bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Evolution of Colloid Administration in Burn Resuscitation
Authors: Fidler Philip , Lineaweaver William 
Published: March 2022

Abstract
Colloid administration in acute resuscitation of burn injuries is being increasingly recognized as an important part of fluid management for these injuries. Such clinical experience, along with possibilities of endothelial preservation by colloid solutions, could lead to a major reconsideration of early colloid administration in burn resuscitation.
Genomic Epidemiology of SARS-CoV-2 in Seychelles, 2020-2021
Authors: Morobe John Mwita , Pool Brigitte , Marie Lina , Didon Dwayne , Lambisia Arnold W. , Makori Timothy , Mohammed Khadija Said , de Laurent Zaydah R. , Ndwiga Leonard , Mburu Maureen W. , Moraa Edidah , Murunga Nickson , Musyoki Jennifer , Mwacharo Jedida , Nyamako Lydia , Riako Debra , Ephnatus Pariken , Gambo Faith , Naimani Josephine , Namulondo Joyce , Tembo Susan Zimba , Ogendi Edwin , Balde Thierno , Dratibi Fred Athanasius , Ahmed Yahaya Ali , Gumede Nicksy , Achilla Rachel A. , Borus Peter K. , Wanjohi Dorcas , Tessema Sofonias K. , Mwangangi Joseph , Bejon Philip , Nokes D. James , Ochola-Oyier Lynette Isabella , Githinji George , Biscornet Leon , Agoti Charles N. 
Published: March 2022

ABSTRACTSeychelles, an archipelago of 155 islands in the Indian Ocean, had confirmed 24,788 cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by the 31st December 2021. The first SARS-CoV-2 cases in Seychelles were reported on the 14th of March 2020, but cases remained low until January 2021, when a surge of SARS-CoV-2 cases was observed on the islands. Here, we investigated the potential drivers of the surge by genomic analysis 1,056 SARS-CoV-2 positive samples collected in Seychelles between 14th March 2020 and 31st December 2021. The Seychelles genomes were classified into 32 Pango lineages, 1,042 of which fell within four variants of concern i.e., Alpha, Beta, Delta and Omicron. Sporadic cases of SARS-CoV-2 detected in Seychelles in 2020 were mainly of lineage B.1 (European origin) but this lineage was rapidly replaced by Beta variant starting January 2021, and which was also subsequently replaced by the Delta variant in May 2021 that dominated till November 2021 when Omicron cases were identified. Using ancestral state reconstruction approach, we estimated at least 78 independent SARS-CoV-2 introduction events into Seychelles during the study period. Majority of viral introductions into Seychelles occurred in 2021, despite substantial COVID-19 restrictions in place during this period. We conclude that the surge of SARS-CoV-2 cases in Seychelles in January 2021 was primarily due to the introduction of more transmissible SARS-CoV-2 variants into the islands.
Large scale brain network dynamics in very preterm children and relationship with socio-emotional outcomes
Authors: Siffredi Vanessa , Liverani Maria Chiara , Freitas Lorena G. A. , Tadros D. , Farouj Y. , Tolsa Cristina Borradori , Van De Ville Dimitri , Hüppi Petra Susan , Hà-Vinh Leuchter Russia 
Published: March 2022

AbstractChildren born very preterm (VPT; < 32 completed weeks of gestation) are at high risk of neurodevelopmental and neurobehavioral difficulties associated with atypical brain maturation. The analysis of large-scale brain network dynamics during rest allows to investigate brain functional connectivity and their association with behavioural outcomes. Of interest, prematurity has been associated with atypical socio-emotional development with significant implications for the forming of peer relationships, adaptive functioning, academic achievement and mental health. In this study, we extracted dynamic functional connectivity by using the innovation-driven co-activation patterns (iCAPs) framework in preterm and full-term children aged 6 to 9 to explore changes in spatial organisation, laterality and temporal dynamics of spontaneous large-scale brain activity. Multivariate pattern analysis was used to explore potential biomarkers for socio-emotional difficulties in preterm children. Results show a spatial organisation of 13 networks retrieved comparable to full-term controls. Dynamic features and lateralisation of network brain activity were also comparable across groups for all large-scale brain networks. Despite apparent similarities in terms of dynamical functional connectivity parameters, multivariate pattern analysis unveiled group differences in their associations with socio-emotional abilities. While a pattern of decreased engagement in certain brain networks were associated with better socio-emotional abilities in full-term controls; in the VPT group, better socio-emotional abilities were associated with coordination of activity across different networks, i.e., coupling duration between different pairs of networks. It is possible that group differences reflect reduced degree of maturation of functional architecture in the VPT group for socio-emotional abilities.
Mechanistic modeling-guided optimization of microneedle-based skin patch for rapid transdermal delivery of naloxone for opioid overdose treatment
Authors: Tijani Akeemat , Dogra Prashant , Peláez Maria J. , Wang Zhihui , Cristini Vittorio , Puri Ashana 
Published: March 2022

