bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incidence of Bowel Wall Swelling Induced by Iodine-Contrast Media and Its Association With Gastrointestinal Manifestation
Authors: Ishii Shiro , Yamakuni Ryo , Tsuchiya Takao , Yamaki Anna , Hara Junko , Sugawara Shigeyasu , Sekino Hirofumi , Fukushima Kenji , Ito Hiroshi 
Published: August 2023

Purpose
The aim of this study was to investigate the incidence of bowel wall swelling after iodine-contrast media injection and its relationship with gastrointestinal symptoms.

Methods
The incidence of bowel wall swelling was examined in 75 patients who showed adverse reactions to iodine-contrast media (AR[+] group) and 75 controls without adverse reactions (AR[−] group). Bowel wall swelling was identified if there was increased wall thickness on postcontrast computed tomography when compared with precontrast computed tomography. Swelling less than 2-fold of the original wall thickness was defined as grade 1 bowel angioedema, and swelling more than 2-fold was defined as grade 2.

Results
The incidence of bowel wall swelling was significantly higher in the AR(+) group (26.6%) than in the AR(−) group (10.6%) (P = 0.01). Grade 1 bowel wall swelling was observed in 12.0% and 10.7% of AR(+) and AR(−) groups, respectively, whereas grade 2 was observed in 14.7% and 0%, respectively. Bowel wall swelling was observed in the duodenum and jejunum but not in the stomach, ileum, or colon in any patient in either group. In the AR(+) group, nausea and/or vomiting was observed in 15 patients, among whom bowel wall swelling was observed in 9 patients (60%). The frequency of nausea and/or vomiting was significantly higher in the patients with bowel wall swelling (45.0%, 9/20) compared with those without (10.9%, 6/55).

Conclusion
Bowel wall swelling was more frequent and severe in patients with adverse reactions to iodine-contrast media than those without and was associated with nausea and/or vomiting.
Correlation Between Intranodular Vessels and Tumor Invasiveness of Lung Adenocarcinoma Presenting as Ground-glass Nodules
Authors: Zhao Baolian , Wang Xiang , Sun Ke , Kang Han , Zhang Kai , Yin Hongkun , Liu Kai , Xiao Yi , Liu Shiyuan 
Published: August 2023

Purpose:
To evaluate the role of quantitative features of intranodular vessels based on deep learning in distinguishing pulmonary adenocarcinoma invasiveness.

Materials and Methods:
This retrospective study included 512 confirmed ground-glass nodules from 474 patients with 241 precursor glandular lesions (PGL), 126 minimally invasive adenocarcinomas (MIA), and 145 invasive adenocarcinomas (IAC). The pulmonary blood vessels were reconstructed on noncontrast computed tomography images using deep learning-based region-segmentation and region-growing techniques. The presence of intranodular vessels was evaluated based on the automatic calculation of vessel prevalence, vascular categories, and vessel volume percentage. Further comparisons were made between different invasive groups by the Mantel-Haenszel χ2 test, χ2 test, and analysis of variance.

Results:
The detection rate of intranodular vessels in PGL (33.2%) was significantly lower than that of MIA (46.8%, P = 0.011) and IAC (55.2%, P < 0.001), while the vascular categories were similar (all P > 0.05). Vascular changes were more common in IAC and MIA than in PGL, mainly in increased vessel volume percentage (12.4 ± 19.0% vs. 6.3 ± 13.1% vs. 3.9 ± 9.4%, P < 0.001). The average intranodular artery and vein volume percentage of IAC (7.5 ± 14.0% and 5.0 ± 10.1%) was higher than that of PGL (2.1 ± 6.9% and 1.7 ± 5.8%) and MIA (3.2 ± 9.1% and 3.1 ± 8.7%), with statistical significance (all P < 0.05).

