bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cold Pulsatile Machine Perfusion Versus Static Cold Storage for Kidneys Donated After Circulatory Death: A Multicenter Randomized Controlled Trial
Authors: Summers Dominic M. , Ahmad Niaz , Randle Lucy V. , O’Sullivan Ann-Marie , Johnson Rachel J. , Collett David , Attia Magdy , Clancy Marc , Tavakoli Afshin , Akyol Murat , Jamieson Neville V. , Bradley J. Andrew , J.E. Watson Christopher 
Published: August 2019

Background.
The benefits of cold pulsatile machine perfusion (MP) for the storage and transportation of kidneys donated after circulatory death are disputed. We conducted a UK-based multicenter, randomized controlled trial to compare outcomes of kidneys stored with MP versus static cold storage (CS).

Methods.
Fifty-one pairs of kidneys donated after circulatory death were randomly allocated to receive static CS or cold pulsatile MP. The primary endpoint, delayed graft function, was analyzed by “intention-to-treat” evaluation.

Results.
There was no difference in the incidence of delayed graft function between CS and MP (32/51 (62.8%) and 30/51 (58.8%) P = 0.69, respectively), although the trial stopped early due to difficulty with recruitment. There was no difference in the incidence of acute rejection, or in graft or patient survival between the CS and MP groups. Median estimated glomerular filtration rate at 3 months following transplantation was significantly lower in the CS group compared with MP (CS 34 mL/min IQR 26–44 vs MP 45 mL/min IQR 36–60, P = 0.006), although there was no significant difference in estimated glomerular filtration rate between CS and MP at 12 months posttransplant.

Conclusions.
This study is underpowered, which limits definitive conclusions about the use of MP, as an alternative to static CS. It did not demonstrate that the use of MP reduces the incidence of delayed graft function in donation after circulatory death kidney transplantation.
Listening difficulties in children: Behavior and brain activation produced by dichotic listening of CV syllables
Authors: Moore David R. , Hugdahl Kenneth , Stewart Hannah J. , Vannest Jennifer , Perdew Audrey J. , Sloat Nicholette T. , Cash Erin , Hunter Lisa L 
Published: August 2019

AbstractListening difficulties (LiD), also known as auditory processing disorders, are common in children with and without hearing loss. Impaired interactions between the two ears have been proposed as an important component of LiD. Previous studies have focused on testing using multiple sequential dichotic digits that carry a substantial memory load and executive control demands. We examined the ability of 6-13 year old children with normal audiometric thresholds to identify and selectively attend to dichotically presented CV syllables using the Bergen Dichotic Listening Test (BDLT;www.dichoticlistening.com). Children were recruited as typically developing (TD; n=39) or having LiD (n=35) based primarily on composite score of the ECLiPS caregiver report. Different single syllables (ba, da, ga, pa, ta, ka) were presented simultaneously to each ear (6×36 trials). Children reported the syllable heard most clearly (non-forced, NF) or the syllable presented to the right (forced, FR) or left (FL) ear. Interaural level differences (ILDs) manipulated bottom-up perceptual salience. Dichotic listening data (correct responses, Laterality Index) were analyzed initially by group (LiD, TD), age, report method (NF, FR, FL) and ILD (0, ± 15 dB) and compared with speech-in-noise thresholds (LiSN-S) and cognitive performance (NIH Toolbox). fMRI measured brain activation produced by a receptive speech task that segregated speech, phonetic and intelligibility components. Some activated areas (planum temporale, inferior frontal gyrus and orbitofrontal cortex) were correlated with dichotic results in TD children only.Neither group, age nor report method affected the Laterality Index of right/left recall. However, a significant interaction was found between ear, group and ILD. Children with LiD were more influenced by large ILDs, especially favoring the left ear, than were TD children. Neural activity associated with Speech, Phonetic and Intelligibility sentence cues did not significantly differ between groups. Significant correlations between brain activity level and BDLT were found in several frontal and temporal locations for the TD but not for the LiD group.Children with LiD were more influenced by large ILDs, especially favoring the left ear, than were TD children and were thus less able to modulate performance through attention, and more driven by the physical properties of the acoustic stimuli.
Genetic and molecular mechanism for distinct clinical phenotypes conveyed by allelic truncating mutations implicated in FBN1
Authors: Lin Mao , Liu Zhenlei , Liu Gang , Zhao Sen , Li Chao , Chen Weisheng , Akdemir Zeynep Coban , Lin Jiachen , Song Xiaofei , Wang Shengru , Xu Qiming , Zhao Yanxue , Wang Lianlei , Zhang Yuanqiang , Yan Zihui , Liu Sen , Liu Jiaqi , Chen Yixin , Yang Xu , Sun Tianshu , Yang Xin-Zhuang , Niu Yuchen , Li Xiaoxin , You Wesley , Qiu Bintao , Ding Chen , Liu Pengfei , Zhang Shuyang , Carvalho Claudia M. B. , Posey Jennifer E. , Qiu Guixing , Lupski James R. , Wu Zhihong , Zhang Jianguo , Wu Nan ,   on behalf of the Deciphering Disorders Involving Scoliosis and COmorbidities (DISCO) study
Published: August 2019

