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A link between smoking behaviors and the risk of hidradenitis suppurativa in diabetic patients
Introduction Hidradenitis suppurativa (HS) is a chronic, inflammatory skin condition characterized by painful, recurrent abscesses and tunnels under the skin. It is influenced by a complex interplay of genetic, environmental, and metabolic factors. Smoking, diabetes mellitus, obesity, and other metabolic disorders have been identified as risk factors for HS, potentially exacerbating the severity and progression of the condition. Given the higher prevalence of HS in individuals with type 2 diabetes mellitus (T2DM), understanding modifiable risk factors such as smoking is crucial for improving patient outcomes. Objectives To investigate the association between changes in smoking intensity and the risk of HS in patients with T2DM, with the goal of elucidating how smoking contributes to the development or worsening of HS in this high-risk population. Methods This retrospective cohort study analyzed data from the Korean National Health Insurance Service, comprising 1,705,427 participants. The study examined smoking status, changes in smoking intensity, and the incidence of HS in individuals with T2DM, adjusting for potential confounders such as age, gender, and comorbid conditions. Results The study found a 23.6% increased risk of HS in individuals who continued smoking compared to nonsmokers (adjusted hazard ratio (aHR), 1.236; 95% confidence interval (CI), 1.075–1.421). Additionally, participants with increased cigarette consumption had a 28.5% higher risk of HS compared to nonsmokers (aHR, 1.285; 95% CI, 1.048–1.577). However, no significant differences were observed in the association between changes in smoking intensity and the risk of HS when stratified by BMI. Conclusions This study highlights the association between smoking and the increased risk of HS in individuals with T2DM, underscoring the importance of smoking cessation as a potential strategy for mitigating HS risk in at-risk DM populations. Additional research is needed to further explore the mechanisms by which smoking exacerbates HS in T2DM and to identify effective interventions for this group.
A preliminary study using luminol-enhanced intraoperative bile duct imaging technique in rabbits
Viscoelastic N‑cadherin-like interactions maintain neural progenitor cell stemness within 3D matrices
TNFAIP9 protects against the development of the early stage of chronic kidney disease: Focus on inflammation and fibrosis
Tumor necrosis factor alpha-induced protein 9 (TNFAIP9) is a crucial effector molecule that protects cells from inflammatory and metabolic damage. This study focuses on investigating the role and regulatory mechanisms of TNFAIP9 in the progression of chronic kidney disease (CKD). By analyzing CKD-related datasets from the GEO database, we discovered that TNFAIP9 was upregulated in CKD patients and CKD mice compared to their normal controls. To elucidate the functional role of TNFAIP9, we established a mouse model of CKD through a two-step 5/6 nephrectomy (Nx). The experimental mice were transduced with an adenoviral vector to express TNFAIP9. The results showed that mice undergoing 5/6-Nx developed evident renal impairment, inflammation, and fibrosis. Overexpression of TNFAIP9 resulted in the remission of renal impairment, a decreased inflammatory response, and a reduced expression of fibrotic markers. In vitro, human renal tubular epithelial human kidney-2 (HK-2) cells were exposed to tumor necrosis factor-alpha (TNF-α) or transforming growth factor-beta (TGF-β) to simulate inflammatory and fibrotic conditions, respectively. Then, the overexpression plasmid or small interfering RNA (siRNA) targeting TNFAIP9 was transfected into HK-2 cells to either overexpress or knock down the target protein. Overexpression of TNFAIP9 reduced the TNF-α-induced inflammatory response, while its knockdown amplified it. Likewise, overexpression of TNFAIP9 decreased the TGF-β-induced fibrosis, whereas its knockdown heightened it. In summary, it is suggested that TNFAIP9 plays a protective role against the early stage of CKD by suppressing renal inflammation and fibrosis. Therefore, targeting TNFAIP9 could be a promising therapeutic approach for CKD.
Quantifying the welfare impact of air asphyxia in rainbow trout slaughter for policy and practice
SWI/SNF ATPase silenced HLF potentiates lung metastasis in solid cancers
Abstract Metastasis is the main cause of cancer-related deaths, yet the underlying mechanisms remain elusive. Here, using clear cell renal cell carcinoma (ccRCC), a tumor type with frequent lung metastases, we conduct an in vivo genome-wide CRISPR-Cas9 screen and identify HLF as a potent suppressor of lung metastasis. HLF depletion enhances ccRCC cell migration and lung metastasis, whereas HLF overexpression abrogates these effects. In ccRCC patients, HLF expression is reduced at metastatic sites and associates with epigenetic silencing mediated by the SWI/SNF ATPase subunit BRG1. HLF levels negatively correlate with migration potential in collagen. Mechanistically, HLF regulates LPXN expression, modulating the integration of collagen’s mechanical cues with the actin cytoskeleton through Paxillin, thereby suppressing cancer cell migration and lung metastasis. Overexpression of HLF or pharmacological inhibition of BRG1 reduces cell invasion across multiple cancer types. Our findings suggest that targeting the BRG1-HLF axis offers a promising therapeutic strategy for combating metastatic cancers.
