Biology subjects

Razavi, M.

Publications and source records attributed to Razavi, M..

7 recordsLinked to original sources

bioRxiv2026

Design of a Conductive Hydrogel Coating to Improve Catheter-Tissue Coupling in Radiofrequency Ablation

Radiofrequency ablation is a mainstay of cardiac rhythm management despite high recurrence rates. Current radiofrequency ablation catheters are limited by poor contact with trabeculated cardiac tissue that promotes uneven heating with hot spots that cause collateral damage and regions of incomplete ablation that promote recurrence. Herein, we report on a conductive hydrogel coating of radiofrequency ablation catheters to improve tissue contact while promoting efficient energy transfer. A method was developed to graft a polyether urethane diacrylamide hydrogel to the distal tip of the catheter that maintained stable adhesion following drying, sterilization, and rehydration. The coating also remained intact after passage through an introducer sheath and 50 cycles of radiofrequency ablation at clinical power. The hydrogel-coated catheter demonstrated enhanced tissue contact that was dependent on hydrogel modulus. Hydrogel-mediated ablation prevented steam pop incidence and generated homogeneous lesions in an ex vivo ablation model; however, increased hydrogel conductivity is needed to achieve comparable lesion dimensions as the bare metal catheter and prevent coating damage at higher power. Collectively, these results establish a tunable hydrogel coating method that addresses limitations of conventional radiofrequency ablation and offers a promising approach to enhance the safety and efficacy of cardiac ablation therapies.

bioengineering↗

bioRxiv2026

Structure-informed Siamese graph neural networks classify CirA missense variants with implications for cefiderocol susceptibility

Cefiderocol uptake in Enterobacterales depends partly on TonB-dependent catecholate transporters, including CirA, yet the functional interpretation of CirA missense variation remains limited by an absence of large experimental phenotype datasets. Here we describe a structure-informed Siamese graph neural network (GNN) framework designed to prioritise CirA missense variants that are likely to impair transporter function and thereby contribute to reduced cefiderocol susceptibility. Because large experimental datasets of CirA missense phenotypes are not available, we trained the model on a synthetic mutant set generated from structurally motivated rules applied to the CirA reference structure (AlphaFold model, UniProt P17315). Each residue was represented using protein language model embeddings, backbone geometry, and amino-acid identity, and paired wild-type and mutant graphs were compared through a shared encoder. On synthetic held-out benchmarks, the model achieved strong classification performance on a position-held-out split (macro-F1 = 0.989 against synthetic labels). Applied to a collection of Escherichia coli CirA protein sequences, the framework prioritised a subset of variants as high-confidence non-benign candidates and assigned many others to review or abstain categories, reflecting predictive uncertainty outside the synthetic training distribution. A post-hoc severity-ranking scheme triages disruptive candidates for follow-up. This framework demonstrates that structure-informed synthetic data generation paired with Siamese GNN inference can bridge the gap between sequence-level genomic surveillance and mechanistic functional prediction of outer-membrane transporter variants.

bioinformatics↗

bioRxiv2023

Eliminating steam pops and improving lesion safety in atrial ablation with conductive hydrogels

BackgroundAtrial fibrillation (AF) is a significant burden worldwide, and the existing treatments leave much to be desired. There are, however, opportunities to improve the safety and efficacy of the most popular treatment, radiofrequency (RF) cardiac ablation, using conductive hydrogels as an ablation mediator. MethodsLesions were created in ex vivo ventricular tissues using bare metal traditional RF catheters and three different hydrogels with varying conductivities to assess the effect of conductivity on lesion formation. Similar procedures were performed in atrial/esophageal tissue stacks to mimic physiological AF ablation and demonstrate the initial safety profile of conductive hydrogel-mediated ablation. ResultsThe hydrogel mediated lesions were overall shallower and narrower than bare metal, and also exhibited less char and improved lesion homogeneity. The hydrogel also eliminated steam pops. Finally, the hydrogel appeared to be more thermally protective of the esophagus in the atrial/esophageal tissue stack, greatly reducing the lesion formation on the esophagus while still achieving transmural lesions in the atrial tissue. ConclusionsHydrogel-mediated RF ablation holds promise as a novel method to improve ablation outcomes for AF patients. Future work will confirm this in vivo and establish the chemistry required to create a conductive hydrogel coating for RF ablation catheters.

