bluuebunny/crossref_metadata_2025_split huggingface dataset:
Progress towards improving homing and engraftment of hematopoietic stem cells for clinical transplantation
Authors: Huang Xinxin , Broxmeyer Hal E. 
Published: May 2019

Purpose of review
Hematopoietic cell transplantation (HCT) is a life-saving treatment for a variety of hematological and nonhematological disorders. Successful clinical outcomes after transplantation rely on adequate hematopoietic stem cell (HSC) numbers, and the homing and subsequent short-term and long-term engraftment of these cells in the bone marrow. Enhancing the homing capability of HSCs has the potential for high impact on improving HCT and patient survival.

Recent findings
There are a number of ways to enhance HSC engraftment. Neutralizing negative epigenetic regulation by histone deacetylase 5 (HDAC5) increases surface CXCR4 expression and promotes human HSC homing and engraftment in immune-deficient NSG (NOD.Cg-Prkdcscid IL2rgtm1Wjl/Sz) mice. Short-term treatment of cells with glucocorticoids, pharmacological stabilization of hypoxia-inducible factor (HIF)-1α, increasing membrane lipid raft aggregation, and inhibition of dipeptidyl peptidase 4 (DPP4) facilitates HSC homing and engraftment. Added to these procedures, modulating the mitochondria permeability transition pore (MPTP) to mitigate ambient air-induced extra physiological oxygen stress/shock (EPHOSS) by hypoxic harvest and processing, or using cyclosporine A during air collection increases functional HSC numbers and improves HSC engraftment.

Summary
A better understanding of the regulation of human HSC homing mediated by various signaling pathways will facilitate development of more efficient means to enhance HCT efficacy.
Case Report: Retinal Toxicity Secondary to Ritonavir
Authors: Louie Alyssa K. , Jones Heather N. 
Published: May 2019

SIGNIFICANCE
Because patients with HIV have increased life expectancies with the advent of new drug therapies, complications from iatrogenic syndromes such as drug toxicity can occur. Ritonavir-induced retinal toxicity is one such complication but has rarely been reported in the literature.

PURPOSE
This case report describes a patient with bilateral maculopathy and bone spicule–like pigmentary changes in the midperipheral retina due to ritonavir use. In addition, novel optical coherence tomography findings are described.

CASE REPORT
A 53-year-old man presented with gradual-onset blurry vision and difficulty seeing at night. He had been diagnosed as having HIV infection 19 years prior and had previously taken ritonavir for 7 years as part of highly active antiretroviral therapy. Best-corrected acuities were 20/30 in the right eye and 20/25 in the left eye. Clinical examination revealed a subtle annular pattern of retinal pigment epithelium mottling around the fovea and bone spicule–like pigment changes in the midperiphery of both retinas. Optical coherence tomography imaging revealed abnormal subfoveal hyperreflectivity of the ellipsoid zone with relative attenuation centrally, annular parafoveal ellipsoid zone loss, and punctate hyperreflectivity within the ellipsoid zone more eccentrically. Fundus autofluorescence in both eyes showed annular hyperautofluorescence in the parafoveal region, geographic hyperautofluorescence in the areas underlying the midperipheral pigmentary changes, and discrete patches of hyperautofluorescence along the far inferotemporal arcades in areas that appeared normal with biomicroscopy. A diagnosis of retinal toxicity secondary to ritonavir use was made based on the patient's history and clinical examination.

CONCLUSIONS
Ritonavir retinal toxicity seems to be an uncommon adverse event that can cause decreased visual function. This case report provides further evidence of the retinal toxicity and reviews the reported clinical and optical coherence tomography manifestations of the disease.
Case Report: Varicella-zoster Encephalitis with Acute Retinal Necrosis and Oculomotor Nerve Palsy
Authors: Quan Steven Charles , Skondra Dimitra 
Published: May 2019

SIGNIFICANCE
Varicella-zoster virus is a common cause of morbidity and vision loss in patients worldwide. It can affect any structure of the eye, from keratitis to acute retinal necrosis. Rapid diagnosis and treatment significantly improve clinical outcomes and quality of life.

PURPOSE
The purpose of this study was to demonstrate a case where urgent referral to the emergency department was required to treat a patient with disseminated herpes zoster infection.

