bluuebunny/crossref_metadata_2025 huggingface dataset:
One-pot biosynthesis of CdS quantum dots through in vitro regeneration of hairy roots of Rhaphanus sativus L. And their apoptosis effect on MCF-7 and AGS cancerous human cell lines
Authors: Gholami Zahra , Dadmehr Mehdi , Babaeian Jelodar Nadali , Hosseini Morteza , oroojalian Fatemeh , Pakdin Parizi Ali
Published: January 2020

Development of green based synthesis of nanoparticles has been regarded as a novel and safe alternative method compared to conventional methods. Semiconductor cadmium sulfide quantum dots (CdS QDs) possess unique biological and medical applications includes labeling cells, diagnosing of diseases and imaging intercellular events. The present paper reports the biosynthesis of CdS QDs through aqueous extracts of the regenerated hairy roots of Rhaphanus sativus L. as the organic source for both reducing and stabilizing of Cd and S precursor ions. The characterization of synthesized QDs showed maximum absorbance peak of 460 nm and fluorescence spectrum of cadmium sulfide at 530 nm. The results of Transmission Electron Microscope (TEM) and EDS analysis demonstrated that the particles were morphologically spherical with size distribution between 2–7 nm and confirmed presence of CdS QDs. Fourier transform infrared spectroscopy (FT-IR) also showed the active presence of aromatic, amino, and carboxyl groups on the surface of quantum dots. Cytotoxicity effect of the synthesized CdS QDs on two cell lines include MCF-7 breast cancer and AGS gastric cancer were assayed through MTT assay. The results showed significant inhibitory effects of synthesized QDs on treated cells in a dose dependent manner. It was also concluded that CdS QDs had more apoptosis effect on MCF-7 cells rather than AGS cell lines. The obtained results clearly illustrated that the synthesis of CdS quantum dots with standard features would be possible through cost-effective, reliable, environmentally friendly and less toxic alternative method compared to chemical and physical processes and the MTT toxicity assay also illustrated the significant apoptotic effects of synthesized CdS QDs on carcinogenesis.
Optimization of WEDM parameters for Mg-Zn-RE-Zr alloy using Passing Vehicle Search algorithm
Authors: Sheth Mohak , Sheth Nisarg , Radadia Nishil , Parsana Sohil , Savsani Vimal , Mishra R K , Arivarasu M , Prabhu T Ram
Published: January 2020

Wire Electric Discharge Machining (WEDM) is a high precision spark machining capable of cutting electrically conductive materials of varying hardness and/or having complex shapes. Since the last decade, focus has increased on magnesium alloys because of their high specific strength and inelasticity, excellent damping properties. The addition of Rare Earth (RE) improves creep and corrosion resistant properties thus rendering them highly useful for several aerospace applications. In the present study, parametric optimization of WEDM on Mg-Zn-RE-Zr alloy is performed using a novel meta-heuristic algorithm-Passing Vehicle Search (PVS). The control parameters considered are current, pulse-on time, pulse-off time and wire feed rate. Response Surface Methodology (RSM) philosophy is implemented through Central Composite Design (CCD) to formulate the mathematical model of Average Surface Roughness (Ra). The adequacy of obtained quadratic model is established using Analysis of Variance (ANOVA). The PVS algorithm employs a population based search method by emulating the algebraic characteristics of vehicles over-taking on a two-lane highway from an initial solution set. Results of optimization through PVS are compared against standard real coded Genetic Algorithm. A remarkable improvement was observed which is critical while considering aerospace standards. This kind of analysis could be useful for production process planning in the aerospace industry.
Wavelength-stabilized DBR high-power diode laser
Authors: Paoletti R , Coriasso C , Meneghini G , Gaziano F , Gotta P , Codato S , Maina A , Morello G , De Melchiorre P , Pippione G , Riva E , Rosso M , Stano A , Gattiglio M
Published: January 2020

This paper reports a wavelength-stabilized high-power diode laser emitting up to 14 W CW in the 9xx nm range. Wavelength stabilization is achieved by a distributed Bragg reflector (DBR) monolithically integrated in the diode laser chip. Key features are identical layer epitaxy (ILE) and the use of a multiple-order electron beam lithography (EBL) optical confining grating. ILE avoids any regrowth or complex technology processes, while EBL multiple-order grating allows narrow-band back reflection and effective lateral optical confinement, and makes it possible to stabilize multiple wavelengths on the same wafer using a manufacturable and reliable technology. DBR diode lasers with different pitches, whose wavelengths were 3 nm spaced, were fabricated and high spectral purity (95% optical power within about 0.6 nm) and wavelength stability were measured. Moreover, the high uniformity of performances across the wafer with different emitted wavelengths demonstrates the maturity of the proposed technology for high-yield, high-volume laser diode production for wavelength-stabilized applications. A multi-emitter module, including ten DBR diode lasers, collimating and focusing optics, showed 100 W CW wavelength-stabilized output power at 14 A in a 135 μm core optical fiber within 0.17 NA. Single diode lasers, or multi-emitter modules, can be used to combine high-power optical beams by wavelength division multiplexing (WDM) using dichroic optics, scaling up beam power to the kW range and maintaining optical beam quality.
The domestication syndrome in vegetatively propagated field crops
Authors: Denham Tim , Barton Huw , Castillo Cristina , Crowther Alison , Dotte-Sarout Emilie , Florin S Anna , Pritchard Jenifer , Barron Aleese , Zhang Yekun , Fuller Dorian Q
Published: January 2020

