bluuebunny/crossref_metadata_2025_split huggingface dataset:
Continuous non-invasive hemodynamic monitoring in early onset severe preeclampsia
Authors: Ackerman-Banks Christina M , Bhinder Jasjit , Eder Maxwell , Heerdt Paul , Sugeng Lissa , Testani Jeffrey , Alian Aymen , Lipkind Heather , Velazquez Eric , Reddy Uma , Chou Josephine C 
Published: April 2023

AbstractObjectivesContinuous hemodynamic monitoring offers the opportunity to individualize management in severe preeclampsia (PEC). We compared cardiac output (CO) and systemic vascular resistance (SVR) measured by bioreactance (NICOM), Clearsite™ Fingercuff [CS), and 3D-echocardiography (3DE).Study DesignThis prospective observational study included 12 pregnant patients with early PEC. CO and SVR were measured simultaneously by NICOM, CS, and 3DE antepartum and 1-2 days postpartum. Using 3DE as the standard, CS and NICOM interchangeability, precision, accuracy, and correlation were assessed.ResultsCompared to 3DE-CO, CS-CO was highly correlated (R2=0.70, p=<0.0001) with low percentage error (PE 29%) which met criteria for interchangeablity. CS-SVR had strong correlation (R2=0.81, p=<0.0001) and low PE (29%). While CS tended to slightly overestimate CO (bias +2.05 +/-1.18 L/min, limit of agreement (LOA) -0.20-4.31) and underestimate SVR (bias -279 +/-156 dyes/sec/cm5; LOA -580-18.4) these differences were unlikely to be clinically significant. Thus CS could be interchangeable with 3DE for CO and SVR. NICOM-CO had only moderate correlation with 3DE-CO (R2=0.29, p=0.01) with high PE (52%) above threshold for interchangeability. NICOM-CO had low mean bias (−1.2 +/-1.68 L/min) but wide 95% LOA (−4.41 - 2.14) suggesting adequate accuracy but low precision in relation to 3DE-CO. NICOM-SVR had poor correlation with 3DE-SVR (R2=0.32, p=0.001) with high PE (67%), relatively low mean bias (238 +/-256), and wide 95% LOA (– 655–1131). NICOM did not meet the criteria for interchangeable with 3DE for CO and SVR.ConclusionsClearsite Fingercuff, but not NICOM, has potential to be clinically useful for CO and SVR monitoring in severe preeclampsia.
Differentiation of Fungal, Viral, and Bacterial Sepsis using Multimodal Deep Learning
Authors: Boussina Aaron , Ramesh Karthik , Arora Himanshu , Ratadiya Pratik , Nemati Shamim 
Published: April 2023

AbstractSepsis is a major cause of morbidity and mortality worldwide, and is caused by bacterial infection in a majority of cases. However, fungal sepsis often carries a higher mortality rate both due to its prevalence in immunocompromised patients as well as delayed recognition. Using chest x-rays, associated radiology reports, and structured patient data from the MIMIC-IV clinical dataset, the authors present a machine learning methodology to differentiate between bacterial, fungal, and viral sepsis. Model performance shows AUCs of 0.81, 0.83, 0.79 for detecting bacterial, fungal, and viral sepsis respectively, with best performance achieved using embeddings from image reports and structured clinical data. By improving early detection of an often missed causative septic agent, predictive models could facilitate earlier treatment of non-bacterial sepsis with resultant associated mortality reduction.
Comparison of the carotid corrected flow time and tidal volume challenge for assessing fluid responsiveness in robot-assisted laparoscopic surgery
Authors: Tang Xixi , Chen Qi , Huang Zejun , An Ran , Liang Jingqiu , Liu Hongliang 
Published: April 2023