bioengineering↗

bioRxiv2022

Doomed by popularity: The broad use of the Pm8 resistance gene in wheat resulted in hypermutation of the AvrPm8 gene in the powdery mildew pathogen

O_LIThe Pm8 resistance gene against the powdery mildew disease has been introgressed from rye into wheat as part of a large 1BL.1RS chromosomal translocation. Due to its high agronomic value, this translocation has seen continuous global use since the 1960s on large growth areas, even after Pm8 resistance was overcome. This allows studying the effect of long and widespread resistance gene use on a pathogen population. C_LIO_LIUsing genome wide association studies in a global population of wheat mildew isolates, we identified the avirulence effector AvrPm8 specifically recognized by Pm8. C_LIO_LIHaplovariant mining in the global population revealed 17 virulent haplotypes of the AvrPm8 gene that grouped into two categories. The first one from geographically diverse regions comprised two single amino acid polymorphisms at the same position in the AvrPm8 protein, which we confirmed to be crucial for recognition by Pm8. The second category consisted of numerous destructive mutations to the AvrPm8 open reading frame. C_LIO_LIMost individual gain-of-virulence mutations were found in geographically restricted regions, indicating they occurred recently as a consequence of the frequent Pm8 use. We conclude that both standing genetic variation as well as locally occurring new mutations contributed to the global breakdown of the Pm8 resistance gene introgression. C_LI

plant biology↗

bioRxiv2021

Towards prevention of re-entrant arrhythmias: Injectable hydrogel electrodes enable direct capture of previously inaccessible cardiac tissues

Re-entrant arrhythmias--the leading cause of sudden cardiac death--are caused by diseased myocardial tissue and consequent delayed myocardial conduction. Access to the coronary veins that cross the "culprit" scar regions where re-entry originates can provide improved pacing to these delayed regions, offering a novel opportunity to prevent ventricular arrhythmias and circumvent the need for painful defibrillation, risky cardiac ablation, or toxic and often ineffective antiarrhythmic medications. However, there are no pacing electrodes which are small or focal enough to navigate these tributaries. To address this need, we have developed an injectable conductive hydrogel that can fill the epicardial coronary veins and their mid-myocardial tributaries. When connected to a standard pacing lead, these injected hydrogels can be converted into flexible electrodes that directly pace the previously inaccessible mid-myocardial tissue. In our two-component system, hydrogel precursor solutions can be injected through a dual lumen catheter in a minimally invasive deployment strategy to provide direct access to the diseased regions with precision and ease. Mixing of the two solutions upon injection into the vein activates redox-initiated crosslinking of the gel for rapid in situ cure without an external stimulus. An ex vivo porcine model was used to identify the requisite viscosity and cure rate for gel retention and homogeneity. Ionic species added to the hydrogel precursor solutions conferred conductivity above target myocardium values that was retained after implantation. Successful in vivo deployment demonstrated that the hydrogel electrode filled the anterior interventricular vein with extension into the septal (mid-myocardial) venous tributaries to depths far more distal and refined than any current technologies allow. In addition to successful capture and pacing of the heart, analysis of surface ECG tracings revealed a novel pacing observation highly specific for and suggestive of capture of extensive swaths of septal myocardial tissue. This is the first report of an injectable electrode used to successfully pace the mid-myocardium and mimic physiologic conduction. Furthermore, in vivo cardiac electroanatomical mapping studies in an ablation scar model showed uniform capture along the hydrogel in the vessels as well as increased capture area compared to point pacing. Collectively, these findings demonstrate that this injectable hydrogel electrode can be deployed to scarred regions of the heart to provide a reliable pacing modality that most closely resembles native conduction with the potential to eliminate delayed myocardial conduction and associated re-entry. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=179 SRC="FIGDIR/small/467102v2_ufig1.gif" ALT="Figure 1"> View larger version (50K): org.highwire.dtl.DTLVardef@1577526org.highwire.dtl.DTLVardef@cc510dorg.highwire.dtl.DTLVardef@1dd426eorg.highwire.dtl.DTLVardef@1346aab_HPS_FORMAT_FIGEXP M_FIG C_FIG One Sentence SummaryInjectable hydrogel electrodes achieve pacing that mimics physiologic conduction by capturing midmyocardial tissue

