ABSTRACT
Significance: Photoacoustic imaging (PAI) promises to measure spatially resolved blood oxygen saturation but suffers from a lack of accurate and robust spectral unmixing methods to deliver on this promise. Accurate blood oxygenation estimation could have important clinical applications from cancer detection to quantifying inflammation. Aim: We address the inflexibility of existing data-driven methods for estimating blood oxygenation in PAI by introducing a recurrent neural network architecture. Approach: We created 25 simulated training dataset variations to assess neural network performance. We used a long short-term memory network to implement a wavelength-flexible network architecture and proposed the Jensen-Shannon divergence to predict the most suitable training dataset. Results: The network architecture can flexibly handle the input wavelengths and outperforms linear unmixing and the previously proposed learned spectral decoloring method. Small changes in the training data significantly affect the accuracy of our method, but we find that the Jensen-Shannon divergence correlates with the estimation error and is thus suitable for predicting the most appropriate training datasets for any given application. Conclusions: A flexible data-driven network architecture combined with the Jensen-Shannon divergence to predict the best training data set provides a promising direction that might enable robust data-driven photoacoustic oximetry for clinical use cases.
Subject(s)
Neural Networks, Computer , Oximetry , Photoacoustic Techniques , Photoacoustic Techniques/methods , Oximetry/methods , Humans , Oxygen/blood , Oxygen Saturation/physiology , AlgorithmsABSTRACT
The development of x-ray free electron laser (XFEL) light sources and serial crystallography methodologies has led to a revolution in protein crystallography, enabling the determination of previously unobtainable protein structures and near-atomic resolution of otherwise poorly diffracting protein crystals. However, to utilize XFEL sources efficiently demands the continuous, rapid delivery of a large number of difficult-to-handle microcrystals to the x-ray beam. A recently developed fixed-target system, in which crystals of interest are enclosed within a sample holder, which is rastered through the x-ray beam, is discussed in detail in this Perspective. The fixed target is easy to use, maintains sample hydration, and can be readily modified to allow a broad range of sample types and different beamline requirements. Recent innovations demonstrate the potential of such microfluidic-based fixed targets to be an all-around "workhorse" for serial crystallography measurements. This Perspective will summarize recent advancements in microfluidic fixed targets for serial crystallography, examine needs for future development, and guide users in designing, choosing, and utilizing a fixed-target sample delivery device for their system.
ABSTRACT
Over the past two decades, serial X-ray crystallography has enabled the structure determination of a wide range of proteins. With the advent of X-ray free-electron lasers (XFELs), ever-smaller crystals have yielded high-resolution diffraction and structure determination. A crucial need to continue advancement is the efficient delivery of fragile and micrometre-sized crystals to the X-ray beam intersection. This paper presents an improved design of an all-polymer microfluidic `chip' for room-temperature fixed-target serial crystallography that can be tailored to broadly meet the needs of users at either synchrotron or XFEL light sources. The chips are designed to be customized around different types of crystals and offer users a friendly, quick, convenient, ultra-low-cost and robust sample-delivery platform. Compared with the previous iteration of the chip [Gilbile et al. (2021), Lab Chip, 21, 4831-4845], the new design eliminates cleanroom fabrication. It has a larger imaging area to volume, while maintaining crystal hydration stability for both in situ crystallization or direct crystal slurry loading. Crystals of two model proteins, lysozyme and thaumatin, were used to validate the effectiveness of the design at both synchrotron (lysozyme and thaumatin) and XFEL (lysozyme only) facilities, yielding complete data sets with resolutions of 1.42, 1.48 and 1.70â Å, respectively. Overall, the improved chip design, ease of fabrication and high modifiability create a powerful, all-around sample-delivery tool that structural biologists can quickly adopt, especially in cases of limited sample volume and small, fragile crystals.
Subject(s)
Cycloparaffins , Muramidase , Crystallography , Muramidase/chemistry , Microfluidics/methods , Temperature , Equipment Design , Crystallography, X-Ray , Proteins , PolymersABSTRACT
BACKGROUND: There is paucity of data on Atrial Fibrillation (AF) management and associated clinical outcomes among Asian Americans. This study sought to investigate baseline risk factor profiles, racial disparities in clinical management and adverse clinical outcomes among White and Asian Americans. METHODS: We used National Cardiovascular Data Registry (NCDR®) Practice Innovation and Clinical Excellence (PINNACLE) registry and linked Centers of Medicare and Medicaid Services data to identify Asian and White patients with AF between January 1, 2013-June 30, 2018. We compared rates of baseline risk factors, management strategies (rate versus rhythm control), anticoagulation use and rates of adverse events between racial groups. The two race groups were compared using hierarchical multivariable adjusted regression models to account for site and confounders. RESULTS: In total, 1,359,827 patients (18,793 Asians and 1,341,034 Whites) were included in our analysis. Compared to White Americans, Asian Americans were more likely to use a rate control strategy (Odds Ratio [OR]: 1.20, 95% Confidence Interval [CI]: 1.15-1.25) and lower odds of rhythm control strategy (atrial ablations, cardioversions, or use of antiarrhythmic drugs) (OR: 0.83, 95% CI: 0.80-0.87) in adjusted analysis. Use of oral anticoagulants and direct oral anticoagulants were similar. There were no significant race-based differences in likelihood of all-cause mortality, stroke, and bleeding requiring hospitalization. Analyses performed using propensity score matching were consistent with the main results. CONCLUSIONS: Asian Americans with AF have a lower likelihood of being managed with rhythm control strategies. Overall use of OAC and AF related adverse events remain similar between the two racial groups.
