bluuebunny/crossref_metadata_2025_split huggingface dataset:
Silent Hypoxia in Coronavirus disease-2019: Is it more dangerous?-A retrospective cohort study
Authors: Sirohiya Prashant , Elavarasi Arunmozhimaran , Raju Sagiraju Hari Krishna , Baruah Madhusmita , Gupta Nishkarsh , Garg Rohit Kumar , Paul Saurav Sekhar , Ratre Brajesh Kumar , Singh Ram , Kumar Balbir , Vig Saurabh , Pandit Anuja , Kumar Abhishek , Garg Rakesh , Meena Ved Prakash , Mittal Saurabh , Pahuja Saurabh , Das Nupur , Dwivedi Tanima , Gupta Ritu , Kumar Sunil , Pandey Manisha , Mishra Abhinav , Matharoo Karanvir Singh , Mohan Anant , Guleria Randeep , Bhatnagar Sushma 
Published: August 2021

AbstractBackgroundHypoxia in patients with COVID-19 is one of the strongest predictors of mortality. Silent hypoxia is characterized by the presence of hypoxia without dyspnea.. Silent hypoxia has been shown to affect the outcomes in previous studies.Research QuestionAre the outcomes in patients presenting with silent hypoxia different from those presenting with dyspneic hypoxia?Study design and MethodsThis was a retrospective study of a cohort of patients with SARS-CoV-2 infection who were hypoxic at presentation. Clinical, laboratory, and treatment parameters in patients with silent hypoxia and dyspneic hypoxia were compared. Multivariate logistic regression models were fitted to identify the factors predicting mortality.ResultsAmong 2080 patients with COVID-19 admitted to our hospital, 811 patients were hypoxic with SpO2<94% at the time of presentation. 174 (21.45%) did not have dyspnea since the onset of COVID-19 symptoms. 5.2% of patients were completely asymptomatic for COVID-19 and were found to be hypoxic only on pulse oximetry. The case fatality rate in patients with silent hypoxia was 45.4% as compared to 40.03% in dyspneic hypoxic patients (P=0.202). The odds ratio of death was 1.1 (95% CI 0.41-2.97) in the patients with silent hypoxia after adjusting for baseline characteristics, laboratory parameters, treatment, and in-hospital complications, which did not reach statistical significance (P=0.851).InterpretationSilent hypoxia may be the only presenting feature of COVID-19. Since the case fatality rate is comparable between silent and dyspneic hypoxia, it should be recognized early and treated as aggressively. Since home isolation is recommended in patients with COVID-19, it is essential to use pulse oximetry at the home setting to identify these patients.
A Large-Scale Investigation of White Matter Microstructural Associations with Reading Ability
Authors: Meisler Steven L. , Gabrieli John D.E. 
Published: August 2021

AbstractReading involves the functioning of a widely distributed brain network, and white matter tracts are responsible for transmitting information between constituent network nodes. Several studies have analyzed fiber bundle microstructural properties to shed insights into the neural basis of reading abilities and disabilities. Findings have been inconsistent, potentially due to small sample sizes and varying methodology. To address this, we analyzed a large data set of 686 children ages 5-18 using state-of-the-art neuroimaging acquisitions and processing techniques. We searched for associations between fractional anisotropy (FA) and single-word and single-nonword reading skills in children with diverse reading abilities across multiple tracts previously thought to contribute to reading. We also looked for group differences in tract FA between typically reading children and children with reading disabilities. FA of the white matter increased with age across all participants. There were no significant correlations between overall reading abilities and tract FAs across all children, and no significant group differences in tract FA between children with and without reading disabilities. There were associations between FA and nonword reading ability in older children (ages 9 and above). Higher FA in the right superior longitudinal fasciculus (SLF) and left inferior cerebellar peduncle (ICP) correlated with better nonword reading skills. These results suggest that letter-sound correspondence skills, as measured by nonword reading, are associated with greater white matter coherence among older children in these two tracts, as indexed by higher FA.
Allele expression biases in mixed-ploid sugarcane accessions
Authors: Correr Fernando Henrique , Furtado Agnelo , Garcia Antonio Augusto Franco , Henry Robert James , Margarido Gabriel Rodrigues Alves 
Published: August 2021

