bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optimal thromboprophylaxis strategies in non-critically ill patients with COVID-19 pneumonia. The PROTHROMCOVID Randomized Controlled Trial
Authors: Muñoz-Rivas Nuria , Aibar Jesús , Gabara-Xancó Cristina , Trueba-Vicente Ángela , Urbelz-Pérez Ana , Gómez-Del Olmo Vicente , Demelo-Rodriguez Pablo , Rivera-Gallego Alberto , Bosch-Nicolau Pau , Perez-Pinar Montserrat , Rios-Prego Mónica , Madridano-Cobo Olga , Ramos-Alonso Laura , Alonso-Carrillo Jesús , Francisco-Albelsa Iria , Martí-Saez Edelmira , Maestre-Peiró Ana , Méndez-Bailón Manuel , Hernández-Rivas José Ángel , Torres-Macho Juan ,   The PROTHROMCOVID Trial investigators
Published: May 2022

AbstractBackgroundHospitalized patients with COVID-19 are at increased risk for thrombosis, acute respiratory distress syndrome and death. The optimal dosage of thromboprophylaxis is unknown.ObjectiveTo evaluate the efficacy and safety of tinzaparin in prophylactic, intermediate, and therapeutic doses in non-critical patients admitted for COVID-19 pneumonia.Design, setting, and participantsRandomized controlled, multicenter trial (PROTHROMCOVID) enrolling non-critical, hospitalized adult patients with COVID-19 pneumonia.InterventionsPatients were randomized to prophylactic (4500 IU), intermediate (100 IU/kg), or therapeutic (175 IU/kg) doses of tinzaparin during hospitalization, followed by 7 days of prophylactic tinzaparin at discharge.MeasurementsThe primary efficacy outcome was a composite endpoint of symptomatic systemic thrombotic events, need for invasive or non-invasive mechanical ventilation, or death within 30 days. The main safety outcome was major bleeding at 30 days.ResultsOf the 311 subjects randomized, 300 were included in the analysis (mean [SD] age, 56.7 [14.6] years; males, 182 [60.7%]. The composite endpoint at 30 days from randomization occurred in 58 patients (19.3%) of the total population; 19 (17.1 %) in the prophylactic group, 20 (22.1%) in the intermediate group, and 19 (18.5%) in the therapeutic dose group (P= 0.72). No major bleeding event was reported; non-major bleeding was observed in 3.7% of patients, with no intergroup differences.ConclusionsIn non-critically ill COVID-19 patients, intermediate or full-dose tinzaparin compared to standard prophylactic doses did not appear to increase benefit regarding the likelihood of thrombotic event, non-invasive ventilation or high-flow oxygen, or death.Trial RegistrationClinicalTrials.gov Identifier (NCT04730856).FundingThis independent research initiative was supported by Leo-Pharma; Tinzaparin was provided by Leo Pharma.
Knockout of mitogen-activated protein kinase 3 causes barley root resistance against Fusarium graminearum
Authors: Basheer Jasim , Vadovič Pavol , Šamajová Olga , Melicher Pavol , Komis George , Křenek Pavel , Králová Michaela , Pechan Tibor , Ovečka Miroslav , Takáč Tomáš , Šamaj Jozef 
Published: May 2022

AbstractThe roles of mitogen-activated protein kinases (MAPKs) in plant-fungal pathogenic interactions are less understood in crops. Here, microscopic, phenotyping, proteomic and biochemical analyses revealed that independent TALEN-based knockout lines of Hordeum vulgare MITOGEN-ACTIVATED PROTEIN KINASE 3 (HvMPK3 KO) were resistant against Fusarium graminearum infection. When co-cultured with roots of the HvMPK3 KO lines, F. graminearum hyphae were excluded to the extracellular space, the growth pattern of hyphae was considerably deregulated, mycelia development was less efficient and number of appressoria and their penetration potential were significantly reduced. Intracellular penetration of hyphae was preceded by the massive production of reactive oxygen species (ROS) in attacked cells of the wild type, but it was mitigated in the HvMPK3 KO lines. Suppression of ROS production in these lines coincided with the elevated abundances of catalase and ascorbate peroxidase. Moreover, differential proteomic analysis revealed downregulation of defense-related proteins in wild type, and the upregulation of peroxidases, lipid transfer proteins, and cysteine proteases in HvMPK3 KO lines after 24h of F. graminearum inoculation. Consistently with proteomic analysis, microscopic observations showed an enhanced suberin accumulation in roots of HvMPK3 KO lines, most likely contributing to the arrested infection by F. graminearum. These results suggest that TALEN-based knockout of HvMPK3 leads to the barley root resistance against Fusarium root rot.
Statin intolerance – Prevalence and practical management in a specialized lipid clinic
Authors: Turdo Yannick , Collet Tinh-Hai 
Published: May 2022

