A User's Guide to Machine Learning for Polymeric Biomaterials.

The development of novel biomaterials is a challenging process, complicated by a design space with high dimensionality. Requirements for performance in the complex biological environment lead to difficult a priori rational design choices and time-consuming empirical trial-and-error experimentation. Modern data science practices, especially artificial intelligence (AI)/machine learning (ML), offer the promise to help accelerate the identification and testing of next-generation biomaterials. However, it can be a daunting task for biomaterial scientists unfamiliar with modern ML techniques to begin incorporating these useful tools into their development pipeline. This Perspective lays the foundation for a basic understanding of ML while providing a step-by-step guide to new users on how to begin implementing these techniques. A tutorial Python script has been developed walking users through the application of an ML pipeline using data from a real biomaterial design challenge based on group's research. This tutorial provides an opportunity for readers to see and experiment with ML and its syntax in Python. The Google Colab notebook can be easily accessed and copied from the following URL: www.gormleylab.com/MLcolab.

Republished:Aspiration catheter failure leading to carotid-cavernous fistula during stroke thrombectomy.

Endovascular thrombectomy in acute ischaemic stroke commonly uses aspiration catheters, either alone or in combination with stent retrievers. The Penumbra Aspiration System (Penumbra, Alameda, California, USA) was first approved by the US Food and Drug Administration in 2007, with low reported device-related complications. We present a case of a previously unreported complication related to malfunction of a Penumbra aspiration catheter during stroke thrombectomy resulting in a carotid-cavernous fistula.

Comparative Analysis of Radiology Trainee Burnout Using the Maslach Burnout Inventory and Oldenburg Burnout Inventory.

BACKGROUND: Burnout is an individualized response to imbalances between job demands and resources that has predominantly been evaluated with the Maslach Burnout Inventory (MBI). There are other instruments not validated among healthcare providers that may be comparable to the MBI. Utilizing alternative measurements can allow researchers to assess wellness with a larger array of questions. OBJECTIVE: We explored differences between the MBI- Human Services Survey for Medical Personnel (MBI-HSS [MP]) and Oldenburg Burnout Inventory (OLBI) in evaluating emotional exhaustion (EE)/exhaustion and depersonalization (DP)/disengagement. METHODS: We administered the MBI-HSS (MP) and OLBI to United States (US) radiology trainees during three,1-month intervals in April 2018, October 2018, and April 2019. Student's T-tests or ANOVA was used to evaluate differences between demographic groups and burnout scores in the MBI-HSS (MP) and OBLI. Non-inferiority analysis was completed to evaluate if the OBLI was not inferior to the MBI-HSS (MP) in how its subscales measure exhaustion and disengagement. The MBI-HSS (MP) subtotals for EE and DP were compared with the OLBI scores for exhaustion and disengagement using two-tailed paired T-tests for each trainee. RESULTS: Of 2823 trainees emailed, 770 (27.3%) responded. The mean EE Maslach score was 21/54, and the mean DP Maslach score was 8/30. The average OBLI exhaustion and disengagement score was 2.38 and 2.22, respectively. Comparative analysis of completed MBI-HSS (MP) and OLBI subscales yielded no significant difference between the EE/exhaustion (t(496)=1.038; p=0.30) or DP/disengagement (t(498)=0.084; p=0.933) subscales. CONCLUSIONS: Our national study of radiology trainees demonstrated that the OLBI was not inferior in assessing exhaustion and disengagement to the EE and DP subscales of the MBI-HSS (MP).

Martini 3 Coarse-Grained Force Field for Carbohydrates.

The Martini 3 force field is a full reparametrization of the Martini coarse-grained model for biomolecular simulations. Due to the improved interaction balance, it allows for a more accurate description of condensed phase systems. In the present work, we develop a consistent strategy to parametrize carbohydrate molecules accurately within the framework of Martini 3. In particular, we develop a canonical mapping scheme which decomposes arbitrarily large carbohydrates into a limited number of fragments. Bead types for these fragments have been assigned by matching physicochemical properties of mono- and disaccharides. In addition, guidelines for assigning bonds, angles, and dihedrals were developed. These guidelines enable a more accurate description of carbohydrate conformations than in the Martini 2 force field. We show that models obtained with this approach are able to accurately reproduce osmotic pressures of carbohydrate water solutions. Furthermore, we provide evidence that the model differentiates correctly the solubility of the polyglucoses dextran (water-soluble) and cellulose (water insoluble but soluble in ionic liquids). Finally, we demonstrate that the new building blocks can be applied to glycolipids. We show they are able to reproduce membrane properties and induce binding of peripheral membrane proteins. These test cases demonstrate the validity and transferability of our approach.

