bluuebunny/crossref_metadata_2025_split huggingface dataset:
No wire? No problem: Resuscitative endovascular balloon occlusion of the aorta can be performed effectively and more rapidly with a wire-free device
Authors: Romagnoli Anna Noel , Teeter William , Wasicek Philip , Gamble William Bryan , Hu Peter , Stein Deborah , Scalea Thomas , Brenner Megan 
Published: June 2018

BACKGROUND
A wire-free device is available for resuscitative endovascular balloon occlusion of the aorta (REBOA) providing aortic occlusion (AO) without lengthy platform guide-wires and large sheaths.

METHODS
This was a retrospective, single-institution review of patients who received REBOA from May 2014 to September 2017. Timing of procedural steps was measured in seconds using time-stamped videography.

RESULTS
Seventy-four patients received REBOA: 29 with a platform guidewire, 12-Fr sheath, and balloon catheter (W group), and 45 with a 7-Fr sheath and wire-free device (WF group). Mean age (p = 0.22) and ISS (p = 0.80) were similar between groups. Fifty-nine patients received REBOA at Zone 1, 15 patients at Zone 3. There was no difference in median [interquartile range] time to common femoral artery (CFA) access between the WF (194 [98–313] seconds) and W (193 [126–280] seconds) groups (p = 0.96). Both median time to AO after CFA access (WF, 158 [109–264] seconds vs. W, 307 [222–390] seconds, p < 0.001) and median total procedural time (WF, 366 [263–596] seconds vs. W, 511 [441–597] seconds; p = 0.012) were significantly shorter with the wire-free system. The rates of percutaneous versus open CFA access was not different between groups (p = 0.48). Both groups had a similar physiologic response to AO as measured by pre- and post-AO SBP (p = 0.86). Overall mortality rate was 74%, 90% in the W group, and 64% in the WF group (p = 0.027). The procedure-related complication rate was not significantly different between groups with regard to compartment syndrome (W, 3% vs. WF, 4%, p = 1.0), access-related complications (W, 0 vs. WF, 6%, p = 0.28), or systemic complication (W, 0 vs. WF, 9%, p = 0.15).

CONCLUSION
Once CFA access is obtained, AO with a smaller wire-free device reduces procedural time by approximately 50%. When perfusion to proximal organs is essential, the seconds saved to achieve AO may contribute to improved mortality. Time to obtain CFA access is not dependent on introducer sheath size.

LEVEL OF EVIDENCE
Therapeutic, level V.
Transcranial Direct Current Stimulation in the Acute Depressive Episode
Authors: Borrione Lucas , Moffa Adriano H. , Martin Donel , Loo Colleen K. , Brunoni Andre R. 
Published: June 2018

Abstract
Major depressive disorder is a severe, refractory mental disorder. Only one third of patients treated with antidepressants achieve remission after 3 trials, while subject to adverse effects. Therefore, the investigation of alternative treatments is paramount. The aim of this systematic review was to summarize the most recent evidence of transcranial direct current stimulation (tDCS) intervention for the acute phase of major depressive disorder. A PubMed search was performed including the terms “transcranial direct current stimulation” OR “transcranial direct stimulation” OR “tDCS” AND “major depressive disorder” OR “major depression” OR “depression” AND “trial.” The search was conducted from inception until February 2018. Our search yielded initially 165 results, and 14 randomized clinical trials were included according to eligibility criteria. Most studies were pilot studies, with mixed findings. Two large randomized clinical trials recently published also presented primary negative findings. Study protocols usually used anodal left/cathodal right dorsolateral prefrontal cortex stimulation, 1 to 2.5 mA, and 5 to 20 tDCS sessions. We discuss the limitations of the included trials, such as sample and tDCS parameters heterogeneity between studies. To conclude, tDCS seems to be safe and devoid of serious adverse effects, although robust efficacy has not been consistently demonstrated in clinical trials assessing an acute treatment course of up to 4 weeks. Further directions are discussed, such as parameter individualization, investigation of biological markers, and home-use tDCS.
Let’s talk about cardiac T1 mapping
Authors: Hafyane Tarik , Karakuzu Agah , Duquette Catherine , Mongeon François-Pierre , Cohen-Adad Julien , Jerosch-Herold Michael , Friedrich Matthias G. , Stikov Nikola 
Published: June 2018

