bluuebunny/crossref_metadata_2025 huggingface dataset:
Research on atrial fibrillation diagnosis in electrocardiograms based on CLA-AF model
Authors: Si Jiajia , Bao Yiliang , Chen Fengling , Wang Yue , Zeng Meimei , He Nongyue , Chen Zhu , Guo Yuan
Published: November 2024

Aims

The electrocardiogram (ECG) is the primary method for diagnosing atrial fibrillation (AF), but interpreting ECGs can be time-consuming and labour-intensive, which deserves more exploration.

Methods and results

We collected ECG data from 6590 patients as YY2023, classified as Normal, AF, and Other. Convolutional Neural Network (CNN), bidirectional Long Short-Term Memory (BiLSTM), and Attention construct the AF recognition model CNN BiLSTM Attention-Atrial Fibrillation (CLA-AF). The generalization ability of the model is validated on public datasets CPSC2018, PhysioNet2017, and PTB-XL, and we explored the performance of oversampling, resampling, and hybrid datasets. Finally, additional PhysioNet2021 was added to validate the robustness and applicability in different clinical settings. We employed the SHapley Additive exPlanations (SHAP) method to interpret the model’s predictions. The F1-score, Precision, and area under the ROC curve (AUC) of the CLA-AF model on YY2023 are 0.956, 0.970, and 1.00, respectively. Similarly, the AUC on CPSC2018, PhysioNet2017, and PTB-XL reached above 0.95, demonstrating its strong generalization ability. After oversampling PhysioNet2017, F1-score and Recall improved by 0.156 and 0.260. Generalization ability varied with sampling frequency. The model trained from the hybrid dataset has the most robust generalization ability, achieving an AUC of 0.96 or more. The AUC of PhysioNet2021 is 1.00, which proves the applicability of CLA-AF. The SHAP values visualization results demonstrate that the model’s interpretation of AF aligns with the diagnostic criteria of AF.

Conclusion

The CLA-AF model demonstrates a high accuracy in recognizing AF from ECG, exhibiting remarkable applicability and robustness in diverse clinical settings.
Guidelines at a crossroad: comparing European and American guidelines regarding the use of imaging in peripheral vascular arterial disease and aortic disease
Authors: Liga Riccardo , Hostalrich Aurelien , Gimelli Alessia , Ricco Jean-Baptiste
Published: November 2024

This review examines the differences and similarities between the European and American guidelines concerning the use of imaging in the diagnosis and management of peripheral arterial disease (PAD) and aortic disease. PAD and aortic conditions contribute significantly to global cardiovascular morbidity and mortality; yet, they are often underdiagnosed and undertreated. Imaging plays a critical role in addressing this gap, with the European Society of Cardiology and American Cardiac Society offering different approaches to diagnostic and interventional imaging modalities. The review highlights that while both guidelines endorse duplex ultrasound as the first-line imaging method for PAD, discrepancies arise in the use of advanced modalities such as computed tomography angiography and magnetic resonance angiography. The European guidelines adopts a more conservative approach, reserving these advanced techniques for specific clinical scenarios, whereas the American guidelines places a stronger emphasis on comprehensive imaging for all patients with suspected PAD. The review also compares the guidelines on aortic disease, noting consensus on the role of computed tomography angiography and magnetic resonance angiography for aortic aneurysm diagnosis, but with differences in the emphasis on transoesophageal echocardiography, which is more strongly recommended by the American guidelines for acute cases. The manuscript calls for harmonization of these guidelines to streamline clinical practice and improve patient outcomes.
On the adjoint state method for the gradient computation in full waveform inversion: a complete mathematical derivation for the (visco-)elastodynamics approximation
Authors: Métivier L , Brossier R
Published: November 2024

High-resolution seismic imaging at all scales using full waveform inversion is now routinely used in the industry and in the academy. One key element for the success of this approach is a numerical method, named adjoint state method, originally designed for optimization problems constrained by partial differential equations, a category to which full waveform inversion belongs. This method provides an efficient way to compute the gradient of the full waveform inversion misfit function, which is the most computationally demanding task in the implementation of full waveform inversion. While well known, the complete and rigorous mathematical derivation of the adjoint state method for full waveform inversion remains missing in the scientific bibliography. The aim of this study is to remedy this lack. The derivation is performed in general settings, that is in the elastodynamics approximation, with and without considering viscosity. Through the calculus, the mechanism of the adjoint state strategy makes clear the connection between the incident and adjoint fields, especially regarding their initial and boundary conditions. The impact of introducing the viscosity is carefully analysed. The resulting gradient formulas are analysed and shown to be consistent with already published ones. The generic approach which is adopted also makes it possible to derive misfit function gradients with respect to other quantities than the subsurface mechanical parameters, for instance with respect to the initial or the boundary conditions, which could be of interest for specific applications where the reconstructed parameters are not only volumetric mechanical parameters but boundary parameters or initial field values.
The development of the Community Deprivation Index and its application to accountable care organizations
Authors: Robst John , Cogburn Ryan , Forlines Grayson , Frazier Lex , Kautter John
Published: November 2024

