bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinician and patient experience of neurology telephone consultations during the COVID-19 pandemic
Authors: Nakornchai Tagore , Conci Elena , Hensiek Anke , Brown J William L 
Published: September 2021

AbstractBackgroundTelephone consultations are already employed in specific neurological settings. At Cambridge University Hospitals, the COVID-19 pandemic initially prompted almost all face-to-face appointments to be delivered by telephone, providing a uniquely unselected population to assess.ObjectivesWe explored patient and clinician experience of telephone consultations; and whether telephone consultations might be preferable for pre-identifiable subgroups of patients after the pandemic.MethodsClinicians delivering neurological consultations converted to telephone between April-July 2020 were invited to complete a questionnaire following each consult (430 respondents) and the corresponding patients were subsequently surveyed (290 respondents). The questionnaires assessed clinician and patient goal achievement (and the reasons for any dissatisfaction). Clinicians also described consultation duration (in comparison to face-to-face) while patients detailed comparative convenience and preference.ResultsThe majority of clinicians (335/430, 78%) and patients (227/290, 78%) achieved their consultation goals by telephone, particularly during follow-up consultations (clinicians 272/329, 83%, patients 176/216, 81%) and in some disease subgroups (e.g. seizures/epilepsy (clinicians 114/122 (93%), patients 71/81 (88%)). 95% of telephone consultations were estimated to take the same or less time than an equivalent face-to-face consultation. Most patients found telephone consultations convenient (69%) with 149/211 (71%) indicating they would like telephone or video consultations to play some role in their future follow-up.ConclusionTelephone consultations appear effective, convenient and popular in prespecified subgroups of neurological outpatients. Further work comparing telephone, video and face-to-face consultations across multiple centres is now needed.
Direct neuronal conversion of microglia/macrophages reinstates neurological function after stroke
Authors: Irie Takashi , Matsuda Taito , Hayashi Yoshinori , Kamiya Akihide , Kira Jun-ichi , Nakashima Kinichi 
Published: September 2021

AbstractIschaemic brain injury causes permanent neuronal loss, which often results in persistent severe neurological dysfunctions. Although generating new neurons in the injured brain would be an ideal approach to replenish the lost neurons for repairing the damage, the adult mammalian brain retains only limited neurogenic capability. Here, we show that direct conversion of microglia/macrophages into neurons in the brain has great potential as a therapeutic strategy for ischaemic brain injury. After transient middle cerebral artery occlusion in adult mice, microglia/macrophages converge at the lesion core of the striatum, where neuronal loss is prominent. Targeted expression of a neurogenic transcription factor, NeuroD1, in microglia/macrophages in the injured striatum enables their conversion into induced neuronal cells that functionally integrate into the existing neuronal circuits. Furthermore, NeuroD1-mediated induced neuronal cell generation significantly improves neurological function in the mouse stroke model, and ablation of these cells abolishes the gained functional recovery. Our findings thus demonstrate that neuronal conversion contributes directly to functional recovery after stroke and shed further light on the development of therapies for ischaemic brain injury by in situ neuronal conversion technology.
Broadscale evolutionary analysis of eukaryotic DDE transposons
Authors: Dupeyron Mathilde , Baril Tobias , Hayward Alexander 
Published: September 2021

AbstractDDE transposons are widespread selfish genetic elements, often comprising a large proportion of eukaryotic genomic content. DDE transposons have also made important contributions to varied host functions during eukaryotic evolution, and their transposases may be the most abundant and ubiquitous genes in nature. Yet much remains unknown about their basic biology. We employ a broadscale screen of DDE transposase diversity to characterise major evolutionary patterns for all 19 DDE transposon superfamilies. We identify considerable variation in DDE transposon superfamily size, and find a dominant association with animal hosts. While few DDE transposon superfamilies specialise in plants or fungi, the four largest superfamilies contain major plant-associated clades, at least partially underlying their relative success. We recover a pattern of host conservation among DDE transposon lineages, punctuated by occasional horizontal transfer to distantly related hosts. Host range and horizontal transfer are strongly positively correlated with DDE transposon superfamily size, arguing against variation in the capacity for generalism. We find that rates of horizontal transfer decrease sharply with increasing levels of host taxonomy, supporting the existence of host-associated barriers to DDE transposon spread. Overall, despite their relatively simple genetic structure, our results imply that trade-offs in host adaptation are important in defining DDE transposon-host relationships and evolution. In addition, our study provides a phylogenetic framework to facilitate the identification and further analysis of DDE transposons.
Rapid evolution and strain turnover in the infant gut microbiome
Authors: Chen Daisy W. , Garud Nandita R. 
Published: September 2021

