bluuebunny/crossref_metadata_2025_split huggingface dataset:
Desmoplastic small round cell tumor is dependent on the EWS-WT1 transcription factor
Authors: Gedminas Jenna M. , Chasse Maggie H. , McBrairty Mitchell , Beddows Ian , Kitchen-Goosen Susan M. , Grohar Patrick J. 
Published: April 2020

AbstractDesmoplastic small round cell tumor (DSRCT) is a rare and aggressive soft-tissue malignancy with a poor overall survival and no effective therapeutic options. The tumor is believed to be dependent on the continued activity of the oncogenic EWS-WT1 transcription factor. However, the dependence of the tumor on EWS-WT1 has not been well established. In addition, there are no studies exploring the downstream transcriptional program across multiple cell lines. In this study, we have developed a novel approach to selectively silence EWS-WT1 without impacting either wild-type EWSR1 or WT1. We show a clear dependence of the tumor on EWS-WT1 in two different cell lines, BER and JN-DSCRT-1. In addition, we identify and validate important downstream target pathways commonly dysregulated in other translocation-positive sarcomas, including PRC2, mTOR, and TGFB. Surprisingly, there is striking overlap between the EWS-WT1 and EWS-FLI1 gene signatures, despite the fact that the DNA-binding domain of the fusion proteins, WT1 and FLI1, is structurally unique and classified as different types of transcription factors. This study provides important insight into the biology of this disease relative to other translocation-positive sarcomas, and the basis for the therapeutic targeting of EWS-WT1 for this disease that has limited therapeutic options.
A framework for the computational prediction and analysis of non-coding RNAs in microbial environmental populations and their experimental validation
Authors: Lott Steffen C , Voigt Karsten , Lambrecht S Joke , Hess Wolfgang R , Steglich Claudia 
Published: April 2020

Abstract
Small regulatory RNAs and antisense RNAs play important roles in the regulation of gene expression in bacteria but are underexplored, especially in natural populations. While environmentally relevant microbes often are not amenable to genetic manipulation or cannot be cultivated in the laboratory, extensive metagenomic and metatranscriptomic datasets for these organisms might be available. Hence, dedicated workflows for specific analyses are needed to fully benefit from this information. Here, we identified abundant sRNAs from oceanic environmental populations of the ecologically important primary producer Prochlorococcus starting from a metatranscriptomic differential RNA-Seq (mdRNA-Seq) dataset. We tracked their homologs in laboratory isolates, and we provide a framework for their further detailed characterization. Several of the experimentally validated sRNAs responded to ecologically relevant changes in cultivation conditions. The expression of the here newly discovered sRNA Yfr28 was highly stimulated in low-nitrogen conditions. Its predicted top targets include mRNAs encoding cell division proteins, a sigma factor, and several enzymes and transporters, suggesting a pivotal role of Yfr28 in the coordination of primary metabolism and cell division. A cis-encoded antisense RNA was identified as a possible positive regulator of atpF encoding subunit b’ of the ATP synthase complex. The presented workflow will also be useful for other environmentally relevant microorganisms for which experimental validation abilities are frequently limiting although there is wealth of sequence information available.
A draft genome assembly of spotted hyena, Crocuta crocuta
Authors: Yang Chentao , Li Fang , Xiong Zijun , Koepfli Klaus-Peter , Ryder Oliver , Perelman Polina , Li Qiye , Zhang Guojie 
Published: April 2020

AbstractThe spotted hyena (Crocuta crocuta), one of the largest terrestrial predators native to sub-Saharan Africa, is well known for its matriarchal social system and large-sized social group in which larger females dominate smaller males. Spotted hyenas are highly adaptable predators as they both actively hunt prey and scavenge kills by other predators, and possess an enhanced hypercarnivorous dentition that allows them to crack open bones and thereby feed on nearly all parts of a carcass. Here, we present a high-quality genome assembly of C. crocuta that was generated using a hybrid assembly strategy with Illumina multi-size libraries. A genome of about 2.3 Gb was generated with a scaffold N50 length of 7.2 Mb. More than 35.28% genome region was identified as repetitive elements, and 22,747 protein-coding genes were identified in the genome, with 97.45% of these annotated by databases. This high-quality genome will provide an opportunity to gain insight into the evolution of social behavior and social cognition in mammals, as well as for population genetics and metagenomics studies.
Effects of β2-receptor stimulation by indacaterol in chronic heart failure treated with selective or non-selective β-blockers: a randomized trial
Authors: Contini Mauro , Spadafora Emanuele , Barbieri Simone , Gugliandolo Paola , Salvioni Elisabetta , Magini Alessandra , Apostolo Anna , Palermo Pietro , Alimento Marina , Agostoni Piergiuseppe 
Published: April 2020

