bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of neutrophil typing in homeostatic resilience protective model of inflammatory preconditioning
Authors: Li Liyuan , Zhang Xinfang , Yu Hongmei , Yan Chao , Sun Jicheng , Qi Yan , Gou Yawei , Zhang Mingming , Wang Shengnan , Li Haokun , Nie Wenying , Wang Renhao , Jiang Jiashan , Gao Feng , Li Xinyu , Shi Qinghong , Song Lina , Wang Fang , Xu Xuesong , Sun Wei 
Published: August 2023

AbstractSepsis is a systemic inflammatory response syndrome (SIRS) characterized by a dysregulated host response to infection that results in organ dysfunction. The response of neutrophils to early inflammation is critical, interferon regulatory factors 4 (IRF4) and interferon regulatory factors 5 (IRF5) are expressed in most cell types of the immune system, but the relationship between the role of IRF4 and IRF5 in preconditioning-protected septic peritonitis mouse model and neutrophils response remains unknown. In this study, we used anE.coli-induced septic peritonitis mouse model and zebrafish model to explore the relationship between neutrophil inflammation and IRF subtype changes in the process of septic peritonitis. Mechanistically, we found that the protein complex formed by polymorphonuclear neutrophils (PMN) and IRF5/MyD88 can secrete pro-inflammatory factors and directly kill invading bacteria.Author SummaryNumerous animal and clinical sepsis studies have shown that markedly impaired recruitment of neutrophils to sites of infection and failure to clear bacteria contribute to excessive inflammation and increased mortality in sepsis. In our previous work, we established anEscherichia coli(E.coli) lethal septic peritonitis model and a preconditioning-protected septic peritonitis mouse model. In the early stage of septic peritonitis, a large number of PMN infiltrate the peritoneal cavity, which produces an inflammatory response to invasive bacteria. In this study, the switching process between pro-inflammatory and anti-inflammatory attracted our attention. Our research shows that IRF5-IRF4 regulatory axis leads to a PMN phenotype switch in sepsis and the expression of IRF5 and IRF4 was related to PMN pro-inflammatory (N1 type) and anti-inflammatory (N2 type) phenotypes, respectively.
Comparing Continuous versus Intermittent-Threshold Drainage Strategies for Spinal Perfusion Pressure Optimization in Patients with Acute Traumatic Spinal Cord Injuries
Authors: Lavadi Raj Swaroop , Shanahan Regan , Hamilton David Kojo , Buell Thomas James , Agarwal Nitin , Puccio Ava , Okonkwo David Okwudi , Fields Daryl Pinion 
Published: August 2023

ABSTRACTStudy DesignA cross-sectional study.ObjectiveThe primary objective of this study is to compare the efficacy of continuous versus threshold drainage strategies for maintaining spinal cord perfusion pressure (SCPP) in patients with new traumatic spinal cord injuries (SCI).SettingLevel 1 trauma center.MethodsA retrospective study of 19 patients with traumatic SCIs. SCPP was optimized at the discretion of the managing clinician using either vasopressors to increase mean arterial pressure or cerebral spinal fluid (CSF) drainage to decrease intrathecal pressure. Six patients were managed with continuous drainage (CSF drained at regular intervals regardless of SCPP) and 13 had CSF drained only when SCPP fell below 65mmHg (i.e. threshold drainage). Intrathecal pressure, SCPP, mean arterial pressure, and vasopressor utilization were compared using univariate T-test statistical analysis.ResultsThe cohort included over 1500 time points from 19 patients. While there was no difference in rates of sub-optimal SCPP (< 65mmHg; p = 0.257), patients managed with threshold drainage were more likely to exhibit critically-low SCPP (< 50 mmHg; p = 0.003) despite also having lower average intrathecal pressures (p < 0.001). There were no differences in average SCPP, MAP, or vasopressor utilization between the two groups (p > 0.05).ConclusionsAcute SCI patients managed with continuous CSF drainage were less likely to exhibit critically-low SCPPs, previously shown to be associated with worse clinical recovery. A larger, prospective cohort is needed to validate the impact of CSF drainage strategies on long-term SCI outcomes.
Assessing ChatGPT’s Mastery of Bloom’s Taxonomy using psychosomatic medicine exam questions
Authors: Herrmann-Werner Anne , Festl-Wietek Teresa , Holderried Friederike , Herschbach Lea , Griewatz Jan , Masters Ken , Zipfel Stephan , Mahling Moritz 
Published: August 2023