ABSTRACTWhile the ecological dynamics of the infant gut microbiome have been intensely studied, relatively little is known about the evolutionary dynamics in the infant gut microbiome. Here we analyze longitudinal fecal metagenomic data from >700 infants and their mothers over the first year of life and find that the evolutionary dynamics in infant gut microbiomes are distinct from that of adults. We find evidence for almost 100-fold increase in the rate of evolution and strain turnover in the infant gut compared to healthy adults, with the mother-infant transition at delivery being a particularly dynamic period in which gene loss dominates. Within a few months after birth, these dynamics stabilize, and gene gains become increasingly frequent as the microbiome matures. We furthermore find that evolutionary changes in infants show signatures of being seeded by a mixture ofde novomutations and transmissions of pre-evolved lineages from the broader family. Several of these evolutionary changes occur in parallel in multiple infants, highlighting candidate genes that may play important roles in the development of the infant gut microbiome. Our results point to a picture of a volatile infant gut microbiome characterized by rapid evolutionary and ecological change in the early days of life.
Injectable Liposome-based Supramolecular Hydrogels for the Programmable Release of Multiple Protein Drugs
Authors: Correa Santiago , Grosskopf Abigail K. , Klich John H. , Hernandez Hector Lopez , Appel Eric A. 
Published: September 2021

AbstractDirecting and manipulating biological functions is at the heart of next-generation biomedical initiatives such as tissue and immuno-engineering. Yet, the ambitious goal of engineering complex biological networks requires the ability to precisely perturb specific signaling pathways at distinct times and places. Using lipid nanotechnology and the principles of supramolecular self-assembly, we have developed an injectable liposomal nanocomposite hydrogel platform to precisely control drug presentation through programing of the co-release of multiple protein drugs. These liposomal hydrogels exhibited robust shear-thinning and self-healing behaviors enabling facile injectability for local drug delivery applications. By integrating modular lipid nanotechnology into this hydrogel platform, we introduced multiple mechanisms of protein release based on liposome surface chemistry. When injected into immuno-competent mice, these liposomal hydrogels exhibited formulation-dependent rates of dissolution and excellent biocompatibility. To fully validate the utility of this system for multi-protein delivery, we demonstrated the synchronized, sustained, and localized release of IgG antibody and IL-12 cytokine in vivo, despite the significant size differences between these two proteins. Overall, these liposomal nanocomposite hydrogels are a highly modular platform technology with the ability the mediate orthogonal modes of protein release and the potential to precisely coordinate biological cues both in vitro and in vivo.
SARS- CoV-2 viroporins: A multi-omics insight from nucleotides to amino acids
Authors: Sarkar Manish , Etheimer Paul , Hannothiaux Victor , Saha Soham 
Published: September 2021