Self-motivated effects of teachers’ supportive behaviors on students’ intentions of online continuous learning -- based on educational digital transformation
The study explored the factors influencing students’ online continuous learning intentions (CLI) based on educational digital transformation (EDT). The theoretical model was based on the technology acceptance model (TAM), and two dimensions were proposed: flow experience (FE) and teachers’ supportive behaviors (TSBs). It studied how these variables directly or indirectly affected students’ intentions to CLI within EDT. The constructed model was validated by exploiting a partial least squares structural equation modeling approach (PLS-SEM) based on the valid data from 614 students from five private universities in China. The results suggested that (a) the construct TSBs, including teachers’ social support, teachers’ intellectual support, and teachers’ instrument support, had a positive impact on students’ intentions of online continuing learning within EDT; (b) perceived ease of use (PEU) had a positive effect on perceived usefulness (PU), flow experience (FE) and CLI; (c) perceived usefulness (PU) had an effect on FE and CLI; (d) flow experience (FE) had a positive effect on CLI. The findings offered valuable insights for academicians, higher institution administrators, researchers, and higher education policy-makers in enhancing students’ learning based on educational digital transformation.
Multifaceted characteristics of acoustic emission damage and precursor indicators of instability in sandstone under cyclic impact loading
C-to-N atom swapping and skeletal editing in indoles and benzofurans
Abstract Skeletal editing comprises the structural reorganization of compounds. Such editing can be achieved through atom swapping, atom insertion, atom deletion or reorganization of the compound’s backbone structure1,2. Conducted at a late stage in drug development campaigns, skeletal editing enables diversification of an existing pharmacophore, enhancing the efficiency of drug development. Instead of constructing a heteroarene classically from basic building blocks, structural variants are readily accessible directly starting from a lead compound or approved pharmacophore. Here we present C to N atom swapping in indoles at the C2 position to give indazoles through oxidative cleavage of the indole heteroarene core and subsequent ring closure. Reactions proceed through ring-opened oximes as intermediates. These ring deconstructed intermediates can also be diverted into benzimidazoles resulting in an overall C to N atom swapping with concomitant skeletal reorganization. The same structural diverting strategies are equally well applicable to benzofurans leading to either benzisoxazoles or benzoxazoles. The compound classes obtained through these methods—indazoles3,4, benzisoxazoles5, benzimidazoles6,7 and benzoxazoles8—are biologically relevant moieties found as substructures in natural products and pharmaceuticals. The procedures introduced substantially enlarge the methods portfolio in the emerging field of skeletal editing.
A gatekeeper sympathetic control of lacrimal tear secretion and dry eye onset through the NA-Adra1a-Ucp2 pathway
Augmented Ensemble Model (AEM) for health trends prediction on social networks
Social Media has given an exponential rise to an ever-connected world. Health data that was earlier viewed as hospital records or clinical records is now being shared as text over social media. Information and updates regarding the outbreak of a pandemic, clinical visit results, general health updates, etc., are being analyzed. The data is now shared more frequently in various formats such as images, text, documents, and videos. With fast streaming systems and no constraints on storage spaces, all this shared rich media data is quite voluminous and informative. For shared health data such as discussions on ailments, hospital visits, general health well-being updates, and drug research updates via official Twitter handles of various pharmaceutical companies and healthcare organizations, a unique level of challenge is posed for analysis of this data. The text indicating the ailment often varies from proper medical jargon to common names for the same, whereas the intent is the same in predicting the disease or ailment term. This paper focuses on how we can extract and analyze health-related data exchanged on social media and introduce an Augmented Ensemble Model (AEM), which identifies the frequently shared topics and discussions about health on social networks, to predict the emerging health trends. The analytical model works with chronological datasets to deduce text classification of topics related to health. This Hybrid Model uses text data augmentation to address class imbalance for health terms and further employs a clustering technique for location-based aggregation. An algorithm for health terms Word Vector Embedding model is formulated. This Word Vector model is further used in Text Data Augmentation to reduce the class imbalance. We evaluate the accuracy of the classifiers by constructing a Machine Learning pipeline. For our Augmented Ensemble Model, the Text classification accuracy is evaluated after the augmentation using a voting ensemble technique, and a greater accuracy has been observed. Emerging health trends are analyzed via temporal classification and location-wise aggregation of the health terms. This model demonstrates that a Text Augmented Ensemble Machine Learning approach for health topics is more efficient than the conventional Machine Learning classification technique(s).
