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Atrial Burst Pacing for Induction Testing Prolongs Procedure Time Without Improving O...
Yuma Gibo
Jumpei Saito

Yuma Gibo

and 14 more

April 17, 2025
Background Although pulmonary vein isolation (PVI) is a cornerstone treatment for atrial fibrillation (AF), recurrence remains a significant challenge. Post-PVI atrial burst pacing is used to unmask latent arrhythmogenic substrates and guide further ablation; however, the efficacy of the induction test itself in reducing recurrence remains unclear. Methods This single-center retrospective study evaluated 289 patients who underwent initial catheter ablation for AF between June 2021 and June 2023. Patients were divided into two groups: induction test (n=248) and non-induction test (n=41). In the induction test group, atrial burst pacing was performed after PVI, with additional ablation carried out at the operator’s discretion if AF or atrial tachycardia (AT) was induced. The primary endpoint was AF/AT recurrence beyond a three-month blanking period. Secondary endpoints included procedure duration and complication rates. Results The one-year recurrence-free survival was 76.0% in the induction test group versus 79.8% in the non-induction test group (p=0.412), indicating no significant difference. Among patients in the induction test group, 67.2% exhibited no inducible AF/AT, 25.7% had inducible AF/AT treated with cardioversion, and 7.1% underwent additional ablation. Fractionated atrial electrogram ablation was performed significantly more frequently in the induction test group (12.86% vs. 2.08%, p=0.030). The procedure time was significantly shorter in the non-induction test group (128.1±39.5 vs. 145.2±39.6 minutes, p=0.007). Complication rates were comparable between the two groups (1.24% vs. 2.08%, p=0.650). Conclusions Induction testing with atrial burst pacing following PVI did not reduce AF recurrence but significantly increased procedure duration. These findings suggest that omitting inducibility testing may enhance procedural efficiency without adversely affecting clinical outcomes.
Fluoroless Mapping and Ablation with Integration of a Pentaspline Pulsed Field Cathet...
Ayesha Shaik
Tri Nguyen

Ayesha Shaik

and 3 more

April 17, 2025
Introduction: Fluoroless mapping and ablation using Pentaspline pulsed field ablation catheter has many advantages. This can be achieved using “tripolar configuration” which enables high-quality electroanatomical maps, improved ability to localize EGMs, minimize use of additional mapping catheter when compared to the standard bipole configuration. We aimed to evaluate the benefits of using tripolar configuration in fluoroless atrial fibrillation ablation when compared to the standard bipolar configuration. Methods: The study was approved by the local Institutional Review Board. This study aims to compare a standard method of pinning the pentaspline catheter to an alternative “tripolar pinning” technique. In the tripolar pinning configuration, visualization of not only the 3rd electrode but also the “interpolation of electrode 1, 2, & 4 on each spline is done. Procedures were performed under general anesthesia, EnsiteX system (Abbott, Abbott Park, IL) was used for mapping. Intracardiac echo and electroanatomical map was used to identify catheter location and identify local EGMs. Tripole and standard bipole signals were displayed on the same page to evaluate the signals pre and post each PFA application. Results: Ablation was performed in 59 cases (42 males, average age 65 (30 – 85); 17 females, average age 74 (59 – 83)) in which we configured the catheter in tripole for comparison with the standard bipole setup. Geometry and post voltage maps were created using the tripolar signals in 40 of the 59 patients. Average case duration was 85 minutes (53 – 198; PVI alone 70 minutes (53 – 97)). The average number of PFA applications was 48 (31 – 72). Standard bipole EGMs demonstrated a large far field component when compared to tripole configuration. Ectopic atrial foci, atrial flutters were successfully mapped and ablated in four and five patients respectively. We were able to demonstrate line of block across mitral isthmus and cavotricuspid isthmus ablation. In cases where mapping was performed, geometry creation with the tripoles allowed for field scaling on Ensite X. Conclusion: Integration of the pentaspline pulsed field ablation catheter with the tripolar configuration is feasible and facilitates fluoroless PVI.
The Evolution of Autonomous Systems for Planetary Cave Exploration: A Review
Sarah Swinton
Daniel Mitchell

