Design and Usability of an Open-Source, Low-Cost Flexible Laryngoscope for Resource-Limited Settings.

Importance: Endoscopes are paramount to the practice of otolaryngology. To provide physicians in low-middle-income countries with adequate tools to treat otolaryngologic problems, it is necessary to create a low-cost sustainable option. Objective: To describe the design and usability of an open-source, low-cost flexible laryngoscope that addresses the lack of affordable and accessible methods for otolaryngologic visualization in resource-limited settings. Design, Setting, and Participants: This quality improvement study used a mixed-methods approach, including a technical description of device design as well as quantitative and qualitative survey evaluation of device usability. Engineering involved device design, sourcing or manufacturing individual components, fabricating a prototype, and iterative testing. Key assumptions and needs for the device were identified in collaboration with otolaryngologists in Zimbabwe, and designed and simulated by biomedical engineers in a US university laboratory. Board-certified otolaryngologists at a single US university hospital trialed a completed prototype on simulated airways between May 2023 and June 2023. Main Outcomes and Measures: Technical details on the design of the device are provided. Otolaryngologist gave feedback on device characteristics, maneuverability, and visualization using the System Usability Scale, a customized Likert-scale questionnaire (5-point scale), and semistructured interviews. Results: A functional prototype meeting requirements was completed consisting of a distal-chip camera, spring bending tip, handle housing the control mechanism and electronics, and flexible polyether block amide-coated silicone sheath housing the camera and control wires; an external monitor provided real-time visualization and ability to store data. A total of 14 otolaryngologists participated in the device review. The mean (SD) System Usability Scale score was 88.93 (10.08), suggesting excellent usability. The device was rated highly for ease of set up, physical attributes, image quality, and functionality. Conclusions and Relevance: This quality improvement study described the design of a novel open-source low-cost flexible laryngoscope that external review with otolaryngologists suggests was usable and feasible in various resource-limited environments. Future work is needed to translate the model into a clinical setting.

MarkovHC: Markov hierarchical clustering for the topological structure of high-dimensional single-cell omics data with transition pathway and critical point detection.

Clustering cells and depicting the lineage relationship among cell subpopulations are fundamental tasks in single-cell omics studies. However, existing analytical methods face challenges in stratifying cells, tracking cellular trajectories, and identifying critical points of cell transitions. To overcome these, we proposed a novel Markov hierarchical clustering algorithm (MarkovHC), a topological clustering method that leverages the metastability of exponentially perturbed Markov chains for systematically reconstructing the cellular landscape. Briefly, MarkovHC starts with local connectivity and density derived from the input and outputs a hierarchical structure for the data. We firstly benchmarked MarkovHC on five simulated datasets and ten public single-cell datasets with known labels. Then, we used MarkovHC to investigate the multi-level architectures and transition processes during human embryo preimplantation development and gastric cancer procession. MarkovHC found heterogeneous cell states and sub-cell types in lineage-specific progenitor cells and revealed the most possible transition paths and critical points in the cellular processes. These results demonstrated MarkovHC's effectiveness in facilitating the stratification of cells, identification of cell populations, and characterization of cellular trajectories and critical points.

Comprehensive pregnancy monitoring with a network of wireless, soft, and flexible sensors in high- and low-resource health settings.

Vital signs monitoring is a fundamental component of ensuring the health and safety of women and newborns during pregnancy, labor, and childbirth. This monitoring is often the first step in early detection of pregnancy abnormalities, providing an opportunity for prompt, effective intervention to prevent maternal and neonatal morbidity and mortality. Contemporary pregnancy monitoring systems require numerous devices wired to large base units; at least five separate devices with distinct user interfaces are commonly used to detect uterine contractility, maternal blood oxygenation, temperature, heart rate, blood pressure, and fetal heart rate. Current monitoring technologies are expensive and complex with implementation challenges in low-resource settings where maternal morbidity and mortality is the greatest. We present an integrated monitoring platform leveraging advanced flexible electronics, wireless connectivity, and compatibility with a wide range of low-cost mobile devices. Three flexible, soft, and low-profile sensors offer comprehensive vital signs monitoring for both women and fetuses with time-synchronized operation, including advanced parameters such as continuous cuffless blood pressure, electrohysterography-derived uterine monitoring, and automated body position classification. Successful field trials of pregnant women between 25 and 41 wk of gestation in both high-resource settings (n = 91) and low-resource settings (n = 485) demonstrate the system's performance, usability, and safety.

