bluuebunny/crossref_metadata_2025_split huggingface dataset:
Untangling the ecological signal in the dental morphology in the bat superfamily Noctilionoidea
Authors: López-Aguirre Camilo , Hand Suzanne J , Simmons Nancy B , Silcox Mary T 
Published: July 2021

AbstractDiet has been linked to the diversification of the bat superfamily Noctilionoidea, a group that underwent an impressive ecological adaptive radiation within Mammalia. For decades, studies have explored morphological adaptations and diversity of noctilionoid bats to reveal traits associated with their ecological diversity. Surprisingly, despite such interest and recent application of novel techniques, ecomorphological studies have failed to fully resolve the link between diet and a critical component of the feeding apparatus: dental morphology. Using multivariate dental topographic analysis and phylogenetic comparative methods, we examined the phylogenetic, biological and ecological signal in the dental morphology of noctilionoid bats. Analysing the lower first molars of 110 species, we explored relationships between diet and dental morphology, accounting for three different dimensions of diet (guild, composition and breadth). Phylogenetic and size-dependent structuring of the dental topography data shows it does not correlate only to diet, highlighting the need to account for multiple sources of variation. Frugivorous noctilionoids have sharper molars than other previously reported frugivorous mammals. Nectarivorous noctilionoids showed reduced lower molar crown height and steepness, whereas animalivorous species had larger molars. Dietary composition suggested that the intensity of exploitation of a resource is also linked to different dimensions of dental morphology. Increasing carnivory positively correlated with MA, explaining the highest proportion of its variation, and increasing frugivory explained the highest proportion of variation in all other variables. Dietary breadth showed generalist species have sharper, more topographically-complex molars, whereas specialist herbivores and specialist animalivores fell at opposite ends in the range of tooth steepness and crown height. Together, the results suggest that adaptations affecting different attributes of dental morphology likely facilitated the dietary diversity and specialisation found in Noctilionoidea.
Individual difference in addiction-like behaviors and choice between cocaine versus food in Heterogeneous Stock rats
Authors: Sedighim Sharona , Carrette Lieselot LG , Venniro Marco , Shaham Yavin , de Guglielmo Giordano , George Olivier 
Published: July 2021

AbstractRationale and objectivesRecent studies reported that when given a mutually exclusive choice between cocaine and palatable food, most rats prefer the non-drug reward over cocaine. However, these studies used rat strains with limited genetic and behavioral diversity. Here, we used a unique outbred strain of rats (Heterogeneous Stock, HS) that mimic the genetic variability of humans.MethodsWe first identified individual differences in addiction-like behaviors (low and high). Next, we tested choice between cocaine and palatable food using a discrete choice procedure. We characterized the individual differences using an Addiction score that incorporates key features of addiction: escalated intake, highly motivated responding (progressive ratio), and responding despite adverse consequences (footshock punishment). We assessed food vs. cocaine choice at different drug-free days (without pre-trial cocaine self administration) during acquisition of cocaine self-administration or after escalation of cocaine self-administration. We also assessed drug vs. food choice immediately after 1-, 2-, or 6-h cocaine self-administration.ResultsIndependent of the addiction score, without pre-trial coccaine (1 or more abstinence days) HS rats strongly preferred the palatable food over cocaine, even if the food reward was delayed or its size was reduced. However, rats with high but not low addiction score modestly increased cocaine choice immediately after 1-, 2- or 6-h cocaine self-administration.ConclusionsLike other strains, HS rats strongly prefer palatable food over cocaine. Individual differences in addiction score were associated with increased drug choice in the presence but not absence (abstinence) of cocaine. The HS strain may be useful in studies on mechanisms of addiction vulnerability.
Cytolytic memory CD4+ T cell clonotypes are expanded during Plasmodium falciparum infection
Authors: Furtado Raquel , Delahaye Fabien , Zhang Jinghang , Sung Joowhan , Karell Paul , Kim Ryung S. , Caillat-Zucman Sophie , Liang Li , Felgner Philip , Bauleni Andy , Gama Syze , Buchwald Andrea , Taylor Terrie , Seydel Karl , Laufer Miriam , Daily Johanna P. , Lauvau Grégoire 
Published: July 2021

