bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of the COVID-19 pandemic on short-term cancer survival in the United Kingdom: a cohort analysis
Authors: Barclay Nicola L , Burkard Theresa , Burn Edward , Delmestri Antonella , Dominguez Andrea Miquel , Golozar Asieh , Guarner-Argente Carlos , Avilés-Jurado Francesc Xavier , Man Wai Yi , Serrano Àlvar Roselló , Rosen Andreas Weinberger , Tan Eng Hooi , Tietzova Ilona ,   OPTIMA Consortium, Alhambra Daniel Prieto , Newby Danielle 
Published: September 2023

ABSTRACTObjectivesThe COVID-19 pandemic profoundly affected healthcare systems and patients. There is a pressing need to comprehend the collateral effects of the pandemic on noncommunicable diseases. Here we examined the impact of the COVID-19 pandemic on shortterm cancer survival in the United Kingdom (UK). We hypothesised that short-term survival from nine cancers would be reduced during the pandemic, particularly cancers that benefit from screening and early detection (e.g., breast and colorectal cancer).DesignPopulation-based cohort study.SettingElectronic health records from UK primary care Clinical Practice Research Datalink (CPRD) GOLD database.ParticipantsThere were 12,259,744 eligible patients aged ≥18 years with ≥one year of prior history identified from January 2000 to December 2021.Main outcome measuresWe estimated age-standardised incidence rates (IR) and short-term (one- and two-year) survival of several common cancers (breast, colorectal, head and neck, liver, lung, oesophagus, pancreatic, prostate, and stomach cancer) from 2000 to 2019 (in five-year strata) compared to 2020 to 2021 using the Kaplan-Meier method.ResultsApart from pancreatic cancer, IRs decreased for all cancers in 2020 and recovered to different extents in 2021. Short-term survival improved for most cancers between 2000 to 2019, but then declined for those diagnosed in 2020 to 2021.This was most pronounced for colorectal cancer, with one-year survival falling from 79.3% [95% confidence interval: 78.5%-80.1%] in 2015 to 2019 to 76.3% [74.6%-78.1%] for those diagnosed in 2020 to 2021.ConclusionShort-term survival for many cancers was impacted by the management of the COVID-19 pandemic in the UK. This decline was most prominent for colorectal cancer, with reductions in survivorship equivalent to returning to mortality seen in the first decade of the 2000s. These results illustrate the need for an immediate and well-funded investment in resolving the current backlog in cancer screening and diagnostic procedures in the UK National Health Service to improve patient outcomes.
Choice of Ultrafilter affects Recovery Rate of Bacteriophages
Authors: Larsen Frej , Offersen Simone Margaard , Li Viktoria Rose , Ling Deng , Nielsen Dennis Sandris , Rasmussen Torben Sølbeck 
Published: September 2023

AbstractStudies into the viral fraction of complex microbial communities like in the mammalian gut have recently garnered much interest. Yet there is still no standardized protocol for extracting viruses from such samples, and the protocols that exist employ procedures that skew the viral community of the sample one way or another. The first step of the extraction pipeline often consists of basic filtering of macromolecules and bacteria, yet even this affects the viruses in a strain-specific manner. In this study we investigate a protocol for viral extraction based on ultrafiltration and6 how the choice of ultrafilter might influence the viral community. Clinical samples (feces, vaginal7 swabs, and tracheal suction samples) were spiked with a mock community of known phages (T4,8 c2, Φ6, Φ29, Φx174, and Φ2972), filtered, and quantified by spot and plaque assays to estimate the9 loss in recovery. Especially the enveloped Φ6 phage is severely affected by choice of filter, but also10 tailed phages such as T4 and c2 have a reduced infectivity after ultrafiltration. We conclude that11 the pore size of ultrafilters may affect the recovery of phages in a strain- and sample dependent12 manner, suggesting the need for greater thought when selecting filters for virus extraction.
The Dynamics of Synthesis and Localization of Jumbo Phage RNA Polymerases inside Infected Cells
Authors: Antonova Daria , Belousova Viktoriia V. , Zhivkoplyas Erik , Sobinina Mariia , Artamonova Tatyana , Vishnyakov Innokentii E. , Kurdyumova Inna , Arseniev Anatoly , Morozova Natalia , Severinov Konstantin , Khodorkovskii Mikhail , Yakunina Maria V. 
Published: September 2023