Conclusions:
The quantitative analysis of intranodular vessels on noncontrast computed tomography images demonstrated that the ground-glass nodules with increased internal vessel prevalence and volume percentages had higher possibility of tumor invasiveness.
Klebsiella pneumoniae Co-infection Leads to Fatal Pneumonia in SARS-CoV-2-infected Mice
Authors: Villalva Crystal , Patil Girish , Narayanan Sai , Chanda Debarati , Ghimire Roshan , Snider Timothy , Ramachandran Akhilesh , Channappanavar Rudragouda , More Sunil 
Published: August 2023

AbstractSARS-CoV-2 patients have been reported to have high rates of secondaryKlebsiella pneumoniaeinfections.Klebsiella pneumoniaeis a commensal that is typically found in the respiratory and gastrointestinal tracts. However, it can cause severe disease when a person’s immune system is compromised. Despite a high number ofK. pneumoniaecases reported in SARS-CoV-2 patients, a co-infection animal model evaluating the pathogenesis is not available. We describe a mouse model to study disease pathogenesis of SARS-CoV-2 andK. pneumoniaeco-infection. BALB/cJ mice were inoculated with mouse-adapted SARS-CoV-2 followed by a challenge withK. pneumoniae. Mice were monitored for body weight change, clinical signs, and survival during infection. The bacterial load, viral titers, immune cell accumulation and phenotype, and histopathology were evaluated in the lungs. The co-infected mice showed severe clinical disease and a higher mortality rate within 48 h ofK. pneumoniaeinfection. The co-infected mice had significantly elevated bacterial load in the lungs, however, viral loads were similar between co-infected and single-infected mice. Histopathology of co-infected mice showed severe bronchointerstitial pneumonia with copious intralesional bacteria. Flow cytometry analysis showed significantly higher numbers of neutrophils and macrophages in the lungs. Collectively, our results demonstrated that co-infection of SARS-CoV-2 withK. pneumoniaecauses severe disease with increased mortality in mice.
Targeted Amplification and Genetic Sequencing of the Severe Acute Respiratory Syndrome Coronavirus 2 Surface Glycoprotein
Authors: Keller Matthew W. , Keong Lisa M. , Rambo-Martin Benjamin L. , Hassell Norman , Lacek Kristine , Wilson Malania M. , Kirby Marie K. , Liddell Jimma , Owuor D. Collins , Sheth Mili , Madden Joseph , Lee Justin S. , Kondor Rebecca J. , Wentworth David E. , Barnes John R. 
Published: August 2023

AbstractThe SARS-CoV-2 spike protein is a highly immunogenic and mutable protein that is the target of vaccine prevention and antibody therapeutics. This makes the encoding S-gene an important sequencing target. The SARS-CoV-2 sequencing community overwhelmingly adopted tiling amplicon-based strategies for sequencing the entire genome. As the virus evolved, primer mismatches inevitably led to amplicon drop-out. Given the exposure of the spike protein to host antibodies, mutation occurred here most rapidly, leading to amplicon failure over the most insightful region of the genome. To mitigate this, we developed SpikeSeq, a targeted method to amplify and sequence the S-gene. We evaluated 20 distinct primer designs through iterativein silicoandin vitrotesting to select the optimal primer pairs and run conditions. Once selected, periodicin silicoanalysis monitor primer conservation as SARS-CoV-2 evolves. Despite being designed during the Beta wave, the selected primers remain > 99% conserved through Omicron as of 2023-04-14. To validate the final design, we compared SpikeSeq data and National SARS-CoV-2 Strain Surveillance whole-genome data for 321 matching samples. Consensus sequences for the two methods were highly identical (99.998%) across the S-gene. SpikeSeq can serve as a complement to whole-genome surveillance or be leveraged where only S-gene sequencing is of interest. While SpikeSeq is adaptable to other sequencing platforms, the Nanopore platform validated here is compatible with low to moderate throughputs, and its simplicity better enables users to achieve accurate results, even in low resource settings.
Comparative Analysis of Methods to Reduce Activation Signature Gene Expression in PBMCs
Authors: Andriamboavonjy Lovatiana , MacDonald Adam , Hamilton Laura K. , Labrecque Marjorie , Boivin Marie-Noёlle , Karamchandani Jason , Stratton Jo Anne , Tetreault Martine 
Published: August 2023