AbstractPurposeWe aimed to evaluate the ability of carotid corrected flow time assessed by ultrasound to predict fluid responsiveness in patients undergoing robot-assisted laparoscopic gynecological surgery in the modified head-down lithotomy position.MethodsThis prospective single-center study conducted at the Chongqing University Cancer Hospital included patients undergoing robot-assisted laparoscopic surgery in the modified head-down lithotomy position. Carotid doppler parameters and hemodynamic data, including corrected flow time, pulse pressure variation (PPV), stroke volume variation, and stroke volume index at a tidal volume of 6 mL/kg predicted body weight and after increasing the tidal volume to 8 mL/kg predicted body weight (tidal volume challenge), respectively, were measured. Fluid responsiveness was defined as a stroke volume index ≥10% increase after volume expansion.ResultsAmong the 52 patients included, 26 were classified as fluid responders and 26 as non-responders based on the stroke volume index. The area under the receiver operating characteristic curve values measured to predict the fluid responsiveness to corrected flow time and changes in PPV (ΔPPV6–8) after tidal volume challenge were 0.82 [95% confidence interval (CI): 0.705–0.937; P < 0.0001] and 0.85 (95% CI: 0.740–0.956; P < 0.0001), respectively. Both values were higher than those for PPV at a tidal volume of 8 mL/kg (0.79, 95% CI: 0.674–0.911; P = 0003). The optimal cut-off values for corrected flow time and ΔPPV6–8were 356.5 ms and >1%, respectively.ConclusionThe change in PPV after tidal volume challenge and corrected flow time reliably predicted fluid responsiveness in patients undergoing robot-assisted laparoscopic gynecological surgery in the modified head-down lithotomy position.Trial registrationChinese Clinical Trial Register (CHiCTR2200060573)
A rapid and bidirectional reporter of neural activity reveals neural correlates of social behaviors inDrosophila
Authors: Bonheur Moise , Swartz Kurtis J. , Metcalf Melissa G. , Zhukovskaya Anna , Mehta Avirut , Connors Kristin E. , Barasch Julia G. , Wen Xinke , Jamieson Andrew R. , Martin Kelsey C. , Axel Richard , Hattori Daisuke 
Published: April 2023

ABSTRACTNeural activity is modulated over different timescales encompassing sub-seconds to days reflecting changes in external environment, internal state, and behavior. UsingDrosophilaas a model, we have developed a rapid and bidirectional reporter that provides a robust cellular readout of recent neural activity. This reporter utilizes nuclear vs cytoplasmic distribution of CREB-regulated transcriptional coactivator, CRTC. Subcellular distribution of GFP-tagged CRTC (CRTC::GFP) bidirectionally changes on the order of minutes and reflects both increases and decreases in neural activity. We establish an automated machine-learning-based routine for efficient quantification of reporter signal. Using this reporter, we demonstrate acute mating- evoked activation of peptidergic neurons. We further investigate the functional role of the master courtship regulator gene,fruitless, and show thatfruitlessis necessary to ensure activation of male arousal neurons by female cues. Together, our results establish CRTC::GFP as a bidirectional reporter of recent neural activity suitable for examining neural correlates in behavioral contexts.
Engrailed-1Promotes Pancreatic Cancer Metastasis
Authors: Xu Jihao , Roe Jae-Seok , Lee EunJung , Tonelli Claudia , Somerville Tim D.D. , Yao Melissa , Milazzo Joseph P. , Tiriac Herve , Kolarzyk Ania M. , Lee Esak , Grem Jean L. , Lazenby Audrey J. , Grunkemeyer James A. , Hollingsworth Michael A. , Borowsky Alexander D. , Park Youngkyu , Vakoc Christopher R. , Tuveson David A. , Hwang Chang-Il 
Published: April 2023

AbstractEngrailed-1(EN1) is a critical homeodomain transcription factor (TF) required for neuronal survival, and EN1 expression has been shown to promote aggressive forms of triple negative breast cancer. Here, we report thatEN1is aberrantly expressed in a subset of pancreatic ductal adenocarcinoma (PDA) patients with poor outcomes. EN1 predominantly repressed its target genes through direct binding to gene enhancers and promoters, implicating a role in the acquisition of mesenchymal cell properties. Gain- and loss-of-function experiments demonstrated thatEN1promoted PDA transformation and metastasisin vitroandin vivo. Our findings nominate the targeting ofEN1and downstream pathways in aggressive PDA.
Wide-field calcium imaging of cortical activation and functional connectivity in externally- and internally-driven locomotion
Authors: West Sarah L. , Gerhart Morgan L. , Ebner Timothy J. 
Published: April 2023