Sarah Swinton

and 4 more

April 17, 2025
The exploration of Subsurface Access Points (SAPs), such as lava tubes on the Moon and Mars, has gained significant interest due to their potential as stable environments shielded from surface radiation and temperature extremes. These sites are considered high-value targets for detecting water, signs of ancient life, and assessing their suitability as habitats for human missions. However, SAP exploration presents significant challenges, including navigating unknown and hazardous terrains, operating in low-light conditions, and managing limited communication capabilities. Recent advances in high-resolution imaging, Synthetic Aperture Radar (SAR), and other sensing technologies have enabled better identification and characterization of SAPs, providing critical data for potential exploration missions. This review presents a structured critical analysis of the challenges in planetary cave exploration and evaluates the state of the art robotic platforms which offer a cost-effective and safe alternative to human exploration in hazardous environments, in addition to sensor technologies that aid the understanding of SAPs such as seismic studies, geological characterization, and biosignature detection. This article emphasizes the advantages of multi-robot teams in generating comprehensive datasets and improving mission resilience. By combining the unique capabilities of heterogeneous robotic systems, these teams represent a crucial step toward enabling the exploration of SAPs and advancing our understanding of planetary subsurface environments.
Research on Optimal Configuration Method of Distributed Synchronous Condensers for Re...
Haoshuai Jia
Renqing Feng

Haoshuai Jia

and 6 more

April 17, 2025
To address the transient voltage stability and inter-regional power transmission fluctuations caused by the integration of distributed renewable energy into distribution networks, a distributed synchronous condenser optimal allocation method considering transient processes is proposed. First, based on the transient voltage safety ride-through standards for renewable energy, the transient voltage fluctuations and power transmission deviations of grid-connected buses under different operating conditions are analyzed, and a time-section-based transient voltage safety evaluation index is proposed. Second, an index for improving the transient voltage safety level is established, which is used to determine the installation locations of distributed synchronous condensers. On this basis, the objective function and constraints for synchronous condenser capacity allocation are formulated, and the optimization problem is solved using the Beetle Swarm Optimization (BSO) algorithm. Finally, the rationality of the distributed synchronous condenser installation locations and capacity optimization is verified through an improved IEEE 33-bus system. Simulation results demonstrate that after the optimal allocation of distributed synchronous condensers, the voltage of renewable energy buses in the distribution network meets the specified transient voltage safety ride-through standards, and the power transmission deviation is significantly reduced, validating the correctness of the conclusions and the effectiveness of the proposed method.
Comparative Effectiveness and Safety of Conduction System Pacing versus Biventricular...
Qing Jin
Xingbiao Ren

Qing Jin

and 2 more

April 17, 2025
Background: Biventricular pacing (BVP) and conduction system pacing (CSP) can enhance pacing-induced cardiomyopathy (PICM) patients’ clinical outcomes, yet guidelines lack a specified preferred pacing strategy. This meta-analysis compares the efficacy and safety of CSP and BVP in PICM patients. Methods: Databases including PubMed, Cochrane Library, Web of Science, and Embase were searched from their establishment to February 2025, Data analysis was performed using Stata 17. Results: Eighteen observational studies involving 679 patients with PICM were included, among which 322 patients were treated with BVP and 357 patients with CSP. Results showed CSP group had a greater QRS duration (QRSd) reduction than BVP group (MD = -54.61 ms, 95% CI: -59.67, -49.54 vs MD = -28.22 ms, 95% CI: -32.13, -24.31; P < 0.001). After 14-months follow-up, CSP group had a higher response rate (84.0% vs 66.4%) and lower incidences of adverse outcomes and device-related complications (9.6% vs 17.2%) than BVP group. Subgroup analysis showed His bundle pacing (HBP) was associated with greater QRSd shortening and stable pacing thresholds, while left bundle branch area pacing (LBBAP) had lower thresholds. Conclusions: The results indicate that CSP is superior to BVP in improving PICM patients’ clinical outcomes, suggesting that CSP may be a promising alternative pacing strategy for PICM patients. However, since most of the included studies were case series, there are certain limitations in the results. Large-scale randomized controlled trials are required to further verify the effectiveness and safety of CSP in PICM.
Independence, Social Accountability and Scope of Responsibilities: A Comparative Stud...
Zhijia Tian