Prediction of thermophysical properties of R-454B based on molecular dynamic simulation and SAFT-based equation of state
Abstract R-454B is an excellent choice for refrigeration systems due to its environmentally friendly profile. In this study, the thermophysical properties of R-454B refrigerant are predicted using molecular dynamics (MD) simulations coupled with a SAFT-based equation of state (EoS). Since experimental data on the thermophysical properties of R-454B are generally scarce in technical applications, exploring these properties is essential. In this work, the COMPASS force field is employed to develop the MD simulations. The saturated density, vapor pressure, and isobaric heat capacity of R-454B were simulated. The average ARD% for the isobaric heat capacity was approximately 7.66% over the temperature range of 273.15–303.15 K. The PC-SAFT equation of state (EoS) was coupled with MD simulation to predict the thermodynamic properties of R-454B across a broad range of pressures and temperatures. In this regard, the PC-SAFT model parameters were adjusted using the simulated saturated liquid density and vapor pressure data. The obtained PC-SAFT model parameters were utilized to predict the speed of sound, specific heat capacity, and Joule–Thomson coefficient of R-454B. The results indicate that the proposed model can satisfactorily predict the vapor and liquid thermophysical properties of R-454B. This methodology can be employed to estimate second-order derivative thermodynamic properties of novel refrigerants prior to synthesis, potentially reducing the costs and time associated with experimental development.
Enhanced deglacial carbon transport by Pacific southern-sourced intermediate and mode water
Growth monitoring and promotion program services utilization patterns between home-based and facility-based delivery methods: A comparative analysis
Background In Bangladesh, utilization of government health facility-based growth monitoring and promotion (GMP) services is notably low, prompting non-governmental organizations (NGOs) to collaborate with the government to enhance GMP service utilization through home-based delivery. Despite this, there is limited information available on home-based GMP service utilization. This study aimed to investigate the utilization of GMP services between home-based and facility-based programs and identifying key factors and barriers to caregiver engagement with GMP services in rural Bangladesh. Methods A descriptive mixed-method study was conducted across six sub-districts from August to December 2019. Three sub-districts with home-based GMP services provided by NGOs were compared with three neighboring sub-districts offering government facility-based GMP services. A total of 3038 randomly selected mothers and children under one year old were included in the quantitative part of the study. Quantitative surveys include information on household socio-demographic information, GMP service components, knowledge, utilization, barriers, and qualitative approaches were used for data collection on caregivers and service providers perspectives on GMP services. Descriptive statistics were conducted for sociodemographic characteristics, caregivers’ knowledge, perception and barriers to utilization of GMP services. Student’s t-tests and chi-square tests were used to compare quantitative and qualitative variables between both GMP arms. Risk ratios (RR) with 95% confidence intervals were calculated to compare GMP knowledge. Simple logistic regression identified GMP service use levels and related barriers. Multiple logistic regression was employed to determine statistically significant associations between GMP utilization and independent variables such as caregivers who heard about GMP or GMP cards, were members of an NGO, and lacked interest in GMP services at p-value <0.05 and adjusted risk ratio (ARR) values. Thematic analysis of qualitative data was performed. Results were triangulated across sources. Results Children’s average age was 9.8 months, with a 1:1 male-to-female ratio in both groups (home-based vs. facility-based: 51.9% vs. 50.0%). Home-based GMP services exhibited higher utilization rates, with more children receiving weight and length measurements and caregivers receiving counseling than facility-based services (40% vs. 0% utilization, respectively). Caregivers’ utilization of GMP services in home-based areas was positively influenced by their knowledge of GMP or GMP cards (Adjusted risk ratio, ARR: 37.4) and their involvement with an NGO, association, or health program (ARR: 1.3). Caregivers in home-based GMP areas relied on NGO staff for service delivery, while those in facility-based areas reported no outreach from government health workers and lacked access to GMP cards due to supply issues. Across both areas, low awareness of GMP services and the absence of incentives contributed to limited utilization. Conclusion GMP service utilization remains low in rural Mymensingh district of Bangladesh. Home-based GMP service utilization was 40% but none of the caregivers utilized facility-based GMP services. Higher utilization in home-based areas was linked to caregiver awareness, access to GMP cards, and NGO involvement, while key barriers included lack of government outreach, supply gaps, and absence of incentives. To improve GMP coverage, government programs should enhance community level outreach, ensure consistent supply of growth cards, and consider integrating small incentives to motivate caregivers.
