PMechDB: A Public Database of Elementary Polar Reaction Steps.

Most online chemical reaction databases are not publicly accessible or are fully downloadable. These databases tend to contain reactions in noncanonicalized formats and often lack comprehensive information regarding reaction pathways, intermediates, and byproducts. Within the few publicly available databases, reactions are typically stored in the form of unbalanced, overall transformations with minimal interpretability of the underlying chemistry. These limitations present significant obstacles to data-driven applications including the development of machine learning models. As an effort to overcome these challenges, we introduce PMechDB, a publicly accessible platform designed to curate, aggregate, and share polar chemical reaction data in the form of elementary reaction steps. Our initial version of PMechDB consists of over 100,000 such steps. In the PMechDB, all reactions are stored as canonicalized and balanced elementary steps, featuring accurate atom mapping and arrow-pushing mechanisms. As an online interactive database, PMechDB provides multiple interfaces that enable users to search, download, and upload chemical reactions. We anticipate that the public availability of PMechDB and its standardized data representation will prove beneficial for chemoinformatics research and education and the development of data-driven, interpretable models for predicting reactions and pathways. PMechDB platform is accessible online at https://deeprxn.ics.uci.edu/pmechdb.

Accurate Host-Guest Binding Free Energies Using the AMOEBA Polarizable Force Field.

A grand challenge of computational biophysics is accurate prediction of interactions between molecules. Molecular dynamics (MD) simulations have recently gained much interest as a tool to directly compute rigorous intermolecular binding affinities. The choice of a fixed point-charge or polarizable multipole force field used in MD is a topic of ongoing discussion. To compare alternative methods, we participated in the SAMPL7 and SAMPL8 Gibb octaacid host-guest challenges to assess the Atomic Multipole Optimized Energetics for Biomolecular Applications (AMOEBA) polarizable multipole force field. Advantages of AMOEBA over fixed charge models include improved representation of molecular electrostatic potentials and better description of water occupying the unligated host cavity. Prospective predictions for 26 host-guest systems exhibit a mean unsigned error vs experiment of 0.848 kcal/mol across all absolute binding free energies, demonstrating excellent agreement between computational and experimental results. In addition, we explore two topics related to the inclusion of ions in MD simulations: use of a neutral co-alchemical protocol and the effect of salt concentration on binding affinity. Use of the co-alchemical method minimally affects computed energies, but salt concentration significantly perturbs our binding results. Higher salt concentration strengthens binding through classical charge screening. In particular, added Na+ ions screen negatively charged carboxylate groups near the binding cavity, thereby diminishing repulsive coulomb interactions with negatively charged guests. Overall, the AMOEBA results demonstrate the accuracy available through a force field providing a detailed energetic description of the four octaacid hosts and 13 charged organic guests. Use of the AMOEBA polarizable atomic multipole force field in conjunction with an alchemical free energy protocol can achieve chemical accuracy in application to realistic molecular systems.

Using telemedicine to facilitate social distancing in otolaryngology: A systematic review.

OBJECTIVES: As the coronavirus 2019 pandemic puts strains on current models of otolaryngology practice, telemedicine is an attractive way for otolaryngologists to reduce in-person appointments while still addressing the health of their patients. This systematic review of the literature aims to identify the evidence basis for using telemedicine in otolaryngology practice to limit person-to-person interactions while achieving comparable quality to in-person services. METHODS: The authors gathered articles from three databases (Embase, PubMed and Web of Science), performed a comprehensive literature review of articles published on telemedicine since 2002, and selected articles for inclusion based on their relevance to otolaryngology and the potential of the intervention to improve patient social distancing. RESULTS: A total of 7153 articles were identified from the initial query. After review, 35 met the inclusion criteria. Of the included articles, 32 (91%), found their specific telemedicine intervention to be effective when compared to in-person services. Twenty articles (57%) were related to remote otoscopy. Other telemedical interventions included videoconferencing for peri-operative visits, diagnosis of peritonsillar abscess, telephone-based voice evaluations and evaluation of nasal fractures. CONCLUSIONS: Video-otoscopy is the most well-supported telemedical intervention which limits physical contact between otolaryngologists and their patients. Other interventions have also demonstrated efficacy but have yet to be as widely validated as video-otoscopy. Telehealth facilitators play a key role in providing high-quality telehealth services. More invasive procedures, such as laryngoscopy, require further evidence to demonstrate definite benefits in a telemedicine setting.