AbstractNaloxone, an FDA approved opioid inhibitor, used to reverse opioid overdose complications has up till date faced challenges associated with its delivery. Limitations include the use of invasive delivery forms and the need for frequent redosing due to its short half-life. Further, the use of the non-invasive commercially available intranasal form is faced with limitations such as nasal epistaxis and inability to use the intranasal channel due to nasal trauma common in addicts from frequent drug snorting. The goal of the current study was to design a rapidly dissolving polymeric microneedle (MN) patch with delivery and pharmacokinetic properties comparable to that seen with the commercially available NAL products, eliminating their highlighted limitations. Factors such as drug loading and polymer strength influenced the fabrication of the MNs. Compared to passive permeation, a reduced lag time of about 5-15 min was observed with a significant drug flux of 15.09 ± 7.68 μg/cm2/h seen in the first 1 h (p<0.05) with an array of 100 needles (500 µm long). Increasing the MN length and density (no. of needles/unit area) made a significant difference in the amount permeated and flux (p<0.05), with latter being more influential. Further, through a mechanistic model of drug release from the patch, integrated with pharmacokinetic modeling, we optimized the design of the patch to reproduce in-silico the clinical pharmacokinetics of NAL obtained through commercial intramuscular and intranasal devices. Model simulations and analyses revealed the significance of needle base diameter and needle count in improving systemic pharmacokinetics of NAL.
Numb-associated kinases are required for SARS-CoV-2 infection and are cellular targets for therapy
Authors: Karim Marwah , Saul Sirle , Ghita Luca , Sahoo Malaya Kumar , Ye Chengjin , Bhalla Nishank , Jin Jing , Park Jun-Gyu , Martinez-Gualda Belén , East Michael Patrick , Johnson Gary L. , Pinsky Benjamin A. , Martinez-Sobrido Luis , Asquith Christopher R. M. , Narayanan Aarthi , De Jonghe Steven , Einav Shirit 
Published: March 2022

AbstractThe coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to pose serious threats to global health. We previously reported that AAK1, BIKE and GAK, members of the Numb-associated kinase family, control intracellular trafficking of multiple RNA viruses during viral entry and assembly/egress. Here, using both genetic and pharmacological approaches, we probe the functional relevance of NAKs for SARS-CoV-2 infection. siRNA-mediated depletion of AAK1, BIKE, GAK, and STK16, the fourth member of the NAK family, suppressed SARS-CoV-2 infection in human lung epithelial cells. Both known and novel small molecules with potent AAK1/BIKE, GAK or STK16 activity suppressed SARS-CoV-2 infection. Moreover, combination treatment with the approved anti-cancer drugs, sunitinib and erlotinib, with potent anti-AAK1/BIKE and GAK activity, respectively, demonstrated synergistic effect against SARS-CoV-2 infection in vitro. Time-of-addition experiments revealed that pharmacological inhibition of AAK1 and BIKE suppressed viral entry as well as late stages of the SARS-CoV-2 life cycle. Lastly, suppression of NAKs expression by siRNAs inhibited entry of both wild type and SARS-CoV-2 pseudovirus. These findings provide insight into the roles of NAKs in SARS-CoV-2 infection and establish a proof-of-principle that pharmacological inhibition of NAKs can be potentially used as a host-targeted approach to treat SARS-CoV-2 with potential implications to other coronaviruses.
High neutralizing antibody levels against SARS-CoV-2 Omicron BA.1 and BA.2 after UB-612 vaccine booster
Authors: Guirakhoo Farshad , Wang Shixia , Wang Chang Yi , Kuo Hui-Kai , Peng Wen-Jiun , Liu Hope , Wang Lixia , Johnson Marina , Hunt Adam , Hu Mei Mei , Monath Thomas P. , Rumyantsev Alexander , Goldblatt David 
Published: March 2022