There is strong interest among policymakers to adjust for area-level deprivation when making payments to providers because such areas have traditionally been underserved. The Medicare Accountable Care Organization Realizing Equity, Access, and Community Health (ACO REACH) model provides higher payments to ACOs serving areas with greater deprivation. Area Deprivation Index (ADI) is the primary component to measure deprivation for ACO REACH. The ADI is a commonly used deprivation index, but there are concerns about its methodology, primarily its use of nonstandardized deprivation factors. Prior research indicates the ADI is mainly determined by home values, which does not allow it to adequately capture deprivation in urban areas. This paper revises and updates the ADI, using American Community Survey data to compute a census block group deprivation index, the Community Deprivation Index (CDI). The CDI standardizes the deprivation factors to be unit neutral, applies statistical shrinkage to account for the imprecise measurement of the factors, updates several factors, and reweights the factors using the most recently available data. Validation tests suggest the CDI exhibits higher correlations with several health outcome/utilization measures than the ADI. The CDI will better serve policymakers by improving identification of urban areas with higher deprivation.
Processing Strategy for Deep Imaging Beneath Complex Shallow Structures Under Shallow Water: a Case Study in the Enping Sag
Authors: Zhang Weiwei , Xu Leyi , Zhang Zhizhong , Chen Zhaoming , Liu Ling , Chen Renjie , Zhang Xiaozhao
Published: November 2024

As offshore exploration targets deeper parts of shallow-water areas in the eastern South China Sea, an increasing number of hydrocarbon discoveries have been made in recent years, and the difficulty of such exploration has increased. One such challenge lies in mid-depth imaging beneath complex shallow geological structures. When a seismic wave penetrates through groups of densely distributed fractures and/or volcanic rocks, only a fraction of the energy reaches the target depth. As the ray path becomes complex, the middle to deep imaging quality becomes significantly poorer. In this study we applied three techniques: 3D joint source and receiver deghosting and zero-phasing, dynamic resolution time-lag full waveform inversion (DR-TLFWI), and least square Q-compensated Kirchhoff pre-stack depth migration (LSQPSDM), to improve the related seismic data and ultimately improve the imaging quality beneath complex shallow geological structures in the shallow-water environment of the eastern South China Sea, providing better subsurface understanding for the exploration of this area.
Use of qPCR to monitor 2,4-dinitroanisole degrading bacteria in water and soil slurry cultures
Authors: Waidner Lisa A , Daniel Carrie E , Kovar Sarah E , Spain Jim C
Published: November 2024

Prediction and process monitoring during natural attenuation, bioremediation, and biotreatment require effective strategies for detection and enumeration of the responsible bacteria. The use of 2,4-dinitroanisole (DNAN) as a component of insensitive munitions leads to environmental contamination of firing ranges and manufacturing waste streams. Nocardioides sp. strain JS1661 degrades DNAN under aerobic conditions via a pathway involving an unusual DNAN demethylase. We used the deeply branched sequences of DNAN degradation functional genes as a target for development of a molecular method for detection of the bacteria. A qPCR assay was designed for the junction between dnhA and dnhB, the adjacent genes encoding DNAN demethylase. The assay allowed reproducible enumeration of JS1661 during growth in liquid media and soil slurries. Results were consistent with biodegradation of DNAN, accumulation of products, and classical biomass estimates, including most probable number and OD600. The results provide a sensitive and specific molecular method for prediction of degradation potential and process evaluation during degradation of DNAN.

One-Sentence Summary

A unique target sequence in functional genes enables the design of a simple and specific qPCR assay for enumeration of aerobic 2,4-dinitroanisole-degrading bacteria in soil and water.
Molecular insights into AGS3’s role in spindle orientation: a biochemical perspective
Authors: Yu Shi , Ji Jie , Weng Jingwei , Liu Zhijun , Wang Wenning
Published: November 2024

The intrinsic regulation of spindle orientation during asymmetric cell division depends on the evolutionarily conserved protein complex LGN (Pins)/NuMA (Mud)/Gα⋅GDP. While the role of LGN and its Drosophila orthologue Pins is well-established, the function of AGS3, the paralogue of LGN, in spindle orientation during cell division remains controversial. This study substantiates the contentious nature of AGS3’s function through systematic biochemical characterizations. The results confirm the high conservation of AGS3 in its functional structural domains, similar to LGN, and its comparable ability to bind to partners including NuMA, Insc, and Gαi3⋅GDP. However, in contrast to LGN, AGS3 and the microtubule-binding protein NuMA are unable to form stable hetero-hexamers or higher-order oligomeric complexes that are pivotal for effective regulation of spindle orientation. It was found that this notable difference between AGS3 and LGN stems from the N-terminal sequence preceding the conserved TPR motifs, which spans ∼20 residues. Furthermore, our findings substantiate the disruptive effect of Insc on the oligomeric AGS3/NuMA complex, while showing no impact on the oligomeric LGN/NuMA complex. Consequently, Insc emerges as an additional regulatory factor that distinguishes the functional roles of AGS3 and LGN, leading to the impairment of AGS3’s ability to actively reorient the mitotic spindle. These results elucidate the molecular basis underlying the observed functional disparity in spindle orientation between LGN and AGS3, providing valuable insights into the regulation of cell division at the molecular level.
T-Minkowski Noncommutative Spacetimes II: Classical Field Theory
Authors: Mercati Flavio
Published: November 2024

