Recent Advances in BODIPY Compounds: Synthetic Methods, Optical and Nonlinear Optical Properties, and Their Medical Applications.

Organoboron compounds are attracting immense research interest due to their wide range of applications. Particularly, low-coordinate organoboron complexes are receiving more attention due to their improbable optical and nonlinear optical properties, which makes them better candidates for medical applications. In this review, we summarize the various synthetic methods including multicomponent reactions, microwave-assisted and traditional pathways of organoboron complexes, and their optical and nonlinear properties. This review also includes the usage of organoboron complexes in various fields including biomedical applications.

Organotin Dyes Bearing Anionic Boron Clusters as Cell-Staining Fluorescent Probes.

Within the cell nucleus, in the nucleoli, ribosomal RNAs are synthesized and participate in several biological processes. To better understand nucleoli-related processes, their visualization is often required, for which specific markers are needed. Herein, we report the design of novel fluorescent organotin compounds derived from 4-hydroxy-N'-((2-hydroxynaphthalen-1-yl)methylene)benzohydrazide and their cytoplasm and nucleoli staining of B16F10 cells in vitro. Tin compounds bearing an aliphatic carbon chain (-C12 H25 ) and an electron-donating group (-OH) were prepared, and the latter could be derivatized to bear the boron cluster anions [B12 H12 ]2- and [3,3'-Co(1,2-C2 B9 H11 )2 ]- (COSAN). All of the conjugates have been fully characterized and their luminescence properties have been assessed. In general, they show good quantum yields in solution (24-49 %), those for the COSAN derivatives being lower. Remarkably, the linking of [B12 H12 ]2- and COSAN to the complexes made them more soluble, without being detrimental to their luminescence properties. Living B16F10 cells were treated with all of the compounds to determine their fluorescence staining properties; the compounds bearing the aliphatic chain showed a reduced staining capacity due to the formation of aggregates. Notably, the complexes bearing different boron clusters showed different staining effects; those bearing [B12 H12 ]2- showed extraordinary staining of the nucleoli and cytoplasm, whereas those bearing COSAN were only detected in the cytoplasm. The remarkable fluorescence staining properties shown by these organotin compounds make them excellent candidates for fluorescence bioimaging in vitro.

Fluorescent Molecular Rotors of Organoboron Compounds from Schiff Bases: Synthesis, Viscosity, Reversible Thermochromism, Cytotoxicity, and Bioimaging Cells.

We report the design, synthesis, and characterization of two new fluorescent molecular rotors of boron derived from Schiff bases: (2,4,8,10-tetra-tert-butyl-6-phenyldibenzo[d,h][1,3,6,2]dioxazaboronine (3) and 1,4-bis(2,4,8,10-tetra-tert-butyldibenzo[d,h][1,3,6,2]dioxazaboronin-6-yl)benzene (4), as well as the free ligand 2-[[(3,5-di-tert-butyl-2-hydroxyphenyl)imino]methyl]-4,6-di-tert-butylphenol 1. All compounds were fully characterized by NMR (1H, 11B, and 13C), IR, UV/vis, fluorescence spectroscopy, and high-resolution mass spectrometry. The crystal structures of 3 and 4 showed tetracoordinated boron atoms with semiplanar skeleton ligands. The free rotation of the fluorescent molecular rotor, only observed in the binuclear compound, was decreased with increasing viscosity, while the quantum yield was increased. Interestingly, the property of reversible thermochromism was found in organoboron 4 in the solid state. DFT calculations to determine the both complexes have free rotation around the CPh-B1 bond. The boron compounds 3 and 4 have shown low cytotoxicity activity in cell line A-431 and low green staining in cells.

Unpaired intra-operative OCT (iOCT) video super-resolution with contrastive learning.

Regenerative therapies show promise in reversing sight loss caused by degenerative eye diseases. Their precise subretinal delivery can be facilitated by robotic systems alongside with Intra-operative Optical Coherence Tomography (iOCT). However, iOCT's real-time retinal layer information is compromised by inferior image quality. To address this limitation, we introduce an unpaired video super-resolution methodology for iOCT quality enhancement. A recurrent network is proposed to leverage temporal information from iOCT sequences, and spatial information from pre-operatively acquired OCT images. Additionally, a patchwise contrastive loss enables unpaired super-resolution. Extensive quantitative analysis demonstrates that our approach outperforms existing state-of-the-art iOCT super-resolution models. Furthermore, ablation studies showcase the importance of temporal aggregation and contrastive loss in elevating iOCT quality. A qualitative study involving expert clinicians also confirms this improvement. The comprehensive evaluation demonstrates our method's potential to enhance the iOCT image quality, thereby facilitating successful guidance for regenerative therapies.

