bluuebunny/crossref_metadata_2025_split huggingface dataset:
Erysipelothrix rhusiopathiae-associated bloodstream infection in a patient with systemic lupus erythematosus: a case report and literature review
Authors: Lo Calvin Ka-Fung , Schonhofer Cole , Mina Neil , Masud Shazia , Wong Patrick Ho Pun , Chapman Michael G. 
Published: October 2024

Introduction

Systemic human infections caused by Erysipelothrix rhusiopathiae have been increasingly reported especially within immunocompromised hosts and those with significant occupational exposure to livestock and aquatic animals. We report a case of Erysipelothrix rhusiopathiae bacteremia in a patient with systemic lupus erythematosus (SLE) and present a literature review on clinical outcomes and microbiologic diagnosis for this organism.

Case Presentation

A 43-year-old female patient was reporting a 1-month history of intermittent fevers. She recently increased her immunosuppression medication for her underlying SLE on advice of her rheumatologist. The patient sustained a finger laceration from butchering cattle meat two weeks after onset of her initial symptoms, with worsening index finger swelling and increased febrile episodes. Two weeks post-injury, multiple blood cultures were drawn and each isolated Gram-positive bacilli. Given her recurrent intermittent fevers, there was concern for ongoing infection and therefore intravenous vancomycin was started with prompt referral to outpatient parenteral antibiotic therapy clinic. The Gram-positive bacillus was confirmed as Erysipelothrix rhusiopathiae via MALDI-TOF analysis. Given intrinsic resistance to vancomycin, vancomycin was switched to intravenous ceftriaxone as targeted antimicrobial therapy for two weeks. Reassuringly, there was no echocardiographic evidence of infective endocarditis warranting prolonged treatment course. Post-treatment, she remained symptom-free with resolution of joint symptoms and fevers.

Conclusion

Our report illustrates a case of Erysipelothrix rhusiopathiae bacteremia from a immunodeficient host, with prompt microbiologic diagnosis and intervention with appropriate antimicrobial coverage. Literature reflects the rarity of this infection, predilections to specific susceptible hosts and the importance for raising awareness of zoonotic infections.
An Open-Label, Interventional, Prospective, Real-World Evidence Study to Evaluate a Multimodal Wound Matrix in Patients with Refractory Wounds
Authors: Dhillon Yadwinder , Mulder Gerit , Patel Keyur D. , Moya Luis , Boghossian Gerard , Swain David , McLafferty Robert B. , Perez Kelly , Nguyen Jessica , Wilkinson Natalie , Arragon Jessica , Contreras Lilia , Geiger Donna , Cummings Ryan , LaVigne Brenda , Bell Desmond P. , Bakewell Suzanne J. 
Published: October 2024

ABSTRACTObjectiveThe objective of this open-label, interventional, prospective clinical study was to evaluate the effectiveness of a multimodal wound matrix (MWM), formulated for the treatment of chronic, non- healing wounds that had failed prior therapies. The overall response rate was the proportion of patients that had greater than 40% reduction in size after 4 weeks of treatment. Secondary objectives included the percentage area reduction (PAR) after 4 and 12 weeks, incidence of ulcers closing, and changes in quality of life.ApproachAn open-label, interventional, prospective cohort, real-world evidence study was conducted at 8 US wound care sites. Criteria included chronic non-healing wounds of multiple etiologies in patients with extensive comorbidities. Results were compared to data from the US Wound Registry.Results111 patients entered the screening phase and 63 were treated. 54 wounds were eligible for the dataset that included 18 DFUs, 19 VLUs, 2 pressure injuries, 1 surgical, 1 lower extremity wound, and 12 unclassified etiologies. The objective response rate was 42%. The 4-week PAR was 34%. The 12-week PAR was 66%. 18 wounds closed by week 12.InnovationMWM is a formulation technology developed to address the major obstacles that prevent healing. Results were evaluated in a patient population with extensive comorbidities who had failed prior treatments and would be generally excluded from controlled trials.ConclusionThe results from this study support the contention that the multimodal wound matrix achieves substantial clinical improvement in a complex patient population not enrolled in clinical trials and demonstrates an advancement in wound management.
An analysis of buprenorphine distribution patterns among pharmacies and hospitals in the United States from 2019-2023
Authors: Gikoska Maria , Florio Anna K. , George Andrew , Piper Brian J. 
Published: October 2024