Development and validation of an objective scoring tool to evaluate surgical dissection: Dissection Assessment for Robotic Technique (DART).

Purpose: Evaluation of surgical competency has important implications for training new surgeons, accreditation, and improving patient outcomes. A method to specifically evaluate dissection performance does not yet exist. This project aimed to design a tool to assess surgical dissection quality. Methods: Delphi method was used to validate structure and content of the dissection evaluation. A multi-institutional and multi-disciplinary panel of 14 expert surgeons systematically evaluated each element of the dissection tool. Ten blinded reviewers evaluated 46 de-identified videos of pelvic lymph node and seminal vesicle dissections during the robot-assisted radical prostatectomy. Inter-rater variability was calculated using prevalence-adjusted and bias-adjusted kappa. The area under the curve from receiver operating characteristic curve was used to assess discrimination power for overall DART scores as well as domains in discriminating trainees (≤100 robotic cases) from experts (>100). Results: Four rounds of Delphi method achieved language and content validity in 27/28 elements. Use of 3- or 5-point scale remained contested; thus, both scales were evaluated during validation. The 3-point scale showed improved kappa for each domain. Experts demonstrated significantly greater total scores on both scales (3-point, p< 0.001; 5-point, p< 0.001). The ability to distinguish experience was equivalent for total score on both scales (3-point AUC= 0.92, CI 0.82-1.00, 5-point AUC= 0.92, CI 0.83-1.00). Conclusions: We present the development and validation of Dissection Assessment for Robotic Technique (DART), an objective and reproducible 3-point surgical assessment to evaluate tissue dissection. DART can effectively differentiate levels of surgeon experience and can be used in multiple surgical steps.

Reliable, low-cost, fully integrated hydration sensors for monitoring and diagnosis of inflammatory skin diseases in any environment.

Present-day dermatological diagnostic tools are expensive, time-consuming, require substantial operational expertise, and typically probe only the superficial layers of skin (~15 µm). We introduce a soft, battery-free, noninvasive, reusable skin hydration sensor (SHS) adherable to most of the body surface. The platform measures volumetric water content (up to ~1 mm in depth) and wirelessly transmits data to any near-field communication-compatible smartphone. The SHS is readily manufacturable, comprises unique powering and encapsulation strategies, and achieves high measurement precision (±5% volumetric water content) and resolution (±0.015°C skin surface temperature). Validation on n = 16 healthy/normal human participants reveals an average skin water content of ~63% across multiple body locations. Pilot studies on patients with atopic dermatitis (AD), psoriasis, urticaria, xerosis cutis, and rosacea highlight the diagnostic capability of the SHS (P AD = 0.0034) and its ability to study impact of topical treatments on skin diseases.

Costs and Complications Associated With Resection of Supratentorial Tumors With and Without the Operative Microscope in the United States.

BACKGROUND: The operative microscope, a commonly used tool in neurosurgery, is critical in many supratentorial tumor cases. However, use of operating microscope for supratentorial tumor varies by surgeon. OBJECTIVES: To assess complication rates, readmissions, and costs associated with operative microscope use in supratentorial resections. METHODS: A retrospective analysis was conducted using a national administrative database to identify patients with glioma or brain metastases who underwent supratentorial resection between 2007 and 2016. Univariate and multivariate analyses were used to assess 30-day complications, readmissions, and costs between patients who underwent resection with and without use of microscope. RESULTS: The cohort included 12,058 glioma patients and 5433 metastasis patients. Rates of microscope use varied by state from 19.0% to 68.6%. Microscope use was associated with $5228.90 in additional costs of index hospitalization among glioma patients (P <0.001), and $2824.00 among metastasis patients (P <0.001). Rates of intraoperative cerebral edema were lower among the microscope cohort than among the nonmicroscope cohort (P <0.027). Microscope use was associated with a slight reduction in 30-day rates of neurological complications (14.7% vs. 16.7%, P = 0.048), specifically in nonspecific cerebrovascular complications. There were no differences in rates of other complications, readmissions, or 30-day postoperative costs. CONCLUSIONS: Use of operative microscope for supratentorial resections varies by state and is associated with higher cost of surgery. Microscope use may be associated with lower rates of intraoperative cerebral edema and some cerebrovascular complications, but is not associated with significant differences in other complications, readmissions, or 30-day costs.