AbstractThe molecular and genetic mechanisms by which different single nucleotide variant (SNV) alleles in specific genes, or at the same genetic locus, bring about distinct disease phenotypes often remain unclear. Allelic truncating mutations of fibrillin-1(FBN1) cause either classical Marfan syndrome (MFS) or a more severe phenotype associated with Marfanoid-progeroid-lipodystrophy syndrome (MPLS). A total of three Marfan syndrome/Marfanoid patients (2 singletons and 1 parent-offspring trio) were recruited. Targeted next-generation sequencing was performed on all the participants. We analyzed the molecular diagnosis, patient clinical features, and the potential molecular mechanism involved in the MPLS subject in our cohort. We investigated a small cohort, consisting of two classical MFS and one MPLS patient from China, whose clinical presentation included scoliosis potentially requiring surgical intervention. We provide evidence that most nonsense and frameshift mutations lead to FBN1 null alleles due to mutant mRNA transcript degradation. In contrast, the more severe disease phenotype, MPLS, is caused by mutant mRNAs that are predicted to escape the nonsense mediated decay (NMD) surveillance pathway, making a mutant protein that exerts a dominant negative interference effect to FBN1 thus generating a gain-of-function (GoF) rather than a loss-of-function (LoF) allele as in MFS. Overall, we provide direct evidence that a dominant negative interaction of FBN1 potentially explains the distinct clinical phenotype in MPLS patients through genetic and functional analysis of the first Chinese patient with MPLS. Moreover, our study expands the mutation spectrum of FBN1 and highlights the potential molecular mechanism for MPLS patients.
An altered metabolism could contribute to the low activation of neonatal CD8+T cells
Authors: Antonio Sánchez-Villanueva José , Otoniel Rodríguez-Jorge , Oscar Ramírez-Pliego , Gabriela Rosas Salgado , Wassim Abou-Jaoudé , Céline Hernandez , Aurélien Naldi , Denis Thieffry , Angélica Santana María 
Published: August 2019

AbstractA low response of neonatal T cells to infections contributes to a high incidence of morbidity and mortality of neonates. Here we evaluated the impact of the cytoplasmic and mitochondrial levels of Reactive Oxygen Species (ROS) of adult and neonatal CD8+T cells on their activation potential. We further constructed a logical model to decipher the interplay of metabolism and ROS on T cell signaling. Our model captures the interplay between antigen recognition, ROS and metabolic status in T cell responses. This model displays alternative stable states corresponding to different cell fates, i.e. quiescent, activated and anergic states, depending on ROS status. Stochastic simulations with this model further indicate that differences in ROS status at the cell population level tentatively explain the lower activation rate of neonatal compared to adult CD8+T cells upon TCR engagement.
Cortical excitation-inhibition ratio mediates the effect of pre-attentive auditory processing deficits on interpersonal difficulties
Authors: Ford Talitha C. , Woods Will , Enticott Peter G. , Crewther David P. 
Published: August 2019

