Miracle-dz/UniFAR-FTUs huggingface dataset:
Population pharmacokinetic modeling and simulation of HPPH in Chinese patients with esophageal carcinoma

Abstract 1. 2-[1-Hexyloxyethyl]-2-devinyl pyropheophorbide-a (HPPH), a second-generation photosensitizer, has been widely employed in photodynamic therapy (PDT) for the treatment of malignant lesions. The objective of this study was to characterize the pharmacokinetics of HPPH in Chinese patients using a population pharmacokinetic (PopPK) approach. 2. For the first time, a PopPK model of HPPH for Chinese (n = 20) was developed (registration number: CTR20160425). The pharmacokinetics of HPPH was described by a three-compartment model with linear elimination. Through the stepwise addition (p < 0.05) and backward elimination (p < 0.001) approach, fat-free mass (FFM) was identified to be the most significant covariate and V1 increased with FFM. Visual predictive check (VPC) was employed for the evaluation of the final model. Subsequent full covariate analysis indicated that FFM has considerable impact (∼30%) on HPPH exposure and fat mass also has a modest (∼25%) impact. 3. The simulations suggested that a dose adjustment of HPPH may be necessary for Chinese and the dose of 3 mg/m2 should be appropriate. HPPH exposure increases with fat mass while being inversely related to FFM. HPPH-PDT for overweight patients should be monitored with more caution and PDT conditions should be optimized if necessary.
A Combined Approach of Field Data and Earth Observation for Coastal Risk Assessment

The traditional approach for coastal monitoring consists in ground investigations that are burdensome both in terms of logistics and costs, on a national or even regional scale. Earth Observation (EO) techniques can represent a cost-effective alternative for a wide scale coastal monitoring. Thanks to the all-weather day/night radar imaging capability and to the nationwide acquisition plan named MapItaly, devised by the Italian Space Agency and active since 2010, COSMO-SkyMed (CSK) constellation is able to provide X-band images covering the Italian territory. However, any remote sensing approach must be accurately calibrated and corrected taking into account the marine conditions. Therefore, in situ data are essential for proper EO data selection, geocoding, tidal corrections and validation of EO products. A combined semi-automatic technique for coastal risk assessment and monitoring, named COSMO-Beach, is presented here, integrating ground truths with EO data, as well as its application on two different test sites in Apulia Region (South Italy). The research has shown that CSK data for coastal monitoring ensure a shoreline detection accuracy lower than image pixel resolution, and also providing several advantages: low-cost data, a short revisit period, operational continuity and a low computational time.
Systems engineering and human factors support of a system of novel EHR-integrated tools to prevent harm in the hospital

We established a Patient Safety Learning Laboratory comprising 2 core and 3 individual project teams to introduce a suite of digital health tools integrated with our electronic health record to identify, assess, and mitigate threats to patient safety in real time. One of the core teams employed systems engineering (SE) and human factors (HF) methods to analyze problems, design and develop improvements to intervention components, support implementation, and evaluate the system of systems as an integrated whole. Of the 29 participants, 19 and 16 participated in surveys and focus groups, respectively, about their perception of SE and HF. We identified 7 themes regarding use of the 12 SE and HF methods over the 4-year project. Qualitative methods (interviews, focus, groups, observations, usability testing) were most frequently used, typically by individual project teams, and generated the most insight. Quantitative methods (failure mode and effects analysis, simulation modeling) typically were used by the SE and HF core team but generated variable insight. A decentralized project structure led to challenges using these SE and HF methods at the project and systems level. We offer recommendations and insights for using SE and HF to support digital health patient safety initiatives.
Formative Assessment of Performance in Diagnostic Ultrasound Using Simulation and Quantitative and Objective Metrics.