Outcomes and Costs Following Ommaya Placement with Thrombocytopenia Among U.S. Patients with Cancer.

BACKGROUND: Placement of Ommaya reservoirs for the administration of intrathecal chemotherapy may be complicated by comorbid thrombocytopenia among patients with hematologic or leptomeningeal disease. Aggregated data on risks of Ommaya placement among thrombocytopenic patients are lacking. This study assesses complications, revision rates, and costs associated with Ommaya placement among patients with thrombocytopenia in a large population sample. METHODS: Using a national administrative database, this retrospective study identifies a cohort of adult patients with cancer who underwent Ommaya placement between 2007 and 2016. Preoperative thrombocytopenia was defined as diagnosis of secondary thrombocytopenia, bleeding event, procedure to control bleeding, or platelet transfusion, within 30 days before index admission. Univariate and multivariate analyses were performed to assess costs, 30-day complications, readmissions, and revisions among patients with and without preoperative thrombocytopenia. RESULTS: The analytic cohort included 1652 patients, of whom 29.3% met criteria for preoperative thrombocytopenia. In-hospital mortality rates were 7.7% among patients thrombocytopenia with versus 1.2% among patients without thrombocytopenia (P < 0.001). Preoperative thrombocytopenia was associated with 14.5 times greater hazard of intracranial hemorrhage within 30 days following Ommaya placement, occurring in 25.6% versus 2.0% of patients with and without thrombocytopenia, respectively (P < 0.014). Revision rates did not differ significantly between patients with and without thrombocytopenia. Thrombocytopenia was associated with longer length of stay (7.4 vs. 13.9 days, P < 0.001) and additional $10,000 per patient in costs of index hospitalization (P < 0.001). CONCLUSIONS: This is the largest study to date documenting costs and complication rates of Ommaya placement in patients with and without thrombocytopenia.

A Passive Mixing Microfluidic Urinary Albumin Chip for Chronic Kidney Disease Assessment.

Urinary albumin level is an important indicator of kidney damage in chronic kidney disease (CKD) but effective routine albumin detection tools are lacking. In this paper, we developed a low-cost and high accuracy microfluidic urinary albumin chip (UAL-Chip) to rapidly measure albumin in urine. The UAL-Chip offers three major features: (1) we incorporated a fluorescent reaction assay into the chip to improve the detection accuracy; (2) we constructed a passive and continuous mixing module in the chip that provides user-friendly operation and greater signal stability; (3) we applied a pressure-balancing strategy based on the immiscible oil coverage that achieves precise control of the sample-dye mixing ratio. We validated the UAL-Chip using both albumin standards and urine samples from 12 CKD patients and achieved an estimated limit of detection (LOD) of 5.2 µg/mL. The albumin levels in CKD patients' urine samples measured by UAL-Chip is consistent with the traditional well-plate measurements and clinical results. We foresee the potential of extending this passive and precise mixing platform to assess various disease biomarkers.

Reconstructing cell cycle pseudo time-series via single-cell transcriptome data.