Healthcare provider-targeted mobile applications to diagnose, screen, or monitor communicable diseases of public health importance in low- and middle-income countries: A systematic review.

Communicable diseases remain a leading cause of death and disability in low- and middle-income countries (LMICs). mHealth technologies carry considerable promise for managing these disorders within resource-poor settings, but many existing applications exclusively represent digital versions of existing guidelines or clinical calculators, communication facilitators, or patient self-management tools. We thus systematically searched PubMed, Web of Science, and Cochrane Central for studies published between January 2007 and October 2019 involving technologies that were mobile phone- or tablet-based; able to screen for, diagnose, or monitor a communicable disease of importance in LMICs; and targeted health professionals as primary users. We excluded technologies that digitized existing paper-based tools or facilitated communication (i.e., knowledge-based algorithms). Extracted data included disease category, pathogen type, diagnostic method, intervention purpose, study/target population, sample size, study methodology, development stage, accessory requirement, country of development, operating system, and cost. Given the search timeline, studies involving COVID-19 were not included in the analysis. Of 13,262 studies identified by the screen, 33 met inclusion criteria. 12% were randomized clinical trials (RCTs), with 58% of publications representing technical descriptions. 62% of studies had 100 or fewer subjects. All studied technologies involved diagnosis or screening steps; none addressed the monitoring of infections. 52% focused on priority diseases (HIV, malaria, tuberculosis), but only 12% addressed a neglected tropical disease. Although most reported studies were priced under 20USD at time of publication, two thirds of the records did not yet specify a cost for the study technology. We conclude that there are only a small number of mHealth technologies focusing on innovative methods of screening and diagnosing communicable diseases potentially of use in LMICs. Rigorous RCTs, analyses with large sample size, and technologies assisting in the monitoring of diseases are needed.

4-[(E)-(4-Fluoro-benzyl-idene)amino]-benzoic acid.

In the title compound, C(14)H(10)FNO(2), the benzene rings make a dihedral angle of 57.50 (13)°, and the molecule has an E configuration about the C=N bond. In the crystal, molecules are linked via pairs of O-H⋯O hydrogen bonds, forming inversion dimers.

A systematic review of healthcare provider-targeted mobile applications for non-communicable diseases in low- and middle-income countries.

Mobile health (mHealth) interventions hold promise for addressing the epidemic of noncommunicable diseases (NCDs) in low- and middle-income countries (LMICs) by assisting healthcare providers managing these disorders in low-resource settings. We aimed to systematically identify and assess provider-facing mHealth applications used to screen for, diagnose, or monitor NCDs in LMICs. In this systematic review, we searched the indexing databases of PubMed, Web of Science, and Cochrane Central for studies published between January 2007 and October 2019. We included studies of technologies that were: (i) mobile phone- or tablet-based, (ii) able to screen for, diagnose, or monitor an NCD of public health importance in LMICs, and (iii) targeting health professionals as users. We extracted disease type, intervention purpose, target population, study population, sample size, study methodology, technology stage, country of development, operating system, and cost. Our initial search retrieved 13,262 studies, 315 of which met inclusion criteria and were analyzed. Cardiology was the most common clinical domain of the technologies evaluated, with 89 publications. mHealth innovations were predominantly developed using Apple's iOS operating system. Cost data were provided in only 50 studies, but most technologies for which this information was available cost less than 20 USD. Only 24 innovations targeted the ten NCDs responsible for the greatest number of disability-adjusted life years lost globally. Most publications evaluated products created in high-income countries. Reported mHealth technologies are well-developed, but their implementation in LMICs faces operating system incompatibility and a relative neglect of NCDs causing the greatest disease burden.

Surgical biomicroscopy-guided intra-operative optical coherence tomography (iOCT) image super-resolution.

