bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of Long COVID on Health-Related Quality-of-Life using OpenPROMPT
Authors: Carlile Oliver , Briggs Andrew , Henderson Alasdair D , Butler-Cole Ben FC , Tazare John , Tomlinson Laurie A , Marks Michael , Jit Mark , Lin Liang-Yu , Bates Chris , Parry John , Bacon Sebastian CJ , Dillingham Iain , Dennison William A , Costello Ruth E , Walker Alex J , Hulme William , Goldacre Ben , Mehrkar Amir , MacKenna Brian ,   The OpenSAFELY Collaborative, Herrett Emily , Eggo Rosalind M 
Published: December 2023

AbstractBackgroundLong COVID is a major problem affecting patient health, the health service, and the workforce. To optimise the design of future interventions against COVID-19, and to better plan and allocate health resources, it is critical to quantify the health and economic burden of this novel condition.MethodsWith the approval of NHS England, we developed OpenPROMPT, a UK cohort study measuring the impact of long COVID on health-related quality-of-life (HRQoL). OpenPROMPT invited responses to Patient Reported Outcome Measures (PROMs) using a smartphone application and recruited between November 2022 and October 2023. We used the validated EuroQol EQ-5D questionnaire with the UK Value Set to develop disutility scores (1-utility) for respondents with and without Long COVID using linear mixed models, and we calculated subsequent Quality-Adjusted Life-Months (QALMs) for long COVID.ResultsWe used data from 6,070 participants where 24.7% self-reported long COVID. In multivariable regressions, long COVID had a consistent impact on HRQoL, showing a high probability of reporting loss in quality-of-life (OR: 22, 95% CI:12.35-39.29) compared with people who did not report long COVID. Reporting a disability was the largest predictor of losses of HRQoL (OR: 60.2, 95% CI: 27.79-130.57) across survey responses. Self-reported long COVID was associated with an 0.37 QALM loss.ConclusionsWe found substantial impacts on quality-of-life due to long COVID, representing a major burden on patients and the health service. We highlight the need for continued support and research for long COVID, as HRQoL scores compared unfavourably to patients with conditions such as multiple sclerosis, heart failure, and renal disease.
Rapid, concerted switching of the neural code in inferotemporal cortex
Authors: Shi Yuelin , Bi Dasheng , Hesse Janis K. , Lanfranchi Frank F. , Chen Shi , Tsao Doris Y. 
Published: December 2023

AbstractA fundamental paradigm in neuroscience is the concept of neural coding through tuning functions1. According to this idea, neurons encode stimuli through fixed mappings of stimulus features to firing rates. Here, we report that the tuning of visual neurons can rapidly and coherently change across a population to attend to a whole and its parts. We set out to investigate a longstanding debate concerning whether inferotemporal (IT) cortex uses a specialized code for representing specific types of objects or whether it uses a general code that applies to any object. We found that face cells in macaque IT cortex initially adopted a general code optimized for face detection. But following a rapid, concerted population event lasting < 20 ms, the neural code transformed into a face-specific one with two striking properties: (i) response gradients to principal detection-related dimensions reversed direction, and (ii) new tuning developed to multiple higher feature space dimensions supporting fine face discrimination. These dynamics were face specific and did not occur in response to objects. Overall, these results show that, for faces, face cells shift from detection to discrimination by switching from an object-general code to a face-specific code. More broadly, our results suggest a novel mechanism for neural representation: concerted, stimulus-dependent switching of the neural code used by a cortical area.
A Kaspar Hauser experiment for innateness of numerical cognition
Authors: Lorenzi Elena , Perrino Matilde , Messina Andrea , Zanon Mirko , Vallortigara Giorgio 
Published: December 2023

AbstractWhether non-symbolic encoding of quantity is predisposed at birth with dedicated hard-wired neural circuits is debated. Here we presented newly-hatched visually naive chicks with stimuli (flashing dots) of either identical or different numerousness (with a ratio 1:3) with their continuous physical appearance (size, contour length, density, convex hull) randomly changing. Chicks spontaneously tell apart the stimuli on the basis of the number of elements. Upon presentation of either fixed or changing numerousness chicks also showed different expression of early genec-fosin the visual Wulst, the hippocampal formation, the intermediate medial mesopallium, and the caudal part of the nidopallium caudolaterale. The results support the hypothesis that the ability to discriminate quantities does not require any specific instructive experience. Evidence for innateness of non-symbolic numerical cognition have implications for both neurobiology and philosophy of mathematics.
Substrate promiscuity of theEscherichia colixanthine oxidase
Authors: Kronborg Kristina , Zhang Yong Everett 
Published: December 2023