AbstractThe highly transmissible Omicron variant has caused high rates of breakthrough infections among vaccinated and convalescent individuals. Here, we demonstrate that a booster dose of UB-612 vaccine candidate delivered 7-9 months after primary vaccination increases neutralizing antibody levels by 131-, 61- and 49-fold against ancestral SARS-CoV-2, Omicron BA.1 and BA.2 variants, respectively. Based on the RBD protein binding antibody responses, we estimated a ∼95% efficacy against symptomatic COVID-19 caused by the ancestral strain after a UB-612 booster. Our results support UB-612 vaccine as a potent booster against current and emerging SARS-CoV-2 variants.
IL-27 skews TNF-alpha-induced inflammatory microenvironment in keratinocytes
Authors: Aioi Akihiro , Imamichi Tomozumi 
Published: March 2022

AbstractInflammaging has received considerable attention because aging is characterized by low-grade, chronic and asymptomatic inflammation, concomitant with increased blood levels of senescence-associated secretory phenotype (SASP) factors, including IL-1, IL-6, IL-8, IL-18 and tumor necrosis factor-alpha (TNF-alpha). On the other hand, IL-27 is not categorized as SASP factors though it is known that IL-27 has pleiotropic roles in inflammation. Here, we evaluated the interaction between TNF-alpha and IL-27 in the context of low-grade inflammation by using in HaCaT cells. TNF-alpha induced significant upregulation of IL-6 and IL-8 through the experimental concentrations (~10 ng/ml) of TNF-alpha, while the mRNA expression levels of IL-1RA, IL-10 and IL-18BP were unchanged. After confirming the expression of IL-27 receptor in HaCaT cells, we examined the effects of IL-27 alone on the cytokine expression. IL-27 alone significantly enhanced mRNA expression levels of IL-10 and IL-18BP by 1.61-fold and 1.46-fold, respectively, and also enhanced mRNA expression levels of IL-6 by 2.32-fold. In the presence of 100 ng/ml IL-27, the expression levels of anti-inflammatory cytokines, IL-1RA, IL-10 and IL-18BP, were significantly upregulated with the treatment of a physiological concentration (1 ng/ml) TNF-alpha. Taken together, a high concentration of IL-27 exhibits anti-inflammatory effects in the presence of a low concentration of TNF-alpha when keratinocytes are the recipient of IL-27 signaling, suggesting the anti-inflammatory roles of IL-27 in inflammaging may be regulated by TNF-alpha concentration.
A dataset of 5 million city trees: species clustering and climate effects in urban forests
Authors: McCoy Dakota E. , Goulet-Scott Benjamin , Meng Weilin , Atahan Bulent Furkan , Kiros Hana , Nishino Misako , Kartesz John 
Published: March 2022

AbstractSustainable cities depend on urban forests. City trees improve our health, clean the air, store CO2, and cool local temperatures. Comparatively less is known about urban forests as ecosystems, particularly their spatial composition, nativity statuses, biodiversity, and tree health. Here, we assembled and standardized a new dataset of N=5,132,890 trees from 63 of the largest US cities with detailed information on location, health, nativity status, and species. We further designed new tools to analyze the ecosystem structure of urban forests, including spatial clustering and abundance of native trees, and validate these tools in comparison to past methods. We show that city trees are significantly clustered by species in 93% of cities, potentially increasing pest vulnerability (even in cities with biodiverse urban forests). Further, non-native species significantly homogenize urban forests across cities, while native trees comprise 0.44%-85.6% (median=45.6%) of city tree populations. Native trees are less frequent in drier cities, and indeed climate significantly shapes both nativity and biodiversity in urban forests. Parks are more biodiverse than urban settings. Compared to past work which focused primarily on canopy cover and species richness, we show the importance of analyzing spatial composition and nativity statuses in urban forests (and we created new datasets and tools to do so). This dataset could be analyzed in combination with citizen-science datasets on bird, insect, or plant biodiversity; social and demographic data; or data on the physical environment. Urban forests offer a rare opportunity to intentionally design biodiverse, heterogenous, rich ecosystems.
In vivolow-intensity magnetic pulses durably alter neocortical neuron excitability and spontaneous activity
Authors: Boyer Manon , Baudin Paul , Stengel Chloé , Valero-Cabre Antoni , Lohof Ann M. , Charpier Stéphane , Sherrard Rachel M. , Mahon Séverine 
Published: March 2022

