Echocardiographic diagnosis and clinical implications of wide-open tricuspid regurgitation for evaluating right ventricular dysfunction in the emergency department.

The tricuspid regurgitation pressure gradient (TRPG) reflects the difference in pressure between the right ventricle and right atrium (ΔPRV-RA). Its estimation by echocardiography correlates well with that obtained using right-heart catheterization. An elevated TRPG is an important marker for identifying right ventricular dysfunction in both the acute and chronic settings. However, in the "wide-open" variant of TR, the TRPG counterintuitively falls. Failure to recognize this potential pitfall and underlying pathophysiology can cause underestimation of the severity of right ventricular dysfunction. This could lead to erroneous fluid tolerance assessments, and potentially harmful resuscitative and airway management strategies. In this manuscript, we illustrate the pathophysiology and potential pitfall of wide-open TR through a series of cases in which emergency physicians made the diagnosis using cardiac point-of-care ultrasound. To our knowledge, this clinical series is the first to demonstrate recognition of the paradoxically-low TRPG of wide-open TR, which guided appropriate management of critically ill patients in the emergency department.

A Randomised Clinical Trial of the Safety and Pharmacokinetics of VRC07-523LS Administered via Different Routes and Doses (HVTN 127/HPTN 087).

Background: Broadly neutralizing antibodies (bnAbs) are a promising approach for HIV-1 prevention. In the only bnAb HIV prevention efficacy studies to date, the Antibody Mediated Prevention (AMP) trials, a CD4-binding site targeting bnAb, VRC01, administered intravenously (IV), demonstrated 75% prevention efficacy against highly neutralization-sensitive viruses but was ineffective against less sensitive viruses. Greater efficacy is required before passively administered bnAbs become a viable option for HIV prevention; furthermore subcutaneous (SC) or intramuscular (IM) administration may be preferred. VRC07-523LS is a next-generation bnAb targeting the CD4-binding site and was engineered for increased neutralization breadth and half-life. Methods: Participants were recruited between 02 February 2018 and 09 October 2018. 124 healthy participants without HIV were randomized to receive five VRC07-523LS administrations via IV (T1: 2.5 mg/kg, T2: 5 mg/kg, T3: 20 mg/kg), SC (T4: 2.5 mg/kg, T5: 5 mg/kg) or IM (T6: 2.5 mg/kg or P6: placebo) routes at four-month intervals. Safety data were collected for 144 weeks following the first administration. VRC07-523LS serum concentrations were measured by ELISA after the first dose through Day 112 in all participants and by binding antibody multiplex assay (BAMA) thereafter in 60 participants (10 per treatment group) through Day 784. Compartmental population pharmacokinetic (PK) analyses were conducted to evaluate the VRC07-523LS serum pharmacokinetics. Neutralization activity was measured in a TZM-bl assay and anti-drug antibodies (ADA) were assayed using a tiered bridging assay testing strategy. Results: Injections were well-tolerated, with mild pain or tenderness reported commonly in the SC and IM groups, and mild to moderate erythema or induration reported commonly in the SC groups. Infusions were generally well-tolerated, with infusion reactions reported in 3 of 20 participants in the 20 mg/kg IV group. Peak geometric mean (GM) concentrations (95% confidence intervals) following the first administration were 29.0 µg/mL (25.2, 33.4), 58.5 µg/mL (49.4, 69.3), and 257.2 µg/mL (127.5, 518.9) in T1-T3 with IV dosing; 10.8 µg/mL (8.8, 13.3) and 22.8 µg/mL (20.1, 25.9) in T4-T5 with SC dosing; and 16.4 µg/mL (14.7, 18.2) in T6 with IM dosing. Trough GM concentrations immediately prior to the second administration were 3.4 µg/mL (2.5, 4.6), 6.5 µg/mL (5.6, 7.5), and 27.2 µg/mL (23.9, 31.0) with IV dosing; 0.97 µg/mL (0.65, 1.4) and 3.1 µg/mL (2.2, 4.3) with SC dosing, and 2.6 µg/mL (2.05, 3.31) with IM dosing. Peak VRC07-523LS serum concentrations increased linearly with the administered dose. At a given dose, peak and trough concentrations, as well as serum neutralization titres, were highest in the IV groups, reflecting the lower bioavailability following SC and IM administration. A single participant was found to have low titre ADA at a lone timepoint. VRC07-523LS has an estimated mean half-life of 42 days (95% CI: 40.5, 43.5), approximately twice as long as VRC01. Conclusions: VRC07-523LS was safe and well-tolerated across a range of doses and routes and is a promising long-acting bnAb for inclusion in HIV-1 prevention regimens.