AbstractThe neural dynamics underlying self-initiated versus sensory driven movements is central to understanding volitional action. Upstream motor cortices are associated with the generation of internally-driven movements over externally-driven. Here we directly compare cortical dynamics during internally- versus externally-driven locomotion using wide-field Ca2+imaging. We find that secondary motor cortex (M2) plays a larger role in internally-driven spontaneous locomotion transitions, with increased M2 functional connectivity during starting and stopping than in the externally-driven, motorized treadmill locomotion. This is not the case in steady-state walk. In addition, motorized treadmill and spontaneous locomotion are characterized by markedly different patterns of cortical activation and functional connectivity at the different behavior periods. Furthermore, the patterns of fluorescence activation and connectivity are uncorrelated. These experiments reveal widespread and striking differences in the cortical control of internally- and externally-driven locomotion, with M2 playing a major role in the preparation and execution of the self-initiated state.
Predicting depression risk in early adolescence via multimodal brain imaging
Authors: Gracia-Tabuenca Zeus , Barbeau Elise B. , Xia Yu , Chai Xiaoqian 
Published: April 2023

ABSTRACTDepression is an incapacitating psychiatric disorder with high prevalence in adolescent populations that is influenced by many risk factors, including family history of depression. The ability to predict who may develop depression before adolescence, when rates of depression increase markedly, is important for early intervention and prevention. Using a large longitudinal sample from the Adolescent Brain Cognitive Development (ABCD) Study (2658 participants after imaging quality control, between 9-10 years at baseline), we applied machine learning methods on a set of comprehensive multimodal neuroimaging features to predict depression risk at the two-year follow-up from the baseline visit. Features include derivatives from structural MRI, diffusion tensor imaging, and task and rest functional MRI. A rigorous cross-validation method of leave-one-site-out was used. Additionally, we tested the prediction models in a high-risk group of participants with parental history of depression (N=625). The results showed all brain features had prediction scores significantly better than expected by chance. When predicting depression onset in the high-risk group, brain features from resting-state functional connectomes showed the best classification performance, outperforming other brain features based on structural MRI and task-based fMRI. Results demonstrate that the functional connectivity of the brain can predict the risk of depression in early adolescence better than other univariate neuroimaging derivatives, highlighting the key role of the interacting elements of the connectome capturing more individual variability in psychopathology compared to measures of single brain regions.
Secreted HLA Fc-Fusion Profiles Immunopeptidome in Hypoxic PDAC and Cellular Senescence
Authors: Rettko Nicholas J. , Kirkemo Lisa L. , Wells James A. 
Published: April 2023

ABSTRACTHuman leukocyte antigens (HLA) display peptides largely from intracellular proteins on the surface of cells in major histocompatibility complex (MHC)-peptide complexes. These complexes provide a biological window into the cell, and peptides derived from disease-associated antigens can serve as biomarkers and therapeutic targets. Thus, proper identification of peptides and the corresponding presenting HLA allele in disease phenotypes is important for the design and execution of therapeutic strategies using engineered T-cell receptors or antibodies. Yet, current mass spectrometry methods for profiling the immunopeptidome typically require large and complex sample inputs, complicating the study of several disease phenotypes and lowering the confidence of both peptide and allele identification. Here, we describe a novel secreted HLA (sHLA) Fc-fusion construct that allows for simple peptide identification from single HLA alleles in two important disease models: hypoxic pancreatic ductal adenocarcinoma (PDAC) and cellular senescence. We identify hypoxia and senescence-associated peptides that could act as future targets for immunotherapy. More generally, the method streamlines the time between sample preparation and injection from days to hours, yielding allele-restricted target identification in a temporally controlled manner. Overall, this method identified >30,000 unique HLA-associated peptides across two different HLA alleles and seven cell lines. Notably, ∼9,300 of these unique HLA-associated peptides had previously not been identified in the Immune Epitope Database. We believe the sHLA Fc-fusion capture technology will accelerate the study of the immunopeptidome as therapeutic interest in HLA-peptide complexes increases in cancer and beyond.
The lymphatic system favours survival of a uniqueT. bruceipopulation, and its invasion results in major host pathology
Authors: Machado Henrique , De Niz Mariana 
Published: April 2023