SummaryAllele-specific expression (ASE) represents differences in the magnitude of expression between alleles of the same gene. This is not straightforward for polyploids, especially autopolyploids, as knowledge about the dose of each allele is required for accurate estimation of ASE. This is the case for the genomically complex Saccharum species, characterized by high levels of ploidy and aneuploidy. We used a Beta-Binomial model to test for allelic imbalance in Saccharum, with adaptations for mixed-ploid organisms. The hierarchical Beta-Binomial model was used to test if allele expression followed the expectation based on genomic allele dosage. The highest frequencies of ASE occurred in sugarcane hybrids, suggesting a possible influence of interspecific hybridization in these genotypes. For all accessions, ASEGs were less frequent than those with balanced allelic expression. These genes were related to a broad range of processes, mostly associated with general metabolism, organelles, responses to stress and responses to stimuli. In addition, the frequency of ASEGs in high-level functional terms was similar among the genotypes, with a few genes associated with more specific biological processes. We hypothesize that ASE in Saccharum is largely a genotype-specific phenomenon, as a large number of ASEGs were exclusive to individual accessions.
The brain selectively tunes to unfamiliar voices during sleep
Authors: Ameen Mohamed S. , Heib Dominik PJ , Blume Christine , Schabus Manuel 
Published: August 2021

AbstractThe brain continues to respond selectively to environmental stimuli even during sleep. However, the functional role of such responses, and whether they reflect information processing or rather sensory inhibition is not fully understood.Here, we presented 17 human sleepers (14 females) with their own name and two unfamiliar first names, spoken by either a familiar voice (FV) or an unfamiliar voice (UFV), while recording polysomnography during a full night’s sleep. We detected K-complexes, sleep spindles, and micro-arousals, and then assessed event-related potentials, oscillatory power as well as intertrial phase synchronization in response to the different stimuli presented during non-rapid eye movement (NREM) sleep.We show that UFVs evoke more K-complexes and micro-arousals than FVs. When both stimuli evoke a K-complex, we observed larger evoked potentials, higher oscillatory power in the high beta (>16Hz) frequency range, and stronger time-locking in the delta band (1-4 Hz) in response to UFVs relative to FVs. Crucially, these differences in brain responses disappear when no K-complexes are evoked by the auditory stimuli.Our findings highlight discrepancies in brain responses to auditory stimuli based on their relevance to the sleeper and propose a key role for K-complexes in the modulation of sensory processing during sleep. We argue that such content-specific, dynamic reactivity to external sensory information enables the brain to enter a ‘sentinel processing mode’ in which it engages in the many important processes that are ongoing during sleep while still maintaining the ability to process vital information in the surrounding.Significance statementPrevious research has shown that sensory processing continues during sleep. Here, we studied the capacity of the sleeping brain to extract and process relevant sensory information. We presented sleepers with their own names and unfamiliar names spoken by either a familiar (FV) or an unfamiliar voice (UFV). During non-rapid eye movement (NREM) sleep, UFVs elicited more K-complexes and micro-arousals than FVs. By contrasting stimuli which evoked K-complexes, we demonstrate that UFVs triggered larger evoked potentials, stronger time-locking in the delta (1-4Hz) band, and higher oscillatory power (>16Hz) relative to FVs. These differences in brain responses disappeared when no K-complexes were evoked. Our results suggest a pivotal role for K-complexes in the selective processing of relevant information during NREM sleep.
Infection-Induced Dermal Lymphatic Zippering Restricts Viral Dissemination from Skin and Promotes Anti-Viral CD8+ T Cell Expansion
Authors: Churchill Madeline J. , du Bois Haley , Heim Taylor A. , Mudianto Tenny , Steele Maria M. , Nolz Jeffrey C. , Lund Amanda W. 
Published: August 2021