Dynamic Motion and Human Agents Facilitate Visual Nonadjacent Dependency Learning.

Many events that humans and other species experience contain regularities in which certain elements within an event predict certain others. While some of these regularities involve tracking the co-occurrences between temporally adjacent stimuli, others involve tracking the co-occurrences between temporally distant stimuli (i.e., nonadjacent dependencies, NADs). Prior research shows robust learning of adjacent dependencies in humans and other species, whereas learning NADs is more difficult, and often requires support from properties of the stimulus to help learners notice the NADs. Here, we report on seven experiments that examined NAD learning from various types of visual stimuli, exploring the effects of dynamic motion on adults' NAD learning from visual sequences involving human and nonhuman agents. We tested adults' NAD learning from visual sequences of human actions, object transformations, static images of human postures, and static images of an object in different postures. We found that dynamic motion aids the acquisition of NADs. We also found that learning NADs in sequences involving human agents is more robust compared to sequences involving nonhuman objects. We propose that dynamic motion and human agents both independently result in richer representations that provide a stronger signal for NAD learning.

Delayed Iatrogenic Bladder Rupture Diagnosed by POCUS in the Emergency Department.

Bladder rupture is an uncommon injury that leads to significant morbidity and mortality. Though occurring mostly due to trauma, this life-threatening pathology may also occur spontaneously or after a procedure such as transurethral resection of bladder tumor (TURBT). Computed tomography (CT) cystography is the standard imaging modality for diagnosis. However, this test is unlikely to be ordered in a patient with undifferentiated abdominal pain unless there is specific suspicion for this diagnosis. In our emergency department, a 48 year-old male with history of bladder cancer and TURBT two weeks prior to arrival presented with severe abdominal pain and difficulty urinating for 3 days. Point of care ultrasound (POCUS) revealed an irregularly shaped bladder, likely site of bladder rupture, and large amount of abdominal free fluid with sediment. These findings prompted an expedited diagnostic CT scan with cystography. Emergent exploratory laparotomy ultimately confirmed a small bladder defect with 2.5 L of urinary ascites. The diagnosis of non-traumatic bladder rupture can be overlooked in patients presenting with a peritonitic abdominen. The typically ordered test for such patients is standard CT, which carries a high false-negative rate for bladder rupture. This case highlights the utility of POCUS in facilitating a rapid diagnosis.

Engineering collagenous analogs of connective tissue extracellular matrix.

Connective tissue extracellular matrix (ECM) consists of an interwoven network of contiguous collagen fibers that regulate cell activity, direct biological function, and guide tissue homeostasis throughout life. Recently, ECM analogs have emerged as a unique ex vivo culture platform for studying healthy and diseased tissues and in the latter, enabling the screening for and development of therapeutic regimen. Since these tissue models can mitigate the concern that observations from animal models do not always translate clinically, the design and production of a collagenous ECM analogue with relevant chemistry and nano- to micro-scale architecture remains a frontier challenge in the field. Therefore, the objectives of this study are two-fold- first, to apply green electrospinning approaches to the fabrication of an ECM analog with nanoscale mimicry and second, to systematically optimize collagen crosslinking in order to produce a stable, collagen-like substrate with continuous fibrous architecture that supports human cell culture and phenotypic expression. Specifically, the "green" electrospinning solvent acetic acid was evaluated for biofabrication of gelatin-based meshes, followed by the optimization of glutaraldehyde (GTA) crosslinking under controlled ambient conditions. These efforts led to the production of a collagen-like mesh with nano- and micro-scale cues, fibrous continuity with little batch-to-batch variability, and proven stability in both dry and wet conditions. Moreover, the as-fabricated mesh architecture and native chemistry were preserved with augmented mechanical properties. These meshes supported the in vitro expansion of stem cells and the production of a mineralized matrix by human osteoblast-like cells. Collectively these findings demonstrate the potential of green fabrication in the production of a collagen-like ECM analog with physiological relevance. Future studies will explore the potential of this high-fidelity platform for elucidating cell-matrix interactions and their relevance in connective tissue healing.