AbstractSeveral lines of evidence identify aberrant excitatory-inhibitory neural processes across autism and schizophrenia spectrum disorders, particularly within the psychosocial domain. Such neural processes include increased excitatory glutamate and reduced inhibitory GABA concentrations, which may affect auditory pre-attentive processing as indexed by the mismatch negativity (MMN); thus, an excitation-inhibition imbalance might lead to aberrant MMN, which might in turn drive the relationship between the MMN and psychosocial difficulties. This research has the potential to enhance the neurochemical understanding of the relationship between electrophysiology (MMN) and behavioural/clinical measures (psychosocial difficulties).Thirty-eight adults (18 male, 18-40 years) completed the Schizotypal Personality Questionnaire (SPQ) and Autism-Spectrum Quotient (AQ). Glutamate and GABA concentrations in bilateral superior temporal cortex (STC) were quantified using proton magnetic resonance spectroscopy (1H-MRS) while auditory MMN to a duration deviant was measured with magnetoencephalography. Spearman correlations probed the relationships between STC glutamate/GABA ratios, MMN amplitude and latency, and AQ and SPQ dimensions. Mediation effects of glutamate/GABA ratios on the relationship between MMN and AQ-SPQ dimensions were probed using causal mediation analysis.Only SPQ-interpersonal and AQ-communication were significantly correlated with right hemisphere glutamate/GABA ratios and MMN latency (ps<.05), which were themselves correlated (p=.038). Two mediation models were investigated, with right MMN latency as predictor and SPQ-interpersonal and AQ-communication as outcome variables. Right STC glutamate/GABA ratios significantly mediated the relationship between MMN latency and SPQ-interpersonal scores (ß=86.6, p=.033), but only partially mediated the relationship between MMN latency and AQ-communication scores (ß=21.0, p=.093).These findings support the growing body of literature pointing toward an excitation-inhibition imbalance that is central to psychosocial functioning across multi-dimensional spectrum disorders, such as autism and schizophrenia, and provides neurochemical indicators of the processes that underlie psychosocial dysfunction.
Impact of global warming on insects: are tropical species more vulnerable than temperate species?
Authors: Johansson Frank , Orizaola Germán , Nilsson-Örtman Viktor 
Published: August 2019

AbstractThe magnitude and ecological impact of climate change varies with latitude. Several recent models have shown that tropical ectotherms face the greatest risk from warming because they currently experience temperatures much closer to their physiological optimum than temperate taxa. Even a small increase in temperature may thus result in steep fitness declines in tropical species but increased fitness in temperate species. This prediction, however, is based on a model that does not account for latitudinal differences in activity periods. Temperate species in particular may often experience considerably higher temperatures than expected during the active season. Here, we integrate data on insect warming tolerance and temperature-dependent development to re-evaluate latitudinal trends in thermal safety margins after accounting for latitudinal trends in insect seasonal activity. Our analyses suggest that temperate and tropical species differ far less in thermal safety margins than commonly assumed, and thus face a similar risk from warming.
COUP-TFI/Nr2f1 orchestrates intrinsic neuronal activity during cortical area patterning
Authors: del Pino Isabel , Tocco Chiara , Magrinelli Elia , Marcantoni Andrea , Ferraguto Celeste , Tomagra Giulia , Bertacchi Michele , Alfano Christian , Leinekugel Xavier , Frick Andreas , Studer Michèle 
Published: August 2019

ABSTRACTThe formation of functional cortical maps in the cerebral cortex results from a timely regulated interaction between intrinsic genetic mechanisms and electrical activity. To understand how transcriptional regulation influences network activity and neuronal excitability within the neocortex, we used mice deficient for the area mapping gene Nr2f1 (also known as COUP-TFI), a key determinant of somatosensory area specification during development. We found that cortical loss of Nr2f1 impacts on spontaneous network activity and synchronization at perinatal stages. In addition, we observed alterations in the intrinsic excitability and morphological features of layer V pyramidal neurons. Accordingly, we identified distinct voltage-gated ion channels regulated by Nr2f1 that might directly influence intrinsic bioelectrical properties during critical time windows of somatosensory cortex specification. Together, our data suggest a tight link between Nr2f1 and neuronal excitability in the developmental sequence that ultimately sculpts the emergence of cortical network activity within the immature neocortex.
Distinct neurocomputational mechanisms support informational and normative conformity
Authors: Mahmoodi Ali , Nili Hamed , Bang Dan , Mehring Carsten , Bahrami Bahador 
Published: August 2019