Subject(s)
Atrial Fibrillation , Stroke , Aged , Anticoagulants , Asian , Atrial Fibrillation/diagnosis , Atrial Fibrillation/therapy , Humans , Medicare , Registries , Risk Factors , United States/epidemiologyABSTRACT
OBJECTIVE: This study aimed to investigate the association between age and the risk of 30-day unplanned readmission among adult patients with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI). METHODS: This retrospective analysis included patients from the Nationwide Readmissions Database with AMI who underwent PCI during 2013-2014. We used multivariable logistic regression model to calculate adjusted odds ratios (AORs) for risk of readmission. To examine potential non-linear association, we performed logistic regression with restricted cubic splines (RCS). RESULTS: Of the 492 550 patients with AMI aged above 18 years undergoing PCI during the index hospitalisation, 48 630 (9.87%) were readmitted within 30 days. Although the crude readmission rate of younger patients (aged 18-54 years) was the lowest (7.27%), younger patients had higher risk of readmission compared with patients aged 55-64 years for all-causes (AOR 1.06 (1.01 to 1.11), p=0.0129) and specific causes, such as AMI and chest pain (both cardiac and non-specific) after adjusted for covariates. Patients aged 65-74 years were at lower risk of all-cause readmission. Older patients (age ≥75 years) had higher risk of readmission for heart failure (AOR 1.50 (1.29 to 1.74)) and infection (AOR 1.44 (1.16 to 1.79)), but lower risk for chest pain. RCS analyses showed a U-shaped relationship between age and readmission risk. CONCLUSIONS: Our results suggest higher risk of readmission in younger patients for all-cause unplanned readmission after adjusted for covariates. The trends of readmission risk along with age were different for specific causes. Age-targeted initiatives are warranted to reduce preventable readmissions in patients with AMI undergoing PCI.
Subject(s)
Myocardial Infarction/therapy , Patient Readmission , Percutaneous Coronary Intervention/adverse effects , Adolescent , Adult , Age Factors , Aged , Databases, Factual , Female , Humans , Male , Middle Aged , Myocardial Infarction/diagnosis , Myocardial Infarction/epidemiology , Retrospective Studies , Risk Assessment , Risk Factors , Time Factors , Treatment Outcome , United States , Young AdultABSTRACT
Tunable bioprinting materials are capable of creating a broad spectrum of physiological mimicking 3D models enabling in vitro studies that more accurately resemble in vivo conditions. Tailoring the material properties of the bioink such that it achieves both bioprintability and biomimicry remains a key challenge. Here we report the development of engineered composite hydrogels consisting of gelatin and alginate components. The composite gels are demonstrated as a cell-laden bioink to build 3D bioprinted in vitro breast tumor models. The initial mechanical characteristics of each composite hydrogel are correlated to cell proliferation rates and cell spheroid morphology spanning month long culture conditions. MDA-MB-231 breast cancer cells show gel formulation-dependency on the rates and frequency of self-assembly into multicellular tumor spheroids (MCTS). Hydrogel compositions comprised of decreasing alginate concentrations, and increasing gelatin concentrations, result in gels that are mechanically soft and contain a greater number of cell-adhesion moieties driving the development of large MCTS; conversely gels containing increasing alginate, and decreasing gelatin concentrations are mechanically stiffer, with fewer cell-adhesion moieties present in the composite gels yielding smaller and less viable MCTS. These composite hydrogels can be used in the biofabrication of tunable in vitro systems that mimic both the mechanical and biochemical properties of the native tumor stroma.