AbstractIntroductionLarge language models (LLMs) such as GPT-4 are increasingly used in medicine and medical education. However, these models are prone to “hallucinations” – outputs that sound convincing while being factually incorrect. It is currently unknown how these errors by LLMs relate to the different cognitive levels defined in Bloom’s Taxonomy.MethodsWe used a large dataset of psychosomatic medicine multiple-choice questions (MCQ) (N = 307) with real-world results derived from medical school exams. GPT-4 answered the MCQs using two distinct prompt versions – detailed and short. The answers were analysed using a quantitative and qualitative approach. We focussed on incorrectly answered questions, categorizing reasoning errors according to Bloom’s Taxonomy.ResultsGPT-4’s performance in answering exam questions yielded a high success rate: 93% (284/307) for the detailed prompt and 91% (278/307) for the short prompt. Questions answered correctly by GPT-4 had a statistically significant higher difficulty compared to questions that GPT-4 answered incorrectly (p=0.002 for the detailed prompt and p<0.001 for the short prompt). Independent of the prompt, GPT-4’s lowest exam performance was 78.9%, always surpassing the pass threshold. Our qualitative analysis of incorrect answers, based on Bloom’s Taxonomy, showed errors mainly in the “remember” (29/68) and “understand” (23/68) cognitive levels. Specific issues arose in recalling details, understanding conceptual relationships, and adhering to standardized guidelines.DiscussionGPT-4 displayed a remarkable success rate when confronted with psychosomatic medicine multiple-choice exam questions, aligning with previous findings. When evaluated against Bloom’s hierarchical framework, our data revealed that GPT-4 occasionally ignored specific facts (“remember”), provided illogical reasoning (“understand”), or failed to apply concepts to a new situation (“apply”). These errors, though confidently presented, could be attributed to inherent model biases and the tendency to generate outputs that maximize likelihood.ConclusionWhile GPT-4 mostly excels at medical exam questions, discerning its occasional cognitive errors is crucial.
Durability for 12 months of antibody response to a booster dose of monovalent BNT162b2 in adults who had initially received 2 doses of inactivated vaccine
Authors: Shiu Eunice Y. C. , Cheng Samuel M. S. , Martín-Sánchez Mario , Au Niki Y. M. , Chan Karl C. K. , Li John K. C. , Fung Lison W. C. , Luk Leo L. H. , Chaothai Sara , Kwan Tsz Chun , Ip Dennis K. M. , Leung Gabriel M. , Poon Leo L. M. , Peiris J. S. Malik , Leung Nancy H. L. , Cowling Benjamin J. 
Published: August 2023

ABSTRACTWe administered BNT162b2 as a third dose to 314 adults ≥30 years of age who had previously received 2 doses of inactivated vaccine. We collected blood samples before the third dose and again after 1, 6 and 12 months, and found stable levels of antibody responses to the ancestral strain and Omicron BA.2 at 6-12 months after receipt of the BNT162b2 third dose, with increased antibody levels in individuals who also received a fourth vaccine dose or reported a SARS-CoV-2 infection during follow-up.
EXPRESSION OF VARIABILITY OF THE CYP2C19*2 GENE IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION FROM A SOUTH AMERICAN HOSPITAL AND ITS FUTURE RELEVANCE IN THE INTERACTION BETWEEN GENETICS AND CARDIOLOGY
Authors: Dulcey Sarmiento Luis Andres , Theran Leon Juan Sebastián , Gomez Jaime , Parales Strauch Rafael Guillermo , Caltagirone Raimondo , Blanco Pimiento Edgar Camilo , Ciliberti Artavia María Paula , Martinez Juan Camilo , Peña Valentina Cabrera , Amaya Maria Camila 
Published: August 2023

