bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of in silico designed inhibitors targeting MelF (Rv1936) against Mycobacterium marinum within macrophages
Authors: Dharra Renu , Radhakrishnan V. S. , Prasad Tulika , Thakur Zoozeal , Cirillo Jeffrey D. , Sheoran Abhishek , Pandey Amit K. , Kulharia Mahesh , Mehta Promod K. 
Published: July 2019

AbstractWe recently identified inhibitors targeting Mycobacterium marinum MelF (Rv1936) by in silico analysis, which exhibited bacteriostatic/bactericidal activity against M. marinum and M. tuberculosis in vitro. Herein, we evaluated the effect of best four inhibitors (# 5175552, # 6513745, # 5255829, # 9125618) obtained from the ChemBridge compound libraries, on intracellular replication and persistence of bacteria within IFN-γ activated murine RAW264.7 and human THP-1 macrophages infected with M. marinum. Inhibitors # 5175552 and # 6513745 significantly reduced (p < 0.05) the intracellular replication of bacilli during day 7 post-infection (p.i.) within RAW264.7 and THP-1 macrophages infected at multiplicity of infection (MOI) of ~1.0. These observations were substantiated by electron microscopy, which revealed the protective effect of # 5175552 in clearing the bacilli inside murine macrophages. Strikingly, # 6513745 displayed synergism with isoniazid against M. marinum in murine macrophages, whereas # 5175552 significantly suppressed (p < 0.05) the persistent bacilli during day 10–14 p.i. in infected RAW264.7 and THP-1 macrophages (MOI of ~ 0.1). Moreover, # 5175552 and # 6513745 were non-cytotoxic to host macrophages at both 1X and 5X MIC. Further validation of these inhibitors against M. tuberculosis-infected macrophages and animal models has potential for development as novel anti-tubercular agents.
Generating kinetic environments to study dynamic cellular processes in single cells
Authors: Thiemicke Alexander , Jashnsaz Hossein , Li Guoliang , Neuert Gregor 
Published: July 2019

AbstractCells of any organism are consistently exposed to changes over time in their environment. The kinetics by which these changes occur are critical for the cellular response and fate decision. It is therefore important to control the temporal changes of extracellular stimuli precisely to understand biological mechanisms in a quantitative manner. Most current cell culture and biochemical studies focus on instant changes in the environment and therefore neglect the importance of kinetic environments. To address these shortcomings, we developed two experimental methodologies to precisely control the environment of single cells. These methodologies are compatible with standard biochemistry, molecular, cell and quantitative biology assays. We demonstrate applicability by obtaining time series and time point measurements in both live and fixed cells. We demonstrate the feasibility of the methodology in yeast and mammalian cell culture in combination with widely used assays such as flow cytometry, time-lapse microscopy and single-molecule RNA Fluorescentin-situHybridization (smFISH). Our experimental methodologies are easy to implement in most laboratory settings and allows the study of kinetic environments in a wide range of assays and different cell culture conditions.
The association between childbirth, breastfeeding, and uterine fibroids: an observational study
Authors: Delli Carpini Giovanni , Morini Stefano , Papiccio Maria , Serri Matteo , Damiani Valentina , Grelloni Camilla , Clemente Nicolò , Ciavattini Andrea 
Published: July 2019