SummaryPreserving thein vivocell transcriptome is essential for accurate profiling, yet factors during cell isolation including timeex vivoand temperature induce artifactual gene expression, particularly in stress-responsive immune cells. In this study, we investigated two methods to mitigateex vivoactivation signature gene (ASG) expression in peripheral blood mononuclear cells (PBMCs): transcription and translation inhibitors (TTis) and cold temperatures during isolation. Comparative analysis of PBMCs isolated with TTis revealed reduced ASG expression. However, TTi treatment impaired responsiveness to LPS stimulation in subsequentin vitroexperiments. In contrast, cold isolation methods also prevented ASG expression; up to a point where the addition of TTis during cold isolation offered minimal additional advantage. These findings highlight the importance of considering the advantages and drawbacks of different isolation methods to ensure accurate interpretation of PBMC transcriptomic profiles.HighlightsTraditional room temperature isolation methods trigger activation signature gene expression in PBMCs, even when rapidly isolated, whereas 4°C isolation methods do not.Transcription and translation inhibitors and cold processing techniques reduce activation signature gene expression via shared mechanisms.PBMCs treated with transcription and translation inhibitors lose responsiveness to external stimuli.Cold isolation methods offer a suitable and inexpensive alternative to mitigate activation signature gene expression in PBMCs.
Childhood-onset asthma is characterized by airway epithelial hillock-to-squamous differentiation in early life
Authors: Kersten Elin T.G. , Pett J. Patrick , Malmström Kristiina , Chun Yoojin , Jonker Marnix R. , Wilbrey-Clark Anna , Worlock Kaylee B , van den Berge Maarten , Vermeulen Roel C.H. , Vonk Judith M. , Sebire Neil , Lohi Jouko , Timens Wim , Teichmann Sarah A , Bunyavanich Supinda , Nikolić Marko Z. , Nawijn Martijn C. , Mäkelä Mika J. , Meyer Kerstin B. , Koppelman Gerard H. 
Published: August 2023

AbstractChildhood-onset asthma is characterized by Type 2-inflammation and airway wall remodeling, but mechanisms of asthma development in the first years of life remain unclear. Here, we investigate transcriptional changes in airway wall biopsies of 22 symptomatic one year old children and relate these to asthma at school age. We demonstrate that pre-asthmatic children (n = 10) overexpressed a gene signature characteristic for an airway epithelial differentiation trajectory via hillock cells towards squamous cells (adjusted p-value 8.06e-16), whilst there was no association with gene signatures of Type 2-inflammation or eosinophil activation. Genes expressed along this trajectory are linked to an altered epithelial barrier function, innate immune activation and extracellular matrix remodeling. Functional GWAS analysis supports a causal link between childhood-onset, but not adult-onset asthma, and the hillock-squamous cell differentiation trajectory. Next, we confirmed the presence of hillock-like cells at the RNA and protein level in pediatric upper and lower airway samples. These findings identify a novel mechanism by which an aberrant airway epithelial differentiation trajectory may contribute to a pre-asthmatic state, highlighting the difference between the early origins of childhood-onset asthma and adult asthma, and point to possible new targets for the early diagnosis and treatment of asthma in the first two years of life.One Sentence SummaryRNA sequencing in bronchial biopsies from wheezing infants and children < 2 years shows evidence for an airway epithelial hillock-to-squamous differentiation pathway that marks the development of asthma.
Evolution of alternative reproductive systems inBacillusstick insects
Authors: Lavanchy Guillaume , Brandt Alexander , Bastardot Marc , Dumas Zoe , Labedan Marjorie , Massy Morgane , Toubiana William , TranVan Patrick , Luchetti Andrea , Scali Valerio , Mantovani Barbara , Schwander Tanja 
Published: August 2023

AbstractReproduction is a key feature of all organisms, yet the way in which it is achieved varies greatly across the tree of life. One striking example of this variation is the stick insect genusBacillus, in which five different reproductive modes have been described: sex, facultative and obligate parthenogenesis, and two highly unusual reproductive modes: hybridogenesis and androgenesis. Under hybridogenesis, the entire genome from the paternal species is eliminated, and replaced each generation by mating with the corresponding species. Under androgenesis, an egg is fertilized but the developing diploid offspring bear two paternal genomes, and no maternal genome, as a consequence of unknown mechanisms. Here, we re-evaluate previous descriptions ofBacilluslineages and the proposed F1hybrid ancestries of the hybridogenetic and obligately parthenogenetic lineages (based on allozymes and karyotypes) from Sicily, where all these reproductive modes are found. We generate a chromosome-level genome assembly for a facultative parthenogenetic species (B. rossius) and combine extensive field sampling with RADseq and mtDNA data. We identify and genetically corroborate all previously described species and confirm the ancestry of hybrid lineages. All hybrid lineages have fully retained their F1 hybrid constitution throughout the genome, indicating that the elimination of the paternal genome in hybridogens is always complete and that obligate parthenogenesis inBacillushybrid species is not associated with an erosion of heterozygosity as known in other hybrid asexuals. Our results provide a stepping stone towards understanding the transitions between reproductive modes and the proximate mechanisms of genome elimination.
Multiscale Rheology of Aging Cancer Spheroids
Authors: Gnanachandran Kajangi , Berardi Massimiliano , Skar Asmus , Pyka-Fościak Grażyna , Pabijan Joanna , Alonso Javier Lopez , Akca B. Imran , Lekka Małgorzata 
Published: August 2023