CASE REPORT
This is a rare case of varicella-zoster virus encephalitis in a 70-year-old immunocompetent white man who initially presented to the eye clinic for vertical diplopia and floaters. He also had prior thoracic dermatomal rash, followed by new-onset headaches and cerebellar ataxia. Examination revealed a partial oculomotor nerve palsy in the right eye with bilateral optic disc edema and areas of retinitis consistent with acute retinal necrosis in both eyes. Polymerase chain reaction analysis of his aqueous humor and cerebrospinal fluid confirmed an active zoster infection. He received combination systemic and intravitreal antiviral medication until his retinitis resolved but required adjustments for recalcitrant disease and drug-induced nephrotoxicity. While on maintenance dosing of oral valacyclovir, he experienced reactivation in the form of bilateral vasculitis, which was successfully managed once restarting therapeutic oral dosing.

CONCLUSIONS
This case describes a successful clinical course of acute retinal necrosis with strategies for its treatment in the setting of varicella-zoster encephalitis. Antiviral medication should be given as soon as possible, as prompt treatment has been shown to improve patient outcomes, although prognosis is typically poor in these cases. Multiple specialists are often needed to address different clinical challenges, including central nervous system involvement, viral strain resistance, disease reactivation, and drug toxicity.
Glaucoma Patient Preferences for Video Education on Eye Drop Technique
Authors: Davis Scott A. , Carpenter Delesha M. , Blalock Susan J. , Budenz Donald L. , Lee Charles , Muir Kelly W. , Robin Alan L. , Sleath Betsy 
Published: May 2019

SIGNIFICANCE
Glaucoma patients express a strong need for practical instruction on instilling eye drops correctly. To maximize the benefit of a video intervention to improve eye drop technique, patients recommend that video education be provided both in the clinic setting and online.

PURPOSE
The purposes of this study were to (1) describe glaucoma patients' perspectives on how to improve an online eye drop technique video and how to disseminate it to other glaucoma patients and (2) examine how these perspectives differ across demographics.

METHODS
Glaucoma patients (N = 43) who viewed an online eye drop technique educational video as part of a randomized controlled trial were interviewed to assess their overall rating of the video on a 4-point scale, with whom they had watched the video, whether they would recommend the video to others, how the video helped them, how they would recommend improving the video, and how they would like the video to be disseminated to other glaucoma patients.

RESULTS
Patients' mean (SD) rating of the video was 3.4 (0.8), with a higher mean rating of 3.8 among African Americans (P = .02). All 43 patients said that they would recommend that others watch the video. Patients most commonly said that the video helped them learn to block the tear duct correctly, put the cap down on its side, mix the medication correctly, and close the eye after instillation. Patients preferred viewing the video in the doctor's office examination room and a website.

CONCLUSIONS
Eye drop technique videos should be disseminated in the doctor's office and online. Health systems that integrate educational videos into their everyday practice may be able to use technique videos to improve patient technique at low cost and little time burden to the provider.
Silicone Implant Illness: Science versus Myth?
Authors: Rohrich Rod J. , Kaplan Jordan , Dayan Erez 
Published: May 2019

Summary:
The purpose of this Special Topic article is to present the current state of scientific evidence related to the safety of silicone breast implants. There is presently overwhelming evidence to support the safety of silicone breast implants. Ultimately, the decision to obtain, keep, or remove breast implants is the choice of the patient. If a patient chooses to have her breast implants removed, it is important to find a board-certified plastic surgeon with expertise in breast surgery. Ongoing studies are strongly encouraged in all areas, from cancer detection to autoimmune disease, as we strive for improved patient safety, patient awareness, and patient education. To the best of our body of scientific knowledge to date, there have not been any concrete or evidence-based studies or peer-reviewed data concerning the formation of a new syndrome: “silicone implant illness.” Silicone breast implants are used in nearly 300,000 breast augmentation and 100,000 breast reconstruction operations annually in the United States.
1
Silicone gel–filled implants were first approved by the U.S. Food and Drug Administration in 1962. Since that time, few medical devices have been studied as closely for their safety and associated adverse outcomes. Despite multiple generations of implant shells and gel fillers, the basic components remain as originally designed.
2,3
Novel engraftment and T cell differentiation of human hematopoietic cells inArt-/-IL2RG-/SCID pigs
Authors: Boettcher Adeline N , Li Yunsheng , Ahrens Amanda P. , Kiupel Matti , Byrne Kristen A. , Loving Crystal L. , Cino-Ozuna A. Giselle , Wiarda Jayne E. , Adur Malavika , Schultz Blythe , Swanson Jack J. , Snella Elizabeth M. , Ho Chak-Sum (Sam) , Charley Sara E. , Kiefer Zoe E. , Cunnick Joan E. , Powell Ellis J. , Dell’Anna Giuseppe , Jens Jackie , Sathe Swanand , Goldman Frederick , Westin Erik R. , Dekkers Jack C. M. , Ross Jason W. , Tuggle Christopher K. 
Published: May 2019

