Miracle-dz/UniFAR-FTUs huggingface dataset:
Cutaneous Epithelial to Mesenchymal Transition Activator ZEB1 Regulates Wound Angiogenesis and Closure in a Glycemic Status–Dependent Manner

Epithelial to mesenchymal transition (EMT) and wound vascularization are two critical interrelated processes that enable cutaneous wound healing. Zinc finger E-box binding homeobox 1 (ZEB1), primarily studied in the context of tumor biology, is a potent EMT activator. ZEB1 is also known to contribute to endothelial cell survival as well as stimulate tumor angiogenesis. The role of ZEB1 in cutaneous wounds was assessed using Zeb1+/− mice, as Zeb1−/− mice are not viable. Quantitative stable isotope labeling by amino acids in cell culture (SILAC) proteomics was used to elucidate the effect of elevated ZEB1, as noted during hyperglycemia. Under different glycemic conditions, ZEB1 binding to E-cadherin promoter was investigated using chromatin immunoprecipitation. Cutaneous wounding resulted in loss of epithelial marker E-cadherin with concomitant gain of ZEB1. The dominant proteins downregulated after ZEB1 overexpression functionally represented adherens junction pathway. Zeb1+/− mice exhibited compromised wound closure complicated by defective EMT and poor wound angiogenesis. Under hyperglycemic conditions, ZEB1 lost its ability to bind E-cadherin promoter. Keratinocyte E-cadherin, thus upregulated, resisted EMT required for wound healing. Diabetic wound healing was improved in ZEB+/− as well as in db/db mice subjected to ZEB1 knockdown. This work recognizes ZEB1 as a key regulator of cutaneous wound healing that is of particular relevance to diabetic wound complication.
The Digitization of the ICU: An Evaluation of Usability and Hospital-Wide Acceptability

This paper explores the impact of an electronic medication management system (EMMS) on users in an intensive care unit using the Unified Theory and Use of Technology constructs. It also explores the impact of having a consistent EMMS hospital wide, as it is the first Australian hospital to implement the same EMMS hospital wide. The research model was evaluated using survey data from 100 nurses, doctors and pharmacists both within the ICU and externally, to assess the usability and acceptability of the system. Results showed that performance expectancy, effort expectancy, social influence and facilitating condition all correlate with overall user satisfaction. Overall, teams external to the ICU are in strong favor of its implementation whist user acceptance from within the ICU itself is poor.
Trends in medication adherence in HIV patients in the US, 2001 to 2012: an observational cohort study

Adherence to antiretroviral therapy (ART) is essential to reduce HIV‐related morbidity and mortality as well as the risk of virological failure and HIV transmission. We determined the trends in ART adherence during the periods of therapeutic advances, wider use of ART and greater attention to ART adherence. To understand the general trends in medication adherence, we compared ART adherence with medications for other common chronic conditions.
User-Centered Design of the C3-Cloud Platform for Elderly with Multiple Diseases - Functional Requirements and Application Testing

The number of patients with multimorbidity has been steadily increasing in the modern aging societies. The European C3-Cloud project provides a multidisciplinary and patient-centered "Collaborative Care and Cure-system" for the management of elderly with multimorbidity, enabling continuous coordination of care activities between multidisciplinary care teams (MDTs), patients and informal caregivers (ICG). In this study various components of the infrastructure were tested to fulfill the functional requirements and the entire system was subjected to an early application testing involving different groups of end-users. MDTs from participating European regions were involved in requirement elicitation and test formulation, resulting in 57 questions, distributed via an internet platform to 48 test participants (22 MDTs, 26 patients) from three pilot sites. The results indicate a high level of satisfaction with all components. Early testing also provided feedback for technical improvement of the entire system, and the paper points out useful evaluation methods.
Adding Instructiveness to IHE-XDS Based Electronic Health Records

eHealth system users need adequate, timely access to health-related information; including the functionality of alerting and notifications on events. This was addressed through requirements engineering techniques. The analysis resulted in a requirements' list and architecture based on IHE standards. Patients, professionals and administrators were identified as main actors, core notification attributes were type and transport channel, and notifications always event-triggered. One challenge is system-based data access events, potentially leading to an invalid triggering of events.
The long-term consequences of antibiotic therapy: Role of colonic short-chain fatty acids (SCFA) system and intestinal barrier integrity

