bluuebunny/crossref_metadata_2025_split huggingface dataset:
High-Specific-Activity 131I-MIBG for the Treatment of Advanced Pheochromocytoma and Paraganglioma
Authors: Al-Ward Ruaa , Brondani Vania Balderrama , Sawani Sahar , Potter Cheryl L. , Xu Guofan , Waguespack Steven G. , Varghese Jeena , Habra Mouhammed Amir , Lu Yang , Jimenez Camilo 
Published: April 2024

Background
Metastatic pheochromocytomas and paragangliomas (MPPGLs) are rare tumors with limited treatment options. High-specific-activity 131I-MIBG (HSA-131I-MIBG) is the only US Food and Drug Administration–approved therapy for MPPGL. We studied the efficacy and safety of HSA-131I-MIBG in routine clinical practice.

Patients and Methods
The primary endpoints were objective response rate (ORR) and disease control rate (DCR). Secondary endpoints were duration of response, blood pressure control, safety, overall and progression-free survival rates, MIBG uptake, and correlations with genetic background.

Results
The study included 25 patients. Twenty-four patients had distant metastases, 17 (68%) had hormonally active tumors, and 13 (52%) had previously received antineoplastic treatment. In 24 evaluable patients, the ORR was 38%, including 2 patients with complete response, and the DCR was 83%; median time to response was 12.5 months (95% confidence interval, 4.6–25.1). Twelve patients had sporadic disease, among whom the ORR was 25% and DCR was 83%. Twelve patients had hereditary disease (SDHB, VHL, RET); among these, the ORR was 50%, and DCR was 83%. Plasma metanephrines normalized in 30% of patients and improved by greater than 50% in 46%. Sixteen patients had hormonally active tumors and hypertension; in 9 (56%) of these, blood pressure normalized, leading to discontinuation of antihypertensive therapy.
The most common adverse events were grades 1–2 nausea/vomiting and transient bone marrow suppression. One patient developed premature ovarian failure. Reversible grades 3–4 myelosuppression were seen in 7 patients (28%). One patient had fatal pneumonitis.

Conclusions
HSA-131I-MIBG is associated with a high DCR in patients with MPPGL, regardless of underlying genetic mutation.
Chemokine Receptor 4–Targeted PET/CT With 68Ga-Pentixather Detects More Lesions Than 68Ga-Pentixafor PET/CT in Multiple Myeloma
Authors: Yang Qiao , Zhang Fujing , Hao Zhixin , Zhuang Junling , Huo Li 
Published: April 2024

Abstract
An 83-year-old woman with newly diagnosed multiple myeloma (MM) was enrolled in our 68Ga-pentixather and 68Ga-pentixafor PET/CT trial for evaluation of tumor burden. 68Ga-pentixather PET/CT detected more focal bone lesions, and the uptake levels of focal bone lesions on 68Ga-pentixather PET/CT were higher than those on 68Ga-pentixafor PET/CT. This suggests that 68Ga-pentixather PET/CT may be an alternative imaging modality and more sensitive in detecting MM lesions than 68Ga-pentixafor PET/CT.
Planning Angiography for 90Y-Radioembolization Demonstrates a Variety of Unusual Extrahepatic Perfusion Patterns
Authors: Benson Andrea , Koo Sonya J. , Berman Zachary 
Published: April 2024

Abstract
In preparation for 90Y radioembolization for hepatic malignancies, hepatic angiography is performed with intra-arterial delivery of 99mTc-macroaggregated albumin (MAA), known as premapping. This initial procedure allows for evaluation of standard/variant hepatic arterial anatomy using MAA as a surrogate marker for the delivery of 90Y to visualize the likely distribution of 90Y. Premapping allows for the assessment of at-risk extrahepatic targets and for the quantification of hepatopulmonary shunting. We present cases where MAA scintigraphic images reveal unusual perfusion patterns in hepatic cancers, treated with 90Y glass microspheres (Therasphere; Boston Scientific, Marlborough, MA).
Scheduled Follow-Up and Association with Emergency Department Use and Readmission after Trauma
Authors: Smith Sophia M , Zhao Xuewei , Kenzik Kelly , Michael Cara , Jenkins Kendall , Sanchez Sabrina E 
Published: April 2024

BACKGROUND:
After traumatic injury, 13% to 14% of patients use the emergency department (ED) and 11% are readmitted within 30 days. Decreasing ED visits and readmission represents a target for quality improvement. This cohort study evaluates risk factors for ED visits and readmission after trauma, focusing on outpatient follow-up.