Background

Vegetatively propagated crops are globally significant in terms of current agricultural production, as well as for understanding the long-term history of early agriculture and plant domestication. Today, significant field crops include sugarcane (Saccharum officinarum), potato (Solanum tuberosum), manioc (Manihot esculenta), bananas and plantains (Musa cvs), sweet potato (Ipomoea batatas), yams (Dioscorea spp.) and taro (Colocasia esculenta). In comparison with sexually reproduced crops, especially cereals and legumes, the domestication syndrome in vegetatively propagated field crops is poorly defined.

Aims and Scope

Here, a range of phenotypic traits potentially comprising a syndrome associated with early domestication of vegetatively propagated field crops is proposed, including: mode of reproduction, yield of edible portion, ease of harvesting, defensive adaptations, timing of production and plant architecture. The archaeobotanical visibility of these syndrome traits is considered with a view to the reconstruction of the geographical and historical pathways of domestication for vegetatively propagated field crops in the past.

Conclusions

Although convergent phenotypic traits are identified, none of them are ubiquitous and some are divergent. In contrast to cereals and legumes, several traits seem to represent varying degrees of plastic response to growth environment and practices of cultivation, as opposed to solely morphogenetic ‘fixation’.
A novel methodSEPromfor prokaryotic promoter prediction based on DNA structure and energetics
Authors: Mishra Akhilesh , Dhanda Sahil , Siwach Priyanka , Aggarwal Shruti , Jayaram B
Published: January 2020

Motivation

Despite conservation in general architecture of promoters and protein–DNA interaction interface of RNA polymerases among various prokaryotes, identification of promoter regions in the whole genome sequences remains a daunting challenge. The available tools for promoter prediction do not seem to address the problem satisfactorily, apparently because the biochemical nature of promoter signals is yet to be understood fully. Using 28 structural and 3 energetic parameters, we found that prokaryotic promoter regions have a unique structural and energy state, quite distinct from that of coding regions and the information for this signature state is in-built in their sequences. We developed a novel promoter prediction tool from these 31 parameters using various statistical techniques.

Results

Here, we introduce SEProm, a novel tool that is developed by studying and utilizing the in-built structural and energy information of DNA sequences, which is applicable to all prokaryotes including archaea. Compared to five most recent, diverged and current best available tools, SEProm performs much better, predicting promoters with an ‘F-value’ of 82.04 and ‘Precision’ of 81.08. The next best ‘F-value’ was obtained with PromPredict (72.14) followed by BProm (68.37). On the basis of ‘Precision’ value, the next best ‘Precision’ was observed for Pepper (75.39) followed by PromPredict (72.01). SEProm maintained the lead even when comparison was done on two test organisms (not involved in training for SEProm).

Availability and implementation

The software is freely available with easy to follow instructions (www.scfbio-iitd.res.in/software/TSS_Predict.jsp).

Supplementary information

Supplementary data are available at Bioinformatics online.
Lep-Anchor: automated construction of linkage map anchored haploid genomes
Authors: Rastas Pasi
Published: January 2020

Motivation

Linkage mapping provides a practical way to anchor de novo genome assemblies into chromosomes and to detect chimeric or otherwise erroneous contigs. Such anchoring improves with higher number of markers and individuals, as long as the mapping software can handle all the information. Recent software Lep-MAP3 can robustly construct linkage maps for millions of genotyped markers and on thousands of individuals, providing optimal maps for genome anchoring. For such large datasets, automated and robust genome anchoring tool is especially valuable and can significantly reduce intensive computational and manual work involved.

Results

Here, we present a software Lep-Anchor (LA) to anchor genome assemblies automatically using dense linkage maps. As the main novelty, it takes into account the uncertainty of the linkage map positions caused by low recombination regions, cross type or poor mapping data quality. Furthermore, it can automatically detect and cut chimeric contigs, and use contig–contig, single read or alternative genome assembly alignments as additional information on contig order and orientations and to collapse haplotype contigs. We demonstrate the performance of LA using real data and show that it outperforms ALLMAPS on anchoring completeness and speed. Accuracy-wise LA and ALLMAPS are about equal, but at the expense of lower completeness of ALLMAPS. The software Chromonomer was faster than the other two methods but has major limitations and is lower in accuracy. We also show that with additional information, such as contig–contig and read alignments, the anchoring completeness can be improved by up to 70% without significant loss in accuracy. Based on simulated data, we conclude that the anchoring accuracy can be improved by utilizing information about map position uncertainty. Accuracy is the rate of contigs in correct orientation and completeness is the number contigs with inferred orientation.