PURPOSE: Intra-retinal delivery of novel sight-restoring therapies will require the precision of robotic systems accompanied by excellent visualisation of retinal layers. Intra-operative Optical Coherence Tomography (iOCT) provides cross-sectional retinal images in real time but at the cost of image quality that is insufficient for intra-retinal therapy delivery.This paper proposes a super-resolution methodology that improves iOCT image quality leveraging spatiotemporal consistency of incoming iOCT video streams. METHODS: To overcome the absence of ground truth high-resolution (HR) images, we first generate HR iOCT images by fusing spatially aligned iOCT video frames. Then, we automatically assess the quality of the HR images on key retinal layers using a deep semantic segmentation model. Finally, we use image-to-image translation models (Pix2Pix and CycleGAN) to enhance the quality of LR images via quality transfer from the estimated HR domain. RESULTS: Our proposed methodology generates iOCT images of improved quality according to both full-reference and no-reference metrics. A qualitative study with expert clinicians also confirms the improvement in the delineation of pertinent layers and in the reduction of artefacts. Furthermore, our approach outperforms conventional denoising filters and the learning-based state-of-the-art. CONCLUSIONS: The results indicate that the learning-based methods using the estimated, through our pipeline, HR domain can be used to enhance the iOCT image quality. Therefore, the proposed method can computationally augment the capabilities of iOCT imaging helping this modality support the vitreoretinal surgical interventions of the future.

Organotin Schiff bases as halofluorochromic dyes: green synthesis, chemio-photophysical characterization, DFT, and their fluorescent bioimaging in vitro.

Fluorescent bioimaging is an excellent tool in cellular biology, and it will be a powerful technique in modern medicine as a noninvasive imaging technology where tumoral and normal cells must be distinguished. One of the differences between normal and cancer cells is the intracellular pH. Therefore, the design and synthesis of pH-responsive fluorescent materials are required. Organotin Schiff bases showed halofluorochromic behavior in solution. Microwave-assisted synthesis showed better reaction times and chemical yields compared with conventional heating. All compounds were fully characterized by spectroscopic and spectrometric techniques. The halofluorochromism study showed that some molecules in acidic media have the maximum luminescence intensity due to protonation. All the fluorescent tin complexes showed cell staining on hepatocyte and MCF-7 cells by confocal microscopy. The theoretical study has enabled us to rationalize the optical properties and the halofluorochromism for compounds 1 and 2 synthesized in this work. Our results showed that the emission decrease, in the acid and basic media for compounds 1 and 2, respectively, is caused by intramolecular charge transfer (ICT) deactivation.

Learned optical flow for intra-operative tracking of the retinal fundus.

PURPOSE: Sustained delivery of regenerative retinal therapies by robotic systems requires intra-operative tracking of the retinal fundus. We propose a supervised deep convolutional neural network to densely predict semantic segmentation and optical flow of the retina as mutually supportive tasks, implicitly inpainting retinal flow information missing due to occlusion by surgical tools. METHODS: As manual annotation of optical flow is infeasible, we propose a flexible algorithm for generation of large synthetic training datasets on the basis of given intra-operative retinal images. We evaluate optical flow estimation by tracking a grid and sparsely annotated ground truth points on a benchmark of challenging real intra-operative clips obtained from an extensive internally acquired dataset encompassing representative vitreoretinal surgical cases. RESULTS: The U-Net-based network trained on the synthetic dataset is shown to generalise well to the benchmark of real surgical videos. When used to track retinal points of interest, our flow estimation outperforms variational baseline methods on clips containing tool motions which occlude the points of interest, as is routinely observed in intra-operatively recorded surgery videos. CONCLUSIONS: The results indicate that complex synthetic training datasets can be used to specifically guide optical flow estimation. Our proposed algorithm therefore lays the foundation for a robust system which can assist with intra-operative tracking of moving surgical targets even when occluded.

Deep iterative vessel segmentation in OCT angiography.

This paper addresses retinal vessel segmentation on optical coherence tomography angiography (OCT-A) images of the human retina. Our approach is motivated by the need for high precision image-guided delivery of regenerative therapies in vitreo-retinal surgery. OCT-A visualizes macular vasculature, the main landmark of the surgically targeted area, at a level of detail and spatial extent unattainable by other imaging modalities. Thus, automatic extraction of detailed vessel maps can ultimately inform surgical planning. We address the task of delineation of the Superficial Vascular Plexus in 2D Maximum Intensity Projections (MIP) of OCT-A using convolutional neural networks that iteratively refine the quality of the produced vessel segmentations. We demonstrate that the proposed approach compares favourably to alternative network baselines and graph-based methodologies through extensive experimental analysis, using data collected from 50 subjects, including both individuals that underwent surgery for structural macular abnormalities and healthy subjects. Additionally, we demonstrate generalization to 3D segmentation and narrower field-of-view OCT-A. In the future, the extracted vessel maps will be leveraged for surgical planning and semi-automated intraoperative navigation in vitreo-retinal surgery.