This paper is the second part of a series that develops the mathematical framework necessary for studying field theories on “T-Minkowski” noncommutative spacetimes. These spacetimes constitute a class of noncommutative geometries, introduced in Part I, that are each invariant under distinct quantum-group deformations of the Poincaré group. All these noncommutative geometries possess certain physically desirable characteristics, which allow me to develop all the tools of differential geometry and functional analysis that are necessary in order to build consistent and T-Poincaré-invariant noncommutative classical field theories.
Incidence and severity of community acquired pneumonias in children before and after the COVID-19 pandemic
Authors: Koliou Maria G , Aristidou Athina , Mazeri Stella , Nikolopoulos Georgios , Argyrou Maria , Haralambous Christos , Elia Avraam , Yiallouros Panayiotis
Published: November 2024

Background

During the first year of the covid-19 pandemic the adoption of non-pharmacological interventions (NPI), resulted in a significant fall in the incidence of respiratory tract infections. However, after the relaxation of these restrictions some of these infections have returned. This study evaluates the incidence and severity of community acquired pneumonias (CAPs) in children before and after the onset of pandemic.

Methods

Characteristics of CAPs admitted to Archbishop Makarios Hospital, between March 2016 and February 2023 were reviewed. Comparison was made between the first, second and third pandemic year, and the four pre-pandemic years.

Results

The mean annual number of admissions in the pre-pandemic years was 32 and dropped to 11 during the first pandemic year. However, admissions increased again in the second year of the pandemic to 41 (increase by 28%), and this increase was sustained into the third year. The proportion of complicated pneumonias, approximately doubled, from 20% in the pre-pandemic years to 35% and 33% in the second and third pandemic year, respectively.

Conclusions

During the first year the use of NPIs appeared to have decreased the incidence of pneumonias. However, during the second and third pandemic years, an increase in the numbers and severity of pneumonias was noted.
tonalli: an asexual genetic code to characterize APOGEE-2 stellar spectra. I. Validation with synthetic and solar spectra
Authors: Adame Lucía , Román-Zúñiga Carlos , Hernández Jesús , López-Valdivia Ricardo , Sánchez Edilberto
Published: November 2024

We present tonalli, a spectroscopic analysis python code that efficiently predicts effective temperature, stellar surface gravity, metallicity, $\alpha$-element abundance, and rotational and radial velocities for stars with effective temperatures between 3200 and 6250 K, observed with the Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2). tonalli implements an asexual genetic algorithm to optimize the finding of the best comparison between a target spectrum and the continuum-normalized synthetic spectra library from the Model Atmospheres with a Radiative and Convective Scheme (MARCS), which is interpolated in each generation. Using simulated observed spectra and the APOGEE-2 solar spectrum of Vesta, we study the performance, limitations, accuracy, and precision of our tool. Finally, a Monte Carlo realization was implemented to estimate the uncertainties of each derived stellar parameter.
”Short” Versus “Long” Duration of Untreated Psychosis in People with First-Episode Psychosis: A Systematic Review and Meta-Analysis of Baseline Status and Follow-Up Outcomes
Authors: Catalan Ana , Salazar de Pablo Gonzalo , Aymerich Claudia , Guinart Daniel , Goena Javier , Madaria Lander , Pacho Malein , Alameda Luis , Garrido-Torres Nathalia , Pedruzo Borja , Rubio Jose M , Gonzalez-Torres Miguel Angel , Fusar-Poli Paolo , Correll Christoph U
Published: November 2024

Background and Hypothesis

Duration of untreated psychosis (DUP) has been linked to worse mental health outcomes in psychotic disorders. We meta-analytically studied the relationship between “long” vs. “short” DUP and mental health outcomes.

Study Design

This PRISMA/MOOSE-compliant meta-analysis searched for nonoverlapping individual studies from database inception until November 01, 2023, reporting data from author-defined “short”/”long” DUP (according to author’s definition) in patients with first-episode psychosis (FEP). We compared differences between “short”/”long” DUP groups at baseline and/or follow-up in continuous and binary outcomes. We conducted random-effects meta-analyses, stratified analyses, heterogeneity analyses, meta-regression analyses, and quality assessment (PROSPERO: CRD42023479321).

Study Results

From 16,055 citations, 34 studies were included (n = 6,425, age = 27.5 ± 7.1 years, males = 60.4%, white = 70.2%, DUP: mean = 60.8 ± 43.8 weeks, median = 52.5, interquartile range = 31.3, 68.0 weeks, follow-up = 19.2 ± 35.0 months). The definition of “short”/”long” varies significantly between the studies. Compared to “short” DUP (mean = 10.2 ± 11.2 weeks), “long” DUP (mean = 58.8 ± 76.4 weeks) was associated with higher baseline Positive and Negative Syndrome Scale (PANSS) negative (k = 14, ES = 0.45, 95%CI = 0.16, 0.74) and Scale for the Assessment of Negative Symptoms (k = 7, ES = 0.29, 95%CI = 0.11, 0.47) scores, lower remission (k = 7, OR = 0.40, 95%CI = 0.24, 0.67) and more suicide attempts (k = 4, OR = 2.01, 95%CI = 1.36, 2.96). At follow-up, compared to “short” DUP, “long” DUP was associated with lower Global Assessment of Functioning (k = 4, ES = −0.63, 95%CI = −0.83, −0.43) and higher PANSS negative subscale scores (k = 5, ES = 0.66, 95%CI = 0.05, 1.27).

