Search bioRxiv⌕ Search

Biology subjects

Jastrzebski, M.

Publications and source records attributed to Jastrzebski, M..

5 recordsLinked to original sources

Using a GPT-5-driven autonomous lab to optimize the cost and titer of cell-free protein synthesis

We used an autonomous lab, comprising a large language model (LLM) and a fully automated cloud laboratory, to optimize the cost efficiency of cell-free protein synthesis (CFPS). By conducting iterative optimization, the LLM-driven autonomous lab was able to achieve a 40% reduction in the specific cost ($/g protein) of CFPS relative to the state of the art (SOTA). This cost reduction was accompanied by a 27% increase in protein production titer (g/L). Iterative experimental design, experiment execution, data capture and analysis, data interpretation, and new hypothesis generation were all handled by the LLM-driven autonomous lab. The interface between OpenAIs GPT-5 LLM and Ginkgo Bioworks cloud laboratory incorporated built-in validation checks via a Pydantic schema to ensure that AI-designed experiments were properly specified. Experimental designs were translated into programmatic specification of multi-instrument biological workflows by Ginkgos Catalyst software and executed on Ginkgos Reconfigurable Automation Cart (RAC) laboratory automation platform, with human intervention largely limited to reagent and consumables preparation, loading and unloading. By integrating LLMs with programmatic control of a cloud lab, we demonstrate that an LLM-driven autonomous lab can successfully perform a real-world scientific task, highlighting the potential of AI-driven autonomous labs for scientific advancement.

synthetic biology↗

Programmed deep septal pacing for the diagnosis of left bundle branch capture.

BackgroundDuring permanent deep septal pacing, it is important to confirm left bundle branch (LBB) capture.\n\nObjectiveThe effective refractory period (ERP) of the working myocardium is different than the ERP of the LBB; we hypothesized that it should be possible to differentiate LBB capture from septal myocardial capture using programmed extra-stimulus technique.\n\nMethodsIn consecutive patients undergoing pacemaker implantation who received pacing lead in a deep septal position programmed pacing was delivered from this lead. Responses to programmed pacing were categorized on the basis of QRS morphology of the extrastimuli as: myocardial (broader QRS, often slurred), selective (narrower QRS, preceded by an isoelectric interval) or non-diagnostic (unequivocal change).\n\nResultsProgrammed deep septal pacing was performed 269 times in 143 patients; in every patient with the use of an 8-beat basic drive train of 600 ms and when possible also during supraventricular rhythm. Responses diagnostic for LBB capture were observed in 114 (79.7%) of patients. Selective LBB paced QRS was more often seen when premature beats were introduced during the intrinsic rhythm rather than after the basic drive train. The average septal-myocardial refractory period was significantly shorter than the LBB refractory period: 263.0{+/-}34.4 ms vs. 318.0{+/-}37.4 ms.\n\nConclusionsA novel maneuver for the diagnosis of LBB capture during deep septal pacing, was formulated, assessed and found as diagnostically valuable. This method, based on the differences in refractoriness between LBB and the septal myocardium is unique in enabling the visualization of components of the usually fused, non-selective LBB paced QRS complex.\n\nGraphical abstract O_FIG_DISPLAY_L [Figure 1] M_FIG_DISPLAY C_FIG_DISPLAY

physiology↗

Electrocardiographic characterization of non-selective His bundle pacing. Validation of novel diagnostic criteria.

AimsPermanent His bundle (HB) pacing is usually accompanied by simultaneous capture of the adjacent right ventricular (RV) myocardium - this is described as a non-selective (ns)-HB pacing. Our aim was to identify ECG criteria for loss of HB capture during ns-HB pacing.\n\nMethodsConsecutive patients with permanent HB pacing were recruited. Surface 12-lead ECGs during ns-HB pacing and loss of HB capture (RV-only capture) were obtained. ECG criteria for loss/presence of HB capture were identified. In the validation phase these criteria and the \"HB ECG algorithm\" were tested by two blinded observers using a separate, sizable set of ECGs.\n\nResultsA total of 353 ECG (226 ns-HB and 128 RV-only) were obtained from 226 patients with permanent HB pacing devices. QRS notch/slur in left ventricular leads and R-wave peak time in lead V6 were identified as the best features for differentiation. The 2-step HB ECG algorithm based on these features correctly classified 87.1% of cases with sensitivity and specificity of 93.2% and 83.9%, respectively. Moreover, the proposed criteria for definitive diagnosis of ns-HB capture (no QRS slur/notch in leads I, V1, V4-V6 and the R-wave peak time in V6 [≤] 100 ms) presented 100% specificity.\n\nConclusionA novel ECG algorithm for the diagnosis of loss of HB capture and novel criteria for definitive confirmation of HB capture were formulated and validated. Practical application of these criteria during implant and follow-up of patients with HB pacing devices is feasible.\n\nCondensed AbstractThe 2-step ECG algorithm for loss of His bundle capture based on surface ECG analysis is proposed and validated. This method correctly classified 87.1% of cases with a sensitivity and specificity of 93.2% and 83.9%, respectively.\n\nWhats NewO_LIThis is the first study that analyzes QRS characteristics during non-selective His bundle pacing in a sizable cohort of patients.\nC_LIO_LIPrecise criteria and a novel algorithm for electrocardiographic diagnosis of loss of HB capture during presumed non-selective HB pacing were validated.\nC_LIO_LIQRS notch/slur in left ventricular leads was identified as a simple and reproducible feature indicating loss of HB capture or lack/loss of correction of intraventricular conduction disturbances.\nC_LIO_LIAssessment of R-wave peak time in lead V6 rather than QRS duration for diagnosis of ns-HB pacing was validated.\nC_LI

physiology↗

His bundle has shorter chronaxie than adjacent ventricular myocardium: Implications for pacemaker programming.