Zhijia Tian

April 17, 2025
This study takes the National Disease Prevention and Control Agency of China (NDCPA) and the European Center for Disease Prevention and Control (ECDC) as representatives to compare the reform paths of disease control agencies after Covid-19 under China and Europe context. By drawing on existing analytical framework and analyzing the content of the laws, regulations and official documents of the two agencies, this paper systematically evaluates them in terms of the three dimensions: institutional independence, social accountability, and scope of responsibilities. The results show that compared with ECDC as an independent agency, NDCPA still has a huge gap in terms of institutional independence and social accountability, yet its responsibilities are more comprehensive. Superficially, the establishment of the NDCPA has enhanced the strength and administrative status in China’s public health crisis governance system, but it is essentially a consolidation of the previous structure under the domination of the administrative force, and its professionalism is still subject to the government at all levels and lacks a clear guarantee at the legal level. ECDC’s authority has grown during the past transboundary public health crises, and its role has gradually increased from technical support to policy coordinator, but its power mainly relies on the EU mandate to cooperate with member states, and their professional advice lacks coercive force, requiring greater commitment from member states to achieve more cohesive and effective transboundary health governance.
Effectiveness of Molnupiravir for the Treatment of COVID-19: A Systematic Literature...
Samantha G. Bromfield
Ramu Periyasamy

Samantha G. Bromfield

and 4 more

April 17, 2025
Molnupiravir (MOV), an oral antiviral, is prescribed to treat adult patients with mild-to-moderate COVID-19 at risk of progressing to severe disease. This systematic literature review assessed the real-world effectiveness of MOV for reducing the progression to severe COVID-19 outcomes in clinical settings, including high-risk or special populations (type 2 diabetes, chronic respiratory diseases, immunocompromised conditions, older adults, and nursing home residents). Studies comparing MOV-treated with untreated groups of non-hospitalized adults at risk of progression to severe COVID-19 outcomes (hospitalization, death, and the composite of hospitalization/death) were identified from EMBASE and PubMed (January 1, 2021‒May 24, 2024). Twenty-one general and special population studies were included. General population studies (n=16) showed that MOV reduced the risk of death, hospitalization, and hospitalization/death. Special population studies (n=10; five additional and five general population articles with subgroups of interest) also showed that MOV reduced the risk of the same outcomes, with a more pronounced effect in older adults (≥60 years). The wide range of risk reduction observed might be attributed to variability in COVID-19 hospitalization guidelines and vaccination coverage. Findings support the effectiveness of MOV in reducing the risk of hospitalization, death, and hospitalization/death compared with untreated groups, including high-risk adults with underlying comorbidities.
Comparative analysis of chloroplast genomes of 19 Saxifraga species, mostly from Euro...
Zhenning Leng
Zhe Pang

Zhenning Leng

and 4 more

April 17, 2025
Complete chloroplast genome sequences are wildly used in the analyses of phylogenetic relationships among angiosperms. As a species-rich genus, species diversity centers of Saxifraga L. include mountainous regions of Eurasia, such as the Alps and the Qinghai-Tibetan Plateau (QTP) sensu lato. However, to date, dataset of chloroplast genomes of Saxifraga has concentrated in the QTP species, those from European Alps are largely unavailable, which hinders comprehensive comparative and evolutionary analyses of chloroplast genomes in this genus. Here, complete chloroplast genomes of 19 Saxifraga species were de novo sequenced, assembled and annotated, of which 15 species from Alps are first reported. Subsequent comparative analysis and phylogenetic reconstruction were also conducted. Chloroplast genome length of the 19 Saxifraga species range from 149,217 bp to 152,282 bp with a typical quadripartite structure. All individual chloroplast genome included in this study contains 113 unique genes, including 79 protein-coding genes, four rRNAs and 30 tRNAs. The IR boundaries keep relatively conserved with minor expansion in S. consanguinea. mVISTA analysis and identification of polymorphic loci for molecular markers shows that six intergenic regions (ndhC-trnV, psbE-petL, rpl32-trnL, rps16-trnQ, trnF-ndhJ, trnS-trnG) can be selected as the potential DNA barcodes. A total of 1204 SSRs, 433 tandem repeats and 534 Large sequence repeats were identified in the 19 Saxifraga chloroplast genomes. The codon usage analysis revealed that Saxifraga chloroplast genome codon prefers to end in A/T. Phylogenetic reconstruction of 33 species (31 Saxifraga species included) based on 75 common protein coding genes received high bootstrap support values for nearly all identified nodes, and revealed a tree topology similar to previous studies.
Tirzepatide - Induced Diabetic Ketoacidosis in a Patient with Type 1 Diabetes: A Case...
Umna Hussain
Mooza Al-Hail