Boron Schiff bases derived from α-amino acids as nucleoli/cytoplasm cell-staining fluorescent probes in vitro.

The size, shape, and number of nucleoli in a cell's nucleus might help to distinguish a malignant from a benign tumor. Cellular biology and histopathology often require better visualization to understand nucleoli-related processes, thus organelle-specific fluorescent markers are needed. Here, we report the design, synthesis, and fully chemo-photophysical characterization of fluorescent boron Schiff bases (BOSCHIBAs), derived from α-amino acids (i.e., phenylalanine, tyrosine and tryptophan), with nucleoli- and cytoplasm-specific staining in cells. It is the first time that Boron Schiff bases derived from α-amino acids act as notorious dual (nucleoli and cytoplasm) cell-staining fluorescent probes. The boron derivatives not only showed good photostability and acceptable quantum yields (∼5%) in solution, but also exhibited low cytotoxicity (>90% cell viability at 0.1 and 1 µg mL-1), which make them good candidates to be used in medical diagnosis.

Quantum chemical elucidation of the turn-on luminescence mechanism in two new Schiff bases as selective chemosensors of Zn2+: synthesis, theory and bioimaging applications.

We report the synthesis and characterization of two new selective zinc sensors (S,E)-11-amino-8-((2,4-di-tert-butyl-1-hydroxybenzylidene) amino)-11-oxopentanoic acid (A) and (S,E)-11-amino-8-((8-hydroxybenzylidene)amino)-11-oxopentanoic acid (B) based on a Schiff base and an amino acid. The fluorescent probes, after binding to Zn2+ ions, presented an enhancement in fluorescent emission intensity up to 30 times (ϕ = A 50.10 and B 18.14%). The estimated LOD for compounds A and B was 1.17 and 1.20 µM respectively (mixture of acetonitrile : water 1 : 1). Theoretical research has enabled us to rationalize the behaviours of the two selective sensors to Zn2+ synthesized in this work. Our results showed that in the free sensors, PET and ESIPT are responsible for the quenching of the luminescence and that the turn-on of luminescence upon coordination to Zn2+ is mainly induced by the elimination of the PET, which is deeply analysed through EDA, NOCV, molecular structures, excited states and electronic transitions via TD-DFT computations. Confocal fluorescence microscopy experiments demonstrate that compound A could be used as a fluorescent probe for Zn2+ in living cells.

Correction: Quantum chemical elucidation of the turn-on luminescence mechanism in two new Schiff bases as selective chemosensors of Zn2+: synthesis, theory and bioimaging applications.

[This corrects the article DOI: 10.1039/C9RA05010H.].

Involvement of endothelial Man and Gal-binding lectins in sensing the flow in coronary arteries.

The coronary endothelial luminal membrane (CELM) glycocalyx has diverse molecules involved in blood flow signal transduction. Evidence suggests that some of these structures may be lectinic. To test this, we synthesized two monosaccharide polymers (Mon-Pols) made of Mannose (Man-Pol) or Galactose (Gal-Pol) covalently coupled to Dextran (70 kDa) and used them as lectin affinity probes. In situ intracoronary infusion of both polymers resulted in CELM-binding but only Man-Pol caused a reduction in flow-induced positive inotropism and dromotropism. To demonstrate that our lectinic probes could bind to CELM lectins, a representative CELM protein fraction was isolated via intracoronary infusion of a cationic silica colloid and either Mannose- or Galactose-binding lectins were purified from the CELM protein fraction using the corresponding Mon-Pol affinity chromatography resin. Resin-bound CELM proteins were eluted with the corresponding monosaccharide. 2D-SDS-PAGE (pH 4-7) revealed 9 Mannose- and approximately 100 Galactose-selective CELM lectins. In summary, the CELM glycocalyx contains Mannose- and Galactose-binding lectins that may be involved in translating coronary flow into a cardiac parenchymal response.

Implementing Systems Medicine: A Medical Informatics Perspective.