AbstractTrypanosoma bruceicolonize and multiply in the blood vasculature, as well as in various organs of the host’s body. Lymph nodes have been previously shown to harbour large numbers of parasites, and the lymphatic system has been proposed as a key site that allowsT. bruceidistribution through, and colonization of the mammalian body. However, visualization of host-pathogen interactions in the lymphatic system has never captured dynamic events with high spatial and temporal resolution throughout infection. In our work, we used a mixture of tools including intravital microscopy andex vivoimaging to studyT. bruceidistribution in 20 sets of lymph nodes. We demonstrate that lymph node colonization byT. bruceiis different across lymph node sets, with the most heavily colonized being the draining lymph nodes of main tissue reservoirs: the gonadal adipose tissue and pancreas. Moreover, we show that the lymphatic vasculature is a pivotal site for parasite dispersal, and altering this colonization by blocking LYVE-1 (i.e. surface receptor of lymphatic vessel endothelial cells) is detrimental for parasite survival. Additionally, parasites within the lymphatic vasculature have unique morphological and behavioural characteristics, different to those found in the blood, demonstrating a physical separation of environments across both types of vasculature. Finally, we demonstrate that the lymph nodes and the lymphatic vasculature undergoes significant alterations duringT. bruceiinfection, resulting in oedema throughout the host’s body.
In vivoexchange of glucose and lactate between photoreceptors and the retinal pigment epithelium
Authors: Hass Daniel T. , Giering Elizabeth , Han John Y.S. , Bisbach Celia M. , Pandey Kriti , Robbings Brian M. , Mundinger Thomas O. , Nolan Nicholas D. , Tsang Stephen H. , Peachey Neal S. , Philp Nancy J. , Hurley James B. 
Published: April 2023

AbstractPhotoreceptors in the retina of a vertebrate’s eye are supported by a tissue adjacent to the retina, the retinal pigment epithelium (RPE). The RPE delivers glucose to the outer retina, consumes photoreceptor outer segments discs, and regenerates 11-cis-retinal. Here we address the question of whether photoreceptors also provide metabolic support to the RPE. We use complementary approaches and animal models to show that glucose is the primary fuel for the retina, that photoreceptors are the primary cell type in the retina to consume glucose, and that lactate derived from photoreceptor glucose consumption is transported to and catabolized by the RPE. These data rigorously support and extend the concept of a metabolic ecosystem between photoreceptors and RPE.
Comprehensive analysis of nasal IgA antibodies induced by intranasal administration of the SARS-CoV-2 spike protein
Authors: Waki Kentarou , Tani Hideki , Kawahara Eigo , Saga Yumiko , Shimada Takahisa , Yamazaki Emiko , Koike Seiichi , Morinaga Yoshitomo , Isobe Masaharu , Kurosawa Nobuyuki 
Published: April 2023

AbstractIntranasal vaccination is an attractive strategy for preventing COVID-19 disease as it stimulates the production of multimeric secretory immunoglobulin A (IgA), the predominant antibody isotype in the mucosal immune system, at the target site of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry. Currently, intranasal vaccine efficacy is evaluated based on the measurement of polyclonal antibody titers in nasal lavage fluid. However, how individual multimeric secretory IgA protects the mucosa from SARS-CoV-2 infection remains to be elucidated. To understand the precise contribution and molecular nature of multimeric secretory IgA induced by intranasal vaccines, we developed 99 monoclonal IgA clones from nasal mucosa and 114 monoclonal IgA or IgG clones from nonmucosal tissues of mice that were intranasally immunized with the SARS-CoV-2 spike protein. The nonmucosal IgA clones exhibited shared origins and common and unique somatic mutations with the related nasal IgA clones, indicating that the antigen-specific plasma cells in the nonmucosal tissues originated from B cells stimulated at the nasal mucosa. Comparing the spike protein binding reactivity, angiotensin-converting enzyme-2-blocking andin vitroSARS-CoV-2 virus neutralization of monomeric and multimeric secretory IgA pairs recognizing different epitopes showed that even non-neutralizing monomeric IgAs, which represents 70% of the nasal IgA repertoire, can protect against SARS-CoV-2 infection when expressed as multimeric secretory IgAs. We also demonstrated that the intranasal administration of multimeric secretory IgA delivered as prophylaxis in the hamster model reduced infection-induced weight loss. Our investigation is the first to demonstrate the function of nasal IgA at the monoclonal level, showing that nasal immunization can provide effective immunity against SARS-CoV-2 by inducing multimeric secretory IgAs at the target site of the virus infection.
Redundant and distinct roles of two 14-3-3 proteins inFusarium sacchari, pathogen of sugarcane Pokkah boeng disease
Authors: Chen Yuejia , Yao Ziting , Zhao Lixian , Yu Mei , Qin Siying , Zou Chengwu , Chen Baoshan 
Published: April 2023

