Analogical mapping across sensory modalities and evidence for a general analogy factor.

Analogy is a central component of human cognition. Analogical "mapping" of similarities between pieces of information present in our experiences supports cognitive and social development, classroom learning, and creative insights and innovation. To date, analogical mapping has primarily been studied within separate modalities of information (e.g., verbal analogies between words, visuo-spatial analogies between objects). However, human experience, in development and adulthood, includes highly variegated information (e.g., words, sounds, objects) received via multiple sensory and information-processing pathways (e.g., visual vs. auditory pathways). Whereas cross-modal correspondences (e.g., between pitch and height) have been observed, the correspondences were between individual items, rather than between relations. Thus, analogical mapping (characterized by second-order relations between relations) has not been directly tested as a basis for cross-modal correspondence. Here, we devised novel cross-modality analogical stimuli (lines-to-sounds, lines-to-words, words-to-sounds) that explicated second-order comparisons between relations. In four samples across three studies-participants demonstrated well-above-chance identification of cross-modal second-order relations, providing robust evidence of analogy across modalities. Further, performance across all analogy types was explained by a single factor, indicating a modality-general analogical ability (i.e., an "analo-g" factor). Analo-g explained performance over-and-above fluid intelligence as well as verbal and spatial abilities, though a stronger relationship to verbal than visuo-spatial ability emerged, consistent with verbal/semantic contributions to analogy. The present data suggests novel questions about our ability to find/learn second-order relations among the diverse information sources that populate human experience, and about cross-modal human and AI analogical mapping in developmental, educational, and creative contexts.

Evaluating sources of technical variability in the mechano-node-pore sensing pipeline and their effect on the reproducibility of single-cell mechanical phenotyping.

Cellular mechanical properties can reveal physiologically relevant characteristics in many cell types, and several groups have developed microfluidics-based platforms to perform high-throughput single-cell mechanical testing. However, prior work has performed only limited characterization of these platforms' technical variability and reproducibility. Here, we evaluate the repeatability performance of mechano-node-pore sensing, a single-cell mechanical phenotyping platform developed by our research group. We measured the degree to which device-to-device variability and semi-manual data processing affected this platform's measurements of single-cell mechanical properties. We demonstrated high repeatability across the entire technology pipeline even for novice users. We then compared results from identical mechano-node-pore sensing experiments performed by researchers in two different laboratories with different analytical instruments, demonstrating that the mechanical testing results from these two locations are in agreement. Our findings quantify the expectation of technical variability in mechano-node-pore sensing even in minimally experienced hands. Most importantly, we find that the repeatability performance we measured is fully sufficient for interpreting biologically relevant single-cell mechanical measurements with high confidence.

Multiplexed DNA-Directed Patterning of Antibodies for Applications in Cell Subpopulation Analysis.

Antibodies provide the functional biospecificity that has enabled the development of sensors, diagnostic tools, and assays in both laboratory and clinical settings. However, as multimarker screening becomes increasingly necessary due to the heterogeneity and complexity of human pathology, new methods must be developed that are capable of coordinating the precise assembly of multiple, distinct antibodies. To address this technological challenge, we engineered a bottom-up, high-throughput method in which DNA patterns, comprising unique 20-base pair oligonucleotides, are patterned onto a substrate using photolithography. These microfabricated surface patterns are programmed to hybridize with, and instruct the multiplexed assembly of, antibodies conjugated with the complementary DNA strands. We demonstrate that this simple, yet robust, approach preserves the antibody-binding functionality in two common applications: antibody-based cell capture and label-free surface marker screening. Using a simple proof-of-concept capture device, we achieved high purity separation of a breast cancer cell line, MCF-7, from a blood cell line, Jurkat, with capture purities of 77.4% and 96.6% when using antibodies specific for the respective cell types. We also show that antigen-antibody interactions slow cell trajectories in flow in the next-generation microfluidic node-pore sensing (NPS) device, enabling the differentiation of MCF-7 and Jurkat cells based on EpCAM surface-marker expression. Finally, we use a next-generation NPS device patterned with antibodies against E-cadherin, N-cadherin, and ß-integrin-three markers that are associated with epithelial-mesenchymal transitions-to perform label-free surface marker screening of MCF10A, MCF-7, and Hs 578T breast epithelial cells. Our high-throughput, highly versatile technique enables rapid development of customized, antibody-based assays across a host of diverse diseases and research thrusts.

3D printed microfluidic devices for circulating tumor cells (CTCs) isolation.