Conclusions

In FEP, longer DUP is related to greater baseline negative symptoms, less remission, and more suicide attempts, as well as greater postbaseline negative symptom severity and functional disability. To what degree longer DUP contributes to poorer outcomes or whether DUP only correlates with these outcomes requires further study. A greater consensus on the definition of long DUP is needed to make comparisons between studies more feasible.
An Alternative Fixation Technique for the Treatment of Comminuted Intra-Articular Distal Clavicle Fractures Using Contoured Reconstruction Bridging Plate
Authors: Abdelhamed Romeih Mohamed , Elsoudany Hossam A.
Published: November 2024

Background:

Comminuted intra-articular distal end clavicular fractures are rare type fractures, which cannot be fixed with standard fixation methods. This work aimed to study an alternative fixation technique for the treatment of comminuted intra-articular distal clavicle fractures using the contoured reconstruction bridging plate.

Methods:

The prospective study was conducted from August 2017 and March 2023 on 17 patients with highly comminuted intra-articular distal end clavicular fractures (Robinson type 3B2), managed by ORIF using a contoured reconstruction plate with coracoclavicular screws augmentation through the plate, bridging the AC joint in the age group of 18 to 50 years. Functional outcomes were evaluated at the final follow-up 12 months after plate removal, which was done after the full union of the fracture, using the modified shoulder score for distal clavicle fractures.

Results:

Time until the achievement of radiologic union ranged from 6 to 20 weeks (mean=15.8). Postoperative complications were superficial infection in 5.88% of patients and hardware symptoms in 5.88% of patients. Satisfactory results were excellent in 58.82% of patients and good in 41.18% of patients. The mean modified shoulder score was 16.2 at the final follow-up of 12 months after plate removal.

Conclusion:

In comminuted intra-articular distal end clavicular fractures which are not amenable for fixation with the standard methods, we recommend using a low-profile contoured reconstruction plate bridging the AC joint, with coracoclavicular screws augmentation as an alternative method of fixation with satisfactory results to restore normal anatomy, preserve AC joint motion, and reduce arthritic changes.
A Novel Rat Model to Simulate Positive Margins in the Wound Bed of a Resected Sarcoma
Authors: Singh Gurtej , Kaymakcalan Omer , Hays Thomas R. , Abbas Adam , Sridevan Sruthi , Kaur Jasleen , Rathi Sourish , Marquez Jocellie , Ghazizadeh Soosan , Tavernier Felix , Boyce Brendan F. , Khan Sami U. , Khan Fazel A. , Bui Duc T. , Dagum Alexander B.
Published: November 2024

Background:

One reason for local recurrence is the presence of positive surgical margins after tumor resection. An animal model accurately representing the microtumor burden will improve our understanding of these surgical margins. Using a rat model, we report a new methodology for creating microscopic tumors.

Methods:

Four different cell densities (1000, 10,000, 100,000, and 500,000 cells) of virus-induced Rous sarcoma XC cells (ATCC CCL-165) were topically added to 1.0 cm × 1.0 cm full-thickness wounds of male Rowett nude rats. Both Tegaderm and Tensoplast were then used to dress the wounds. After 9 days, the wound beds were excised, stained with hematoxylin and eosin, and analyzed using National Institutes of Health Image J software.

Results:

Better healing of the wound beds was observed for the smaller 2 cell densities (1000 and 10,000) as opposed to the higher 2 densities (100,000 and 500,000). The 2 higher cell density groups had gross identifiable tumors that extended deep through the dermis. On the other hand, the smaller cell density groups had microscopic tumor masses. Inflammation was present in all groups irrespective of the initial tumor cell densities, whereas hemorrhage was present only in the 2 higher cell density groups.

Conclusions:

This methodology can create a clinically relevant scenario of positive surgical margins after tumor resection. This induction method is simple, reasonably quick to use, and requires minimal surgical expertise. This approach could also develop microscopically positive margins for a much more comprehensive array of cancers.
Exploring Information Needs and Educational Preferences of Individuals Referred to Cardiac Rehabilitation Before Program Start
Authors: Delgado Bomtempo Ana Paula , Konidis Renee , Aultman Crystal , Barry-Hickey Danielle , Ghisi Gabriela Lima de Melo
Published: November 2024

Purpose:

To explore information needs and educational preferences of individuals referred to cardiac rehabilitation (CR) before program start.

Methods:

This cross-sectional study was conducted from June 2023 to February 2024. Referred patients were contacted via email, which included a link to a website providing information about the CR program, and instructional videos. Data were collected through surveys that assessed health literacy levels, information needs (using the short version of the Information Needs in CR), frequently asked questions, delivery preferences, and engagement/satisfaction with educational resources.

Results:

Throughout the study period, the CR center received 2571 referrals, of which 881 individuals were eligible for the study, and 467 (mean age 66.4 ± 12.2 years; 36% women) consented and completed questionnaires. Information needs were highest for CR and diagnosis/treatment and lowest for nutrition and risk factors. The study revealed significant differences in the perceived importance of information needs across various sociodemographic and clinical characteristics, including age (P = .01), educational level (P = .009), work status (P = .04), main reason for CR referral (P < .001), and health literacy (P = .02). Moreover, participants identified key areas of interest and concern related to their CR journey. These included inquiries about safe exercise initiation, pre-stress test instructions, and personalized exercise plans, among others. It was also observed that the majority of participants engaged with the educational materials provided and indicated high levels of satisfaction.