AbstractAimsStatins are recommended as first-line treatment to prevent cardiovascular disease, but high rates of adverse events and subsequent discontinuation can prevent effective treatment in some patients. We aimed to describe the intensity, nature and frequency of adverse effects caused by statins and other lipid-lowering drugs, and to assess their association with clinical predictors and treatment strategies.MethodsThis is a retrospective study of 121 consecutive unselected patients followed at a specialized lipid referral clinic in Lausanne University Hospital, Switzerland, in 2018 whose clinical data spanned 2016 until 2019.ResultsAdverse effects were reported by 58% of patients, causing musculoskeletal (72%), neurologic (40%), gastrointestinal (25%) and other (25%) symptoms. Gastrointestinal symptoms affected 35% of women, but only 12% of men (p=0.06). Statins caused more adverse effects than other drugs, with atorvastatin (63%) and simvastatin (64%) achieving the lowest rates, pravastatin (87%) and fluvastatin (100%) the highest. Fenofibrate was associated with significantly less frequent adverse effects than statins (22% vs. 57%, p=0.006). Adaptation and termination of the treatment led to 86% and 88% lower intensity of symptoms, respectively.ConclusionWhile the predominance of musculoskeletal symptoms caused by lipid-lowering drugs is known, symptoms affecting other organ systems should not be ignored. Statins were the lipid-lowering drug class with the highest rates of adverse effects. To maintain compliance and cardiovascular prevention, treatment strategies such as a change of dosage, frequency of administration, daily timing, or switching active substance can contribute to better tolerance of statin treatment. Further investigation is needed to establish specific treatment strategies for individual patient profiles.
Non-invasive Fluorescence Imaging of Gut Commensal Bacteria in Live Mice
Authors: Apostolos Alexis J. , Chordia Mahendra D. , Kolli Sree H. , Rutkowski Melanie R. , Pires Marcos M. 
Published: May 2022

AbstractIn mammals, gut commensal microbiota interact extensively with the host and the same interactions can be dysregulated in diseased states. The development of methods to monitor gut microbiota in vivo can lead to improved foundational understanding of the biological events underpinning these interactions. The current standard for non-invasive monitoring of gut bacteria entails classification by 16S rRNA sequencing from fecal samples. This method has many advantages but also has serious limitations, especially for monitoring dynamic changes in the gut of live animals. In recent years, several imaging techniques have been widely adopted that afford non-invasive assessment of animal subjects – most notably in cancer biology; however, these technical gains have not translated to the imaging of gut bacterial communities. Herein, we describe a method to non-invasively image commensal bacteria based on the specific metabolic labeling of bacterial cell walls to illuminate the gut bacteria of live mice. This tagging strategy may additionally provide unprecedented insight into cell wall turnover of gut commensals, which has implications for bacterial cellular growth and division, in a live animal.
Temporal and spatial patterns of vertebrate extinctions during the Anthropocene
Authors: Pincheira-Donoso Daniel , Harvey Lilly P. , Guirguis Jacinta , Goodyear Luke E. B. , Finn Catherine , Johnson Jack V. , Grattarola Florencia 
Published: May 2022