Availability and implementation

Lep-Anchor is available with the source code under GNU general public license from http://sourceforge.net/projects/lep-anchor. All the scripts and code used to produce the reported results are included with Lep-Anchor.
Treatment of Human Plague: A Systematic Review of Published Aggregate Data on Antimicrobial Efficacy, 1939–2019
Authors: Godfred-Cato Shana , Cooley Katharine M , Fleck-Derderian Shannon , Becksted Heidi A , Russell Zachary , Meaney-Delman Dana , Mead Paul S , Nelson Christina A
Published: January 2020

Background

Plague, caused by the bacterium Yersinia pestis, has killed millions in historic pandemics and continues to cause sporadic outbreaks. Numerous antimicrobials are considered effective for treating plague; however, well-defined information on the relative efficacy of various treatments is lacking. We conducted a systematic review of published data on antimicrobial treatment of plague reported in aggregate.

Methods

We searched databases including Embase, Medline, CINAHL, Cochrane Library, and others for publications with terms related to plague and antimicrobials. Articles were included if they contained 1) a group of patients treated for plague, with outcomes reported by antimicrobial regimen, and 2) laboratory evidence of Y. pestis infection or an epidemiologic link to patients with laboratory evidence of Y. pestis. Case fatality rate by antimicrobial regimen was calculated.

Results

In total, 5837 articles were identified; among these, 26 articles published between 1939 and 2008 met inclusion criteria. A total of 2631 cases of human plague reported within these articles were included. Among cases classified by primary clinical form of plague, 93.6% were bubonic, 5.9% pneumonic, and 0.5% septicemic with associated case fatalities of 14.2%, 31.1%, and 20.0%, respectively. Case fatality rate among patients who received monotherapy with tetracyclines, chloramphenicol, aminoglycosides, or sulfonamides was 1.3%, 1.4%, 7.5%, and 20.2%, respectively. Fluoroquinolones were only given as part of combination therapy. Penicillin was associated with a case fatality rate of 75%.

Conclusions

Tetracyclines, chloramphenicol, and aminoglycosides were associated with the lowest case fatality rates of all antimicrobials used for treatment of plague. Additional research is needed to determine the efficacy of fluoroquinolones as monotherapy.
The Silence Speaks, but We Do Not Listen: Synonymous c.1824C>T Gene Variant in the Last Exon of the Prothrombin Gene as a New Prothrombotic Risk Factor
Authors: Pruner Iva , Farm Maria , Tomic Branko , Gvozdenov Maja , Kovac Mirjana , Miljic Predrag , Soutari Nida Mahmoud Hourani , Antovic Aleksandra , Radojkovic Dragica , Antovic Jovan , Djordjevic Valentina
Published: January 2020

Background

Thrombosis is a major global disease burden with almost 60% of cases related to underlying heredity and most cases still idiopathic. Synonymous single nucleotide polymorphisms (sSNPs) are considered silent and phenotypically neutral. Our previous study revealed a novel synonymous FII c.1824C>T variant as a potential risk factor for pregnancy loss, but it has not yet been associated with thrombotic diseases.

Methods

To determine the frequency of the FII c.1824C>T variant we have sequenced patients’ DNA. Prothrombin RNA expression was measured by quantitative PCR. Functional analyses included routine hemostasis tests, western blotting and ELISA to determine prothrombin levels in plasma, and global hemostasis assays for thrombin and fibrin generation in carriers of the FII c.1824C>T variant. Scanning electron microscopy was used to examine the structure of fibrin clots.

Results

Frequency of the FII c.1824C>T variant was significantly increased in patients with venous thromboembolism and cerebrovascular insult. Examination in vitro demonstrated increased expression of prothrombin mRNA in FII c.1824T transfected cells. Our ex vivo study of FII c.1824C>T carriers showed that the presence of this variant was associated with hyperprothrombinemia, hypofibrinolysis, and formation of densely packed fibrin clots resistant to fibrinolysis.

Conclusion

Our data indicate that FII c.1824C>T, although a synonymous variant, leads to the development of a prothrombotic phenotype and could represent a new prothrombotic risk factor. As a silent variant, FII c.1824C>T would probably be overlooked during genetic screening, and our results show that it could not be detected in routine laboratory tests.
miR-TV: an interactive microRNA Target Viewer for microRNA and target gene expression interrogation for human cancer studies
Authors: Pan Chao-Yu , Lin Wen-Chang
Published: January 2020

MicroRNAs (miRNAs) have been identified in many organisms, and they are essential for gene expression regulation in many critical cellular processes. The expression levels of these genes and miRNAs are closely associated with the progression of diseases such as cancers. Furthermore, survival analysis is a significant indicator for evaluating the criticality of these cellular processes in cancer progression. We established a web tool, miRNA Target Viewer (miR-TV), which integrates 5p-arm and 3p-arm miRNA expression profiles, mRNA target gene expression levels in healthy and cancer populations, and clinical data of cancer patients and their survival information. The developed miR-TV obtained miRNA-seq, mRNA-seq and clinical data from the Cancer Genome Atlas and potential miRNA target gene predictions from miRDB, targetScan and miRanda. The data presentation was implemented using the D3 javascript toolkit. The D3 toolkit is frequently used to provide an easy-to-use interactive interface. Our miR-TV provides a user-friendly and interactive interface, which can be beneficial for biomedical researchers to freely interrogate miRNA expression information and their potential target genes. We believe that such a data visualization bioinformatics tool is excellent for obtaining information from massive biological data.