AbstractPigs with severe combined immunodeficiency (SCID) are an emerging biomedical animal model. Swine are anatomically and physiologically more similar to humans than mice, making them an invaluable tool for preclinical regenerative medicine and cancer research. One essential step in further developing this model is the immunological humanization of SCID pigs. In this work we have generated T-B-NK-SCID pigs through site directed CRISPR/Cas9 mutagenesis ofIL2RGwithin a naturally occurringDCLRE1C(Artemis)-/-genetic background. We confirmedArt-/-IL2RG-/Ypigs lacked T, B, and NK cells in both peripheral blood and lymphoid tissues. Additionally, we and successfully performed a bone marrow transplant on oneArt-/-IL2RG-/Ymale SCID pig with a bone marrow from a complete swine leukocyte antigen (SLA) matched donor without conditioning to reconstitute porcine T and NK cells. Next, we performedin uteroinjections of cultured human CD34+selected cord blood cells into the fetalArt-/-IL2RG-/YSCID pigs. At birth, human CD45+CD3ε+cells were detected in peripheral blood ofin uteroinjected SCID piglets. Human leukocytes were also detected within the bone marrow, spleen, liver, thymus, and mesenteric lymph nodes of these animals. Taken together, we describe critical steps forwards the development of an immunologically humanized SCID pig model.One sentence summaryWe have generated a T-B-NK-SCID pig model through site directed mutagenesis ofIL2RGin a naturally occurringArtemisnull background and show successful engraftment of human T and B cells in blood and lymphoid organs afterin uteroinjection of human hematopoietic stem cells.
Mapping interactions of microbial metabolites and human receptors
Authors: Colosimo Dominic A. , Kohn Jeffrey A. , Luo Peter M. , Han Sun M. , Pickard Amanda J. , Rao Arka , Cross Justin R. , Cohen Louis J. , Brady Sean F. 
Published: May 2019

AbstractDespite evidence linking the human microbiome to health and disease, the mechanistic details of how the microbiota affects human physiology remain largely unknown. Metabolites encoded by bacteria are expected to play an integral role in the microbiota’s effect on its human host. Assigning function to these metabolites is therefore critical to determining the molecular underpinnings of the host-microbe relationship and ultimately developing microbiota inspired therapies. Here we use large-scale functional screening of small molecules produced by individual members of a simplified human microbiota to identify bacterial metabolites that agonize G-protein coupled receptors (GPCR). This analysis revealed a complex network of metabolite host receptor interactions and guided our identification of multiple microbiota derived agonists of GPCRs associated with diverse biological functions within the nervous and immune systems, among others. Collectively, the metabolite-receptor pairs we uncovered indicate that diverse aspects of human health are potentially modulated by structurally simple metabolites arising from primary bacterial metabolism.Statement of SignificanceBacteria residing within the human body have been shown to influence human health. It is likely that physiological responses to the human microbiota are mediated by the collection of small molecules encoded within these bacteria. In this study we use direct functional screening of small molecules produced by individual members of a simplified human microbiota to identify new G protein coupled receptor-metabolite interactions that seek to explain the molecular underpinnings of the microbiota’s influence on its human host.
Dividing subpopulation of Escherichia coli in stationary phase
Authors: Jõers Arvi , Liske Eliis , Tenson Tanel 
Published: May 2019

