Magnetic particle image scanner based on asymmetric core-filled electromagnetic actuator.

Monitoring the distribution of magnetic nanoparticles (MNPs) in the vascular system is an important task for the advancement of precision therapeutics and drug delivery. Despite active targeting using active motilities, it is required to visualize the position and concentration of carriers that reach the target, to promote the development of this technology. In this work, a feasibility study is presented on a tomographic scanner that allows monitoring of the injected carriers quantitatively in a relatively short interval. The device is based on a small-animal-scale asymmetric magnetic platform integrated with magnetic particle imaging technology. An optimized isotropic field-free region (FFR) generation method using a magnetic manipulation system (MMS) is derived and numerically investigated. The in-vitro and in-vivo tracking performances are demonstrated with a high position accuracy of approximately 1 mm. A newly proposed tracking method was developed, specialized in vascular system, with quick scanning time (about 1s). In this paper, the primary function of the proposed system is to track magnetic particles using a magnetic manipulation system. Through this, proposed method enables the conventional magnetic actuation systems to upgrade the functionalities of both manipulation and localization of magnetic objects.

Treatment of Ischemic Stroke by Atorvastatin-Loaded PEGylated Liposome.

There is insufficient evidence on the effect of nanoparticles, particularly liposomes loaded with a statin, on acute ischemic stroke. We investigated the impact of atorvastatin-loaded PEG (polyethylene glycol) conjugated liposomes (LipoStatin) on the outcomes in rats with cerebral ischemia-reperfusion. PEGylated liposome loaded with atorvastatin was developed as a nanoparticle to specifically accumulate in an ischemic region and release the drug to ameliorate the harmful effects of the stroke. LipoStatin was administered to rats with transient middle cerebral artery occlusion through the tail vein immediately after reperfusion (LipoStatin group). LipoStatin efficiently accumulated at the cerebral ischemic injury site of the rat. The LipoStatin group showed a significantly reduced infarct volume (p < 0.01) in brain micro-MR imaging and improved neurological function recovery compared to the control group (p < 0.05). In addition, markedly improved brain metabolism using fluorine-18 fluorodeoxyglucose micro-PET/CT imaging was demonstrated in the LipoStatin group compared with the control group (p < 0.01). Mechanistically, as a result of evaluation through IL-1 beta, TNF-alpha, ICAM-1, and Iba-1 mRNA expression levels at 5 days after cerebral ischemia, LipoStatin showed significant anti-inflammatory effects. Protein expression of occludin, JAM-A, Caveolin-1, and eNOS by western blot at 3 days and fluorescent images at 7 days showed considerable recovery of blood-brain barrier breakdown and endothelial dysfunction. PEGylated LipoStatin can be more effectively delivered to the ischemic brain and may have significant neuroprotective effects. Thus, PEGylated LipoStatin can be further developed as a promising targeted therapy for ischemic stroke and other major vascular diseases.

Rice Basic Helix-Loop-Helix 079 (OsbHLH079) Delays Leaf Senescence by Attenuating ABA Signaling.

Leaf senescence represents the final phase of leaf development and is characterized by a highly organized degenerative process involving the active translocation of nutrients from senescing leaves to growing tissues or storage organs. To date, a large number of senescence-associated transcription factors (sen-TFs) have been identified that regulate the initiation and progression of leaf senescence. Many of these TFs, including NAC (NAM/ATAF1/2/CUC2), WRKY, and MYB TFs, have been implicated in modulating the expression of downstream senescence-associated genes (SAGs) and chlorophyll degradation genes (CDGs) under the control of phytohormones. However, the involvement of basic helix-loop-helix (bHLH) TFs in leaf senescence has been less investigated. Here, we show that OsbHLH079 delays both natural senescence and dark-induced senescence: Overexpression of OsbHLH079 led to a stay-green phenotype, whereas osbhlh079 knockout mutation displayed accelerated leaf senescence. Similar to other sen-TFs, OsbHLH079 showed a gradual escalation in expression as leaves underwent senescence. During this process, the mRNA levels of SAGs and CDGs remained relatively low in OsbHLH079 overexpressors, but increased sharply in osbhlh079 mutants, suggesting that OsbHLH079 negatively regulates the transcription of SAGs and CDGs under senescence conditions. Additionally, we found that OsbHLH079 delays ABA-induced senescence. Subsequent RT-qPCR and dual-luciferase reporter assays revealed that OsbHLH079 downregulates the expression of ABA signaling genes, such as OsABF2, OsABF4, OsABI5, and OsNAP. Taken together, these results demonstrate that OsbHLH079 functions in delaying leaf yellowing by attenuating the ABA responses.

