Miracle-dz/UniFAR-FTUs huggingface dataset:
Acquired Resistance Mutations to ALK Inhibitors Identified by Single Circulating Tumor Cell Sequencing in ALK-Rearranged Non–Small-Cell Lung Cancer

Purpose: Patients with anaplastic lymphoma kinase (ALK)–rearranged non–small-cell lung cancer (NSCLC) inevitably develop resistance to ALK inhibitors. New diagnostic strategies are needed to assess resistance mechanisms and provide patients with the most effective therapy. We asked whether single circulating tumor cell (CTC) sequencing can inform on resistance mutations to ALK inhibitors and underlying tumor heterogeneity in ALK-rearranged NSCLC. Experimental Design: Resistance mutations were investigated in CTCs isolated at the single-cell level from patients at disease progression on crizotinib (n = 14) or lorlatinib (n = 3). Three strategies including filter laser-capture microdissection, fluorescence activated cell sorting, and the DEPArray were used. One hundred twenty-six CTC pools and 56 single CTCs were isolated and sequenced. Hotspot regions over 48 cancer-related genes and 14 ALK mutations were examined to identify ALK-independent and ALK-dependent resistance mechanisms. Results: Multiple mutations in various genes in ALK-independent pathways were predominantly identified in CTCs of crizotinib-resistant patients. The RTK-KRAS (EGFR, KRAS, BRAF genes) and TP53 pathways were recurrently mutated. In one lorlatinib-resistant patient, two single CTCs out of 12 harbored ALK compound mutations. CTC-1 harbored the ALKG1202R/F1174C compound mutation virtually similar to ALKG1202R/F1174L present in the corresponding tumor biopsy. CTC-10 harbored a second ALKG1202R/T1151M compound mutation not detected in the tumor biopsy. By copy-number analysis, CTC-1 and the tumor biopsy had similar profiles, whereas CTC-10 harbored multiple copy-number alterations and whole-genome duplication. Conclusions: Our results highlight the genetic heterogeneity and clinical utility of CTCs to identify therapeutic resistance mutations in ALK-rearranged patients. Single CTC sequencing may be a unique tool to assess heterogeneous resistance mechanisms and help clinicians for treatment personalization and resistance options to ALK-targeted therapies.
Two-step regulation of trachealess ensures tight coupling of cell fate with morphogenesis in the Drosophila trachea

During organogenesis, inductive signals cause cell differentiation and morphogenesis. However, how these phenomena are coordinated to form functional organs is poorly understood. Here, we show that cell differentiation of the Drosophila trachea is sequentially determined in two steps and that the second step is synchronous with the invagination of the epithelial sheet. The master gene trachealess is dispensable for the initiation of invagination, while it is essential for maintaining the invaginated structure, suggesting that tracheal morphogenesis and differentiation are separately induced. trachealess expression starts in bipotential tracheal/epidermal placode cells. After invagination, its expression is maintained in the invaginated cells but is extinguished in the remaining sheet cells. A trachealess cis-regulatory module that shows both tracheal enhancer activity and silencer activity in the surface epidermal sheet was identified. We propose that the coupling of trachealess expression with the invaginated structure ensures that only invaginated cells canalize robustly into the tracheal fate.
Governance and Sustainability of an Open Source Electronic Health Record: An Interpretive Case Study of OpenDolphin in Japan

Electronic Health Records (EHRs) are at the heart of reforms aiming for improving the efficiency and quality of citizens healthcare services. Although there is still some skepticism, open source (OS) EHR is a growing phenomenon in health informatics. Given the widespread adoption of OS software (OSS) in several domains, including operating systems, and enterprise systems, the repeated shortfalls faced by healthcare organizations with dominant proprietary EHRs create an opportunity for other alternatives, such as OSS to demonstrate their abilities in addressing these well-documented problems, including inflexibility, high costs, and low interoperability. However, scholars have expressed extensive concerns about the sustainability of OS EHR. Recognizing that OSS project sustainability relies on their governance arrangements, this case study reports on the evolution of the governance and sustainability of a Japanese OS EHR project and provides rich insights to other open source EHR initiative stakeholders, including physicians, developers, researchers, and policymakers.
ApiAppS: A Project to Study and Help Practitioners in Recommending mHealth Apps and Devices to Their Patients