Massively Parallelized Molecular Force Manipulation with On-Demand Thermal and Optical Control.

In single-molecule force spectroscopy (SMFS), a tethered molecule is stretched using a specialized instrument to study how macromolecules extend under force. One problem in SMFS is the serial and slow nature of the measurements, performed one molecule at a time. To address this long-standing challenge, we report on the origami polymer force clamp (OPFC) which enables parallelized manipulation of the mechanical forces experienced by molecules without the need for dedicated SMFS instruments or surface tethering. The OPFC positions target molecules between a rigid nanoscale DNA origami beam and a responsive polymer particle that shrinks on demand. As a proof-of-concept, we record the steady state and time-resolved mechanical unfolding dynamics of DNA hairpins using the fluorescence signal from ensembles of molecules and confirm our conclusion using modeling.

The Path of Most Resistance: A Rare Instance of Metastatic Pancreatic Adenocarcinoma Identified Within Skeletal Muscle.

Soft tissue neoplastic metastases, specifically to the skeletal muscle, are uncommon in comparison to metastases within the abdomen, thorax, or intracranial regions. Specifically, pancreatic adenocarcinoma with skeletal muscle metastasis is a rare clinical phenomenon and is hardly reported. There is a high mortality rate after the diagnosis of metastatic pancreatic adenocarcinoma, attributed to inadequate screening and advanced staging upon incidental discovery. Rarely, metastatic lesions manifest in the skeletal muscle and are hardly documented. Some of the factors that deter skeletal muscle tumor implantation include the deficiency of skeletal muscle mediators and genetic makeup of the primary tumor. Surgical resection of pancreatic adenocarcinoma with adjuvant chemotherapy demonstrates the best prognosis; however, surgical management is usually limited to patients without known metastatic disease. Alternative treatment options such as chemotherapy and radiotherapy are used in the palliative care setting. Here, we present the case of a patient with previously diagnosed and treated pancreatic adenocarcinoma in remission, with biopsy-proven metastases isolated within the skeletal muscle.

Systematic review of three-dimensional printing for simulation training of interventional radiology trainees.

RATIONALE AND OBJECTIVES: Three-dimensional (3D) printing has been utilized as a means of producing high-quality simulation models for trainees in procedure-intensive or surgical subspecialties. However, less is known about its role for trainee education within interventional radiology (IR). Thus, the purpose of this review was to assess the state of current literature regarding the use of 3D printed simulation models in IR procedural simulation experiences. MATERIALS AND METHODS: A literature query was conducted through April 2020 for articles discussing three-dimensional printing for simulations in PubMed, Embase, CINAHL, Web of Science, and the Cochrane library databases using key terms relating to 3D printing, radiology, simulation, training, and interventional radiology. RESULTS: We identified a scarcity of published sources, 4 total articles, that appraised the use of three-dimensional printing for simulation training in IR. While trainee feedback is generally supportive of the use of three-dimensional printing within the field, current applications utilizing 3D printed models are heterogeneous, reflecting a lack of best practices standards in the realm of medical education. CONCLUSIONS: Presently available literature endorses the use of three-dimensional printing within interventional radiology as a teaching tool. Literature documenting the benefits of 3D printed models for IR simulation has the potential to expand within the field, as it offers a straightforward, sustainable, and reproducible means for hands-on training that ought to be standardized.

Pinpointing the neural signatures of single-exposure visual recognition memory.

Memories of the images that we have seen are thought to be reflected in the reduction of neural responses in high-level visual areas such as inferotemporal (IT) cortex, a phenomenon known as repetition suppression (RS). We challenged this hypothesis with a task that required rhesus monkeys to report whether images were novel or repeated while ignoring variations in contrast, a stimulus attribute that is also known to modulate the overall IT response. The monkeys' behavior was largely contrast invariant, contrary to the predictions of an RS-inspired decoder, which could not distinguish responses to images that are repeated from those that are of lower contrast. However, the monkeys' behavioral patterns were well predicted by a linearly decodable variant in which the total spike count was corrected for contrast modulation. These results suggest that the IT neural activity pattern that best aligns with single-exposure visual recognition memory behavior is not RS but rather sensory referenced suppression: reductions in IT population response magnitude, corrected for sensory modulation.