AbstractA change of mind in response to social influence could be driven by informational conformity to increase accuracy, or by normative conformity to comply with social norms such as reciprocity. Disentangling the behavioural, cognitive and neurobiological underpinnings of informational and normative conformity have proven elusive. Here, participants underwent fMRI while performing a perceptual task that involved both advice-taking and advice-giving to human and computer partners. The concurrent inclusion of two different social roles and two different social partners revealed distinct behavioural and neural markers for informational and normative conformity. dACC BOLD response tracked informational conformity towards both human and computer but tracked normative conformity only when interacting with human. A network of brain areas (dmPFC and TPJ) that tracked normative conformity increased their functional coupling with the dACC when interacting with humans. These findings enable differentiating the neural mechanisms by which different types of conformity shape social changes of mind.
Development and validation of a multidimensional composite pain scale for Rabbit (CANCRS) in a clinical environment
Authors: Banchi Penelope , Quaranta Giuseppe , Ricci Alessandro , Degerfeld Mitzy Mauthe von 
Published: August 2019

AbstractThe main objective of this study was to develop a multidimensional composite pain scale for assessing and quantifying pain in rabbits (CANCRS); to this purpose, Rabbit Grimace Scale (RbtGS) and a scale including clinical parameters (CPS) were merged; the two scales performances were also evaluated individually, in order to validate RbtGS in a clinical setting and to verify clinical parameters usefulness in detecting pain.Rabbits (n=116) were evaluated by two raters, who could be veterinarians (V) or veterinary medicine students (S). Raters were asked to report the time needed for any evaluation and a total score, in order to define a pain class. Pain classes (No pain, Discomfort, Moderate pain and Severe pain) matched presumptive pain classes and accordingly, the validity of the three scales was measured using Chi-square test.Patients (n=69) were evaluated by one V and one S, allowing to assess the impact that the experience has on the results. Inter-rater reliability was tested for each scale using intra-class correlation coefficient (ICC) and for each parameter of the CANCRS using Cohen’s kappa. Validity results show that only CANCRS and RbtGS efficiently reveal pain, but both tend to underestimate it.Inter-rater reliability was very good for both CANCRS and CPS, suggesting that experience has little influence on the results; rater’s experience has a greater impact using RbtGS.Inter-rater agreement was at least good for each parameter.In conclusion, CPS alone is neither effective or reliable in quantifying pain.The RbtGS is a useful tool in clinical practice, when coping with many rabbit breeds; however, training is beneficial for a better use of the scale.The CANCRS is easy and fast to use and enrich RbtGS with some clinical parameters that should be monitored during any clinical examination, leading to a more exhaustive evaluation of the patient.
A highly parallel, automated platform enabling individual or sequential ChIP of histone marks and transcription factors
Authors: Dainese Riccardo , Gardeux Vincent , Llimos Gerard , Alpern Daniel , Jiang Jia Yuan , Alves Meireles-Filho Antonio Carlos , Deplancke Bart 
Published: August 2019

AbstractDespite its popularity, chromatin immunoprecipitation followed by sequencing (ChIP-seq) remains a tedious (>2d), manually intensive, low-sensitivity and low-throughput approach. Here, we combine principles of microengineering, surface chemistry and molecular biology to address the major limitations of standard ChIP-seq. The resulting approach, FloChIP, automates and miniaturizes ChIP in a beadless fashion while facilitating the downstream library preparation process through on-chip chromatin tagmentation. FloChIP is fast (<2h), has a wide dynamic range (from 106 to 500 cells), is high-throughput (up to 64 parallel, antibody- or sample-multiplexed experiments) and is compatible with both histone mark and transcription factor ChIP. In addition, FloChIP’s interconnected design allows for straightforward chromatin re-immunoprecipitation, thus constituting the first example of a microfluidic sequential ChIP-seq system. Finally, we demonstrate FloChIP’s high-throughput capacity by performing ChIP-seq of the transcription factor MEF2A in 32 distinct human lymphoblastoid cell lines, providing novel insights into the main factors driving collaborative DNA binding of MEF2A and into its role in B-cell-specific gene regulation. Together, our results validate FloChIP as a flexible and reproducible automated solution for individual or sequential ChIP-seq.
Lipid digestion and autophagy are critical energy providers during acute glucose depletion in Saccharomyces cerevisiae
Authors: Weber Carmen A. , Sekar Karthik , Tang Jeffrey H. , Warmer Philipp , Sauer Uwe , Weis Karsten 
Published: August 2019