The ApiAppS ongoing project aims to provide physicians with a decision support system for the prescription / recommendation of mHealth technologies. We describe the context and the components of the project which includes: 1) a technical part on modelling and implementing the decision support system, and 2) a psychosocial investigation part designed to have a better knowledge of general practitioners (GPs) and patients' expectations, beliefs and practices.
Visualization of H atoms in the X‐ray crystal structure of photoactive yellow protein: Does it contain low‐barrier hydrogen bonds?

The hydrogen bond (HB) between 4‐hydroxycinnamic acid (HC4) and glutamic acid E46 of photoactive yellow protein is exceptionally strong. In the 0.82‐å resolution X‐ray structure for this protein (PDB ID: 1NWZ), the OH…O distance is only 2.57 å. The position of the H atom between these two O atoms has not been determined in that structure, and in the absence of that information, it is impossible to determine whether or not this HB is a low‐barrier HB (LBHB), as was proposed recently based on neutron structures of this protein (Yamaguchi et al., Proceedings of the National Academy of Sciences of the United States of America, 2009, 106: 440–444). Residual electron density maps computed using the 1NWZ data reveal that this H atom is 0.92 å from the Oε2 atom of E46 and 1.67 å from the O4′ of HC4, and that the OH…O bond angle is 167°. These observations indicate that E46 is protonated, and HC4 is deprotonated, as was originally suggested, and that the HB in question is not an LBHB.
MAOA‐VNTR genotype affects structural and functional connectivity in distributed brain networks

Previous studies have linked the low expression variant of a variable number of tandem repeat polymorphism in the monoamine oxidase A gene (MAOA‐L) to the risk for impulsivity and aggression, brain developmental abnormalities, altered cortico‐limbic circuit function, and an exaggerated neural serotonergic tone. However, the neurobiological effects of this variant on human brain network architecture are incompletely understood. We studied healthy individuals and used multimodal neuroimaging (sample size range: 219–284 across modalities) and network‐based statistics (NBS) to probe the specificity of MAOA‐L‐related connectomic alterations to cortical‐limbic circuits and the emotion processing domain. We assessed the spatial distribution of affected links across several neuroimaging tasks and data modalities to identify potential alterations in network architecture. Our results revealed a distributed network of node links with a significantly increased connectivity in MAOA‐L carriers compared to the carriers of the high expression (H) variant. The hyperconnectivity phenotype primarily consisted of between‐lobe (“anisocoupled”) network links and showed a pronounced involvement of frontal‐temporal connections. Hyperconnectivity was observed across functional magnetic resonance imaging (fMRI) of implicit emotion processing (pFWE = .037), resting‐state fMRI (pFWE = .022), and diffusion tensor imaging (pFWE = .044) data, while no effects were seen in fMRI data of another cognitive domain, that is, spatial working memory (pFWE = .540). These observations are in line with prior research on the MAOA‐L variant and complement these existing data by novel insights into the specificity and spatial distribution of the neurogenetic effects. Our work highlights the value of multimodal network connectomic approaches for imaging genetics.
Pain During "Noncomplex" Electrophysiological Studies and Cardiac Rhythm Device Surgery.