Conclusion:

This study revealed patient preferences regarding educational content, delivery format, and areas of interest/concern related to CR prior to program start, providing valuable insights for improving the delivery and effectiveness of such programs.
Effect of Exercise-Based Cardiac Rehabilitation on Patients With Chronic Heart Failure After Transcatheter Aortic Valve Replacement
Authors: Song Jingjin , Chen Xiang , Wang Bin , Cheng Ye , Wang Yan
Published: November 2024

Purpose:

The objective of this study was to assess the effect of exercise-based cardiac rehabilitation (CR) with individualized exercise prescription in patients with chronic heart failure (HF) undergoing transcatheter aortic valve replacement (TAVR) in a randomized controlled trial.

Methods:

A total of 60 patients with chronic HF who received TAVR treatment were randomly divided into the control group (n = 30) and exercise training (ET) group (n = 30). The control group was treated with conventional rehabilitation, and the ET group was given personalized exercise-based CR based on a cardiopulmonary exercise test (CPX). The CPX parameters, echocardiography, 6-minute walk test distance, and quality of life were evaluated in the two groups.

Results:

All patients who completed symptom-restricted CPX showed no complications. After the 12-week rehabilitation period, the levels of anaerobic threshold, peak oxygen uptake, peak oxygen pulse, peak power, left ventricular ejection fraction, and 6-minute walk test distance in the ET group were significantly higher than those in the control group (P < .05). Scores on the Minnesota Life with Heart Failure Questionnaire in the ET group were lower than those in the control group (P < .05).

Conclusion:

Exercise-based CR significantly improves cardiopulmonary function, exercise tolerance, and quality of life in patients with chronic HF who undergo TAVR.
Assessing the risk of postnatal depression in mothers receiving the health visiting service: a best practice implementation project
Authors: Holland Amanda , Raymond Rachel , Jones Kim
Published: November 2024

Objectives:

The project aimed to assess health visitors’ concordance with evidence-based criteria regarding identification and support of postnatal depression in mothers receiving the health visiting service.

Introduction:

Timely identification is critical to support mothers at risk of postnatal depression. Undetected and untreated postnatal depression can result in severe consequences for the mother's health, infant health and development, and well-being of the family as a whole. Due to their unique role of universal home visiting, health visitors are ideally placed to identify and support mothers, and evidence-based practice is key to positive outcomes.

Methods:

A baseline audit was carried out using evidence-based audit and feedback informed by the JBI Model for EBHC and guided by the seven-phase implementation framework, involving 12 health visitors and 60 health visiting records from one health board in Wales, UK. The first step involved project development and generating evidence. A baseline audit was completed and a training program on perinatal and infant mental health was implemented. Finally, a post-implementation audit was completed involving 6 health visitors and 30 health visiting records.

Results:

Receiving training in perinatal and infant mental health resulted in an improvement in baseline audit results. Health visitor concordance with best practice guidelines increased, with three of the six criteria in the post-implementation audit reaching 100% concordance, and two other criteria increasing to 83% and 93%, respectively.

Conclusion:

The implementation project achieved improvements in concordance with best practice recommendations for identifying and supporting mothers experiencing, or at risk of experiencing, postnatal depression.

Spanish abstract:

http://links.lww.com/IJEBH/A293
What is beautiful is still good: the attractiveness halo effect in the era of beauty filters
Authors: Gulati Aditya , Martínez-Garcia Marina , Fernández Daniel , Lozano Miguel Angel , Lepri Bruno , Oliver Nuria
Published: November 2024

The impact of cognitive biases on decision-making in the digital world remains under-explored despite its well-documented effects in physical contexts. This paper addresses this gap by investigating the attractiveness halo effect using AI-based beauty filters. We conduct a large-scale online user study involving 2748 participants who rated facial images from a diverse set of 462 distinct individuals in two conditions: original and attractive after applying a beauty filter. Our study reveals that the
same
individuals receive statistically significantly higher ratings of attractiveness and other traits, such as intelligence and trustworthiness, in the attractive condition. We also study the impact of age, gender and ethnicity and identify a weakening of the halo effect in the beautified condition, resolving conflicting findings from the literature and suggesting that filters could mitigate this cognitive bias. Finally, our findings raise ethical concerns regarding the use of beauty filters.
Modulating Prefrontal Cortex Activity to Alleviate Stress-Induced Working Memory Deficits: A Transcranial Direct Current (tDCS) Study
Authors: Roy Sumit , Fan Yan , Mosayebi Samani Mohsen , Claus Maren , Yavari Fatemeh , Kleinsorge Thomas , Nitsche Michael A.
Published: November 2024