AbstractAlveolar β2-receptor blockade worsens lung diffusion in heart failure (HF). This effect could be mitigated by stimulating alveolar β2-receptors. We investigated the safety and the effects of indacaterol on lung diffusion, lung mechanics, sleep respiratory behavior, cardiac rhythm, welfare, and exercise performance in HF patients treated with a selective (bisoprolol) or a non-selective (carvedilol) β-blocker. Study procedures were performed before and after indacaterol and placebo treatments according to a cross-over, randomized, double-blind protocol in forty-four patients (27 on bisoprolol and 17 on carvedilol). No differences between indacaterol and placebo were observed in the whole population except for a significantly higher VE/VCO2 slope and lower maximal PETCO2 during exercise with indacaterol, entirely due to the difference in the bisoprolol group (VE/VCO2 31.8 ± 5.9 vs. 28.5 ± 5.6, p < 0.0001 and maximal PETCO2 36.7 ± 5.5 vs. 37.7 ± 5.8 mmHg, p < 0.02 with indacaterol and placebo, respectively). In carvedilol, indacaterol was associated with a higher peak heart rate (119 ± 34 vs. 113 ± 30 bpm, with indacaterol and placebo) and a lower prevalence of hypopnea during sleep (3.8 [0.0;6.3] vs. 5.8 [2.9;10.5] events/hour, with indacaterol and placebo). Inhaled indacaterol is well tolerated in HF patients, it does not influence lung diffusion, and, in bisoprolol, it increases ventilation response to exercise.
Exploitation of fibrin-based signaling niche for deriving progenitors from human adipose-derived mesenchymal stem cells towards potential neural engineering applications
Authors: Chandrababu Krishnapriya , Senan Manesh , Krishnan Lissy K. 
Published: April 2020

AbstractAdipose-derived mesenchymal stem cells (hADMSC) retaining proliferation and multi-differentiation potential may support the central nervous system (CNS) regeneration. Multipotency of MSC may result in both desirable and undesirable cells, post-transplantation. A better strategy to attain desired cells may be in vitro commitment of hADMSCs to uni-/bi- potent neural progenitor cells (NPCs), prior to transplantation. Derivation of stable NPCs may require a suitable niche eliciting proliferation and differentiation signals. The present study designed a biomimetic niche comprising insoluble fibrin supported adhesion matrix and exogenously added growth factors (GFs) for deriving different neural cells and established the role of Notch and Wnt signals for proliferation and differentiation of hADMSCs, respectively. The stable transformation of hADMSCs into neurospheres (NS) comprising Nestin+ve NPCs was achieved consistently. Slight modifications of niche enable differentiation of NS to NPCs; NPCs to neurons; NPCs to oligodendrocyte progenitor cells (OPCs); and OPCs to oligodendrocytes (OLG). Fibrin plays a crucial role in the conversion of hADMSC to NS and NPCs to OPCs; but, not essential for OPC to OLG maturation. Co-survival and cell-cell interaction of NPC derived neurons and OPCs promoting OLG maturation is illustrated. The designed biomimetic niche shows the potential for directing autologous ADMSCs to neural cells for applications in regenerative medicine.
Duplication with structural modification through extrachromosomal circular and lariat DNA in the human genome
Authors: Takahashi Kazuki K. , Innan Hideki 
Published: April 2020