BACKGROUND We developed simulator-based tools for assessing provider competence in transthoracic echocardiography (TTE) and vascular duplex scanning. METHODS Psychomotor (technical) skill in TTE image acquisition was calculated from the deviation angle of an acquired image from the anatomically correct view. We applied this metric for formative assessment to give feedback to learners and evaluate curricula.Psychomotor skill in vascular ultrasound was measured in terms of dexterity and image plane location; cognitive skill was assessed from measurements of blood flow velocity, parameter settings, and diagnosis. The validity of the vascular simulator was assessed from the accuracy with which experts can measure peak systolic blood flow velocity (PSV). RESULTS In the TTE simulator, the skill metric enabled immediate feedback, formative assessment of curriculum efficacy, and comparison of curriculum outcomes. The vascular duplex ultrasound simulator also provided feedback, and experts' measurements of PSV deviated from actual PSV in the model by <10%. CONCLUSIONS Skill in acquiring diagnostic ultrasound images of organs and vessels can be measured using simulation in an objective, quantitative, and standardized manner. Current applications are provision of feedback to learners to enable training without direct faculty oversight and formative assessment of curricula. Simulator-based metrics could also be applied for summative assessment.
Current Progress in Pharmacogenetics of Second-Line Antidiabetic Medications: Towards Precision Medicine for Type 2 Diabetes

Precision medicine is a scientific and medical practice for personalized therapy based on patients’ individual genetic, environmental, and lifestyle characteristics. Pharmacogenetics and pharmacogenomics are also rapidly developing and expanding as a key element of precision medicine, in which the association between individual genetic variabilities and drug disposition and therapeutic responses are investigated. Type 2 diabetes (T2D) is a chronic metabolic disorder characterized by hyperglycemia mainly associated with insulin resistance, with the risk of clinically important cardiovascular, neurological, and renal complications. The latest consensus report from the American Diabetes Association and European Association for the Study of Diabetes (ADA-EASD) on the management of T2D recommends preferential use of glucagon-like peptide-1 (GLP-1) receptor agonists, sodium-glucose cotransporter-2 (SGLT2) inhibitors, and some dipeptidyl peptidase-4 (DPP-4) inhibitors after initial metformin monotherapy for diabetic patients with established atherosclerotic cardiovascular or chronic kidney disease, and with risk of hypoglycemia or body weight-related problems. In this review article, we summarized current progress on pharmacogenetics of newer second-line antidiabetic medications in clinical practices and discussed their therapeutic implications for precision medicine in T2D management. Several biomarkers associated with drug responses have been identified from extensive clinical pharmacogenetic studies, and functional variations in these genes have been shown to significantly affect drug-related glycemic control, adverse reactions, and risk of diabetic complications. More comprehensive pharmacogenetic research in various clinical settings will clarify the therapeutic implications of these genes, which may be useful tools for precision medicine in the treatment and prevention of T2D and its complications.
Biomimetic Membranes with Transmembrane Proteins: State-of-the-Art in Transmembrane Protein Applications

In biological cells, membrane proteins are the most crucial component for the maintenance of cell physiology and processes, including ion transportation, cell signaling, cell adhesion, and recognition of signal molecules. Therefore, researchers have proposed a number of membrane platforms to mimic the biological cell environment for transmembrane protein incorporation. The performance and selectivity of these transmembrane proteins based biomimetic platforms are far superior to those of traditional material platforms, but their lack of stability and scalability rule out their commercial presence. This review highlights the development of transmembrane protein-based biomimetic platforms for four major applications, which are biosensors, molecular interaction studies, energy harvesting, and water purification. We summarize the fundamental principles and recent progress in transmembrane protein biomimetic platforms for each application, discuss their limitations, and present future outlooks for industrial implementation.
MicroRNA Shuttle from Cell-To-Cell by Exosomes and Its Impact in Cancer

The identification of exosomes, their link to multivesicular bodies and their potential role as a messenger vehicle between cancer and healthy cells opens up a new approach to the study of intercellular signaling. Furthermore, the fact that their main cargo is likely to be microRNAs (miRNAs) provides the possibility of the transfer of such molecules to control activities in the recipient cells. This review concerns a brief overview of the biogenesis of both exosomes and miRNAs together with the movement of such structures between cells. The possible roles of miRNAs in the development and progression of breast, ovarian and prostate cancers are discussed.
CytoBackBone: an algorithm for merging of phenotypic information from different cytometric profiles