Retroperitoneal spindle cell tumor: a case report.

Spindle cell tumors exhibit a relatively low occurrence rate and can manifest in various locations within the human body, including soft tissues and bones. The process of making a diagnosis is supported by conducting pathological and immunohistochemical tests. A 50-year-old female patient visited the hospital with abdominal pain that lasted about a week. Magnetic resonance imaging of the pelvis showed that this mass was independent and was not a lymph node mass, but a retroperitoneal sarcoma type mass. As part of the treatment, the mass was surgically excised, and a supracervical hysterectomy was carried out. The tumor was wrapped in a grayish-white capsule and showed a lobulating pattern. Retroperitoneal spindle cell tumors, particularly those occurring in abdominal soft tissues, are infrequently observed. Histopathological diagnosis is done in stages, and when cases are ambiguous, immunohistochemistry can provide valuable guidance in the right direction.

Women's Employment in Industries and Risk of Preeclampsia and Gestational Diabetes: A National Population Study of Republic of Korea.

Background: Some working conditions may pose a higher physical or psychological demand to pregnant women leading to increased risks of pregnancy complications. Objectives: We assessed the association of woman's employment status and the industrial classification with obstetric complications. Methods: We conducted a national population study using the National Health Information Service database of Republic of Korea. Our analysis encompassed 1,316,310 women who experienced first-order live births in 2010-2019. We collected data on the employment status and the industrial classification of women, as well as their diagnoses of preeclampsia (PE) and gestational diabetes mellitus (GDM) classified as A1 (well controlled by diet) or A2 (requiring medication). We calculated odds ratios (aORs) of complications per employment, and each industrial classification was adjusted for individual risk factors. Results: Most (64.7%) were in employment during pregnancy. Manufacturing (16.4%) and the health and social (16.2%) work represented the most prevalent industries. The health and social work exhibited a higher risk of PE (aOR = 1.11, 95% confidence interval [CI]: 1.03-1.21), while the manufacturing industry demonstrated a higher risk of class A2 GDM (1.20, 95% CI: 1.03-1.41) than financial intermediation. When analyzing both classes of GDM, women who worked in public administration and defense/social security showed higher risk of class A1 GDM (1.04, 95% CI: 1.01, 1.07). When comparing high-risk industries with nonemployment, the health and social work showed a comparable risk of PE (1.02, 95% CI: 0.97, 1.07). Conclusion: Employment was associated with overall lower risks of obstetric complications. Health and social service work can counteract the healthy worker effect in relation to PE. This highlights the importance of further elucidating specific occupational risk factors within the high-risk industries.

Does the father's job matter? Parental occupation and preterm birth in Korea.