AbstractDuplication plays an important role in creating drastic changes in genome evolution. In addition to well-known tandem duplication, duplication can occur such that a duplicated DNA fragment is inserted at another location in the genome. Here, we report several genomic regions in the human genome that could be best explained by two types of insertion-based duplication mechanisms, where a duplicated DNA fragment was modified structurally and then inserted into the genome. In one process, the DNA fragment is turned into an extrachromosomal circular DNA, cut somewhere in the circle, and reintegrated into another location in the genome. And in the other, the DNA fragment forms a “lariat structure” with a “knot”, the strand is swapped at the knot, and is then reintegrated into the genome. Our results suggest that insertion-based duplication may not be a simple process; it may involve a complicated procedures such as structural modification before reintegration. However, the molecular mechanism has yet to be fully understood.
Microencapsulated Insulin-Like Growth Factor-1 therapy improves cardiac function and reduces fibrosis in a porcine acute myocardial infarction model
Authors: Báez-Díaz Claudia , Blanco-Blázquez Virginia , Sánchez-Margallo Francisco-Miguel , Bayes-Genis Antoni , González Irene , Abad Ana , Steendam Rob , Franssen Okke , Palacios Itziar , Sánchez Belén , Gálvez-Montón Carolina , Crisóstomo Verónica 
Published: April 2020

AbstractInsulin-like growth factor-1 (IGF-1) has demonstrated beneficial effects after myocardial infarction (MI). Microencapsulation of IGF-1 could potentially improve results. We aimed to test the effect of an intracoronary (IC) infusion of microencapsulated IGF-1 in a swine acute MI model. For that purpose IC injection of a 10 ml solution of 5 × 106 IGF-1 loaded microspheres (MSPs) (n = 8, IGF-1 MSPs), 5 × 106 unloaded MSPs (n = 9; MSPs) or saline (n = 7; CON) was performed 48 hours post-MI. Left ventricular ejection fraction (LVEF), indexed ventricular volumes and infarct size (IS) were determined by cardiac magnetic resonance at pre-injection and 10 weeks. Animals were euthanized at 10 weeks, and myocardial fibrosis and vascular density were analysed. End-study LVEF was significantly greater in IGF-1 MSPs compared to MSPs and CON, while ventricular volumes exhibited no significant differences between groups. IS decreased over time in all groups. Collagen volume fraction on the infarct area was significantly reduced in IGF-1 MSPs compared to CON and MSPs. Vascular density analysis of infarct and border zones showed no significant differences between groups. In conclusion, the IC injection of 5 × 106 IGF-1 loaded MSPs in a porcine acute MI model successfully improves cardiac function and limits myocardial fibrosis, which could be clinically relevant.
An outbreak of gastroenteritis by emerging norovirus GII.2[P16] in a kindergarten in Kota Kinabalu, Malaysian Borneo
Authors: Ahmed Kamruddin , Dony Jiloris Julian Frederick , Mori Daisuke , Haw Liaw Yun , Giloi Nelbon , Jeffree Mohammad Saffree , Iha Hidekatsu 
Published: April 2020

AbstractOutbreaks of diarrhea in kindergartens are underreported and frequently go unnoticed in developing countries. To better understand the etiology this study was performed during an outbreak of diarrhea in a kindergarten in Sabah, Malaysia. Outbreak investigation was performed according to the standard procedures. In this outbreak a total of 34 (36.5%) children and 4 (30.8%) teachers suffered from gastroenteritis. Stool samples from seven children and 13 teachers were tested for rotavirus and norovirus. During the investigation stool samples were collected and sent in cold chain to the laboratory. The samples were subjected to rotavirus enzyme linked immunosorbent assay, and reverse transcription PCR for norovirus. All samples were negative for rotavirus but positive for norovirus. To determine the genogroup and genotype of norovirus, nucleotide sequencing of the amplicons was performed. All norovirus from the outbreak was of genotype GII.2[16]. To determine the relatedness of the strains phylogenetic analysis was done using neighbor-joining method. Phylogenetically these strains were highly related to GII.2[P16] noroviruses from China and Japan. This study provided evidence that a diarrheal outbreak in a kindergarten was caused by GII.2[P16] norovirus which is an emerging strain in East Asia and Europe.
Increasing efficiency of high numerical aperture metasurfaces using the grating averaging technique
Authors: Arbabi Amir , Arbabi Ehsan , Mansouree Mahdad , Han Seunghoon , Kamali Seyedeh Mahsa , Horie Yu , Faraon Andrei 
Published: April 2020