bioengineering↗

bioRxiv2020

Multimodal-Multisensory Experiments: Design and Implementation

The human mind is multimodal. Yet most behavioral studies rely on century-old measures of behavior - task accuracy and latency (response time). Multimodal and multisensory analysis of human behavior creates a better understanding of how the mind works. The problem is that designing and implementing these experiments is technically complex and costly. This paper introduces versatile and economical means of developing multimodal-multisensory human experiments. We provide an experimental design framework that automatically integrates and synchronizes measures including electroencephalogram (EEG), galvanic skin response (GSR), eye-tracking, virtual reality (VR), body movement, mouse/cursor motion and response time. Unlike proprietary systems (e.g., iMotions), our system is free and open-source; it integrates PsychoPy, Unity and Lab Streaming Layer (LSL). The system embeds LSL inside PsychoPy/Unity for the synchronization of multiple sensory signals - gaze motion, electroencephalogram (EEG), galvanic skin response (GSR), mouse/cursor movement, and body motion - with low-cost consumer-grade devices in a simple behavioral task designed by PsychoPy and a virtual reality environment designed by Unity. This tutorial shows a step-by-step process by which a complex multimodal-multisensory experiment can be designed and implemented in a few hours. When conducting the experiment, all of the data synchronization and recoding of the data to disk will be done automatically.

neuroscience↗

bioRxiv2019

Multiplexed measurement of protein biomarkers in high-frequency longitudinal dried blood spot (DBS) samples: characterization of inflammatory responses

A detailed understanding of changes in blood protein biomarkers occuring in individuals over time would enable truly personalized approaches to health and disease monitoring. Such measurements could reveal smaller, earlier departures from normal baseline levels of biomarkers thus allowing better disease detection and treatment monitoring. Current practice, however, generally involves infrequent, sporadic biomarker testing, and this undersampling likely fails to capture important biological phenomena. Here we report the use of a robust multiplex immuno-mass spectrometric method (SISCAPA) to measure a panel of clinically-relevant proteins in a unique collection of 1,522 dried blood spots collected longitudinally by 8 individuals over periods of up to 9 years, with daily sampling during some intervals. Analytical workflow CVs of 2-6% for most assays were achieved by normalizing DBS plasma volume using a set of 3 minimally varying proteins, facilitating temporal analysis of both high- and low-amplitude biomarker changes compared to personalized baselines. The biomarkers included a panel of 9 positive and 5 negative acute phase response (inflammatory) proteins, allowing longitudinal analysis of inflammation markers associated with major and minor infections, influenza vaccination, recovery from hip-replacement surgery and Crohns disease. The results illustrate complex time-dependent \"biomarker trajectories\" on multiple timescales and provide a basis for detailed personalized models of inflammation dynamics. The striking stability of most biomarker protein levels over time, combined with the convenience of self-sampling and low cost of multiplexed measurements using mass spectrometry, provide a new window into the temporal dynamics of disease processes. The extensive results obtained using this high throughput approach offer a new source of precision biomarker big data amenable to machine learning approaches and application to more personalized health monitoring.

systems biology↗