Epidemiological studies revealed that antibiotics exposure increases a risk of inflammatory bowel diseases (IBD) development. It remained largely unknown how antibiotic-induced dysbiosis confers the risk for enhanced inflammatory response. The aim of the present study was to test the hypothesis that SCFAs, their receptors and transporters mediate the antibiotic long-term effects on the functional state of colonic mucosa and susceptibility to the experimental colitis. Male Wistar rats were treated daily for 14 days with antibiotic ceftriaxone (300 mg/kg, i.m.) or vehicle; euthanized by CO2 inhalation followed by cervical dislocation in 1, 14 or 56 days after antibiotic withdrawal. We found increased cecum weight and sustained changes in microbiota composition after ceftriaxone treatment with increased number of conditionally pathogenic enterobacteria, E. coli, Clostridium, Staphylococcus spp. and hemolytic bacteria even at 56 days after antibiotic withdrawal. The concentration of SCFAs was decreased after ceftriaxone withdrawal. We found decreased immunoreactivity of the FFA2, FFA3 receptors, SMCT1 and increased MCT1 & MCT4 transporters of SCFAs in colon mucosa. These changes evoked a significant shift in colonic mucosal homeostasis: the disturbance of oxidant-antioxidant balance; activation of redox-sensitive transcription factor HIF1α and ERK1/2 MAP kinase; increased colonic epithelial permeability and bacterial translocation to blood; morphological remodeling of the colonic tissue. Ceftriaxone pretreatment significantly reinforced inflammation during experimental colitis 56 days after ceftriaxone withdrawal, which was confirmed by increased histopathology of colitis, Goblet cell dysfunction, colonic dilatation and wall thickening, and increased serum levels of inflammatory cytokines (TNF-α and IL-10). Since the recognition of the importance of microbiota metabolic activity rather than their composition in the development of inflammatory disorders, e.g. IBD, the present study is the first report on the role of the SCFA system in the long lasting side effects of antibiotic treatment and its implication in IBD development.
The Potential Physiological Role of γ-Tocopherol in Human Health: A Qualitative Review

Abstract Chronic aging-related diseases result in the greatest burden to the health care system, yet there is little agreement on optimal levels of vitamins or the functional significance of many other dietary molecules in disease prevention. This review presents accumulated information regarding the role of γ-tocopherol in the prevention of nitrogen oxide-mediated damage and its impact on aging-related diseases. γ-Tocopherol is ubiquitous in the diet and levels appear to be physiologically regulated such that levels rise in response to inflammation and deficiencies in certain key vitamins. The unique antioxidant properties of γ-tocopherol, whereby DNA-damaging nitrogen dioxide is rapidly converted to nitric oxide, suggest a mechanistic justification for a functional role in the prevention of DNA damage over time. Data from cell, animal, and human studies indicate that γ-tocopherol appears to have significant beneficial effects, protecting cells from inflammatory damage; however, interpretation of epidemiologic studies is complex due to the paradoxical rise in levels of γ-tocopherol in response to known etiologic risk factors. Current knowledge of its antioxidant mechanism of action, apparent physiological regulation, and impact on various enzymatic pathways suggests γ-tocopherol may have a functional role in maintaining human health. Its utility as a biomarker and the consequences of its deficiency deserve further study.
Construction and Composition of the Squid Pen from Doryteuthis pealeii