This study explores the impact of stress on working memory (WM) performance, and the potential mitigating effects of transcranial direct current stimulation (tDCS) over the left dorsolateral prefrontal cortex (dlPFC) and ventromedial prefrontal cortex (vmPFC). The study had a crossover, randomized, single-blind, sham-controlled design, with stress induction as within-subject and stimulation condition as between-subject factors. We assessed stress-induced WM deficits using aversive video clips to induce stress and a verbal n-back task to assess WM performance. We analyzed physiological (cortisol and heart rate), behavioral, and electroencephalographic (EEG) changes due to stress before, during, and after WM task performance and their modulation by tDCS. Stress impaired WM performance in the sham stimulation condition for the 3-back load, but not for 2-back or 4-back loads in the WM task, and was associated with elevated physiological stress markers. tDCS over the vmPFC led to better WM task performance while stimulation over the dlPFC did not. Active tDCS with both dlPFC and vmPFC stimulation blunted cortisol release in stress conditions compared to sham. The EEG analysis revealed potential mechanisms explaining the behavioral effects of vmPFC stimulation. vmPFC stimulation led to a decreased P200 event-related potential (ERP) component compared to the sham stimulation condition and resulted in higher task-related alpha desynchronization, indicating reduced distractions and better focus during task performance. This study thus shows that the vmPFC might be a potential target for mitigating the effects of stress on WM performance, and contributes to the development of targeted interventions for stress-related cognitive impairments.
Exercise intensity shapes acute and prolonged immune and extracellular vesicle responses in older adults
Authors: Garza Alejandra P. , Morton Lorena , Motsch Anna-Lena , Puta Christian , Stiebler Marvin , Lading Yves , Schreiber Stefanie , Braun-Dullaeus Rüdiger , Müller Patrick , Dunay Ildiko R.
Published: November 2024

Regular physical activity is a cornerstone of healthy aging, offering a wide range of benefits, including the modulation of immune regulation and reduction of chronic inflammation. With aging closely linked to persistent, low-grade inflammation, i.e. inflammaging, the effects of exercise intensity on acute immune responses in older adults remain not fully understood. In this study, we explored how moderate and intense acute continuous exercise impact immune cell activation, cytokine production and large extracellular vesicle (lEV) release in healthy elderly individuals. Fourteen participants completed a moderate continuous exercise intervention (60% VO2maxfor 30 minutes), while nineteen engaged in an intense continuous exercise session until exhaustion. Blood samples were collected at baseline, and at 1- and 24-hours post-exercise. Immune cell characterization by flow cytometry revealed distinct changes in monocyte subsets and NK cells activation across both exercise intensities. Intense exercise was associated with elevated proinflammatory TNFα levels, accumulation of circulating plasma-derived lEV and changes in their surface marker expression after 24 hours. Additionally, we identified sex-specific differences, including distinct activation profiles in innate immunity, alterations in EV release from CD4+and HLA+ cells, and an exercise-induced increase in IL-6 observed exclusively in females. These findings suggest that moderate continuous acute exercise enhances immune cell activation without altering cell counts, while intense continuous exercise triggers acute proinflammatory immune response. Further research should clarify the long-term implications and fundamental mechanisms of exercise-induced immune modulation in aging populations.

Key points summary

Diminished immune function upon aging is increasing disease risk. This study examines how tailored acute exercise interventions stimulate immune regulation in older adults addressing age-related inflammatory challenges.

Acute continuous moderate and intense exercise elicit distinct immune responses in elderly individuals with marked differences between sexes. Interestingly, IL-6 levels increased 30 min moderate exercise exclusively in females.

Exercise promotes the release of extracellular vesicles (EVs) and modulates peripheral immunity, suggesting a potent mechanism by which physical activity supports immune resilience in aging.

Tailored acute exercise regimens for older adults may enhance immune health, mitigating age-related inflammatory risks and enhancing resilience.

This study emphasizes the need for further research on exercise-driven modulation focusing on sex differences and their implications for targeted interventions upon aging.
An epigenetic basis for sustained inflammatory epithelial progenitor cell states in Crohn’s disease
Authors: Karakasheva Tatiana A. , Morral Martinez Clara , Zhou Yusen , Qui Jingya , Chen Xinyi E. , Soto Gloria E. , Nettleford Shaneice K. , Hix Olivia T. , Roach Daana M. , Laguerta Alyssa M. , Thadi Anusha , Edwards Rachael M. , Aleynick Daniel , Weinbrom Sarah , Borodyanskaya Elizaveta , Pickering Oliver H. , Fulton MaryKate , Chen Chia-Hui , Peterson Bella V. , Hagen Erik B. , Yannuzzi Ian P. , Haider Zainab , Cramer Zvi , Conrad Maire , Li Ning , Bewtra Meenakshi , Uzun Yasin , Tan Kai , Kelsen Judith R. , Minn Andy J. , Lengner Christopher J. , Hamilton Kathryn E.
Published: November 2024

Defining consequential differences in intestinal epithelial stem cells in healthy humans versus those with inflammatory bowel disease (Crohn’s disease and ulcerative colitis) is essential for the development of much needed therapies to restore the epithelial barrier and maintain its fidelity. Employing single cell transcriptomic/epigenomic approaches and colonoid models from children and adults with Crohn’s disease led us to identify an inflammatory secretory progenitor (ISP) cell state present almost exclusively in patients with Crohn’s disease compared to control subjects. ISPs exhibit gene expression profiles consistent with normal secretory progenitor cells but concomitantly express a suite of distinguishing pro-inflammatory genes. Mechanistically, ISPs exhibit open chromatin and gene expression of ISP signature genes. While these ISP-specific genes are not expressed in intestinal stem cells, their chromatin is accessible in Crohn’s disease stem cells suggesting that ISP genes are epigenetically poised in stem cells and are transcriptionally activated in ISP cells in the presence of inflammatory stimuli. Consistently, Crohn’s disease colonoids exhibit sustained ISP gene expression that can be elicited further with pro-inflammatory cytokines or via co-culture with pro-inflammatory macrophages. In summary, we define differences in the epithelial stem and progenitor compartment of patients with Crohn’s disease suggesting aberrant stem cell differentiation and inflammatory gene expression arises during disease.