Abstract Motivation Flow and mass cytometry are experimental techniques used to measure the level of proteins expressed by cells at the single-cell resolution. Several algorithms were developed in flow cytometry to increase the number of simultaneously measurable markers. These approaches aim to combine phenotypic information of different cytometric profiles obtained from different cytometry panels. Results We present here a new algorithm, called CytoBackBone, which can merge phenotypic information from different cytometric profiles. This algorithm is based on nearest-neighbor imputation, but introduces the notion of acceptable and non-ambiguous nearest neighbors. We used mass cytometry data to illustrate the merging of cytometric profiles obtained by the CytoBackBone algorithm. Availability and implementation CytoBackBone is implemented in R and the source code is available at https://github.com/tchitchek-lab/CytoBackBone. Supplementary information Supplementary data are available at Bioinformatics online.
Perioperative Treatment in Resectable Gastric Cancer: Current Perspectives and Future Directions

Gastric cancer (GC) is the fifth-most common cancer worldwide and an important cause of cancer-related-death. The growing knowledge of its molecular pathogenesis has shown that GC is not a single entity, but a constellation of different diseases, each with its own molecular and clinical characteristics. Currently, surgery represents the only curative approach for localized GC, but only 20% of patients (pts) showed resectable disease at diagnosis and, even in case of curative resection, the prognosis remains poor due to the high rate of disease relapse. In this context, multimodal perioperative approaches were developed in western and eastern countries in order to decrease relapse rates and improve survival. However, there is little consensus about the optimal treatment for non-metastatic GC. In this review, we summarize the current status and future developments of perioperative chemotherapy in resectable GC, attempting to find clear answers to the real problems in clinical practice.
Effect of Oral Physiology Parameters on In-Mouth Aroma Compound Release Using Lipoprotein Matrices: An In Vitro Approach

Temporal aroma compound release during eating is a function of the physicochemical properties of the food matrix, aroma compounds, and oral physiology of individuals. However, the influence of each parameter on the release of each aroma component should be clarified. Two flavored lipoprotein matrices varying in composition were chewed in a chewing simulator that reproduced most of the physiological functions of the mouth. Aroma compound releases (butanoic acid, 2-heptanone, ethyl butyrate, 3-octanone, and 2-nonanone) were followed in real time by direct connection of the device to APCI-MS (atmospheric pressure chemical ionization mass spectrometry). Each oral parameter was controlled and decoupled using the in vitro device. The food matrix composition had only a low impact on aroma compound release, but the controlled oral parameters had significantly different influences on the release of aroma compounds according to their physicochemical characteristics. The release of certain compounds seemed more sensitive to bite force, while others seemed more sensitive to the shearing angle. The salivary flow rate primarily influenced the more hydrophobic compounds. Significant interactions were also observed between shear angle, salivary flow rate, and lipoprotein matrix composition, mainly for the release of the more hydrophobic volatile compounds; this needs further investigations to be clarified.
The Effect of Preoperative Education on Psychological, Clinical and Economic Outcomes in Elective Spinal Surgery: A Systematic Review

Psychosocial factors related to different degrees of clinical impairment and quality of life in the preoperative period may influence outcomes from elective spine surgery. Patients have expressed a need for individualized information given in sufficient quantities and at the appropriate time. Therefore, this review article aims to determine whether a preoperative education session improves clinical, psychological and economic outcomes in elective spinal surgery. PubMed, Cochrane Library, CINAHL Complete, Medline Complete and PsychINFO were searched in July 2018 for randomized clinical trials to evaluate the effects of a preoperative education intervention on psychological, clinical and economic outcomes in spinal surgery. The search yielded 78 results, of which eleven papers (seven studies) were relevant for inclusion. From these results, there is limited, fair-quality evidence that supports the inclusion of a preoperative education session for improving clinical (pain, function and disability), economic (quality-adjusted life years, healthcare expenditure, direct and indirect costs) and psychological outcomes (anxiety, depression and fear-avoidance beliefs) from spinal surgery. Other benefits are reported to be improved patient knowledge, feelings of better preparation, reduced negative thinking and increased levels of physical activity after the intervention. No differences in quality of life, return to work, physical indicators or postoperative complications were reported. From the limited evidence, it is not possible to conclusively recommend that preoperative education should be delivered as a standalone intervention before elective spine surgery; however, given the low risk profile and promising benefits, future research in this area is warranted.
Actin filaments regulate microtubule growth at the centrosome