ABSTRACTBackgroundRecent reports have shown that T1 mapping sequences agree in phantoms, but exhibit significant differences in vivo. To characterize these differences in the heart, one needs to consider the effects of magnetization transfer (MT) and the T2 relaxation time in the most commonly used cardiac T1 mapping sequences (MOLLI, ShMOLLI and SASHA).MethodsSix explanted pig hearts were scanned weekly over a period of six weeks on a 3T system with the MOLLI, ShMOLLI, SASHA sequences and an inversion recovery sequence as reference. The T1 bias was computed as the difference between MOLLI, ShMOLLI, SASHA and the reference T1 values. We applied robust correlation statistics to assess the relationships between T1, T2 and MT. All data are publicly available at: http://neuropoly.pub/pigHeartsData.ResultsA systematic T1 bias was present for all sequences, with MOLLI and ShMOLLI underestimating T1 and SASHA slightly overestimating T1 compared to the reference. The correlation of T1 bias with T2 was weak and insignificant. However, MT showed significant associations with T1 bias for all sequences. Our analysis is also available at: http://neuropoly.pub/pigHeartsInteractive.ConclusionWe investigated cardiac T1 mapping sequences in a setting that allowed us to explore their accuracy and their dependence on T2 and MT effects. The T2 effects were not significant, and could not explain the T1 bias of MOLLI, ShMOLLI, SASHA with respect to the reference. On the other hand, the T1 biases exhibited a strong correlation with MT. We conclude that inaccuracies in cardiac T1 mapping are primarily due to magnetization transfer.
New genetic signals for lung function highlight pathways and pleiotropy, and chronic obstructive pulmonary disease associations across multiple ancestries
Authors: Shrine Nick , Guyatt Anna L , Erzurumluoglu A Mesut , Jackson Victoria E , Hobbs Brian D , Melbourne Carl , Batini Chiara , Fawcett Katherine A , Song Kijoung , Sakornsakolpat Phuwanat , Li Xingnan , Boxall Ruth , Reeve Nicola F , Obeidat Ma’en , Zhao Jing Hua , Wielscher Matthias , Society Scientific Group Understanding , Weiss Stefan , Kentistou Katherine A , Cook James P , Sun Benjamin B , Zhou Jian , Hui Jennie , Karrasch Stefan , Imboden Medea , Harris Sarah E , Marten Jonathan , Enroth Stefan , Kerr Shona M , Surakka Ida , Vitart Veronique , Lehtimäki Terho , Allen Richard J , Bakke Per S , Beaty Terri H , Bleecker Eugene R , Bossé Yohan , Brandsma Corry-Anke , Chen Zhengming , Crapo James D , Danesh John , DeMeo Dawn L , Dudbridge Frank , Ewert Ralf , Gieger Christian , Gulsvik Amund , Hansell Anna L , Hao Ke , Hoffman Josh D , Hokanson John , Homuth Georg , Joshi Peter K , Joubert Philippe , Langenberg Claudia , Li Xuan , Li Liming , Lin Kuang , Lind Lars , Locantore Nick , Luan Jian’an , Mahajan Anubha , Maranville Joseph C , Murray Alison , Nickle David C , Packer Richard , Parker Margaret M , Paynton Megan L , Porteous David , Prokopenko Dmitry , Qiao Dandi , Rawal Rajesh , Runz Heiko , Sayers Ian , Sin Don D , H Smith Blair , Artigas María Soler , Sparrow David , Tal-Singer Ruth , Timmers Paul RHJ , Van den Berge Maarten , Whittaker John C , Woodruff Prescott , M Yerges Armstrong Laura , Troyanskaya Olga G , Raitakari Olli T , Kähönen Mika , Polasek Ozren , Gyllensten Ulf , Rudan Igor , Deary Ian J , Probst-Hensch Nicole M , Schulz Holger , James Alan L , Wilson James F , Stubbe Beate , Zeggini Eleftheria , Jarvelin Marjo-Riitta , Wareham Nick , Silverman Edwin K , Hayward Caroline , Morris Andrew P , Butterworth Adam S , Scott Robert A , Walters Robin G , Meyers Deborah A , Cho Michael H , Strachan David P , Hall Ian P , Tobin Martin D , Wain Louise V 
Published: June 2018