A mixed methods study evaluating acceptability of a daily COVID-19 testing regimen with a mobile-app connected, at-home, rapid antigen test: Implications for current and future pandemics.

BACKGROUND: Widespread use of at-home rapid COVID-19 antigen tests has been proposed as an important public health intervention to interrupt chains of transmission. Antigen tests may be preferred over PCR because they provide on-demand results for relatively low cost and can identify people when they are most likely to be infectious, particularly when used daily. Yet the extent to which a frequent antigen testing intervention will result in a positive public health impact for COVID-19 will depend on high acceptability and high adherence to such regimens. METHODS: We conducted a mixed-methods study assessing acceptability of and adherence to a daily at-home mobile-app connected rapid antigen testing regimen among employees of a US-based media company. Acceptability was assessed across seven domains of the Theoretical Framework of Acceptability. RESULTS: Among 31 study participants, acceptability of the daily testing intervention was generally high, with participants reporting high perceived effectiveness, intervention coherence, and self-efficacy; positive affective attitude; acceptable degree of burden and opportunity cost; and assessing the intervention as ethical. 71% reported a preference to test daily using an at-home antigen test than weekly employment-based PCR. Mean adherence to the 21-day testing regimen was 88% with 43% of participants achieving 100% adherence, 48% testing at least every other day, and 10% testing less than every other day. CONCLUSIONS: Despite overall high acceptability and adherence, we identified three implementation challenges that must be addressed for frequent serial testing for COVID-19 to be implemented at scale and have a positive public health impact. First, users need guidance on how and when to adapt testing frequencies to different epidemiological conditions. Second, users and institutions need guidelines for how to safely store and share test results. Third, implementation of serial testing strategies must prioritize health equity and protect those most vulnerable to COVID-19.

Microbial nanocellulose biotextiles for a circular materials economy.

The synthesis and bottom-up assembly of nanocellulose by microbes offers unique advantages to tune and meet key design criteria-rapid renewability, low toxicity, scalability, performance, and degradability-for multi-functional, circular economy textiles. However, development of green processing methods that meet these criteria remains a major research challenge. Here, we harness microbial biofabrication of nanocellulose and draw inspiration from ancient textile techniques to engineer sustainable biotextiles with a circular life cycle. The unique molecular self-organization of microbial nanocellulose (MC) combined with bio-phosphorylation with a lecithin treatment yields a compostable material with superior mechanical and flame-retardant properties. Specifically, treatment of MC with a lecithin-phosphocholine emulsion makes sites available to modulate cellulose cross-linking through hydroxyl, phosphate and methylene groups, increasing the interaction between cellulose chains. The resultant bioleather exhibits enhanced tensile strength and high ductility. Bio-phosphorylation with lecithin also redirects the combustion pathway from levoglucosan production towards the formation of foaming char as an insulating oxygen barrier, for outstanding flame retardance. Controlled color modulation is demonstrated with natural dyes. Life cycle impact assessment reveals that MC bioleather has up to an order of magnitude lower carbon footprint than conventional textiles, and a thousandfold reduction in the carcinogenic impact of leather production. Eliminating the use of hazardous substances, these high performance materials disrupt linear production models and strategically eliminate its toxicity and negative climate impacts, with widespread application in fashion, interiors and construction. Importantly, the biotextile approach developed in this study demonstrates the potential of biofabrication coupled with green chemistry for a circular materials economy.

Systematically exploring repurposing effects of antihypertensives.

With availability of voluminous sets of observational data, an empirical paradigm to screen for drug repurposing opportunities (i.e., beneficial effects of drugs on nonindicated outcomes) is feasible. In this article, we use a linked claims and electronic health record database to comprehensively explore repurposing effects of antihypertensive drugs. We follow a target trial emulation framework for causal inference to emulate randomized controlled trials estimating confounding adjusted effects of antihypertensives on each of 262 outcomes of interest. We then fit hierarchical models to the results as a form of postprocessing to account for multiple comparisons and to sift through the results in a principled way. Our motivation is twofold. We seek both to surface genuinely intriguing drug repurposing opportunities and to elucidate through a real application some study design decisions and potential biases that arise in this context.