BackgroundStrength-duration curves for permanent His bundle (HB) pacing are potentially important for pacemaker programming.\n\nObjectiveWe aimed to calculate strength-duration curve and chronaxie of the His bundle (HB) and of the adjacent right ventricular (RV) working myocardium and to analyze zones of selective HB capture and battery current drain when pacing at different pulse durations (PDs).\n\nMethodsConsecutive patients with permanent HB pacing were studied. The RV and HB capture thresholds were assessed at several PDs. Battery current drain and zones of selective HB capture at PDs of 0.1, 0.2, 0.4 and 1.0 ms were determined.\n\nResultsIn the whole group (n =127) the HB chronaxie was shorter than the RV chronaxie. This difference was driven by patients with selective HB pacing (HB chronaxie of 0.47 vs RV chronaxie of 0.79 ms). Strength-duration curve for HB had lower rheobase and its steep portion started at shorter PDs thus creating wider distance - zone of programmable selective HB pacing - between the HB and RV strength-duration curves at shorter PDs. The battery current drain was lower with pacing at PDs of 0.1 - 0.4 ms vs 1.0 ms. Chronaxie adjusted PDs offered lowest current drain.\n\nConclusionFor the first time the strength-duration curves for permanent selective and non-selective HB pacing were determined. Selective HB capture and battery longevity can be promoted by shorter PDs (0.2 ms). Longer PDs (1.0 ms) offer bigger safety margin for RV capture and may be preferable if simultaneous RV capture during HB pacing is desired.\n\n\n\nO_FIG O_LINKSMALLFIG WIDTH=198 HEIGHT=200 SRC=\"FIGDIR/small/623348v1_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (66K):\norg.highwire.dtl.DTLVardef@9f7f35org.highwire.dtl.DTLVardef@15870e4org.highwire.dtl.DTLVardef@15bbdbdorg.highwire.dtl.DTLVardef@5f434_HPS_FORMAT_FIGEXP M_FIG C_FIG

physiology↗

Programmed His bundle pacing - a novel maneuver for the diagnosis of His bundle capture

BackgroundDuring permanent non-selective (ns) His bundle (HB) pacing, it is crucial to confirm HB capture / exclude that only right ventricle (RV)-myocardial septal pacing is present. Because the effective refractory period (ERP) of the working myocardium is different than the ERP of the HB, we hypothesized that it should be possible to differentiate ns-HB capture from RV-myocardial capture using programmed extra-stimulus technique.\n\nMethodsIn consecutive patients during HB pacemaker implantation, programmed HB pacing was delivered from the screwed-in HB pacing lead. Premature beats were introduced at 10 ms steps during intrinsic rhythm and also after a drive train of 600 ms. The longest coupling interval that resulted in an abrupt change of QRS morphology was considered equal to ERP of HB or RV-myocardium.\n\nResultsProgrammed HB pacing was performed from 50 different sites in 32 patients. In 34/36 cases of ns-HB pacing, the RV-myocardial ERP was shorter than HB ERP (271.8{+/-}38 ms vs 353.0{+/-}30 ms, p < 0.0001). Programmed HB pacing using a drive train resulted in a typical abrupt change of paced QRS morphology: from ns-HB to RV-myocardial QRS (34/36 cases) or to selective HB QRS (2/36 cases). Programmed HB pacing delivered during supraventricular rhythm resulted in obtaining selective HB QRS in 20/34 and RV-myocardial QRS in 14/34 of the ns-HB cases. In RV-myocardial only pacing cases (\"false ns-HB pacing\", n=14), such responses were not observed - the QRS morphology remained stable. Therefore, the PHB pacing correctly diagnosed all ns-HB cases and all RV-myocardial pacing cases.\n\nConclusionsA novel maneuver for the diagnosis of HB capture, based on the differences in ERP between HB and myocardium was formulated, assessed and found as diagnostically valuable. This method is unique in enabling to visualize selective HB QRS in patients with otherwise obligatory ns-HB pacing (RV-myocardial capture threshold < HB capture threshold).\n\nWhat this study addsO_LIProgrammed His bundle pacing - a novel and straightforward method for unquestionable diagnosis of His bundle capture during non-selective pacing was developed and assessed.\nC_LIO_LIA method for visualization of selective HB capture QRS in patients with obligatory non-selective pacing (myocardial capture threshold < His bundle capture threshold) was discovered and physiology behind it explained.\nC_LI

physiology↗