The rigidity and relatively primitive modes of operation of catheters equipped with sensing or actuation elements impede their conformal contact with soft-tissue surfaces, limit the scope of their uses, lengthen surgical times and increase the need for advanced surgical skills. Here, we report materials, device designs and fabrication approaches for integrating advanced electronic functionality with catheters for minimally invasive forms of cardiac surgery. By using multiphysics modelling, plastic heart models and Langendorff animal and human hearts, we show that soft electronic arrays in multilayer configurations on endocardial balloon catheters can establish conformal contact with curved tissue surfaces, support high-density spatiotemporal mapping of temperature, pressure and electrophysiological parameters and allow for programmable electrical stimulation, radiofrequency ablation and irreversible electroporation. Integrating multimodal and multiplexing capabilities into minimally invasive surgical instruments may improve surgical performance and patient outcomes.Minimally invasive surgeries involve the insertion of advanced diagnostic and therapeutic tools through small percutaneous incisions for treatment of cardiovascular diseases, cancers and other health conditions, with fast recovery times and low risks compared with those of conventional procedures 1,2 . Catheters represent one of the most compelling devices for such purposes due to their capabilities in deploying medical devices (for example, intravascular stents or heart-valve prostheses), capturing information during surgical procedures (for example, force, temperature or electrograms) and/or delivering forces, electromagnetic energy, thermal stimuli and/or biomaterials (for example, drugs, cells or nanoparticles) to targeted sites on or within soft tissues 3,4 . Although these catheter-based approaches have widespread uses in modern medicine, they suffer from (1) mechanical rigidity or insufficient compliance, leading to non-ideal interfaces with soft tissues and low coupling efficiency 5 , Han et al.

The COVID-19 pandemic has resulted in an alarming increase in hate incidents directed toward Asian Americans and Pacific Islanders (AAPIs), including verbal harassment and physical assault, spurring the nationwide #StopAsianHate movement. This rise in anti-Asian sentiment is occurring at a critical time of racial reckoning across the United States, galvanized by the Black Lives Matter movement, and of medical student calls for the implementation of antiracist medical curricula. AAPIs are stereotyped by the model minority myth, which posits that AAPIs are educated, hardworking, and therefore able to achieve high levels of success. This myth acts as a racial wedge between minorities and perpetuates harm that is pervasive throughout the field of medicine. Critically, the frequent aggregation of all AAPI subgroups as one monolithic community obfuscates socioeconomic and cultural differences across the AAPI diaspora while reinforcing the model minority myth. Here, the authors illustrate how the model minority myth and data aggregation have negatively affected the recruitment and advancement of diverse AAPI medical students, physicians, and faculty. Additionally, the authors discuss how data aggregation obscures health disparities across the AAPI diaspora and how the model minority myth influences the illness experiences of AAPI patients. Importantly, the authors outline specific actionable policies and reforms that medical schools can implement to combat anti-Asian sentiment and support the AAPI community.

Ly6 proteins are endogenous prototoxins found in most animals. They show striking structural and functional parallels to snake α-neurotoxins, including regulation of ion channels and cholinergic signaling. However, the structural contributions of Ly6 proteins to regulation of effector molecules is poorly understood. This question is particularly relevant to the Ly6 protein QUIVER/SLEEPLESS (QVR/SSS), which has previously been shown to suppress excitability and synaptic transmission by upregulating potassium (K) channels and downregulating nicotinic acetylcholine receptors (nAChRs) in wake-promoting neurons to facilitate sleep in Drosophila. Using deletion mutagenesis, co-immunoprecipitations, ion flux assays, surface labeling and confocal microscopy, we demonstrate that only loop 2 is required for many of the previously described properties of SSS in transfected cells, including interactions with K channels and nAChRs. Collectively our data suggest that QVR/SSS, and by extension perhaps other Ly6 proteins, target effector molecules using limited protein motifs. Mapping these motifs may be useful in rational design of drugs that mimic or suppress Ly6-effector interactions to modulate nervous system function.

α7 nicotinic acetylcholine receptors (nAChRs) are widely expressed in the brain where they promote fast cholinergic synaptic transmission and serve important neuromodulatory functions. However, their high permeability to Ca2+also predisposes them to contribute to disease states. Here, using transfected HEK-tsa cells and primary cultured hippocampal neurons from male and female rats, we demonstrate that two proteins called Ly6h and NACHO compete for access to α7 subunits, operating together but in opposition to maintain α7 assembly and activity within a narrow range that is optimal for neuronal function and viability. Using mixed gender human temporal cortex and cultured hippocampal neurons from rats we further show that this balance is perturbed during Alzheimer's disease (AD) because of amyloid β (Aβ)-driven reduction in Ly6h, with severe reduction leading to increased phosphorylated tau and α7-mediated neurotoxicity. Ly6h release into human CSF is also correlated with AD severity. Thus, Ly6h links cholinergic signaling, Aβ and phosphorylated tau and may serve as a novel marker for AD progression.SIGNIFICANCE STATEMENTOne of the earliest and most persistent hypotheses regarding Alzheimer's disease (AD) attributes cognitive impairment to loss of cholinergic signaling. More recently, interest has focused on crucial roles for amyloid β (Aβ) and phosphorylated tau in Alzheimer's pathogenesis. Here, we demonstrate that these elements are linked by Ly6h and its counterpart, NACHO, functioning in opposition to maintain assembly of nicotinic acetylcholine receptors (nAChRs) within the physiological range. Our data suggests that Aβ shifts the balance away from Ly6h and toward NACHO, resulting in increased assembly of Ca2+-permeable nAChRs and thus a conversion of basal cholinergic to neurotoxic signaling.