STUDY DESIGN:
We conducted a retrospective chart review of adult trauma admissions from January 1, 2018, to December 31, 2021. Our primary exposure was outpatient follow-up, primary outcome was ED use, and secondary outcome was readmission. Multivariable logistic regression evaluated the association between primary exposure and outcomes, adjusting for factors identified on unadjusted analysis.

RESULTS:
In total, 2,266 patients met inclusion criteria, with an 11.3% ED visit rate and 4.1% readmission rate. Attending follow-up did not have a significant association with ED visit (odds ratio 0.99, 95% CI 0.99 to 2.01, p = 0.05) or readmission rate (odds ratio 1.68, 95% CI 0.95 to 2.99, p = 0.08). Significant associations with ED use included non-White race, depression, anxiety, substance use disorder, discharge disposition, and being discharged with lines or drains. Significant associations with readmission included depression, anxiety, and discharge disposition.

CONCLUSIONS:
Emphasizing outpatient follow-up in trauma patients is not an effective target to decrease ED use or readmission. Future studies should focus on supporting patients with mental health comorbidities and investigating interventions to optimally engage with trauma patients after hospital discharge.
Contribution of autosomal rare andde novovariants to sex differences in autism
Authors: Koko Mahmoud , Satterstrom F. Kyle ,   Autism Sequencing Consortium,   APEX consortium, Warrier Varun , Martin Hilary 
Published: April 2024

AbstractAutism is four times more prevalent in males than females. To study whether this reflects a difference in genetic predisposition attributed to autosomal rare variants, we evaluated the sex differences in effect size of damaging protein-truncating and missense variants on autism predisposition in 47,061 autistic individuals, then compared effect sizes between individuals with and without cognitive impairment or motor delay. Although these variants mediated differential likelihood of autism with versus without motor or cognitive impairment, their effect sizes on the liability scale did not differ significantly by sex exome-wide or in genes sex-differentially expressed in the cortex. Although de novo mutations were enriched in genes with male-biased expression in the fetal cortex, the liability they conferred did not differ significantly from other genes with similar loss-of-function intolerance and sex-averaged cortical expression. In summary, autosomal rare coding variants confer similar liability for autism in females and males.
Deep-learning protein structure predictions suggest likely molecular functions for three uncharacterised polytopic membrane proteins from theP. falciparumapicoplast
Authors: Murphy David L. , Mesdaghi Shahram , Rodríguez Filomeno Sánchez , Simpkin Adam J. , Elliott Luc , Rigden Daniel J. 
Published: April 2024

AbstractMalaria is a burdensome disease to humanity caused chiefly by the still poorly understood parasite genusPlasmodium. Much of the pathogenic success of these and other related parasites is due to the presence of the apicoplast, a comparatively poorly characterised biosynthetic organelle containing many proteins of unknown function. Here we present AlphaFold2 protein structure predictions together with furtherin silicoanalyses to infer molecular functions for the three uncharacterised transmembrane apicoplast proteins PF3D7_0622700, PF3D7_0908100 and PF3D7_1021300. The targets PF3D7_0622700 and PF3D7_0908100 are shown herein to belong to the polytopic Major Facilitator and Cation-Proton Antiporter and Anion Transporter superfamilies respectively, confirming previous suspicions for PF3D7_0908100 of a transporter function. Importantly, our docking screens further suggest pyridoxal-5-phosphate may be transported by PF3D7_0622700, and PF3D7_0908100 likely transports a larger negatively charged metabolite. These findings will help direct experimental assays to confirm what apicoplast metabolites these proteins may transport. PF3D7_1021300 is proposed to possess a six transmembrane alpha-helix domain of a currently unknown fold which may also possess a transporter molecular function. This work highlights the power of high accuracy protein structure predictions to illuminate proteins of unknown structure and function.
The maternal and fetal metabolic and immune landscapes of gestational diabetes mellitus
Authors: Ni Duan , Nanan Ralph 
Published: April 2024