AbstractThe ability to tolerate and thrive in diverse environments is paramount to all living organisms, and many organisms spend a large part of their lifetime in starvation. Upon acute glucose starvation, yeast cells undergo drastic physiological and metabolic changes and reestablish a constant - though lower – level of energy production within minutes. The molecules that are rapidly metabolized to fuel energy production under these conditions are unknown. Here, we combine metabolomics and genetics, to characterize the cells’ response to acute glucose depletion and identify pathways that ensure survival during starvation. We show that the ability to respire is essential for maintaining the energy status and to ensure viability during starvation. Measuring the cells’ immediate metabolic response, we find that central metabolites drastically deplete and that the intracellular AMP to ATP ratio strongly increases within 20-30 seconds. Furthermore, we detect changes in both amino acid and lipid metabolite levels. Consistent with this, bulk autophagy, a process that frees amino acids, as well as lipid degradation via β-oxidation contribute in parallel to energy maintenance upon acute starvation. In addition, both these pathways ensure long-term survival during starvation. Thus, our results identify bulk autophagy and β-oxidation as important energy providers during acute glucose starvation.
BactMAP: an R package for integrating, analyzing and visualizing bacterial microscopy data
Authors: van Raaphorst Renske , Kjos Morten , Veening Jan-Willem 
Published: August 2019

AbstractHigh-throughput analyses of single-cell microscopy data is a critical tool within the field of bacterial cell biology. Several programs have been developed to specifically segment bacterial cells from phase-contrast images. Together with spot and object detection algorithms, these programs offer powerful approaches to quantify observations from microscopy data, ranging from cell-to-cell genealogy to localization and movement of proteins. Most segmentation programs contain specific post-processing and plotting options, but these options vary between programs and possibilities to optimize or alter the outputs are often limited. Therefore, we developed BactMAP (Bacterial toolbox for Microscopy Analysis & Plotting), a software package that allows researchers to transform cell segmentation and spot detection data generated by different programs automatically into various plots. Furthermore, BactMAP makes it possible to perform custom analyses and change the layout of the output. Because BactMAP works independently of segmentation and detection programs, inputs from different sources can be compared within the same analysis pipeline. BactMAP runs in R, which enables the use of advanced statistical analysis tools as well as easily adjustable plot graphics in every operating system. Using BactMAP we visualize key cell cycle parameters in Bacillus subtilis and Staphylococcus aureus, and demonstrate that the DNA replication forks in Streptococcus pneumoniae dissociate and associate before splitting of the cell, after the Z-ring is formed at the new quarter positions. BactMAP is available from https://veeninglab.com/bactmap.
Guano morphology reveals ecological information in British bats
Authors: Ware Roselyn Lydia , Garrod Benjamin , Macdonald Hannah , Allaby Robin G 
Published: August 2019

1.0.AbstractBats are primary consumers of nocturnal insects, disperse nutrients across landscapes, and are excellent bioindicators of an ecosystem’s health, however four of the seventeen Great British species are listed as declining. In this study we aim to investigate the link between bat guano morphology and diet, specifically looking at the ability to predict 1) species, 2) dietary guild and 3) bat size, using guano morphology alone. It was found that guano morphology overlapped too much to make predictions on species however, in some cases, it could be used to predict dietary guild or size.
Towards development of a statistical framework to evaluate myotonic dystrophy type 1 mRNA biomarkers in the context of a clinical trial
Authors: Kurkiewicz Adam , Cooper Anneli , McIlwaine Emily , Cumming Sarah A. , Adam Berit , Krahe Ralf , Puymirat Jack , Schoser Benedikt , Timchenko Lubov , Ashizawa Tetsuo , Thornton Charles , Rogers Simon , McClure John , Monckton Darren G 
Published: August 2019

AbstractMyotonic dystrophy type 1 (DM1) is a rare genetic disorder, characterised by muscular dystrophy, myotonia, and other symptoms. DM1 is caused by the expansion of a CTG repeat in the 3’-untranslated region of DMPK. Longer CTG expansions are associated with greater symptom severity and earlier age at onset. The primary mechanism of pathogenesis is thought to be mediated by a gain of function of the CUG-containing RNA, that leads to trans-dysregulation of RNA metabolism of many other genes. Specifically, the alternative splicing (AS) and alternative polyadenylation (APA) of many genes is known to be disrupted. In the context of clinical trials of emerging DM1 treatments, it is important to be able to objectively quantify treatment efficacy at the level of molecular biomarkers. We show how previously described candidate mRNA biomarkers can be used to model an effective reduction in CTG length, using modern high-dimensional statistics (machine learning), and a blood and muscle mRNA microarray dataset. We show how this model could be used to detect treatment effects in the context of a clinical trial.