BACKGROUND There are only limited data about peri-interventional pain during cardiac electrophysiological procedures without analgosedation. In this study, peri-interventional pain and recollection of it after the intervention were evaluated. METHODS A total of 101 patients (43 electrophysiological/ablation procedures and 58 device surgeries) reported pain on a numerical rating scale (NRS; 0-10) before (pre), during (peri), and after (post) the intervention. Maximum pain (maxNRS) and the average of pain (meanNRS) were used for statistical analysis. Peri-interventional pain was compared with postinterventional data of the recollection of peri-interventional pain (peri-post). Patients were allocated into 2 groups (with 51 and 50 patients, respectively) to evaluate the mode of patient-staff interaction on pain recollection. Depressive, anxiety, and somatic symptom scales (Patient Health Questionnaire-15, Generalized Anxiety Disorder-7, and Patient Health Questionnaire-15) were used to analyze their influence on pain recollection. RESULTS In total, 49.6% of patients (n = 50) complained of moderate to severe pain (maxNRS) at least once during the procedure. The comparison between peri and peri-post data revealed the following (median (range)-maxNRS, peri: 3 (0-10) versus peri-post: 4 (0-9) (ns), and meanNRS, peri: 1.4 (0-7) versus peri-post: 2.0 (0-6) (ns). The mode of patient-staff interaction had no influence on pain. No effect was found for psychosocial factor concerning pain and the recollection of pain. The results of the linear regression showed no influence of low-dose midazolam on recollection of pain. CONCLUSION Half of the patients reported moderate to severe pain at least once during cardiac electrophysiological procedures without analgosedation. However, on average, patients reported only low pain levels. Postinterventional derived data on discomfort reflect the peri-interventional situation.
Query Translation Between AQL and CQL

Secondary use of electronic health records using data aggregation systems (DAS) with standardized access interfaces (e.g. openEHR, i2b2, FHIR) have become an attractive approach to support clinical research. In order to increase the volume of underlying patient data, multiple DASs at different institutions can be connected to research networks. Two obstacles to connect a DAS to such a network are the syntactical differences between the involved DAS query interfaces and differences in the data models the DASs operate on. The current work presents an approach to tackle both problems by translating queries from a DAS using openEHR's query language AQL (Archetype Query Language) into queries using the query language CQL (Clinical Quality Language) and vice versa. For the subset of queries which are expressible in both query languages the presented approach is well feasible.
A CONTROL-VOLUME FINITE-ELEMENT METHOD (CVFEM) FOR UNSTEADY, INCOMPRESSIBLE, VISCOUS FLUID FLOWS

A control-volume finite-element method (CVFEM), to simulate unsteady, incompressible, and viscous fluid flows, using nine-noded quadrilateral elements, has been developed. The Navier-Stokes equations in primitive variables u-v-p are the mathematical model of the flows. A technique of upwind, known as MAW, Mass-Weighted Interpolation, was extended for the finite element employed in this work. The set of nonlinear partial differential equations was integrated, and after using interpolation functions and time discretization, the algebraic system of equations was solved by using the frontal method of solution. Results obtained for some benchmark problems compared favorably with available results from the literature.
The clinical effects of antibiotic prophylaxis for hysteroscopic procedures

Abstract Background: Hysteroscopic procedures were widely applied but the clinical effects of antibiotic prophylaxis for these operations were not specifically addressed. In current study, we aimed to investigate the role of prophylactic antibiotics in hysteroscopic procedures by meta-analysis. Methods: We conducted literature retrieval in electronic databases, including MEDLINE, EMBASE, and Cochrane Central, to identify relevant randomized controlled trials (RCTs) investigating the clinical effects of antibiotic prophylaxis for hysteroscopic procedures. The postoperative infection rate was selected for pooled estimation. The I2 index statistic was used to assess heterogeneity. Publication bias was evaluated using funnel plots and Egger test. Sensitivity analysis based on different subcategories was conducted to examine the stability of the main results. Results: Four RCTs including 2221 patients were identified for the final quantitative analysis. Pooled estimation indicated no significant difference in infection rate between the antibiotic prophylaxis group and control group (test for OR: Z = 0.50, P = .616; 95% CI: 0.987–1.008). Sensitivity analysis based on surgical procedure, antibiotic application, follow-up time and administration time revealed similar results. Conclusion: Based on current objective evidence, we conclude that antibiotic prophylaxis exhibits no clinical benefit for hysteroscopic procedures. Therefore, it is not recommended. Meanwhile, more high-quality RCTs are needed to support our conclusion.
Detecting Drug Non-Compliance in Internet Fora Using Information Retrieval and Machine Learning Approaches