AbstractLymphatic vessels are often considered passive conduits that rapidly flush antigenic material, pathogens, and cells to draining lymph nodes. Recent evidence, however, suggests that lymphatic vessels actively regulate diverse processes from antigen transport to leukocyte trafficking and dietary lipid absorption. Here we tested the hypothesis that dermal lymphatic transport is dynamic and contributes to innate host defense during viral infection. We demonstrate that cutaneous vaccinia virus infection activates the tightening of lymphatic interendothelial junctions, termed zippering, in a VEGFA/VEGFR2-dependent manner. Both antibody-mediated blockade of VEGFA/VEGFR2 and lymphatic-specific deletion of Vegfr2 impaired lymphatic capillary zippering and increased fluid flux out of tissue. Strikingly, inhibition of lymphatic zippering allows viral dissemination to draining lymph nodes independent of dendritic cell migration and impairs CD8+ T cell priming. These data indicate that infection-induced dermal lymphatic capillary zippering is a context-dependent, active mechanism of innate host defense that limits interstitial fluid and virion flux and promotes protective, anti-viral CD8+ T cell responses.SummaryCutaneous infection with vaccinia virus induces VEGFR2-dependent dermal lymphatic capillary zippering. This tightening of lymphatic junctions exacerbates tissue edema, sequesters virus, and promotes anti-viral CD8+ T cell responses. Dermal lymphatic capillaries are therefore an active component of innate host defense.
KLF4 induces Mesenchymal - Epithelial Transition (MET) by suppressing multiple EMT-inducing transcription factors
Authors: Subbalakshmi Ayalur Raghu , Sahoo Sarthak , McMullen Isabelle , Saxena Aaditya Narayan , Venugopal Sudhanva Kalasapura , Somarelli Jason , Jolly Mohit Kumar 
Published: August 2021

AbstractEpithelial-Mesenchymal Plasticity (EMP) refers to reversible dynamic processes where cells can transition from epithelial to mesenchymal (EMT) or from mesenchymal to epithelial (MET) phenotypes. Both these processes are modulated by multiple transcription factors acting in concert. While EMT-inducing transcription factors (TFs) – TWIST1/2, ZEB1/2, SNAIL1/2/3, GSC, FOXC2 – are well-characterized, the MET-inducing TFs are relatively poorly understood (OVOL1/2, GRHL1/2). Here, using mechanism-based mathematical modeling, we show that the transcription factor KLF4 can delay the onset of EMT by suppressing multiple EMT-TFs. Our simulations suggest that KLF4 overexpression can promote phenotypic shift toward a more epithelial state, an observation suggested by negative correlation of KLF4 with EMT-TFs and with transcriptomic based EMT scoring metrics in cancer cell lines. We also show that the influence of KLF4 in modulating EMT dynamics can be strengthened by its ability to inhibit cell-state transitions at an epigenetic level. Thus, KLF4 can inhibit EMT through multiple parallel paths and can act as a putative MET-TF. KLF4 associates with patient survival metrics across multiple cancers in a context-specific manner, highlighting the complex association of EMP with patient survival.
Extensive incorporation, polarisation and improved maturation of transplanted human cones in a murine cone degeneration model
Authors: Gasparini Sylvia J , Tessmer Karen , Reh Miriam , Wieneke Stephanie , Carido Madalena , Völkner Manuela , Borsch Oliver , Swiersy Anka , Zuzic Marta , Goureau Olivier , Kurth Thomas , Busskamp Volker , Zeck Günther , Karl Mike O , Ader Marius 
Published: August 2021

SummaryOnce human photoreceptors die, they do not regenerate, thus photoreceptor transplantation has emerged as a potential treatment approach for blinding diseases. Improvements in transplant organization, donor cell maturation and synaptic connectivity to the host will be critical in advancing this technology to clinical practice. Unlike the unstructured grafts of prior cell suspension transplantations into end-stage degeneration models, we describe extensive incorporation of iPSC retinal organoid-derived human photoreceptors into mice with cone dysfunction. This incorporative phenotype was validated in both cone-only as well as pan-photoreceptor transplantations. Rather than forming a glial barrier, Müller cells extend throughout the graft, even forming a common outer limiting membrane. Donor-host interaction appears to promote polarisation as well as development of morphological features critical for light detection, namely formation of inner and well stacked outer segments oriented towards the RPE. Putative synapse formation and graft function is evident both at a structural and electrophysiological level. Overall, these results show that human photoreceptors interact readily with a partially degenerated retina. Moreover, incorporation into the host retina appears to be beneficial to graft maturation, polarisation and function.HighlightsGeneration of the first human iPSC cone reporter lineHuman cones extensively incorporate into the retina of mice with cone degenerationDonor cone age and time in vivo are important factors for transplant incorporationIncorporation into the host retina correlates with graft polarisationImproved photoreceptor maturation after transplantation in vivo vs. in vitroRe-establishment of cone-mediated light-responses in the cone deficient mouse
Deep molecular characterization linked to drug response profiling of pancreatic ductal adenocarcinoma using patient-derived organoids
Authors: Le Blanc Solange , Ishaque Naveed , Jabs Julia , Bauer Tobias , Schuth Sebastian , Hu Qing , Debnath Olivia , Ten Foo Wei , Leonhardt Carl-Stephan , König Anna-Katharina , Bieg Matthias , Eckert Christoph , Gaida Matthias M. , Volkmar Michael , Hübschmann Daniel , Schenk Miriam , Offringa Rienk , Giese Nathalia A. , Schlesner Matthias , Büchler Markus W. , Eils Roland , Conrad Christian , Strobel Oliver 
Published: August 2021