AbstractThe human-induced annihilation of modern biodiversity is dragging the planet into a mass extinction that has already altered patterns of life globally. Among vertebrates, over 500 species have become extinct or possibly extinct in the last five centuries – an extinction rate that would have taken several millennia without human intervention. Vertebrate extinctions have often been quantified as cumulative counts that reveal sharp increases in losses over time. Here, we quantify global tetrapod extinctions since the 1400s using numbers of species losses across successive and independent time periods until present. Our results reveal that extinctions were low and fundamentally restricted to islands in pre-industrial times, experiencing a significant increase and spread over continental mainland following the onset of the industrial revolution. Recent amphibian extinctions alarmingly exceed the extinctions of all tetrapods, while extinctions of island birds account for a third of all extinctions. Finally, we quantified the relationship between human population growth (HPG, as a proxy for aggregate human effects on the environment) and extinctions between 1800-2000, to then predict that an estimated 838 tetrapod species will go extinct between 2030-2100 based on United Nations HPG projections. These findings further warn humanity about the need to sustainably control HPG and the destructive impacts of rapid environmental change on ecosystems worldwide.
Minute-scale Periodicity of Neuronal Firing in the Human Entorhinal Cortex
Authors: Aghajan Zahra M. , Kreiman Gabriel , Fried Itzhak 
Published: May 2022

AbstractGrid cells in the entorhinal cortex demonstrate spatially periodic firing patterns, which are thought to provide a map of space on behaviorally relevant length scales. It is unknown, however, whether such periodicity exists for behaviorally relevant time scales in the human brain. Here we investigated neuronal firing during a temporally continuous uninterrupted experience by presenting fourteen neurosurgical patients with an audiovisual video while recording single neuron activity from multiple brain regions. We report on a set of units that modulate their activity in a strikingly periodic manner across different timescales—from seconds to many minutes. These cells were most prevalent in the entorhinal cortex. Time within the video could be decoded from their population activity. Furthermore, these cells remapped their dominant periodicity to shorter timescales during a subsequent recognition memory task. When the audiovisual sequence was presented at two different speeds (regular and faster), a significant percentage of these temporally periodic cells (TPCs) maintained their timescales, suggesting a degree of invariance with respect to the narrative content. The temporal periodicity of TPCs may complement the spatial periodicity of grid cells Whether these cells provide scalable spatiotemporal metrics for encoding and retrieval of human experience warrants future investigations.
A quantitative eDNA-based method to monitor fish spawning in lakes: application to European perch and whitefish
Authors: Vautier Marine , Chardon Cécile , Goulon Chloé , Guillard Jean , Domaizon Isabelle 
Published: May 2022

AbstractThere is an urgent need to evaluate the effects of anthropogenic pressures and climatic change on fish populations’ dynamics. When monitored in lakes, the spawning of fish is generally assessed using traditional, mostly destructive or damaging, methods as gillnetting and collection of fertilized eggs.Over the last decade, environmental DNA (eDNA) based methods have been widely developed for the detection of aquatic species, offering a non-invasive alternative method to conventional biomonitoring tools. In particular, the emergence of new methods as the droplet digital PCR (ddPCR) offer the possibility to quantify an absolute eDNA signal in a very sensitive way and at a low cost.Here, we developed and implemented a quantitative eDNA method to monitor the spawning activity of two fish species, European perch and whitefish. ddPCR protocols were formalized based on existing and newly designed COI primers, and were applied during four spawning periods in lake Geneva.The results demonstrate the efficiency of eDNA coupled with ddPCR to identify the timing and duration of the spawning periods, as well as the peak of the spawning activity for the targeted species. In addition, the use of a control species (i.e., quantification of the eDNA signal of a fish that does not reproduce during the monitoring period) was shown to be relevant to clearly discriminate fluctuations of the eDNA signal associated to the spawning activity from the baseline eDNA signal. For future implementation, we recommend using an integrative sampling strategy (e.g., pooled samples for a give station) to smooth the local variability of the eDNA signal. These results show that we reached an operational level to use these non-invasive eDNA methods to monitor the spawning periods of these two fish species in large lakes.
RanBP1 plays an essential role in directed migration of neural crest cells during development
Authors: Barriga Elias H , Alasaadi Delan N , Mencarelli Chiara , Mayor Roberto , Pichaud Franck 
Published: May 2022