Development and performance of a point-of-care rapid antigen test for detection of SARS-COV-2 variants.

Background: SARS-CoV-2 antigen-based tests are well-calibrated to infectiousness and have a critical role to play in the COVID-19 public health response. We report the development and performance of a unique lateral flow immunoassay (LFA). Methods: Combinations of several monoclonal antibodies targeting multiple antigenic sites on the SARS-CoV-2 nucleocapsid protein (NP) were isolated, evaluated, and chosen for the development of a LFA termed CoV-SCAN (BioMedomics, Inc.). Clinical point-of-care studies in symptomatic and asymptomatic individuals were conducted to evaluate positive predictive agreement (PPA) and negative predictive agreement (NPA) with RT-PCR as comparator. Results: In laboratory testing, CoV-SCAN detected 14 recombinant N-proteins of SARS-CoV-2 variants with sensitivity in the range of 0.2-3.2 ng/mL, and 10 authentic SARS-CoV-2 variants with sensitivity in the range of 1.6-12.5 TCID50/swab. No cross reactivity was observed with other human coronaviruses or other respiratory pathogens. In clinical point-of-care testing on 148 individuals over age 2 with symptoms of ≤5 days, PPA was 87.2% (CI 95: 78.3-94.8%) and NPA was 100% (CI 95: 94.2-100%). In another 884 asymptomatic individuals, PPA was 85.7% (CI 95: 42.1-99.6%) and 99.7% (99.0-99.9%). Overall, CoV-SCAN detected over 97.2% of specimens with CT values <30 and 93.8% of nasal swab specimens with the Omicron variant, even within the first 2 days after symptom onset. Conclusions: The unique construction of CoV-SCAN using two pairs of monoclonal antibodies has resulted in a test with high performance that remains durable across multiple variants in both laboratory and clinical evaluations. CoV-SCAN should identify almost all individuals harboring infectious SARS-CoV-2. Summary: Unique construction of a point-of-care rapid antigen test using two pairs of monoclonal antibodies has led to good performance that remained durable across multiple variants in laboratory and clinical evaluations. Test should identify almost all individuals harboring infectious SARS-CoV-2.

Biomonitoring of Polybrominated Dioxins & Furans, Polychlorinated Dioxins & Furans, and Dioxin Like Polychlorinated Biphenyls in Vietnamese Female Electronic Waste Recyclers.

OBJECTIVE: E-waste is rising globally. This is a follow up to our study reporting metals/polybrominated diphenyl ethers (PBDE's)/polychlorinated biphenyls (PCBs) in female e-waste recyclers. Here we report polybrominated, polychlorinated dioxins/furans, and dioxin-like polychlorinated biphenyls in these same workers. METHODS: Female Vietnamese recyclers and non-recyclers recruited; blood samples collected. Polybrominated, polychlorinated dioxins/furans, and dioxin-like polychlorinated biphenyls levels compared in recyclers, non-recyclers, and National Health and Nutrition Examination Surveys (NHANES). RESULTS: Recyclers >non-recyclers: 12378-PBDD, 2378-TBDF, 12378-PCDF, 123478-HxCDF, 123678-HxCDF, 1234678-HpCDF, PCB-126. Non-recyclers >NHANES: 123478-HxCDF, 123678-HxCDF, 234678- HxCDF, PCB-126, PCB-169. NHANES >non-recyclers: 12378-PCDD, 123478-HxCDD, 123678-HxCDD, 123789-HxCDD, 1234678-HpCDD, 123789-HxCDF, 1234678-HpCDF, 1234789-HpCDF, OCDF, PCB-81, PCB-114, PCB-156, PCB-157, PCB-167, PCB-189. Recyclers >NHANES: S: 2378-TeCDF, 12378-PCDF, 23478-PCDF, 123478-HxCDF, 123678- HxCDF, 234678-HxCDF, PCB-126. NHANES >recyclers: 12378-PCDD, 123478-HxCDD, 123678-HxCDD, 123789-HxCDD, 1234678-HpCDD, OCDD, 123789-HxCDF, 1234678-HpCDF, 1234789-HpCDF, OCDF, PCB- 81, PCB-114, PCB-156, PCB-157, PCB-189. CONCLUSION: 12378 PCDD, 2378-TCDD, PCB 126 makeup most total dioxin equivalences (TEQs) in AQ5 these workers, indicating increased exposure; remediation indicated.