OBJECTIVES: Limited evidence is available regarding the impact of paternal occupation and its combined effect with maternal occupation on preterm birth. Therefore, we assessed the association of maternal and paternal occupations with preterm birth. METHODS: We used the national birth data of Korea between 2010 and 2020. Parental occupations were divided into 5 categories: (1) managers; (2) professionals, technicians, and related workers; (3) clerks and support workers; (4) service and sales workers; and (5) manual workers. A multinomial logistic regression model was used to calculate the adjusted odds ratios (aORs) of extremely, very, and moderate-to-late preterm births per occupational category considering individual risk factors. RESULTS: For the 4,004,976 singleton births, 40.2% of mothers and 95.5% of fathers were employed. Compared to non-employment, employment was associated with a lower risk of preterm birth. Among employed mothers, service and sales occupations were associated with a higher risk of preterm birth than managerial occupations (aOR, 1.06; 95% confidence interval [CI], 1.01 to 1.10 for moderate-to-late preterm births). The father's manual occupation was associated with a higher risk of preterm birth (aOR, 1.09; 95% CI, 1.05 to 1.13 for moderate-to-late preterm) than managerial occupations. When both parents had high-risk occupations, the risk of preterm birth was higher than in cases where only the mother or neither of the parents had a high-risk occupation. CONCLUSIONS: Paternal occupation was associated with preterm birth regardless of maternal employment and occupation and modified the effect of maternal occupation. Detailed occupational environment data are needed to identify the paternal exposures that increase the risk.

OsMYB7 determines leaf angle at the late developmental stage of lamina joints in rice.

Leaf angle shapes plant architecture, allowing for optimal light interception to maximize photosynthesis and yield, and therefore is a crucial agronomic trait. Here, we show that the rice (Oryza sativa L.) R2R3-type MYB transcription factor OsMYB7 determines leaf angle in a developmental stage-specific manner. OsMYB7-overexpressing lines produced wide-angled leaves and osmyb7 knockout mutants exhibited erect leaves. This phenotype was restricted to the lamina joints at the late developmental stage. In agreement with these observations, OsMYB7 was preferentially expressed in the lamina joints of post-mature leaves. Since OsMYB7 homologs are transcriptional repressors of lignin biosynthesis, we examined whether OsMYB7 might inhibit thickening of secondary cell walls. Although OsMYB7 repressed lignin biosynthesis, it enhanced thickening of sclerenchyma cell walls by elevating cellulose contents at the lamina joints. Furthermore, we found that OsMYB7 affects endogenous auxin levels in lamina joints, and the adaxial cells of lamina joints in OsMYB7-overexpressing lines and osmyb7 knockout mutants exhibited enhanced and reduced elongation, respectively, compared to the wild type. These results suggest that OsMYB7 promotes leaf inclination partially through decreasing free auxin levels and promoting cell elongation at the adaxial side of lamina joints.

A prediction model for magnetic particle imaging-based magnetic hyperthermia applied to a brain tumor model.

BACKGROUND AND OBJECTIVE: Brain tumor is a global health concern at the moment. Thus far, the only treatments available are radiotherapy and chemotherapy, which have several drawbacks such as low survival rates and low treatment efficacy due to obstruction of the blood-brain barrier. Magnetic hyperthermia (MH) using magnetic nanoparticles (MNPs) is a promising non-invasive approach that has the potential for tumor treatment in deep tissues. Due to the limitations of the current drug-targeting systems, only a small proportion of the injected MNPs can be delivered to the desired area and the rest are distributed throughout the body. Thus, the application of conventional MH can lead to damage to healthy tissues. METHODS: Magnetic particle imaging (MPI)-guided treatment platform for MH is an emerging approach that can be used for spatial localization of MH to arbitrarily selected regions by using the MPI magnetic field gradient. Although the feasibility of this method has been demonstrated experimentally, a multidimensional prediction model, which is of crucial importance for treatment planning, has not yet been developed. Hence, in this study, the time dependent magnetization equation derived by Martsenyuk, Raikher, and Shliomis (which is a macroscopic equation of motion derived from the Fokker-Planck equation for particles with Brownian relaxation mechanism) and the bio-heat equations have been used to develop and investigate a three-dimensional model that predicts specific loss power (SLP), its spatio-thermal resolution (temperature distribution), and the fraction of damage in brain tumors. RESULTS: Based on the simulation results, the spatio-thermal resolution in focused heating depends, in a complex manner, on several parameters ranging from MNPs properties to magnetic fields characteristics, and coils configuration. However, to achieve a high performance in focused heating, the direction and the relative amplitude of the AC magnetic heating field with respect to the magnetic field gradient are among the most important parameters that need to be optimized. The temperature distribution and fraction of the damage in a simple brain model bearing a tumor were also obtained. CONCLUSIONS: The complexity in the relationship between the MNPs properties and fields parameter imposes a trade-off between the heating efficiency of MNPs and the accuracy (resolution) of the focused heating. Therefore, the system configuration and field parameters should be chosen carefully for each specific treatment scenario. In future, the results of the model are expected to lead to the development of an MPI-guided MH treatment platform for brain tumor therapy. However, for more accurate quantitative results in such a platform, a magnetization dynamics model that takes into account coupled Néel-Brownian relaxation mechanism in the MNPs should be developed.