Umna Hussain

and 3 more

April 17, 2025
Title Page:Tirzepatide - Induced Diabetic Ketoacidosis in a Patient with Type 1 Diabetes: A Case ReportUmna Hussain 1*, Mooza, Al-Hail 1, Wadha Al-Fahaidi 1, Mohanad Faisal 21College of Medicine, QU Health, Qatar University, Doha, 2713, Qatar2 Internal medicine department, Hamad Medical Corporation, Doha, Qatar.*corresponding author, email: uh2003540@qu.edu.qa
A Case of Covid ILD with Significant Response to Systemic Steroids
Mujtaba Azhar Siddiqui
Unsa Khan

Mujtaba Azhar Siddiqui

and 3 more

April 17, 2025
A document by Mujtaba Azhar Siddiqui. Click on the document to view its contents.
The stress-responsive protein REDD1 drives diabetic myocardial injury via activation...
Yongjun Hu
Siao Wen

Yongjun Hu

and 7 more

April 17, 2025
Diabetic cardiomyopathy (DCM), a lethal cardiovascular complication of diabetes, lacks effective therapies. Regulated in development and DNA damage response 1 (REDD1), a stress-responsive gene implicated in diabetic pathologies, was investigated for its role in autophagy and ferroptosis during DCM progression. Diabetic mice (high-fat diet/streptozotocin-induced) and high glucose (HG)-exposed human AC16 cardiomyocytes were utilized. REDD1 expression was analyzed via RT-qPCR/western blot. Cardiac function, fibrosis (H&E/Masson staining), metabolic parameters (blood glucose, insulin resistance), autophagy (LC3-II/p62, immunofluorescence), and ferroptosis (iron overload, lipid peroxidation, Mito-FerroGreen) were assessed. REDD1 was upregulated in diabetic hearts and HG-treated cardiomyocytes. REDD1 ablation in mice attenuated hyperglycemia, restored cardiac function, reduced hypertrophy/fibrosis, and suppressed autophagy/ferroptosis. In vitro, REDD1 knockdown enhanced cardiomyocyte viability (CCK-8 assay) and mitigated injury (lactate dehydrogenase release). Mechanistically, REDD1 silencing reduced ferroptosis, which was dependent on autophagy inhibition, as both rapamycin (autophagy activator) and Erastin (ferroptosis inducer) partially reversed the protective effects of REDD1 siRNA. These findings identify REDD1 as a critical mediator of DCM via autophagy-driven ferroptosis, offering a novel therapeutic target for diabetic cardiovascular complications.
Electricity Generation from Mass ‫ﺗو‬ ‫ﻟﯾد‬ ‫اﻟطﺎﻗﺔ‬ ‫اﻟﻛﮭرﺑﺎﺋﯾﺔ‬ ‫ﻣن‬ ‫اﻟﻛﺗﻠﺔ‬
Faisal Mutrik Aldhman

Faisal Mutrik Aldhman

April 17, 2025
• This publication has been written in two languages, English and Arabic, both containing the same content, and they have been attached in a single file for the freedom of reading and choice, with English being the language adopted for discussion and presentation.
Dissecting Cardiovascular Responses to a Fixed-Interval Volitional Sighing Task Using...
Neel Muzumdar
Kelly Sun

Neel Muzumdar

and 6 more

April 17, 2025
Background: Sighing is integral to psychophysiological regulation. Volitional sighing tasks have been developed to overcome methodological issues of studying naturalistic sighing and advance research on sigh physiology. This study uses fixed-interval volitional sighing (FIVS), which rhythmically paces sighs at different frequencies, to dissect cardiovascular and autonomic responses during FIVS and explore potential sex differences in cardiovascular response dynamics. Methods: Healthy college students (n=250, 65% female) completed a baseline task and two FIVS tasks (0.033Hz and 0.066Hz) while continuous HR, BP, and respiration were measured. Using a mixed model and a priori cardiorespiratory assumptions, we isolated HR, low-frequency heart rate variability (LF-HRV), high-frequency HRV (HF-HRV), pulse transit time variability (PTTv), and mean arterial pressure (MAP) responses to sighing. Results: FIVS produced non-habituating cardiovascular responses with spectral peaks corresponding to sighing frequency. HR, LF-HRV, PTTv, and MAP increased significantly from baseline to both FIVS tasks, with greater changes observed during 0.066Hz FIVS. HF-HRV decreased only during the 0.066Hz task. Males exhibited greater increases than females in HR and PTTv, but smaller decreases in HF-HRV, from baseline to the FIVS tasks. Conclusions: Volitional sighing directly elicits graded cardiac, vascular, and autonomic responses in a frequency-dependent manner. These responses support sighing as a sympathetic challenge, which, like strenuous physical activity, may lead to longer-term improvements in autonomic balance. Sex differences in cardiovascular mobilization processes indicate potentially distinct regulatory mechanisms. This research advances our understanding of sigh physiology and suggests FIVS may serve as a valuable tool for assessing subtle variations in cardiovascular function.
Early detection of anthropogenic impacts on headwater streams in Patagonia through hy...
Paulo Moreno-Meynard