Predictors Between the Subcomponents of Burnout Among Radiology Trainees.

OBJECTIVE: The aim of this study was to investigate the effect of various predictors on burnout among radiology residents during their training. METHODS: In this cross-sectional analysis, we distributed the Maslach Burnout Index for Medical Personnel (MBI-HSS [MP]) to eligible United States (US) radiology residents. Covariates of interest included age, child status, debt burden, partner status, and self-identified gender. Primary outcomes include MBI-HSS (MP) subcomponent scores - emotional exhaustion (EE), depersonalization (DP), and personal accomplishment (PA). Mann-Whitney tests were used to compare averages between groups. RESULTS: Out of the 770 of 2823 residents (27.3%) who responded, 488 of 770 completed the MBI-HSS (MP). During the R1 year, male sex was associated with marginally higher PA scores (36.5 versus 33.5; P = .029). Having children or a partner was associated with lower EE scores (18.7 versus 26.8, P = .012; 22 versus 28.9, P = .022, respectively) and higher PA scores (37 vs 32.7, P = .024; 35 versus 31.3, P = .039, respectively) among the R3 cohort. Reporting debt < $200,000 was associated with lower EE scores among the R3 (21.2 versus 27.3, P = .028) and R4 (16.4 versus 21.9, P = .033) cohort. DISCUSSION: There are several predictors of burnout that transiently impact residents at different years of training and primarily impact EE or PA, but not DP scores. R3 residents' scores are most sensitive to these covariates.

Exploration of the Relationship Between the Subcomponents of Burnout Throughout Radiology Training.

PURPOSE: The aim of this study was to investigate the relationship between the subcomponents of burnout and year of training among radiology residents. METHODS: In this cross-sectional analysis, the Maslach Burnout Inventory Human Services Survey for Medical Personnel (MBI-HSS [MP]) was distributed to eligible United States (US) radiology residents. Primary outcomes included the MBI-HSS (MP) subcomponents: emotional exhaustion (EE), depersonalization (DP), and personal accomplishment (PA). Multivariate analysis of variance, tests of between-subjects effects, and Tukey post hoc analysis with 95% confidence interval were conducted. RESULTS: A total of 770 of 2,823 residents (27.3%) responded, with 488 of 770 completing the MBI-HSS (MP). There was a statistically significant difference in subcomponent scores between cohorts based on year of training (P < .005) and a statistically significant effect between year of training and EE (P < .05) and DP (P < .005), but not PA. Third-year (R3) residents reported a higher frequency of EE than first-year (R1) residents and a higher frequency of DP than R1 and second-year (R2) residents. Fourth-year (R4) residents reported more DP than R1 residents. CONCLUSIONS: This analysis shows variation in burnout subcomponents during training, with the highest recorded EE and DP means and lowest recorded PA means among R3 residents. Although these findings demonstrate evidence of burnout among radiology residents, mean subcomponent scores for EE (21.3) and DP (8.4) were lower and for PA (35.1) was higher for all trainees than in previous studies assessing radiology residents, which correlates with less burnout. DP was the only subcomponent that remained statistically elevated between matriculating R1 and graduating R4 residents.

Automation and data-driven design of polymer therapeutics.

Polymers are uniquely suited for drug delivery and biomaterial applications due to tunable structural parameters such as length, composition, architecture, and valency. To facilitate designs, researchers may explore combinatorial libraries in a high throughput fashion to correlate structure to function. However, traditional polymerization reactions including controlled living radical polymerization (CLRP) and ring-opening polymerization (ROP) require inert reaction conditions and extensive expertise to implement. With the advent of air-tolerance and automation, several polymerization techniques are now compatible with well plates and can be carried out at the benchtop, making high throughput synthesis and high throughput screening (HTS) possible. To avoid HTS pitfalls often described as "fishing expeditions," it is crucial to employ intelligent and big data approaches to maximize experimental efficiency. This is where the disruptive technologies of machine learning (ML) and artificial intelligence (AI) will likely play a role. In fact, ML and AI are already impacting small molecule drug discovery and showing signs of emerging in drug delivery. In this review, we present state-of-the-art research in drug delivery, gene delivery, antimicrobial polymers, and bioactive polymers alongside data-driven developments in drug design and organic synthesis. From this insight, important lessons are revealed for the polymer therapeutics community including the value of a closed loop design-build-test-learn workflow. This is an exciting time as researchers will gain the ability to fully explore the polymer structural landscape and establish quantitative structure-property relationships (QSPRs) with biological significance.

