bluuebunny/crossref_metadata_2025_split huggingface dataset:
Experience with instrumental methods in radiopharmacy as a tool of radiation protection optimization
Authors: Budinsky Michal , Kozakova Sarka 
Published: October 2019

Abstract

Background:
The purpose of our study is to evaluate the effect of instrumental methods in radiopharmacy on radiation exposure of the staff preparing radiopharmaceuticals.

Methods:
Instrumental methods in radiopharmacy are used since 2004 as a tool of radiation protection optimization for the pharmacists after positron-emission tomography (PET) introduction to the department of nuclear medicine of Masaryk Memorial Cancer Institute (MMCI) in 2003. During 14 years of providing PET radiopharmaceuticals, different equipment and processes were used—DDS-A, μDDS-A and KARl100 (all Tema Sinergie). The increase in a number of instrumental equipment—2 μDDS-A and 1 KARl100, allows preparing 3 different radiopharmaceutical for PET (either [18F]FDG, [18F]FLT, [18F]NaF, [18F]choline, [18F]Vizamyl, [18C]methionine) in 1 day. The radiation exposure to the radiopharmacists was evaluated from ring dosimeters.

Results:
The introduction of PET in 2003 led to rise of the radiation dose over legislation limits to the radiopharmacists with personal maximum of 814.4 mSv/y for hands. As a tool of optimization, instrumental preparing radiopharmaceuticals for PET using DDS-A was introduced. In 2004, rapid reduction of radiation dose was recorded to personal maximum of 106.97 mSv/y for hands. The increase of number and types of PET radiopharmaceuticals used during 1 day required upgrade of equipment used and increase in its number. In 2009, former DDS-A was replaced by 2 μDDS-A. Another tool, KARl100 was installed in 2016. This led to further significant reduction of radiation dose to personal maximum of 24.91 mSv/y for hands.

Conclusions:
Introduction of PET and the need to prepare several different types of radiopharmaceutical lead to rise of radiation exposure and received dose of radiopharmacists. Introduction of instrumental methods in radiopharmacy is a tool for radiation protection optimization. In conclusion, it is the possible to state that instrumental methods in radiopharmacy have a significant effect on radiation protection of the radiopharmacists.
Assessment of medication use process in adult oncology unit of Tikur Anbesa Specialized Hospital
Authors: Gessese Yohannes A. , Fenta Teferi G. , Weldegiorgis Mathewos A. 
Published: October 2019

Abstract

Background:
Chemotherapy errors affect several steps of medication-use process. A reduction of errors and toxicities, and an increase in error awareness, dose verification, proper documentation, and appropriateness of supportive care treatment are important. The present study was conducted to assess the medication-use process and dose-related errors in an outpatient adult oncology unit of Tikur Anbesa Specialized Hospital.

Methods:
An institutional-based cross-sectional study was conducted in an oncology outpatient adult oncology unit of Tikur Anbesa Specialized Hospital between May 1 and June 30, 2012. A total of 212 patient records for 583 chemotherapy administrations were reviewed during the study period.

Results:
The overall dose-related error rate was found to be 228 (39.1%). Specific rate of dose-related errors were (under dosing 58 (25.4%), overdosing 52 (22.8%), inaccurately reconstituted doses 106 (46.5%), and inappropriately adjusted doses 12 (5.3%). Dose labeling and documentation of appropriate time of administration for each chemotherapy preparation were not evident in the unit records. Only 3/14 dose verifications and 3 dose documentation processes were found. Supportive care treatment was not performed according to the recommended standards. Of the 23 equipment and supplies needed for chemotherapy preparation and administration, only 8 were available.

Conclusions:
The findings of our study indicate that the medication-use process in an outpatient adult oncology unit was below expected standards in 2012. The hospital and the school of pharmacy should give emphasis on the establishment of pharmacist run oncology pharmacy for chemotherapy preparation. Policies and guidelines for chemotherapy mixing and administration service and standardization of the process workflow should be developed.
Marjolin Ulcer
Authors: Chaturvedi Gaurav , Gupta Ashish Kumar , Das Saikat , Gohil Amish Jayantilal , Lamba Shashank 
Published: October 2019

Introduction
Marjolin ulcer is a rare skin malignancy. Marjolin ulcer arises in zones of long-standing scars, inflammation, or chronic wounds.

