bluuebunny/crossref_metadata_2025_split huggingface dataset:
Large language model-based information extraction from free-text radiology reports: a scoping review protocol
Authors: Reichenpfader Daniel , Müller Henning , Denecke Kerstin 
Published: August 2023

AbstractIntroductionRadiological imaging is one of the most frequently performed diagnostic tests worldwide. The free text contained in radiology reports is currently only rarely utilized for secondary use, including research and predictive analysis. However, this data might be made available by means of information extraction (IE), based on natural language processing (NLP). Recently, a new approach to NLP, large language models (LLMs), has gained momentum and continues to improve performance. The objective of this scoping review is to show the state of research regarding IE from free-text radiology reports based on LLMs, to investigate applied methods, and to guide future research by showing open challenges and limitations of current approaches. To our knowledge, no systematic nor scoping review of IE of radiology reports, based on LLMs, has been conducted yet. Existing publications are outdated and do not comprise LLM-based models.Methods and analysisThis protocol is designed based on the JBI manual for evidence synthesis, chapter 11.2: “Development of a scoping review protocol”. Inclusion criteria and a search strategy comprising four databases (PubMed, IEEE Xplore, Web of Science Core Collection, ACM Digital Library) are defined. Furthermore, we describe the screening process, data charting, analysis and presentation of extracted data.Ethics and disseminationThis protocol describes the methodology of a scoping literature review and does not comprise research on or with humans, animals or their data. Therefore, no ethical approval is required. After the publication of this protocol and the conduct of the review, its results are going to be published in an open access journal dedicated to biomedical informatics/ digital health.Strengths and limitations of this studyThis scoping review protocol strictly adheres to standardized guidelines for scoping review conduction, including JBI Manual for Evidence Synthesis and the PRISMA-ScR guideline.The search strategy comprises four databases: PubMed, IEEE Xplore, Web of Science Core Collection, and ACM Digital Library.This scoping review will close the knowledge gap present in the field of information extraction from radiology reports caused by the recent rapid technical process.According to the nature of a scoping review, identified sources of evidence are not critically appraised.The results of the scoping review will serve as a basis for defining further research directions regarding information extraction from radiology reports.
Plasma protein biomarkers distinguish Multisystem Inflammatory Syndrome in Children (MIS-C) from other pediatric infectious and inflammatory diseases
Authors: Yeoh Sophya , Estrada-Rivadeneyra Diego , Jackson Heather , Keren Ilana , Galassini Rachel , Cooray Samantha , Shah Priyen , Agyeman Philipp , Basmaci Romain , Carrol Enitan , Emonts Marieke , Fink Colin , Kuijpers Taco , Torres Federico Martinon- , Mommert-Tripon Marine , Paulus Stephane , Pokorn Marko , Rojo Pablo , Romani Lorenza , Schlapbach Luregn , Schweintzger Nina , Shen Ching-Fen , Tsolia Maria , Usuf Effua , Van der Flier Michiel , Vermont Clementien , Both Ulrich Von , Yeung Shunmay , Zavadska Dace , Coin Lachlan , Cunnington Aubrey , Herberg Jethro , Levin Michael , Kaforou Myrsini , Hamilton Shea ,   UK KD Genetics Consortia
Published: August 2023

ABSTRACTBackgroundMultisystem inflammatory syndrome in children (MIS-C) is a rare but serious hyperinflammatory complication following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The mechanisms underpinning the pathophysiology of MIS-C are poorly understood. Moreover, clinically distinguishing MIS-C from other childhood infectious and inflammatory conditions, such as Kawasaki Disease (KD) or severe bacterial and viral infections is challenging due to overlapping clinical and laboratory features. We aimed to determine a set of plasma protein biomarkers that could discriminate MIS-C from those other diseases.MethodsSeven candidate protein biomarkers for MIS-C were selected based on literature and from whole blood RNA-Sequencing data from patients with MIS-C and other diseases. Plasma concentrations of ARG1, CCL20, CD163, CORIN, CXCL9, PCSK9 and ADAMTS2 were quantified in MIS-C (n=22), KD (n=23), definite bacterial (DB; n=28) and viral (DV, n=27) disease, and healthy controls (n=8). Logistic regression models were used to determine the discriminatory ability of individual proteins and protein combinations to identify MIS-C, and association with severity of illness.ResultsPlasma levels of CD163, CXCL9, and PCSK9 were significantly elevated in MIS-C with a combined AUC of 86% (95% CI: 76.8%-95.1%) for discriminating MIS-C from other childhood diseases. Lower ARG1 and CORIN plasma levels were significantly associated with severe MIS-C cases requiring oxygen, inotropes or with shock.ConclusionOur findings demonstrate the feasibility of a host protein biomarker signature for MIS-C and may provide new insight into its pathophysiology.
Population Pharmacokinetics and Target Attainment Analysis of Vancomycin after Intermittent Dosing in Adults with Cystic Fibrosis
Authors: Yellepeddi Venkata K. , Lindley Bryn , Radetich Emi , Kumar Shaun , Bhakta Zubin , Leclair Laurie , Parrot Madison , Young David C. 
Published: August 2023