Aspiration catheter failure leading to carotid-cavernous fistula during stroke thrombectomy.

Endovascular thrombectomy in acute ischaemic stroke commonly uses aspiration catheters, either alone or in combination with stent retrievers. The Penumbra Aspiration System (Penumbra, Alameda, California, USA) was first approved by the US Food and Drug Administration in 2007, with low reported device-related complications. We present a case of a previously unreported complication related to malfunction of a Penumbra aspiration catheter during stroke thrombectomy resulting in a carotid-cavernous fistula.

Live-cell super-resolved PAINT imaging of piconewton cellular traction forces.

Despite the vital role of mechanical forces in biology, it still remains a challenge to image cellular force with sub-100-nm resolution. Here, we present tension points accumulation for imaging in nanoscale topography (tPAINT), integrating molecular tension probes with the DNA points accumulation for imaging in nanoscale topography (DNA-PAINT) technique to map piconewton mechanical events with ~25-nm resolution. To perform live-cell dynamic tension imaging, we engineered reversible probes with a cryptic docking site revealed only when the probe experiences forces exceeding a defined mechanical threshold (~7-21 pN). Additionally, we report a second type of irreversible tPAINT probe that exposes its cryptic docking site permanently and thus integrates force history over time, offering improved spatial resolution in exchange for temporal dynamics. We applied both types of tPAINT probes to map integrin receptor forces in live human platelets and mouse embryonic fibroblasts. Importantly, tPAINT revealed a link between platelet forces at the leading edge of cells and the dynamic actin-rich ring nucleated by the Arp2/3 complex.

Programmable Assembly of Iron Oxide Nanoparticles Using DNA Origami.

Magnetic iron oxide nanoparticles (IONPs) have received significant interest for the use in biomedical applications. The assembly of IONPs into larger superstructures has been used to modify the properties and functionality of these particles. For example, the clustering of IONPs can lead to improvements in MRI contrast generation, changes in heat generation during magnetic fluid hyperthermia, and alterations to pharmacokinetics and biodistribution. Nevertheless, the IONP clustering leads to significant heterogeneity in the assembly. Here, we demonstrate a method for using DNA origami to precisely control the number and positions of IONPs. We also showed how this technique can be used to module the functionality of IONP clusters by showing how MRI contrast generation efficiency can be tuned by altering the number and spacing of IONPs. Finally, we show that these property changes can be dynamically regulated, demonstrating the possibility for this technology to be used in biosensing applications.

Mind the gap: A novel endovascular technique to repair a transected vessel.

Level one trauma centers experience horrific injuries on a regular basis. Blunt or penetrating trauma causing vascular injuries are treated by surgeons and interventional radiologists. When a blood vessel is completely transected, the ends of the vessel retract and vasospasm occurs as a normal survival response. When this phenomenon occurs, it is sometimes impossible to reattach the two ends of the injured vessel by surgical means and a bypass graft is often required. However, from an endovascular perspective, covered stents can serve as a vascular bypass as well. The limiting factor with an endovascular approach is the ability to successfully gain wire access across the injured vessel. The technique described in this manuscript describes a "rendezvous" method of repairing a transected axillosubclavian artery from a high-speed motorcycle accident using a steerable microcatheter. Initially, multiple failed attempts to cross the injured vessel were encountered despite using a wide variety of conventional guidewires and catheters. A steerable microcatheter was then used to safely and effectively navigate more than 15 cm through soft tissue to the opposite end of the vessel. In this critically ill patient, this technique significantly reduced the procedural time when compared to our previous experiences repairing arterial transections using traditional catheters.

Tunable DNA Origami Motors Translocate Ballistically Over µm Distances at nm/s Speeds.

Inspired by biological motor proteins, that efficiently convert chemical fuel to unidirectional motion, there has been considerable interest in developing synthetic analogues. Among the synthetic motors created thus far, DNA motors that undertake discrete steps on RNA tracks have shown the greatest promise. Nonetheless, DNA nanomotors lack intrinsic directionality, are low speed and take a limited number of steps prior to stalling or dissociation. Herein, we report the first example of a highly tunable DNA origami motor that moves linearly over micron distances at an average speed of 40 nm/min. Importantly, nanomotors move unidirectionally without intervention through an external force field or a patterned track. Because DNA origami enables precise testing of nanoscale structure-function relationships, we were able to experimentally study the role of motor shape, chassis flexibility, leg distribution, and total number of legs in tuning performance. An anisotropic rigid chassis coupled with a high density of legs maximizes nanomotor speed and endurance.

