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To describe demographics and imaging and compare findings and symptoms at presentation in a large cohort of persons with cricopharyngeus muscle dysfunction (CPMD) with and without hypopharyngeal diverticula.Prospective, multicenter cohort study of all individuals enrolled in the Prospective OUtcomes of Cricopharyngeal Hypertonicity (POUCH) Collaborative. Patient survey, comorbidities, radiography, laryngoscopy findings, and patient-reported outcome measures (e.g., Eating Assessment Tool [EAT-10]) data were abstracted from a REDCap database and summarized using means, medians, percentages, and frequencies. Diagnostic categories were compared using analysis of variance.A total of 250 persons were included. The mean age (standard deviation [SD]) of the cohort was 69.0 (11.2). Forty-two percent identified as female. Zenker diverticula (ZD) was diagnosed in 85.2%, 9.2% with CPMD without diverticula, 4.4% with a Killian Jamieson diverticula (KJD), and 1.2% traction-type diverticula. There were no differences between diagnostic categories in regard to age, gender, and duration of symptoms (p = 0.25, 0.19, 0.45). The mean (SD) EAT-10 score for each group was 17.1 (10.1) for ZD, 20.2 (9.3) for CPMD, and 10.3 (9.4) for KJD. Patients with isolated CPMD had significantly greater EAT-10 scores compared to the other diagnostic groups (p = 0.03).ZD is the most common, followed by CPMD without diverticula, KJD, and traction-type. Patients with isolated obstructing CPMD may be more symptomatic than persons with ZD or KJD.Level 4 Laryngoscope, 2022.

Organelle positioning in cells is associated with various metabolic functions and signaling in unicellular organisms. Specifically, the microalga Chlamydomonas reinhardtii repositions its mitochondria, depending on the levels of inorganic carbon. Mitochondria are typically randomly distributed in the Chlamydomonas cytoplasm, but relocate toward the cell periphery at low inorganic carbon levels. This mitochondrial relocation is linked with the carbon-concentrating mechanism, but its significance is not yet thoroughly understood. A genotypic understanding of this relocation would require a high-throughput method to isolate rare mutant cells not exhibiting this relocation. However, this task is technically challenging due to the complex intracellular morphological difference between mutant and wild-type cells, rendering conventional non-image-based high-event-rate methods unsuitable. Here, we report our demonstration of intelligent image-activated cell sorting by mitochondrial localization. Specifically, we applied an intelligent image-activated cell sorting system to sort for C. reinhardtii cells displaying no mitochondrial relocation. We trained a convolutional neural network (CNN) to distinguish the cell types based on the complex morphology of their mitochondria. The CNN was employed to perform image-activated sorting for the mutant cell type at 180 events per second, which is 1-2 orders of magnitude faster than automated microscopy with robotic pipetting, resulting in an enhancement of the concentration from 5% to 56.5% corresponding to an enrichment factor of 11.3. These results show the potential of image-activated cell sorting for connecting genotype-phenotype relations for rare-cell populations, which require a high throughput and could lead to a better understanding of metabolic functions in cells.

Imaging flow cytometry (IFC) has become a powerful tool for diverse biomedical applications by virtue of its ability to image single cells in a high-throughput manner. However, there remains a challenge posed by the fundamental trade-off between throughput, sensitivity, and spatial resolution. Here we present deep-learning-enhanced imaging flow cytometry (dIFC) that circumvents this trade-off by implementing an image restoration algorithm on a virtual-freezing fluorescence imaging (VIFFI) flow cytometry platform, enabling higher throughput without sacrificing sensitivity and spatial resolution. A key component of dIFC is a high-resolution (HR) image generator that synthesizes "virtual" HR images from the corresponding low-resolution (LR) images acquired with a low-magnification lens (10×/0.4-NA). For IFC, a low-magnification lens is favorable because of reduced image blur of cells flowing at a higher speed, which allows higher throughput. We trained and developed the HR image generator with an architecture containing two generative adversarial networks (GANs). Furthermore, we developed dIFC as a method by combining the trained generator and IFC. We characterized dIFC using