ABSTRACTVancomycin is the first-line agent to treat pulmonary infections caused by methicillin-resistantStaphylococcus aureus(MRSA) in people with cystic fibrosis (PwCF). However, there is no consensus on vancomycin dosing in this population among health institutions, and there is large variability in dosing regimens across the United States. In this study, we characterized the pharmacokinetics (PK) of vancomycin in PwCF using a population PK approach. The clinical PK data to develop the population PK model was obtained from vancomycin therapeutic monitoring data from PwCF undergoing treatment for infections due to MRSA. The population PK model was then used to perform comprehensive Monte Carlo simulations to evaluate the probability of target attainment (PTA) of 12 different dosing scenarios. The area under the curve to minimum inhibitory concentration ratio (AUC/MIC) ≥ 400 mg*h/L was used as a target for PTA analysis. A total of 181 vancomycin plasma concentrations were included in the analysis. A onecompartment model with first-order elimination best described the data. Weight significantly influenced the vancomycin PK (p< 0.05). In the final model, clearance was estimated as 5.52 L/h/70 kg, and the volume of distribution was 31.5 L/70 kg. The PTA analysis showed that at lower MIC levels (MIC = 1), doses greater than and equal to 1000 mg every 8 hours and 1250 mg every 12 hours resulted in >90% PTA. The PTA results from this study may potentially inform the design of vancomycin dosing regimens to treat pulmonary infections due to MRSA in PwCF.
The changes in blood flow velocity in the internal jugular vein under conditions of variable intrapulmonic pressure and gravitational effect
Authors: Kasatkin Anton , Urakov Aleksandr , Kuvshinov Ivan , Zhulkov Nikita 
Published: August 2023

AbstractBackgroundWe explored the dynamics of changes in the blood flow velocity in the internal jugular vein (IJV) under conditions of changing intrapulmonary pressure and gravitational influence in healthy volunteers.MethodsColor duplex ultrasonography of the right IJV was performed in 25 healthy volunteers of both genders. The dopplergram of the blood flow spectrum was recorded in the right IJV in the horizontal supine position of the participants, and 3 minutes after the volunteers had attained the new position due to the lifting the bed back section at the 30°. We recorded the maximum (Max) and minimum (Min) linear of blood flow velocity (cm/s). In each position, the measurements were carried out sequentially at positive end-expiratory pressure (PEEP) values of 0, 5, 10 cmH2O after 3 minutes by process of changing the level of PEEP. Quantitative data were presented as arithmetic mean (M), standard deviation (SD) and compared using the Wilcoxon rank-sum test.ResultsOur data demonstrated that negatively related influence of continuous positive airway pressure on IJV blood flow velocity: Max/Min 57.40±13.10/20.68±7.80 cm/s (PEEP 0 cmH2O), 39.00±18.80/14.63±4.90 (PEEP 5 cmH2O), 30.83±7.30/13.25±2.90 (PEEP 10 cmH2O). The blood flow velocity values are increased after 30° head elevation in PEEP 5 and 10 cmH2O in comparison to 0° values.ConclusionsThe constant positive airway pressure 5-10 cmH2O in a person in supine position decreasing blood flow velocity in IJV. The 30° head elevation eliminates this effect.
Magnitude of Psychological Distress among Medical and Non-medical Students during the Late Phase of COVID-19 Pandemic in West Bengal: A Cross-sectional Study
Authors: Das Udisa , Ganguly Arunima , Haldar Dibakar , Mukhopadhyay Asish 
Published: August 2023