AbstractThe bacterial growth cycle contains different phases: after the growth substrate is exhausted of the toxic waste products accumulate the growth stops. In this non-growing culture the number of colony forming bacteria remains constant or starts to decrease. It has been shown that during prolonged incubation there is constant growth and death of bacteria and certain mutant populations take over the culture. Here we show that the dynamic cell division and death balance can be obtained even before mutants take over the culture.
Novel Pure αVβ3 Integrin Antagonists That Do Not Induce Receptor Extension, Prime the Receptor, or Enhance Angiogenesis at Low Concentrations
Authors: Li Jihong , Fukase Yoshiyuki , Shang Yi , Zou Wei , Muñoz-Félix José M. , Buitrago Lorena , Buitrago Lorena , van Agthoven Johannes , Zhang Yixiao , Hara Ryoma , Tanaka Yuta , Okamoto Rei , Yasui Takeshi , Nakahata Takashi , Imaeda Toshihiro , Aso Kazuyoshi , Zhou Yuchen , Locuson Charles , Nesic Dragana , Duggan Mark , Takagi Junichi , Vaughan Roger D. , Walz Thomas , Hodivala-Dilke Kairbaan , Teitelbaum Steven L. , Amin Arnaout M. , Filizola Marta , Foley Michael A. , Coller Barry S. 
Published: May 2019

AbstractThe integrin αVβ3 receptor has been implicated in several important diseases, but no αVβ3 antagonists are approved for human therapy. One possible limitation of current small-molecule antagonists is their ability to induce a major conformational change in the receptor that induces it to adopt a high-affinity ligand-binding state. In response, we used structural inferences from a pure peptide antagonist to design the small-molecule pure antagonists TDI-4161 and TDI-3761. Both compounds inhibit αVβ3-mediated cell adhesion to αVβ3 ligands, but do not induce the conformational change as judged by antibody binding, electron microscopy, X-ray crystallography, and receptor priming studies. Both compounds demonstrated the favorable property of inhibiting bone resorptionin vitro, supporting potential value in treating osteoporosis. Neither, however, had the unfavorable property of the αVβ3 antagonist cilengitide of paradoxically enhancing aortic sprout angiogenesis at concentrations below its IC50, which correlates with cilengitide’s enhancement of tumor growthin vivo.Significance StatementαVβ3 is a potential therapeutic target for several important human diseases, but there are currently no αVβ3 antagonists approved for human therapy. Current candidates are primarily based on the Arg-Gly-Asp (RGD) motif and act as partial agonists in that they induce αVβ3 to undergo a conformational change that converts it into a high-affinity ligand-binding state. We have used structure-guided design to produce pure small-molecule αVβ3 antagonists that do not induce the conformational change as judged by protein crystallography, electron microscopy, and receptor priming. These compounds inhibit αVβ3-mediated bone resorptionin vitro, but unlike the partial agonist cilengitide, do not enhance angiogenesis at low doses, a property that correlates with low-dose cilengitide’s enhancement of tumor growthin vivo. These pure αVβ3 antagonists can help define αVβ3’s role in animal models. If they demonstrate benefits over partial agonists in these model systems, they may be appropriate to consider for human therapy.
A minimal model for microbial biodiversity can reproduce experimentally observed ecological patterns
Authors: Marsland Robert , Cui Wenping , Mehta Pankaj 
Published: May 2019

AbstractSurveys of microbial biodiversity such as the Earth Microbiome Project (EMP) and the Human Microbiome Project (HMP) have revealed robust ecological patterns across different environments. A major goal in ecology is to leverage these patterns to identify the ecological processes shaping microbial ecosystems. One promising approach is to use minimal models that can relate mechanistic assumptions at the microbe scale to community-level patterns. Here, we demonstrate the utility of this approach by showing that the Microbial Consumer Resource Model (MiCRM) – a minimal model for microbial communities with resource competition, metabolic crossfeeding and stochastic colonization – can qualitatively reproduce patterns found in survey data including compositional gradients, dissimilarity/overlap correlations, richness/harshness correlations, and nestedness of community composition. By using the MiCRM to generate synthetic data with different environmental and taxonomical structure, we show that large scale patterns in the EMP can be reproduced by considering the energetic cost of surviving in harsh environments and HMP patterns may reflect the importance of environmental filtering in shaping competition. We also show that recently discovered dissimilarity-overlap correlations in the HMP likely arise from communities that share similar environments rather than reflecting universal dynamics. We identify ecologically meaningful changes in parameters that alter or destroy each one of these patterns, suggesting new mechanistic hypotheses for further investigation. These findings highlight the promise of minimal models for microbial ecology.
Trajectory-based differential expression analysis for single-cell sequencing data
Authors: Van den Berge Koen , de Bézieux Hector Roux , Street Kelly , Saelens Wouter , Cannoodt Robrecht , Saeys Yvan , Dudoit Sandrine , Clement Lieven 
Published: May 2019