Systems medicine is a paradigm for translating in silico methods developed for modelling biological systems into the field of medicine. Such approaches rely on the integration of as many data sources as possible, both in the dimension of disease knowledge and patient data. This is a challenging task that can only be implemented in clinical routine with the help of suitable information technology from the field of Medical Informatics. For the research project "Clinically-applicable, omics-based assessment of survival, side effects, and targets in multiple myeloma" (CLIOMMICS) we developed a prototypical systems medicine application system. It is based on a three-level-architecture covering data representation, decision support, and user interface. The core decision support component is implemented as a case-based reasoning engine. However, the architecture follows a modular design that allows to replace individual components as needed.

Recent Advances in Synthesis and Properties of Hybrid Halide Perovskites for Photovoltaics.

The progress made by the scientific community in emerging photovoltaic technologies over the past two decades has been outstanding. Numerous methods have been developed for the preparation of hybrid organic-inorganic perovskite solar cells. The power conversion efficiency has been up to 14% by a one-step vacuum deposition technique. A serious concern is the toxicity of the materials. In this review, several methods aimed at resolving these problems to some extent have been compiled, including eco-friendly synthesis. Further efficiency enhancements are expected following optimization, and a better fundamental understanding of the internal electron charge transfer, electron-hole diffusion to the corresponding layers, flexibility, and stability-dependent bandgaps is reported. This paper explores the green synthesis of organic-inorganic perovskites for industrialization. Concerning the above facts, a simple low-cost model called "dispersed photovoltaic cells" is presented.

From Bench to Bedside: A View on Bioinformatics Pipelines.

Although sequencing technology has become widely available in recent years, the steps in bioinformatics pipelines are time-consuming and barely standardized. New tools to improve individual steps in a pipeline are frequently published and configurations can be quickly adapted to use new versions. We performed case studies with a representative set of pipeline management tools using the GEP-R pipeline, and a qualitative study of different software packages covering relevant classes of software tools. We use a software toolset of R environment, Docker, KNIME, and BPEL to review our first aim of technical and organizational challenges. We propose snapshotting, documentation management, and a hybrid approach for our second aim of approaches to reproducibility. In order to have fully reproducible results derived from raw data, we think that it is necessary to archive biomedical analysis pipelines and their necessary software components.

Thinner abuse alters peak of frequency of EEG spectra analyses.

STUDY OBJECTIVE: The aim of the investigation was to use electroencephalography (EEG) to study whether long-term thinner abuse may result in the slowing, disorganization and asymmetry of the EEG cortical rhythms. METHOD: Twenty-two patients attending with antecedent of thinner abuse only, and twenty two controls without alcohol, smoking, and drug abuse in the same age range and gender were studied. EEG recording were compared by means of the analyses of peak of frequency (POF), frequency of disorganization, and asymmetry of the background activity in patients and controls at rest eyes-closed condition in electrodes P3, P4, O1, and O2. RESULTS: Significant differences in POF among groups was observed in P3 and P4 location showing lower values in thinner abusers, but not in O1 and O2 locations. Frequencies of disorganization and asymmetry showed significantly higher proportions in thinner abusers. Bivariate correlations among POF at the four electrode location and time of thinner abuse showed significant values. However after partial correlation calculation correcting for age, significant values disappeared. CONCLUSION: Thus thinner abuse relates with slowing of POF in the EEG of patients with thinner abuse associated with disorganization, and asymmetry depending on time of abuse.

Biosynthesis of glycoproteins in the pathogenic fungus Candida albicans: activation of dolichol phosphate mannose synthase by cAMP-mediated protein phosphorylation.

Following incubation with ATP and a cAMP-dependent protein kinase under optimal conditions of lipid acceptor, phospholipid and metal ion requirements, the transfer activity of partially purified dolichol phosphate mannose synthase (DPMS) increased about 60% and this activation correlated with a 50% increase in V(max) with no alteration in the apparent K(m) for GDP-Manose. Phosphorylation with [gamma-(32)P]ATP resulted in the labeling of several polypeptides, one of which exhibited the molecular weight of the enzyme (30 kDa) and was also recognized using a specific anti-DPMS monoclonal antibody. This and the fact that the phosphate label could be removed by an alkaline phosphatase indicate that Candida DPMS may be regulated by phosphorylation-dephosphorylation, a mechanism that has been proposed for the enzyme in other organisms.