AbstractBackgroundCOVID-19 led to drastic changes worldwide which has affected mental health especially, of the vulnerable student population.AimThis study aimed to assess psychological distress due to COVID-19 in students during the late phase of pandemic and to establish correlation of academic course, socio-demographics and knowledge-attitude-practices (KAP) with depression and anxiety. An online cross-sectional survey was conducted among medical and non-medical students in Kolkata, from March to April 2022.MethodsA cross-sectional survey was done using purposive and snowball sampling methods. Survey questionnaire was circulated via Google forms through social media. It included Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, Fear of COVID-19 scale 2020, KAP regarding COVID-19 and socio-demographics. Data were analyzed using appropriate statistical methods with the Statistical Package for the Social Sciences (Version 22.0). P value of less than 0.05 was considered significant.ResultsTotal of 442 responses were received. After excluding incomplete responses, the final sample comprised 219 medical and 202 non-medical students. Majority of the participants were male (58.67%). Overall prevalence of depression was 58.42% in non-MBBS and 81.73% in MBBS students. Whereas, the overall prevalence of anxiety was 50.99% in non-MBBS and 76.25% in MBBS students. MBBS participants had significantly better scores for knowledge and attitude (p=0.000 in both). Depression was higher in those with previous history of psychiatric illness (p=0.015). Anxiety was influenced by residence (p=0.003), mode of travel to college (p=0.002), history of relatives or friends affected by COVID-19 (p= 0.005).ConclusionPrevalence of depression and anxiety in college students, especially among medical students, was higher in present study mainly due to long-term indirect effects of the pandemic. This calls for employing student wellness activities and provision of better mental health services across colleges in India.Key MessagesDepression and anxiety was observed to be higher especially among medical students. Previous history of psychiatric illness was found to be a correlate of depression. Anxiety was revealed to be influenced by residence, mode of travel to college, and history of family, friends or relatives affected by COVID-19.
Iron rescues glucose-mediated photosynthesis repression during lipid accumulation in the green algaChromochloris zofingiensis
Authors: Jeffers Tim L. , Purvine Samuel O. , Nicora Carrie D. , McCombs Ryan , Upadhyaya Shivani , Stroumza Adrien , Whang Ken , Gallaher Sean D. , Dohnalkova Alice , Merchant Sabeeha S. , Lipton Mary , Niyogi Krishna K. , Roth Melissa S. 
Published: August 2023

AbstractEnergy status and nutrients regulate photosynthetic protein expression. The unicellular green algaChromochloris zofingiensisswitches off photosynthesis in the presence of exogenous glucose (+Glc) in a process that depends on hexokinase (HXK1). Here, we show that this response requires that cells lack sufficient iron (−Fe). Cells grown in −Fe+Glc accumulate triacylglycerol (TAG) while losing photosynthesis and thylakoid membranes. However, cells with an iron supplement (+Fe+Glc) maintain photosynthesis and thylakoids while still accumulating TAG. Proteomic analysis shows that known photosynthetic proteins are most depleted in heterotrophy, alongside hundreds of uncharacterized, conserved proteins. Photosynthesis repression is associated with enzyme and transporter regulation that redirects iron resources to (a) respiratory instead of photosynthetic complexes and (b) a ferredoxin-dependent desaturase pathway supporting TAG accumulation rather than thylakoid lipid synthesis. Combining insights from diverse organisms from green algae to vascular plants, we show how iron and trophic constraints on metabolism aid gene discovery for photosynthesis and biofuel production.
Extrachromosomal Telomeres Derived from Excessive Strand Displacements
Authors: Lee Junyeop , Lee Jina , Sohn Eric J. , Taglialatela Angelo , O’Sullivan Roderick J. , Ciccia Alberto , Min Jaewon 
Published: August 2023

AbstractAlternative Lengthening of Telomeres (ALT) is a telomere maintenance mechanism mediated by break-induced replication (BIR), evident in approximately 15% of human cancers. A characteristic feature of ALT cancers is the presence of C-circles, circular single-stranded telomeric DNAs composed of C-rich sequences. Despite the fact that extrachromosomal C-rich single-stranded DNAs (ssDNAs), unique to ALT cells, are considered potential precursors of C-circles, their generation process remains undefined. Here, we introduce a highly sensitive method to detect single stranded telomeric DNA, called 4SET (Strand-Specific Southern-blot for Single-stranded Extrachromosomal Telomeres) assay. Utilizing 4SET, we are able to capture C-rich single stranded DNAs that are near 200 to 1500 nucleotides in size. Both linear C-rich ssDNAs and C-circles are abundant in the fractions of cytoplasm and nucleoplasm, which supports the idea that linear C-rich ssDNA accumulation may indeed precede C-circle formation. We also found that C-rich ssDNAs originate during Okazaki fragment processing during lagging strand DNA synthesis. The generation of C-rich ssDNA requires CST-PP (CTC1/STN1/TEN1-PRIMASE-Polymerase alpha) complex-mediated priming of the C-strand DNA synthesis and subsequent excessive strand displacement of the C-rich strand mediated by the DNA Polymerase delta and the BLM helicase. Our work proposes a new model for the generation of C-rich ssDNAs and C-circles during ALT-mediated telomere elongation.
Dynamics of the adhesion complex of the human pathogensMycoplasma pneumoniae and Mycoplasma genitalium
Authors: Vizarraga David , Kawamoto Akihiro , Marcos-Silva Marina , Martín Jesús , Makino Fumiaki , Miyata Tomoko , Roel-Touris Jorge , Marcos Enrique , Pich Òscar Q. , Aparicio David , Fita Ignacio , Miyata Makoto , Piñol Jaume , Namba Keiichi , Kenri Tsuyoshi 
Published: August 2023