AbstractObjectivesGestational diabetes mellitus (GDM) is the most common pregnancy-related medical complication. It is characterized by the development of hyperglycaemia during pregnancy and is known to lead to higher risk of metabolic disorders and other pathologies in both mothers and offsprings. Some studies probed the impacts of GDM, focusing on specific organs like placenta or adipose tissue, but so far, a systematic overview is lacking. Here, we aimed to curate a comprehensive atlas from currently available transcriptomic data for GDM, to comprehensively unravel how GDM influences the metabolic and immune landscapes in affected pregnancy.MethodsRNA-sequencing (RNA-seq) data for maternal subcutaneous and omental fat, peripheral blood mononuclear cells (PBMCs), and fetal umbilical vein endothelial cells (HUVECs), amniocytes and cord blood mononuclear cells (CBMCs); and single-cell RNA sequencing (scRNA-seq) data for placenta and CBMCs were collated from previous publications. Comparative analyses and gene set enrichment analyses (GSEA) were carried out for the control versus GDM pregnancy.ResultsMaternal metabolic landscapes were consistently shifted by GDM, with reduced oxidative phosphorylation and fatty acid metabolism in maternal adipose tissues and PBMCs. GDM also caused inflammation solely in maternal subcutaneous fat. scRNA-seq analysis of placenta revealed that GDM reduced granulocytes and myelocytes but increased extravillous trophoblast cells. GDM also differentially impacted the metabolic and immune signals in different placental cell subsets. Contrarily, metabolisms in fetal compartments were minimally influenced by GDM. However, they consistently exhibited elevated inflammatory signals.ConclusionGDM differentially reprogrammed the maternal and fetal metabolisms and immunity.
Microglial-Mediated Prevention of Axonal Degeneration in the Injured Spinal Cord: Insights from anIn VivoImaging Study
Authors: Wu Wanjie , He Yingzhu , Chen Yujun , Fu Yiming , He Sicong , Liu Kai , Qu Jianan Y. 
Published: April 2024

ABSTRACTMicroglia, the primary immune cells in the central nervous system, play a critical role in regulating neuronal function and fate through their interaction with neurons. Despite extensive research, the specific functions and mechanisms of microglia-neuron interactions remain incompletely understood. In this study, we demonstrate that microglia establish direct contact with myelinated axons at Nodes of Ranvier in the spinal cord of mice. Under normal physiological conditions, microglia-node contact occurs in a random scanning pattern and is associated with neuronal activity. However, in response to axonal injury, microglia rapidly transform their contact into a robust wrapping form, preventing acute axonal degeneration from extending beyond the nodes. This neuroprotective wrapping behavior of microglia is dependent on the function of their P2Y12 receptors, which may be activated by ATP released through axonal volume-activated anion channels at the nodes. Additionally, voltage-gated sodium channels (NaV) contribute to the interaction between nodes and glial cells following injury, and inhibition of NaV delays axonal degeneration. Throughin vivoimaging, our findings reveal a neuroprotective role of microglia during the acute phase of spinal cord injury, achieved through a novel form of neuron-glia interaction.
Markov Field network model of multi-modal data predicts effects of immune system perturbations on intravenous BCG vaccination in macaques
Authors: Wang Shu , Myers Amy J , Irvine Edward B , Wang Chuangqi , Maiello Pauline , Rodgers Mark A , Tomko Jaime , Kracinovsky Kara , Borish H. Jacob , Chao Michael C , Mugahid Douaa , Darrah Patricia A , Seder Robert A , Roederer Mario , Scanga Charles A , Lin Philana Ling , Alter Galit , Fortune Sarah M , Flynn JoAnne L , Lauffenburger Douglas A 
Published: April 2024