Non-compliance situations happen when patients do not follow their prescriptions and take actions that lead to potentially harmful situations. Although such situations are dangerous, patients usually do not report them to their physicians. Hence, it is necessary to study other sources of information. We propose to study online health fora. The purpose of our work is to explore online health fora with supervised classification and information retrieval methods in order to identify messages that contain drug non-compliance. The supervised classification method permits detection of non-compliance with up to 0.824 F-measure, while the information retrieval method permits detection non-compliance with up to 0.529 F-measure. For some fine-grained categories and new data, it shows up to 0.65-0.70 Precision.
Data-based continuous-time modelling of environmental systems

In this paper, we argue that many environmental processes are more naturally defined in the context of continuous-time differential equation models, normally derived by the application of natural laws, such as mass and energy conservation. As a result, there are advantages if such models are estimated directly in this continuous-time differential equation form, rather than being formulated and estimated as discrete-time models. This paper discusses these advantages and briefly describes the key features of the two toolboxes for use with MATLAB which support the advanced time-domain methods for directly identifying linear continuous-time models from discrete-time data. The arguments presented in the paper are finally illustrated by a practical example in which the proposed data-based approach to direct CT modelling is applied to a set of rainfall-flow data.
Preconditions for Enabling Advanced Patient-Centered Decision Support on a National Knowledge Information Infrastructure

In Western healthcare, an important goal is to provide clinical decision support "for the right healthcare personnel, in the right situation, at the right time". In this poster, we use a qualitative approach to outline the preconditions for enabling such advanced patient-centered decision support. This study indicates that establishing a national knowledge information infrastructure demands well-defined national standards, codes, and terminologies, as well as structured clinical data. An extensive governance structure is also required.
Development and preliminary results of an Electronic Medical Record (EMR)-integrated smartphone telemedicine program to deliver asthma care remotely

Introduction Technology-based interventions that can function within real-world practice and improve outcomes without increasing provider burden are needed, yet few successfully cross the research-to-practice divide. This paper describes the process of developing a clinically integrated smartphone-telemedicine program for adults with asthma and results from proof-of-concept testing. Methods We used a contextually grounded intervention development approach and May's implementation theory to design the intervention, with emphasis on systems capabilities and stakeholder needs. The intervention incorporated symptom monitoring by smartphone, smartphone telemedicine visits and self-management training with a nurse, and clinical decision-support software, which provided automated calculations of asthma severity, control and step-wise therapy. Seven adults (aged 18–40 y) engaged in a 3-month beta-test. Asthma outcomes (control, quality of life, FEV1) and healthcare utilisation patterns were measured at baseline and end-of-study. Results Each participant averaged four telemedicine visits (94% patient satisfaction). All participants had uncontrolled asthma at baseline; end-of-study 5/7 classified as well-controlled. Mean asthma control improved 1.55 points (CI = 0.59–2.51); quality of life improved 1.91 points (CI = 0.50–3.31), FEV1 percent predicted increased 14.86% (CI = −3.09–32.80): effect sizes of d = 1.16, 1.09, and 0.96, respectively. Preventive healthcare utilisation increased significantly (1.86 visits/year vs. 0.28/year prior, CI 0.67–2.47) as did prescriptions for controller medications (9.29 prescriptions/year vs. 1.57 prescriptions/year, CI 4.85–10.58). Discussion Smartphone telemedicine may be an effective means to improve outcomes and deliver asthma care remotely. However, careful attention to systems capabilities and stakeholder acceptability is needed to ensure successful integration with practice. Clinical Trials registration #: NCT03648203
Named Entity Recognition in Chinese Electronic Medical Records Based on the Model of Bidirectional Long Short-Term Memory with a Conditional Random Field Layer