The centrosome is the main microtubule-organizing centre. It also organizes a local network of actin filaments. However, the precise function of the actin network at the centrosome is not well understood. Here we show that increasing densities of actin filaments at the centrosome of lymphocytes were correlated with reduced amounts of microtubules. Furthermore, lymphocyte activation resulted in centrosomal-actin disassembly and an increase in microtubule number. To further investigate the direct crosstalk between actin and microtubules at the centrosome, we performed in vitro reconstitution assays based on (i) purified centrosomes and (ii) on the co-micropatterning of microtubule seeds and actin filaments. The two assays demonstrated that actin filaments perturb microtubule growth by steric hindrance. Finally, we showed that cell adhesion and spreading leads to lower densities of centrosomal actin thus resulting in higher microtubule growth. Hence we propose a novel mechanism by which the number of centrosomal microtubules is regulated by cell adhesion and actin-network architecture.
Myocardial strain imaging: review of general principles, validation, and sources of discrepancies

Abstract Myocardial tissue tracking imaging techniques have been developed for a more accurate evaluation of myocardial deformation (i.e. strain), with the potential to overcome the limitations of ejection fraction (EF) and to contribute, incremental to EF, to the diagnosis and prognosis in cardiac diseases. While most of the deformation imaging techniques are based on the similar principles of detecting and tracking specific patterns within an image, there are intra- and inter-imaging modality inconsistencies limiting the wide clinical applicability of strain. In this review, we aimed to describe the particularities of the echocardiographic and cardiac magnetic resonance deformation techniques, in order to understand the discrepancies in strain measurement, focusing on the potential sources of variation: related to the software used to analyse the data, to the different physics of image acquisition and the different principles of 2D vs. 3D approaches. As strain measurements are not interchangeable, it is highly desirable to work with validated strain assessment tools, in order to derive information from evidence-based data. There is, however, a lack of solid validation of the current tissue tracking techniques, as only a few of the commercial deformation imaging softwares have been properly investigated. We have, therefore, addressed in this review the neglected issue of suboptimal validation of tissue tracking techniques, in order to advocate for this matter.
Caliciviridae Other Than Noroviruses

Besides noroviruses, the Caliciviridae family comprises four other accepted genera: Sapovirus, Lagovirus, Vesivirus, and Nebovirus. There are six new genera proposed: Recovirus, Valovirus, Bavovirus, Nacovirus, Minovirus, and Salovirus. All Caliciviridae have closely related genome structures, but are genetically and antigenically highly diverse and infect a wide range of mammalian host species including humans. Recombination in nature is not infrequent for most of the Caliciviridae, contributing to their diversity. Sapovirus infections cause diarrhoea in pigs, humans and other mammalian hosts. Lagovirus infections cause systemic haemorrhagic disease in rabbits and hares, and vesivirus infections lead to lung disease in cats, vesicular disease in swine, and exanthema and diseases of the reproductive system in large sea mammals. Neboviruses are an enteric pathogen of cattle, differing from bovine norovirus. At present, only a few selected caliciviruses can be propagated in cell culture (permanent cell lines or enteroids), and for most of the cultivatable caliciviruses helper virus-free, plasmid only-based reverse genetics systems have been established. The replication cycles of the caliciviruses are similar as far as they have been explored: viruses interact with a multitude of cell surface attachment factors (glycans) and co-receptors (proteins) for adsorption and penetration, use cellular membranes for the formation of replication complexes and have developed mechanisms to circumvent innate immune responses. Vaccines have been developed against lagoviruses and vesiviruses, and are under development against human noroviruses.
Association of Gene Polymorphisms With Primary Open Angle Glaucoma: A Systematic Review and Meta-Analysis.