AbstractA nucleus-like structure composed of phage-encoded proteins and containing replicating viral DNA is formed inPseudomonas aeruginosacells infected by jumbo bacteriophage phiKZ. The PhiKZ genes are transcribed independently from host RNA polymerase (RNAP) by two RNAPs encoded by the phage. The virion RNAP (vRNAP) transcribes early viral genes and must be injected into the cell with phage DNA. The non-virion RNAP (nvRNAP) is composed of early genes products and transcribes late viral genes. In this work, the dynamics of phage RNAPs localization during phage phiKZ infection was studied. We provide direct evidence of PhiKZ vRNAP injection in infected cells and show that it is excluded from the phage nucleus. The nvRNAP is synthesized shortly after the onset of infection and localizes in the nucleus. We propose that spatial separation of two phage RNAPs allows coordinated expression of phage genes belonging to different temporal classes.
Mapping glymphatic solute transportation through the perivascular space of hippocampal arterioles with 14 Tesla MRI
Authors: Zhou Xiaoqing Alice , Man Weitao , Liu Xiaochen , Choi Sangcheon , Jiang Yuanyuan , Hike David , Cid Lidia Gomez , Lin Changrun , Nedergaard Maiken , Yu Xin 
Published: September 2023

AbstractThe perivascular space (PVS) plays a crucial role in facilitating the clearance of waste products and the exchange of cerebrospinal fluid and interstitial fluid in the central nervous system. While optical imaging methods identify the glymphatic transport of fluorescent tracers through PVS of surface-diving arteries, their limited depth penetration impedes the study of glymphatic dynamics in deep brain regions. In this study, we introduced a novel high-resolution dynamic contrast-enhanced MRI mapping approach based on single-vessel multi-gradient-echo methods. This technique allowed the differentiation of penetrating arterioles and venules from adjacent parenchymal tissue voxels and enabled the detection of Gd-enhanced signals coupled to PVS of penetrating arterioles in the deep cortex and hippocampus. By directly infusing Gd into the lateral ventricle, we eliminated delays in cerebrospinal fluid flow and focused on PVS Gd transport through PVS of hippocampal arterioles. The study revealed significant PVS-specific Gd signal enhancements, shedding light on glymphatic function in deep brain regions. These findings advance our understanding of brain-wide glymphatic dynamics and hold potential implications for neurological conditions characterized by impaired waste clearance, warranting further exploration of their clinical relevance and therapeutic applications.
Timing Control of Purkinje Cell Outputs by Dual cAMP Actions on Axonal Action Potential and Transmitter Release
Authors: Furukawa Kei , Inoshita Takuma , Kawaguchi Shin-ya 
Published: September 2023

AbstractAll-or-none digital signaling based on high-fidelity action potentials (APs) in neuronal axons is pivotal for the temporally precise sending of identical outputs rapidly to widespread multiple target cells. However, technical limitation to directly measure the signaling in small size of intact axonal structures has hindered the evaluation of high-fidelity signal propagation. Here, using direct recordings from axonal trunks and/or terminals of cerebellar Purkinje cells in culture and slice, we demonstrate that the timing of axonal output is delayed by the second messenger cAMP without clear changes of transmission efficacy. Slowed axonal signaling upon cAMP increase was ascribed to negative control of axonal Na+channels, leading to smaller and hence slower conduction of APs specifically at an axon. On the other hand, a facilitatory effect of cAMP on presynaptic transmitter release, which generally operates at various CNS synapses, was also evident as augmented release probability in Purkinje cell axon terminals, compensating for weakening of release by the reduction of Ca2+influx upon smaller AP. Taken these results together, ourtour-de-forcefunctional dissection of inhibitory axonal signaling unveiled a dynamic control of synaptic output timing by cAMP keeping output strength constant.
A hierarchical atlas of the human cerebellum for functional precision mapping
Authors: Nettekoven Caroline , Zhi Da , Shahshahani Ladan , Luísa Pinho Ana , Saadon-Grosman Noam , Buckner Randy Lee , Diedrichsen Jörn 
Published: September 2023