AbstractCancer spheroids offer a valuable experimental model that mimics the complexity and heterogeneity of solid tumors. Characterizing their mechanical response is crucial for understanding tumor development, progression, and drug response. Currently, whole live spheroids are analyzed primarily using image analysis, which is challenging, requires extended incubation times, and has limited imaging depth. Here, we present a new label-free approach for characterizing sub-superficial structures of bladder cancer spheroids and measuring their mechanical response at three distinct stages of cancer progression. We study the microrheological changes induced by aging at the cellular and cluster levels by conducting a multi-physics characterization and modeling approach. We find that spheroids exhibit viscoelastic behavior that can be described by fractional models. We show that spheroids are mechanically heterogeneous, with strong depth and time-dependent variations associated with evolving structural features. Our approach opens new possibilities to study 3Din vitromodels, paving the way for the discovery of novel and more precise procedure in cancer diagnosis based on the use of mechanomarkers.
High-intensity physiological activation disrupts the neural signatures of conflict processing
Authors: Avancini Chiara , Ciria Luis F. , Alameda Clara , Palenciano Ana Francisca , Canales-Johnson Andrés , Bekinschtein Tristan , Sanabria Daniel 
Published: August 2023

ABSTRACTPhysical activation fluctuates throughout the day. Previous studies have shown that during periods of reduced activation, cognitive control remains resilient due to neural compensatory mechanisms. In this study, we in-vestigated the effects of high physical activation on both behavioural and neural markers of cognitive control. We hypothesized that while behavioural measures of cognitive control would remain intact during periods of high activation, there would be observable changes in neural correlates. In our electroencephalography study, we manipulated levels of physical activation through physical exercise. Although we observed no significant impact on behavioural measures of cognitive conflict, both univariate and multivariate time-frequency markers proved unreliable under conditions of high activation. Moreover, there was no modulation of whole-brain connectivity measures by physical activation. We suggest that this dissociation between behavioural and neural measures indicates that the human cognitive control system remains resilient even at high activation, possibly due to underlying neural compensatory mechanisms.
Clearwing butterflies challenge the thermal melanism hypothesis
Authors: Ossola Violaine , Pottier Fabien , Pinna Charline , Bougiouri Katia , Tournié Aurélie , Michelin Anne , Andraud Christine , Gomez Doris , Elias Marianne 
Published: August 2023

AbstractIn contrast to most butterflies harboring opaque wing colorations, some species display large transparent patches on their wings. Wing transparency, which entails a dramatic reduction of pigmentation, raises the question of potential costs for vital functions, such as thermoregulation, especially along climatic gradients. The thermal melanism hypothesis posits that darker colorations should be favored in colder environments, which enables them to absorb more radiation and maintain a body temperature compatible with activity. This prediction extends to the near infrared (NIR) range, which represents a large proportion of solar radiation. Here we assess the implications of wing transparency for light absorption and thermal properties in 42 butterfly species from the neotropical tribe Ithomiini that range the extent of transparency, from fully opaque to highly transparent, and we test whether those species conform to the prediction of the thermal melanism hypothesis. We find that transparent wings are less efficient than opaque wings to absorb light across UV, Visible and NIR wavelength ranges, and are also less efficient to collect heat. Moreover, dark coloration occupies a lower proportion of wing area as altitude increases, and ithomiine species harbor more transparency at higher altitudes, where climatic conditions are colder, going strongly against the prediction of the thermal melanism hypothesis. We discuss these surprising results in light of recent studies suggesting that factors other than adaptation to cold, such as predation pressure, physiology or behavior, may have driven the evolution of wing patterns in Ithomiini.Significance StatementThe thermal melanism hypothesis predicts that organisms should be darker and absorb solar radiation more efficiently in colder environments. The Neotropical butterflies Ithomiini are unusual in that many species harbor large transparent patches on their wings, raising questions related to their efficacy of solar radiation absorption and heating capacities. We investigate optical and thermal properties of several ithomiine species along a climatic gradient. We find that transparent wings are less efficient at absorbing radiation and collecting heat. Unexpectedly, the proportion of transparent species increases with altitude, challenging the thermal melanism hypothesis and suggesting that factors other than adaptation to cold, such as predation pressure, may have driven the evolution of wing patterns in Ithomiini.
Mechanical forces control the valency of the malaria adhesin VAR2CSA by exposing cryptic glycan binding sites
Authors: Roessner Rita , Michelarakis Nicholas , Gräter Frauke , Aponte-Santamaría Camilo 
Published: August 2023