Combining electrospun nanofibers with cell-encapsulating hydrogel fibers for neural tissue engineering.

A promising component of biomaterial constructs for neural tissue engineering are electrospun fibers, which differentiate stem cells and neurons as well as direct neurite growth. However, means of protecting neurons, glia, and stem cells seeded on electrospun fibers between lab and surgical suite have yet to be developed. Here we report an effort to accomplish this using cell-encapsulating hydrogel fibers made by interfacial polyelectrolyte complexation (IPC). IPC-hydrogel fibers were created by interfacing acid-soluble chitosan (AsC) and cell-containing alginate and spinning them on bundles of aligned electrospun fibers. Primary spinal astrocytes, cortical neurons, or L929 fibroblasts were mixed into alginate hydrogels prior to IPC-fiber spinning. The viability of each cell type was assessed at 30 min, 4 h, 1 d, and 7 d after encapsulation in IPC hydrogels. Some neurons were encapsulated in IPC-hydrogel fibers made from water-soluble chitosan (WsC). Neurons were also stained with Tuj1 and assessed for neurite extension. Neuron survival in AsC-fibers was worse than astrocytes in AsC-fibers (p < 0.05) and neurons in WsC-fibers (p < 0.05). As expected, neuron and glia survival was worse than L929 fibroblasts (p < 0.05). Neurons in IPC-hydrogel fibers fabricated with WsC extended neurites robustly, while none in AsC fibers did. Neurons remaining inside IPC-hydrogel fibers extended neurites inside them, while others de-encapsulated, extending neurites on electrospun fibers, which did not fully integrate with IPC-hydrogel fibers. This study demonstrates that primary neurons and astrocytes can be encapsulated in IPC-hydrogel fibers at good percentages of survival. IPC hydrogel technology may be a useful tool for encapsulating neural and other cells on electrospun fiber scaffolds.

Nanofibrous scaffolds for the guidance of stem cell-derived neurons for auditory nerve regeneration.

Impairment of spiral ganglion neurons (SGNs) of the auditory nerve is a major cause for hearing loss occurring independently or in addition to sensory hair cell damage. Unfortunately, mammalian SGNs lack the potential for autonomous regeneration. Stem cell based therapy is a promising approach for auditory nerve regeneration, but proper integration of exogenous cells into the auditory circuit remains a fundamental challenge. Here, we present novel nanofibrous scaffolds designed to guide the integration of human stem cell-derived neurons in the internal auditory meatus (IAM), the foramen allowing passage of the spiral ganglion to the auditory brainstem. Human embryonic stem cells (hESC) were differentiated into neural precursor cells (NPCs) and seeded onto aligned nanofiber mats. The NPCs terminally differentiated into glutamatergic neurons with high efficiency, and neurite projections aligned with nanofibers in vitro. Scaffolds were assembled by seeding GFP-labeled NPCs on nanofibers integrated in a polymer sheath. Biocompatibility and functionality of the NPC-seeded scaffolds were evaluated in vivo in deafened guinea pigs (Cavia porcellus). To this end, we established an ouabain-based deafening procedure that depleted an average 72% of SGNs from apex to base of the cochleae and caused profound hearing loss. Further, we developed a surgical procedure to implant seeded scaffolds directly into the guinea pig IAM. No evidence of an inflammatory response was observed, but post-surgery tissue repair appeared to be facilitated by infiltrating Schwann cells. While NPC survival was found to be poor, both subjects implanted with NPC-seeded and cell-free control scaffolds showed partial recovery of electrically-evoked auditory brainstem thresholds. Thus, while future studies must address cell survival, nanofibrous scaffolds pose a promising strategy for auditory nerve regeneration.

"Heart Bone"--The Case for the IHI Open School as Connector: A Model for Integrating Quality Improvement and Patient Safety into Health Professions Curricula.