Isolation of circulating tumor cells (CTCs) from blood samples has important prognostic and therapeutic implications for cancer treatments, but the process is very challenging due to the low concentration of CTCs. In this study, we report a novel 3D printed microfluidic device functionalized with anti-EpCAM (epithelial cell adhesion molecule) antibodies to isolate CTCs from human blood samples. A 3D printing technology was utilized with specially designed interior structures to fabricate a microfluidic device with high surface area and fluid flow manipulation, increasing capture efficiency of tumor cells. These devices with the optimal flow rate (1 mL/h) and channel length (2 cm) were demonstrated to test three kinds of EpCAM positive cancer cell lines (MCF-7 breast cancer, SW480 colon cancer, and PC3 prostate cancer), and one kind of EpCAM negative cancer cell line (293T kidney cancer). Experimentally, the capture efficiency higher than 90% has been achieved, and the isolation of MCF-7 tumor cells from spiked human blood samples has also been demonstrated. Combined with DNA-based detection (e.g. polymerase chain reaction or DNA sequencing), the detection and analysis of released DNAs from captured tumor cells could be another future direction for clinical diagnosis and cancer treatment.

Simulation of carotid artery stenting reduces training procedure and fluoroscopy times.

OBJECTIVE: Outcomes from carotid artery stenting (CAS) are related to experience and technical expertise of the operator. Simulation of CAS may enhance clinical proficiency. We interrogated the impact of endovascular simulation of CAS procedures in operators who are at various stages of training. METHODS: Twelve trainees (students [n = 4]; junior surgery residents, postgraduate year [PGY] 1-3 [n = 4]; and senior surgery residents or fellows, PGY 4-7 [n = 4]) were apprised of characteristics of an endovascular simulator and CAS procedures. This was followed by four independent sessions that were assessed for objective measures including procedure and fluoroscopy times and contrast agent use. A qualitative analysis grading steps of CAS by two observers using a Likert scale was performed. One-way analysis of variance and paired t-tests were employed for data analysis. RESULTS: For all participants (n = 12), procedure times (mean, 920 ± 279 seconds for the first session vs 454 ± 156 seconds for the fourth session; P < .01; confidence interval [CI], 315-621) and fluoroscopy cumulative times (mean, 421 ± 230 seconds for the first session vs 222 ± 102 seconds for the fourth session; P < .01; CI, 78-285) decreased with progression of cases. Students and PGY 1-3 residents decreased their procedure times significantly in comparison of initial and final sessions (P < .05 and P < .01, respectively). For all groups, fluoroscopy cumulative times were reduced, and this decrement was significant in the PGY 1-3 cohort (mean, 444 ± 8 seconds for the first session vs 265 ± 51 seconds for the fourth session; P < .01; CI, 81-276). Initial CAS procedure times were significantly different between groups (P < .05), but this was observed to resolve by the final case at study completion. Qualitatively, the Likert scores of students and PGY 1-3 residents significantly improved with case repetition, specifically in the following steps: (1) cannulation of common carotid artery and (2) sizing and deployment of embolic protection device. Senior operators (PGY 4-7) demonstrated consistently better performance overall with minimal change in scoring with case repetition. CONCLUSIONS: Practice leads to improvements in endovascular simulator procedure and fluoroscopy times, especially for more novice trainees. Initial operator performance gaps can be approximated with a few sessions to expected proficiency. Incorporation of endovascular simulators in residency training may assist in shortening the learning curve in rarer endovascular procedures.

Endovascular aneurysm repair simulation can lead to decreased fluoroscopy time and accurately delineate the proximal seal zone.