Paulo Moreno-Meynard

and 5 more

April 21, 2025
Headwater streams and associated watersheds are highly relevant and responsive units of observation and management in terms of landscape-level drivers such as changes in land use/soils and climate forcing. Nevertheless, hydrologic indicators of alteration are rarely applied at such small scale, moreover in Chile, small watersheds (<10 km2) are poorly represented within the national hydrological monitoring network. We analysed two systems of indicators of hydrological alteration based on 2-6 years of high-frequency discharge observations, from a network of 12 small watersheds in western Chilean Patagonia, consisting of four sites representing a wide climatic gradient (precipitation 700-2000 mm/year), and evaluating within each group the effect of two land use conditions (reference and impacted sites). We found that the effects of land use changes on streamflow based on short-term datasets were more strongly linked to event dynamics with sub-daily indicators, compared to a lower predictive power of seasonal dynamics with daily indicators. Daily indicators were also important to evaluate changes in flows from land use, presumably a result of altered evapotranspiration regimes, with strongest effects in dry climate zones. We conclude with a proposal for a safe operating space in headwater stream catchments based on monitoring and early detection hydrological indicators, whose implementation would be relevance for public policies for mitigation of current and projected land use change.
Spatial-Frequency Feature Fusion Based Deepfake Detection with Mask Supervision
Yilin Zhang
Zhuocheng Wu

Yilin Zhang

and 5 more

April 17, 2025
In recent years,artificial intelligence technologies have been widely used, bringing security, convenience, and certain risks. Deepfake techniques raise significant security concerns by manipulating facial images to create convincing but false representations. We introduce a novel mask-supervision-based deep forgery detection method to improve the detection performance in this context. Our approach corrects the model’s focus on irrelevant regions through mask supervision, using pixel-level labels to guide the model towards synthetic regions of the face, ensuring more accurate extraction of spatial features. In addition, we incorporate a frequency-domain feature extraction module that exploits the robustness of frequency-domain cues to compression artifacts. We first preprocess the input image and then feed it into the mask supervision and frequency domain feature extraction modules. The mask supervision module extracts intermediate features using the HRNet network and refines the spatial features by guiding the prediction mask with the true mask. The frequency domain module extracts the features by applying the $DCT$ transform and filtering in different frequency bands. Finally, the spatial and frequency domain features are connected to the classification network to output the final prediction results. Experimental results show that our method maintains good robustness in compressed scenarios.
Emotional Climate Recognition in Speech-based Conversations: Leveraging Deep Bispectr...
Ghada Alhussein
Mohanad Alkhodari

Ghada Alhussein

and 4 more

April 17, 2025
The growing availability and variety of conversational data on multiple platforms have sparked a rising interest in dynamic emotion recognition.Speech plays a crucial role in establishing a dynamic emotional climate (EC) during peer conversation. In this study, we introduce a novel approach, DeepBispec, which utilizes deep bispectral conversational speech processing to extract features that can be utilized for predicting the emotions expressed during the conversation. Incorporating bispectrum images into a CNN model, DeepBispec extracts deep features, combines them with Affect dynamics (AD), and conducts EC classification.Three open data-sets proposed,i.e., K-EmoCon, IEMOCAP, and SEWA were used to test and cross-validate on DeepBispec in terms of EC arousal/valence level classification. The experimental results have shown that combining deep features with AD enhanced the performance of DeepBispec from an accuracy of 79% for EC arousal to 81.4% with AD and an average accuracy of 76.8% for EC valence to 77.5% with AD for K-EmoCon. IEMOCAP data-set displays similar trend with an average accuracy of 77.2% for arousal increasing to 79.6% and an increase from 65.7% to 73.6% for valance. The results show that the proposed approach outperforms other state-of-the-art approaches, including deep learning architectures like CNN and LSTM, in the domain of speech-based emotion recognition.The Bispectrum-based features capture the emotional content of the voice signal in a unique manner that conventional DL models do not achieve.
FLASHApp: Interactive Data Analysis and Visualization for Top-Down Proteomics
Tom Müller
Jihyung Kim