AbstractPlasmodium falciparum (Pf) malaria causes high rates of morbidity and mortality and lacks a sufficiently effective vaccine. Clinical immunity develops in residents of malaria endemic regions which confers reduced clinical symptoms during infection and protection against severe disease. We hypothesized that understanding the immune mechanisms of clinical immunity could inform vaccine design to improve efficacy. We compared the peripheral blood cellular and humoral immune responses during a mild episode of Pf malaria infection. Participants were classified as either clinically susceptible or clinically protected, based on the number of recurrent clinical infections over an 18-month longitudinal study in a malaria endemic region in Malawi. Susceptible participants had three or more recurrent clinical episodes while clinically immune individuals had one or none. Protected participants exhibited higher plasma immunoglobulin G (IgG) breadth and titers against Pf antigens, and greater antibody (Ab)-dependent Pf opsonization compared to susceptible participants. Using high dimensional mass cytometry (CyTOF), spectral flow cytometry and single-cell transcriptomic analyses, we identified expanded memory CD4+ T cell clones sharing identical T cell receptor clonotypes in the blood of protected participants during malaria infection. These cells express a strong cytolytic T helper 1 effector program with transcripts encoding granzymes (A, B, H, M), granulysin, NKG7 and the Zeb2 master transcriptional regulator of terminally differentiated effector T cells. Memory CD4+ T cells expressing Zeb2+ were CD39hiTIGIThi and expressed multiple chemotactic and checkpoint inhibitory receptors, although the cellular levels of several of these receptors were reduced in protected compared to susceptible individuals. We propose that clonally expanded Zeb2+ cytolytic memory CD4+ Th1 cells could represent essential contributors to clinical immunity against Pf malaria.One Sentence SummaryA population of cytolytic memory CD4+ T cells is clonally expanded in patients with Plasmodium falciparum malaria and has reduced chemotactic and inhibitory receptor expression in patients with naturally acquired clinical malaria immunity.
Development of Visual Response Selectivity in Cortical GABAergic Interneurons
Authors: Chang Jeremy T. , Fitzpatrick David 
Published: July 2021

AbstractThe visual cortex of carnivores and primates displays a high degree of modular network organization characterized by local clustering and structured long-range correlations of activity and functional properties. Excitatory networks display modular organization before the onset of sensory experience, but the developmental timeline for modular networks of GABAergic interneurons, remains under-explored. Using in vivo calcium imaging of the ferret visual cortex, we find evidence that before visual experience, interneurons display weak orientation tuning and widespread non-specific activation in response to visual stimuli. Modular organization and orientation tuning are evident with as little as one week of visual experience. Furthermore, we find that the development of orientation tuning requires visual experience, while the reduction in widespread network activity does not. Thus, the maturation of inhibitory cortical networks occurs in a delayed, parallel process relative to excitatory neurons.
Breakout Rooms, Polling, and Chat, Oh My! The Development and Validation of Online COPUS
Authors: Pusey Téa S. , Valencia Andrea Presas , Signorini Adriana , Kranzfelder Petra 
Published: July 2021

AbstractWe developed and validated a new classroom observation protocol, Online COPUS (E-COPUS), to measure teaching and learning practices in the online learning environment. We collected COPUS and E-COPUS data from 40 STEM courses before, during the transition, and continuation of emergency remote teaching (ERT). Through weekly discussions among observers, we adjusted six of the original instructor COPUS code descriptions and six of the original student code descriptions to fit the online learning environment. We trained 23 observers to conduct E-COPUS utilizing both in-person and online lecture recordings. To validate E- COPUS, we consulted an expert panel of science educators and education researchers to provide feedback on our code descriptions and complete a matching activity with our E-COPUS code descriptions. We further examined E-COPUS by analyzing the teaching and learning practices of 6 instructors across in-person and online instruction and found that the online functions of breakout rooms, polling, and the chat were utilized to promote active learning activities in the online learning environment. As we prepare for teaching in the future, it is important to have formative assessment tools designed for all course formats to support assessment and improvement of teaching practices in college STEM classrooms.
hECA: the cell-centric assembly of a cell atlas
Authors: Chen Sijie , Luo Yanting , Gao Haoxiang , Li Fanhong , Li Jiaqi , Chen Yixin , You Renke , Hao Minsheng , Bian Haiyang , Xi Xi , Li Wenrui , Li Weiyu , Ye Mingli , Meng Qiuchen , Zou Ziheng , Li Chen , Li Haochen , Zhang Yangyuan , Cui Yanfei , Wei Lei , Chen Fufeng , Wang Xiaowo , Lv Hairong , Hua Kui , Jiang Rui , Zhang Xuegong 
Published: July 2021