Material and methods
The present study was conducted to assess the demographic profile and identify the predictors of recurrence in 55 patients with Marjolin ulcer admitted over 10 years. Patients underwent either wide local excision with 2-cm peripheral margin or amputation if clinically indicated due to joint involvement. Lymph nodes were dissected if found positive. Patients received adjuvant radiotherapy if tumor clearance was less than 4 mm or the draining lymph nodes were positive.

Results
Of the total 55 cases (mean age, 48.75 years; range, 24–74 years), 34 were men and 21 were women (male/female, 1.6:1). The most common cause of injury was flame burn (n = 32, 58%) followed by trauma (n = 10, 18%). The lower limb was frequently affected (n = 38, 69.1%). Twenty-six patients with resection margins less than 4 mm had received adjuvant radiotherapy. Among the 55 patients, 6 (11%) had undergone lymph node dissection. Local recurrence was noted within 18 months in 9 (16.35%) patients, of which 5 patients had a tumor-free margin of less than 4 mm. We found 2 predictors for local recurrence. First, moderately differentiated squamous cell carcinoma (P = 0.04) and, second, patients with lymph node involvement (P = 0.001).

Conclusion
Marjolin ulcer is a high-risk skin tumor. Patients with positive lymph node or with moderately differentiated squamous cell carcinoma have high chances of recurrence. Frequent and intense follow-up is required for at least 2 years.
Prediction pipeline for discovery of regulatory motifs associated with Brugia malayi molting
Authors: Grote Alexandra , Li Yichao , Liu Canhui , Voronin Denis , Geber Adam , Lustigman Sara , Unnasch Thomas R. , Welch Lonnie , Ghedin Elodie 
Published: October 2019

AbstractFilarial nematodes can cause debilitating diseases in humans. They have complicated life cycles involving an insect vector and mammalian hosts, and they go through a number of developmental molts. While whole genome sequences of parasitic worms are now available, very little is known about transcription factor (TF) binding sites and their cognate transcription factors that play a role in regulating development. To address this gap, we developed a novel motif prediction pipeline, Emotif Alpha, that integrates ten different motif discovery algorithms, multiple statistical tests, and a comparative analysis of conserved elements between the filarial worms Brugia malayi and Onchocerca volvulus, and the free-living nematode Caenorhabditis elegans. We identified stage-specific TF binding motifs in B. malayi, with a particular focus on those potentially involved in the L3-L4 molt, a stage important for the establishment of infection in the mammalian host. Using an in vitro molting system, we tested and validated three of these motifs demonstrating the accuracy of the motif prediction pipeline.
Natural IgE promotes epithelial hyperplasia and inflammation-driven tumour growth
Authors: Hayes Mark David , Ward Sophie , Crawford Greg , Seoane Rocio Castro , Jackson William David , Kipling David , Voehringer David , Dunn-Walters Deborah , Strid Jessica 
Published: October 2019

AbstractIgE is the least abundant circulating antibody class but is constitutively present in healthy tissues bound to resident cells via its high-affinity receptor, FcεRI. The physiological role of endogenous IgE is unclear but it is suggested to provide host protection against a variety of noxious environmental substances and parasitic infections at epithelial barrier surfaces. Here we show that skin inflammation enhances levels of IgE with natural specificities and with a similar repertoire, VDJ rearrangements and CDRH3 characteristics as in healthy tissue. IgE-bearing basophils are recruited to inflamed skin via CXCL12 and TSLP/IL-3-dependent upregulation of CXCR4. In the inflamed skin, IgE/FcεRI-signalling in basophils promotes epithelial cell growth and differentiation, partly through histamine engagement of H1R and H4R. Furthermore, this natural IgE response strongly drives tumour outgrowth of epithelial cells harbouring oncogenic mutation. These findings indicate that natural IgE support skin barrier defences however during chronic tissue inflammation this may be subverted to promote tumour growth.
ISG15/USP18/STAT2 is a molecular hub regulating autocrine IFN I-mediated control of Dengue and Zika virus replication
Authors: Espada Constanza Eleonora , da Rocha Edroaldo Lummertz , Ricciardi-Jorge Taissa , dos Santos Adara Aurea , Soares Zamira Guerra , Malaquias Greicy , Patrício Daniel Oliveira , Kozlova Edgar Gonzalez , dos Santos Paula Fernandes , Bordignon Juliano , Sanford Thomas J. , Fajardo Teodoro , Sweeney Trevor R. , Báfica André , Mansur Daniel Santos 
Published: October 2019