AbstractOne of the important advantages of optical metasurfaces over conventional diffractive optical elements is their capability to efficiently deflect light by large angles. However, metasurfaces are conventionally designed using approaches that are optimal for small deflection angles and their performance for designing high numerical aperture devices is not well quantified. Here we introduce and apply a technique for the estimation of the efficiency of high numerical aperture metasurfaces. The technique is based on a particular coherent averaging of diffraction coefficients of periodic blazed gratings and can be used to compare the performance of different metasurface designs in implementing high numerical aperture devices. Unlike optimization-based methods that rely on full-wave simulations and are only practicable in designing small metasurfaces, the gradient averaging technique allows for the design of arbitrarily large metasurfaces. Using this technique, we identify an unconventional metasurface design and experimentally demonstrate a metalens with a numerical aperture of 0.78 and a measured focusing efficiency of 77%. The grating averaging is a versatile technique applicable to many types of gradient metasurfaces, thus enabling highly efficient metasurface components and systems.
Genetic factors associated with response to as-needed aflibercept therapy for typical neovascular age-related macular degeneration and polypoidal choroidal vasculopathy
Authors: Yoneyama Seigo , Sakurada Yoichi , Kikushima Wataru , Sugiyama Atsushi , Matsubara Mio , Fukuda Yoshiko , Tanabe Naohiko , Parikh Ravi , Mabuchi Fumihiko , Kashiwagi Kenji , Iijima Hiroyuki 
Published: April 2020

AbstractIn the present study, we investigated the association between susceptible genetic variants to age-related macular degeneration (AMD) and response to as-needed intravitreal aflibercept injection (IAI) therapy for exudative AMD including both typical neovascular AMD and polypoidal choroidal vasculopathy (PCV) over 12-months. A total of 234 patients with exudative AMD were initially treated with 3 monthly IAI and thereafter as-needed IAI over 12 months. Seven variants of 6 genes including ARMS2 A69S (rs10490924), CFH (I62V:rs800292 and rs1329428), C2-CFB-SKIV2L(rs429608), C3 (rs2241394), CETP (rs3764261) and ADAMTS-9 (rs6795735) were genotyped for all participants using TaqMan technology. After adjusting for age, gender, baseline BCVA and AMD subtype, A (protective) allele of C2-CFB-SKIV2L rs429608 was associated with visual improvement at 12-month (P = 0.003). Retreatment was associated with T(risk) allele of ARMS2 A69S (P = 2.0 × 10−4; hazard ratio: 2.18:95%CI: 1.47-3.24) and C(risk) allele of CFH rs1329428 (P = 2.0 × 10−3; hazard ratio: 1.74:95%CI: 1.16–2.59) after adjusting for the baseline confounders. The need for additional injections was also associated with T allele of ARMS2 A69S (P = 1.0 × 10−5) and C allele of CFH rs1329428 (P = 3.0 × 10−3) after adjusting for the baseline confounders. The variants of ARMS2 and CFH are informative for both physicians and patients to predict recurrence and to quantify the need for additional injections.
44Ti ejecta in young supernova remnants
Authors: Weinberger Christoph , Diehl Roland , Pleintinger Moritz M. M. , Siegert Thomas , Greiner Jochen 
Published: April 2020

Context. Tracing unstable isotopes produced in supernova nucleosynthesis provides a direct diagnostic of supernova explosion physics. Theoretical models predict an extensive variety of scenarios, which can be constrained through observations of the abundant isotopes 56Ni and 44Ti. Direct evidence of the latter was previously found only in two core-collapse supernova events, and appears to be absent in thermonuclear supernovae.
Aims. We aim to to constrain the supernova progenitor types of Cassiopeia A, SN 1987A, Vela Jr., G1.9+0.3, SN1572, and SN1604 through their 44Ti ejecta masses and explosion kinematics.
Methods. We analyzed INTEGRAL/SPI observations of the candidate sources utilizing an empirically motivated high-precision background model. We analyzed the three dominant spectroscopically resolved de-excitation lines at 68, 78, and 1157 keV emitted in the decay chain of 44Ti→44Sc→44Ca. The fluxes allow the determination of the production yields of 44Ti. Remnant kinematics were obtained from the Doppler characteristics of the lines.
Results. We find a significant signal for Cassiopeia A in all three lines with a combined significance of 5.4σ. The fluxes are (3.3 ± 0.9) × 10−5 ph cm−2 s−1, and (4.2 ± 1.0) × 10−5 ph cm−2 s−1 for the 44Ti and 44Sc decay, respectively. This corresponds to a mass of (2.4 ± 0.7) × 10−4 M⊙ and (3.1 ± 0.8) × 10−4 M⊙, respectively. We obtain higher fluxes for 44Ti with our analysis of Cassiopeia A than were obtained in previous analyses. We discuss potential differences. We interpret the line width from Doppler broadening as expansion velocity of (6400 ± 1900) km s−1. We do not find any significant signal for any other candidate sources.
Conclusions. We obtain a high 44Ti ejecta mass for Cassiopeia A that is in disagreement with ejecta yields from symmetric 2D models. Upper limits for the other core-collapse supernovae are in agreement with model predictions and previous studies. The upper limits we find for the three thermonuclear supernovae (G1.9+0.3, SN1572 and SN1604) consistently exclude the double detonation and pure helium deflagration models as progenitors.
Cherchez votre clown ! Comment lever les freins à la relation soignant-soigné
Authors: Biaud Odile , Biaud Jean-Michel 
Published: April 2020