The pen, or gladius, of the squid is an internalized shell. It serves as a site of attachment for important muscle groups and as a protective barrier for the visceral organs. The pen’s durability and flexibility are derived from its unique composition of chitin and protein. We report the characterization of the structure, development, and composition of pens from Doryteuthis pealeii. The nanofibrils of the polysaccharide β-chitin are arranged in an aligned configuration in only specific regions of the pen. Chitin is secreted early in development, enabling us to characterize the changes in pen morphology prior to hatching. The chitin and proteins are assembled in the shell sac surrounded by fluid that has a significantly different ionic composition from squid plasma. Two groups of proteins are associated with the pen: those on its surface and those embedded within the pen. Only 20 proteins are identified as embedded within the pen. Embedded proteins are classified into six groups, including chitin associated, protease, protease inhibitors, intracellular, extracellular matrix, and those that are unknown. The pen proteins share many conserved domains with proteins from other chitinous structures. We conclude that the pen is one of the least complex, load-bearing, chitin-rich structures currently known and is amenable to further studies to elucidate natural construction mechanisms using chitin and protein.
Hyper-Activation of STAT3 Sustains Progression of Non-Papillary Basal-Type Bladder Cancer via FOSL1 Regulome

Urothelial bladder cancer (UBC) are classified into luminal and basal subtypes showing distinct molecular features and clinical behaviour. Recent in silico data have proposed the activation on the Signal Transducer and Activator of Transcription 3 (STAT3) as relevant transcription factor in UBC. To answer this question, we have combined the retrospective analysis of clinical samples, functional assays on cell lines, interrogation of public UBC datasets and a murine model of basal-type UBC. Immunohistochemistry on a retrospective UBC cohort uncovered that STAT3 Y705 phosphorylation (pSTAT3) is significantly increased in infiltrating basal-type UBC compared to luminal UBC. In vitro, STAT3 silencing in UBC cell lines significantly reduced tumor cell viability and invasion. Gene expression profile of UBC cell lines combined with the analysis of the Cancer Genome Atlas (TCGA) and GSE32894 UBC datasets showed that increased expression of a set of STAT3 targets predicts basal-type, propensity to local progression and worse prognosis. MYC and FOSL1 represent relevant STAT3 downstream targets, as validated by their co-localization in pSTAT3+ UBC cancer cells. These findings were largely reproduced in the BBN-induced murine model of basal-type UBC. Of note, FOSL1 protein resulted strongly expressed in the non-papillary UBC pathway and FOSL1-regulated transcripts were significantly enriched in the transition from NMIBC to MIBC, as indicated by the interrogation of the GSE32894 dataset. The blockade of the STAT3 pathway might represent a novel treatment option for these neoplasms. Monitoring pSTAT3 and the downstream targets, particularly FOSL1, could provide meaningful levels of UBC stratification.
Unsupervised Phrase-Level Query Rewriting for Assisting Search in Clinical Free Text

We report on the pilot evaluation of an experimental query-based search functionality that enables phrase-level query rewriting in an unsupervised way. It is intended for supporting search in clinical text. Qualitative evaluation is done by three clinicans using a prototype search tool. They report that they find the tested search functionality to be beneficial for making query-based searching in clinical text more efficient.
The MeSH-Gram Neural Network Model: Extending Word Embedding Vectors with MeSH Concepts for Semantic Similarity

Eliciting semantic similarity between concepts remains a challenging task. Recent approaches founded on embedding vectors have gained in popularity as they have risen to efficiently capture semantic relationships. The underlying idea is that two words that have close meaning gather similar contexts. In this study, we propose a new neural network model, named MeSH-gram, which relies on a straightforward approach that extends the skip-gram neural network model by considering MeSH (Medical Subject Headings) descriptors instead of words. Trained on publicly available PubMed/MEDLINE corpus, MeSH-gram is evaluated on reference standards manually annotated for semantic similarity. MeSH-gram is first compared to skip-gram with vectors of size 300 and at several windows' contexts. A deeper comparison is performed with twenty existing models. All the obtained results with Spearman's rank correlations between human scores and computed similarities show that MeSH-gram (i) outperforms the skip-gram model and (ii) is comparable to the best methods that need more computation and external resources.
Perceptions and Preferences About Granular Data Sharing and Privacy of Behavioral Health Patients

