App-based assessment of memory functions in patients after transfemoral aortic valve replacement

BACKGROUND Transfemoral aortic valve replacement(TAVR)is the standard treatment for elderly patients with aortic valve stenosis.Although safe and well-established,there is a risk of intraprocedural hemodynamic instability and silent cerebral embolism,which can lead to a decline in neurocognitive function and dementia.In clinical practice,comprehensive cognitive testing is difficult to perform.AI-assisted digital applications may help to optimize diagnosis and monitoring.METHODS Neurocognitive function was assessed by validated psychometric tests using“Δelta-App”,which uses artificial intelligence and computational linguistic methods for extraction and analysis.Memory function was assessed using the‘Consortium to Establish a Registry for Alzheimer’s Disease’(CERAD)word list and digit span task(DST)before TAVR and before hospital discharge.The study is registered in the German Register of Clinical Trials(https://drks.de/search/de/trial/DRKS00020813).RESULTS From October 2020 until March 2022,141 patients were enrolled at University Hospital Heart Centre Brandenburg.Mean age was 81±6 years,42.6%were women.Time between the pre-and post-interventional test was on average 6±3 days.Memory function before TAVR was found to be below average in relation to age and educational level.The pre-post TAVR comparison showed significant improvements in the wordlist repeat,P<0.001 and wordlist recall test of CERAD,P<0.001.There were no changes in the digital span test.CONCLUSIONS Despite impaired preoperative memory function before TAVR,no global negative effect on memory function after TVAR was detected.The improvements shown in the word list test should be interpreted as usual learning effects in this task.

A MoClo-Compatible Toolbox of ECF Sigma Factor-Based Regulatory Switches for Proteobacterial Chassis

The construction of complex synthetic gene circuits with predetermined and reliable output depends on orthogonal regulatory parts that do not inadvertently interfere with the host machinery or with other circuit components.Previously,extracytoplasmic function sigma factors(ECFs),a diverse group of alternative sigma factors with distinct promoter specificities,were shown to have great potential as context-independent regulators,but so far,they have only been used in a few model species.Here,we show that the alphaproteobacterium Sinorhizobium meliloti,which has been proposed as a plant-associated bacterial chassis for synthetic biology,has a similar phylogenetic ECF acceptance range as the gammaproteobacterium Escherichia coli.A common set of orthogonal ECF-based regulators that can be used in both bacterial hosts was identified and used to create 2-step delay circuits.The genetic circuits were implemented in single copy in E.coli by chromosomal integration using an established method that utilizes bacteriophage integrases.In S.meliloti,we demonstrated the usability of single-copy pABC plasmids as equivalent carriers of the synthetic circuits.The circuits were either implemented on a single pABC or modularly distributed on 3 such plasmids.In addition,we provide a toolbox containing pABC plasmids compatible with the Golden Gate(MoClo)cloning standard and a library of basic parts that enable the construction of ECF-based circuits in S.meliloti and in E.coli.This work contributes to building a context-independent and species-overarching ECF-based toolbox for synthetic biology applications.