AbstractReduced lung function predicts mortality and is key to the diagnosis of COPD. In a genome-wide association study in 400,102 individuals of European ancestry, we define 279 lung function signals, one-half of which are new. In combination these variants strongly predict COPD in deeply-phenotyped patient populations. Furthermore, the combined effect of these variants showed generalisability across smokers and never-smokers, and across ancestral groups. We highlight biological pathways, known and potential drug targets for COPD and, in phenome-wide association studies, autoimmune-related and other pleiotropic effects of lung function associated variants. This new genetic evidence has potential to improve future preventive and therapeutic strategies for COPD.
Amot regulates neuronal dendritic tree through Yap1
Authors: Rojek Katarzyna O. , Krzemień Joanna , Doleżyczek Hubert , Boguszewski Paweł M. , Kaczmarek Leszek , Konopka Witold , Rylski Marcin , Jaworski Jacek , Holmgren Lars , Prószyński Tomasz J. 
Published: June 2018

ABSTRACTThe Amot-Yap1 complex plays a major role in the regulation of cell contact inhibition, cellular polarity and growth. However, the function of Angiomotin (Amot) and Hippo pathway transcription co-activator Yap1 in the central nervous system remains unclear. In this study, we demonstrate that Amot is a critical mediator of dendritic morphogenesis in cultured hippocampal cells and Purkinje cells in the brain. Amot function in developing hippocampal neurons depends on interactions with Yap1, which is also indispensable for dendrite growth and arborization in vitro. Conditional deletion of Amot or Yap1 in neurons leads to impaired morphogenesis of Purkinje cell dendritic trees, decreased cerebellar size, and causes defects in locomotor coordination of mutant animals. Thus, our studies identified Amot and Yap1 as novel regulators of dendritic tree morphogenesis.
Trophic interaction modifications disrupt the structure and stability of food webs
Authors: Terry J. Christopher D. , Morris Rebecca J. , Bonsall Michael B. 
Published: June 2018

AbstractTrophic interaction modifications, where a consumer-resource interaction is influenced by an additional species, are established as being prevalent throughout ecological networks. Despite this, their influence on the structure of interaction distributions within communities has not yet been examined. Although empirical information about the distribution of interaction modifications is currently sparse, the non-trophic effects they induce will be structured by the underlying network of trophic interactions. Here we test the impact of interaction modifications, introduced under a range of distributional assumptions to artificial and empirical trophic networks, on the overall structure of interactions within communities. We show that local stability and reactivity is critically dependent on the inter-relationship between the trophic and non-trophic effects. Depending on their distribution, interaction modifications can generate significant additional structure to community interactions making analyses of the stability of ecological systems based solely on trophic networks unreliable. Empirical information on the topological and strength distributions of interaction modifications will be a key part of understanding the dynamics of communities.
Getting there and staying there: supporting and enabling persistent human life on Mars using synthetic natural rubber, self-healing materials, and biological batteries
Authors: Acharya Nischal , Baker Natalie , Bravo Marilu Krystal , Gu Katie , Harken Sierra , Herschl Michael Howland , Petersen Addie , Pirozzi Ileana , Spangle Dylan , Sun Gordon , Vuong Brian , Averesch Nils J.H. , Fujishima Kosuke , Kalkus Trevor! J. , Rogers Kara J. Helmke , Rothschild Lynn J. 
Published: June 2018

AbstractPlanetary exploration requires a balance between preemptive planning and financial feasibility. The risk of mid-mission equipment failure, power shortages, or supply depletion incentivizes precautionary measures, but the financial strain of sending unnecessary mass into space limits this practice.To balance the two, our team explored the advantages of biological solutions, namely the self-sustaining abilities of low-mass organisms, to make planetary exploration more self-sufficient and economical. Prioritizing repair over replacement, we are developing self-healing materials embedded with Bacillus subtilis. For longer-lasting energy, we are designing a “biobactery” using linearly oriented Escherichia coli to generate power. For renewable materials, we are engineering bacteria to synthesize and degrade rubber. Individually, these projects offer sustainable alternatives for repair, power, and materials. But when combined, these consolidated insights can provide us with the power to get to Mars and resources to sustain us while we’re there.
Impaired hematopoiesis and leukemia development in mice with a conditional “knock-in” allele of a mutant splicing factor geneU2af1
Authors: Fei Dennis Liang , Zhen Tao , Durham Benjamin , Ferrarone John , Zhang Tuo , Garrett Lisa , Yoshimi Akihide , Abdel-Wahab Omar , Bradley Robert K. , Liu Paul , Varmus Harold 
Published: June 2018