Little is known about data sharing preferences for care and research of behavioral health patients. Eighty-six behavioral health patients (n = 37 Latinos; n = 32 with serious mental illness) completed questionnaires, in either English or Spanish, with items assessing their views on privacy and sensitivity of health record information. Most patients (82.5%) considered mental health information as sensitive. In general, there was a direct correspondence between perceived sensitivity of information and willingness to share with all or some providers. A main motivation for sharing data with providers was improving the patient's own care (77.8%). Most participants (96.5%) indicated they would be extremely to somewhat willing to share their data for research with their care facilities and universities. Follow-up patient interviews are being conducted to further elucidate these findings.
ParaDrop: An Edge Computing Platform in Home Gateways

The last decade has seen a rapid diversification of computing platforms, devices, and services. For example, desktops used to be the primary computing platform until the turn of the century. Since then, laptops and more recently handheld devices such as laptops and tablets have been widely adopted. Wearable devices and the Internet of things (IoT) are the latest trends in this space. This has also led to widespread adoption of the “cloud” as a ubiquitous platform for supporting applications and services across these different devices. Simultaneously, cloud computing platforms, such as Amazon EC2 and Google App Engine, have become a popular approach to provide ubiquitous access to services across different user devices. Third-party developers have come to rely on cloud computing platforms to provide high quality services to their end users, since they are reliable, always on, and robust. Netflix and Dropbox are examples of popular cloud-based services. Cloud services require developers to host services, applications, and data on off-site data centers. But, due to application-specific reasons, a growing number of high quality services restrict computational tasks to be colocated with the end user. For example, latency-sensitive applications require the backend service to be located to a user’s current location. Over the years, a number of research threads have proposed that a better end-user experience is possible if the computation is performed close to the end user. This is typically referred to as “edge computing” and comes in various flavors including: cyber foraging [1], cloudlets [2], and more recently fog computing [3].
Development of a Method for Extracting Structured Dose Information from Free-Text Electronic Prescriptions

In this study, we sought to develop an automatic parser tool for unstructured free-text electronic prescriptions, focusing specifically on defining the daily dose. We manually coded a set of electronic discharge prescriptions and established the most reliable rules to structure the medication data. A named-entity recognition (NER) parser tool was implemented, which was capable of identifying 90% of the doses and 86% of the frequencies from 255 dosage instructions.
Using Health Information Exchange: Usability and Usefulness Evaluation

Health information exchange (HIE) is implemented in Quebec, Canada to improve the exchange and use of clinical information for decision making in the province's health care system. The objective of this mixed-method approach study was to evaluate the usage, usability, and usefulness of an electronic health record (EHR) to access and import clinical information from a centralized HIE. First, a heuristic analysis was performed of three different commercial EHRs, using end users to analyze the integration feature through think aloud protocols. Second, interviews were conducted with advanced users to describe the usefulness. Third, usage data were analyzed to describe the level of use of each data domain, per EHR and user. The results show that usefulness is high for medication data; leading to greater use of this domain, its relation to integration, and meets the needs of general practitioners. Difficulties in the implementation processes reduced the potential of this system.
3D Printing of Bioceramic Scaffolds—Barriers to the Clinical Translation: From Promise to Reality, and Future Perspectives