Named entity recognition in electronic medical records is of great significance to the construction of medical knowledge maps. This paper proposes a model of bidirectional Long Short-Term Memory with a conditional random field layer(BiLSTM-CRF). In terms of simultaneously identifying 5 types of clinical entities from CCKS2018 Chinese EHRs corpus, the BiLSTM-CRF model finally achieved better performance than the baseline CRF model (F-score of 84.23% vs 82.49%).
Assisting Phytoremediation of Heavy Metals Using Chemical Amendments

Phytoremediation is one of the safer, economical, and environment-friendly techniques in which plants are used to recover polluted soils, particularly those containing toxic organic substances and heavy metals. However, it is considered as a slow form of remediation, as plants take time to grow and flourish. Various amendments, including the augmentation of certain chemical substances i.e., ethylenediamine tetraacetic acid (EDTA), ethylene glycol tetra acetic acid (EGTA), and sodium dodecyl sulfate (SDS) have been used to induce and enhance the phytoextraction capacity in plants. Several reports show that chemical amendments can improve the metal accumulation in different plant parts without actually affecting the growth of the plant. This raises a question about the amount and mechanisms of chemical amendments that may be needed for potentially good plant growth and metal phytoremediation. This review provides a detailed discussion on the mechanisms undertaken by three important chemical amendments that are widely used in enhancing phytoremediation (i.e., EDTA, EGTA, and SDS) to support plant growth as well as soil phytoremediation. A core part of this review focuses on the recent advances that have been made using chemical amendments in assisting metal phytoremediation.
Linking Exome Sequencing Data with Drug Response Aberrations

Next-generation sequencing has prompted the development of numerous -omics applications. Along with experimental procedures, various computational pipelines became available to address the inherent complexities concerning the volume and quality of data. These pipelines are effective and routinely applied; however, interpreting their outcomes into actionable evidence is still poorly addressed. In this context, this work proposes a method for translating patient genomic profiles to drug response aberrations by integrating pharmacogenomic data into sequencing data analysis pipelines.
Evaluation of a Mobile Application to Enhance Medication Management Following Hospital Discharge: Study Protocol for a Pilot Randomized Controlled Trial

Over 3 million hospitalizations and 17 million ER visits occur in Canada each year. A substantial proportion of these encounters are preventable and attributable to medication non- adherence. Non-adherence to medication changes during discharge increases the risk of adverse events post-discharge. A mobile application was developed to improve medication management of post-discharge patients. A pilot randomized controlled trial was conducted to assess the application's usability and efficacy in decreasing non-adherence to medication changes made at discharge.
CTPA, DECT, MRI, V/Q Scan, and SPECT/CT V/Q for the noninvasive diagnosis of chronic thromboembolic pulmonary hypertension

Abstract Background: To determine the diagnostic accuracy of techniques with chronic thromboembolic pulmonary hypertension (CTEPH) patients via a protocol for systemic review and network meta-analysis. Methods: We will search PubMed, EMBASE, Web of Science, and Google Scholar from inception to October 1, 2018. The reference lists of the retrieved articles are also consulted. Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) will be used to assess the risk of bias in each study. The direct meta-analyses, network meta-analyses, and ranking of competing diagnostic tests will be used by STATA 12.0 and WINBUGS 1.4. Heterogeneity and inconsistency are assessed. Results: This study is ongoing, will be submitted to a peer-reviewed journal publication once completed. Conclusion: This study will provide a comprehensive evidence summary of diagnostic test accuracy in detecting the CTEPH, and can help patients and clinicians to select appropriate or best diagnostic test. Ethics and Communication: No ethical approval and patient consent are required, because it is based on published researches. PROSPERO registration number: CRD42019121279.