ABSTRACTThe human cerebellum is activated by a wide variety of cognitive and motor tasks. Previous functional atlases have relied on single task-based or resting-state fMRI datasets. Here, we present a functional atlas that integrates information from 7 large-scale datasets, outperforming existing group atlasses. The new atlas has three further advantages: First, the atlas allows for precision mapping in individuals: The integration of the probabilistic group atlas with an individual localizer scan results in a marked improvement in prediction of individual boundaries. Second, we provide both asymmetric and symmetric versions of the atlas. The symmetric version, which is obtained by constraining the boundaries to be the same across hemispheres, is especially useful in studying functional lateralization. Finally, the regions are hierarchically organized across 3 levels, allowing analyses at the appropriate level of granularity. Overall, the new atlas is an important resource for the study of the interdigitated functional organization of the human cerebellum in health and disease.
Analysis of rhizosphere fungal community of agricultural crops cultivated in laboratory experiments on Chernevaya taiga soil
Authors: Kravchenko Irina , Rayko Mikhail , Sokornova Sophie , Tikhonova Ekaterina , Konopkin Aleksey , Lapidus Alla 
Published: September 2023

AbstractChernevaya taiga in Western Siberia, Russia, is a special environment with fertile soil, extraordinarily high herbaceous plant sizes, and incredibly quick rates of plant residues breakdown. We postulated that a unique rhizospheric fungal community would be created when growing crops on chernevaya soil, which has never been used for agriculture. These may be the source for the novel effective biostimulator and biocontrol fungal agents for modern agriculture. In this study, we analyzed the fungal communities in the rhizosphere of spring wheat and radish cultivated in greenhouse experiments on chernevaya and control soils using high-throughput ITS sequencing. Additionally reprehensive fungal strains were isolated and examined for the stimulation of wheat seedlings growth. The research shows that Ascomycota and Mortierellomycota were the most abundant phyla in the rhizospheric fungal community, mainly composed ofMortierellaspecies. The control soils were abundant in Mucoromycota, represented mostly byMucorandUmbelopsis. Potentially plant-pathogenic fungiFusarium and Oidiodendronwere found only in the rhizosphere of crops grown in the control soil. Whereas plants grown on chernevaya soil have a wide variety of possible biocontrol fungi. Novel fungal isolates demonstrated stimulating effect on the growth and biomass accumulation of wheat seedlings. The findings of the study imply that the creation of biorational products for crop growth and protection may depend on the taxonomic composition analysis of the rhizospheric mycobiota of the crops growing on the soil with the unique characteristics.
Identifying key species in meta-communities
Authors: Rollin Guillaume , Lages José , Gauzens Benoit 
Published: September 2023

AbstractWith the ongoing biodiversity crisis, identifying which species are of particular importance to prevent the extinction of other species has become a pressing issue. However, most approaches to detect these important species are made at a local (i.e, community) level, without considering the potential effect of species dispersion in a landscape.We present a modified PageRank algorithm to determine the importance of species in meta-communities based on two sets of networks: food webs that depict local trophic interactions and landscape networks representing the movement of species across different habitat patches.We show that (i) what is considered an important species changes between isolated communities and meta-communities and (ii) the importance of a species in a meta-community depends on the position of its habitat patch in the landscape network.Our results stress the need for a global consideration of space in the identification of important species.
Early language experience modulates the cortical tracking of speech
Authors: Pérez-Navarro Jose , Klimovich-Gray Anastasia , Lizarazu Mikel , Piazza Giorgio , Molinaro Nicola , Lallier Marie 
Published: September 2023

SummaryCortical tracking of speech is relevant for the development of speech perception skills. However, no study to date has explored whether and how cortical tracking of speech is shaped by accumulated language experience, the central question of this study. In 35 bilingual children (6 y.o.) with considerably bigger experience in one language, we collected electroencephalography data while they listened to continuous speech in their two languages. Cortical tracking of speech was assessed at acoustic-temporal and lexico-semantic levels. Children showed more robust acoustic-temporal tracking in the least experienced language, and more sensitive cortical tracking of semantic information in the most experienced language. Additionally, and only for the most experienced language, acoustic-temporal tracking was specifically linked to phonological abilities, and lexico-semantic tracking to vocabulary knowledge. Our results indicate that accumulated linguistic experience is a relevant maturational factor for the cortical tracking of speech at different levels during early language acquisition.
GluK1 kainate receptors are necessary for functional maturation of parvalbumin interneurons regulating amygdala circuit function
Authors: Haikonen Joni , Srinivasan Rakenduvadhana , Ojanen Simo , Rhee Jun Kyu , Ryazantseva Maria , Zumaraite Gabija , Lauri Sari E. 
Published: September 2023