HIGHLIGHTS

We identify an inflammatory secretory progenitor cell state in endoscopically non-inflamed tissue from pediatric and adult patients with Crohn’s disease.

Crohn’s disease epithelial stem and progenitor cells display increased chromatin accessibility preceding the emergence of inflammatory secretory progenitor cell states.

Crohn’s disease colonoids from non-inflamed regions contain inflammatory secretory progenitor cells in the absence of inflammatory stimuli

Inflammatory secretory progenitor cells expand in colonoid culture in response to cytokine stimulation or co-culture with pro-inflammatory macrophages
Characterizing cytosine methylation of polymorphic human transposable element insertions using human pangenome resources
Authors: Zhuo Xiaoyu , Tomlinson Chad , Belter Edward A. , Kuntala Prashant Kumar , Saintilnord Wesley N. , Lindsay Tina , Macias Juan , Fulton Robert S. , Wang Ting
Published: November 2024

Cytosine methylation is an important epigenetic modification that plays a crucial role in genomic regulation. The conventional second generation sequencing based bisulfite conversion methods used to interrogate cytosine methylation require comparing bisulfited-treated reads with a reference genome for methylation calling. Therefore, it cannot characterize the methylation of unaligned regions. Taking advantage of the recent improvement of the third generation sequencing, we investigated the methylation pattern of human lymphoblastoid cell lines (LCLs) of non-reference insertions from the human population, with a focus on polymorphic transposable elements. We first characterized whole-genome CpG methylation using both SMRT and nanopore technology and benchmarked their performance against WGBS using five human LCLs included in the draft Human Pangenome Reference. Both methods are highly correlated with the conventional WGBS results across the genome. The level of differences between PacBio and ONT on the same sample is comparable with that of two replicates of WGBS of the same sample. Using long-read data from the draft Human Pangenome Reference, we characterized CpG methylation of non-reference insertions, especially polymorphic transposable elements. We focused on addressing two questions: 1) do newly inserted TEs adopt the methylation pattern of their genomic context? and 2) do methylation spread from new TE insertions to their flanking regions? We found that most non-TE insertions exhibit DNA methylation pattern consistent with their genomic context, but TE insertions are consistently methylated, with a few exceptions. We also found limited methylation spreading from Alu/L1 insertions to their flanking genomic regions. We investigated INDEL frequency in both hypermethylated and hypomethylated CpG islands and found INDELs are enriched in hypermethylated CpG islands. Our work demonstrated the methylation calling capability of the 3rd generation sequencing and its unique advantage in characterizing epigenomic features within non-reference positions.
TMVisDB: Annotation and 3D-visualization of transmembrane proteins
Authors: Olenyi Tobias , Marquet Céline , Grekova Anastasia , Houri Leen , Heinzinger Michael , Dallago Christian , Rost Burkhard
Published: November 2024

Since the rise of cellular life, transmembrane proteins (TMPs) have been crucial to various cellular processes through their central role as gates and gatekeepers. Despite their importance, experimental high-resolution structures for TMPs remain underrepresented due to experimental challenges. Given its performance leap, structure predictions have begun to close the gap. However, identifying the membrane regions and topology in three-dimensional structure files on a large scale still requires additionalin silicopredictions. Here, we introduceTMVisDBto sieve through millions of predicted structures for TMPs. This resource enables both browsing through 46 million predicted TMPs and visualizing them along with their topological annotations without having to tap into costly predictions of the AlphaFold3-style.TMVisDBjoinsAlphaFoldDBstructure predictions and transmembrane topology predictions from the protein language model (pLM) based methodTMbed. We showcase the utility of TMVisDB for the analysis of proteins through two use cases, namely the B-lymphocyte antigen CD20(Homo sapiens) and the cellulose synthase (Novosphingobium sp. P6W). We demonstrate the value ofTMVisDBfor large-scale analyses through findings pertaining to all TMPs predicted for the human proteome. TMVisDB is freely available athttps://tmvisdb.rostlab.org
Shroom3-Rock interaction and profibrotic function: Resolving mechanism of an intronic CKD risk allele
Authors: Reghuvaran Anand , Kumar Ashwani , Lin Qisheng , Rajeevan Nallakandi , Sun Zeguo , Shi Hongmei , Barsotti Gabriel , Tanvir EM , Pell John , Perincheri Sudhir , Wei Chengguo , Planoutene Marina , Eichmann Anne , Mas Valeria , Zhang Weijia , Das Bhaskar , Cantley Lloyd , Xu Leyuan , He Cijiang John , Menon Madhav C
Published: November 2024

