Wireless Battery-free and Fully Implantable Organ Interfaces.

Advances in soft materials, miniaturized electronics, sensors, stimulators, radios, and battery-free power supplies are resulting in a new generation of fully implantable organ interfaces that leverage volumetric reduction and soft mechanics by eliminating electrochemical power storage. This device class offers the ability to provide high-fidelity readouts of physiological processes, enables stimulation, and allows control over organs to realize new therapeutic and diagnostic paradigms. Driven by seamless integration with connected infrastructure, these devices enable personalized digital medicine. Key to advances are carefully designed material, electrophysical, electrochemical, and electromagnetic systems that form implantables with mechanical properties closely matched to the target organ to deliver functionality that supports high-fidelity sensors and stimulators. The elimination of electrochemical power supplies enables control over device operation, anywhere from acute, to lifetimes matching the target subject with physical dimensions that supports imperceptible operation. This review provides a comprehensive overview of the basic building blocks of battery-free organ interfaces and related topics such as implantation, delivery, sterilization, and user acceptance. State of the art examples categorized by organ system and an outlook of interconnection and advanced strategies for computation leveraging the consistent power influx to elevate functionality of this device class over current battery-powered strategies is highlighted.

Biosymbiotic platform for chronic long-range monitoring of biosignals in limited resource settings.

Remote patient monitoring is a critical component of digital medicine, and the COVID-19 pandemic has further highlighted its importance. Wearable sensors aimed at noninvasive extraction and transmission of high-fidelity physiological data provide an avenue toward at-home diagnostics and therapeutics; however, the infrastructure requirements for such devices limit their use to areas with well-established connectivity. This accentuates the socioeconomic and geopolitical gap in digital health technology and points toward a need to provide access in areas that have limited resources. Low-power wide area network (LPWAN) protocols, such as LoRa, may provide an avenue toward connectivity in these settings; however, there has been limited work on realizing wearable devices with this functionality because of power and electromagnetic constraints. In this work, we introduce wearables with electromagnetic, electronic, and mechanical features provided by a biosymbiotic platform to realize high-fidelity biosignals transmission of 15 miles without the need for satellite infrastructure. The platform implements wireless power transfer for interaction-free recharging, enabling long-term and uninterrupted use over weeks without the need for the user to interact with the devices. This work presents demonstration of a continuously wearable device with this long-range capability that has the potential to serve resource-constrained and remote areas, providing equitable access to digital health.

Fully implanted battery-free high power platform for chronic spinal and muscular functional electrical stimulation.

Electrical stimulation of the neuromuscular system holds promise for both scientific and therapeutic biomedical applications. Supplying and maintaining the power necessary to drive stimulation chronically is a fundamental challenge in these applications, especially when high voltages or currents are required. Wireless systems, in which energy is supplied through near field power transfer, could eliminate complications caused by battery packs or external connections, but currently do not provide the harvested power and voltages required for applications such as muscle stimulation. Here, we introduce a passive resonator optimized power transfer design that overcomes these limitations, enabling voltage compliances of ± 20 V and power over 300 mW at device volumes of 0.2 cm2, thereby improving power transfer 500% over previous systems. We show that this improved performance enables multichannel, biphasic, current-controlled operation at clinically relevant voltage and current ranges with digital control and telemetry in freely behaving animals. Preliminary chronic results indicate that implanted devices remain operational over 6 weeks in both intact and spinal cord injured rats and are capable of producing fine control of spinal and muscle stimulation.

happi: a hierarchical approach to pangenomics inference.

Recovering metagenome-assembled genomes (MAGs) from shotgun sequencing data is an increasingly common task in microbiome studies, as MAGs provide deeper insight into the functional potential of both culturable and non-culturable microorganisms. However, metagenome-assembled genomes vary in quality and may contain omissions and contamination. These errors present challenges for detecting genes and comparing gene enrichment across sample types. To address this, we propose happi, an approach to testing hypotheses about gene enrichment that accounts for genome quality. We illustrate the advantages of happi over existing approaches using published Saccharibacteria MAGs, Streptococcus thermophilus MAGs, and via simulation.

Hybrid staged approach to subclavian artery aneurysm repair with aberrant dominant left vertebral artery.