AbstractThe aim of this study was to investigate the effect of childbirth and breastfeeding on uterine fibroids and to identify the factors associated with size variations. This was a monocenter observational study carried on women with a sonographic diagnosis of uterine fibroids from January 2007 to December 2016, with no indication for immediate treatment, and who became pregnant within one year from diagnosis. All patients were re-evaluated six months after delivery. Fibroid diameters were compared between pre-pregnancy period, first, second, third trimester and post-delivery. The rate of “regressed” (growth of diameter <−40%), “unchanged” (growth of diameter between −40% and +40%) or “increased” (growth of diameter >+40%) fibroids at the post-delivery evaluation with respect to the pre-pregnancy state was calculated. One-hundred fifty-seven women were included in the final analysis. At the post-delivery ultrasound, a significant reduction of the fibroid diameter with respect to all previous examinations was observed, and there was no evidence of 67 (37.2%) fibroids. Ongoing breastfeeding was positively associated with an “unchanged” or “regressed” fibroid diameter (adOR 3.23, 95%CI: 1.35–7.70, p < 0.01). Smaller pre-gravidic fibroids were more likely to return to pre-pregnancy dimensions or to regress, with a cut-off of 32 mm for lactating women and of 26 mm for non-lactating women. In conclusion, fibroids seem to return to pre-pregnancy dimensions or to regress in the post-partum period. This process may be sustained by uterine involution and hormonal variations, with an additional role of breastfeeding.
Circulating CXCR3+ Tfh cells positively correlate with neutralizing antibody responses in HCV-infected patients
Authors: Zhang Jian , Liu Wenpei , Wen Bo , Xie Ting , Tang Ping , Hu Yabin , Huang Liyan , Jin Kun , Zhang Ping , Liu Ziyan , Niu Ling , Qu Xiaowang 
Published: July 2019

AbstractCirculating T follicular helper (cTfh) cells have been identified as counterparts of germinal center Tfh (GC Tfh) cells in humans and can support T-dependent B cell maturation and antibody production in vitro. However, the role of cTfh cells in neutralizing antibody (nAb) responses in HCV infection remains unclear. Here, we characterized the phenotype and function of cTfh cells and demonstrated the associations of cTfh cells and their subsets with nAb responses in HCV infection. A total of 38 HCV-infected individuals and 28 healthy controls were enrolled from a pool of injection drug users. The frequency and function of blood Tfh cells were analyzed by flow cytometry. The titers and breadths of serum nAbs were measured using HCV pseudo-particle neutralization assays. Herein, we report several key observations. First, HCV infection skewed cTfh toward CXCR3+ cTfh cell differentiation. Second, the frequency of CXCR3+ cTfh cells positively correlated with HCV nAb titers and breadths. Third, CXCR3+ cTfh cells showed higher expression of Tfh-associated molecules (PD-1, ICOS, IL-21, Bcl-6) compared with CXCR3− cTfh cells from individuals with HCV infection. Coculture of cTfh cells and autologous memory B cells in vitro indicated that CXCR3+ cTfh cells show a superior ability to support HCV E2-specific B cell expansion compared with CXCR3− cTfh cells from individuals with HCV infection. HCV infection skews cTfh cells toward CXCR3-biased Tfh cell differentiation, which positively correlates with the magnitude and breadth of the HCV nAb response. It is our hope that these findings will provide insights for the rational design of a nAb-based HCV vaccine.
Intra-articularly injected mesenchymal stem cells promote cartilage regeneration, but do not permanently engraft in distant organs
Authors: Satué María , Schüler Christiane , Ginner Nikole , Erben Reinhold G. 
Published: July 2019

AbstractIntra-articular (IA) injection of mesenchymal stem cells (MSCs) promotes articular cartilage repair. However, cell fate and action after transplantation remain unclear. This study aimed at evaluating the biodistribution and efficacy of MSCs after IA injection. We used an immunocompetent, dual transgenic rat model, which is based on donor rats ubiquitously expressing heat stable human placental alkaline phosphatase (ALPP), and recipient rats expressing a heat sensitive ALPP form. A focal cartilage defect was created in the patellofemoral groove of recipient rats. Bone marrow-derived MSCs isolated from donor rats were injected into the synovial cavity of recipients, and cell tracking was performed in distant organs and knees over 6 months post-injection. A few donor MSCs were observed in the lung of one of the recipients, 1 day post-injection. We failed to detect donor MSCs in any of the studied tissues at all later time points. IA-injected MSCs remained in the synovial cavity, engrafted within the cartilage lesion, and were detectable up to 1 month post-injection. Although the number of MSCs decreased over time, MSCs injection promoted cartilage regeneration as evidenced by histology and immunofluorescent collagen staining. Our study supports the safety and efficacy of using MSCs for cartilage repair via IA delivery.
In vivo two-photon microscopy of the human eye
Authors: Ávila Francisco J. , Gambín Adrián , Artal Pablo , Bueno Juan M. 
Published: July 2019