Database URL: http://mirtv.ibms.sinica.edu.tw
Risk of perioperative coronary stent stenosis or occlusion in patients with previous percutaneous coronary intervention undergoing coronary artery bypass grafting surgery
Authors: Grieshaber Philippe , Oswald Irina , Albert Marc , Reents Wilko , Zacher Michael , Roth Peter , Niemann Bernd , Dörr Oliver , Krüger Tobias , Nef Holger , Sodah Ayman , Hamm Christian , Schlensak Christian , Diegeler Anno , Sedding Daniel , Franke Ulrich , Boening Andreas
Published: January 2020

OBJECTIVES

There is an ongoing discussion about how to treat coronary stents during bypass surgery: Should patent stents be left alone and the stented vessels be ungrafted, or should every stented coronary artery receive a bypass graft? This study aims to determine the relevance of perioperative stent stenosis or occlusion on postoperative outcomes up to 3 years postoperatively.

METHODS

Patients undergoing coronary artery bypass grafting surgery (CABG) (±concomitant procedures) with previous percutaneous coronary intervention from 4 centres were prospectively included in this observatory study between April 2015 and June 2017. A coronary angiography was conducted between the fifth and seventh postoperative days. The preoperative and postoperative angiograms were assessed in a core laboratory, assessing the patencies of coronary stents and bypass grafts. The core lab investigators were blinded to the patients’ characteristics and perioperative course.

RESULTS

A total of 107 patients were included in the study. In the postoperative coronary angiography, 265 bypass grafts and 189 coronary stents were examined angiographically. Ninety-seven percent of preoperatively patent stents remained patent. New coronary stent stenoses were observed in 5 patients (4.7%). All 5 patients were asymptomatic and managed conservatively. Bypass stenoses were observed in 12 patients (11%), of whom were managed conservatively, 4 underwent percutaneous coronary intervention and 1 underwent redo-CABG. Two years postoperatively, 97% of patients were alive. Patients with new stent stenosis tended to have a better survival compared with patients with bypass stenosis (100% vs 73%; P = 0.09) up to 3 years postoperatively.

CONCLUSIONS

Perioperative coronary stent stenosis occurs rarely. It is safe to leave a patently stented coronary vessel without bypass grafting.
Stool Reducing Sugars and Stool pH Are Poor Screening Tests for Intestinal Disaccharidase Deficiencies in Children
Authors: Erickson J Alan , Case Kristin , Neider Cole , Johnson Lisa M
Published: January 2020

Background

Tests for stool reducing sugars and stool pH are ordered for children with osmotic diarrhea to screen for carbohydrate malabsorption.

Methods

We compared the results of the two screening tests, stool reducing sugars and stool pH, with a more definitive result from an intestinal tissue disaccharidase activity assay ordered for pediatric patients (<18 years old). Overall, 159 patients had results for tissue disaccharidase and stool reducing sugars, but only 115 had additional results of stool pH. Forty-six of the 159 patients had mild, moderate, or severe disaccharidase deficiencies. The sensitivity and specificity of the screening tests were calculated for individual disaccharidase deficiencies. In addition, trends of abnormal tissue disaccharidase, stool reducing sugars, and stool pH results were examined in different age groups.

Results

The sensitivities for stool reducing sugars and stool pH were 9% to 28% and specificities were 74% to 81% for individual disaccharidase deficiencies. Infants (0 years of age) had the highest percentage of abnormal results across all three tests; however, the positive predicative values were 54% and 50% for stool reducing sugars and stool pH, respectively.

Conclusions

The screening tests, stool reducing sugars and stool pH, had low sensitivity compared with results of measured tissue disaccharidase activity in pediatric patients. Infants had the highest percentage of abnormal results for all three tests, but the screening tests still performed poorly in that age group. This study suggests that stool reducing sugars and stool pH should not be used as screening tests for carbohydrate malabsorption due to disaccharidase deficiencies in pediatric patients.
Demographic and Burn Injury-Specific Variables Associated with Limited Joint Mobility at Discharge in a Multicenter Study
Authors: Lensing Jonathan , Wibbenmeyer Lucy , Liao Junlin , Parry Ingrid , Kowalske Karen , Reg Richard , Schneider Jeffrey C
Published: January 2020

Burn scar contractures. Existing research on contractures is limited by incomplete analysis of potential contributing variables and differing protocols. This study expands the exploration of contributing variables to include surgery and rehabilitation treatment-related factors. Additionally, this study quantifies direct patient therapy time and patient exposure to rehabilitation prevention therapies. Data from subjects enrolled in the prospective Burn Patient Acuity Demographics, Scar Contractures and Rehabilitation Treatment Related to Patient Outcome Study (ACT) were analyzed to determine variables related to a limited range of motion (limROM) in seven joints and 18 motions (forearm supination) at discharge. Chi-squared and Student’s t-test were used accordingly. Multivariate analysis was performed at the patient and joint motion level to control for confounders. Of the 300-member study group, 259 (86.3%) patients had limROM at discharge. Variables independently related to the development of moderate-to-severe limROM on the patient level were larger TBSA, having skin grafted and prolonged bed rest. Variables independently related to moderate–severe limROM on the joint motion level were the percentage of cutaneous functional unit (CFU) burned (P = .044), increase in the length of stay, weight gain, poor compliance with rehabilitation therapy and lower extremity joint burns. Rates of limROM are increased in patients who had larger burns, required surgery, had a greater percentage of the associated CFU burned, and had lower extremity burns. Attention to adequate pain control to ensure rehabilitation tolerance and early ambulation may also decrease limROM at discharge and quicker return to pre-burn activities and employment.
The Economic Impacts and Management of Spotted Wing Drosophila (Drosophila Suzukii): The Case of Wild Blueberries in Maine
Authors: Yeh D Adeline , Drummond Francis A , Gómez Miguel I , Fan Xiaoli
Published: January 2020