In this review, we summarize the challenges of the three-dimensional (3D) printing of porous bioceramics and their translational hurdles to clinical applications. The state-of-the-art of the major 3D printing techniques (powder-based and slurry-based), their limitations and key processing parameters are discussed in detail. The significant roadblocks that prevent implementation of 3D printed bioceramics in tissue engineering strategies, and medical applications are outlined, and the future directions where new research may overcome the limitations are proposed. In recent years, there has been an increasing demand for a nanoscale control in 3D fabrication of bioceramic scaffolds via emerging techniques such as digital light processing, two-photon polymerization, or large area maskless photopolymerization. However, these techniques are still in a developmental stage and not capable of fabrication of large-sized bioceramic scaffolds; thus, there is a lack of sufficient data to evaluate their contribution. This review will also not cover polymer matrix composites reinforced with particulate bioceramics, hydrogels reinforced with particulate bioceramics, polymers coated with bioceramics and non-porous bioceramics.
Facilitating Clinical Trial Recruitment by Recommending Cost-Efficient Medical Exams

Clinical trials are key and essential processes for researchers to develop new treatments as well as evaluate their effectiveness and safety, whilst more than half of all clinical trials experience delays, which leads to a considerable amount of cost. In this paper, we present a cost-effective framework to reduce the time and monetary cost in the stage of recruiting and screening eligible clinical trial participants. By leveraging patients' observed conditions and the cost of medical examinations, the proposed framework uses collaborative filtering techniques to predict the utilized cost for the to-do medical examinations and then rank patients and medical examinations. The preliminary experiment results indicate that the framework is promising to reduce the cost spent on medical examinations by three quarters or even more and accelerate the recruitment process in the screening stage.
Evaluation of oxidative DNA damage in pigeon erythrocytes using DNA breakage detection-fluorescence in situ hybridization (DBD-FISH)

ABSTRACT DNA breakage detection-fluorescence in situ hybridization (DBD-FISH) enables detection and quantification of DNA breakage in the entire genome or within specific DNA sequences in single cells. We used this method to visualize and evaluate DNA damage in pigeon erythrocytes that were induced by elevated temperature and hydrogen peroxide. We also examined morphological changes in the cell nuclei. DBD-FISH demonstrated a significant increase of DNA damage in a temperature dependent manner, which resulted in nuclear abnormalities associated with apoptotic cells. These cells gave strong nuclear fluorescent signals that indicated cell death.
Tissue and Plasma EGFR Mutation Analysis in the FLAURA Trial: Osimertinib versus Comparator EGFR Tyrosine Kinase Inhibitor as First-Line Treatment in Patients with EGFR-Mutated Advanced Non–Small Cell Lung Cancer

Purpose: To assess the utility of the cobas EGFR Mutation Test, with tissue and plasma, for first-line osimertinib therapy for patients with EGFR-mutated (EGFRm; Ex19del and/or L858R) advanced or metastatic non–small cell lung cancer (NSCLC) from the FLAURA study (NCT02296125). Experimental Design: Tumor tissue EGFRm status was determined at screening using the central cobas tissue test or a local tissue test. Baseline circulating tumor (ct)DNA EGFRm status was retrospectively determined with the central cobas plasma test. Results: Of 994 patients screened, 556 were randomized (289 and 267 with central and local EGFR test results, respectively) and 438 failed screening. Of those randomized from local EGFR test results, 217 patients had available central test results; 211/217 (97%) were retrospectively confirmed EGFRm positive by central cobas tissue test. Using reference central cobas tissue test results, positive percent agreements with cobas plasma test results for Ex19del and L858R detection were 79% [95% confidence interval (CI), 74–84] and 68% (95% CI, 61–75), respectively. Progression-free survival (PFS) superiority with osimertinib over comparator EGFR-TKI remained consistent irrespective of randomization route (central/local EGFRm-positive tissue test). In both treatment arms, PFS was prolonged in plasma ctDNA EGFRm-negative (23.5 and 15.0 months) versus -positive patients (15.2 and 9.7 months). Conclusions: Our results support utility of cobas tissue and plasma testing to aid selection of patients with EGFRm advanced NSCLC for first-line osimertinib treatment. Lack of EGFRm detection in plasma was associated with prolonged PFS versus patients plasma EGFRm positive, potentially due to patients having lower tumor burden.