AbstractPpnN is a cytosolic nucleosidase that cleaves nucleotide monophosphates to nucleobases and ribose-5-phosphate and plays a crucial role in regulating bacterial competitive fitness and persistence. To quantify the PpnN reaction, here we developed an enzyme-coupled assay, wherein PpnN hydrolyzes IMP to hypoxanthine, which is then converted by xanthine oxidase (XO) into xanthine, uric acid and hydrogen peroxide. The detection of hydrogen peroxide via horseradish peroxidase and Amplex Red provides a measure of PpnN enzymatic activity. Surprisingly, we found that in addition to IMP, other nucleotides like GMP significantly increased the signal, suggesting that the corresponding nucleobases might also be substrates for XO. Direct tests by using guanine confirmed XO’s capacity to use it as a substrate, albeit less effectively than hypoxanthine. These findings suggest a potential guanine aminohydrolase activity ofE. coliXO and broaden our understanding of nucleobase metabolism in bacterial systems.
Cultivation of host-adaptedCryptosporidium parvumandCryptosporidium hominisusing enteroids for cryopreservation of isolates and transcriptomic studies of infection
Authors: Deng Miner , Hou Tianyi , Mao Xinjie , Zhang Jie , Yang Fuxian , Wei Yanting , Tang Yongping , Zeng Wanting , Huang Wanyi , Li Na , Feng Yaoyu , Xiao Lihua , Guo Yaqiong 
Published: December 2023

ABSTRACTCryptosporidium hominisandCryptosporidium parvumare major causes of severe diarrhea in humans. Comparative studies of them are hampered by the lack of effective cultivation and cryopreservation methods, especially forC. hominis. Here, we described adapted murine enteroids for the cultivation of oneC. parvumIId subtype and nonhuman primate-adaptedC. hominisIb, Im, and In subtypes, which allowed the complete development of the pathogens, producing oocysts infectious to mice. Using the system, we developed a novel cryopreservation method forCryptosporidiumisolates. In comparative RNA-seq analyses ofC. hominiscultures, the enteroid system generated significantly more transcriptomic responses of both pathogen and host genes than the conventional HCT-8 cell system. In particular, the infection was shown to upregulate PI3K-Akt, Wnt, Ras,TNF, NF-κB, IL-17, MAPK, and innate immunity signaling pathways and downregulate Wnt and Hippo signaling pathways, host cell metabolism, and parasites in enteroid cultures had significantly higher expression of genes involved in oocyst formation. Therefore, the new culture model provides a valuable tool for comparative studies of the biology of divergentCryptosporidiumspecies.IMPORTANCEThe two dominant species for human cryptosporidiosis,Cryptosporidium hominisandCryptosporidium parvum, differ significantly in host range and virulence. Up to date, biological studies ofCryptosporidiumspp. are almost exclusively done with bovine-adapted IIa subtypes ofC. parvum, which is the species with effective laboratory animal models and in vitro cultivation methods. Here, we describe modified procedures for the generation of murine enteroids for successful cultivation of both nonhuman primate-adaptedC. hominissubtypes and aC. parvumIId subtype, producing oocysts infective to mice. In addition, we have developed a novel cryopreservation method using the system for long-term storage ofCryptosporidiumisolates. RNA-seq analyses ofC. hominiscultures indicate that the enteroid culture system generates host and pathogen transcriptomic responses similar to those in natural infection. This new development alleviates a technical bottleneck in cryptosporidiosis research, and provides an example for other difficult-to-culture pathogens of major public health importance.
Bacterial pathogens dynamic during multi-species infections
Authors: Barny Marie-Anne , Thieffry Sylvia , Gomes de Faria Christelle , Thebault Elisa , Pédron Jacques 
Published: December 2023