SummaryAnalysis of multi-modal datasets can identify multi-scale interactions underlying biological systems, but can be beset by spurious connections due to indirect impacts propagating through an unmapped biological network. For example, studies in macaques have shown that BCG vaccination by an intravenous route protects against tuberculosis, correlating with changes across various immune data modes. To eliminate spurious correlations and identify critical immune interactions in a public multi-modal dataset (systems serology, cytokines, cytometry) of vaccinated macaques, we applied Markov Fields (MF), a data-driven approach that explains vaccine efficacy and immune correlations via multivariate network paths, without requiring large numbers of samples (i.e. macaques) relative to multivariate features. Furthermore, we find that integrating multiple data modes with MFs helps to remove spurious connections. Finally, we used the MF to predict outcomes of perturbations at various immune nodes, including a B-cell depletion that induced network-wide shifts without reducing vaccine protection, which we validated experimentally.
Post-senescence reproductive rebound inDaphniaassociated with reversal of age-related transcriptional changes
Authors: Dua Ishaan , Pearson A. Catherine , Lowman Rachael L. , Peshkin Leonid , Yampolsky Lev Y. 
Published: April 2024

AbstractA long-lived species of zooplankton microcrustaceans,Daphnia magna,sometimes exhibits late-life rebound of reproduction, briefly reversing reproductive senescence. Such events are often interpreted as terminal investment in anticipation of imminent mortality. We demonstrate that such post-senescence reproductive events (PSREs) neither cause not anticipate increased mortality. We analyze an RNAseq experiment comparing young, old reproductively senescent, and old PSREDaphniafemales. We first show that overall age-related transcriptional changes are dominated by the increase transcription of guanidine monophosphate synthases and guanylate cyclases, as well as two groups of presumed transposon-encoded proteins and by a drop in transcription of protein synthesis-related genes. We then focus on gene families and functional groups in which full or partial reversal of age-related transcriptional changes occur. This analysis reveals reversal, in the PSRE individuals, of age-related up-regulation of apolipoproteins D, lysosomal lipases, and peptidases and of age-related down-regulation of E3 ubiquitin kinases, V-type proton ATPases, and numerous proteins related to mitochondrial and muscle functions. While it is not certain which of these changes enable reproductive rejuvenation, and which are by-products of processes that lead to it, we present some evidence that post-senescence reproductive events are associated with the reversal of age-related protein and lipid aggregates removal, apoptosis, and with restoration of mitochondrial integrity.Significance statementAdvances in aging studies revealed the need to extend the old-age health and functionality data from theDrosophila-C.elegans-yeast triad of model organisms to include those that combine the advantages of non-vertebrate models with stronger similarities to mammalian aging. This paper presents a previously unreported phenomenon: reproductive “rejuvenation” inDaphnia– a classic and a re-emerging choice model for longevity studies. These postsenescence reproductive episodes result in fecundity similar to that of young individuals and are accompanied by transcriptional shifts, often reverting age-related changes to youthful levels. Transcripts that show such reversal point to restoration of aggregate removal and of mitochondrial function. We believe that this finding opens a novel window of research towards mechanistic understanding of healthy aging.
Order of amino acid recruitment into the genetic code resolved by Last Universal Common Ancestor’s protein domains
Authors: Wehbi Sawsan , Wheeler Andrew , Morel Benoit , Manepalli Nandini , Minh Bui Quang , Lauretta Dante S. , Masel Joanna 
Published: April 2024