Drosophila suzukii (Matsumura), or spotted wing drosophila, has become a major pest concern for berry growers in the United States. In this study, we evaluated the economic impacts of D. suzukii on the Maine wild blueberry industry from two perspectives. The first analysis estimated the state-level economic impacts of D. suzukii on the wild blueberry industry in Maine in the absence of control. We found that D. suzukii could result in drastic revenue losses to the industry, which could be over $6.8 million under the worst-case scenario (assuming a 30% yield reduction). In the second analysis, we used Monte Carlo simulation to compare the expected revenues under different management strategies for a typical wild blueberry farm in Maine. The analysis focused on a decision-making week during the harvesting season, which the grower can choose in between three control strategies: no-control, early harvest, or insecticide application. The results suggested that insecticide applications are not economically optimal in most low infestation risk scenarios. Furthermore, although the early harvest strategy is one of the strategies to avoid D. suzukii infestations for wild blueberry production in Maine, the tradeoff is the revenue loss from the unripe crop. Using the simulation results, we summarized optimal harvest timing regarding the fruit maturity level under different D. suzukii infestation risk scenarios, which can minimize the revenue loss from adopting the early harvest management strategy.
The ‘culture of two’: Communication accommodation in ravens’ (Corvus corax) nonvocal signaling
Authors: Luef Eva Maria , Ter Maat Andries , Jäger Manuela , Pika Simone
Published: January 2020

The theory of communication accommodation refers to linguistic processes through which human interactants—consciously or subconsciously—shift their speech and gesture styles to resemble those of their conversation partners. This phenomenon represents a crucial feature of human language and is particularly pronounced in affiliative and/or strong relationships. Communication accommodation is suggested to reflect a need for social integration or identification with other individuals and, as such, plays an important role in communication within closely-knit social units and in particular monogamous relationships. Concerning nonhuman animals, the phenomenon of communication accommodation has received relatively little research attention. Here, we tested whether common ravens (Corvus corax), which are known for their sophisticated communicative skills and lifelong monogamous pair bonds, accommodate their nonvocal signals within a relationship (i.e., pair-partners). Specifically, we investigated whether the nonvocal signals exchanged within pairs become synchronized over time. Our results provided evidence that raven pairs matched their repertoires, with recipients reciprocating the signals of their communication partners in relation to time spent together. This study thus strengthens the hypothesis that the motives to form and maintain affiliate relationships may have been crucial in boosting not only cognitive but also communicative abilities, and provides insight into the role social bonding might have played in the evolution of communicative plasticity.
Hypersingular Integral Equations Arising in the Boundary Value Problems of the Elasticity Theory
Authors: Mkhitaryan S M , Mkrtchyan M S , Kanetsyan E G
Published: January 2020

The exact solutions of a class of hypersingular integral equations with kernels $\left( {s-x} \right)^{-2}$, $\left( {\sin \frac{s-x}{2}} \right)^{-2}$, $\left( {\sinh \frac{s-x}{2}} \right)^{-2},\cos \frac{s-x}{2}\left( {\sin \frac{s-x}{2}} \right)^{-2}$, $\cosh \frac{s-x}{2}\left( {\sinh \frac{s-x}{2}} \right)^{-2}$ are obtained where the integrals must be interpreted as Hadamard finite-part integrals. Problems of cracks in elastic bodies of various canonical forms under antiplane and plane deformations, where the crack edges are loaded symmetrically, lead to such equations. These problems, in turn, lead to mixed boundary value problems of the mathematical theory of elasticity for a half-plane, a circle, a strip and a wedge.
Playing the fields: Theorizing research impact and its assessment
Authors: Williams Kate
Published: January 2020

How research is assessed affects what types of knowledge are valued, incentivized, and rewarded. An increasingly important element of contemporary research evaluation is the measurement of the wider impact of research (e.g. benefit to society, culture or economy). Although the measurement of impact has been highly contested, the area is under-theorized and dominated by pragmatic research policy imperatives. Informed by a sociological perspective, this article intervenes in this context by reframing research impact as the attainment and maintenance of capital (i.e. symbolic power or status) in various fields beyond academia. It argues that research impact occurs at the intersection of these fields of power. The article shows that impact involves various combinations of capital from the scholarly field, the field of politics, the field of application, the media field, and the economic field, which provide credibility, authority, utility, visibility, and weight, respectively. In exploring the forms of worth and value that underpin the pursuit of legitimacy in these fields, the article provides a new theoretical framework for understanding research impact and its assessment.
CELLULAR DOSE DISTRIBUTIONS OF INHALED RADON PROGENY AMONG DIFFERENT LOBES OF THE HUMAN LUNG
Authors: Hofmann Werner , Winkler-Heil Renate
Published: January 2020