ABSTRACTCollective cell migration is essential for embryonic development, tissue regeneration and repair, and has been implicated in pathological conditions such as cancer metastasis. It is, in part, directed by external cues that promote front-to-rear polarity in individual cells. However, our understanding of the pathways that underpin the directional movement of cells in response to external cues remains incomplete. To examine this issue we made use of neural crest cells (NC), which migrate as a collective during development to generate vital structures including bones and cartilage. Using a candidate approach, we found an essential role for Ran-binding protein 1 (RanBP1), a key effector of the nucleocytoplasmic transport pathway, in enabling directed migration of these cells. Our results indicate that RanBP1 is required for establishing front-to-rear polarity, so that NCs are able to chemotax. Moreover, our work suggests that RanBP1 function in chemotaxis involves the polarity kinase LKB1/PAR4. We envisage that regulated nuclear export of LKB1 through Ran/RanBP1 is a key regulatory step required for establishing front-to-rear polarity and thus chemotaxis, during NC collective migration.
Pathophysiology of Dyt1 dystonia is mediated by spinal cord dysfunction
Authors: Pocratsky Amanda M. , Nascimento Filipe , Özyurt M. Görkem , White Ian J. , Sullivan Roisin , O’Callaghan Benjamin J. , Smith Calvin C. , Surana Sunaina , Beato Marco , Brownstone Robert M. 
Published: May 2022

SummaryDystonia, a neurological disorder defined by abnormal postures and disorganised movements, is considered to be a neural circuit disorder with dysfunction arising within and between multiple brain regions. Given that spinal circuits constitute the final pathway for motor control, we sought to determine their contribution to the movement disorder. Focusing on the most common inherited dystonia, DYT1-TOR1A, we confined a conditional knockout ofTor1ato the spinal cord and dorsal root ganglia (DRG) and found that these mice recapitulated the phenotype of the human condition, developing early onset generalised torsional dystonia. Physiologically, these mice bore the hallmark features of dystonia: spontaneous contractions at rest, excessive sustained contractions during voluntary movements including co-contractions of motor antagonists, and altered sensory-motor reflexes. Furthermore, spinal locomotor circuits were impaired. Together, these data challenge current understanding of dystonia, and lead to broader insights into spinal cord function and movement disorder pathophysiology.
Manipulating the rapid consolidation periods in a learning task affects general skills more than statistical learning
Authors: Szücs-Bencze Laura , Fanuel Lison , Szabó Nikoletta , Quentin Romain , Nemeth Dezso , Vékony Teodóra 
Published: May 2022

AbstractMemory consolidation processes have traditionally been investigated from the perspective of hours or days. However, the latest developments in memory research showed that memory consolidation processes could occur even within seconds, possibly due to the neural replay of just-practiced memory traces during short breaks. Here, we investigate this rapid form of consolidation during statistical learning. We aim to answer (a) whether this rapid consolidation occurs in implicit statistical learning and general skill learning and (b) whether the duration of rest periods affects these two learning types differently. Participants performed a widely used statistical learning task - the Alternating Serial Reaction Time (ASRT) task - that enables us to measure implicit statistical and general skill learning separately. The ASRT task consisted of 25 learning blocks with a rest period between the blocks. In a between-subjects design, the length of the rest periods was fixed at 15 or 30 seconds, or the participants could control the length themselves. We found that the duration of rest periods does not affect the amount of statistical knowledge acquired but does change the dynamics of learning. Shorter rest periods led to better learning during the learning blocks, whereas longer rest periods promoted learning also in the between block rest periods, possibly due to the higher amount of replay. Moreover, we found weaker general skill learning in the self-paced group than in the fixed rest period groups. These results suggest that distinct learning processes are differently affected by the duration of short rest periods.
A Versatile Enhanced Freeze-Substitution Protocol for Volume Electron Microscopy
Authors: Bélanger Sébastien , Berensmann Heather , Baena Valentina , Duncan Keith , Meyers Blake C. , Narayan Kedar , Czymmek Kirk J 
Published: May 2022