To assess barium esophagram (BAS) as a diagnostic marker for patients with Killian Jamieson diverticula (KJD).Prospective, multicenter cohort study of individuals enrolled in the Prospective OUtcomes of Cricopharyngeus Hypertonicity (POUCH) Collaborative. Patient demographics, comorbidities, radiographic imaging reports, laryngoscopy findings, patient-reported outcome measures (PROM), and operative reporting were abstracted from a REDCap database and summarized using means, medians, percentages, frequencies. Paired t-tests and Wilcoxon Signed Rank test were used to test pre- to post-operative differences in RSI, EAT-10, and VHI-10 scores. Diagnostic test evaluation including sensitivity, specificity, positive, and negative predictive value with 95% confidence intervals were calculated comparing BAS findings to operative report.A total of 287 persons were enrolled; 13 (4%) patients were identified with confirmed KJD on operative reports. 100% underwent open transcervical excision. BAS has a 46.2% (95% confidence interval [CI]: 23.2, 70.9) sensitivity and 97.8% (95% CI: 95.3, 99.0) specificity in detecting a KJD and 50% (95% CI: 25.4, 74.6) positive predictive value but 97.4% (95%CI: 94.8, 98.7) negative predictive value. Preoperatively, patients reported mean (SD) RSI and EAT-10 of 19.4 (9) and 8.3 (7.5) accordingly. Postoperatively, patients reported mean (SD) RSI and EAT-10 as 5.4 (6.2) and 2.3 (3.3). Both changes in RSI and EAT-10 were statistically significant (p = 0.008, p = 0.03).KJD are rare and represent5% of hypopharyngeal diverticula undergoing surgical intervention. Open transcervical surgery significantly improves symptoms of dysphagia. BAS has high specificity but low sensitivity in detecting KJD.Level 4 Laryngoscope, 2022.

In the past few decades, microalgae-based bioremediation methods for treating heavy metal (HM)-polluted wastewater have attracted much attention by virtue of their environment friendliness, cost efficiency, and sustainability. However, their HM removal efficiency is far from practical use. Directed evolution is expected to be effective for developing microalgae with a much higher HM removal efficiency, but there is no non-invasive or label-free indicator to identify them. Here, we present an intelligent cellular morphological indicator for identifying the HM removal efficiency of Euglena gracilis in a non-invasive and label-free manner. Specifically, we show a strong monotonic correlation (Spearman's ρ = -0.82, P = 2.1 × 10-5) between a morphological meta-feature recognized via our machine learning algorithms and the Cu2+ removal efficiency of 19 E. gracilis clones. Our findings firmly suggest that the morphology of E. gracilis cells can serve as an effective HM removal efficiency indicator and hence have great potential, when combined with a high-throughput image-activated cell sorter, for directed-evolution-based development of E. gracilis with an extremely high HM removal efficiency for practical wastewater treatment worldwide.

Artificial intelligence (AI) has dramatically changed the landscape of science, industry, defence, and medicine in the last several years. Supported by considerably enhanced computational power and cloud storage, the field of AI has shifted from mostly theoretical studies in the discipline of computer science to diverse real-life applications such as drug design, material discovery, speech recognition, self-driving cars, advertising, finance, medical imaging, and astronomical observation, where AI-produced outcomes have been proven to be comparable or even superior to the performance of human experts. In these applications, what is essentially important for the development of AI is the data needed for machine learning. Despite its prominent importance, the very first process of the AI development, namely data collection and data preparation, is typically the most laborious task and is often a limiting factor of constructing functional AI algorithms. Lab-on-a-chip technology, in particular microfluidics, is a powerful platform for both the construction and implementation of AI in a large-scale, cost-effective, high-throughput, automated, and multiplexed manner, thereby overcoming the above bottleneck. On this platform, high-throughput imaging is a critical tool as it can generate high-content information (e.g., size, shape, structure, composition, interaction) of objects on a large scale. High-throughput imaging can also be paired with sorting and DNA/RNA sequencing to conduct a massive survey of phenotype-genotype relations whose data is too complex to analyze with traditional computational tools, but is analyzable with the power of AI. In addition to its function as a data provider, lab-on-a-chip technology can also be employed to implement the developed AI for accurate identification, characterization, classification, and prediction of objects in mixed, heterogeneous, or unknown samples. In this review article, motivated by the excellent synergy between AI and lab-on-a-chip technology, we outline fundamental elements, recent advances, future challenges, and emerging opportunities of AI with lab-on-a-chip technology or "AI on a chip" for short.