SUMMARYSingle-cell omics data can characterize multifaceted features of massive cells and bring significant insights to biomedical researches. The accumulation of single-cell data provides growing resources for constructing atlases for all cells of a human organ or the whole body. The true assembly of a cell atlas should be cell-centric rather than file-centric. We proposed a unified information framework enabling seamless cell-centric data assembly and developed a human Ensemble Cell Atlas (hECA) as an instance. hECA version 1.0 assembled scRNA-seq data across multiple studies into one orchestrated data repository. It contains 1,093,299 labeled cells and metadata from 116 published human single-cell studies, covering 38 human organs and 11 systems. We invented three methods of applications based on the cell-centric assembly: “In data” cell sorting enables targeted data retrieval in the full atlas with customizable logic expressions; The “quantitative portraiture” system provides a multi-view presentation of biological entities (organs, cell types, and genes) of multiple granularities; The customizable reference creation allows users to use the cell-centric assembly to generate references for their own cell type annotations. Case studies on agile construction of user-defined sub-atlases and “in data” investigation of CAR-T off-targets in multiple organs showed the great potential of cell-centric atlas assembly.
Accelerating long-read analysis on modern CPUs
Authors: Kalikar Saurabh , Jain Chirag , Md Vasimuddin , Misra Sanchit 
Published: July 2021

AbstractLong read sequencing is now routinely used at scale for genomics and transcriptomics applications. Mapping of long reads or a draft genome assembly to a reference sequence is often one of the most time consuming steps in these applications. Here, we present techniques to accelerate minimap2, a widely used software for mapping. We present multiple optimizations using SIMD parallelization, efficient cache utilization and a learned index data structure to accelerate its three main computational modules, i.e., seeding, chaining and pairwise sequence alignment. These result in reduction of end-to-end mapping time of minimap2 by up to 1.8 × while maintaining identical output.
The precedence effect in spatial hearing emerges only late in the auditory pathway
Authors: Li Kongyan , Auksztulewicz Ryszard , Chan Chloe H. K. , Mishra Ambika Prasad , Schnupp Jan W. H. 
Published: July 2021

AbstractBackgroundTo localize sound sources accurately in a reverberant environment, human binaural hearing strongly favors analyzing the initial wave front of sounds. Behavioral studies of this “precedence effect” have so far largely been confined to human subjects, limiting the scope of complementary physiological approaches. Similarly, physiological studies have mostly looked at neural responses in the inferior colliculus, or used modeling of cochlear mechanics in an attempt to identify likely underlying mechanisms. Studies capable of providing a direct comparison of neural coding and behavioral measures of sound localization under the precedence effect are lacking.ResultsWe adapted a “temporal weighting function” paradigm for use in laboratory rats. The animals learned to lateralize click trains in which each click in the train had a different interaural time difference. Computing the “perceptual weight” of each click in the train revealed a strong onset bias, very similar to that reported for humans. Follow-on electrocorticographic recording experiments revealed that onset weighting of ITDs is a robust feature of the cortical population response, but interestingly it often fails to manifest at individual cortical recording sites.ConclusionWhile previous studies suggested that the precedence effect may be caused by cochlear mechanics or inhibitory circuitry in the brainstem and midbrain, our results indicate that the precedence effect is not fully developed at the level of individual recording sites in auditory cortex, but robust and consistent precedence effects are observable at the level of cortical population responses. This indicates that the precedence effect is significantly “higher order” than has hitherto been assumed.
Convergence of MCR-8.2 and chromosome-mediated resistance to colistin and tigecycline in an NDM-5-producing ST656 Klebsiella pneumoniae from a lung transplant patient
Authors: Zhao Jiankang , Li Ziyao , Zhang Yulin , Liu Xinmeng , Xiong Zhujia , Fan Yanyan , Zou Xiaohui , Lu Binghuai , Cao Bin 
Published: July 2021