AbstractTrajectory inference has radically enhanced single-cell RNA-seq research by enabling the study of dynamic changes in gene expression levels during biological processes such as the cell cycle, cell type differentiation, and cellular activation. Downstream of trajectory inference, it is vital to discover genes that are associated with the lineages in the trajectory to illuminate the underlying biological processes. Furthermore, genes that are differentially expressed between developmental/activational lineages might be highly relevant to further unravel the system under study. Current data analysis procedures, however, typically cluster cells and assess differential expression between the clusters, which fails to exploit the continuous resolution provided by trajectory inference to its full potential. The few available non-cluster-based methods only assess broad differences in gene expression between lineages, hence failing to pinpoint the exact types of divergence. We introduce a powerful generalized additive model framework based on the negative binomial distribution that allows flexible inference of (i) within-lineage differential expression by detecting associations between gene expression and pseudotime over an entire lineage or by comparing gene expression between points/regions within the lineage and (ii) between-lineage differential expression by comparing gene expression between lineages over the entire lineages or at specific points/regions. By incorporating observation-level weights, the model additionally allows to account for zero inflation, commonly observed in single-cell RNA-seq data from full-length protocols. We evaluate the method on simulated and real datasets from droplet-based and full-length protocols, and show that the flexible inference framework is capable of yielding biological insights through a clear interpretation of the data.
Functional integration of “undead” neurons in the olfactory system
Authors: Prieto-Godino Lucia L. , Silbering Ana F. , Khallaf Mohammed A. , Cruchet Steeve , Bojkowska Karolina , Pradervand Sylvain , Hansson Bill S. , Knaden Markus , Benton Richard 
Published: May 2019

ABSTRACTProgrammed cell death (PCD) is widespread during neurodevelopment, typically eliminating the surpluses of neuronal production. Employing theDrosophilaolfactory system, we examined the potential of cells fated to die to contribute to circuit evolution. Inhibition of PCD is sufficient to generate many new cells that express neural markers and exhibit odor-evoked activity. These “undead” neurons express a subset of olfactory receptors that, intriguingly, is enriched for recent receptor duplicates and include some normally found in other chemosensory organs and life-stages. Moreover, undead neuron axons integrate into the olfactory circuitry in the brain, forming novel receptor/glomerular couplings. Comparison of homologous olfactory lineages across drosophilids reveals natural examples of fate changes from death to a functional neuron. Finally, we provide evidence that PCD contributes to evolutionary differences in carbon dioxide-sensing circuit formation inDrosophilaand mosquitoes. These results reveal the remarkable potential of alterations in PCD patterning to evolve new neural pathways.
Evidence for purifying selection on conserved noncoding elements in the genome ofDrosophila melanogaster
Authors: Tristan Berr , Aurelie Peticca , Annabelle Haudry 
Published: May 2019

AbstractIdentification of regulatory regions within genomes is a key challenge for understanding the influence of functional traits on species evolution. Development of whole-genome sequencing programs in the early 2000s has been associated with the rise of comparative genomics as a powerful tool for predicting functional regions in genomes, using structural characteristics of DNA sequences. Conserved Noncoding Elements (CNEs,i.e. untranslated sequences highly similar across divergent species) were early identified as candidate regulatory regions in metazoans, plants, and fungi. CNEs have been repeatedly discriminated from mutational cold-spots, but only few studies have assessed their functional relevance at a genome-wide scale. In the present study, we used a whole-genome alignment of 27 insect species to build a coherent mapping of CNEs in the genome ofDrosophila melanogaster. We then exploited polymorphism data from 48 European populations ofD. melanogasterto estimate levels of nucleotide diversity and adaptive evolution in CNEs. We show here that about 35% ofD. melanogasterautosomes fall into conserved noncoding regions that exhibit reduced genetic diversity and undergo purifying selection. In addition, we report six insertions of Transposable Elements (TEs) in the genome ofD. melanogastershowing high levels of conservation across Drosophila species. Half of these insertions are located in untranslated transcribed regions (UTRs) of genes involved in developmental pathways and thus represent potential relics of ancient TE domestication events.