AbstractCOVID-19 is caused by SARS-CoV-2 which has so far affected more than 500 million people worldwide and killed over 6 million as of 1st May, 2022. The approved emergency-use vaccines were lifesaving to such a devastating pandemic. Viroporins are important players of the life cycle of SARS-CoV-2 and are primary to its pathogenesis. We studied the two prominent viroporins of SARS-CoV-2 (i) Orf3a and (ii) Envelope (E) protein from a sequential and structural point of view. Orf3a is a cation selective viral ion channel which has been shown to disrupt the endosomal pathways. E protein is one of the most conserved proteins among the SARS-CoV proteome which affects the ERGIC related pathways. The aqueous medium through the viroporins mediates the non-selective translocation of cations, affecting ionic homeostasis in the host cellular compartments. This ionic imbalance could potentially lead to increased inflammatory response in the host cell. Our results shed light into the mechanism of viroporin action, which can be potentially leveraged for the development of antiviral therapeutics. Our results corroborate with previously published transcriptomic data from COVID-19 infected lung alveolar cells where inflammatory responses and molecular regulators directly impacted by ion channelling were upregulated.
Human neutrophils are not activated by Zika virus but reduce the infection of susceptible cells
Authors: Aggio Juliana Bernardi , Porto Bárbara Nery , dos Santos Claudia Nunes Duarte , Mosimann Ana Luiza Pamplona , Wowk Pryscilla Fanini 
Published: September 2021

AbstractZika virus (ZIKV) emergence highlighted the need for a deeper understanding on virus-host interaction to pave the development of antiviral therapies. The present work aimed to address the response of neutrophils during ZIKV infection. Neutrophils are an important effector cell in innate immunity involved in the host response to neurotropic arboviruses. Our results indicate that human neutrophils were not permissive to Asian or African ZIKV strains replication. Indeed, after stimulation with ZIKV, neutrophils were not primed against the virus as evaluated by the absence of CD11b modulation, secretion of inflammatory cytokines and granule content, production of reactive oxygen species and neutrophil extracellular traps formation. Overall, neutrophils did not affect ZIKV infectivity. Moreover, ZIKV infection of primary innate immune cells in vitro did not trigger neutrophil migration. However, neutrophil co-cultured with ZIKV susceptible cells (A549) resulted in lower frequencies of infection on A549 cells by cell-to-cell contact. In vivo, neutrophil depletion from immunocompetent mice did not affect ZIKV spreading to the draining lymph nodes. The data suggest human neutrophils do not play a per se antiviral role against ZIKV, but these cells might participate in an infected environment shaping the ZIKV infection in other target cells.
Survival prediction with Bayesian Networks in more than 6000 non-small cell lung cancer patients
Authors: Dekker A.L.A.J. , Hope A. , Lambin P. , Lindsay P. 
Published: September 2021

AbstractA model that predicts survival in lung cancer as a function of treatment choices would be valuable for decision support. In this study we built data flow tasks and a data warehouse to collect from clinical databases a large non-small cell lung cancer dataset from MAASTRO (N=1781) and from Princess Margaret Hospital (PMH, N=4591). We learned Bayesian Network (BN) models for survival prediction from the MAASTRO data and evaluated the models in the PMH dataset. The BN model based on stage and radiotherapy dose had a high predictive accuracy (AUC 0.917). The model correctly showed that radical radiotherapy (>60Gy) is beneficial for non-small cell lung cancer patients and that this benefit is disease stage dependent.
An integrated in silico-in vitro approach for identification of therapeutic drug targets for osteoarthritis
Authors: Lesage Raphaëlle , Ferrao Blanco Mauricio N. , Narcisi Roberto , Welting Tim , van Osch Gerjo J.V.M. , Geris Liesbet 
Published: September 2021

ABSTRACTWithout the availability of disease-modifying drugs, there is an unmet therapeutic need for osteoarthritic patients. During osteoarthritis, the homeostasis of articular chondrocytes is dysregulated and a phenotypical transition called hypertrophy occurs, leading to cartilage degeneration. Targeting this phenotypic transition has emerged as a potential therapeutic strategy. Chondrocyte phenotype maintenance and switch are controlled by an intricate network of intracellular factors, each influenced by a myriad of feedback mechanisms, making it challenging to intuitively predict treatment outcomes. In this study, we developed a regulatory network model using knowledge-based and data-driven modelling technologies. The in silico high-throughput screening of (pairwise) perturbations operated with that network model highlighted conditions impacting the hypertrophic switch. Several combinations were tested in a murine cell line and primary chondrocytes to validate the predicted conditions’ potential. Our in silico-in vitro strategy opens a new route for developing osteoarthritis targeting therapies by refining the early stages of drug discovery.
Neural oscillation coupling selectively predicts speech reception in young children with Autism Spectrum Disorder
Authors: Wang Xiaoyue , Delgado Jaime , Marchesotti Silvia , Kojovic Nada , Sperdin Holger Franz , Rihs Tonia A. , Schaer Marie , Giraud Anne-Lise 
Published: September 2021