Basal and secretory cell doses in the different lobes of the human lung following inhalation of short-lived radon progeny were calculated for a five-lobe asymmetric, stochastic lung model, considering the non-uniform ventilation of the lobes. Dose calculations for defined exposure conditions revealed that the upper lobes receive higher doses than the average bronchial dose for the whole lung, with the right upper lobe receiving the highest dose. The resulting inter-lobar distribution of cellular bronchial doses indicated that the non-uniform lung morphometry is the dominating factor, while non-uniform ventilation only slightly enhances the lobar differences. The comparison of average lobe-specific bronchial doses with the average bronchial dose for the whole lung allows the calculation of lobe-specific dose weighting factors, which can be used to convert average bronchial doses based on symmetric airway generation or bronchial compartment models to lobar bronchial doses.
High Levels of Insensitivity to Phosphonate Fungicides in Pseudoperonospora humuli
Authors: Gent David H. , Block Mary , Claassen Briana J.
Published: January 2020

Phosphonate (phosphite; HPO3−2) is fungicidal against oomycetes and certain other organisms. The Fungicide Resistance Action Committee has deemed phosphonate to be at low risk of resistance development, and reduced sensitivity to phosphonate has been reported only occasionally in plant pathogens. Reduced sensitivity to the fungicide fosetyl-Al was documented in the hop downy mildew pathogen, Pseudoperonospora humuli, in the early 2000s, but disease caused by insensitive isolates could still be managed commercially if the fungicide rate was doubled from 2.24 to 4.48 kg/ha. In this research, we document the occurrence of isolates of P. humuli in Oregon that possess even higher levels of insensitivity to fosetyl-Al and other phosphonate fungicides. The median estimated effective concentration required to reduce infection by 50% (EC50) for isolates collected from two farms reporting disease control failures was 2.7% (vol/vol) phosphonate (range = 1.6 to 164.2), which was 1.6 times (range = 0.9 to 96.0) the maximum labeled rate of the phosphonate fungicide utilized. In contrast, the median EC50 for isolates obtained from experimental plots that have received only a single application of a phosphonate fungicide was 0.6% (vol/vol) phosphonate (range = 0.11 to 2.3) or 0.3 times the maximum allowable rate. Sensitivity of isolates to a phosphorous acid fungicide, fosetyl-Al, and a plant nutrient product containing an unspecified level of phosphorous acid were linearly related. Insensitivity to the maximum allowable rate of a phosphorous acid fungicide was widespread within and among hop farms in Oregon. Among 54 isolates assayed for phosphonate insensitivity, 96% had EC50 values that exceeded the maximum allow rate of the fungicide used in the assays. Field studies conducted in 2 years further demonstrated that a phosphorous fungicide, a nutrient product containing phosphorous acid, and fosetyl-Al failed to provide commercially acceptable suppression of downy mildew when applied at the maximum allowable rates and even double these rates, whereas fungicides with different modes of action provided 91% or greater disease control. The whole of this research indicates that P. humuli has been selected to tolerate fosetyl-Al and other phosphonate fungicides at rates four times greater than those used earlier to obtain satisfactory suppression of downy mildew. This finding has implications for management of the disease not only in Oregon but also, in other production regions should insensitive isolates be introduced on infected planting material.
Interleukin-12 supports in vitro self-renewal of long-term hematopoietic stem cells
Authors: Zhang Shanshan , Morita Maiko , Wang Zhao , Ooehara Jun , Zhang Sen , Xie Miner , Bai Haitao , Yu Wenying , Wang Xiaofang , Dong Fang , Wang Jinhong , Ma Shihui , Yamazaki Satoshi , Ema Hideo
Published: January 2020

Hematopoietic stem cells (HSCs) self-renew or differentiate through division. Cytokines are essential for inducing HSC division, but the optimal cytokine combination to control self-renewal of HSC in vitro remains unclear. In this study, we compared the effects of interleukin-12 (IL-12) and thrombopoietin (TPO) in combination with stem cell factor (SCF) on in vitro self-renewal of HSCs. Single-cell assays were used to overcome the heterogeneity issue of HSCs, and serum-free conditions were newly established to permit reproduction of data. In single-cell cultures, CD150+CD48−CD41−CD34−c-Kit+Sca-1+lineage− HSCs divided significantly more slowly in the presence of SCF+IL-12 compared with cells in the presence of SCF+TPO. Serial transplantation of cells from bulk and clonal cultures revealed that TPO was more effective than IL-12 at supporting in vitro self-renewal of short-term (<6 months) HSCs, resulting in a monophasic reconstitution wave formation, whereas IL-12 was more effective than TPO at supporting the in vitro self-renewal of long-term (>6 months) HSCs, resulting in a biphasic reconstitution wave formation. The control of division rate in HSCs appeared to be crucial for preventing the loss of self-renewal potential from their in vitro culture.
Successful ex vivo expansion of mouse hematopoietic stem cells
Authors: Ema Hideo
Published: January 2020