ABSTRACTMutations affecting the spliceosomal protein U2AF1 are commonly found in myelodysplastic syndromes (MDS) and secondary acute myeloid leukemia (sAML). We have generated mice that carry Cre-dependent “knock-in” alleles ofU2af1(S34F), the murine version of the most common mutant allele ofU2AF1encountered in human cancers. Cre-mediated recombination in murine hematopoietic lineages caused changes in RNA splicing, as well as multilineage cytopenia, macrocytic anemia, decreased hematopoietic stem and progenitor cells, low-grade dysplasias, and impaired transplantability, but without lifespan shortening or leukemia development. In an attempt to identifyU2af1(S34F)-cooperating changes that promote leukemogenesis, we combinedU2af1(S34F) withRunx1deficiency in mice and further treated the mice with a mutagen, N-Ethyl-N-Nitrosourea (ENU). Overall, three of sixteen ENU-treated compound transgenic mice developed AML. However, AML did not arise in mice with other genotypes or without ENU treatment. Sequencing DNA from the three AMLs revealed somatic mutations homologous to those considered to be drivers of human AML, including predicted loss-or gain-of-function mutations inTet2, Gata2, Idh1, andIkzfl.However, the engineeredU2af1(S34F)missense mutation reverted to wild type (WT) in two of the three AML cases, implying thatU2af1(S34F) is dispensable, or even selected against, once leukemia is established.SIGNIFICANCE STATEMENTSomatic mutations in four splicing factor genes (U2AF1, SRSF2, SF3B1, andZRSR2) are found in MDS and MDS-related AML, blood cancers with few effective treatment options. However, the pathophysiological effects of these mutations remain poorly characterized, in part due to the paucity of disease-relevant models. Here, we report the establishment of mouse models to study the most commonU2AF1mutation,U2af1(S34F). Production of the mutant protein specifically in the murine hematopoietic compartment disrupts hematopoiesis in ways resembling human MDS. We further identified deletion of theRunx1gene and other known oncogenic mutations as changes that might collaborate withU2af1(S34F) to give rise to frank AML in mice.
Febrile temperatures increase in vitro antibody affinity for malaria and dengue antigens
Authors: Stan Razvan C. , Françoso Katia S. , Alves Rubens P.S. , Ferreira Luís Carlos S. , Soares Irene S. , de Camargo Maristela M. 
Published: June 2018

AbstractFever is a regulated elevation in the body setpoint temperature and may arise as a result of infectious and noninfectious causes. While beneficial in modulating immune responses to infection, the potential of febrile temperatures in regulating antigen binding affinity to antibodies has not been explored. We have investigated this process under in vitro conditions using selected malaria or dengue antigens and specific monoclonal antibodies, and observed a marked increase in the affinity of these antibody-antigen complexes at 40°C, compared to physiological (37°C) or pathophysiological temperatures (42°C). Induced thermal equilibration of the protein partners at these temperatures, prior to measurements, further increased their binding affinity. These results may indicate an unexpected beneficial and adaptive role for fever in vivo, and highlight the positive role of thermal priming in enhancing protein-protein affinity for samples of scarce availability.
Segmentation of Glomeruli Within Trichrome Images Using Deep Learning
Authors: Kannan Shruti , Morgan Laura A. , Liang Benjamin , Cheung McKenzie G. , Lin Christopher Q. , Mun Dan , Nader Ralph G. , Belghasem Mostafa E. , Henderson Joel M. , Francis Jean M. , Chitalia Vipul C. , Kolachalama Vijaya B. 
Published: June 2018

ABSTRACTIntroductionThe number of glomeruli and glomerulosclerosis evaluated on kidney biopsy slides constitute as standard components of a renal pathology report. Prevailing methods for glomerular assessment remain manual, labor intensive and non-standardized. We developed a deep learning framework to accurately identify and segment glomeruli from digitized images of human kidney biopsies.MethodsTrichrome-stained images (n=275) from renal biopsies of 171 chronic kidney disease patients treated at the Boston Medical Center from 2009-12 were analyzed. A sliding window operation was defined to crop each original image to smaller images. Each cropped image was then evaluated by three experts into three categories: (a) No glomerulus, (b) Normal or partially sclerosed glomerulus and (c) Globally sclerosed glomerulus. This led to identification of 751 unique images representing non­glomerular regions, 611 images with either normal or partially sclerosed (NPS) glomeruli and 134 images with globally sclerosed (GS) glomeruli. A convolutional neural network (CNN) was trained with cropped images as inputs and corresponding labels as output. Using this model, an image processing routine was developed to scan the test data images to segment the GS glomeruli.ResultsThe CNN model was able to accurately discriminate non-glomerular images from NPS and GS images (Performance on test data - Accuracy: 92.67±2.02% and Kappa: 0.8681±0.0392). The segmentation model that was based on the CNN multi-label classifier accurately marked the GS glomeruli on the test data (Matthews correlation coefficient = 0.628).ConclusionThis work demonstrates the power of deep learning for assessing complex histologic structures from digitized human kidney biopsies.
Poor codon optimality as a signal to degrade transcripts with frameshifts
Authors: Schikora-Tamarit Miquel Àngel , Carey Lucas B. 
Published: June 2018