A Machine Learning-Based Initial Difficulty Level Adjustment Method for Balance Exercise on a Trunk Rehabilitation Robot.

Trunk rehabilitation exercises such as those for remediating core stability can help improve the seated balance of patients with weakness or loss of proprioception caused by diseases such as stroke, and aid the recovery of other functions such as gait. However, there has not yet been any reported method for automatically determining the parameters that define exercise difficulty on a trunk rehabilitation robot (TRR) based on data such as the patient's demographic information, balancing ability, and training sequence, etc. We have proposed a machine learning (ML)-based difficulty adjustment method to determine an appropriate virtual damping gain (Dvirtual) of the controller for the TRR's unstable training mode. Training data for the proposed system is obtained from 37 healthy young adults, and the trained ML model thus obtained is tested through experiments with a separate population of 25 healthy young adults. The leave-one-out cross validation results (37 subjects) from the training group for validation of the designed ML model showed 80.90% average accuracy (R2 score) for using the given information to predict the desired difficulty levels, which are represented by the level of balance performance quantified as Mean Velocity Displacement (MVD) of the center of pressure. Statistical analysis (Repeated measures analysis of variance) of subject performance also showed that ground truth difficulty levels from the training data and predicted difficulty levels did not differ significantly under any of the three exercise modes used in this study (Hard, Medium, and Easy), and the standard deviations were reduced by 16.39, 41.39, and 25.68%, respectively. Moreover, the Planar Deviation (PD) of the center of pressure, which was not the target parameter here, also showed results similar to the MVD, which indicates that the predicted Dvirtual affected the difficulty level of balance performance. Therefore, the proposed ML model-based difficulty adjustment method has potential for use with people who have varied balancing abilities.

Magnetothermal-based non-invasive focused magnetic stimulation for functional recovery in chronic stroke treatment.

Magnetic heat-based brain stimulation of specific lesions could promote the restoration of impaired motor function caused by chronic stroke. We delivered localized stimulation by nanoparticle-mediated heat generation within the targeted brain area via focused magnetic stimulation. The middle cerebral artery occlusion model was prepared, and functional recovery in the chronic-phase stroke rat model was demonstrated by the therapeutic application of focused magnetic stimulation. We observed a transient increase in blood-brain barrier permeability at the target site of < 4 mm and metabolic brain activation at the target lesion. After focused magnetic stimulation, the rotarod score increased by 390 ± 28% (p < 0.05) compared to the control group. Standardized uptake value in the focused magnetic stimulation group increased by 2063 ± 748% (p < 0.01) compared to the control group. Moreover, an increase by 24 ± 5% (p < 0.05) was observed in the sham group as well. Our results show that non-invasive focused magnetic stimulation can safely modulate BBB permeability and enhance neural activation for chronic-phase stroke treatment in the targeted deep brain area.

Risk of adverse pregnancy outcomes by maternal occupational status: A national population-based study in South Korea.