PhenoPad: Building AI enabled note-taking interfaces for patient encounters.

Current clinical note-taking approaches cannot capture the entirety of information available from patient encounters and detract from patient-clinician interactions. By surveying healthcare providers' current note-taking practices and attitudes toward new clinical technologies, we developed a patient-centered paradigm for clinical note-taking that makes use of hybrid tablet/keyboard devices and artificial intelligence (AI) technologies. PhenoPad is an intelligent clinical note-taking interface that captures free-form notes and standard phenotypic information via a variety of modalities, including speech and natural language processing techniques, handwriting recognition, and more. The output is unobtrusively presented on mobile devices to clinicians for real-time validation and can be automatically transformed into digital formats that would be compatible with integration into electronic health record systems. Semi-structured interviews and trials in clinical settings rendered positive feedback from both clinicians and patients, demonstrating that AI-enabled clinical note-taking under our design improves ease and breadth of information captured during clinical visits without compromising patient-clinician interactions. We open source a proof-of-concept implementation that can lay the foundation for broader clinical use cases.

Do the outcomes of hip arthroscopy for femoroacetabular impingement change over time?

BACKGROUND: The purpose of this study was to search for changes in functional outcomes of patients undergoing hip arthroscopy for femoroacetabular impingement (FAI) between short and medium-term follow-up. Secondary aims included reporting rates of revision surgery and total hip arthroplasty (THA) at medium-term follow-up. HYPOTHESIS: We hypothesised that patients' functional outcomes would improve between short and medium-term follow-up. PATIENTS AND METHODS: Consecutive patients undergoing hip arthroscopy with a diagnosis of femoroacetabular impingement with labral tears between February 2013 and June 2015 were included. Twelve item international hip outcome tool (iHOT-12) and EuroQol 5D-5L (EQ-5D) scores were collected preoperatively, at short-term and medium-term follow-up. Short-term scores were recorded at a minimum of one year postoperatively and medium-term scores at a minimum of five years postoperatively. Survivorship was assessed with Kaplan-Meier analysis. RESULTS: Short-term outcome data (at median follow-up 1.6 year, Interquartile range [IQR] 1-2.5) was available for 70 of 87 patients (80.5%) and medium-term outcome data (at median follow-up of 6.5 years, IQR 6-7.1) was available for 68 patients (78.2%). Median age at the time of surgery was 31 years (IQR 25-37). The median iHOT-12 scores at short and medium-term follow-up were 72 (IQR 48.75-91.25) and 85.8 (IQR 66.7-96.7) respectively (p<0.001). Medium-term survivorship was 91.2%. Survivorship following labral repair was 94.2%, and 81.3% following labral debridement (p=0.09). DISCUSSION: Patients undergoing hip arthroscopy for FAI reported continued improvement in iHOT-12 scores between short and medium-term follow-up. Medium-term survivorship following FAI surgery may be greater when the labrum is repaired, although comparisons are limited by their differing indications. Conversion to THA was low with just 4 patients (4.6%) undergoing or being listed for THA at final follow-up. LEVEL OF EVIDENCE: IV, Case series.

Three-Dimensional-Printed Flexible Scaffolds Have Tunable Biomimetic Mechanical Properties for Intervertebral Disc Tissue Engineering.