AbstractIntroductionSome Polymorphisms of the CYP2C19 gene are associated with a decrease in the activity of the enzyme they encode, being the case of CYP2C19*2 in causing a lower generation of active metabolite of clopidogrel and therefore a low or null antiplatelet action depending on the genotype present. Antiplatelet therapy, mainly clopidogrel, is considered essential treatment in the management of acute coronary syndromes (ACS).TargetThe frequency of the CYPC19*2 polymorphism, identified as relevant in resistance to clopidogrel, is unknown in the population of this part of South America.MethodsA descriptive, observational and cross-sectional study was designed to determine the frequency of the CYP2C19*2 allele in patients with ACS admitted to a South American hospital during the period between 2015-2016, being the first study to determine polymorphism in our population. fifty-nine adults patients diagnosed with ACS were included, 48 male (81.3%) and 11 female (18.7%), aged between 54 and 86 years. The genotype for the CYP2C19 gene was determined through the PCRRFLP (Restriction Fragments Length Polymorphism) technique from DNA extracted desde peripheral blood .ResultsThe allelic frequency of the CYP2C19*2 polymorphism was 28.5%. Three subgroups of metabolizers were characterized : extensive (*1/*1) 40 (67.8%), intermediate (*1/*2) 17 (28.9%) and poor (*2/*2) 2 (3.3%).ConclusionsThis high number of carriers of the CYP2C19*2 polymorphism in the context of ACS is relevant due to its association with a lower responsiveness to clopidogrel and the possible involvement in the choice of antiplatelet therapy, for which characterization studies are required most appropriate to identify the best therapeutic strategies in our populations through pharmacogenomics.
Predicting the risk of diabetes complications using machine learning and social administrative data in a country with ethnic inequities in health: Aotearoa New Zealand
Authors: Nghiem Nhung , Wilson Nick , Krebs Jeremy , Tran Truyen 
Published: August 2023

ABSTRACTBackgroundIn the age of big data, linked social and administrative health data in combination with machine learning (ML) is being increasingly used to improve prediction in cardiovascular diseases (CVD). We aimed to apply ML methods on extensive national-level health and social administrative datasets to predict future diabetes complications by ethnicity.MethodsFive ML models were used to predict CVD events among all people with known diabetes in the population of New Zealand, utilizing national-level administrative data at the individual level.ResultsThe Xgboost ML model had the best predictive power for predicting CVD events three years into the future among the population with diabetes. The optimization procedure also found limited improvement in AUC by ethnicity. The results indicated no trade-off between model predictive performance and equity gap of prediction by ethnicity. The list of variables of importance was different among different models/ethnic groups, for examples: age, deprivation, having had a hospitalization event, and the number of years living with diabetes.Discussion and conclusionsWe provide further evidence that ML with administrative health data can be used for meaningful future prediction of health outcomes. As such it could be utilized to inform health planning and healthcare resource allocation for diabetes management and the prevention of CVD events. Our results may suggest limited scope for developing prediction models by ethnic group and that the major ways to reduce inequitable health outcomes is probably via improved delivery of prevention and management to those groups with diabetes at highest need.
Real time quantification reveals novel dynamic processes in pancreatic lumenal network establishment and remodeling
Authors: Jackson Abigail Laura , Heilmann Silja , Ebeid Christine , Krivokapic Jelena Miskovic , Romero Herrera Jose Alejandro , Semb Henrik , Nyeng Pia 
Published: August 2023

AbstractDuring embryogenesis dynamic changes in tissue architecture transform primitive anlages to functional organs. Here we document in real time how pancreatic lumens are derived and transformed using a new apical-polarity mouse reporter. Our 4D imaging data reveals dynamic remodeling of apical proteins and lumens to primarily drive each stage of pancreatic duct development. Furthermore, we pinpoint two unique transitions during lumenogenesis. Contrary to current “de novo” models of polarity acquisition, we show that expansion and rearrangement of the pre-existing central primary lumen drives early network growth. We also document how the endocrine promoting niche - a “plexus” of interconnected ducts - is resolved. We show that an arborized network forms by gradual closing of ductal loops, rather than via pruning. These novel tissue dynamics provide a new framework within which cell and molecular signaling can be investigated to better understand the interplay between organ architecture and cell fate.
Chemokine receptor 5 signaling in PFC mediates stress susceptibility in female mice
Authors: Lin Hsiao-Yun , Cathomas Flurin , Li Long , Cuttoli Romain Durand-de , Guevara Christopher , Bayrak Cigdem Sevim , Wang Qian , Gupta Swati , Chan Kenny L. , Shimo Yusuke , Parise Lyonna F. , Yuan Chongzhen , Aubry Antonio V. , Chen Fiona , Wong Jean , Morel Carole , Huntley George W. , Zhang Bin , Russo Scott J. , Wang Jun 
Published: August 2023