AbstractParvalbumin expressing interneurons (PV INs) are key players in the local inhibitory circuits and their developmental maturation coincides with the onset of adult-type network dynamics in the brain. Glutamatergic signaling regulates emergence of the unique PV IN phenotype, yet the receptor mechanisms involved are not fully understood. Here we show that GluK1 subunit containing kainate receptors (KARs) are necessary for development and maintenance of the neurochemical and functional properties of PV INs in the basolateral amygdala (BLA). Ablation of GluK1 expression specifically from PV INs resulted in low parvalbumin expression and loss of characteristic high firing rate throughout development. In addition, we observed reduced spontaneous excitatory synaptic activity at adult GluK1 lacking PV INs. Intriguingly, inactivation of GluK1 expression in adult PV INs was sufficient to abolish the PV phenotype, suggesting a role for GluK1 in dynamic regulation of PV IN maturation state. The PV IN dysfunction in the absence of GluK1 perturbed feedforward inhibition and long-term potentiation (LTP) in the BLA and resulted in developmentally originating changes in the glutamatergic connectivity to BLA principal neurons. Behaviorally, the absence of GluK1 from PV INs associated with hyperactivity and increased fear of novelty. These results indicate a critical role for GluK1 KARs in regulation of PV IN function across development and suggest GluK1 as a potential therapeutic target for pathologies involving PV IN malfunction.
The multiplicity of Thioredoxin systems meets the specific needs of Clostridia
Authors: Anjou Cyril , Lotoux Aurélie , Zhukova Anna , Royer Marie , Caulat Léo C. , Capuzzo Elena , Morvan Claire , Martin-Verstraete Isabelle 
Published: September 2023

ABSTRACTOxidative stress is a highly common stress for cells, which targets proteins with oxidation of cysteine residues. The thioredoxin (Trx) system, which is a ubiquitous system for thiol- and protein-repair, is composed of a thioredoxin (TrxA) and a thioredoxin-reductase (TrxB). TrxAs reduce disulfide bonds of oxidized proteins and are then usually recycled by a single pleiotropic NAD(P)H-dependent TrxB (NTR). However, some Clostridia have also ferredoxin-dependent TrxBs.In this work, we first analyzed the composition of Trx systems across Bacteria. Most of bacteria have only one NTR, but organisms in some Phyla including Firmicutes have several TrxBs. In Firmicutes, this multiplicity of TrxBs is observed only in Clostridia. We thus usedClostridioides difficileas a model to investigate the biological relevance of TrxB multiplicity by studying the physiological roles of the Trx systems in this gut pathogen. Three TrxAs and three TrxBs are present in the 630Δermstrain. We showed that two systems were involved in response to infection-related stresses, allowing survival of vegetative cells to exposure to oxygen, inflammation-related molecules and bile salts. A supplementary TrxB copy present in someC. difficilestrains also contributes to this stress-response arsenal. One of the conserved stress-response Trx system was also found to be present in the sporeviaa dual transcriptional control by different sigma factors. This system contributes to spore survival to hypochlorite and ensure proper germination in the presence of oxygen. Finally, we found that the third Trx system was contributing to sporulation. This involvement was likely linked to the recycling of the glycine-reductase, a Stickland pathway enzyme that allows consumption of glycine, a spore co-germinant.Altogether, our results showed that the multiplicity of Trx systems produced under the control of different regulatory signals and networks and the diversity of TrxBs meet specific needs of Clostridia,i.e., adaptation to strong stress exposure, sporulation and Stickland pathways. More broadly, this multiplicity responds to cell compartmentation and differentiation, which can be transposed to other multiple-TrxBs organisms such as Cyanobacteria or eukaryotes.
DNA methylation shapes the Polycomb landscape during the exit from naïve pluripotency
Authors: Albert Julien Richard , Urli Teresa , Monteagudo-Sánchez Ana , Le Breton Anna , Sultanova Amina , David Angélique , Schulz Mathieu , Greenberg Maxim V.C. 
Published: September 2023