Single-cell mRNA sequencing, which permits whole transcriptional profiling of individual cells, has been widely applied to study growth and development of tissues and tumors. Resolving cell cycle for such groups of cells is significant, but may not be adequately achieved by commonly used approaches. Here we develop a traveling salesman problem and hidden Markov model-based computational method named reCAT, to recover cell cycle along time for unsynchronized single-cell transcriptome data. We independently test reCAT for accuracy and reliability using several data sets. We find that cell cycle genes cluster into two major waves of expression, which correspond to the two well-known checkpoints, G1 and G2. Moreover, we leverage reCAT to exhibit methylation variation along the recovered cell cycle. Thus, reCAT shows the potential to elucidate diverse profiles of cell cycle, as well as other cyclic or circadian processes (e.g., in liver), on single-cell resolution.In single-cell RNA sequencing data of heterogeneous cell populations, cell cycle stage of individual cells would often be informative. Here, the authors introduce a computational model to reconstruct a pseudo-time series from single cell transcriptome data, identify the cell cycle stages, identify candidate cell cycle-regulated genes and recover the methylome changes during the cell cycle.

Rapid and Low-Cost CRP Measurement by Integrating a Paper-Based Microfluidic Immunoassay with Smartphone (CRP-Chip).

Traditional diagnostic tests for chronic diseases are expensive and require a specialized laboratory, therefore limiting their use for point-of-care (PoC) testing. To address this gap, we developed a method for rapid and low-cost C-reactive protein (CRP) detection from blood by integrating a paper-based microfluidic immunoassay with a smartphone (CRP-Chip). We chose CRP for this initial development because it is a strong biomarker of prognosis in chronic heart and kidney disease. The microfluidic immunoassay is realized by lateral flow and gold nanoparticle-based colorimetric detection of the target protein. The test image signal is acquired and analyzed using a commercial smartphone with an attached microlens and a 3D-printed chip-phone interface. The CRP-Chip was validated for detecting CRP in blood samples from chronic kidney disease patients and healthy subjects. The linear detection range of the CRP-Chip is up to 2 µg/mL and the detection limit is 54 ng/mL. The CRP-Chip test result yields high reproducibility and is consistent with the standard ELISA kit. A single CRP-Chip can perform the test in triplicate on a single chip within 15 min for less than 50 US cents of material cost. This CRP-Chip with attractive features of low-cost, fast test speed, and integrated easy operation with smartphones has the potential to enable future clinical PoC chronic disease diagnosis and risk stratification by parallel measurements of a panel of protein biomarkers.

Retrosigmoid Versus Translabyrinthine Approach for Acoustic Neuroma Resection: An Assessment of Complications and Payments in a Longitudinal Administrative Database.

Object Retrosigmoid (RS) and translabyrinthine (TL) surgery remain essential treatment approaches for symptomatic or enlarging acoustic neuromas (ANs). We compared nationwide complication rates and payments, independent of tumor characteristics, for these two strategies. Methods We identified 346 and 130 patients who underwent RS and TL approaches, respectively, for AN resection in the 2010-2012 MarketScan database, which characterizes primarily privately-insured patients from multiple institutions nationwide. Results Although we found no difference in 30-day general neurological or neurosurgical complication rates, in TL procedures there was a decreased risk for postoperative cranial nerve (CN) VII injury (20.2% vs 10.0%, CI 0.23-0.82), dysphagia (10.4% vs 3.1%, CI 0.10-0.78), and dysrhythmia (8.4% vs 2.3%, CI 0.08-0.86). Overall, there was no difference in surgical repair rates of CSF leak; however, intraoperative fat grafting was significantly higher in TL approaches (19.8% vs 60.2%, CI 3.95-9.43). In patients receiving grafts, there was a trend towards a higher repair rate after RS approach, while in those without grafts, there was a trend towards a higher repair rate after TL approach. Median total payments were $16,856 higher after RS approaches ($67,774 vs $50,918, p < 0.0001), without differences in physician or 90-day postoperative payments. Conclusions  Using a nationwide longitudinal database, we observed that the TL, compared to RS, approach for AN resection experienced lower risks of CN VII injury, dysphagia, and dysrhythmia. There was no significant difference in CSF leak repair rates. The payments for RS procedures exceed payments for TL procedures by approximately $17,000. Data from additional years and non-private sources will further clarify these trends.

Cognitive function in older adults according to current socioeconomic status.