AbstractFor infection caused by NDM-5-producing Klebsiella pneumoniae, tigecycline and colistin are the last treatment options. In this study, we characterized the first NDM-5 and MCR-8.2 co-harboring K. pneumoniae clinical isolate, combining with chromosomal gene-mediated resistance to colistin and tigecycline. The K. pneumoniae KP32558 was isolated from the bronchoalveolar lavage fluid from a lung transplant male patient. Whole genome sequencing was carried out using Illumina HiSeq sequencing platform as well as nanopore sequencing method. The K. pneumoniae KP32558 was identified as a pan-drug resistant bacteria, belonged to ST656, and harbored plasmid-encoded blaNDM-5 and mcr-8.2 genes. The blaNDM-5 gene was located on an IncX3 type plasmid, which was successfully transferred to Escherichia coli strain J53 without visible fitness cost. The mcr-8.2 gene was located on a conjugative plasmid pKP32558-2-mcr8. It had two replicons, IncFII(K) and IncQ1, harbored previously by another two mcr-8.2-carrying plasmids pMCR8_020135 and pMCR8_095845. These three plasmids were clustered into the same clade and derived from K. pneumoniae isolates of the same clonal complex, indicating that pKP32558-2-mcr8 may come from pMCR8_020135 and pMCR8_095845 related ancestor. The MIC of KP32558 for colistin was 256 mg/L, the 6 amino acid substitutions in the two-component system may involve in the high-level colistin resistance. The truncation in acrR gene, related to tigecycline resistance, was also identified. K. pneumoniae has evolved a variety of complex resistance mechanisms to the last-resort antimicrobials, close surveillance is urgently needed to monitor the prevalence of this clone.
Comparison of infected and vaccinated transplant recipients highlights the role of Tfh and neutralizing IgG in COVID-19 protection
Authors: Charmetant Xavier , Espi Maxime , Benotmane Ilies , Heibel Francoise , Buron Fanny , Gautier-Vargas Gabriela , Delafosse Marion , Perrin Peggy , Koenig Alice , Cognard Noelle , Levi Charlene , Gallais Floriane , Manière Louis , Rossolillo Paola , Soulier Eric , Pierre Florian , Ovize Anne , Morelon Emmanuel , Defrance Thierry , Fafi-Kremer Samira , Caillard Sophie , Thaunat Olivier 
Published: July 2021

AbstractTransplant recipients, which receive therapeutic immunosuppression to prevent graft rejection, are characterized by high COVID-19-related mortality and defective response to vaccines. Having observed that previous infection by SARS-CoV-2 but not the standard “2 doses” scheme of vaccination, provided complete protection against COVID-19 to transplant recipients, we undertook this translational study to compare the cellular and humoral immune responses of these 2 groups of patients. Neutralizing anti-Receptor Binding Domain (RBD) IgG were identified as the critical immune effectors associated with protection. Generation of anti-RBD IgG was dependent upon spike-specific T follicular helper (Tfh) CD4+ T cells, which acted as limiting checkpoint. Tfh generation was impeded by high dose mycophenolate mofetil in non-responders to vaccine but not in infected patients, suggesting that increasing immunogenicity of vaccine could improve response rate to mRNA vaccine. This theory was validated in two independent prospective cohorts, in which administration of a 3rd dose of vaccine resulted in the generation of anti-RBD IgG in half of non-responders to 2 doses.One sentence summaryThe generation of neutralizing IgG, which protects kidney transplant recipients from COVID-19, requires T follicular helper cells.
Natural Language Word-Embeddings as a glimpse into healthcare at the End Of Life
Authors: Lau Shun , Kraljevic Zeljko , Al-Agil Mohammad , Charing Shelley , Quarterman Alan , Parkes Harold , Metaxa Victoria , Sleeman Katherine , Gao Wei , Dobson Richard , Teo James T , Hopkins Phil 
Published: July 2021