OBJECTIVE: This study examined the association between maternal occupational status and adverse pregnancy outcomes in the general South Korean population. METHODS: We analyzed 1 825 845 employed and non-employed women with a diagnostic code for pregnancy in the National Health Insurance Service (NHIS) database (2010-2019) of South Korea. Based on their employment status and type of occupation, we calculated risk ratios for three adverse outcomes: early abortive outcomes (miscarriage, ectopic pregnancy, and molar pregnancy), stillbirth, and no live birth (diagnosis of pregnancy with no record of live birth thereafter, which include early abortive outcomes and stillbirth) with adjusting for covariates. RESULTS: Overall, 18.0%, 0.7%, and 39.8% ended in early abortive outcomes, stillbirths, and no live births, respectively. The risk of early abortive outcomes and stillbirths was higher in non-employed women than in employed women, while no live births were more frequent in employed women. Those in the health and social work industry showed the highest risk of no live births. Manufacturing jobs (1.030, 95% CI: 1.013, 1.047) and health/social work (1.029, 95% CI: 1.012, 1.046) were associated with an increased risk of early abortive outcomes compared with financial and insurance jobs. Consistently higher risks of no live births were observed in the manufacturing, wholesale/retail trade, education, health/social work, and public/social/personal service occupation. CONCLUSION: Employment during pregnancy and several occupation types were associated with a higher risk of pregnancy loss. Additional research using detailed job activity data is needed to determine specific occupational causes of adverse pregnancy outcomes.

Neisseria gonorrhoeae Infection in Women Increases With Rising Gonococcal Burdens in Partners: Chlamydia Coinfection in Women Increases Gonococcal Burden.

BACKGROUND: Likelihood of Neisseria gonorrhoeae infection in women exposed to male sex partners with increasing N. gonorrhoeae burdens and enhancement by Chlamydia trachomatis is not defined. METHODS: We identified men with urethritis and their regular female sex partners. Exposure to N. gonorrhoeae burdens in men was compared in N. gonorrhoeae-infected versus -uninfected partners. Association of N. gonorrhoeae infection in women with burdens in male partners was estimated using logistic regression. Association of C. trachomatis coinfection and N. gonorrhoeae burdens in women adjusted for burdens in male partners was estimated by linear regression. RESULTS: In total, 1816 men were enrolled; 202 had ≥2 partners, 91 who confirmed monogamy and were enrolled; 77% were married. Seventy were partners of N. gonorrhoeae-infected men; 58 (83%) were N. gonorrhoeae infected, 26 (45%) C. trachomatis coinfected. Infected women had partners with 9.3-fold higher N. gonorrhoeae burdens than partners of uninfected women (P = .0041). Association of N. gonorrhoeae infection in women with upper quartiles of N. gonorrhoeae burdens in partners increased (odds ratios ≥ 2.97)compared to the first quartile (P = .032). N. gonorrhoeae burdens in C. trachomatis-coinfected women were 2.82-fold higher than in C. trachomatis-uninfected women (P = .036). CONCLUSIONS: N. gonorrhoeae infections increased in women whose partners were infected with higher N. gonorrhoeae burdens. C. trachomatis coinfection was associated with increased N. gonorrhoeae burdens in women.

From Low to High Saturation Magnetization in Magnetite Nanoparticles: The Crucial Role of the Molar Ratios Between the Chemicals.

In this study, a comprehensive characterization of iron oxide nanoparticles synthesized by using a simple one-pot thermal decomposition route is presented. In order to obtain monodisperse magnetite nanoparticles with high saturation magnetization, close to the bulk material, the molar ratios between the starting materials (solvents, reducing agents, and surfactants) were varied. Two out of nine conditions investigated in this study resulted in monodisperse iron oxide nanoparticles with high saturation magnetization (90 and 93% of bulk magnetite). The X-ray diffraction analyses along with the inspection of the lattice structure through transmission electron micrographs revealed that the main cause of the reduced magnetization in the other seven samples is likely due to the presence of distortion and microstrain in the particles. Although the thermogravimetric analysis, Raman and Fourier transform infrared spectroscopies confirmed the presence of covalently bonded oleic acid on the surface of all the samples, the particles with higher polydispersity and the lowest surface coating molecules showed the lowest saturation magnetization. Based on the observed results, it could be speculated that the changes in the kinetics of the reactions, induced by varying the molar ratio of the starting chemicals, can lead to the production of the particles with higher polydispersity and/or lattice deformation in their crystal structures. Finally, it was concluded that the experimental conditions for obtaining high-quality iron oxide nanoparticles, particularly the molar ratios and the heating profile, should not be chosen independently; for any specific molar ratio, there may exist a specific heating profile or vice versa. Because this synthetic consideration has rarely been reported in the literature, our results can give insights into the design of iron oxide nanoparticles with high saturation magnetization for different applications.