AbstractPancreatic ductal adenocarcinoma (PDAC) is characterized by high drug resistance and poor prognosis. Novel therapeutic and stratification strategies are urgently needed. Here, we present an integration of in-depth genomic and transcriptomic characterization with drug screening and clinical outcome based on a catalogue of 51 patient-derived tumor organoids (PDOs) from resected PDAC. Known PDAC molecular subtypes and their prognostic value are conserved in organoids. Integration of transcriptomic and drug response profiles suggest a metabolism-mediated modulations of drug resistance. Copy number alterations on chromosome 13q and wild-type status of TP53 emerged as potential novel genomic biomarkers for sensitivity to 5-FU and oxaliplatin treatment, respectively. Functional testing of targeted drugs in PDOs revealed its additional value for genome-driven personalized oncology. Co-deletion of TP53/POLR2A increased vulnerability to RNA polymerase II inhibition, pointing to a promising target for personalized treatment in PDAC.SignificancePatient-derived PDAC organoids hold great promise as surrogate tumor models for personalized oncology. By integrating highly granular molecular, drug sensitivity and clinical data, we demonstrate that PDOs are valid models for molecular characterization and response prediction that also enable identification of novel drug sensitivity biomarkers and resistance mechanisms in PDAC.
Fluorescence lifetime imaging as anin situand label-free readout for the chemical composition of lignin
Authors: Escamez Sacha , Terryn Christine , Gandla Madhavi Latha , Yassin Zakiya , Scheepers Gerhard , Näsholm Torgny , Sundman Ola , Jönsson Leif J. , Lundberg-Felten Judith , Tuominen Hannele , Niittylä Totte , Paës Gabriel 
Published: August 2021

AbstractImportant structures and functions within living organisms rely on naturally fluorescent polymeric molecules such as collagen, keratin, elastin, resilin, or lignin. Theoretical physics predict that fluorescence lifetime of these polymers is related to their chemical composition. We verified this prediction for lignin, a major structural element in plant cell walls and one of the most abundant components of wood. Lignin is composed of different types of phenylpropanoid units, and its composition affects its properties, biological functions, and the utilization of wood biomass. We carried out fluorescence lifetime imaging microscopy (FLIM) measurements of wood cell wall lignin in a population of 90 hybrid aspen trees genetically engineered to display differences in cell wall chemistry and structure. We also measured wood cell wall composition by classical analytical methods in the wood cell walls of these trees. Using statistical modelling and machine learning algorithms, we identified parameters of fluorescence lifetime that predict the content of S-type and G-type lignin units, the two main types of units in the lignin of angiosperm plants. Finally, we show how quantitative measurements of lignin chemical composition by FLIM can reveal the dynamics of lignin biosynthesis in two different biological contexts, includingin vivowhile lignin is being synthesized in the walls of living cells.
Towards Decoding Selective Attention Through Cochlear Implant Electrodes as Sensors in Subjects with Contralateral Acoustic Hearing
Authors: Aldag Nina , Büchner Andreas , Lenarz Thomas , Nogueira Waldo 
Published: August 2021