AbstractChronic stress induces changes in the periphery and the central nervous system (CNS) that contribute to neuropathology and behavioral abnormalities associated with psychiatric disorders. In this study, we examined the impact of peripheral and central inflammation during chronic social defeat stress (CSDS) in female mice. Compared to male mice, we found that female mice exhibited heightened peripheral inflammatory response and identified C-C motif chemokine ligand 5 (CCL5), as a stress-susceptibility marker in females. Blocking CCL5 signaling in the periphery promoted resilience to CSDS. In the brain, stress-susceptible mice displayed increased expression of C-C chemokine receptor 5 (CCR5), a receptor for CCL5, in microglia in the prefrontal cortex (PFC). This upregulation was associated with microglia morphological changes, their increased migration to the blood vessels, and enhanced phagocytosis of synaptic components and vascular material. These changes coincided with neurophysiological alterations and impaired blood-brain barrier (BBB) integrity. By blocking CCR5 signaling specifically in the PFC were able to prevent stress-induced physiological changes and rescue social avoidance behavior. Our findings are the first to demonstrate that stress-mediated dysregulation of the CCL5-CCR5 axis triggers excessive phagocytosis of synaptic materials and neurovascular components by microglia, resulting in disruptions in neurotransmission, reduced BBB integrity, and increased stress susceptibility. Our study provides new insights into the role of cortical microglia in female stress susceptibility and suggests that the CCL5-CCR5 axis may serve as a novel sex-specific therapeutic target for treating psychiatric disorders in females.
Advanced image generation for cancer using diffusion models
Authors: Kidder Benjamin L. 
Published: August 2023

ABSTRACTDeep neural networks have significantly advanced medical image analysis, yet their full potential is often limited by the relatively small dataset sizes. Generative modeling has stimulated attention for its potential applications in the synthesis of medical images. Recent advancements in diffusion models have exhibited a remarkable capacity for producing photorealistic images. Despite this promising development, the application of such models in the generation of medical images remains underexplored. In this study, we explored the potential of using diffusion models to generate medical images, with a particular emphasis on producing brain magnetic resonance imaging (MRI) scans, such as those depicting low-grade gliomas. Additionally, we examined the generation of contrast enhanced spectral mammography (CESM) images, as well as chest and lung X-ray images. Utilizing the Dreambooth platform, we trained stable diffusion models based on text prompts, class and instance images, subsequently prompting the trained models to produce medical images. The generation of medical imaging data presents a viable approach for preserving the anonymity of medical images, effectively reducing the likelihood of patient re-identification during the exchange of data for research. The findings of this study reveal that the application of diffusion models in generating images successfully captures attributes specific to oncology within imaging modalities. Consequently, this research establishes a framework that harnesses the power of artificial intelligence for the generation of cancer medical imagery.
Spatially resolved molecular analysis of host response to medical device implantation using the 3D OrbiSIMS highlights a critical role for lipids
Authors: Suvannapruk Waraporn , Fisher Leanne E , Luckett Jeni C , Edney Max K , Kotowska Anna M , Kim Dong-Hyun , Scurr David J , Ghaemmaghami Amir M , Alexander Morgan R 
Published: August 2023

AbstractA key goal for implanted medical devices is that they do not elicit a detrimental immune response. Macrophages play critical roles in modulation of the host immune response and are the major cells responsible for persistent inflammatory reactions to implanted biomaterials. We investigate two novel immune-instructive polymers that stimulate pro- or anti-inflammatory responses from macrophagesin vitro. These also modulatein vivoforeign body responses (FBR) when implanted subcutaneously in mice as coatings on biomedical grade silicone rubber. The tissue surrounding the implant is mechanically sectioned and imaged to assess the response of the polymers compared to silicone rubber. Immunofluorescent staining reveals responses consistent with pro- or anti-inflammatory responses previously described for these polymers. We apply 3D OrbiSIMS analysis to provide spatial analysis of the metabolite signature in the tissue surrounding the implant for the first time, providing molecular histology insight into the metabolite response in the host tissue. For the pro-inflammatory coating, monoacylglycerols (MG) and diacylglycerols (DG) are observed at increased intensity, while for the anti-inflammatory coating the number of phospholipid species detected decrease and pyridine and pyrimidine levels were elevated. These findings link to observations of small molecule signature from single cell studies of M2 macrophagesin vitrowhere cell and tissue ion intensities were found to correlate suggesting potential for prediction. This illustrates the power of metabolite characterization by the 3D OrbiSIMS to gain insight into the mechanism of bio-instructive materials as medical devices and to inform on the FBR to biomaterials.
Role of Apyrase in Mobilization of Phosphate from Extracellular Nucleotides and in Regulating Phosphate Uptake in Arabidopsis
Authors: Slocum Robert D. , Wang Huan , Tomasevich Alexandra A. , Clark Greg , Roux Stanley J. 
Published: August 2023