SUMMARYThe establishment of a virus infection is the result of the pathogen’s ability to replicate in a hostile environment generated by the host’s immune system. Here, we found that ISG15 restricts Dengue and Zika viruses’ replication through the stabilisation of its binding partner USP18. ISG15 expression was necessary to control DV replication driven by both autocrine and paracrine type one interferon (IFN-I) signalling. Moreover, USP18 competes with NS5-mediated STAT2 degradation, a major mechanism for establishment of flavivirus infection. Strikingly, reconstitution of USP18 in ISG15-deficient cells was sufficient to restore the STAT2’s stability and restrict virus growth, suggesting that the IFNAR-mediated ISG15 activity is also antiviral. Our results add a novel layer of complexity in the virus/host interaction interface and suggest that NS5 has a narrow window of opportunity to degrade STAT2, therefore suppressing host’s IFN-I mediated response and promoting virus replication.IMPORTANCEDisease is an emergent property that results from a microorganism’s ability to replicate in a given host and the latter’s immune response. Here we describe how the immunoregulatory function of ISG15 (an interferon stimulated gene) affects Dengue and Zika virus replication by occupying a niche used by the virus non-structural protein 5 (NS5) to evade host’s immunity. In the absence of ISG15, NS5 efficiently degrades a main signalling hub of innate immunity (STAT2), leading to cell immune suppression and consequently virus growth. This sheds light into how flaviviruses intimately interact with the host immune system and could lead to a host-based therapy target.
Transcriptomic changes due to early, chronic alcohol exposure during cortical development implicate regionalization, cell-type specification, synaptogenesis and WNT signaling as primary determinants of fetal alcohol Spectrum Disorders
Authors: Fischer Máté , Chander Praveen , Kang Huining , Weick Jason P. 
Published: October 2019

AbstractFetal alcohol spectrum disorders (FASD) are described by a cluster of deficits following in utero alcohol exposure, whose effects disproportionately target the cerebral cortex. In vitro and in vivo models of FASD have successfully recapitulated multiple facets of clinical presentations, including morphological and behavioral deficits, but far less is understood regarding the molecular and genetic bases of FASD. In this study, we utilize an in vitro human pluripotent stem cell-based (hPSC) model of corticogenesis to probe the effect of early, chronic alcohol exposure on the transcriptome of developing cortical neurons. We here identify a relatively limited number of significantly altered biological pathways, including regional patterning, cell-type specification, axon guidance and synaptic function. Significant upregulation of WNT signaling-related transcripts, to the exclusion of other secreted morphogens was also observed in alcohol exposed cultures. Lastly, an overall alcohol-associated shift towards an increased caudal profile, at the expense of rostral molecular identity was observed, representing a potentially previously underappreciated FASD phenotype.
Scaffold-free human mesenchymal stem cell construct geometry regulates long bone regeneration
Authors: Herberg Samuel , Varghai Daniel , Alt Daniel S. , Dang Phuong N. , Park Honghyun , Cheng Yuxuan , Shin Jung-Youn , Dikina Anna D. , Boerckel Joel D. , Rolle Marsha W. , Alsberg Eben 
Published: October 2019