AbstractObjectivesFocusing attention on one speaker in a situation with multiple background speakers or noise is referred to as auditory selective attention. Decoding selective attention is an interesting line of research with respect to future brain-guided hearing aids or cochlear implants (CIs) that are designed to adaptively adjust sound processing through cortical feedback loops. This study investigates the feasibility of using the electrodes and backward telemetry of a CI to record electroencephalography (EEG).ApproachThe study population included 6 normal-hearing (NH) listeners and 5 CI users with contralateral acoustic hearing. Cortical auditory evoked potentials (CAEP) and selective attention were recorded using a state-of-the-art high-density scalp EEG and, in the case of CI users, also using two CI electrodes as sensors in combination with the backward telemetry system of these devices (iEEG).Main resultsThe peak amplitudes of the CAEPs recorded with iEEG were lower and the latencies were higher than those recorded with scalp EEG. In the selective attention paradigm with multi-channel scalp EEG the mean decoding accuracy across subjects was 92.0 and 92.5% for NH listeners and CI users, respectively. With single-channel scalp EEG the accuracy decreased to 65.6 and to 75.8% for NH listeners and CI users, respectively, and was above chance level in 9 out of 11 subjects. With the single-channel iEEG, the accuracy for CI users decreased to 70% and was above chance level in 3 out of 5 subjects.SignificanceThis study shows that single-channel EEG is suitable for auditory selective attention decoding, even though it reduces the decoding quality compared to a multi-channel approach. CI-based iEEG can be used for the purpose of recording CAEPs and decoding selective attention. However, the study also points out the need for further technical development for the CI backward telemetry regarding long-term recordings and the optimal sensor positions.
Decadal trend of plankton community change and habitat shoaling in the Arctic gateway recorded by planktonic foraminifera
Authors: Greco Mattia , Werner Kirstin , Zamelczyk Katarzyna , Rasmussen Tine L. , Kucera Michal 
Published: August 2021

AbstractThe Fram Strait plays a crucial role in regulating the heat and sea-ice dynamics in the Arctic. In response to the ongoing global warming, the marine biota of this Arctic gateway is experiencing significant changes with increasing advection of Atlantic species. The footprint of this “Atlantification” has been identified in isolated observations across the plankton community, but a systematic, multi-decadal perspective on how regional climate change facilitates the invasion of Atlantic species and affects the ecology of the resident species is lacking. Here we evaluate a series of 51 depth-resolved plankton profiles collected in the Fram Strait during seven surveys between 1985 and 2015, using planktonic foraminifera as a proxy for changes in both the pelagic community composition and species vertical habitat depth. The time series reveals a progressive shift towards more Atlantic species, occurring independently of changes in local environmental conditions. We conclude that this trend is reflecting higher production of the Atlantic species in the “source” region, from where they are advected into the Fram Strait. At the same time, we observe that the ongoing extensive sea-ice export from the Arctic and associated cooling-induced decline in density and habitat shoaling of the subpolarTurborotalita quinqueloba, whereas the residentNeogloboquadrina pachydermapersists. As a result, the planktonic foraminiferal community and vertical structure in the Fram Strait shifts to a new state, driven by both remote forcing of the Atlantic invaders and local climatic changes acting on the resident species. The strong summer export of Arctic sea ice has so far buffered larger plankton transformation. We predict that if the sea-ice export will decrease, the Arctic gateway will experience rapid restructuring of the pelagic community, even in the absence of further warming. Such a large change in the gateway region will likely propagate into the Arctic proper.
Accurate and automated high-coverage identification of chemically cross-linked peptides with MaxLynx
Authors: Yılmaz Şule , Busch Florian , Nagaraj Nagarjuna , Cox Jürgen 
Published: August 2021

ABSTRACTCross-linking combined with mass spectrometry (XL-MS) provides a wealth of information about the 3D structure of proteins and their interactions. We introduce MaxLynx, a novel computational proteomics workflow for XL-MS integrated into the MaxQuant environment. It is applicable to non-cleavable and MS-cleavable cross linkers. For both we have generalized the Andromeda peptide database search engine to efficiently identify cross-linked peptides. For non-cleavable peptides, we implemented a novel di-peptide Andromeda score, which is the basis for a computationally efficient N-squared search engine. Additionally, partial scores summarize the evidence for the two constituents of the di-peptide individually. A posterior error probability based on total and partial scores is used to control false discovery rates. For MS-cleavable cross linkers a scoring of signature peaks is combined with the conventional Andromeda score on the cleavage products. The MaxQuant 3D-peak detection was improved to ensure more accurate determination of the monoisotopic peak of isotope patterns for heavy molecules, which cross-linked peptides typically are. A wide selection of filtering parameters can replace manual filtering of identifications, which is often necessary when using other pipelines. On benchmark datasets of synthetic peptides, MaxLynx outperforms all other tested software on data for both types of cross linkers as well as on a proteome-wide dataset of cross-linked D. melanogaster cell lysate. The workflow also supports ion-mobility enhanced MS data. MaxLynx runs on Windows and Linux, contains an interactive viewer for displaying annotated cross-linked spectra and is freely available at https://www.maxquant.org/.