Tom Müller

and 8 more

April 17, 2025
Top-down proteomics (TDP) is increasingly being applied in proteoform-resolved biomedical and clinical research. However, the complexity of TDP data demands flexible visualization tools integrated with analysis workflows to streamline interpretation and validation. Existing tools lack adaptability and interactivity, often requiring researchers to invest considerable resources on additional manual processing and analysis to generate publication-ready results and figures. This added layer of manual intervention impacts reproducibility, posing a significant challenge to consistent scientific outcomes. FLASHApp addresses these challenges by offering a web-based, platform-independent application for TDP data analysis and visualization. It integrates key tools like FLASHDeconv, featuring automated processing, interactive publication-ready visualizations, and direct team collaboration via shareable URLs. FLASHApp is open-source software as part of OpenMS and available at https://www.openms.org/FLASHApp/.
Development of a predictive nomogram comprising GLUT1 and clinical characteristics fo...
Li Gong
Yulan Weng

Li Gong

and 9 more

April 17, 2025
Intrahepatic cholangiocarcinoma (iCCA) is a hepatic malignant tumor that arises from the epithelial cells of the intrahepatic bile ducts and its incidence is increasing worldwide. Patients with iCCA have a poor prognosis because of the aggressiveness of the tumor, delayed diagnosis and lack of effective treatment. Therefore, seeking novel molecular biomarkers and accurate assessment of disease progression are critical to optimize treatment strategies for iCCA. Here, we found that the mRNA levels of SLC2A1 (encoding glucose transporter 1, GLUT1) increased significantly in different types of solid tumor tissues, compared with their adjacent normal tissues, through the TCGA database. By further analysis of the protein expression of GLUT1 in 95 paraffin-embedded iCCA samples by immunohistochemistry, we found that GLUT1 expression was significantly upregulated in tumor tissues compared with adjacent non-tumor tissues. Importantly, high GLUT1 expression was significantly correlated with vascular invasion, advanced T stage, advanced N stage and advanced TNM stage. Survival analysis revealed that iCCA patients with high GLUT1 expression had a worse overall survival. In addition, we established a nomogram which incorporated age, tumor size and GLUT1 expression to estimate the prognosis of iCCA. The nomogram exhibited robust discriminatory ability, accuracy, and clinical usefulness in predicting patients’ overall survival after resection. In conclusion, our study clarified the prognostic value of GLUT1 and provided an effective and accurate prognostic model for evaluating the prognosis of iCCA patients.
Effects of Intermittent and Cyclic Inlet Velocities on the Heat Transfer Characterist...
Vivek Mathew Jose

Vivek Mathew Jose

April 17, 2025
The results from the numerical investigations of both steady and unsteady circular turbulent jets impinging orthogonally on a flat surface are presented. The inlet velocity waveforms analysed consist of steady jets, square jets, triangular jets, and sinusoidal jets. In the case of unsteady jets, both intermittent and pulse jets are examined. Reynolds number (Re) ranges from 5100 to 23000, the normalized distance from the nozzle to the target surface (Z/D) spans from 2 to 12, and the frequency(f) varies from 0 to 200. The 3D simulation is carried out using finite volume based software Ansys Fluent. To ascertain the validity of the numerical approach, a rigorous validation process was undertaken, focusing on the Nusselt number, a critical parameter for characterizing heat transfer performance. Baseline studies were conducted on steady jets. Unsteady jets outperform steady jets at low Reynolds numbers. However, as the Reynolds number increases, the heat transfer capabilities of unsteady jets decline in comparison to steady jets, even though there is a marked increase in turbulence intensity for the unsteady jets. There exists a threshold frequency beyond which an unsteady jet demonstrates superior performance compared to its steady equivalent. Among the unsteady jets studied, the intermittent square jet provides the highest effectiveness, whereas the sinusoidal jet exhibits the poorest performance across all operating conditions. The secondary peaks observed in steady jets at low Z/D and high Re are absent in unsteady jets. The boundary layer thickness is maximum for steady jet and minimum for intermittent square jet. The thickness of the boundary layer rises as Z/D increases and diminishes with an increase in f. At higher Z/D, the jet expands more prior to striking the surface, resulting in a thicker boundary layer near the surface.
Clinical and immunological impact of JAK inhibition in concurrent Down Syndrome and S...
Pilar Blanco Lobo
Paula Gilabert Prieto