SummaryCommunication difficulties in autism spectrum disorder (ASD) involve a speech reception deficit, whose biological causes are not yet identified. This deficit could denote atypical neuronal ensemble activity, as reflected by neural oscillations. Atypicalcross-frequency oscillation couplingin particular could disrupt the possibility to jointly track and predict dynamic acoustic stimuli, a dual process that is essential for speech comprehension. Whether such oscillation anomalies can already be found in very young children with ASD, and with what specificity they relate to individual language reception capacity is unknown. In this study, neural activity was collected using EEG in 64 very young children with and without ASD (mean age 3) while they were exposed to naturalistic-continuous speech via an age-appropriate cartoon. EEG power typically associated with phrase-level chunking (delta, 1-3Hz), phonemic encoding (low-gamma, 25-35Hz) and top-down control (beta, 12-20Hz) was markedly reduced in ASD relative to typically developing (TD) children. Speech neural-tracking by delta and theta oscillations was also weaker in ASD than TD children. Critically, children with ASD exhibited slightly atypical theta/gamma coupling (PAC) involving a higher-than-normal gamma frequency, and markedly atypical beta/gamma PAC. Even though many oscillation features were atypical in our sample of 31 very young children with ASD, the beta/gamma coupling anomaly was the single best predictor of individual speech reception difficulties. These findings suggest that early interventions targeting the normalization of low-gamma and low-beta activity, might help young children with ASD to engage more in oral interactions.HighlightsVery young children diagnosed with autism spectrum disorder already present marked alterations of neural oscillatory activity in response to natural speech.The hierarchical processing of phonemic- and syllabic-range information (theta/gamma coupling) is atypical in young ASD children.Speech reception deficit in children with ASD is indexed by abnormal bottom-up (low-gamma) and top-down (low-beta) coordination.
From trend to threat? Assessing the sustainability of wild edible plant foraging by linking local perception to ecological inference
Authors: Giraud Nicolas J. , Kool Anneleen , Karlsen Pål , Annes Alexis , Teixidor-Toneu Irene 
Published: September 2021

AbstractWild edible plants as culturally-appropriate sources of nutrition and for food security are now well-recognised. In Europe, the use of wild edible plants is shifting from a subsistence activity to an emerging trend in high-end gastronomy. The environmental impacts of this shift are poorly known. Foraging is increasingly popular for personal consumption and commercially, not least in the Nordic countries where popularity is fuelled by the New Nordic Food movement. Here, we evaluate if this trend entails biodiversity conservation risks in Norway. In collaboration with the Norwegian Association for Mycology and Foraging, we conducted 18 face-to-face interviews with key stakeholders and we published an online questionnaire filled by 219 recreational and professional foragers. We enquired on what species are harvested, by whom and how, where do foragers learn and what are their perspectives on the sustainability of foraging. We combined these data with an assessment of foraging impact based on foraging pressure, ecological traits and conservation assessments. Our results show that 272 different wild edible plants are foraged and that this is mostly sustainable.However, some risks arise from the harvest of threatened plants, the potential spread of invasive species, and the overharvesting of extremely popular or ‘fashionable’ species. Foraging fosters a strong connection with the natural environment and the majority of foragers report to forage as part of a sustainable lifestyle. We suggest that careful encouragement to forage and the participatory development of local guidelines for sustainable foraging in Norway can enhance people-nature relationships while safeguarding foraged plant populations.
Widespread density dependence of bacterial growth under acid stress
Authors: Fiegna Francesca , Pande Samay , Peitz Hansrainer , Velicer Gregory J. 
Published: September 2021