AbstractFusarium sacchariis one of the most important sugarcane pathogens that causes Pokkah boeng disease (PBD) in China. 14-3-3 proteins have been shown to play vital roles in developmental processes in dimorphic transition, signal transduction and carbon metabolism in some phytopathogenic fungi, but were poorly understood inF. sacchari. In this study, two 14-3-3 protein-encoding genes,FsBmh1andFsBmh2inF. sacchari, were investigated. Although bothFsBmh1andFsBmh2were expressed at vegetative growth stage,FsBmh1was repressed at sporulation stage in vitro. In order to clarify the roles ofFsBmh1andFsBmh2, deletion mutants ΔFsBmh1 and ΔFsBmh2 were constructed. Phenotypic defects, including hyphal branching, hyphal septation, conidiation, spore germination and colony growth, were more severe in ΔFsBmh2 than in ΔFsBmh1, although virulence attenuation was observed in both mutants. To further explore the relationship betweenFsBmh1andFsBmh2, the combination of deletion and silencing (ΔFsBmh/sFsBmh) and overexpression (O-FsBmh) mutants were constructed and characterized. Compared to the single allele deletion, combinations of ΔFsBmh1/sFsBmh2 or ΔFsBmh2/sFsBmh1 showed more severe manifestations in general, suggesting a redundancy in function of the two 14-3-3 genes. Comparative transcriptome analysis revealed that more functional genes were affected in ΔFsBmh2 than in ΔFsBmh1. Redundancy in function betweenFsBmh1andFsBmh2suggests that 14-3-3 is vitally important for the organism and distinction in roles between the two isoforms may be resulted from the divergence in evolution. To the best of our knowledge, this was the first report on the distinct roles of 14-3-3 protein isoforms in a pathogenic fungus. Knowledge gained from this study should be of help to further understand the regulation mechanism of pathogenicity-related traits in fungal pathogens and for the development of new strategy for control of PBD in particular.
DNA Repair Function Scores for 2172 Variants in the BRCA1 Amino-Terminus
Authors: Diabate Mariame , Islam Muhtadi M. , Nagy Gregory , Banerjee Tapahsama , Dhar Shruti , Smith Nahum , Adamovich Aleksandra I. , Starita Lea M. , Parvin Jeffrey D. 
Published: April 2023

ABSTRACTSingle nucleotide variants are the most frequent type of sequence changes detected in the genome and these are frequently variants of uncertain significance (VUS). VUS are changes in DNA for which disease risk association is unknown. Thus, methods that classify the functional impact of a VUS can be used as evidence for variant interpretation. In the case of the breast and ovarian cancer specific tumor suppressor protein, BRCA1, pathogenic missense variants frequently score as loss of function in an assay for homology-directed repair (HDR) of DNA double-strand breaks. We previously published functional results using a multiplexed assay for 1056 amino acid substitutions residues 2-192 in the amino terminus of BRCA1. In this study, we have re-assessed the data from this multiplexed assay using an improved analysis pipeline. These new analysis methods yield functional scores for more variants in the first 192 amino acids of BRCA1, plus we report new results for BRCA1 amino acid residues 193-302. We now present the functional classification of 2172 BRCA1 variants in BRCA1 residues 2-302 using the multiplexed HDR assay. Comparison of the functional determinations of the missense variants with clinically known benign or pathogenic variants indicated 93% sensitivity and 100% specificity for this assay. The results fromBRCA1variants tested in this assay are a resource for clinical geneticists for evidence to evaluate VUS inBRCA1.AUTHOR SUMMARYMost missense substitutions inBRCA1are variants of unknown significance (VUS), and individuals with a VUS inBRCA1cannot know from genetic information alone whether this variant predisposes to breast or ovarian cancer. We apply a multiplexed functional assay for homology directed repair of DNA double strand breaks to assess variant impact on this important BRCA1 protein function. We analyzed 2172 variants in the amino-terminus of BRCA1 and demonstrate that variants that are known as pathogenic have a loss of function in the DNA repair assay. Conversely, variants that are known to be benign are functionally normal in the multiplexed assay. We suggest that these functional determinations of BRCA1 variants can be used to augment the information that clinical cancer geneticists provide to patients who have a VUS inBRCA1.