Intrathoracic subclavian aneurysms are a rare entity, accounting for only a small percentage of all repaired aneurysms. These are repaired to alleviate symptoms and prevent complications of rupture, thrombosis and distal embolization. Most of these are amenable to thoracic endovascular aneurysm repair (TEVAR), which has resulted in an associated reduction in operative mortality. When there is a proximal involvement of the artery, revascularization is recommended prior to TEVAR. Herein, we present the case of a proximal subclavian aneurysm with an aberrant left vertebral artery that originated off the aortic arch. This was repaired using a two staged approach; carotid-subclavian bypass with vertebral artery-transposition followed by TEVAR.

Protamine use in transcarotid arterial revascularization.

OBJECTIVE: The literature suggests that heparin reversal with protamine in transcarotid arterial revascularization (TCAR) decreases postoperative bleeding complications without an increase in stroke or death. However, the dosing of protamine in TCAR has not yet been evaluated. We aimed to evaluate our experience with intraoperative heparin reversal with protamine. METHODS: This was a single-center, retrospective, observational study that evaluated the heparin and protamine doses used during TCAR. All adult patients who underwent TCAR between 9/1/2019 and 4/2/2021 were included. Demographic data was obtained from the Vascular Quality Initiative and protamine/heparin doses were obtained from a chart review. Multivariate logistic regression models were used to assess the association between the protamine/heparin dose ratio and other variables. RESULTS: Sixty-two patients were included. The average protamine/heparin dose ratio used was 0.96 ± 0.12 mg/U; seven had a ratio less than 0.8 mg/U, and one was greater than 1.2 mg/U. Two patients experienced bleeding complications, which were managed non-operatively. No patient with a protamine/heparin ratio greater than 0.8 mg/U had postoperative bleeding. Postoperative bradycardia was observed in 32.3% of patients and hypotension in 35%, with 19% requiring vasopressors. No relationship was identified between the protamine/heparin ratio and bleeding, bradycardia, or hypotension. No 30-day myocardial infarction, stroke or death occurred. CONCLUSIONS: We identified a near 1:1 ratio of a protamine/heparin dosing regimen for the reversal of heparin during TCAR, with postoperative bleeding complications similar to those reported in the literature. However, patients who received a lower protamine/heparin ratio did not experience bleeding complications. In the era of protamine shortages, a future larger-scale study is needed to evaluate the impact of a lower protamine dose on postoperative complications.

Wireless, fully implantable cardiac stimulation and recording with on-device computation for closed-loop pacing and defibrillation.

Monitoring and control of cardiac function are critical for investigation of cardiovascular pathophysiology and developing life-saving therapies. However, chronic stimulation of the heart in freely moving small animal subjects, which offer a variety of genotypes and phenotypes, is currently difficult. Specifically, real-time control of cardiac function with high spatial and temporal resolution is currently not possible. Here, we introduce a wireless battery-free device with on-board computation for real-time cardiac control with multisite stimulation enabling optogenetic modulation of the entire rodent heart. Seamless integration of the biointerface with the heart is enabled by machine learning-guided design of ultrathin arrays. Long-term pacing, recording, and on-board computation are demonstrated in freely moving animals. This device class enables new heart failure models and offers a platform to test real-time therapeutic paradigms over chronic time scales by providing means to control cardiac function continuously over the lifetime of the subject.

Within-City Variation in Ambient Carbon Monoxide Concentrations: Leveraging Low-Cost Monitors in a Spatiotemporal Modeling Framework.