AbstractApyrase (nucleotide triphosphate diphosphohydrolase, NTPDase; EC 3.6.1.5) functions in a variety of plant growth and developmental processes and responses to pathogens, in part, by regulating extracellular ATP (eATP) concentrations. In this study, we investigated possible roles for apyrase in the recruitment of phosphate (Pi) from extracellular nucleotides inArabidopsis thalianaseedlings that constitutively expressapyrase 1(APY1). Under Pi limitation, both WT andAPY1seedlings had decreased Pi contents and a characteristic remodeling of root system architecture (RSA). This phosphate starvation response (PSR) was prevented by uptake of Pi released by metabolism of extracellular NTP, which supported normal seedling growth. In Pi-sufficient media, Pi contents ofAPY1seedlings were higher than in WT seedlings. Addition of NTP reduced the number of LR and decreased Pi contents of WT seedlings but markedly increased both LR and root hair (RH) formation and Pi contents ofAPY1seedlings. Genome-wide expression profiling revealed the repression of PSR genes inAPY1seedlings, relative to WT seedlings, consistent with their elevated Pi contents. The expanded RSA ofAPY1seedlings was correlated with induction of >100 genes involved in regulation of auxin homeostasis, signaling and transport, which previous studies have shown to be increased whenAPY1is overexpressed.APY1regulation of [eNTP] and purinergic signaling may play a role in regulating this auxin response, resulting in enhanced uptake of Pi from the medium, including Pi released by eNTP metabolism.
A suite of selective pressures supports the maintenance of alleles of aDrosophilaimmune peptide
Authors: Mullinax Sarah R. , Darby Andrea M. , Gupta Anjali , Chan Patrick , Smith Brittny R. , Unckless Robert L. 
Published: August 2023

AbstractThe innate immune system provides hosts with a crucial first line of defense against pathogens. While immune genes are often among the fastest evolving genes in the genome, inDrosophila, antimicrobial peptides (AMPs) are notable exceptions. Instead, AMPs may be under balancing selection, such that over evolutionary timescales multiple alleles are maintained in populations. In this study, we focus on theDrosophilaantimicrobial peptide Diptericin A, which has a segregating amino acid polymorphism associated with differential survival after infection with the Gram-negative bacteriaProvidencia rettgeri. Diptericin A also helps control opportunistic gut infections by common Drosophila gut microbes, especially those ofLactobacillus plantarum. In addition to genotypic effects on gut immunity, we also see strong sex-specific effects that are most prominent in flies without functionaldiptericin A. To further characterize differences in microbiomes between differentdiptericingenotypes, we used 16S metagenomics to look at the microbiome composition. We used both lab reared and wild caught flies for our sequencing and looked at overall composition as well as the differential abundance of individual bacterial families. Overall, we find flies that are homozygous for one allele ofdiptericin Aare better equipped to survive a systemic infection fromP. rettgeri, but in general have a shorter lifespans after being fed common gut commensals. Our results suggest a possible mechanism for the maintenance of genetic variation ofdiptericin Athrough the complex interactions of sex, systemic immunity, and the maintenance of the gut microbiome.
Differences in Oligomerization of the SARS-CoV-2 Envelope Protein, Poliovirus VP4, and HIV Vpu
Authors: Townsend Julia A. , Fapohunda Oluwaseun , Wang Zhihan , Pham Hieu , Taylor Michael T. , Kloss Brian , Park Sang Ho , Opella Stanley , Aspinwall Craig A. , Marty Michael T. 
Published: August 2023

ABSTRACTViroporins constitute a class of viral membrane proteins with diverse roles in the viral life cycle. They can self-assemble and form pores within the bilayer that transport substrates, such as ions and genetic material, that are critical to the viral infection cycle. However, there is little known about the oligomeric state of most viroporins. Here, we use native mass spectrometry (MS) in detergent micelles to uncover the patterns of oligomerization of the full-length SARS-CoV-2 envelope (E) protein, poliovirus VP4, and HIV Vpu. Our data suggest that the E protein is a specific dimer, VP4 is exclusively monomeric, and Vpu assembles into a polydisperse mixture of oligomers under these conditions. Overall, these results revealed the diversity in the oligomerization of viroporins, which has implications for mechanisms of their biological functions as well as their potential as therapeutic targets.