AbstractMagnetic brain stimulation is a promising treatment for neurological and psychiatric disorders. However, a better understanding of its effects at the individual neuron level is essential to improve its clinical application. We combined focal low-intensity repetitive transcranial magnetic stimulation (LI-rTMS) to the rat somatosensory cortex with intracellular recordings of subjacent pyramidal neuronsin vivo. Continuous 10 Hz LI-rTMS reliably evoked firing at ∼4-5 Hz during the stimulation period and induced durable attenuation of synaptic activity and spontaneous firing in cortical neurons, through membrane hyperpolarization and a reduced intrinsic excitability. However, inducing firing in individual neurons by repeated intracellular current injection did not reproduce LI-rTMS effects on neuronal properties. These data provide novel understanding of mechanisms underlying magnetic brain stimulation showing that, in addition to inducing biochemical plasticity, even weak magnetic fields can activate neurons and enduringly modulate their excitability.
Engineering Antioxidant and Oxygen-Releasing Lignin Composites to Promote Wound Healing
Authors: Balaji Swathi , Short Walker D. , Padon Benjamin W. , Belgodere Jorge A. , Jimenez Sarah E. , Deoli Naresh T. , Guidry Anna C. , Green Justin C. , Prajapati Tanuj J. , Farouk Fayiz , Kaul Aditya , Son Dongwan , Jung Olivia S. , Astete Carlos E. , Kim Myungwoong , Jung Jangwook P. 
Published: March 2022

ABSTRACTThe application of engineered biomaterials for wound healing has been pursued since the beginning of tissue engineering. Here, we attempt to apply functionalized lignin to confer antioxidation to the extracellular microenvironments of wounds and to deliver oxygen from the dissociation of calcium peroxide for enhanced vascularization and healing responses without eliciting inflammatory responses. Elemental analysis showed 17 times higher quantity of calcium in the oxygen releasing nanoparticles. Lignin composites including the oxygen releasing nanoparticles released around 500 ppm oxygen per day at least for 7 days. By modulating the concentration of the methacrylated gelatin, we were able to maintain the injectability of lignin composite precursors and the stiffness of lignin composites suitable for wound healing after photo-crosslinking.In situformation of lignin composites with the oxygen releasing nanoparticles enhanced the rate of tissue granulation, the formation of blood vessels and the infiltration of α-smooth muscle actin+fibroblasts into the wounds over 7 days. At 30 days after surgery, the lignin composite with oxygen generating nanoparticles remodeled the collagen architecture resembling to the reticular pattern of unwounded collagen with minimal scar formation. Thus, our study shows the potential of functionalized lignin for wound healing applications requiring balanced antioxidation and controlled release of oxygen for enhanced tissue granulation, vascularization and maturation of collagens.
Hybrid conferences: opportunities, challenges and ways forward
Authors: Puccinelli Eleonora , Zeppilli Daniela , Stefanoudis Paris , Wittische-Helou Annaïg , Kermorgant Marjorie , Fuchs Sandra , Sarrazin Jozée , Easton Erin E. , Weber Alexandra Anh-Thu 
Published: March 2022

AbstractHybrid conferences are in-person events that are also accessible online. This type of meeting format was rare pre-COVID-19 but started to become more common recently given the asynchronous global progression of the pandemic and the uneven access and distribution of vaccines that led to a large proportion of participants being unable to attend international conferences in person. Here we report the organization of a middle-sized (581 participants: 159 onsite, 422 online) international hybrid conference that took place in France in September 2021. We highlight particular organizational challenges inherent to this relatively new type of meeting format. Furthermore, we surveyed both in-person and online participants to better understand their conference experience and to propose improvements based on the feedback received. Finally, we compare the advantages and disadvantages of three types of conferences (onsite-only, online-only and hybrid) and suggest that hybrid events should be favored in the future because they offer the most flexibility to participants. We conclude by proposing suggestions and ways forward to maximize accessibility and inclusivity of hybrid conferences.
Barrel cortex development lacks a key stage of hyperconnectivity from deep to superficial layers in a rat model of Absence Epilepsy
Authors: Plutino Simona , Laghouati Emel , Jarre Guillaume , Depaulis Antoine , Guillemain Isabelle , Bureau Ingrid 
Published: March 2022