Study on the Effects of Different Seat and Leg Support Conditions of a Trunk Rehabilitation Robot.

Performance of trunk rehabilitation exercises while sitting on movable surfaces with feet on the ground can increase trunk and leg muscle activations, and constraining the feet to move with the seat isolates control of the trunk. However, there are no detailed studies on the effects of these different leg supports on the trunk and leg muscle activations under unstable and forcefully perturbed seating conditions. We have recently devised a trunk rehabilitation robot that can generate unstable and forcefully perturbed sitting surfaces, and can be used with ground-mounted or seat-connected footrests. In this study, we have evaluated the differences in balance performance, trunk movement and muscle activation (trunk and legs) of fourteen healthy adults caused by the use of these different footrest configurations under the different seating scenarios. The center of pressure and trunk movement results show that the seat-connected footrest may be a more suitable choice for use in a balance recovery focused rehabilitation protocol, while the ground-mounted footrest may be a more suitable choice for a trunk movement focused rehabilitation protocol. Although it is difficult to make a clear selection between footrests due to the mixed trends observed in the muscle activation results, it appears that the seat-connected footrest may be preferable for use with the unstable seat as it causes greater muscle activations. Furthermore, the results provide limited evidence that targeting of a particular muscle group may be possible through careful selection of the seat and footrest conditions. Therefore, it may be possible to utilize the trunk rehabilitation robot to maximize the training outcomes for a wide range of patients through careful selection of training protocols.

Phenylalanine gold nanoclusters as sensing platform for π-π interfering molecules: a case study of iodide.

The photo-physical properties of metal nano clusters are sensitive to their surrounding medium. Fluorescence enhancement, quenching, and changes in the emitted photon properties are usual events in the sensing applications using these nano materials. Combining this sensitivity with unique properties of self-assembled structures opens new opportunities for sensing applications. Here, we synthesized gold nanoclusters by utilizing phenylalanine amino acid as both capping and reducing molecule. Phenylalanine is able to self-assemble to rod-shaped nano structure in which the π-π interaction between the aromatic rings is a major stabilizing force. Any substance as iodide anion or molecule that is able to weaken this interaction influence the fluorescence of metal nano-clusters. Since the building blocks of the self-assembled structure are made through the reaction of gold ions and phenylalanine, the oxidized products and their effect of sensing features are explored.

Highly Optimized Iron Oxide Embedded Poly(Lactic Acid) Nanocomposites for Effective Magnetic Hyperthermia and Biosecurity.