AbstractLiving organisms are error-prone. Every second a single human cell produces over 100 transcripts with a substitution, frameshift or splicing error. Multiple mRNA quality control pathways exist to degrade these transcripts. Many of these pathways involve co-translational regulation of mRNA stability, such as nonsense mediated decay (NMD) and reduced stability of transcripts with suboptimal codon usage. Recent work has shown the existence of a genetic link between NMD and codon-usage mediated mRNA decay. Here we present new computational evidence that, because the codons following most frameshift errors are suboptimal, removal of mRNAs with such errors may be mediated by degradation of mRNAs with sub-optimal codons. Thus, most transcripts that contain frameshifts are subject to two modes of degradation.Author summaryFrameshifting errors are common and mRNA quality control pathways, such as nonsense-mediated decay (NMD), exist to degrade these aberrant transcripts. Recent work has shown the existence of a genetic link between NMD and codon-usage mediated mRNA decay. Here we present computational evidence that these pathways are synergic for removing frameshifts.
Diverse motif ensembles specify non-redundant DNA binding activities of AP-1 family members in macrophages
Authors: Fonseca Gregory J. , Tao Jenhan , Westin Emma M. , Duttke Sascha H. , Spann Nathanael J. , Strid Tobias , Shen Zeyang , Stender Joshua D. , Link Verena M. , Benner Christopher , Glass Christopher K. 
Published: June 2018

ABSTRACTMechanisms by which members of the AP-1 family of transcription factors play both redundant and non-redundant biological roles despite recognizing the same DNA sequence remain poorly understood. To address this question, we investigated the molecular functions and genome-wide DNA binding patterns of AP-1 family members in macrophages. ChIP-sequencing showed overlapping and distinct binding profiles for each factor that were remodeled following TLR4 ligation. Development of a machine learning approach that jointly weighs hundreds of DNA recognition elements yielded dozens of motifs predicted to drive factor-specific binding profiles. Machine learning-based predictions were confirmed by analysis of the effects of mutations in genetically diverse mice and by loss of function experiments. These findings provide evidence that non-redundant genomic locations of different AP-1 family members in macrophages largely result from collaborative interactions with diverse, locus-specific ensembles of transcription factors and suggest a general mechanism for encoding functional specificities of their common recognition motif.
Cerebrovascular Injuries Induce Lymphatic Invasion into Brain Parenchyma to Guide Vascular Regeneration in Zebrafish
Authors: Chen Jingying , He Jianbo , Yang Qifen , Zhang Yaoguang , Luo Lingfei 
Published: June 2018

SUMMARYDamage to regional cerebrovascular network and neuronal tissues occurs during acute cerebrovascular diseases, such as ischemic stroke. The promotion of vascular regeneration is the most promising therapeutic approach. To understand cellular and molecular mechanisms underlying brain vascular regeneration, we developed two zebrafish cerebrovascular injury models using genetic ablation and photochemical thrombosis. Although brain parenchyma is physiologically devoid of lymphatic vasculature, we found that cerebrovascular injuries induce rapid ingrowth of meningeal lymphatics into the injured parenchyma. The ingrown lymphatics on one hand become lumenized drain interstitial fluid to resolve brain edema, on the other hand act as “growing tracks” for nascent blood vessels. The ingrown lymphatic vessels undergo apoptosis and clearance after cerebrovascular regeneration. This study reveals a pathological function of meningeal lymphatics, through previously unexpected ingrowth into brain parenchyma and a newly identified lymphatic function as vascular “growing tracks”.HIGHLIGHTSCerebrovascular injuries induce lymphatic ingrowth into the injured brain parenchyma The ingrown lymphatics drain interstitial fluid to resolve brain edema Nascent blood vessels use the ingrown lymphatic vessels as “growing tracks” The ingrown lymphatic vessels undergo apoptosis after vascular regeneration completes