AbstractSoft rotPectobacteriacea(SRP) gathers more than 30 bacterial species that collectively rot a wide range of plants by producing and secreting a large set of plant cell wall degrading enzymes (PCWDEs). Worldwide potato field surveys identified 15 different SRP species on symptomatic plants and tubers. The abundance of each species observed during outbreaks varies over space and time and the mechanisms driving species shift during outbreak are unknown. Furthermore, multi-species infections are frequently observed and the dynamics of these coinfections are not well understood.To understand the dynamics of coinfections, we set up 16 different synthetic communities of 6 SRP strains to mimic coinfections. The bacteria present in each tested community were representative of 2 different species, with 3 strains per species. These communities were inoculated in potato tubers or on synthetic media and their outcome was followed by amplification and Illumina sequencing of the discriminatory housekeeping genegapA. We also compared disease incidence and bacterial multiplication in potato tubers during mixed-species infection and single-species infection. A species that was unable to induce disease in potato was efficiently maintained and eventually became dominant in some of the communities tested, indicating that cheating can shape dominant species. Modeling indicates that the cost of PCWDEs production and secretion, the rate of potato degradation and the diffusion rate of degraded substrate could favor the cheater species. Interaction outcomes differed between potato tuber and synthetic medium, highlighting the driving effect of environmental conditions, with higher antagonistic interactions observed in potato tubers. Antagonistic interactions were strain specific and not species specific. Toxicity interference was also observed within some communities, allowing the maintenance of strains otherwise sensitive to toxic compounds. Overall, the results indicate that intraspecific competition, cooperation through trophic interaction and toxicity interference contribute to the maintenance of SRP diversity. The implications of these processes for epidemiological surveillance are discussed.
Hi-C assembled genomes of estuarine populations reveal virus-microbe associations and a broad interaction range of a cyanophage
Authors: Rathwell Christina , McKay Cedar , Rocap Gabrielle 
Published: December 2023

AbstractAquatic microbes play key roles in global biogeochemical cycles and their viral-induced mortality influences the flow of carbon and nutrients between the dissolved and particulate pools. However, many microbes remain uncultivated, hindering understanding of their metabolic capabilities and preventing isolation of viruses that infect them. Here we augment metagenomic sequencing with Hi-C, a proximity-linkage method whereby DNA within a cell is physically bound and then sequenced to link contigs within a metagenome that originated from the same cell. In a size-fractioned water sample from beneath the euphotic zone in a hypoxic estuarine fjord in Puget Sound, WA we resolved 49 proximity-linked bins above 50% complete, including 21 Hi-C Assembled Genomes (HAGs) over 90% complete and a nearly complete genome of the eukaryotic green algaPicochlorum. Viral and microbial sequence within the same HAG identified 18 virus-microbe interactions. A myovirus and a siphovirus were associated with 2 different genera within the Saltatorellus clade of Planctomycetes, a phylum for which no virus has been identified. A partialPhycodnaviridaegenome linked to Haptophyte sequence is consistent with contemporaneous observations of a dissipating coccolithophore bloom. A cyanophage S-CAM7-like sequence had a broad interaction range. It was associated with a partialSynechococcusgenome in the >3.0 µm size fraction and with a Gammaproteobacteria related toAlcanivoraxin the 0.2µm-3.0µm fraction. We suggest that viruses produced in surface waters that are shuttled to depth on sinking aggregates may interact with different hosts in deeper waters, providing an important avenue for gene transfer across broad taxonomic ranges.ImportanceAquatic microbes are important in global elemental cycling. Knowing which viruses infect them in the environment remains a challenge. Using Hi-C, a molecular technique to physically link DNA within a cell, we assembled nearly complete genomes of both prokaryotes and eukaryotes from a hypoxic estuary. Hi-C links captured virus-host interactions for known virus-host pairs and for hosts with no previously known viruses. The same virus was linked to two distinct microbes in different size fractions of water, suggesting it has a broad host range. Viral lysis in surface waters generates sinking particles that deliver newly produced viruses to deeper waters where they interact with different potential hosts, providing an opportunity for gene exchange between unrelated microbes.
Paternal-effect genes revealed through semen cryopreservation inPerca fluviatilis
Authors: Panda Abhipsa , Judycka Sylwia , Palińska-Żarska Katarzyna , Debernardis Rossella , Jarmołowicz Sylwia , Jastrzębski Jan , de Almeida Taina Rocha , Błażejewski Maciej , Hliwa Piotr , Krejszeff Sławek , Żarski Daniel 
Published: December 2023