Subject(s)
Alginates/chemistry , Bioprinting/instrumentation , Breast Neoplasms/physiopathology , Gelatin/chemistry , Hydrogels/chemistry , Tissue Engineering/instrumentation , Tissue Scaffolds/chemistry , Bioprinting/methods , Cell Adhesion , Cell Line, Tumor , Cell Proliferation , Humans , Kinetics , Printing, Three-Dimensional , Spheroids, Cellular/chemistry , Spheroids, Cellular/cytology , Tissue Engineering/methodsABSTRACT
RhoB, a member of the Ras homolog gene family and GTPase, regulates intracellular signaling pathways by interfacing with epidermal growth factor receptor (EGFR), Ras, and phosphatidylinositol 3-kinase (PI3K)/Akt to modulate responses in cellular structure and function. Notably, the EGFR, Ras, and PI3K/Akt pathways can lead to downregulation of RhoB, while simultaneously being associated with an increased propensity for tumorigenesis. Functionally, RhoB, part of the Rho GTPase family, regulates intracellular signaling pathways by interfacing with EGFR, RAS, and PI3K/Akt/mammalian target of rapamycin (mTOR), and MYC pathways to modulate responses in cellular structure and function. Notably, the EGFR, Ras, and PI3K/Akt pathways can lead to downregulation of RhoB, while simultaneously being associated with an increased propensity for tumorigenesis. RHOB expression has a complex regulatory backdrop consisting of multiple histone deacetyltransferase (HDACs 1 and 6) and microRNA (miR-19a, -21, and -223)-mediated mechanisms of modifying expression. The interwoven nature of RhoB's regulatory impact and cellular roles in regulating intracellular vesicle trafficking, cell motion, and the cell cycle lays the foundation for analyzing the link between loss of RhoB and tumorigenesis within the context of age-related decline in RhoB. RhoB appears to play a tissue-specific role in tumorigenesis, as such, uncovering and appreciating the potential for restoration of RHOB expression as a mechanism for cancer prevention or therapeutics serves as a practical application. An in-depth assessment of RhoB will serve as a springboard for investigating and characterizing this key component of numerous intracellular messaging and regulatory pathways that may hold the connection between aging and tumorigenesis.
ABSTRACT
Stretchable semiconducting polymers have been developed as a key component to enable skin-like wearable electronics, but their electrical performance must be improved to enable more advanced functionalities. Here, we report a solution processing approach that can achieve multi-scale ordering and alignment of conjugated polymers in stretchable semiconductors to substantially improve their charge carrier mobility. Using solution shearing with a patterned microtrench coating blade, macroscale alignment of conjugated-polymer nanostructures was achieved along the charge transport direction. In conjunction, the nanoscale spatial confinement aligns chain conformation and promotes short-range π-π ordering, substantially reducing the energetic barrier for charge carrier transport. As a result, the mobilities of stretchable conjugated-polymer films have been enhanced up to threefold and maintained under a strain up to 100%. This method may also serve as the basis for large-area manufacturing of stretchable semiconducting films, as demonstrated by the roll-to-roll coating of metre-scale films.
ABSTRACT
The electronic devices that play a vital role in our daily life are primarily based on silicon and are thus rigid, opaque, and relatively heavy. However, new electronics relying on polymer semiconductors are opening up new application spaces like stretchable and self-healing sensors and devices, and these can facilitate the integration of such devices into our homes, our clothing, and even our bodies. While there has been tremendous interest in such technologies, the widespread adoption of these organic electronics requires low-cost manufacturing techniques. Fortunately, the realization of organic electronics can take inspiration from a technology developed since the beginning of the Common Era: printing. This review addresses the critical issues and considerations in the printing methods for organic electronics, outlines the fundamental fluid mechanics, polymer physics, and deposition parameters involved in the fabrication process, and provides future research directions for the next generation of printed polymer electronics.
ABSTRACT
Rapid nanoscale imaging of the bulk heterojunction layer in organic solar cells is essential to the continued development of high-performance devices. Unfortunately, commonly used imaging techniques such as tunneling electron microscopy (TEM) and atomic force microscopy (AFM) suffer from significant drawbacks. For instance, assuming domain identity from phase contrast or topographical features can lead to inaccurate morphological conclusions. Here we demonstrate a technique known as photo-induced force microscopy (PiFM) for imaging organic solar cell bulk heterojunctions with nanoscale chemical specificity. PiFM is a relatively recent scanning probe microscopy technique that combines an AFM tip with a tunable infrared laser to induce a dipole for chemical imaging. Coupling the nanometer resolution of AFM with the chemical specificity of a tuned IR laser, we are able to spatially map the donor and acceptor domains in a model all-polymer bulk heterojunction with resolution approaching 10 nm. Domain size from PiFM images is compared to bulk-averaged results from resonant soft X-ray scattering, indicating excellent quantitative agreement. Further, we demonstrate that in our all-polymer system, the AFM topography, AFM phase, and PiFM show poor correlation, highlighting the need to move beyond standard AFM for morphology characterization of bulk heterojunctions.