INTRODUCTION: Iron oxide magnetic nanoparticles (IONPs) have attracted considerable attention for various biomedical applications owing to their ease of synthesis, strong magnetic properties, and biocompatibility. In particular, IONPs can generate heat under an alternating magnetic field, the effects of which have been extensively studied for magnetic hyperthermia therapy. However, the development of IONPs with high heating efficiency, biocompatibility, and colloidal stability in physiological environments is still required for their safe and effective application in biomedical fields. METHODS: We synthesized magnetic IONP/polymer nanocomposites (MNCs) by embedding IONPs in a poly(L-lactic acid) (PLA) matrix via nanoemulsion. The IONP contents (Fe: 9-22 [w/w]%) in MNCs were varied to investigate their effects on the magnetic and hyperthermia performances based on their optimal interparticle interactions. Further, we explored the stability, cytocompatibility, biodistribution, and in vivo tissue compatibility of the MNCs. RESULTS: The MNCs showed enhanced heating efficiency with over two-fold increase compared to nonembedded bare IONPs. The relationship between the IONP content and heating performance in MNCs was nonmonotonous. The highest heating performance was obtained from MNC2, which contain 13% Fe (w/w), implying that interparticle interactions in MNCs can be optimized to achieve high heating performance. In addition, the MNCs exhibited good colloidal stability under physiological conditions and maintained their heating efficiency during 48 h of incubation in cell culture medium. Both in vitro and in vivo studies revealed excellent biocompatibility of the MNC. CONCLUSION: Our nanocomposites, comprising biocompatible IONPs and PLA, display improved heating efficiency, good colloidal stability, and cytocompatibility, and thus will be beneficial for diverse biomedical applications, including magnetic hyperthermia for cancer treatment.

Artificial Intelligence Assesses Clinicians' Adherence to Asthma Guidelines Using Electronic Health Records.

BACKGROUND: Clinicians' asthma guideline adherence in asthma care is suboptimal. The effort to improve adherence can be enhanced by assessing and monitoring clinicians' adherence to guidelines reflected in electronic health records (EHRs), which require costly manual chart review because many care elements cannot be identified by structured data. OBJECTIVE: This study was designed to demonstrate the feasibility of an artificial intelligence tool using natural language processing (NLP) leveraging the free text EHRs of pediatric patients to extract key components of the 2007 National Asthma Education and Prevention Program guidelines. METHODS: This is a retrospective cross-sectional study using a birth cohort with a diagnosis of asthma at Mayo Clinic between 2003 and 2016. We used 1,039 clinical notes with an asthma diagnosis from a random sample of 300 patients. Rule-based NLP algorithms were developed to identify asthma guideline-congruent elements by examining care description in EHR free text. RESULTS: Natural language processing algorithms demonstrated a sensitivity (0.82-1.0), specificity (0.95-1.0), positive predictive value (0.86-1.0), and negative predictive value (0.92-1.0) against manual chart review for asthma guideline-congruent elements. Assessing medication compliance and inhaler technique assessment were the most challenging elements to assess because of the complexity and wide variety of descriptions. CONCLUSIONS: Natural language processing technologies may enable the automated assessment of clinicians' documentation in EHRs regarding adherence to asthma guidelines and can be a useful population management and research tool to assess and monitor asthma care quality. Multisite studies with a larger sample size are needed to assess the generalizability of these NLP algorithms.

Identification of asthma control factor in clinical notes using a hybrid deep learning model.

BACKGROUND: There are significant variabilities in guideline-concordant documentation in asthma care. However, assessing clinician's documentation is not feasible using only structured data but requires labor-intensive chart review of electronic health records (EHRs). A certain guideline element in asthma control factors, such as review inhaler techniques, requires context understanding to correctly capture from EHR free text. METHODS: The study data consist of two sets: (1) manual chart reviewed data-1039 clinical notes of 300 patients with asthma diagnosis, and (2) weakly labeled data (distant supervision)-27,363 clinical notes from 800 patients with asthma diagnosis. A context-aware language model, Bidirectional Encoder Representations from Transformers (BERT) was developed to identify inhaler techniques in EHR free text. Both original BERT and clinical BioBERT (cBERT) were applied with a cost-sensitivity to deal with imbalanced data. The distant supervision using weak labels by rules was also incorporated to augment the training set and alleviate a costly manual labeling process in the development of a deep learning algorithm. A hybrid approach using post-hoc rules was also explored to fix BERT model errors. The performance of BERT with/without distant supervision, hybrid, and rule-based models were compared in precision, recall, F-score, and accuracy. RESULTS: The BERT models on the original data performed similar to a rule-based model in F1-score (0.837, 0.845, and 0.838 for rules, BERT, and cBERT, respectively). The BERT models with distant supervision produced higher performance (0.853 and 0.880 for BERT and cBERT, respectively) than without distant supervision and a rule-based model. The hybrid models performed best in F1-score of 0.877 and 0.904 over the distant supervision on BERT and cBERT. CONCLUSIONS: The proposed BERT models with distant supervision demonstrated its capability to identify inhaler techniques in EHR free text, and outperformed both the rule-based model and BERT models trained on the original data. With a distant supervision approach, we may alleviate costly manual chart review to generate the large training data required in most deep learning-based models. A hybrid model was able to fix BERT model errors and further improve the performance.