Microalgae-based methods used in heavy metal (HM)-polluted wastewater treatment have attracted increasing attention in recent decades, due to their eco-friendliness, profitability, and sustainability. Unfortunately, their low HM removal efficiency hinders them from practical use. In this work, we report an AI-on-a-chip method, a combination of AI and lab-on-a-chip technology, for identifying Euglena gracilis (a microalgal species) cells with high HM removal efficiency through a morphological meta-feature. In the near future, the implementation of the morphological meta-feature in a high-throughput cell sorting process will pave the way for realizing directed-evolution-based development of microalgae with extremely high HM removal efficiency for practical wastewater treatment worldwide.

Dermabrasion and wire loop electrocautery are controlled scalpel-less procedures to remove superficial skin layers to treat dermal surface irregularities. Their postprocedure healing involves healing by secondary intention. The purpose of this paper is to discuss the use of diamond fraise dermabrasion to improve scars and the use of wire loop electrocautery to treat rhinophyma surface irregularities. Both techniques are minimally invasive and low cost, and at the same time, can significantly improve facial skin deformities. An advantage in using wire loop electrocautery for rhinophyma excision is that it is a simple, economic, and very effective technique to sculpt the nose, with minimal intraoperative bleeding. With dermabrasion, pretreatment and postregimens can help improve postprocedure results. Future efforts to modulate the healing from both of these techniques include the potential use of topical growth factors, autologous platelet-rich plasma, or using stem cells to accelerate collagen formation and reepithelization during the postprocedure period.

A characteristic clinical feature of COVID-19 is the frequent incidence of microvascular thrombosis. In fact, COVID-19 autopsy reports have shown widespread thrombotic microangiopathy characterized by extensive diffuse microthrombi within peripheral capillaries and arterioles in lungs, hearts, and other organs, resulting in multiorgan failure. However, the underlying process of COVID-19-associated microvascular thrombosis remains elusive due to the lack of tools to statistically examine platelet aggregation (i.e., the initiation of microthrombus formation) in detail. Here we present a method for massive image-based profiling, temporal monitoring, and big data analysis of circulating platelets and platelet aggregates in the blood of COVID-19 patients at single-cell resolution, to provide previously unattainable insights into the disease. In fact, our analysis of the image data from 110 hospitalized patients shows the anomalous presence of excessive platelet aggregates in nearly 90% of all COVID-19 patients. Furthermore, results indicate strong links between the concentration of platelet aggregates and the severity, mortality, and respiratory condition of patients with COVID-19. Finally, high-dimensional analysis based on deep learning shows that the disease behaves as systemic thrombosis.

A characteristic clinical feature of COVID-19 is the frequent occurrence of thrombotic events. Furthermore, many cases of multiorgan failure are thrombotic in nature. Since the outbreak of COVID-19, D-dimer testing has been used extensively to evaluate COVID-19-associated thrombosis, but does not provide a complete view of the disease because it probes blood coagulation, but not platelet activity. Due to this limitation, D-dimer testing fails to account for thrombotic events which occur despite low D-dimer levels, such as sudden stroke in young patients and autopsy-identified widespread microthrombi in multiple organs. Here we report the landscape of circulating platelet aggregates in COVID-19 obtained by large-scale single-cell image-based profiling and temporal monitoring of the blood of COVID-19 patients (n = 110). Surprisingly, our analysis shows the anomalous presence of excessive platelet aggregates in nearly 90% of all COVID-19 patients, including those who were not clinically diagnosed with thrombosis and those with low D-dimer levels (≤1 µg/mL). Additionally, results indicate a strong link between the concentration of platelet aggregates and the severity and mortality of COVID-19. Finally, high-dimensional analysis and comparison with other diseases reveal that COVID-19 behaves as a product of thrombosis (localized) and infectious diseases (systemic), as a cause of systemic thrombosis.