AbstractTwo-photon (2P) microscopy is a powerful tool for imaging and exploring label-free biological tissues at high resolution. Although this type of microscopy has been demonstrated in ex vivo ocular tissues of both humans and animal models, imaging the human eye in vivo has always been challenging. This work presents a novel compact 2P microscope for non-contact imaging of the anterior part of the living human eye. The performance of the instrument was tested and the maximum permissible exposure to protect ocular tissues established. To the best of our knowledge, 2P images of the in vivo human cornea, the sclera and the trabecular meshwork are shown for the very first time. Acquired images are of enough quality to visualize collagen arrangement and morphological features of clinical interest. Future implementations of this technique may constitute a potential tool for early diagnosis of ocular diseases at submicron scale.
Imaging axon regeneration within synthetic nerve conduits
Authors: Fogli Barbara , Corthout Nikky , Kerstens Axelle , Bosse Frank , Klimaschewski Lars , Munck Sebastian , Schweigreiter Rüdiger 
Published: July 2019

AbstractWhile axons within the central nervous system (CNS) do not regenerate following injury, those in the peripheral nervous system (PNS) do, although not in a clinically satisfactory manner as only a small proportion of axons exhibit long-distance regeneration. Moreover, functional recovery is hampered by excessive axonal sprouting and aberrant reinnervation of target tissue. In order to investigate the mechanisms governing the regrowth of axons following injury, previous studies have used lesion paradigms of peripheral nerves in rat or mouse models, and reagents or cells have been administered to the lesion site through nerve conduits, aiming to improve early-stage regeneration. Morphological analysis of such in vivo experiments has however been limited by the incompatibility of synthetic nerve conduits with existing tissue-clearing and imaging techniques. We present herein a novel experimental approach that allows high-resolution imaging of individual axons within nerve conduits, together with quantitative assessment of fiber growth. We used a GFP-expressing mouse strain in a lesion model of the sciatic nerve to describe a strategy that combines nerve clearing, chemical treatment of chitosan nerve conduits, and long working distance confocal microscopy with image processing and analysis. This novel experimental setup provides a means of documenting axon growth within the actual conduit during the critical initial stage of regeneration. This will greatly facilitate the development and evaluation of treatment regimens to improve axonal regeneration following nerve damage.
Removal of radioactive cesium from an aqueous solution via bioaccumulation by microalgae and magnetic separation
Authors: Kim Ilgook , Yang Hee-Man , Park Chan Woo , Yoon In-Ho , Seo Bum-Kyoung , Kim Eun-Kyung , Ryu Byung-Gon 
Published: July 2019

AbstractWe evaluated the potential sequestration of cesium (Cs+) by microalgae under heterotrophic growth conditions in an attempt to ultimately develop a system for treatment of radioactive wastewater. Thus, we examined the effects of initial Cs+ concentration (100–500 μM), pH (5–9), K+ and Na+ concentrations (0–20 mg/L), and different organic carbon sources (acetate, glycerol, glucose) on Cs+ removal. Our initial comparison of nine microalgae indicated that Desmodesmus armatus SCK had removed the most Cs+ under various environmental conditions. Addition of organic substrates significantly enhanced Cs+ uptake by D. armatus, even in the presence of a competitive cation (K+). We also applied magnetic nanoparticles coated with a cationic polymer (polyethylenimine) to separate 137Cs-containing microalgal biomass under a magnetic field. Our technique of combining bioaccumulation and magnetic separation successfully removed more than 90% of the radioactive 137Cs from an aqueous medium. These results clearly demonstrate that the method described here is a promising bioremediation technique for treatment of radioactive liquid waste.
Increased LIGHT leading to sFlt-1 elevation underlies the pathogenic link between hydatidiform mole and preeclampsia
Authors: Iriyama Takayuki , Wang Guan , Yoshikawa Midori , Mimura Nobuko , Matsui Haruka , Sayama Seisuke , Kumasawa Keiichi , Nagamatsu Takeshi , Koga Kaori , Kotani Tomomi , Niimi Kaoru , Yamamoto Eiko , Kellems Rodney E. , Xia Yang , Osuga Yutaka , Fujii Tomoyuki 
Published: July 2019