Pilar Blanco Lobo

and 20 more

April 17, 2025
Background: Down syndrome (DS) and STAT1 gain-of-function (GOF) share clinical and molecular features, including persistent inflammation. We aim to investigate whether the coexistence of DS and a STAT1 GOF mutation in a patient synergistically enhance interferon (IFN) signaling and exacerbate inflammatory responses, posing additional management challenges. Methods: Two patients (P1 and P2) were studied: P1, with DS and a heterozygous p.P326S STAT1 variant, and P2, with the STAT1 p.P326S variant only. Individuals with isolated DS or STAT1 GOF served as controls. IFN receptor subunits (IFNγR1/R2 and IFNαR1/R2) and responses to IFNα/γ stimulation were analyzed using flow cytometry and RT-PCR. Whole blood type-I IFN signature and serum cytokines were evaluated using NanoString and Luminex assays, respectively. Results: P1 experienced recurrent infections, chronic mucocutaneous candidiasis, interstitial pneumonitis, and pulmonary hypertension. P2 presented with esophageal candidiasis, dysphagia, and stenosis. The p.P326S variant led to increased STAT1/pSTAT1 levels in response to IFNα/γ. Both patients showed significant clinical improvement with the Janus kinase (JAK) inhibitor ruxolitinib. However, in P1, key biomarkers (STAT1 levels, IFN signature, and cytokines such as TNFα and IL-6) remained altered, indicating persistent inflammation despite clinical improvement. Conclusion: This first report of a STAT1 GOF variant in DS provides a unique ”experiment of nature,” offering insights into the interplay between trisomy 21 and STAT1-mediated immune dysregulation. Although treatment with ruxolitinib demonstrated clinical benefits, the persistent inflammation observed in P1 highlights the need for further strategies to achieve complete immune resolution. These findings emphasize the importance of comprehensive genetic and immunologic assessments in individuals with DS, particularly when immune dysfunction is suspected.
Enhancing Adeno-Associated Virus 2 Capsid Engineering Through Co-Evolutionary Couplin...
Sirimar Laosinwattana
Yiwen Li

Sirimar Laosinwattana

and 4 more

April 17, 2025
Adeno-associated virus (AAV) has emerged as a leading platform for gene therapy. However, to unlock the full potential, their manufacturing yields, stability, and efficacy must all be improved. Rational design is limited by poor predictability and the potential impact of mutations on multiple important vector properties. Directed evolution requires little knowledge or predictability, but requires large libraries, and lacks appropriate selection methods to ensure that all properties needed for successful translation are achieved. Here we bring semi-rational design to AAV capsid engineering, combining co-evolutionary coupling and consensus-based design. We designed 110 mutants at sites with different degrees of coupling and mutated them either back to consensus or with various residue similarities according to BLOSUM62. Seven were selected based on their yields and transduction efficiencies before and after heat treatment. Our results demonstrate that mutations at sites within coupled networks exhibited the highest success rates. The BLOSUM62 selection strategy and consensus design approaches had similar success rates. K-means clustering of mutants further revealed that successful mutants clustered in regions with moderate coupling scores and positive BLOSUM62 values. This study highlights the potential of using evolutionary coupling analysis to guide AAV capsid engineering, suggesting that conservative mutations informed by evolutionary data can improve AAV stability and efficacy.
Spatiotemporal Heterogeneity and Zoning Strategies for Urban Ecological Resilience in...
Xiaotang Xia
Fan Zhou