In the past few decades, microalgae-based bioremediation methods for treating heavy metal (HM)-polluted wastewater have attracted much attention by virtue of their environment friendliness, cost efficiency, and sustainability. However, their HM removal efficiency is far from practical use. Directed evolution is expected to be effective for developing microalgae with a much higher HM removal efficiency, but there is no non-invasive or label-free indicator to identify them. Here, we present an intelligent cellular morphological indicator for identifying the HM removal efficiency of

Microalgae have recently been gaining attention for their versatile uses and environmentally friendly benefits. Accurate characterization and classification of a large population of microalgal cells with single-cell resolution are highly valuable for their diverse applications such as water treatment, biofuel production, food, and nitrogen-fixing biofertilization. Here we demonstrate accurate classification of spherical microalgal species using recently developed frequency-division-multiplexed fluorescence imaging flow cytometry and machine learning. We obtained three-color (bright-field and two-color fluorescence) images of microalgal cells, quantified morphological features of the cells using the images, and classified six microalgae using features via a support vector machine. By virtue of the rich information content of the three-color images of microalgal cells, we classified six microalgae with a high accuracy of 99.8%. Our method can evaluate large populations of microalgal cells with single-cell resolution and hence holds promise for various applications such as environmental monitoring of the hydrosphere.

Fluorescence imaging flow cytometry is an emerging technique for analyzing a large number of cells with high accuracy over conventional flow cytometry by virtue of its imaging capability. Unfortunately, the cell throughput of conventional fluorescence imaging flow cytometers (~1,000 cells/sec) is much lower than that of standard non-imaging flow cytometers due to the use of a CCD image sensor having a limited data transfer rate, making it difficult to analyze a large population of cells. Here we report our experimental demonstration of highly accurate classification of microalgae with a frequency-division-multiplexed confocal imaging flow cytometer (IFC) that enables imaging of every single microalgal cell with an unprecedentedly high throughput of 20,000 cells/sec. The high-speed imaging performance of the IFC is enabled by employing frequency-division-multiplexed confocal microscopy, which uses a sensitive single-pixel photodetector such as an avalanche photodetector or a photomultiplier tube to obtain images of flowing cells. We stained three species of microalgae (Chlamydomonas reinhardtii, Haematococcus lacustris, and Euglena gracilis) with SYTO16 and obtained three-color images of the cells (bright-field, fluorescence staining of nuclei, and autofluorescence of chlorophyll). We extracted 243-dimensional features from each three-color image and employed a support vector machine to classify the cells with the obtained multi-dimensional data. As a result, the cells were successfully classified with an accuracy of 99.7%. Due to the IFC’s multi-color imaging capability with an unprecedentedly high throughput, our technique has a wide variety of potential applications other than microalga classification, such as accurate blood screening and liquid biopsy.

Objectives: To describe a case of the rare complication of facial palsy following preoperative embolization of a juvenile nasopharyngeal angiofibroma (JNA). To illustrate the vascular supply to the facial nerve and as a result, highlight the etiology of the facial nerve palsy. Methods: The angiography and magnetic resonance (MR) imaging of a case of facial palsy following preoperative embolization of a JNA is reviewed. Results: A 13-year-old male developed left-sided facial palsy following preoperative embolization of a left-sided JNA. Evaluation of MR imaging studies and retrospective review of the angiographic data suggested errant embolization of particles into the petrosquamosal branch of the middle meningeal artery (MMA), a branch of the internal maxillary artery (IMA), through collateral vasculature. The petrosquamosal branch of the MMA is the predominant blood supply to the facial nerve in the facial canal. The facial palsy resolved since complete infarction of the nerve was likely prevented by collateral blood supply from the stylomastoid artery. Conclusions: Facial palsy is a potential complication of embolization of the IMA, a branch of the external carotid artery (ECA). This is secondary to ischemia of the facial nerve due to embolization of its vascular supply. Clinicians should be aware of this potential complication and counsel patients accordingly prior to embolization for JNA.