ABSTRACT
BACKGROUND: Bochdalek hernias (BHs) are usually diagnosed in the neonatal period, occurring in 1/2200-1/12,500 live births. There are few reported cases of BHs in adults. Robotic repair has not been described in current literature as opposed to the laparoscopic approach. Here we present a case of an adult with clinical signs of bowel obstruction secondary to a BH which was repaired using a robotic approach. CASE REPORT: A 74-year-old gentleman with past medical history of benign prostatic hyperplasia presented to the emergency department with a 1-week history of nausea, vomiting, diarrhea, and decline in appetite. Computed tomography (CT) imaging of the chest and abdomen revealed elevation of the right hemidiaphragm and evidence of small bowel obstruction. The patient was managed conservatively with nasogastric tube placement and bowel rest. He underwent colonoscopy which could not be completed secondary to a transverse colon stricture which was confirmed by barium enema. Upon repeat CT imaging, the patient was found to have herniated colon through a right-sided diaphragmatic hernia which caused colonic narrowing. The patient's intestinal obstruction improved clinically with continued conservative management and he underwent robotic repair of a right posterior diaphragmatic hernia. The hernia defect was closed with interrupted figure of eight Ethibond sutures. A right-sided chest tube was placed. Intraoperatively, the herniated proximal transverse colon was noted to be ischemic and a right hemicolectomy was performed. He recovered well and was discharged home on postoperative day 5. CONCLUSION: Congenital diaphragmatic hernias usually present in the neonatal period and are rare in adults. Operative repair is recommended and laparoscopic repair has been described. Based on the existing literature regarding laparoscopic repair and the current case report, robotic repair also appears to be a viable and safe option.
Subject(s)
Hernias, Diaphragmatic, Congenital , Herniorrhaphy , Robotic Surgical Procedures , Abdomen/diagnostic imaging , Aged , Hernias, Diaphragmatic, Congenital/diagnostic imaging , Hernias, Diaphragmatic, Congenital/surgery , Humans , Male , Radiography, Thoracic , Tomography, X-Ray ComputedABSTRACT
Conjugated polymers are the key material in thin-film organic optoelectronic devices due to the versatility of these molecules combined with their semiconducting properties. A molecular-scale understanding of conjugated polymers is important to the optimization of the thin-film morphology. We examine the solution-phase behavior of conjugated isoindigo-based donor-acceptor polymer single chains of various chain lengths using atomistic molecular dynamics simulations. Our simulations elucidate the transition from a rod-like to a coil-like conformation from an analysis of normal modes and persistence length. In addition, we find another transition based on the solvent environment, contrasting the coil-like conformation in a good solvent with a globule-like conformation in a poor solvent. Overall, our results provide valuable insights into the transition between conformational regimes for conjugated polymers as a function of both the chain length and the solvent environment, which will help to accurately parametrize higher level models.
ABSTRACT
We describe a compact roll-to-roll (R2R) coater that is capable of tracking the crystallization process of semiconducting polymers during solution printing using X-ray scattering at synchrotron beamlines. An improved understanding of the morphology evolution during the solution-processing of organic semiconductor materials during R2R coating processes is necessary to bridge the gap between "lab" and "fab". The instrument consists of a vacuum chuck to hold the flexible plastic substrate uniformly flat for grazing incidence X-ray scattering. The time resolution of the drying process that is achievable can be tuned by controlling two independent motor speeds, namely, the speed of the moving flexible substrate and the speed of the printer head moving in the opposite direction. With this novel design, we are able to achieve a wide range of drying time resolutions, from tens of milliseconds to seconds. This allows examination of the crystallization process over either fast or slow drying processes depending on coating conditions. Using regioregular poly(3-hexylthiophene-2,5-diyl) (P3HT) and phenyl-C61-butyric acid methyl ester (PCBM) inks based on two different solvents as a model system, we demonstrate the capability of our in situ R2R printing tool by observing two distinct crystallization processes for inks drying from the solvents with different boiling points (evaporation rates). We also observed delayed on-set point for the crystallization of P3HT polymer in the 1:1 P3HT/PCBM BHJ blend, and the inhibited crystallization of the P3HT during the late stage of the drying process.
ABSTRACT
Morphology control of solution coated solar cell materials presents a key challenge limiting their device performance and commercial viability. Here we present a new concept for controlling phase separation during solution printing using an all-polymer bulk heterojunction solar cell as a model system. The key aspect of our method lies in the design of fluid flow using a microstructured printing blade, on the basis of the hypothesis of flow-induced polymer crystallization. Our flow design resulted in a â¼90% increase in the donor thin film crystallinity and reduced microphase separated donor and acceptor domain sizes. The improved morphology enhanced all metrics of solar cell device performance across various printing conditions, specifically leading to higher short-circuit current, fill factor, open circuit voltage and significantly reduced device-to-device variation. We expect our design concept to have broad applications beyond all-polymer solar cells because of its simplicity and versatility.