AbstractKnowledge about paternal-effect genes (the expression of which in progeny is controlled by the paternal genome) in fish is very limited. To explore this issue, we used semen cryopreservation as a specific challenge test for sperm cells, thus enabling selection amidst cryo-sensitivity. We created two groups of Eurasian perch (Perca fluviatilis) as a model – eggs fertilized either with fresh (Fresh group) or cryopreserved (Cryo group) semen from the same male followed by zootechnical-transcriptomic examination of consequences of cryopreservation in obtained progeny (at larval stages). Most of the zootechnical observations were similar in both groups, except the final weight was higher in the Cryo group. Semen cryopreservation appeared to act as a “positive selection” factor, upregulating most paternal-effect genes in the Cryo group. Transcriptomics profile of freshly hatched larvae sourced genes involved in the development of visual perception as paternal-effect genes. Consequently, larvae from the Cryo group exhibited enhanced eyesight, potentially contributing to more efficient foraging and weight gain compared to the Fresh group. This study unveils, for the first time, the significant influence of the paternal genome on the development of the visual system in fish, highlightingpde6g,opn1lw1, andrbp4las novel paternal-effect genes.
Tumor Immune Cell Targeting Chimeras (TICTACs) For Targeted Depletion of Macrophage-Associated Checkpoint Receptors
Authors: Morimoto Mariko , Till Nicholas A. , Bertozzi Carolyn R. 
Published: December 2023

AbstractImmune cells in the tumor microenvironment are not only powerful regulators of immunosuppression and tumorigenesis, but also represent a dominant cell type, with tumor-associated macrophages (TAMs) comprising up to 50% of total cell mass in solid tumors. Immunotherapies such as immune checkpoint inhibitors (ICIs) derive their efficacy from this cancer-immune cell interface, however, immune-related adverse events resulting from systemic blockade remain a significant challenge. To address this need for potent, yet highly tumor-specific immunotherapies, we developed Tumor-Immune Cell Targeting Chimeras (TICTACs), antibody conjugates that are capable of selectively depleting immune checkpoint receptors such as SIRPα from the surface of TAMs. These chimeric molecules consist of a synthetic glycan ligand that binds the C-type lectin CD206, a well-established TAM marker, conjugated to a non-blocking antibody that binds but does not inhibit the checkpoint receptor. By engaging CD206, which constitutively recycles between the plasma membrane and early endosomes, TICTACs facilitate robust removal of the checkpoint receptors from the surface of CD206highmacrophages, while having no effect on CD206lowmacrophages. By decoupling antibody selectivity from its blocking function, we present a new paradigm for developing highly tumor-specific immunotherapies.
Spatial organization of adenylyl cyclase and its impact on dopamine signaling in neurons
Authors: Ripoll Léa , von Zastrow Mark 
Published: December 2023

AbstractThe cAMP cascade is widely recognized to transduce its physiological effects locally through spatially limited cAMP gradients. However, little is known about how the adenylyl cyclase enzymes, which initiate cAMP gradients, are localized. Here we answer this question in physiologically relevant striatal neurons and delineate how AC localization impacts downstream signaling functions. We show that the major striatal AC isoforms are differentially sorted between ciliary and extraciliary domains of the plasma membrane, and that AC9 is uniquely targeted to endosomes. We identify key sorting determinants in the N-terminal cytoplasmic domain responsible for isoform-specific localization. We also show that AC9-containing endosomes accumulate activated dopamine receptors and form an elaborately intertwined network with juxtanuclear PKA stores bound to Golgi membranes. Finally, we show that endosomal localization is critical for AC9 to selectively elevate PKA activity in the nucleus relative to the cytoplasm. These results reveal a precise spatial landscape of the cAMP cascade in neurons and a key role of AC localization in directing downstream signal transduction to the nucleus.
Overall Health Effects of mRNA COVID-19 Vaccines in Children and Adolescents A Systematic Review and Meta-Analysis
Authors: Hoffmann Stine S. , Nielsen Sebastian , Thysen Sanne M. , Duriseti Ram , Benn Christine S. 
Published: December 2023