ABSTRACTBenefits of cooperation intrinsically depend on density because biological interaction requires organismal proximity. Microbial cooperative traits are common, yet systematic tests for a shared cooperative phenotype across diverse species are rare, as are direct tests for the Allee effect - positive density dependence of fitness. Here we test for positive density dependence of growth under acid stress in five phylogenetically widespread bacterial species - three Gram-negative and two Gram-positive - and find the Allee effect in all five. However, social protection from acid stress appears to have evolved by different mechanisms across species. In Myxococcus xanthus, the acid-stress Allee effect is found to be mediated by pH-regulated secretion of a diffusible molecule present in supernatant from high-density cultures. In contrast, growth from low density under acid stress by the other species was not enhanced by high-density supernatant. Additionally, density dependence of Myxococcus fruiting-body formation during starvation is found to increase with acid stress, suggesting that abiotic stresses other than starvation shape the evolution of aggregative development. Our findings suggest that high cell density may protect against acid stress in most bacterial species and in Myxococcus may promote predation on microbes that acidify their local environment by secretion of metabolic byproducts.
Lomitapide, a cholesterol-lowering drug, is an anticancer agent that induces autophagic cell death via inhibiting mTOR
Authors: Lee Boah , Park Seung Ju , Lee Seulgi , Lee Jinwook , Lee Eunbeol , Yoo Eun-Seon , Chung Won-Suk , Sohn Jong-Woo , Oh Byung-Chul , Kim Seyun 
Published: September 2021

AbstractAutophagy is a biological process that maintains cellular homeostasis and regulates the internal cellular environment. Hyperactivating autophagy to trigger cell death has been a suggested therapeutic strategy for cancer treatment. Mechanistic target of rapamycin (mTOR) is a crucial protein kinase that regulates autophagy; therefore, using a structure-based virtual screen analysis, we identified lomitapide, a cholesterol-lowering drug, as a potential mTOR complex 1 (mTORC1) inhibitor. Our results showed that lomitapide directly inhibits mTORC1 in vitro and induces autophagy-dependent cancer cell death by decreasing mTOR signaling, thereby inhibiting the downstream events associated with increased LC3 conversion in various cancer cells (e.g., HCT116 colorectal cancer cells) and tumor xenografts. Lomitapide also significantly suppresses the growth and viability along with elevated autophagy in patient-derived colorectal cancer organoids. Furthermore, a combination of lomitapide and immune checkpoint blocking antibodies synergistically inhibits tumor growth in murine MC-38 or B16-F10 pre-clinical syngeneic tumor models. These results elucidates the direct, tumor-relevant immune-potentiating benefits of mTORC1 inhibition by lomitapide, which complement the current immune checkpoint blockade. This study highlights the potential repurposing of lomitapide as a new therapeutic option for cancer treatment.
The interplay of supercoiling and thymine dimers in DNA
Authors: Lim Wilber , Randisi Ferdinando , Doye Jonathan P. K. , Louis Ard A. 
Published: September 2021

AbstractThymine dimers are a major mutagenic photoproduct induced by UV radiation. While they have been the subject of extensive theoretical and experimental investigations, questions of how DNA supercoiling affects local defect properties, or, conversely, how the presence of such defects changes global supercoiled structure, are largely unexplored. Here we introduce a model of thymine dimers in the oxDNA forcefield, parametrised by comparison to melting experiments and structural measurements of the thymine dimer induced bend angle. We performed extensive molecular dynamics simulations of double-stranded DNA as a function of external twist and force. Compared to undamaged DNA, the presence of a thymine dimer lowers the supercoiling densities at which plectonemes and bubbles occur. For biologically relevant supercoiling densities and forces, thymine dimers can preferentially segregate to the tips of the plectonemes, where they enhance the probability of a localized tip-bubble. This mechanism increases the probability of highly bent and denatured states at the thymine dimer site, which may facilitate repair enzyme binding. Thymine dimer-induced tip-bubbles also pin plectonemes, which may help repair enzymes to locate damage. We hypothesize that the interplay of supercoiling and local defects plays an important role for a wider set of DNA damage repair systems.