Purpose To confirm the association of all reported common polymorphisms with POAG. Methods We searched in PubMed and Web of Science (up to January 10, 2018) for genetic studies of POAG. All case control studies investigating the association between single-nucleotide polymorphisms (SNPs) and POAG risk were included. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated by fixed- or random-effect model. Results This meta-analysis included 108 case control studies involving 35,389 POAG patients and 51,742 controls. The pooled results showed a significant association between 20 SNPs in 12 genes (148Asp/Glu in APE1 gene; rs449647 in APOE gene; rs1052990 and rs4236601 in CAV1/CAV2 gene; rs1799750 in MMP gene; c.603T3A (Met98Lys) in OPTN gene; rs7081455 in PLXDC2 gene; rs1279683 in SLC23A2 gene; 372 T/C in TIMP1 gene; rs1927911, rs2149356, rs4986791, rs7037117, and rs10759930 in TLR4 gene; rs4656461 in TMCO1 gene; 399Arg/Gln in XRCC1 gene; and rs540782, rs547984, and rs693421 in ZP4 gene) with POAG. Conclusions Based on the current meta-analysis, we indicate 20 SNPs in 12 genes (APE1, APOE, CAV1/CAV2, MMP, OPTN, PLXDC2, SLC23A2, TIMP1, TLR4, TMCO1, XRCC1, ZP4) as predictive risk factors for POAG. More studies with large sample sizes and various ethnicities are warranted in the future to provide more powerful evidence.
Global Epidemiology of Mucormycosis

Mucormycosis is an angio-invasive fungal infection, associated with high morbidity and mortality. A change in the epidemiology of mucormycosis has been observed in recent years with the rise in incidence, new causative agents and susceptible population. The rise has been perceived globally, but it is very high in the Asian continent. Though diabetes mellitus overshadow all other risk factors in Asia, post-tuberculosis and chronic renal failure have emerged as new risk groups. The rhino-cerebral form of mucormycosis is most commonly seen in patients with diabetes mellitus, whereas, pulmonary mucormycosis in patients with haematological malignancy and transplant recipients. In immunocompetent hosts, cutaneous mucormycosis is commonly seen following trauma. The intriguing clinical entity, isolated renal mucormycosis in immunocompetent patients is only reported from China and India. A new clinical entity, indolent mucormycosis in nasal sinuses, is recently recognized. The causative agents of mucormycosis vary across different geographic locations. Though Rhizopus arrhizus is the most common agent isolated worldwide, Apophysomyces variabilis is predominant in Asia and Lichtheimia species in Europe. The new causative agents, Rhizopus homothallicus, Mucor irregularis, and Thamnostylum lucknowense are reported from Asia. In conclusion, with the change in epidemiology of mucormycosis country-wise studies are warranted to estimate disease burden in different risk groups, analyse the clinical disease pattern and identify the new etiological agents.
Differential Regulation of Type I and Type III Interferon Signaling

Interferons (IFNs) are very powerful cytokines, which play a key role in combatting pathogen infections by controlling inflammation and immune response by directly inducing anti-pathogen molecular countermeasures. There are three classes of IFNs: type I, type II and type III. While type II IFN is specific for immune cells, type I and III IFNs are expressed by both immune and tissue specific cells. Unlike type I IFNs, type III IFNs have a unique tropism where their signaling and functions are mostly restricted to epithelial cells. As such, this class of IFN has recently emerged as a key player in mucosal immunity. Since the discovery of type III IFNs, the last 15 years of research in the IFN field has focused on understanding whether the induction, the signaling and the function of these powerful cytokines are regulated differently compared to type I IFN-mediated immune response. This review will cover the current state of the knowledge of the similarities and differences in the signaling pathways emanating from type I and type III IFN stimulation.