AbstractScaffold-based bone tissue engineering approaches frequently induce repair processes dissimilar to normal developmental programs. In contrast, biomimetic strategies aim to recapitulate aspects of development through cellular self-organization, morphogenetic pathway activation, and mechanical cues. This may improve regenerative outcome in large long bone defects that cannot heal on their own; however, no study to date has investigated the role of scaffold-free construct geometry, in this case tubes mimicking long bone diaphyses, on bone regeneration. We hypothesized that microparticle-mediated in situ presentation of transforming growth factor-β1 (TGF-β1) and bone morphogenetic protein-2 (BMP-2) to engineered human mesenchymal stem cell (hMSC) tubes induces the endochondral cascade, and that TGF-β1 + BMP-2-presenting hMSC tubes facilitate enhanced endochondral healing of critical-sized femoral segmental defects under delayed in vivo mechanical loading conditions compared to loosely-packed hMSC sheets. Here, localized morphogen presentation imparted early chondrogenic lineage priming, and stimulated robust endochondral differentiation of hMSC tubes in vitro. In an ectopic environment, hMSC tubes formed a cartilage template that was actively remodeled into trabecular bone through endochondral ossification without lengthy predifferentiation. Similarly, hMSC tubes stimulated in vivo cartilage and bone formation and more robust healing in femoral defects compared to hMSC sheets. New bone was formed through endochondral ossification in both groups; however, only hMSC tubes induced regenerate tissue partially resembling normal growth plate architecture. Together, this study demonstrates the interaction between mesenchymal cell condensation geometry, bioavailability of multiple morphogens, and defined in vivo mechanical environment to recapitulate developmental programs for biomimetic bone tissue engineering.Significance StatementEngineered bone constructs must be capable of withstanding and adapting to harsh conditions in a defect site upon implantation, and can be designed to facilitate repair processes that resemble normal developmental programs. Self-assembled tubular human mesenchymal stem cell constructs were engineered to resemble the geometry of long bone diaphyses. By mimicking the cellular, biochemical, and mechanical environment of the endochondral ossification process during embryonic development, successful healing of large femoral segmental defects upon implantation was achieved and the extent was construct geometry dependent. Importantly, results were obtained without a supporting scaffold or lengthy predifferentiation of the tubular constructs. This indicates that adult stem/progenitor cells retain features of embryonic mesenchyme, and supports the concept of developmental engineering for bone regeneration approaches.
Multimodal Neuroimaging-based Prediction of Adult Outcomes in Childhood-onset ADHD using Ensemble Learning Techniques
Authors: Luo Yuyang , Alvarez Tara L. , Halperin Jeffrey M. , Li Xiaobo 
Published: October 2019

ABSTRACTAttention deficit/hyperactivity disorder (ADHD) is a highly prevalent and heterogeneous neurodevelopmental disorder, currently relaying on subjective symptom observations for diagnosis. Machine learning classifiers have been utilized to assist the development of neuroimaging-based biomarkers for objective diagnosis of ADHD. However, the existing basic model-based studies in ADHD reported suboptimal classification performances and inconclusive results, mainly due to the limited flexibility for each type of basic classifiers to appropriately handle multi-dimensional source features with various properties. In this study, we proposed to apply ensemble learning techniques (ELTs) in multimodal neuroimaging data collected from 72 young adults, including 36 probands (18 remitters and 18 persisters of childhood ADHD) and 36 group-matched controls. All the currently available optimization strategies for ELTs (i.e., voting, bagging, boosting and stacking techniques) were tested in a pool of semi-final classification results generated by seven basic classifiers. The high-dimensional neuroimaging features for classification included regional cortical gray matter (GM) thickness and surface area, GM volume of subcortical structures, volume and fractional anisotropy of major white matter fiber tracts, pair-wise regional connectivity and global/nodal topological properties of the functional brain network for cue-evoked attention process. As a result, the bagging-based ELT with the base model of support vector machine achieved the best results, with the most significant improvement of the area under the receiver of operating characteristic curve (0.89 for ADHD vs. controls, and 0.9 for ADHD persisters vs. remitters). We found that features of nodal efficiency in right inferior frontal gyrus, right middle frontal (MFG)-inferior parietal (IPL) functional connectivity, and right amygdala volume significantly contributed to accurate discrimination between ADHD probands and controls; higher nodal efficiency of right MFG greatly contributed to inattentive and hyperactive/impulsive symptom remission, while higher right MFG-IPL functional connectivity strongly linked to symptom persistence in adults with childhood ADHD. Our study also suggested that considering their solidly improved robustness than the commonly implemented basic classifiers, ELTs may have the potential to identify more reliable neurobiological markers for severe brain disorders.
Records of RNA localization through covalent tagging
Authors: Medina-Muñoz Hugo C. , Lapointe Christopher P. , Porter Douglas F. , Wickens Marvin 
Published: October 2019

ABSTRACTRNA movements and localization pervade biology, from embryonic development to disease. To identify RNAs at specific subcellular locations, we anchored a uridine-adding enzyme at those sites, which then marked RNAs in its vicinity with 3’ terminal uridines. RNAs were tagged independent of their translation status, and included not only mRNAs, but also ncRNAs and ncRNA processing intermediates. A battery of RNAs, including the stress sensor,IRE1, were tagged at both ER and mitochondria, and reveal RNAs whose dual localization is conserved from yeast to human cells.
Eye movements as a readout of sensorimotor decision processes
Authors: Fooken Jolande , Spering Miriam 
Published: October 2019