AbstractMycoplasma pneumoniaeis a bacterial wall-less human pathogen and the etiological agent of atypical pneumonia and tracheobronchitis in both adults and children.M. pneumoniaeinfectivity, gliding motility and adherence to host target respiratory epithelial cells are mediated by adhesin proteins P1 and P40/P90 forming a transmembrane complex that binds to sialylated oligosaccharides human cell ligands. Here we report the cryo-EM structure of P1 bound to the Fab fragment of monoclonal antibody P1/MCA4, which stops gliding and induces detachment of motileM. pneumoniaecells. On the contrary, polyclonal antibodies generated against the N-domain of P1 or against the whole ectodomain of P40/P90 have little or no effects on adhesion or motility. The epitope of P1/MCA4, centred on loop Thr1426-Asp1438 in the small C-terminal domain of P1, is inaccessible to antibodies in the “open” conformation of the adhesion complex, when ready for attachment to sialylated oligosaccharides. Mutations in the highly conserved Engelman motifs found in the transmembrane helix of P40/P90 also alter adhesion and motility. During the attachment/detachment cycle of the adhesion complex, the C-terminal domain of P1 experiences large conformational rearrangements that are hindered by the antibodies against the domain. Interfering with the gliding of mycoplasma cells suggests new ways to confrontM. pneumoniaeinfections.
Spatiotemporal resonance in mouse primary visual cortex
Authors: Gulbinaite Rasa , Nazari Mojtaba , Rule Michael E. , Bermudez-Contreras Edgar J. , Cohen Michael X , Mohajerani Majid H. , Heimel J. Alexander 
Published: August 2023

SUMMARYHuman primary visual cortex (V1) responds more strongly, or resonates, when exposed to ∼10, ∼15-20, ∼40-50 Hz rhythmic flickering light. Full-field flicker also evokes perception of hallucinatory geometric patterns, which mathematical models explain as standing-wave formations emerging from periodic forcing at resonant frequencies of the simulated neural network. However, empirical evidence for such flicker-induced standing waves in the visual cortex was missing. We recorded cortical responses to flicker in awake mice using high spatial resolution widefield imaging in combination with high temporal resolution glutamate-sensing fluorescent reporter (iGluSnFR). The temporal frequency tuning curves in the mouse V1 were similar to those observed in humans, showing a banded structure with multiple resonance peaks (8 Hz, 15 Hz, 33 Hz). Spatially, all flicker frequencies evoked responses in V1 corresponding to retinotopic stimulus location, but some evoked additional peaks. These flicker-induced cortical patterns displayed standing wave characteristics and matched linear wave equation solutions in an area restricted to the visual cortex. Taken together, the interaction of periodic traveling waves with cortical area boundaries leads to spatiotemporal activity patterns that may affect perception.
Sister chromatid cohesion halts DNA loop expansion
Authors: Bastié Nathalie , Chapard Christophe , Nejmi Sanae , Mboumba Henri , Thierry Agnès , Beckouët Frederic , Koszul Romain 
Published: August 2023

AbstractEukaryotic genomes are folded into DNA loops mediated by structural maintenance of chromosomes (SMC) complexes such as cohesin, condensin and Smc5/6. This organization regulates different DNA-related processes along the cell cycle such as transcription, recombination, segregation and DNA repair. During G2/M stages, SMC-mediated DNA loops coexist with cohesin complexes involved in sister chromatid cohesion (SCC). However, the articulation between the establishment of SCC and the formation of SMC-mediated DNA loops along the chromatin remains unknown. Here we show that SCC is indeed a barrier to cohesin-mediated DNA loop expansion in G2.
Axon onset remodeling in response to network activity in mouse cortical neurons
Authors: Lehmann Nadja , Markovic Stefan , Thome Christian , Engelhardt Maren 
Published: August 2023