BACKGROUND: Based on human and animal experimental studies, exposure to ambient carbon monoxide (CO) may be associated with cardiovascular disease outcomes, but epidemiological evidence of this link is limited. The number and distribution of ground-level regulatory agency monitors are insufficient to characterize fine-scale variations in CO concentrations. OBJECTIVES: To develop a daily, high-resolution ambient CO exposure prediction model at the city scale. METHODS: We developed a CO prediction model in Baltimore, Maryland, based on a spatiotemporal statistical algorithm with regulatory agency monitoring data and measurements from calibrated low-cost gas monitors. We also evaluated the contribution of three novel parameters to model performance: high-resolution meteorological data, satellite remote sensing data, and copollutant (PM2.5, NO2, and NOx) concentrations. RESULTS: The CO model had spatial cross-validation (CV) R2 and root-mean-square error (RMSE) of 0.70 and 0.02 parts per million (ppm), respectively; the model had temporal CV R2 and RMSE of 0.61 and 0.04 ppm, respectively. The predictions revealed spatially resolved CO hot spots associated with population, traffic, and other nonroad emission sources (e.g., railroads and airport), as well as sharp concentration decreases within short distances from primary roads. DISCUSSION: The three novel parameters did not substantially improve model performance, suggesting that, on its own, our spatiotemporal modeling framework based on geographic features was reliable and robust. As low-cost air monitors become increasingly available, this approach to CO concentration modeling can be generalized to resource-restricted environments to facilitate comprehensive epidemiological research. https://doi.org/10.1289/EHP10889.

Evaluating replicability in microbiome data.

High-throughput sequencing is widely used to study microbial communities. However, choice of laboratory protocol is known to affect the resulting microbiome data, which has an unquantified impact on many comparisons between communities of scientific interest. We propose a novel approach to evaluating replicability in high-dimensional data and apply it to assess the cross-laboratory replicability of signals in microbiome data using the Microbiome Quality Control Project data set. We learn distinctions between samples as measured by a single laboratory and evaluate whether the same distinctions hold in data produced by other laboratories. While most sequencing laboratories can consistently distinguish between samples (median correct classification 87% on genus-level proportion data), these distinctions frequently fail to hold in data from other laboratories (median correct classification 55% across laboratory on genus-level proportion data). As identical samples processed by different laboratories generate substantively different quantitative results, we conclude that 16S sequencing does not reliably resolve differences in human microbiome samples. However, because we observe greater replicability under certain data transformations, our results inform the analysis of microbiome data.

Segment number threshold determines juvenile onset of germline cluster expansion in Platynereis dumerilii.

Development of sexual characters and generation of gametes are tightly coupled with growth. Platynereis dumerilii is a marine annelid that has been used to study germline development and gametogenesis. P. dumerilii has germ cell clusters found across the body in the juvenile worms, and the clusters eventually form the gametes. Like other segmented worms, P. dumerilii grows by adding new segments at its posterior end. The number of segments reflect the growth state of the worms and therefore is a useful and measurable growth state metric to study the growth-reproduction crosstalk. To understand how growth correlates with progression of gametogenesis, we investigated germline development across several developmental stages. We discovered a distinct transition period when worms increase the number of germline clusters at a particular segment number threshold. Additionally, we found that keeping worms short in segment number, by manipulating environmental conditions or via amputations, supported a segment number threshold requirement for germline development. Finally, we asked if these clusters in P. dumerilii play a role in regeneration (as similar free-roaming cells are observed in Hydra and planarian regeneration) and found that the clusters were not required for regeneration in P. dumerilii, suggesting a strictly germline nature. Overall, these molecular analyses suggest a previously unidentified developmental transition dependent on the growth state of juvenile P. dumerilii leading to substantially increased germline expansion.

Cardiopulmonary resuscitation in quaternary neonatal intensive care units: a multicenter study.

BACKGROUND: The reported incidence of cardiopulmonary resuscitation (CPR) in quaternary NICU is approximately 10-times higher than in the delivery room. However, the etiologies and outcomes of CPR in quaternary NICUs are poorly understood. We hypothesized that demographic characteristics, diagnoses, interventions, and arrest etiologies would be associated with survival to discharge after CPR. METHODS: Multicenter retrospective cohort study of four quaternary NICUs over six years (2011-2016). Demographics, resuscitation event data, and post-arrest outcomes were analyzed. The primary outcome was survival to discharge. RESULTS: Of 17,358 patients admitted to four NICUs, 200 (1.1%) experienced a CPR event, and 45.5% of those survived to discharge. Acute respiratory compromise leading to cardiopulmonary arrest occurred in 182 (91%) of the CPR events. Most neonates requiring CPR were on mechanical ventilation (79%) and had central venous access (90%) at the time of arrest. Treatments at the time of the arrest associated with decreased survival to discharge included mechanical ventilation, antibiotics, or vasopressor therapy (p < 0.01). Etiologies of arrest associated with decreased survival to discharge included multisystem organ failure, septic shock, and pneumothorax (p < 0.05). Longer duration of CPR was associated with decreased survival to discharge. The odds of surviving to discharge decreased for infants who had a primarily cardiac arrest and for infants who received epinephrine during the arrest. CONCLUSION: Approximately 1% of neonates admitted to quaternary NICUs require CPR. The most common etiology of arrest is acute respiratory compromise on a ventilator. CPR events with respiratory etiology have a favorable outcome as compared to non-respiratory causes.