Cognitive function may be influenced by education, socioeconomic status, sex, and health status. Furthermore, aging interacts with these factors to influence cognition and dementia risk in late life. Factors that may increase or decrease successful cognitive aging are of critical importance, particularly if they are modifiable. The purpose of this study was to determine if economic status in late life is associated with cognition independent of socioeconomic status in early life. Cross-sectional demographic, socioeconomic, and cognitive function data were obtained in 2592 older adults (average age 71.6 years) from the Center for Disease Control's National Health and Nutrition Examination Survey (NHANES) and analyzed with linear regression modeling. Cognitive function, as measured with a test of processing speed, was significantly associated with poverty index scores after adjusting for educational attainment as an estimate of childhood socioeconomic status, ethnic background, age, health status, and sex (P < 0.001). Our findings suggest that current economic status is independently associated with cognitive function in adults over age 60 years.

Genome-wide localization of protein-DNA binding and histone modification by a Bayesian change-point method with ChIP-seq data.

Next-generation sequencing (NGS) technologies have matured considerably since their introduction and a focus has been placed on developing sophisticated analytical tools to deal with the amassing volumes of data. Chromatin immunoprecipitation sequencing (ChIP-seq), a major application of NGS, is a widely adopted technique for examining protein-DNA interactions and is commonly used to investigate epigenetic signatures of diffuse histone marks. These datasets have notoriously high variance and subtle levels of enrichment across large expanses, making them exceedingly difficult to define. Windows-based, heuristic models and finite-state hidden Markov models (HMMs) have been used with some success in analyzing ChIP-seq data but with lingering limitations. To improve the ability to detect broad regions of enrichment, we developed a stochastic Bayesian Change-Point (BCP) method, which addresses some of these unresolved issues. BCP makes use of recent advances in infinite-state HMMs by obtaining explicit formulas for posterior means of read densities. These posterior means can be used to categorize the genome into enriched and unenriched segments, as is customarily done, or examined for more detailed relationships since the underlying subpeaks are preserved rather than simplified into a binary classification. BCP performs a near exhaustive search of all possible change points between different posterior means at high-resolution to minimize the subjectivity of window sizes and is computationally efficient, due to a speed-up algorithm and the explicit formulas it employs. In the absence of a well-established "gold standard" for diffuse histone mark enrichment, we corroborated BCP's island detection accuracy and reproducibility using various forms of empirical evidence. We show that BCP is especially suited for analysis of diffuse histone ChIP-seq data but also effective in analyzing punctate transcription factor ChIP datasets, making it widely applicable for numerous experiment types.

Novel Markov model of induced pluripotency predicts gene expression changes in reprogramming.

BACKGROUND: Somatic cells can be reprogrammed to induced-pluripotent stem cells (iPSCs) by introducing few reprogramming factors, which challenges the long held view that cell differentiation is irreversible. However, the mechanism of induced pluripotency is still unknown. METHODS: Inspired by the phenomenological reprogramming model of Artyomov et al (2010), we proposed a novel Markov model, stepwise reprogramming Markov (SRM) model, with simpler gene regulation rules and explored various properties of the model with Monte Carlo simulation. We calculated the reprogramming rate and showed that it would increase in the condition of knockdown of somatic transcription factors or inhibition of DNA methylation globally, consistent with the real reprogramming experiments. Furthermore, we demonstrated the utility of our model by testing it with the real dynamic gene expression data spanning across different intermediate stages in the iPS reprogramming process. RESULTS: The gene expression data at several stages in reprogramming and the reprogramming rate under several typically experiment conditions coincided with our simulation results. The function of reprogramming factors and gene expression change during reprogramming could be partly explained by our model reasonably well. CONCLUSIONS: This lands further support on our general rules of gene regulation network in iPSC reprogramming. This model may help uncover the basic mechanism of reprogramming and improve the efficiency of converting somatic cells to iPSCs.

Computational prediction of eukaryotic protein-coding genes.

The human genome sequence is the book of our life. Buried in this large volume are our genes, which are scattered as small DNA fragments throughout the genome and comprise a small percentage of the total text. Finding these indistinct 'needles' in a vast genomic 'haystack' can be extremely challenging. In response to this challenge, computational prediction approaches have proliferated in recent years that predict the location and structure of genes. Here, I discuss these approaches and explain why they have become essential for the analyses of newly sequenced genomes.