AbstractThe development of cortical neuronal wiring is precisely orchestrated and goes through several stages, some of which coincide with critical periods when sensory experience is most influential. In particular, although ascending excitatory and inhibitory projections from the deep layer 5 to upper layers are first strong, they recede by the end of the critical period of their targets cells located in upper layers. Alterations in these transient innervations impair the construction of the later circuits that remain at adulthood, but it is unknown whether they could lead to pathologies. Here, we address this question in a genetic model of Absence Epilepsy, a neuro-developmental disease, where epileptogenesis occurs during the postnatal maturation of barrel cortex, the seizure initiation site. Using functional mapping by laser scanning photostimulation with glutamate uncaging in slices, we investigated the pattern of projections onto layers 2/3 pyramidal cells from 2-week old rats. We found that its maturation skipped the key stage during which pyramidal cells received strong projections from both excitatory and inhibitory neurons located in deep layers. At the same age, neuronal activity recorded in vivo with two-photon functional imaging was organized in fewer clusters than in control rat pups during this transient hyper-innervation. Later, around the onset of typical absence seizures (∼1 month old), over-excitability of cells was observed across layers. Using this genetic model of childhood epilepsy, we provide first evidence that failure to develop this transient hyper-innervation from deep cortical layers plays a role in pathological neural dysfunctions.Significance StatementDuring development of cortex, innervation from deep to upper layers is thought to provide a temporary scaffold for the construction of the circuits that remain at adulthood. Whether an alteration in this sequence causes brain malfunctions in neuro-developmental diseases is unknown. Using functional approaches, we investigated in a genetic model of Absence Epilepsy and control rats the maturation of innervation onto layer 2/3 pyramidal cells of barrel cortex and the cell organization into neuronal assemblies. We found that development in this model lacks this early surge of connectivity with deep layers and the concomitant structuring into multiple assemblies. Later on, at seizure onset, neurons in all layers are hyper-excitable, suggesting this feature of epilepsy develops from prior connectivity defects.
Near telomere-to-telomere nuclear phased chromosomes of the dikaryotic wheat fungus Rhizoctonia cerealis
Authors: Zeng Qingdong , Cao Wenjin , Li Wei , Wu Jianhui , Figueroa Melania , Liu Huiquan , Qin Guowei , Wang Qinhu , Yang Liming , Zhou Yan , Yu Yunxin , Huang Lin , Liu Shengjie , Luo Yuming , Mu Zhiying , Li Xiang , Liu Jiajie , Wang Xiaoting , Wang Changfa , Yuan Fengping , Chen Huaigu , Xu Haibin , Dodds Peter N. , Han Dejun , Kang Zhensheng 
Published: March 2022

AbstractRhizoctonia cerealis (Rce), which causes sharp eyespot, is one of the most destructive wheat pathogens. However, the genetic and molecular virulence mechanisms of Rce have not been elucidated. As a dikaryotic organism, the haplotype phasing of this fungus has not been completed so far. We applied a haplotype phasing algorithm to generate a high-quality near telomere-to-telomere nuclear-phased genome sequence of Rce strain R0301. Sixteen pairs of chromosomes were assigned to the A and B genomes with a total size of 83 Mb. Based on a dual-time course RNA-seq, 25308 genes were predicted. Genes for steroid biosynthesis and starch and sucrose metabolism were significantly enriched, together with many genes encoding carbohydrate-active enzymes (CAZymes) and secreted effector proteins, which should be involved in infection of wheat plants. Population genomic analysis of 31 isolates collected in China during the last forty years suggests that this population has not undergone substantial differentiation over time.ImportanceThe finished genome reference is the basis of revealing pathogens’ biology base. Many efforts have been made to produce the chromosome-scale assembly of fungi. However, the reference of many pathogenic fungi is highly fragmented, which prevents the analysis of genome structure variation, evolution and import pathogenicity genes. Here, we assembly the only chromosome-scale haplotype-phased reference of dikaryotic fungus so far. This assembly achieves the gold standard based on many evaluation software, which indicates that the pipeline developed in this study can be applied to assemble references for other dikaryotic organisms. This work can also promote the research on the globe’s destructive wheat pathogens, sharp eyespot, caused by R. cerealis.