SummaryIn certain subtypes of pyramidal neurons, axons originate from basal dendrites, resulting in an axon-carrying dendrite branch with unique functional characteristics (AcD cells). The number of AcD cells increases during development, however, it is so far unclear whether neurons remodel their axon emergence throughout their lifetime in response to changes in network activity. To test our hypothesis of such large-scale morphological plasticity, we utilizedin vitroandin vivostrategies in mouse primary somatosensory cortex to test whether network activity impacts axon onset. Based on data obtained by immunofluorescence, confocal microscopy and/or live-cell imaging, we show that neurons are indeed capable of changing the onset of their axon origin from somatic to dendritic andvice versawithin a few daysin vitroand that peripheral whisker manipulation and thus changes in sensory input drives large-scale morphological plasticityin vivo.
Exploiting O-GlcNAc transferase promiscuity to dissect site-specific O-GlcNAcylation
Authors: Mitchell Conor W. , Bartual Sergio Galan , Ferenbach Andrew T. , Scavenius Carsten , van Aalten Daan M. F. 
Published: August 2023

AbstractProtein O-GlcNAcylation is an evolutionary conserved post-translational modification catalysed by the nucleocytoplasmic O-GlcNAc transferase (OGT) and reversed by O-GlcNAcase (OGA). How site-specific O-GlcNAcylation modulates a diverse range of cellular processes is largely unknown. A limiting factor in studying this is the lack of accessible techniques capable of producing homogeneously O-GlcNAcylated proteins, in high yield, forin vitrostudies. Here, we exploit the tolerance of OGT for cysteine instead of serine, combined with a co-expressed OGA to achieve site-specific, highly homogeneous mono-glycosylation. Applying this to DDX3X, TAB1, and CK2α, we demonstrate that near-homogeneous mono-S-GlcNAcylation of these proteins promotes DDX3X and CK2α solubility and enables production of mono-S-GlcNAcylated TAB1 crystals, albeit with limited diffraction. Taken together, this work provides a new approach for functional dissection of protein O-GlcNAcylation.
Regulation of inositol 5-phosphatase activity by the C2 domain of SHIP1 and SHIP2
Authors: Bradshaw William J , Kennedy Emma C , Moreira Tiago , Smith Luke A , Chalk Rod , Katis Vittorio L , Benesch Justin LP , Brennan Paul E , Murphy Emma J , Gileadi Opher 
Published: August 2023

AbstractSHIP1, an inositol 5-phosphatase, plays a central role in cellular signalling. As such, it has been implicated in many conditions. Exploiting SHIP1 as a drug target will require structural knowledge and the design of selective small molecules. We have determined apo, and magnesium and phosphate-bound structures of the phosphatase and C2 domains of SHIP1. The C2 domains of SHIP1 and the related SHIP2 modulate the activity of the phosphatase domain. To understand the mechanism, we performed activity assays, hydrogen-deuterium-exchange mass spectrometry and molecular dynamics on SHIP1 and SHIP2. Our findings demonstrate that the influence of the C2 domain is more pronounced for SHIP2 than SHIP1. We determined 91 structures of SHIP1 with fragments bound, with some near the interface between the two domains. We performed a mass spectrometry screen and determined four structures with covalent fragments. These structures could act as starting points for the development of potent, selective probes.
Metabolomic changes associated with acquired resistance toIxodes scapularis
Authors: Cui Yingjun , Matias Jaqueline , Tang Xiaotian , Cibichakravarthy Balasubramanian , DePonte Kathleen , Wu Ming-Jie , Fikrig Erol 
Published: August 2023

AbstractGuinea pigs repeatedly exposed toIxodes scapularisdevelop acquired resistance to the ticks (ATR). The molecular mechanisms of ATR have not been fully elucidated, and partially involve immune responses to proteins in tick saliva. In this study, we examined the metabolome of sera of guinea pigs during the development of ATR. Induction of components of the tyrosine metabolic pathway, including hydroxyphenyllactic acid (HPLA), were associated with ATR. We therefore administered HPLA to mice, an animal that does not develop ATR, and exposed the animals toI. scapularis. We also administered nitisinone, a known inhibitor of tyrosine degradation, to another group of mice. The mortality ofI. scapularisthat fed on mice given HPLA or nitisinone was 26% and 72% respectively, compared with 2% mortality among ticks that fed on control animals. These data indicate that metabolic changes that occur after tick bites contribute to ATR.