AbstractThe current “consensus” order in which amino acids were added to the genetic code is based on potentially biased criteria, such as absence of sulfur-containing amino acids from the Urey-Miller experiment which lacked sulfur. More broadly, abiotic abundance might not reflect biotic abundance in the organisms in which the genetic code evolved. Here, we instead identify which protein domains date to the last universal common ancestor (LUCA), then infer the order of recruitment from deviations of their ancestrally reconstructed amino acid frequencies from the still-ancient post-LUCA controls. We find that smaller amino acids were added to the code earlier, with no additional predictive power in the previous “consensus” order. Metal-binding (cysteine and histidine) and sulfur-containing (cysteine and methionine) amino acids were added to the genetic code much earlier than previously thought. Methionine and histidine were added to the code earlier than expected from their molecular weights, and glutamine later. Early methionine availability is compatible with inferred early use of S-adenosylmethionine, and early histidine with its purine-like structure and the demand for metal-binding. Even more ancient protein sequences — those that had already diversified into multiple distinct copies prior to LUCA — have significantly higher frequencies of aromatic amino acids (tryptophan, tyrosine, phenylalanine and histidine), and lower frequencies of valine and glutamic acid than single copy LUCA sequences. If at least some of these sequences predate the current code, then their distinct enrichment patterns provide hints about earlier, alternative genetic codes.Significance StatementThe order in which the amino acids were added to the genetic code was previously inferred from consensus among forty metrics. Many of these reflect abiotic abundance on ancient Earth. However, the abundances that matter are those within primitive cells that already had sophisticated RNA and perhaps peptide metabolism. Here, we directly infer the order of recruitment from the relative ancestral amino acid frequencies of ancient protein sequences. Small size predicts ancient amino acid enrichment better than the previous consensus metric does. We place metal-binding and sulfur-containing amino acids earlier than previously thought, highlighting the importance of metal-dependent catalysis and sulfur metabolism to ancient life. Understanding early life has implications for our search for life elsewhere in the universe.
An assessment of the teacher completed ‘Early Years Foundation Stage Profile’ as a routine measure of child developmental health
Authors: Mooney Kate E. , Welch Charlie , Palliser Gareth , Cheung Rachael W. , Nielsen Dea , Eddy Lucy H. , Blower Sarah L 
Published: April 2024

AbstractThe routine measurement of children’s developmental health varies across educational settings and systems. The Early Years Foundation Stage Profile (EYFSP) is a routinely recorded measure of a child’s development completed at the end of their first school year, for all children attending school in England and Wales. Despite widespread use for research and educational purposes, the measurement properties are unknown. This study examined the internal consistency and structural validity of the EYFSP, investigating whether the summed item-level scores, which we refer to as the ‘total score’, can be used as a summary of children’s developmental health. It also examined predictive validity of the total score with respect to later academic attainment and behavioural, social, and emotional difficulties.The data source was the longitudinal prospective birth cohort, Born in Bradford (BiB), and routine education data were obtained from Local Authorities. The internal consistency and structural validity of the EYFSP total score were investigated using Confirmatory Factor Analysis and a Rasch model. Predictive validity was assessed using linear mixed effects models for Key Stage 2 (Maths, Reading, Grammar/Punctuation/Spelling), and behavioural, social, and emotional difficulties (Strengths and Difficulties Questionnaire).We found that the EYFSP items demonstrated internal consistency, however, an Item Response model suggested weak structural validity (n=10,589). Mixed effects regression found the EYFSP total score to predict later academic outcomes (n=2711), and behavioural, social, and emotional difficulties (n=984). The EYFSP total score appears to be a reasonable measure of child developmental health, due to having internal consistency and predictive validity. However, caution should be exercised when interpreting scores of children with very close to ‘average’ ability levels.
Induced electric fields inhibit breast cancer growth and metastasis by modulating the immune tumor microenvironment
Authors: Charan Manish , Jones Travis H. , Ahirwar Dinesh K. , Acharya Nandini , Subramaniam Vish V. , Ganju Ramesh K , Song Jonathan W 
Published: April 2024

AbstractDespite tremendous advances in oncology, metastatic triple-negative breast cancer remains difficult to treat and manage with established therapies. Here, we show in mice with orthotopic triple-negative breast tumors that alternating (100 kHz), and low intensity (<1 mV/cm) induced electric fields (iEFs) significantly reduced primary tumor growth and distant lung metastases. Non-contact iEF treatment can be delivered safely and non-invasivelyin vivovia a hollow, rectangular solenoid coil. We discovered that iEF treatment enhances anti-tumor immune responses at both the primary breast and secondary lung sites. In addition, iEF reduces immunosuppressive TME by reducing effector CD8+ T cell exhaustion and the infiltration of immunosuppressive immune cells. Furthermore, iEF treatment reduced lung metastasis by increasing CD8+ T cells and reducing immunosuppressive Gr1+ neutrophils in the lung microenvironment. We also observed that iEFs reduced the metastatic potential of cancer cells by inhibiting epithelial-to-mesenchymal transition. By introducing a non-invasive and non-toxic electrotherapeutic for inhibiting metastatic outgrowth and enhancing anti-tumor immune responsein vivo,treatment with iEF technology could add to a paradigm-shifting strategy for cancer therapy.