The intervertebral disc (IVD) exhibits complex structure and biomechanical function, which supports the weight of the body and permits motion. Surgical treatments for IVD degeneration (e.g., lumbar fusion, disc replacement) often disrupt the mechanical environment of the spine which lead to adjacent segment disease. Alternatively, disc tissue engineering strategies, where cell-seeded hydrogels or fibrous biomaterials are cultured in vitro to promote matrix deposition, do not recapitulate the complex IVD mechanical properties. In this study, we use 3D printing of flexible polylactic acid (FPLA) to fabricate a viscoelastic scaffold with tunable biomimetic mechanics for whole spine motion segment applications. We optimized the mechanical properties of the scaffolds for equilibrium and dynamic moduli in compression and tension by varying fiber spacing or porosity, generating scaffolds with de novo mechanical properties within the physiological range of spine motion segments. The biodegradation analysis of the 3D printed scaffolds showed that FPLA exhibits lower degradation rate and thus has longer mechanical stability than standard PLA. FPLA scaffolds were biocompatible, supporting viability of nucleus pulposus (NP) cells in 2D and in FPLA+hydrogel composites. Composite scaffolds cultured with NP cells maintained baseline physiological mechanical properties and promoted matrix deposition up to 8 weeks in culture. Mesenchymal stromal cells (MSCs) cultured on FPLA adhered to the scaffold and exhibited fibrocartilaginous differentiation. These results demonstrate for the first time that 3D printed FPLA scaffolds have de novo viscoelastic mechanical properties that match the native IVD motion segment in both tension and compression and have the potential to be used as a mechanically stable and biocompatible biomaterial for engineered disc replacement.

Green electrospinning for biomaterials and biofabrication.

Green manufacturing has emerged across industries, propelled by a growing awareness of the negative environmental and health impacts associated with traditional practices. In the biomaterials industry, electrospinning is a ubiquitous fabrication method for producing nano- to micro-scale fibrous meshes that resemble native tissues, but this process traditionally utilizes solvents that are environmentally hazardous and pose a significant barrier to industrial scale-up and clinical translation. Applying sustainability principles to biomaterial production, we have developed a 'green electrospinning' process by systematically testing biologically benign solvents (U.S. Food and Drug Administration Q3C Class 3), and have identified acetic acid as a green solvent that exhibits low ecological impact (global warming potential (GWP) = 1.40 CO2eq. kg/L) and supports a stable electrospinning jet under routine fabrication conditions. By tuning electrospinning parameters, such as needle-plate distance and flow rate, we updated the fabrication of widely utilized biomedical polymers (e.g. poly-α-hydroxyesters, collagen), polymer blends, polymer-ceramic composites, and growth factor delivery systems. Resulting 'green' fibers and composites are comparable to traditional meshes in terms of composition, chemistry, architecture, mechanical properties, and biocompatibility. Interestingly, material properties of green synthetic fibers are more biomimetic than those of traditionally electrospun fibers, doubling in ductility (91.86 ± 35.65 vs. 45 ± 15.07%,n= 10,p< 0.05) without compromising yield strength (1.32 ± 0.26 vs. 1.38 ± 0.32 MPa) or ultimate tensile strength (2.49 ± 0.55 vs. 2.36 ± 0.45 MPa). Most importantly, green electrospinning proves advantageous for biofabrication, rendering a greater protection of growth factors during fiber formation (72.30 ± 1.94 vs. 62.87 ± 2.49% alpha helical content,n= 3,p< 0.05) and recapitulating native ECM mechanics in the fabrication of biopolymer-based meshes (16.57 ± 3.92% ductility, 33.38 ± 30.26 MPa elastic modulus, 1.30 ± 0.19 MPa yield strength, and 2.13 ± 0.36 MPa ultimate tensile strength,n= 10). The eco-conscious approach demonstrated here represents a paradigm shift in biofabrication, and will accelerate the translation of scalable biomaterials and biomimetic scaffolds for tissue engineering and regenerative medicine.

Learning non-adjacent rules and non-adjacent dependencies from human actions in 9-month-old infants.

Seven month old infants can learn simple repetition patterns, such as we-fo-we, and generalize the rules to sequences of new syllables, such as ga-ti-ga. However, repetition rule learning in visual sequences seems more challenging, leading some researchers to claim that this type of rule learning applies preferentially to communicative stimuli. Here we demonstrate that 9-month-old infants can learn repetition rules in sequences of non-communicative dynamic human actions. We also show that when primed with these non-adjacent repetition patterns, infants can learn non-adjacent dependencies that involve memorizing the dependencies between specific human actions-patterns that prior research has shown to be difficult for infants in the visual domain and in speech. We discuss several possible mechanisms that account for the apparent advantage stimuli involving human action sequences has over other kinds of stimuli in supporting non-adjacent dependency learning. We also discuss possible implications for theories of language acquisition.