A Genomic Analysis of Factors Driving lincRNA Diversification: Lessons from Plants.

Transcriptomic analyses from across eukaryotes indicate that most of the genome is transcribed at some point in the developmental trajectory of an organism. One class of these transcripts is termed long intergenic noncoding RNAs (lincRNAs). Recently, attention has focused on understanding the evolutionary dynamics of lincRNAs, particularly their conservation within genomes. Here, we take a comparative genomic and phylogenetic approach to uncover factors influencing lincRNA emergence and persistence in the plant family Brassicaceae, to which Arabidopsis thaliana belongs. We searched 10 genomes across the family for evidence of > 5000 lincRNA loci from A. thaliana From loci conserved in the genomes of multiple species, we built alignments and inferred phylogeny. We then used gene tree/species tree reconciliation to examine the duplication history and timing of emergence of these loci. Emergence of lincRNA loci appears to be linked to local duplication events, but, surprisingly, not whole genome duplication events (WGD), or transposable elements. Interestingly, WGD events are associated with the loss of loci for species having undergone relatively recent polyploidy. Lastly, we identify 1180 loci of the 6480 previously annotated A. thaliana lincRNAs (18%) with elevated levels of conservation. These conserved lincRNAs show higher expression, and are enriched for stress-responsiveness and cis-regulatory motifs known as conserved noncoding sequences (CNSs). These data highlight potential functional pathways and suggest that CNSs may regulate neighboring genes at both the genomic and transcriptomic level. In sum, we provide insight into processes that may influence lincRNA diversification by providing an evolutionary context for previously annotated lincRNAs.

A versatile integrating sphere based photoacoustic sensor for trace gas monitoring.

A compact versatile photoacoustic (PA) sensor for trace gas detection is reported. The sensor is based on an integrating sphere as the PA absorption cell with an organ pipe tube attached to increase the sensitivity of the PA sensor. The versatility and enhancement of the sensitivity of the PA signal is investigated by monitoring specific ro-vibrational lines of CO(2) in the 2 µm wavelength region and of NO(2) in the 405 nm region. The measured enhancement factor of the PA signal exceeds 1200, which is due to the acoustic resonance of the tube and the absorption enhancement of the integrating sphere relatively to a non-resonant single pass cell. It is observed that the background absorption signals are highly attenuated due to the thermal conduction and diffusion effects in the polytetrafluoroethylene cell walls. This demonstrates that careful choice of cell wall materials can be highly beneficial to the sensitivity of the PA sensor. These properties makes the sensor suitable for various practical sensor applications in the ultraviolet (UV) to the near infrared (NIR) wavelength region, including climate, environmental and industrial monitoring.

Cavity-enhanced optical frequency comb spectroscopy: application to human breath analysis.

Broad-bandwidth, high-spectral-resolution optical detection of human breath has identified multiple important biomarkers correlated with specific diseases and metabolic processes. This optical-frequency-comb-based breath analysis system comes with excellent performance in all criteria: high detection sensitivity, ability to identify and distinguish a large number of analytes, and simultaneous, real-time information processing. We demonstrate a minimum detectable absorption of 8 x 10(-10)cm(-1), a spectral resolution of 800 MHz, and 200 nm of spectral coverage from 1.5 to 1.7 microm where strong and unique molecular fingerprints exist for many biomarkers. We present a series of breath measurements including stable isotope ratios of CO(2), breath concentrations of CO, and the presence of trace concentrations of NH(3) in high concentrations of H(2)O.