AbstractImportancePhase 3 randomized controlled trials (RCTs) of mRNA COVID-19 vaccines in children and adolescents showed efficacy in preventing COVID-19 infections. Vaccines may have non-specific effects.ObjectiveConduct a systematic review and meta-analysis of the phase 3 trials to assess overall and non-specific health effects of the mRNA COVID-19 vaccines.Data SourcesPubMed, Embase, Clinical Trials, Web of Science, and regulatory websites were searched for RCTs of mRNA vaccines. The latest trial data was included.Study SelectionAll RCTs conducted with mRNA vaccines BNT162b2 and mRNA-1237 in children and adolescents below 18 years, with placebo, adjuvant, or other vaccines as controls. 1199 studies were screened; six were included in the analysis.Data Extraction and SynthesisData on serious adverse events (“SAEs”) and severe adverse events (“Severe AEs”) as well as organ-specific diseases was extracted following the PRISMA reporting guideline, with a focus on non-specific infectious events. Risk Ratios (RRs) comparing vaccine vs placebo were calculated for each vaccine and combined in Mantel-Haenszel estimates.Main Outcomes and MeasuresThe primary outcomes were SAEs: overall, non-accident SAEs, and infectious SAEs, respectively. Secondary outcomes were Severe AEs and lower respiratory tract infection (LRTI) including RSV.ResultsThe analyses included 25,549 individuals (17,538 received mRNA; 8,011 received placebo). The risk of SAEs was similar for vaccine and placebo recipients. Both mRNA vaccines were associated with increased risk of severe AEs in older children. In a combined analysis, the RR was 3.77 (1.56-9.13[0.4% vs 0.1% in vaccine vs placebo recipients]) in above 5 year-olds, and 0.82 (0.53-1.29)[0.8% vs 0.9%])in younger children, who received a lower dose of vaccine (p=0.003 for same effect in older and younger children). In the younger children, mRNA vaccines were associated with higher risk of LRTI (RR=2.80 (1.32-5.94)[0.6% vs 0.3%]) including a higher risk of RSV infections (RR=2.78 (1.09-7.06)[0.4% vs 0.2%]).Conclusions and RelevancemRNA vaccines did not increase the risk of SAEs but were associated with an increased risk of severe AEs in older children, and an increased risk of LRTI, including RSV, in the young. Further research into the overall and non-specific health effects of mRNA vaccines is warranted.
DrosophilaWg and Evi/Wntless dissociation occurs post apical internalization in the late endosomes
Authors: Sharma Satyam , Chaudhary Varun 
Published: December 2023

AbstractSignaling pathways activated by secreted Wnt ligands play an essential role in tissue development and the progression of diseases, like cancer. Secretion of the lipid-modified Wnt proteins is tightly regulated by a repertoire of intracellular factors. For instance, a membrane protein, Evi/Wntless, interacts with the Wnt ligand in the ER, and it is essential for its further trafficking and release in the extracellular space. After dissociating from the Wnt, the Wnt-unbound Evi is recycled back to the ER via Golgi. However, where in this trafficking path Wnt proteins dissociate from Evi remains unclear. Here, we have used theDrosophilawing epithelium to trace the route of the Evi-Wg (Wnt homolog) complex leading up to their separation. In these polarized cells, Wg is first trafficked to the apical surface, however, the secretion of Wg is believed to occur post-internalization via recycling. Our results show that the Evi-Wg complex is internalized from the apical surface. Furthermore, using antibodies that specifically label the Wnt-unbound Evi, we show that Evi and Wg separation occurs post-internalization in the acidic endosomes. These results refine our understanding of the polarized trafficking of Wg and highlight the importance of Wg endocytosis in its secondary secretion.
The effect of global warming and climate changes on aircraft accidents between 2010-2022
Authors: Akay Tuncer , Tarhan Cevahir 
Published: December 2023

Purpose
One of the sectors most affected by the variable weather events caused by climate change and global warming is the aviation sector. Especially in aircraft accidents, weather events increasing with climate change and global warming are effective. The purpose of this study is to determine how much the change in weather conditions caused by global warming and climate changes affect the aircraft in the world between the years 2010 and 2022.

Design/methodology/approach
In this study, it was investigated which weather events were more effective in aircraft crashes by determining the rates of air events and aircraft crashes in aircraft crashes with a passenger capacity of 12 or more that occurred between 2010 and 2022.

Findings
It is clearly seen that increasing weather conditions with global warming and climate change increase the effect of weather conditions in aircraft crashes.

Originality/value
The difference of this study from other studies is the evaluation of the data of the past 12 years, in which the increasing consequences of global warming and climate change have been felt more. It also reveals the necessity of further research on the effects of weather conditions on aircraft.