method to characterise symptom dynamics and tested their association with subsequent respiratory morbidity. In this birth-cohort of healthy neonates, we prospectively assessed weekly respiratory symptoms during infancy, resulting in a time series of 52 symptom scores. For each infant, we calculated the transition probability between two consecutive symptom scores. We used these transition probabilities to construct a Markov matrix, which characterised symptom dynamics quantitatively using an entropy parameter. Using this parameter, we determined phenotypes by hierarchical clustering. We then studied the association between phenotypes and wheezing at 6 years. In 322 children with complete data for symptom scores during infancy (16 864 observations), we identified three dynamic phenotypes. Compared to the low-risk phenotype, the high-risk phenotype, defined by the highest entropy parameter, was associated with an increased risk of wheezing (odds ratio (OR) 3.01, 95% CI 1.15–7.88) at 6 years. In this phenotype, infants were more often male (64%) and had been exposed to environmental tobacco smoke (31%). In addition, more infants had siblings (67%) and attended childcare (38%). We describe a novel method to objectively characterise dynamics of respiratory symptoms in infancy, which helps identify abnormal clinical susceptibility and recovery patterns of infant airways associated with persistent wheezing.

Purpose. To investigate meibomian gland and tear film function in patients with type 2 diabetes. Methods. This prospective study compared changes in meibomian gland and tear film function in type 2 diabetic patients with nondiabetic patients. Meibomian gland function was evaluated by measuring lipid layer thickness (LLT), grading of meibomian gland loss, lid margin abnormalities, and expression of meibum. Tear film function was assessed by measuring tear breakup time (TBUT), the Schirmer I test, noninvasive breakup time (NIBUT), tear meniscus height (TMH), and corneal fluorescein staining. Results. Meibography scores were significantly higher in the diabetic group compared with the nondiabetic group (p=0.004). The number of expressible glands was significantly lower in the diabetic group in temporal, central, and nasal third of the lower eyelid (nasal: p=0.002; central: p=0.040; and temporal: p=0.039). The lid margin abnormality score was significantly higher in the diabetic group than in the nondiabetic group (p=0.04). There was no statistically significant difference in the tear film function parameters between the two groups. Conclusions. Meibomian gland dysfunction (MGD) in type 2 diabetic patients is more severe compared with nondiabetic patients. Overall, most of the diabetic patients manifest as having asymptomatic MGD.

Hybrid organic−inorganic metal halide perovskite nanocrystals (NCs) are among the candidates for color conversion materials in displays, especially in NC-based micro-light-emitting diode (micro-LED) displays. However, these NCs are still lacking long-term stability, which has hindered their large-scale applications. We mimic the working conditions, which include ultraviolet light illumination at 323 K and three different types of atmosphere (N2, vacuum, and air), respectively, to investigate the stability of CH3NH3PbBr3 NCs embedded in the polyvinylidene fluoride matrix. X-ray diffraction results indicate the generation of NH4Pb2Br5, which is produced from the encapsulated CH3NH3PbBr3 NCs in all three atmospheres, and the decomposition generates a large amount of accompanying interface defects at the surface area of NCs, resulting in the significant decrease of the photoluminescence (PL) intensity. This work highlights the stability-related mechanism of CH3NH3PbBr3 NCs under combined external stresses that mimic operating conditions. In addition, this work also suggests a new method for conducting aging tests and contributes to developing effective routes towards higher stability of perovskite NCs.