Xiaotang Xia

and 2 more

April 17, 2025
Urban Ecological Resilience (UER) is a critical capability for addressing ecological imbalances resulting from the pressures of rapid urbanization. This study developed a comprehensive UER assessment model encompassing three dimensions: adaptability, resistance, and recovery. Utilizing geographic detectors and the Patch-generating Land Use Simulation (PLUS) model, the study analyzed the spatiotemporal evolution and influencing mechanisms of Yichang’s UER from 2003 to 2023. Furthermore, it simulated multiple development scenarios for 2035 and proposed zoning optimization strategies, providing scientific evidence for sustainable ecological development. The results indicated that Yichang’s UER followed a “decline-then-rise” temporal trend. Spatially, higher resilience was observed in the northwest and lower resilience in the southeast, reflecting a heterogeneous spatial distribution. At the regional level, UER was influenced by factors such as ecological protection efforts, agricultural development, and water resource conditions. At the zonal level, ecological protection areas were primarily influenced by industrial development, whereas ecological conservation areas were shaped by the interaction between terrain conditions and ecological protection measures. Resilience-enhancing areas were mainly driven by the availability and management of water resources. Multi-scenario simulations indicated that, under a development model oriented toward water ecology protection, Yichang’s UER significantly outperformed other scenarios. The study proposed a three-tier spatial regulation framework: ”rigid constraints for protection areas, threshold control for conservation areas, and dynamic balance for resilience-enhancing areas.” This framework facilitated the coordinated improvement of UER across the region and offered a reference model for differentiated ecological governance in cities along the middle reaches of the Yangtze River.
Spatiotemporal variation characteristic of soil organic carbon stock in the Huaihe Ri...
Haoxin Zhang
Miaoying An

Haoxin Zhang

and 9 more

April 17, 2025
:The Huaihe River Eco-economic Belt (HREB) is a vital agricultural hub in China, encompassing 11% of the nation’s cultivated land and producing one-sixth of its total grain. Soil organic carbon (SOC), a key indicator of soil fertility, plays a vital role in maintaining soil quality and crop productivity. However, climate change and unresonable land management practices have significantly impacted soil carbon stocks in agricultural ecosystems, leading to soil degradation and reduced crop productivity. The study analyzed the spatial distribution and temporal dynamics of SOC stocks in the HREB from 1980 to 2020, identified the primairy drivers of SOC sequestration, and proposed targeted strategies to enhance carbon storage for sustainable agricultural development. The results showed that soil organic carbon stocks (SOCS) increased by 227.73 Tg over four decades in HREB, with an average sequestration rate of 220.30 kg C ha -1 yr -1, highlighting the significant carbon sink function. Regional SOCS exhibited a ”higher-south, lower-north” spatial pattern, with south-north soil organic carbon density (SOCD) differences of 0.70, 0.57, and 1.04 kg m -2 in 1980, 2010, and 2020, respectively. Soil pH, nitrogen fertilizer input, average annual temperature, and average annual rainfall are the primary explanatory variables influencing the annual variation of SOCD in the regions, with relative importance values of 18.46%, 10.67%, 10.37%, and 8.05%, respectively. Soil pH was the most critical determinant, affecting SOC stabilization through mineral interactions, microbial communities, and enzyme activities. Despite excessive nitrogen application accelerating SOC decomposition, it also enhanced carbon inputs via crop root exudates. Additionally, rising temperatures (+0.39°C per decade) and humid conditions promoted plant and microbial activity, enhancing SOC accumulation. Optimizing soil pH regulation and nitrogen management while adjusting to climate change is crucial for enhancing soil carbon sink capacity and guaranteeing sustainable agricultural production.
Investigating FA-BLG binding mechanisms through spectroscopic and molecular docking a...
Xiaoxia Wang
Zhixi Xun

Xiaoxia Wang

and 7 more

April 17, 2025
This study systematically investigated the interaction mechanism between fulvic acid (FA) and β-lactoglobulin (BLG) using fluorescence spectroscopy, UV-vis absorption, circular dichroism, and molecular docking simulations. The results demonstrated that FA quenches BLG fluorescence through a static quenching mechanism with a binding constant (KA) of approximately 10 3 L/mol and about one binding site (n≈1) at 298 K. Thermodynamic analysis revealed the spontaneous nature of this interaction (ΔG < 0), primarily driven by van der Waals forces and hydrogen bonding (ΔH < 0, ΔS < 0). FRET analysis indicated an intermolecular distance of 3.083 nm, confirming non-radiative energy transfer. Structural characterization showed that FA binding induces conformational changes in BLG, particularly affecting the microenvironment of tryptophan residues. These findings provide valuable insights into the molecular interactions between FA and milk proteins, suggesting potential implications for FA’s biological applications and functional food development.
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