A paper-and-pencil questionnaire outperforms GPT for measuring cognitive vulnerability to depression and predicting depressive symptoms
Sucrose-driven carbon redox rebalancing eliminates the Crabtree effect and boosts energy metabolism in yeast
Abstract Saccharomyces cerevisiae primarily generates energy through glycolysis and respiration. However, the manifestation of the Crabtree effect results in substantial carbon loss and energy inefficiency, which significantly diminishes product yield and escalates substrate costs in microbial cell factories. To address this challenge, we introduce the sucrose phosphorolysis pathway and delete the phosphoglucose isomerase gene PGI1, effectively decoupling glycolysis from respiration and facilitating the metabolic transition of yeast to a Crabtree-negative state. Additionally, a synthetic energy system is engineered to regulate the NADH/NAD+ ratio, ensuring sufficient ATP supply and maintaining redox balance for optimal growth. The reprogrammed yeast strain exhibits significantly higher yields of various non-ethanol compounds, with lactic acid and 3-hydroxypropionic acid production increasing by 8- to 11-fold comparing to the conventional Crabtree-positive strain. This study describes an approach for overcoming the Crabtree effect in yeast, substantially improving energy metabolism, carbon recovery, and product yields.
Reconstruction of missing data in transferred generative adversarial networks with small sample data
Under special working conditions, data collection systems of heavy-duty trains may be faced with a small sample size and missing data when executing measurement, operation, or maintenance tasks. Existing generative modeling methods are ineffective in reconstructing missing data with such a small sample. Hence, we set up a frame of migration learning generative adversarial network for small data samples, in which a new variational autoencoder semantic fusion generative adversarial network (VAE-FGAN) is developed to reconstruct missing data. First a GRU module is introduced in the encoder to fuse the underlying features of the data with higher-level features, which enables the VAE-FGAN to learn the correlation between the measured data through unsupervised training. Second, an SE-NET attention mechanism is introduced into the whole generative network to enhance the expression of the feature extraction network on data features. Finally, parameters are shared through migration learning and pre-training, thereby eliminating the difficulty in training the model due to the small size of certain operation and maintenance data. Experimental results show that the reconstruction accuracy indices MAE and MAPE can be kept below 1.5 when measured data is missing; the reconstructed data also fits well to the distribution trend of the measured data.
Antitumor effects of plasma-activated sodium acetate solution on gastric cancer cells
Adversarial testing of global neuronal workspace and integrated information theories of consciousness
Abstract Different theories explain how subjective experience arises from brain activity 1,2 . These theories have independently accrued evidence, but have not been directly compared 3 . Here we present an open science adversarial collaboration directly juxtaposing integrated information theory (IIT) 4,5 and global neuronal workspace theory (GNWT) 6–10 via a theory-neutral consortium 11–13 . The theory proponents and the consortium developed and preregistered the experimental design, divergent predictions, expected outcomes and interpretation thereof 12 . Human participants ( n = 256) viewed suprathreshold stimuli for variable durations while neural activity was measured with functional magnetic resonance imaging, magnetoencephalography and intracranial electroencephalography. We found information about conscious content in visual, ventrotemporal and inferior frontal cortex, with sustained responses in occipital and lateral temporal cortex reflecting stimulus duration, and content-specific synchronization between frontal and early visual areas. These results align with some predictions of IIT and GNWT, while substantially challenging key tenets of both theories. For IIT, a lack of sustained synchronization within the posterior cortex contradicts the claim that network connectivity specifies consciousness. GNWT is challenged by the general lack of ignition at stimulus offset and limited representation of certain conscious dimensions in the prefrontal cortex. These challenges extend to other theories of consciousness that share some of the predictions tested here 14–17 . Beyond challenging the theories, we present an alternative approach to advance cognitive neuroscience through principled, theory-driven, collaborative research and highlight the need for a quantitative framework for systematic theory testing and building.
Assembly and the gating mechanism of the Pel exopolysaccharide export complex PelBC of Pseudomonas aeruginosa
Abstract The pathogen Pseudomonas aeruginosa enhances its virulence and antibiotic resistance upon formation of durable biofilms. The exopolysaccharides Pel, Psl and alginate essentially contribute to the biofilm matrix, but their secretion mechanisms are barely understood. Here, we reveal the architecture of the outer membrane complex PelBC for Pel export, where the essential periplasmic ring of twelve lipoproteins PelC is mounted on top of the nanodisc-embedded β-barrel PelB. The PelC assembly is stabilized by electrostatic contacts with the periplasmic rim of PelB and via the membrane-anchored acyl chains. The negatively charged interior of the PelB β-barrel forms a route for the cationic Pel exopolysaccharide. The β-barrel is sealed at the extracellular side, but molecular dynamic simulations suggest that the short loop Plug-S is sufficiently flexible to open a tunnel for the exopolysaccharide transport. This gating model is corroborated by single-channel conductivity measurements, where a deletion of Plug-S renders a constitutively open β-barrel. Our structural and functional analysis offers a comprehensive view on this pathogenicity-relevant complex and suggests the route taken by the exopolysaccharide at the final secretion step.