BACKGROUND: The use of simulators for endovascular aneurysm repair (EVAR) is not widespread. We examined whether simulation could improve procedural variables, including operative time and optimizing proximal seal. For the latter, we compared suprarenal vs infrarenal fixation endografts, right femoral vs left femoral main body access, and increasing angulation of the proximal aortic neck. METHODS: Computed tomography angiography was obtained from 18 patients who underwent EVAR at a single institution. Patient cases were uploaded to the ANGIO Mentor endovascular simulator (Simbionix, Cleveland, Ohio) allowing for three-dimensional reconstruction and adapted for simulation with suprarenal fixation (Endurant II; Medtronic Inc, Minneapolis, Minn) and infrarenal fixation (C3; W. L. Gore & Associates Inc, Newark, Del) deployment systems. Three EVAR novices and three experienced surgeons performed 18 cases from each side with each device in randomized order (n = 72 simulations/participant). The cases were stratified into three groups according to the degree of infrarenal angulation: 0° to 20°, 21° to 40°, and 41° to 66°. Statistical analysis used paired t-test and one-way analysis of variance. RESULTS: Mean fluoroscopy time for participants decreased by 48.6% (P < .0001), and total procedure time decreased by 33.8% (P < .0001) when initial cases were compared with final cases. When stent deployment accuracy was evaluated across all cases, seal zone coverage in highly angulated aortic necks was significantly decreased. The infrarenal device resulted in mean aortic neck zone coverage of 91.9%, 89.4%, and 75.4% (P < .0001 by one-way analysis of variance), whereas the suprarenal device yielded 92.9%, 88.7%, and 71.5% (P < .0001) for the 0° to 20°, 21° to 40°, and 41° to 66° cases, respectively. Suprarenal fixation did not increase seal zone coverage. The side of femoral access for the main body did not influence proximal seal zone coverage regardless of infrarenal angulation. CONCLUSIONS: Simulation of EVAR leads to decreased fluoroscopy times for novice and experienced operators. Side of femoral access did not affect precision of proximal endograft landing. The angulated aortic neck leads to decreased proximal seal zone coverage regardless of infrarenal or suprarenal fixation devices.

Thoracoscopic removal of a suture needle from the posterior pericardium after coronary artery bypass grafting.

We demonstrate a minimally-invasive thoracoscopic approach [video-assisted thoracic surgery (VATS)] for removal of a retained pericardial suture needle after standard coronary artery bypass grafting (CABG) surgery. A 46-year-old male presented with unstable angina. His workup demonstrated significant coronary artery disease for which he underwent a six vessel CABG, including entering the left chest for preparation of the left internal mammary artery (LIMA). At seven weeks, a postoperative chest X-ray demonstrated a foreign body (suture needle) present in the cardiac silhouette. Further computed tomography (CT)-scan imaging confirmed the suture needle to be localized in the left inferior-posterior pericardium. The patient underwent a left VATS exploration for removal of the suture needle. The pericardial suture needle was successfully retrieved thoracoscopically. The chest tube was removed on the first postoperative day and the patient was discharged to home on the second postoperative day. The patient's postoperative course and recovery were uneventful. A minimally-invasive approach can be undertaken for the removal of a foreign body even after prior open chest surgery, avoiding the associated morbidity of a repeat sternotomy.

Human infant respiratory syncytial virus (RSV)-specific type 1 and 2 cytokine responses ex vivo during primary RSV infection.

BACKGROUND: Respiratory syncytial virus (RSV) infection is the most common respiratory viral infection resulting in hospitalizations in infants worldwide. Illness severity is likely multifactorial; however, unlike other viral infections, both type 1 and type 2 cytokine responses have been implicated in severe disease. METHODS: We measured RSV-specific cytokine responses ex vivo during primary RSV infection in the blood of 18 infants with polymerase chain reaction-confirmed RSV infection. To focus on primary RSV infection, subjects were all<9 months old. RSV-specific cytokine responses were measured at 3 time points during acute primary RSV infection and at 1 memory time point 3-6 months later. RESULTS: RSV-specific interferon (IFN)- gamma responses were detected in 10 of 18 of infants. Infants with mild disease had higher RSV-specific IFN- gamma memory responses than did those with moderate or severe disease. No consistent correlations between RSV-specific IFN- gamma responses and corticosteroid administration were observed. RSV-specific interleukin (IL)-4 or IL-5 responses to primary RSV infection were detectable in 5 of 18 and 8 of 15 infants, respectively. CONCLUSIONS: During primary RSV infection, many infants demonstrated RSV-specific IFN- gamma responses. The strongest IL-4 and IL-5 responses were detected in 3 infants with severe disease, suggesting that type 2 responses may contribute to the pathogenesis of severe disease.

The balance between influenza- and RSV-specific CD4 T cells secreting IL-10 or IFNgamma in young and healthy-elderly subjects.

Respiratory syncytial virus (RSV) and influenza virus cause severe disease in elderly patients. The balance of pro- and anti-inflammatory cytokines may be critical in determining disease pathogenesis and outcome of infection. The frequencies of CD4 IL-10 (anti-inflammatory)- and CD4 and CD8 IFNgamma (pro-inflammatory)-secreting memory T cells specific for either RSV or influenza were not significantly different between young and elderly groups, although the ratio of IL-10/IFNgamma was significantly reduced in the elderly RSV response. A similar trend was seen for influenza. IFNgamma-secreting CD4 T cells contributed significantly more to anti-RSV than anti-influenza responses in both groups.