AbstractReal-world tasks, such as avoiding obstacles, require a sequence of interdependent decisions to reach accurate motor outcomes. Yet, most studies on primate decision making involve simple one-step choices. Here we investigate how sensorimotor decisions develop over time. In a go/no-go interception task human observers (n=42) judged whether a briefly-presented moving target would pass (interception required) or miss (no hand movement required) a strike box while their eye and hand movements were recorded. Go/no-go decision formation had to occur within the first few hundred milliseconds to allow time-critical interception. We found that the earliest time point at which eye movements started to differentiate decision outcome (go vs. no-go) coincided with hand movement onset. Moreover, eye movements were related to different stages of decision making. Whereas higher eye velocity during smooth pursuit initiation (prior to “whether” decision) was related to higher go/no-go decision accuracy, faster pursuit maintenance was associated with accurate interception timing (“when” decision). These results indicate that pursuit initiation and maintenance are continuously linked to ongoing sensorimotor decision formation.
The majority of histone acetylation is a consequence of transcription
Authors: Martin Benjamin J.E. , Brind’Amour Julie , Jensen Kristoffer N. , Kuzmin Anastasia , Liu Zhen Cheng , Lorincz Matthew , Howe LeAnn J. 
Published: October 2019

AbstractHistone acetylation is a ubiquitous hallmark of transcriptional activity, but whether the link is of a causal or consequential nature is still a matter of debate. In this study we resolve this question. Using both immunoblot analysis and chromatin immunoprecipitation-sequencing (ChIP-seq) in S. cerevisiae, we show that the majority of histone acetylation is dependent on transcription. Loss of histone H4 acetylation upon transcription inhibition is partially explained by depletion of histone acetyltransferases (HATs) from gene bodies, implicating transcription in HAT targeting. Despite this, HAT occupancy alone poorly predicts histone acetylation, suggesting that HAT activity is regulated at a step post-recruitment. Collectively, these data show that the majority of histone acetylation is a consequence of RNAPII promoting both the recruitment and activity of histone acetyltransferases.
Linking Engineered Cells to Their Digital Twins: a Version Control System for Strain Engineering
Authors: Tellechea-Luzardo Jonathan , Widera Paweł , de Lorenzo Victor , Krasnogor Natalio 
Published: October 2019

1.AbstractAs DNA sequencing and synthesis become cheaper and more easily accessible, the scale and complexity of biological engineering projects is set to grow. Yet, although there is an accelerating convergence between biotechnology and computing science, a deficit in software and laboratory techniques diminishes the ability to make biotechnology more agile, reproducible and transparent while, at the same time, limiting the security and safety of synthetic biology constructs. To partially address some of these problems, this paper presents an approach for physically linking engineered cells to their digital footprint - we called it digital twinning. This enables the tracking of the entire engineering history of a cell line in a specialised version control system for collaborative strain engineering.
Inhibition of the Ventral Hippocampus Increases Alcohol Drinking
Authors: Griffin William C. , Rinker Jennifer A. , Woodward John J. , Mulholland Patrick J. , Becker Howard C. 
Published: October 2019

AbstractThe function of the ventral hippocampus (vHC) supports many behaviors, including those related to reward seeking behaviors and drug addiction. We used a mouse model of alcohol dependence and relapse to investigate the role of the vHC in alcohol (ethanol) drinking. One experiment used a chemogenetic approach to inhibit vHC function while ethanol dependent and non-dependent mice had access to ethanol. Interestingly, the non-dependent mice expressing an inhibitory DREADD in the VHC showed a significant increase in ethanol drinking (∼30%) after hM4Di DREADD activation with clozapine-n-oxide (CNO; 3 mg/kg, ip.) compared to vehicle. On the other hand, ethanol dependent mice, which were already drinking significantly more ethanol than non-dependent mice, only had a slight, non-significant increase in drinking after CNO challenge. In a separate group of dependent and non-dependent mice, GCaMP6f calcium-dependent activity was recorded in the vHC while mice were actively drinking ethanol. These data showed that once mice were rendered ethanol dependent and were drinking more ethanol than the non-dependent mice, calcium signaling in the ventral hippocampus decreased (∼45%) in the ethanol dependent mice compared to the non-dependent mice. Together, these findings suggest that ethanol dependence reduces activity of the ventral hippocampus and that reduced function of this brain region contributes to increased ethanol drinking.