AbstractIntroductionPlanning in advance and personalised discussions on limitation of life sustaining treatment (LST) is an indicator of good care. However, there are many linguistic nuances and misunderstandings around dying in hospital as well as inaccuracy in individual-level prognostication.MethodsUsing unsupervised natural language processing (NLP), we explored real-world terminology using phrase clusters with most similar sematic embeddings to “Ceiling of Treatment” and their prognostication value in the electronic health record of an urban teaching hospital.ResultsWord embeddings with most similar to “Ceiling of Treatment” clustered around phrases describing end-of-life care, ceiling of care and resuscitation discussions. The phrases have differing prognostic profile with the highest 7-day mortality in the phrases most implicitly referring to end of life -“terminal care”, “end of life care” (57.5%) and “unsurvivable” (57.6%).ConclusionNLP can quantify and analyse real-world end of life discussions around prognosis and appropriate LST.Patient-friendly Summary(by expert patients: Sherry Charing, Alan Quarterman, Harold Parkes)Discussions between doctors, patients and family in deciding what is the appropriate maximum treatment a specific patient should have based on their clinical condition is complex. Discussions, often involving expressions regarding “End Of Life” care are used to describe the maximum invasive treatments a patient should have or would want. There are a range of expressions used, many with overlapping meanings which can be confusing, not only for the patient and family, but also for doctors reading the patient’s clinical notes. In this study, a computational approach using Artificial Intelligence to read clinical patient notes was carried out by looking at thousands of patient records from a large urban hospital. Expressions that doctors use to describe these discussions were analysed to show the associations of particular words and phrases in relation to mortality. Using a computer analysis for this study it was possible to quantify the use of these expressions and their relation to the “End Of Life”. Through this AI-based approach, real-world use of phrases and language relating “End Of Life” can be analysed to understand how doctors and patients are communicating, and about any possible misunderstandings of language.
Patient stratification reveals the molecular basis of disease comorbidities
Authors: Urda-García Beatriz , Sánchez-Valle Jon , Lepore Rosalba , Valencia Alfonso 
Published: July 2021

AbstractEpidemiological evidence shows that some diseases tend to co-occur; more exactly, certain groups of patients with a given disease are at a higher risk of developing a specific secondary condition. Despite the considerable interest, only a small number of connections between comorbidities and molecular processes have been identified.Here we develop a new approach to generate a disease network that uses the accumulating RNA-seq data on human diseases to significantly match a large number of known comorbidities, providing plausible biological models for such co-occurrences. Furthermore, 64% of the known disease pairs can be explained by analysing groups of patients with similar expression profiles, highlighting the importance of patient stratification in the study of comorbidities.These results solidly support the existence of molecular mechanisms behind many of the known comorbidities. All the information can be explored on a large scale and in detail at http://disease-perception.bsc.es/rgenexcom/.
Complement Regulator Factor H is a Cofactor for Thrombin in both Pro- and Anticoagulant Roles
Authors: McCluskey Genevieve. , Davies Gemma E. , Velounias Rebekah L. , Hughes Tim R. , Morgan B. Paul , Preston Roger J. S. , Collins Peter W. , Jenkins P. Vincent , Heurich Meike 
Published: July 2021

AbstractBackgroundComplement FH (FH) is a key regulator of complement activity whereas thrombin (FIIa) is central to hemostasis with both pro- and anticoagulant functions. Both have separately been shown to have auxiliary activities across the two systems. The purpose of this study was to determine the effect of FH on pro- and anti-coagulant functions and investigate the interaction between FH and thrombin.MethodsTail bleeding time and hemolysis were measured in FH-deficient mice (CFH−/−). Activated partial thromboplastin time (aPTT) was determined in FH-depleted human plasma. FH effect on fibrin clot generation was investigated in turbidity assays and on activated protein C (APC) generation. Binding affinity of thrombin with FH was determined using surface plasmon resonance (SPR).ResultsTail bleeding time in CFH−/− mice was significantly prolonged compared to wild type mice. The aPTT in FH-depleted human plasma was elevated compared to normal plasma and restored by adding back FH to depleted plasma. Accordingly, FH enhanced thrombin-mediated fibrin clot generation by shortening lag time, increasing rate of clot formation and maximum turbidity, and affected clot structure. Despite this, FH also increased the rate of thrombin-mediated protein C (PC) activation, both in the presence and absence of soluble recombinant thrombomodulin (TM). Nanomolar affinity binding of FH with thrombin, but not prothrombin, was confirmed.ConclusionComplement FH binds thrombin with strong affinity and acts as a novel cofactor that enhances both pro- and anticoagulant actions of thrombin. These data highlight an important role for FH in hemostasis.Key pointsAbsence of FH prolongs tail bleeding time in CFH−/− mice and activated partial thromboplastin time (aPTT) is elevated in human FH-depleted plasma.FH acts a cofactor for thrombin by enhancing fibrin generation, altering fibrin clot structure and enhancing TM-thrombin mediated protein C activation