Common intronic enhancer SNPs in Shroom3 associate with CKD in GWAS, although there is paucity of detailed mechanism. Previously, we reported a role for Shroom3 in mediating crosstalk between TGFβ1- & Wnt/Ctnnb1 pathways promoting renal fibrosis (TIF). However, beneficial roles for Shroom3 in proteinuria have also been reported suggesting pleiotropic effects. Here we focused on identifying the specific profibrotic Shroom3 motif. Given known therapeutic roles for Rho-kinase inhibitors in experimental CKD, and the established interaction between Shroom3 and Rock via its ASD2 domain, we hypothesized that Shroom3-mediated ROCK activation played a crucial role in its profibrotic function in high expressors. To test this hypothesis, we developed transgenic mice and cell lines that inducibly overexpressed wild-type- (WT-Sh3) or ASD2-domain deletion- Shroom3 (ASD2Δ-Sh3). Prior scRNAseq data showed that during TIF, Shroom3 and Rock co-expression occurred in injured tubular cells and fibroblasts, highlighting cell-types where this mechanism could be involved. Using HEK293T cells, we first confirmed absent ROCK binding and inhibited TGFβ1-signaling with ASD2Δ-Sh3-overexpression vs WT-Sh3. In mIMCD cells, ASD2Δ-Sh3 overexpression, reduced Rock activation (phospho-MYPT1), pro-fibrotic and pro-inflammatory transcripts vs WT-Sh3. Fibroblast proliferation (3T3) was also reduced with ASD2Δ-Sh3.In vivo, we studied ureteric obstruction (UUO) and Aristolochic nephropathy (AAN) as TIF models. In AAN, inducible global-, or Pan-tubular specific-, WTSh3-overexpression showed increased azotemia, and TIF vs ASD2Δ-Sh3 mice. WT-Sh3 mice consistently showed significant enrichment of Rho-GTPase, TGFβ1- and Wnt/CtnnB1- signaling in kidney transcriptome, paralleling Shroom3-coexpressed genes in tubulo-interstitial transcriptomes from human CKD. In UUO, again WT-Sh3 mice recapitulated increased fibrosis vs ASD2Δ-Sh3. Importantly, ASD2Δ-Sh3 did not develop albuminuria vs WT-Sh3, while mutating a disparate Fyn-binding Shroom3 motif induced albuminuria in mice, suggesting motif-specific roles for Shroom3 in the kidney. Hence, our data show a critical role for the Rock-binding, ASD2-domain in mediating TIF in milieu of Shroom3 excess, with relevance to human CKD.
Social isolation reduces metabolic rate and social preference in Wild-type Zebrafish(Danio rerio)
Authors: Ghosh Arpita , Rao Aakash Madhav , Middha Prarthna , Rai Shambhavi , Rajaraman Bittu Kaveri
Published: November 2024

The adaptive and maladaptive effects of social isolation in various animal models, especially under pathogen stress, have generated particular interest since the COVID-19 pandemic. We examined metabolic, social and movement outcomes induced by a month of visual and olfactory social isolation in adult wild-type zebrafish. Our primary interest was examining metabolic savings and changes in social preference, with movement reduction as a manipulation check for effective social isolation. We found that socially isolated fish demonstrated a significant decrease in metabolic rate, social preference and average speed of movement compared to the pre-intervention baseline. The reduction in metabolic rate could lead to contextually beneficial energy expenditure savings for the fish; however, the more mixed effects of reduced social preference and average speed of movement might only be helpful in environments with a high predatory threat and high food and mate abundance. This study opens up various possibilities to explore the adaptive significance of social isolation in various ecological frameworks.
Host specificity of gastrointestinal parasites in free-ranging sloths from Costa Rica
Authors: Vanderhoeven Ezequiel A. , Florida Madeleine G. , Cliffe Rebecca , Guzman José , Notarnicola Juliana , Kartzinel Tyler R.
Published: November 2024

The diversity and host specificity of gastrointestinal parasites infecting free-ranging sloths is poorly known. We characterized gastrointestinal parasites of two sloth species from Costa Rica— three-fingered sloth (Bradypus variegatus) and two-fingered sloth (Choloepus hoffmanni)—for the first time in both a primary forest and an urban habitat. We asked whether host-parasite interactions were predominantly structured by host identity, the habitats in which hosts occurred, or both. Protozoa and nematode eggs were present in both species, but cestode eggs were recorded only inC. hoffmanni. We found eight parasitic morphotypes, which matches the total number of parasite taxa described in sloths over the past 100 years, and these first reports of gastrointestinal parasites of sloths from primary forest radically expand our knowledge of the general diversity and host specificity of sloth parasites. We found no significant difference in overall parasite richness between sloth species or habitats, but the parasite richness ofC. hoffmanniwas 2-fold greater in the primary forest vs. urban habitat. As no parasite sharing was observed between sloth species, we found strong and significant differences in parasite composition between host species regardless of habitat. InB. variegatus, we observed eggs of four nematode taxa (Spirocercidae, Subuluroidea, Spirurida, Ascaridida) and cysts of Eimeriidae (Apicomplexa). By contrast, inC. hoffmanni, we observed cestodes (Anoplocephalidae), a different nematode from the family Spirocercidae and also cysts of Eimeriidae (Apicomplexa). Many rare taxa were recorded only in samples from the primary forest, and these did not match any sloth parasites that had been previously described in the literature, suggesting that at least some could be undescribed species. Together, these results highlight the need for further research in comparative wildlife parasitology, the characterization of host-parasite transmission networks, and the identification of any intermediate hosts that may be relevant to sloth health.