AbstractHydatidiform moles are known to pose an extremely high risk of severe early-onset preeclampsia if left untreated. TNF superfamily cytokine, LIGHT has recently been reported to contribute to pathophysiology of preeclampsia. The present study aimed to investigate the involvement of LIGHT in hydatidiform moles. We measured the serum levels of LIGHT and sFlt-1 by ELISA in 17 women with complete hydatidiform mole (HM) and 20 gestational-age-matched normal pregnant women (control). As a result, the serum LIGHT levels were significantly higher in HM as compared with those in control (69.9 ± 9.6 pg/ml vs 25.4 ± 5.3 pg/ml, p = 0.0001) and the serum levels of LIGHT were significantly positively correlated with those of sFlt-1 in HM (r = 0.68, p = 0.0029). Immunohistochemical analysis revealed that the expression levels of LIGHT were increased in HM placentas as compared with controls, and LIGHT and sFlt-1 were co-localized in the trophoblast cells of HM. In vitro studies using primary syncytiotrophoblast cells demonstrated that LIGHT directly induced sFlt-1 expression in trophoblast cells. Our results indicated that elevated LIGHT in the trophoblast cells of hydatidiform mole induces sFlt-1, which might underlie the pathogenic mechanism of early-onset preeclampsia developing secondary to molar pregnancies.
Starting to Talk at Age 10 Years: Lessons About the Acquisition of English Speech Sounds in a Rare Case of Severe Congenital But Remediated Motor Disease of Genetic Origin
Authors: Peter Beate , Vose Caitlin , Bruce Laurel , Ingram David 
Published: July 2019

Purpose
This study was conducted to observe speech development in a child whose onset of oral communication was extremely delayed. In rare cases, children are born with physical limitations that temporarily interfere with speech sound production. Whether the development of speech sound production follows the same trajectory as that in typical children at younger ages is not well understood.

Method
We present a child who was wheelchair-bound and communicated nearly exclusively via augmentative and alternative communication devices due to severe congenital motor disease and generalized hypotonia. At age 10 years, her condition improved dramatically with medication after a mutation in a dopamine-related gene was discovered, and she switched entirely to oral communication. Observation of speech development was based on chart reviews, video recordings, and direct testing at age 15 years.

Results
At age 4 years, the participant's attempts at speech showed a small phoneme inventory consisting of early-acquired phonemes and large numbers of common phonological processes. Following the medical intervention at age 10 years, mastery of velars occurred after age 12 years and mastery of liquids was still incomplete at age 15 years.

Conclusions
Findings are consistent with general growth trends in speech sound acquisition that are independent of chronological age. Theoretical considerations regarding the role of motor control in the invariant order of speech sound acquisition are posited, specifically regarding articulatory building blocks. Clinical recommendations include interprofessional management of children with complex motor disease and referrals to genetics professionals in the care of such children.
Visual Analog Scale Ratings and Orthographic Transcription Measures of Sentence Intelligibility in Parkinson's Disease With Variable Listener Exposure
Authors: Abur Defne , Enos Nicole M. , Stepp Cara E. 
Published: July 2019

Purpose
While orthographic transcription (OT) is the gold standard for measures of intelligibility, it is relatively inaccessible to clinicians. This study investigates the relationship between visual analog scale (VAS) ratings and OT measures of intelligibility for speakers with Parkinson's disease (PD), with the eventual goal of developing more clinically feasible assessments of intelligibility.

Method
Twenty speakers with PD and 5 controls read 11 sentences. First, 33 listeners completed an OT task using 1 sentence from each speaker. An additional 33 listeners rated the intelligibility of 1 sentence from each speaker using a VAS, reflecting a minimized exposure VAS (MEV) task. Lastly, 14 additional listeners each rated the intelligibility of all 11 sentences produced by all speakers using a VAS, reflecting an extended exposure VAS (EEV) task. Smaller listener groups were simulated from each VAS task for comparison to scores from the OT task.