AbstractVolume electron microscopy, a powerful approach to generate large three-dimensional cell and tissue volumes at electron microscopy resolutions, is rapidly becoming a routine tool for understanding fundamental and applied biological questions. One of the enabling factors for its adoption has been the development of conventional fixation protocols with improved heavy metal staining. However, freeze-substitution with organic solvent-based fixation and staining has not realized the same level of benefit. Here, we report a straightforward approach including 2% osmium tetroxide, acetone and up to 3% water substitution fluid (compatible with traditional or fast freeze-substitution protocols), warm-up and transition from organic solvent to aqueous 2% OsO4. Once fully hydrated, samples were processed in aqueous based potassium ferrocyanide, thiocarbohydrazide, osmium tetroxide, uranyl acetate and lead acetate before resin infiltration and polymerization. We observed a consistent and substantial increase in heavy metal staining across diverse and difficult-to-fix test organisms and tissue types, including plant tissues, nematodes, yeast, and bacteria. Our approach opens new possibilities to combine the benefits of cryo-preservation with enhanced contrast for volume electron microscopy in diverse organisms.
MobsPy: A Meta-Species Language for Chemical Reaction Networks*
Authors: Cravo Fabricio , Függer Matthias , Nowak Thomas , Prakash Gayathri 
Published: May 2022

AbstractChemical reaction networks are widely used to model biochemical systems. However, when the complexity of these systems increases, the chemical reaction networks are prone to errors in the initial modeling and subsequent updates of the model.We present the Meta-species-oriented Biochemical Systems Language (MobsPy), a language designed to simplify the definition of chemical reaction networks in Python. MobsPy is built around the notion of meta-species, which are sets of species that can be multiplied to create higher-dimensional orthogonal characteristics spaces and inheritance of reactions. Reactions can modify these characteristics. For reactants, queries allow to select a subset from a meta-species and use them in a reaction. For products, queries specify the dimensions in which a modification occurs. We demonstrate the simplification capabilities of the MobsPy language at the hand of a running example and a circuit from literature. The MobsPy Python package includes functions to perform both deterministic and stochastic simulations, as well as easily configurable plotting. The MobsPy package is indexed in the Python Package Index and can thus be installed via pip.
Get the gist of the story: Neural map of topic keywords in multi-speaker environment
Authors: Park Hyojin , Gross Joachim 
Published: May 2022

AbstractNeural representation of lexico-semantics in speech processing has been revealed in recent years. However, to date, how the brain makes sense of the higher-level semantic gist (topic keywords) of a continuous speech remains mysterious. Capitalizing on a generative probabilistic topic modelling algorithm on speech materials to which participants listened while their brain activities were recorded by Magnetoencephalography (MEG), here we show spatio-temporal neural representation of topic keywords in a multi-speaker environment where task-relevant (attended) and -irrelevant (unattended) speech co-exits. We report the difference of neural representation between salient and less salient semantic gist of both attended and unattended speech. Moreover, we show that greater sensitivity to semantically salient unattended speech in the left auditory and motor cortices negatively mediates attended speech comprehension.
Optical mapping compendium of structural variants across global cattle breeds
Authors: Talenti A. , Powell J. , Wragg D. , Chepkwony M. , Fisch A. , Ferreira B.R. , Marcadante M.E.Z. , Santos I.M. , Ezeasor C.K. , Obishakin E.T. , Muhanguzi D. , Amanyire W. , Silwamba I. , Muma J.B. , Mainda G. , Kelly R.F. , Toye P. , Connelley T. , Prendergast J. 
Published: May 2022

AbstractStructural variants (SV) have been linked to important bovine disease phenotypes, but due to the difficulty of their accurate detection with standard sequencing approaches, their role in shaping important traits across cattle breeds is largely unexplored. Optical mapping is an alternative approach for mapping SVs that has been shown to have higher sensitivity than DNA sequencing approaches. The aim of this project was to use optical mapping to develop a high-quality database of structural variation across cattle breeds from different geographical regions, to enable further study of SVs in cattle.To do this we generated 100X Bionano optical mapping data for 18 cattle of nine different ancestries, three continents and both cattle sub-species. In total we identified 13,457 SVs, of which 1,200 putatively overlap coding regions. This resource provides a high-quality set of optical mapping-based SV calls that can be used across studies, from validating DNA sequencing-based SV calls to prioritising candidate functional variants in genetic association studies and expanding our understanding of the role of SVs in cattle evolution.