BACKGROUND: The physician is guardian of the patient and obligated to both the "Science of Medicine" (SOM), defined by the randomized controlled trial, and the "Art of Medicine" (AOM), defined by patient safety (PS) and quality improvement (QI). Historically SOM knowledge has dominated AOM knowledge; however given the frequency of medical harm, a new paradigm is necessary. The Institute for Healthcare Improvement Open School (IHIOS) is accelerating AOM into medical curricula by connecting all stakeholders to the emerging PS and QI sciences, and doing so in an interprofessional manner. METHODS: A South Dakota IHIOS chapter was established in 2011, connecting SOM to AOM knowledge for 600 students from eight schools and thirteen disciplines. Four specific foci included 1) interprofessional pilot project introducing PS and QI into first year curricula, 2) sessions for third-year medical students to assess Open School courses through faculty-facilitated small groups, 3) development of longitudinal quality and safety curricula, 4) integration of OS courses across South Dakota health professions schools. RESULTS: The interprofessional pilot project demonstrated significant learning in 16 of 16 and 13 of 16 (p = 0.05) teaching points. The third-year sessions showed that PS and QI topics are viewed as important especially with faculty-facilitated case studies. Subsequently a longitudinal PS and QI curriculum was implemented. This led to the incorporation of IHIOS courses as core curricula in four South Dakota colleges and eight health disciplines. CONCLUSIONS: Our work was one of the first large-scale efforts to measure learning via the IHIOS through the novel use of the chapter as connector. The model contributes to national efforts for paradigm change through interprofessional education.

FLOWERING BHLH transcriptional activators control expression of the photoperiodic flowering regulator CONSTANS in Arabidopsis.

Many plants monitor day-length changes throughout the year and use the information to precisely regulate the timing of seasonal flowering for maximum reproductive success. In Arabidopsis thaliana, transcriptional regulation of the CONSTANS (CO) gene and posttranslational regulation of CO protein are crucial mechanisms for proper day-length measurement in photoperiodic flowering. Currently, the CYCLING DOF FACTOR proteins are the only transcription factors known to directly regulate CO gene expression, and the mechanisms that directly activate CO transcription have remained unknown. Here we report the identification of four CO transcriptional activators, named FLOWERING BHLH 1 (FBH1), FBH2, FBH3, and FBH4. All FBH proteins are related basic helix-loop-helix-type transcription factors that preferentially bind to the E-box cis-elements in the CO promoter. Overexpression of all FBH genes drastically elevated CO levels and caused early flowering regardless of photoperiod, whereas CO levels were reduced in the fbh quadruple mutants. In addition, FBH1 is expressed in the vascular tissue and bound near the transcription start site of the CO promoter in vivo. Furthermore, FBH homologs in poplar and rice induced CO expression in Arabidopsis. These results indicate that FBH proteins positively regulate CO transcription for photoperiodic flowering and that this mechanism may be conserved in diverse plant species. Our results suggest that the diurnal CO expression pattern is generated by a concert of redundant functions of positive and negative transcriptional regulators.

Internet marketing 101.

In an era when social media sites like YouTube, Facebook, and Twitter dominate the popular press, many surgeons overlook the foundational tactics and strategies necessary for long-term practice development and lead generation on the Internet. This article analyzes common errors made by surgeons during the development and implementation of Web site projects, focusing on the areas of strategy development; domain name identification; site plan creation; design considerations; content development; vendor selection; and launch, promotion, and staff training. The article emphasizes that, because the Web site remains the foundation of a surgeon's branding message, minimizing errors during development and construction is critical, particularly in highly competitive or saturated markets, for today's facial plastic surgery practice.

Internet marketing 401.

For facial plastic surgeons who are already realizing increased patient consultation requests from their online marketing efforts, the primary concern often becomes implementing additional tactics and strategies that can keep their online marketing fresh, relevant, and effective. This article creates a framework for evaluating advanced online marketing opportunities by analyzing each opportunity according to the variables of possible return, average cost to implement, probability of success, and implementation time. Within this framework, 11 distinct tactics are discussed, with special emphasis on the most common marketing needs and challenges of facial plastic surgery practices.