Ex vivo expansion of hematopoietic stem cells (HSCs) is considered the holy grail in stem cell biology and therapy, as it has long been difficult to make this procedure possible. Yamazaki's research team has established new, polyvinyl alcohol-based culture conditions and shown a significant expansion of mouse HSCs from a small number of cells after a month of culture. Surprisingly, expanded HSCs were able to reconstitute unconditioned normal mice. There is generally a technical concern in limiting dilution assay to estimate a fold-expansion of HSCs. But, this work paves the way toward expansion of human HSCs useful for transplantation medicine.
When blood development meets single-cell transcriptomics
Authors: Zhou Jie , Liu Bing , Lan Yu
Published: January 2020

Blood cells arise during embryonic development by three temporally distinct waves. Belonging to the third wave, hematopoietic stem cells (HSCs) are generated from hemogenic endothelium via endothelial-to-hematopoietic transition in mid-gestational embryos. Recently, studies combined with single-cell transcriptomics have provided massive new insights into the molecular evolutions and the underlying mechanisms of distinct waves of hematopoietic specification. In this review, we discuss the current single-cell profiling techniques, the most recent novel findings involved in the generation of distinct waves of blood cells, especially the HSCs, using single-cell transcriptional profiling combined with functional evaluations, and the perspectives to use the accumulating huge single-cell transcriptional data sets to study developmental hematopoiesis.
Transcriptional addiction in mixed lineage leukemia: new avenues for target therapies
Authors: Xiao Ruijing , Wang Honghong , Liang Kaiwei
Published: January 2020

Mixed lineage leukemia (MLL) is an aggressive and refractory blood cancer that predominantly occurs in pediatric patients and is often associated with poor prognosis and dismal outcomes. Thus far, no effective target therapy for the treatment of MLL leukemia is available. MLL leukemia is caused by the rearrangement of MLL genes at 11q23, which generates various MLL chimeric proteins that promote leukemogenesis through transcriptional misregulation of MLL target genes. Biochemical studies on MLL chimeras have identified that the most common partners exist in the superelongation complex (SEC) and DOT1L complex, which activate or sustain MLL target gene expression through processive transcription elongation. The results of these studies indicate a transcription-related mechanism for MLL leukemogenesis and maintenance. In this study, we first review the history of MLL leukemia and its related clinical features. Then, we discuss the biological functions of MLL and MLL chimeras, significant cooperating events, and transcriptional addiction mechanisms in MLL leukemia with an emphasis on potential and rational therapy development. Collectively, we believe that targeting the transcriptional addiction mediated by SEC and the DOT1L complex will provide new avenues for target therapies in MLL leukemia and serve as a novel paradigm for targeting transcriptional addiction in other cancers.
Epigenetic regulation of hematopoietic stem cell homeostasis
Authors: Jiang Penglei , Wang Hui , Zheng Jiachen , Han Yingli , Huang He , Qian Pengxu
Published: January 2020

As one of the best characterized adult stem cells, hematopoietic stem cell (HSC) homeostasis is of great importance to hematopoiesis and immunity due to HSC's abilities of self-renewal and multi-lineage differentiation into functional blood cells. However, excessive self-renewal of HSCs can lead to severe hematopoietic malignancies like leukemia, whereas deficient self-renewal of HSCs may result in HSC exhaustion and eventually apoptosis of specialized cells, giving rise to abnormalities such as immunodeficiency or anemia. How HSC homeostasis is maintained has been studied for decades and regulatory factors can be generally categorized into two classes: genetic factors and epigenetic factors. Although genetic factors such as signaling pathways or transcription factors have been well explored, recent studies have emerged the indispensable roles of epigenetic factors. In this review, we have summarized regulatory mechanisms of HSC homeostasis by epigenetic factors, including DNA methylation, histone modification, chromatin remodeling, non-coding RNAs, and RNA modification, which will facilitate applications such as HSC ex vivo expansion and exploration of novel therapeutic approaches for many hematological diseases.
Molecular mechanisms for stemness maintenance of acute myeloid leukemia stem cells
Authors: Wang Jiazhen , Wang Peipei , Zhang Tiantian , Gao Zhuying , Wang Jing , Feng Mengdie , Yin Rong , Zhang Haojian
Published: January 2020

Human acute myeloid leukemia (AML) is a fatal hematologic malignancy characterized with accumulation of myeloid blasts and differentiation arrest. The development of AML is associated with a serial of genetic and epigenetic alterations mainly occurred in hematopoietic stem and progenitor cells (HSPCs), which change HSPC state at the molecular and cellular levels and transform them into leukemia stem cells (LSCs). LSCs play critical roles in leukemia initiation, progression, and relapse, and need to be eradicated to achieve a cure in clinic. Key to successfully targeting LSCs is to fully understand the unique cellular and molecular mechanisms for maintaining their stemness. Here, we discuss LSCs in AML with a focus on identification of unique biological features of these stem cells to decipher the molecular mechanisms of LSC maintenance.
End-of-Life Care Planning for Lesbian, Gay, Bisexual, and Transgender Individuals
Authors: Lowers Jane
Published: January 2020