Feasibility and safety study of a high resolution wide field-of-view scanning endoscope for circumferential intraluminal intestinal imaging.

Global anal cancer incidence is increasing. High resolution anoscopy (HRA) currently screens for anal cancer, although the definitive test remains unknown. To improve on intraluminal imaging of the anal canal, we conducted a first-in-human study to determine feasibility and safety of a high-resolution, wide field-of-view scanning endoscope. Fourteen patients, under an IRB-approved clinical study, underwent exam under anesthesia, HRA, and imaging with the experimental device. HRA findings were photographed using an in-line camera attached to the colposcope and compared with the scanning endoscope images. Patients were followed up within 2 weeks of the procedure. The imaging device is inserted into the anal canal and the intraluminal surface is digitally photographed in 10 s and uploaded to a computer monitor for review. Ten patients completed imaging with the device. Three patients were not imaged due to severe anal stenosis. One patient was not imaged due to technical device malfunction. The device images were compared to the HRA images. No adverse event attributable to the device was reported. The intraluminal scanning endoscope can be used for circumferential anal canal imaging and is safe for clinical use. Future clinical studies are needed to evaluate the performance of this device.

Darwin's Neural Network: AI-based Strategies for Rapid and Scalable Cell and Coronavirus Screening.

Recent advances in the interdisciplinary scientific field of machine perception, computer vision, and biomedical engineering underpin a collection of machine learning algorithms with a remarkable ability to decipher the contents of microscope and nanoscope images. Machine learning algorithms are transforming the interpretation and analysis of microscope and nanoscope imaging data through use in conjunction with biological imaging modalities. These advances are enabling researchers to carry out real-time experiments that were previously thought to be computationally impossible. Here we adapt the theory of survival of the fittest in the field of computer vision and machine perception to introduce a new framework of multi-class instance segmentation deep learning, Darwin's Neural Network (DNN), to carry out morphometric analysis and classification of COVID19 and MERS-CoV collected in vivo and of multiple mammalian cell types in vitro.

Structure-Function Relationships of the Temporomandibular Joint in Response to Altered Loading.

AIMS: To elucidate the effects of decreased occlusal loading (DOL), with or without reloading (RL), on the structure and bite force function of the mandibular condylar fibrocartilage in skeletally mature male mice. METHODS: At 13 weeks old, 30 wild type (WT) male mice were subjected to: (1) 6 weeks normal loading (NL); (2) 6 weeks DOL; or (3) 4 weeks DOL + 2 weeks RL. Histomorphometry, cell metabolic activity, gene expression of chondrogenic markers, and bite force tests were performed. RESULTS: DOL resulted in a significant increase in apoptosis (P < .0001) and significant decreases in fibrocartilage thickness (P < .05) and hypertrophic chondrocyte markers indian hedgehog and collagen type X (P < .05). A corresponding decrease in bite force was also observed (P < .05). RL treatment resulted in a return to values comparable to NL of chondrogenic maturation markers (P > .10), apoptosis (P > .999), and bite force (P > .90), but not in mandibular condylar fibrocartilage thickness (P > .05). CONCLUSIONS: DOL in skeletally mature mice induces mandibular condylar fibrocartilage atrophy at the hypertrophic cell layer with a corresponding decrease in bite force.

High-speed collagen fiber modeling and orientation quantification for optical coherence tomography imaging.

Quantifying collagen fiber architecture has clinical and scientific relevance across a variety of tissue types and adds functionality to otherwise largely qualitative imaging modalities. Optical coherence tomography (OCT) is uniquely suited for this task due to its ability to capture the collagen microstructure over larger fields of view than traditional microscopy. Existing image processing techniques for quantifying fiber architecture, while accurate and effective, are very slow for processing large datasets and tend to lack structural specificity. We describe here a computationally efficient method for quantifying and visualizing collagen fiber organization. The algorithm is demonstrated on swine atria, bovine anterior cruciate ligament, and human cervical tissue samples. Additionally, we show an improved performance for images with crimped fiber textures and low signal to noise when compared to similar methods.