Pour nous, soignants désireux de proposer le meilleur soin à nos patients, il est primordial d’acquérir une capacité d’écoute afin de percevoir au mieux leurs besoins.
Des freins dans la relation soignants-soignés peuvent être le fait du soignant.
Parmi les différents moyens d’améliorer la qualité de la relation thérapeutique, le travail du clown peut être une approche intéressante, comme nous vous proposons de le découvrir.
Transanal Total Mesorectal Excision: Description of the Technique
Authors: Trépanier Jean-Sébastien , Lacy F. Borja de , Lacy Antonio M. 
Published: April 2020

AbstractSurgery remains the gold standard for the treatment of locally advanced rectal cancer. The most effective approach to reduce locoregional recurrence is total mesorectal excision (TME). However, obtaining an optimal TME is demanding, especially in low rectal tumors and anatomically unfavorable pelvis. Transanal TME (taTME) was developed to facilitate low pelvis dissection and potentially provide optimal outcomes for oncologic resection.Current studies have reported satisfactory short-term outcomes. However, taTME is a technically challenging procedure and must be learned in an appropriate training process to allow for a safe implementation. Previous experience in laparoscopic and transanal surgery is strongly recommended. In this work, we provide a detailed discussion of the technique, based on the realization of more than 400 taTME interventions.
Tips and Tricks
Authors: Albert Matthew , Lee Lawrence 
Published: April 2020

AbstractThe role of transanal total mesorectal excision (taTME) in minimally invasive proctectomy, especially rectal cancer surgery, is increasing. There has been exponential growth in uptake from the initial in vivo case in 2010 to the present day. Early adopters of taTME are well within the mature portions of their learning curve, but there are a significant number of novice taTME surgeons. We have overviewed the critical aspects of patient selection, operating room set-up, and necessary equipment. In particular, we recommend that a one-team approach is used for the early cases, and ideally with an experienced proctor. The important technical pearls that will aid the novice taTME surgeon were also described.
Persistent Left Superior Vena Cava Suggested by an Unusual Central Venous Pressure Waveform
Authors: Dontukurthy Sujana , Yamaguchi Yoshikazu , Tobias Joseph D. 
Published: April 2020

Abstract
Background A persistent left superior vena cava (PLSVC) is the most common congenital anomaly of the thoracic venous return.
Case Description During atrial septal defect repair, a pulmonary artery (PA) catheter was placed via the left internal jugular vein. Although placement of the PA catheter in the main PA was confirmed by transesophageal echocardiography, the central venous pressure (CVP) waveform was abnormal. Intraoperatively, the PA catheter was seen exiting the coronary sinus with the CVP port within the coronary sinus.
Conclusions The diagnosis of PLSVC is discussed and the differential diagnosis of the abnormal “ventricular” pattern of the CVP waveform is reviewed.
Internal Carotid Artery Dissection Treated with C-Guard Stent
Authors: Saal-Zapata Giancarlo , Durand Walter , Valer Dante , Rodríguez Rodolfo 
Published: April 2020

AbstractInternal carotid dissection is the most common cause of stroke in the young population. Stroke, the presence of a pseudoaneurysm, and decreased artery lumen with cerebral flow impairment are indications for treatment. Medical therapy with antithrombotic drugs and endovascular therapy with stenting are the main available options. The C-Guard stent is an open cell mesh-covered dual layer stent that has been mainly used in cases of internal carotid artery stenosis with a post-operative reduction in stroke incidence. Thus, we present two cases of internal carotid artery dissections of the cervical segment treated with the open cell dual-layer C-Guard stent without complications.