Establishing an expert consensus for the operational definitions of asthma-associated infectious and inflammatory multimorbidities for computational algorithms through a modified Delphi technique.

BACKGROUND: A subgroup of patients with asthma has been reported to have an increased risk for asthma-associated infectious and inflammatory multimorbidities (AIMs). To systematically investigate the association of asthma with AIMs using a large patient cohort, it is desired to leverage a broad range of electronic health record (EHR) data sources to automatically identify AIMs accurately and efficiently. METHODS: We established an expert consensus for an operational definition for each AIM from EHR through a modified Delphi technique. A series of questions about the operational definition of 19 AIMS (11 infectious diseases and 8 inflammatory diseases) was generated by a core team of experts who considered feasibility, balance between sensitivity and specificity, and generalizability. Eight internal and 5 external expert panelists were invited to individually complete a series of online questionnaires and provide judgement and feedback throughout three sequential internal rounds and two external rounds. Panelists' responses were collected, descriptive statistics tabulated, and results reported back to the entire group. Following each round the core team of experts made iterative edits to the operational definitions until a moderate (≥ 60%) or strong (≥ 80%) level of consensus among the panel was achieved. RESULTS: Response rates for each Delphi round were 100% in all 5 rounds with the achievement of the following consensus levels: (1) Internal panel consensus: 100% for 8 definitions, 88% for 10 definitions, and 75% for 1 definition, (2) External panel consensus: 100% for 12 definitions and 80% for 7 definitions. CONCLUSIONS: The final operational definitions of AIMs established through a modified Delphi technique can serve as a foundation for developing computational algorithms to automatically identify AIMs from EHRs to enable large scale research studies on patient's multimorbidities associated with asthma.

Comparative Study on Overground Gait of Stroke Survivors With a Conventional Cane and a Haptic Cane.

The conventional cane (single cane) is widely used to promote gait ability of stroke survivors as it provides postural stability by extending the base of support. However, its use can reduce muscle activity in the user's paretic side and cause upper limb neuropathies due to the intermittent and excessive loading of the upper limb. The provision of low magnitude support and speed regulation may result in collective improvement of gait parameters such as symmetry, balance and muscle activation. In this paper, we developed a robotic Haptic Cane (HC) that is composed of a tilted structure with motorized wheels and sensors to allow continuous haptic contact with the ground while moving at a regulated speed, and carried out gait experiments to compare the HC with an Instrumented conventional Cane (IC). The results show that use of the HC involved more continuous ground support force of a comparatively lesser magnitude than the IC, and resulted in greater improvements in the swing symmetry ratio and significant improvements in the step length symmetry ratio. Percentage of Non-Paretic Activity (%NPA) of paretic muscles (vastus medialis obliquus (VMO), semitendinosus (SMT), tibialis anterior (TBA) and gastrocnemius medialis (GCM)) in swing phase was significantly improved by the use of either device at fast speed. However, the use of HC improved %NPA of paretic VMO and SMT more than the use of IC at both preferred and fast speeds. It also significantly improved %NPA of paretic GCM in stance phase. Furthermore, comfortable speed with the HC was higher than with the IC and exhibited better RMS of anteroposterior (AP) tilt. Thus, the developed device with a simple and intuitive mechanism can provide efficient assistance for overground gait of stroke patients with a high possibility of widespread use.