AbstractPlasmodium falciparum (Pf) is responsible for the most lethal form of malaria. VAR2CSA is an adhesin protein expressed by this parasite at the membrane of infected erythrocytes for attachment on the placenta, leading to pregnancy-associated malaria. VAR2CSA is a large 355 kDa multidomain protein composed of nine extracellular domains, a transmembrane helix, and an intracellular domain. VAR2CSA binds to Chondroitin Sulphate A (CSA) of the proteoglycan matrix of the placenta. Shear flow, as the one occurring in blood, has been shown to enhance the (VAR2CSA-mediated) adhesion ofPf-infected erythrocytes on the CSA-matrix. However, the underlying molecular mechanism governing this enhancement has remained elusive. Here, we address this question by using equilibrium, force-probe, and docking-based molecular dynamics simulations. We subjected the VAR2CSA protein–CSA sugar complex to a force mimicking the elongational tension exerted on this system due to the shear of the flowing blood. We show that upon this force exertion, VAR2CSA undergoes a large opening conformational transition before the CSA sugar chain dissociates from its main binding site. This preferential order of events is caused by the orientation of the molecule during elongation as well as the strong electrostatic attraction of the sugar to the main protein binding site. Upon opening, two additional cryptic CSA binding sites get exposed and a functional dodecameric CSA molecule can be stably accommodated at these force-exposed positions. Thus, our results suggest that mechanical forces, increase the avidity of VAR2CSA, by turning it from a monovalent to a multivalent state. We propose this to be the molecular cause of the observed shear-enhanced adherence. Mechanical control of the valency of VAR2CSA is an intriguing hypothesis that can be tested experimentally and which is of relevance for the understanding of the malaria infection and for the development of anti placental-malaria vaccines targeting VAR2CSA.
Jointly modeling deep mutational scans identifies shifted mutational effects among SARS-CoV-2 spike homologs
Authors: Haddox Hugh K. , Galloway Jared G. , Dadonaite Bernadeta , Bloom Jesse D. , Matsen Frederick A. , DeWitt William S. 
Published: August 2023

ABSTRACTDeep mutational scanning (DMS) is a high-throughput experimental technique that measures the effects of thousands of mutations to a protein. These experiments can be performed on multiple homologs of a protein or on the same protein selected under multiple conditions. It is often of biological interest to identify mutations with shifted effects across homologs or conditions. However, it is challenging to determine if observed shifts arise from biological signal or experimental noise. Here, we describe a method for jointly inferring mutational effects across multiple DMS experiments while also identifying mutations that have shifted in their effects among experiments. A key aspect of our method is to regularize the inferred shifts, so that they are nonzero only when strongly supported by the data. We apply this method to DMS experiments that measure how mutations to spike proteins from SARS-CoV-2 variants (Delta, Omicron BA.1, and Omicron BA.2) affect cell entry. Most mutational effects are conserved between these spike homologs, but a fraction have markedly shifted. We experimentally validate a subset of the mutations inferred to have shifted effects, and confirm differences of >1,000-fold in the impact of the same mutation on spike-mediated viral infection across spikes from different SARS-CoV-2 variants. Overall, our work establishes a general approach for comparing sets of DMS experiments to identify biologically important shifts in mutational effects.Significance StatementAmino-acid mutations to a protein have effects that can shift as the protein evolves or is put under new selective pressure. The effects of amino-acid mutations to a specific protein under a defined selective pressure can be measured by deep mutational scanning experiments. Here, we devise an approach to quantify shifts in mutational effects between experiments performed on different homologs (i.e. variants) of the same protein, or on the same protein selected under different conditions. We use this approach to compare experiments performed on three homologs of SARS-CoV-2 spike, identifying mutations that have shifted in their effect on spike-mediated viral infection by >1,000 fold across SARS-CoV-2 variants.