Results

There was a strong relationship between OT and both MEV and EEV. This relationship remained strong (
R
2
≥ .82) even when only 1 listener in MEV and 2 listeners in EEV were simulated per sentence.

Conclusions
VAS ratings may be a suitable alternative to OT measures of sentence intelligibility for PD using listeners with both minimal and extended exposure to the stimuli.
The Feasibility, Utility, and Safety of Communication Interventions With Mechanically Ventilated Intensive Care Unit Patients: A Systematic Review
Authors: Zaga Charissa J. , Berney Sue , Vogel Adam P. 
Published: July 2019

Purpose
The aim of this study was to conduct a systematic review of the literature relating to the feasibility, utility, and safety of augmentative and alternative communication (AAC) interventions and tracheostomy-related communication interventions with mechanically ventilated adult patients in the intensive care unit (ICU).

Method
MEDLINE, Embase, and PsycINFO databases were searched for relevant articles. Studies were included if (a) they were performed in the ICU, (b) they involved participants > 18 years of age, (c) > 85% of participants were mechanically ventilated, and (d) they reported on content that related to the feasibility and/or utility and/or safety of AAC intervention and/or tracheostomy-related communication intervention. Studies were extracted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The levels of evidence for included studies were assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) guidelines.

Results

Forty-eight studies met the inclusion criteria. Different communication interventions relating to intubated and tracheostomized mechanically ventilated patients were reviewed, including (a) communication boards, (b) electrolarynx, (c) high-technology AAC devices, (d) tracheostomy tubes with communication-enabling features, (e) one-way valve in line with the ventilator, (f) ventilator-adjusted leak speech, (g) ventilator adjustments and one-way valve, and (h) multiple interventions. Forty-seven of 48 studies examined the feasibility and utility of the interventions. Sixteen studies examined the safety of the interventions. The included studies were composed of randomized controlled trials (
n
= 2), quasi-experimental studies (
n
= 7), cohort studies (
n
= 8), case–control (
n
= 1), case series (
n
= 23), and case reports (
n
= 7). The levels of evidence varied and ranged from high (
n
= 2), moderate (
n
= 7), low (
n
= 9), and very low (
n
= 30).

Conclusions
There is developing evidence that communication interventions with mechanically ventilated ICU patients are feasible, have utility, and are safe. Further research is warranted to guide speech pathologist–directed intervention to improve patient outcomes and the patient experience in the ICU.
Stellar atmospheric parameters for 754 spectra from the X-shooter Spectral Library
Authors: Arentsen Anke , Prugniel Philippe , Gonneau Anais , Lançon Ariane , Trager Scott , Peletier Reynier , Lyubenova Mariya , Chen Yan-Ping , Falcón Barroso Jesús , Sánchez Blázquez Patricia , Vazdekis Alejandro 
Published: July 2019

Context. The X-shooter Spectral Library (XSL) is an empirical stellar library at medium spectral resolution covering the wavelength range from 3000 Å to 24 800 Å. This library aims to provide a benchmark for stellar population studies.
Aims. In this work, we present a uniform set of stellar atmospheric parameters, effective temperatures, surface gravities, and iron abundances for 754 spectra of 616 XSL stars.
Methods. We used the full-spectrum fitting package ULySS with the empirical MILES library as reference to fit the ultraviolet-blue (UVB) and visible (VIS) spectra. We tested the internal consistency and we compared our results with compilations from the literature.
Results. The stars cover a range of effective temperature 2900 <  Teff <  38 000 K, surface gravity 0 <  logg <  5.7, and iron abundance −2.5 <  [Fe/H] <  +1.0, with a couple of stars extending down to [Fe/H] = −3.9. The precisions of the measurements for the G- and K-type stars are 0.9%, 0.14, and 0.06 in Teff, logg, and [Fe/H], respectively. For the cool giants with logg <  1, the precisions are 2.1%, 0.21, and 0.22, and for the other cool stars these values are 1%, 0.14, and 0.10. For the hotter stars (Teff >  6500 K), these values are 2.6%, 0.20, and 0.10 for the three parameters.