Pipe-Cleaning Plugged Portacaths: How to Unclog an Implanted Port After Development of a Fibrin Sheath.

Industry has long fought the battle to design a vascular catheter that is less thrombogenic. Indwelling catheters provide long-term central venous access, but they develop fibrin sheaths as the vascular system recognizes them as foreign bodies. Peripheral catheters and central catheters can be changed over a guidewire when they form a fibrin sheath or otherwise malfunction. However, totally implantable venous access devices such as a port cannot be easily exchanged over a wire. Therefore, when a port malfunctions, thrombolytics are usually the only option attempted before the port is explanted and a new site is prepared for access. We present a minimally invasive technique demonstrating port salvage that does not require explant.

Covered or Not, Here I Come: Stanford Type B Aortic Dissection Repair With a Covered and Uncovered Stent Hybrid Technique.

The complications resulting from aortic dissections are often devastating. Historically, when a Stanford B aortic dissection extended into the visceral abdominal aorta, only surgical management was considered to limit visceral organ malperfusion. Complications of surgical management for Stanford B aortic dissections are as high as 50%. The inherently high complication and mortality rate for any acute aortic dissection, in addition to the complication rates resulting from surgical management, have demonstrated poor outcomes. This is especially true when aortic dissections involve the visceral segment, where thoracic endovascular aortic repair (TEVAR) becomes limited or contraindicated. In the last two decades, various approaches for TEVAR have improved in both endograft design and interventional technique. The current literature demonstrates improved outcomes for patients that receive TEVAR for Stanford B aortic dissections, including those that involve the visceral segment. Despite favorable prognostic advancement in TEVAR, the proven management complexity of Stanford B aortic dissections continue to reflect the pitfalls of the endovascular devices that are currently available. We describe a covered and uncovered stent hybrid technique in patients with complicated Stanford B aortic dissections involving the visceral segment, considering these deficiencies. Hundred percent technical success was demonstrated in the short and mid-term surveillance periods.

Population response magnitude variation in inferotemporal cortex predicts image memorability.

Most accounts of image and object encoding in inferotemporal cortex (IT) focus on the distinct patterns of spikes that different images evoke across the IT population. By analyzing data collected from IT as monkeys performed a visual memory task, we demonstrate that variation in a complementary coding scheme, the magnitude of the population response, can largely account for how well images will be remembered. To investigate the origin of IT image memorability modulation, we probed convolutional neural network models trained to categorize objects. We found that, like the brain, different natural images evoked different magnitude responses from these networks, and in higher layers, larger magnitude responses were correlated with the images that humans and monkeys find most memorable. Together, these results suggest that variation in IT population response magnitude is a natural consequence of the optimizations required for visual processing, and that this variation has consequences for visual memory.

When Technology Exceeds its Application: The First Reported Reconstruction of the Iliocaval Confluence Using an Aortic Endograft.

Severe venous dysfunction in the setting of subacute iliocaval occlusion is a high cause of morbidity and mortality in patients. Fortunately, the development of the appropriate interventional management has allowed for better patient prognosis, despite device limitations. Severe cases of venous insufficiency, anatomically challenging vasculature, and device failure remain imperative when discussing the caveats for interventional success. The current gold standard of treatment for iliocaval disease has proven to be venoplasty in conjunction with stent placement within thrombotic occlusive areas. Though intuitive for modern day interventionists, this standard is not always forthright, especially when the most prevailing interventions fail to adequately treat certain venous pathologies. In this case, interventional operators must be willing to adapt their technical proficiency and knowledge of readily available devices to successfully treat the progressive nature of venous insufficiency. The following report demonstrates an example of how an interventional operator acclimated their interventional approach to successfully treat a severe and technically challenging case of subacute iliocaval occlusion, using an aortic endograft. In this first documented deployment of an aortic endograft in an iliocaval confluence, the results show resolution of the patient's subacute iliocaval occlusive disease, as well as complete iliocaval patency and the absence of post-procedural complications.