The relative value of facial plastic surgeon personal and practice attributes is relevant to the broader health care system because of increasing out-of-pocket expenses to patients.To determine the relative value of specific facial plastic surgeon personal and practice attributes available online from the perspective of patients.This study consisted of an electronic survey sent to patients by email using choice-based conjoint analysis; surveys were sent between December 2015 and March 2016. Participants had agreed to join email registries to be sent email surveys and promotions at 3 private facial plastic and reconstructive surgery practices. The following surgeon personal and practice attributes and levels were compared: (1) outcome transparency (above average, average, not available); (2) surgical training affiliations (US News and World Reports rankings); (3) online rating site scores (2 [poor], 3, or 4 [excellent] stars); and (4) price ($1×, $2×, and $3× [× = $1500; average cost was set at $2×]).The relative importance of outcome transparency, surgical training affiliations, online rating scores, and price to prospective patients.Overall, 291 patients participated for a completion rate of 68%. Outcome transparency was the most valued attribute (attribute utility range = 141; attribute importance = 35.2%). Price was the least valued attribute (attribute utility range = 58.59; attribute importance = 15.1%). Assuming top-tier affiliations and 4-star ratings, share of market (SOM) was 75.5% for surgeons with above-average outcome transparency priced at $3× compared with those surgeons with no outcomes available priced at $1×. Holding price constant at $2×, surgeons with middle-tier affiliations and 2-star online ratings but above average outcomes achieved 48.4% SOM when compared with those surgeons with top-tier affiliations and 4-star online ratings without available outcomes.Facial plastic surgery patients most value surgeons who publish outcomes. Moreover, they are willing to discount poor rating scores and lower-ranked institutional affiliations when outcome transparency is high. This study demonstrates that outcome transparency is crucial in facial plastic surgery markets.NA.

We present methods of fluorescence confocal microscopy that enable unprecedentedly high frame rate of > 10,000 fps. The methods are based on a frequency-division multiplexing technique, which was originally developed in the field of communication engineering. Specifically, we achieved a broad bandwidth (~400 MHz) of detection signals using a dual- AOD method and overcame limitations in frame rate, due to a scanning device, by using a multi-line focusing method, resulting in a significant increase in frame rate. The methods have potential biomedical applications such as observation of sub-millisecond dynamics in biological tissues, in-vivo three-dimensional imaging, and fluorescence imaging flow cytometry.

Laser-scanning confocal fluorescence microscopy is an indispensable tool for biomedical research by virtue of its high spatial resolution. Its temporal resolution is equally important, but is still inadequate for many applications. Here we present a confocal fluorescence microscope that, for the first time to our knowledge, surpasses the highest possible frame rate constrained only by the fluorescence lifetime of fluorophores (typically a few to several nanoseconds). This microscope is enabled by integrating a broadband, spatially distributed, dual-frequency comb or spatial dual-comb and quadrature amplitude modulation for optimizing spectral efficiency into frequency-division multiplexing with single-pixel photodetection for signal integration. Specifically, we demonstrate confocal fluorescence microscopy at a record high frame rate of 16,000 frames/s. To show its broad biomedical utility, we use the microscope to demonstrate 3D volumetric confocal fluorescence microscopy of cellular dynamics at 104 volumes/s and confocal fluorescence imaging flow cytometry of hematological and microalgal cells at up to 2 m/s.

This series of three patients is the first description of the presentation, clinical course, and endoscopic findings of nasogastric tube-related airway distress, or nasogastric tube syndrome, in infants. We identify key differences in disease features from those described in adults, based on our literature review. Specifically, infant nasogastric tube syndrome presented as significant respiratory distress and postcricoid inflammation without vocal fold immobility. Symptoms resolved more quickly (mean±SD, 2±1 days) than reported in adults. We suggest that nasogastric tube syndrome should be considered in infants with otherwise unexplained respiratory distress, even in the absence of impaired vocal fold mobility.

Objective This study evaluated the acute effects of selective fetoscopic laser photocoagulation (SFLP) on recipient cardiovascular function in a twin-twin transfusion syndrome (TTTS) pregnancy. Study Design This was a retrospective chart review of echocardiographic data in TTTS including right (RV) and left (LV) ventricular Doppler myocardial performance index (MPI); LV and RV end diastolic wall thickness; and umbilical artery (UA), vein (UV), and ductus venosus (DV) Dopplers. The primary outcome measures were improved MPI defined as greater than 10% interval decrease in left and/or right MPI. Data were analyzed by Student t test and Fisher's exact test. Results Sixty-five patients met inclusion criteria. SFLP results in a significant improvement in UV and DV Doppler and an increase in both RV and LV wall thickness. A 10% or greater improvement in recipient LV MPI after SFLP is associated with improved recipient survival as compared with unimproved LV MPI (100% vs 86.1%, P = .05). Conclusion Improved recipient myocardial performance index after SFLP is associated with improvement in recipient survival.