Advance care planning is important for all adults. To facilitate conversations about patients' preferences, clinicians need to be aware of how identities and relationships may shape priorities and concerns. This qualitative study solicited advance care planning priorities among lesbian, gay, bisexual, and transgender (LGBT) individuals to explore whether sexual orientation and gender identity shape concerns about care at the end of life. Data were collected from 30 LGBT adults on the east coast through focus groups and interviews using purposive sampling. Transcribed discussions were analyzed using grounded theory. Participants regarded end of life as any period after the loss of decision-making capacity and felt strongly that individuals in that state would need an advocate to ensure that they were cared for with respect and dignity; many lacked confidence that the health care system would do so without prompting. Participants who had partners or children hoped that family would serve as advocates but worried that they might outlive their partners; participants who were single worried that the advocate role was too great a burden to ask of friends or distant relatives. Providers can encourage open dialogue and more fully capture LGBT patients' needs through sensitive, respectful communication and by creating environmental signals of LGBT inclusivity.
Animal-Assisted Interactions to Alleviate Psychological Symptoms in Patients Receiving Mechanical Ventilation
Authors: Hetland Breanna , Bailey Tanya , Prince-Paul Maryjo
Published: January 2020

Mechanical ventilation is a common life-support intervention for critically ill patients that can cause stressful psychological symptoms. Animal-assisted interactions have been used in a variety of inpatient settings to reduce symptom burden and promote overall well-being. Because of the severity of illness associated with critical care, use of highly technological equipment, and heightened concern for infection control and patient safety, animal-assisted interaction has not been widely adopted in the intensive care unit. This case study of the therapeutic interaction between a canine and a mechanically ventilated patient provides support for the promotion of animal-assisted interactions as an innovative symptom management strategy in the intensive care unit.
How comprehensive is the Cochrane Central Register of Controlled Trials for identifying clinical trial registration?: the protocol of a diagnostic study
Authors: Banno Masahiro , Tsujimoto Yasushi , Kataoka Yuki
Published: January 2020

Objectives

To evaluate whether or not systematic reviewers can use Cochrane Central Register of Controlled Trials (CENTRAL) to identify ongoing and unpublished studies instead of searching International Clinical Trials Registry Platform (ICTRP) and ClinicalTrials.gov (CT.gov).

Methods

This will be a diagnostic accuracy test study. We will collect a consecutive sample of ongoing or unpublished studies on Cochrane Database of Systematic Reviews (CDSRs) during the last six months. We will use all of the records as our reference standard and evaluated whether they are part of the CENTRAL search presented in the CDSRs.

The index test is the CENTRAL search using the search terms in the CDSRs, and the reference standard is the list of ongoing or unpublished studies registered on the ICTRP or CT.gov in the CDSRs.

We will assess the sensitivity and number needed to read.

Ethics & Dissemination

This study does not require ethics approval. We registered this study protocol. We will publish the findings in a peer-reviewed journal and may present them at conferences.

Discussion

This study may lessen the burden of systematic reviewers if this study clarifies CENTRAL search can be used for screening in records about ongoing or unpublished studies.

Registration

UMIN-CTR: UMIN000038981

Author name abbreviations

Masahiro Banno (MB), Yasushi Tsujimoto (YT), Yuki Kataoka (YK)
Automatic detection of generalized paroxysmal fast activity in Lennox-Gastaut syndrome using a bi-modal EEG time-frequency feature
Authors: Omidvarnia Amir , Warren Aaron E.L. , Dalic Linda J. , Pedersen Mangor , Archer John S. , Jackson Graeme
Published: January 2020

Objective

Mark-up of generalized interictal epileptiform discharges (IEDs) on EEG is an important step in the diagnosis and characterization of epilepsy. However, manual EEG mark-up is a time-consuming, subjective, and highly specialized task where the human reviewer needs to visually inspect a large amount of data to facilitate accurate clinical decisions. The objective of this study was to develop a framework for automated detection of generalized paroxysmal fast activity (GPFA), which is a characteristic type of generalized IED seen in scalp EEG recordings of patients with Lennox-Gastaut syndrome (LGS), a severe form of drug-resistant generalized epilepsy.

Methods

We studied 13 children with LGS who had GPFA events in their interictal EEG recordings. Time-frequency information derived from manually marked IEDs across multiple EEG channels was used to automatically detect similar events in each patient’s interictal EEG. We validated true positives and false positives of the proposed spike detection approach using both standalone scalp EEG and simultaneous EEG-functional MRI (EEG-fMRI) recordings.

Results

GPFA events displayed a consistent low-high frequency arrangement in the time-frequency domain. This ‘bi-modal’ spectral feature was most prominent over frontal EEG channels. Our automatic detection approach using this feature identified likely epileptic events with similar time-frequency properties to the manually marked GPFAs. Brain maps of EEG-fMRI signal change during these automatically detected IEDs were comparable to the EEG-fMRI brain maps derived from manual IED mark-up.

Conclusion

GPFA events have a characteristic bi-modal time-frequency feature that can be automatically detected from scalp EEG recordings in patients with LGS. Validity of this time-frequency feature is demonstrated by EEG-fMRI analysis of automatically detected events, which recapitulates the brain maps we have previously shown to underlie generalized IEDs in LGS.

Significance

This study provides a novel methodology that paves the way for quick, automated, and objective inspection of generalized IEDs in LGS. The proposed framework may be extendable to a wider range of epilepsy syndromes in which monitoring the burden of epileptic activity can aid clinical decision-making. For example, automated quantification of generalized discharges may permit faster assessment of treatment response and estimation of future seizure risk.