AbstractIn mammals, 5 methyl-cytosine (5mC) and Polycomb Repressive Complex 2 (PRC2)-deposited histone 3 lysine 27 trimethylation (H3K27me3) are generally mutually exclusive at CpG-rich regions. As mouse embryonic stem cells exit the naïve pluripotent state, there is a massive gain of 5mC coincident with a restriction of broad H3K27me3 to 5mC-free, CpG-rich regions. To formally assess how 5mC shapes the H3K27me3 landscape, we profiled the epigenome of naïve and differentiated cells in the presence and absence of the DNA methylation machinery. Surprisingly, we found that 5mC accumulation is not required to restrict most H3K27me3 domains. We went on to show that this 5mC-independent H3K27me3 restriction is mediated by aberrant expression of the PRC2 antagonistEzhip. At the regions where 5mC appears to genuinely supplant H3K27me3, we identified 68 candidate genes that appeared to require 5mC deposition and/or H3K27me3 depletion for their activation in differentiated cells. Employing site-directed epigenome editing to directly modulate 5mC levels, we demonstrated that 5mC deposition is sufficient to antagonize H3K27me3 deposition and confer gene activation at individual candidates. Altogether, we systematically measured the antagonistic interplay between 5mC and H3K27me3 in a system that recapitulates early embryonic dynamics. Our results suggest that H3K27me3 restraint depends on 5mC, both directly and indirectly. This study also reveals a non-canonical role of 5mC in gene activation, which may be important not only for normal development but also for cancer progression, as oncogenic cells frequently exhibit dynamic replacement of 5mC for H3K27me3 and vice versa.
Monkeybread: A Python toolkit for the analysis of cellular niches in single-cell resolution spatial transcriptomics data
Authors: Bernstein Matthew N. , Scott Dillon , Hession Cynthia C. , Nieuwenhuis Tim , Gerritsen Jacqueline , Tabrizi Siamak , Nandivada Vandana , Huggins Matthew A. , Duan Meixue , Malu Shruti , Tang Ming 
Published: September 2023

SummarySpatial transcriptomics technologies enable the spatially resolved measurement of gene expression within a tissue specimen. With these technologies, researchers can investigate how cells organize into cellular niches which are defined as distinct regions in the tissue comprising a specific composition of cell types or phenotypes. While general-purpose software tools for the exploratory analysis of spatial transcriptomics data exist, there is a need for tools that specialize in the analysis of cellular organization into niches. This can further enhance the downstream application of these data towards drug target discovery, target validation, and biomarker development. We present Monkeybread: A Python toolkit for analyzing cellular organization and intercellular communication in single-cell resolution spatial transcriptomics data. We applied Monkeybread to a human melanoma sample to demonstrate its utility in identifying cellular niches with diverse immunogenic compositions in the tumor microenvironment. We found that these niches were differentially enriched for immunogenic and tolerogenic macrophage populations that could be correlated to T cell abundance. These findings highlight how Monkeybread can be used for revealing underlying biology of the tumor microenvironment, and in the future, for understanding the influence of these niches on response to available treatments and discovery of novel drug targets.
Unveiling the cell biology of hippocampal neurons with dendritic axon origin
Authors: Han Yuhao , Thuenauer Roland , Grünewald Kay , Mikhaylova Marina 
Published: September 2023

SummaryIn mammalian axon-carrying-dendrite (AcD) neurons, the axon emanates from a basal dendrite, instead of the soma, to create a privileged route for action potential generation at the axon initial segment (AIS). However, it is unclear how such unusual morphology is established and whether the structure and function of the AIS in AcD neurons is preserved. Here, we show that the AcD neurons follow an intrinsically encoded developmental program where a single precursor neurite first gives rise to the axon and then to the AcD. The AIS possesses a similar cytoskeletal architecture as the canonical AIS that stems from the soma, and similarly functions as a trafficking barrier to retain axon-specific molecular composition. However, unlike soma-derived AIS, the AIS of AcD neurons does not undergo homeostatic-plasticity, contains less cisternal organelles and receives fewer inhibitory inputs. These distinct features of the AIS could account for the higher intrinsic excitability of AcD neurons.HighlightsThe development of AcD neurons is intrinsically driven and does not depend on specific connectivity patternsAcD neurons generate the axon and AcD from the same precursor neuriteThe stem dendrite of an AcD neuron displays axon-like microtubule organizationSimilar to the AIS emerging from the soma, the AIS of AcD neurons can selectively filter dendritic cargoThe AIS of AcD neurons does not undergo chronic homeostatic plasticity and receives fewer inhibitory inputs