AbstractBackgroundOpioid Use Disorder (OUD) is a debilitating condition characterized by the overuse of prescription opioid medications and the development of physical and/or psychological dependence. Consequences of this condition include chronic impairment, distress, and later life-altering health conditions such as overdose, all of which have been highlighted by the prominence of OUD in the United States in recent years. Buprenorphine is a standard OUD treatment and commonly used for pain management. Understanding changes in distribution patterns across the US is vital for continuing to improve outcomes for OUD patients.MethodsThis study analyzed changes in buprenorphine distribution among pharmacies and hospitals from 2019-2023 to determine temporal patterns and identify state level disparities. The Drug Enforcement Administrations’ Automated Reports and Consolidated Ordering System (ARCOS), US Census Bureau Population Estimates databases, and mortality rates (CDC WONDER) were analyzed. Data were corrected for population to identify patterns of buprenorphine distribution in the US from 2021-2022 and 2022-2023 through examining percent changes in milligrams per 100 population at national and state level.ResultsThe year-to-year percent change of national buprenorphine distribution from pharmacies has remained positive but changed from 12.2% increase from 2019-2020 to a four percent increase every year from 2020-2023. From 2021-2022, there was a +4.9% increase in total grams of buprenorphine distributed to pharmacies and a 95% CI [-5.1, 14.9], with District of Columbia, South Dakota, and Nebraska outside of the 95% CI. Distribution to hospitals increased by 10.2% [-32.3, 52.7] during 2021-2022, with Hawaii, New Hampshire and Delaware being outside of 95% CI. From 2022-2023, there was an increase of +5.7% and 95% CI [-3.5, 14.9] in pharmacy distribution, with states including Washington, Rhode Island and Kansas remaining outside of the 95% CI. Hospital distribution has decreased from twenty percent between 2019-2020 to eighteen percent between 2022-2023. Changes in mortality data from 2022-2023 showed no associations with trends in buprenorphine distribution for those years.ConclusionFollowing increases in buprenorphine distribution during the COVID pandemic, a consistent increase has continued year-over-year in most states and the country overall by both pharmacies and hospitals. Some states (e.g. Rhode Island, Georgia, Washington D.C.) have not followed this pattern. Notably, Hawaii went from the most negative percent change in hospital distribution to the most positive change in the timeframe analyzed. This may offer opportunities to analyze more specific impacts of the increased buprenorphine distribution on populations and their outcomes associated with OUD.
From Past to Present: Pompe Disease, Pseudodeficiency Alleles, and Diagnostic Challenges
Authors: Giliberto Florencia , Buonfiglio Paula Inés , Capellino Gabriel , Massini Carmen Llames , Dalamón Viviana , Luce Leonela , Carcione Micaela 
Published: October 2024

AbstractPompe disease is an autosomal recessive disorder caused byGAAvariants leading to acid alpha-glucosidase deficiency. Diagnosis is challenging due to the variable phenotypic presentation and overlap with other conditions. Traditionally, diagnosis relies on measuring enzyme activity, but next-generation sequencing (NGS) advancements have improved accuracy. However, interpreting variants is complex, especially because pseudodeficiency alleles mimic disease-causing variants. We present two patients harboring the pseudodeficiency allele NM_000152.5(GAA):c.271G>A, p.Asp91Asn, which is confusing due to inaccurate reports and results related to enzymatic activity. The first case was a recently published controversial case of a 700-year-old mummy in which the authors classified the variant as pathogenic. The second patient had symptoms compatible with late-onset Pompe disease and was homozygous for the variant. We aimed to determine the correct variant classification usingGAA:c.271G>A as a model and to achieve a genetic diagnosis of the second patient. This variant was analyzed following international guidelines (ACMG-AMP) and reviewed with the Lysosomal Diseases Variant Curation Expert Panel. The second patient underwent NGS. We demonstrated thatGAA:c.271G>A meets the criterion of being classified as benign for Pompe. Additionally, the second patient carried a heterozygous pathogenicPABPN1variant associated with oculopharyngeal muscular dystrophy, which better explained the clinical features. This underscores the importance of expanding the genetic analysis in the presence of pseudodeficiency alleles that can mask the true cause of the disease and highlights the fact that an accurate diagnosis should adhere to guidelines on variant curation to reduce the risk of misdiagnosis, which could result in inadequate care and risky medical decisions.Graphical abstract
Impaired semantic control in the logopenic variant of primary progressive aphasia
Authors: Henderson Shalom K. , Ramanan Siddharth , Rouse Matthew A. , Cope Thomas E. , Halai Ajay D. , Patterson Karalyn E. , Rowe James B. , Lambon Ralph Matthew A. 
Published: October 2024

AbstractWe investigated semantic cognition in the logopenic variant of primary progressive aphasia (lvPPA), including (i) the status of verbal and non-verbal semantic performance; and (ii) whether the semantic deficit reflects impaired semantic control. Oura priorihypothesis that individuals with lvPPA would exhibit semantic control impairments was motivated by the anatomical overlap between the temporoparietal atrophy typically associated with lvPPA and lesions associated with post-stroke semantic aphasia (SA) and Wernicke’s aphasia (WA), which cause heteromodal semantic control impairments. We addressed the presence, type (semantic representation and semantic control; verbal and non-verbal), and progression of semantic deficits in lvPPA. Since most people with lvPPA have Alzheimer’s disease (AD) pathology and are part of a broader multidimensional phenotype space encompassing AD subtypes, we compared semantic performance in lvPPA and typical amnestic AD (tAD). Given the differences in lesion and atrophy patterns in SA and WAversussemantic dementia/semantic-variant PPA patients, our second aim was to examine atrophy patterns in people with lvPPA and tAD compared to age-matched controls. Twenty-seven patients participated in the study. People were grouped into those meeting consensus criteria for lvPPA (N = 10) and others who may have previously satisfied definitions of lvPPA but had progressed with multi-domain cognitive impairments (herein referred to as “lvPPA+”; N = 8). People with tAD (N = 9) were relatively preserved across verbal and non-verbal semantic assessments. LvPPA patients were impaired on both verbal and non-verbal semantic tasks and their impairments showed the hallmark characteristics of a semantic control deficit. LvPPA and lvPPA+ patients showed effects of varying semantic control demands, positive cueing effects, and correlated performance between semantic and executive tasks. Whole-brain voxel-based morphometry, comparing each of the patient groups to age-matched controls, revealed significantly reduced grey and white matter in the bilateral hippocampi and lateral temporal regions in tAD patients. The lvPPA group exhibited an asymmetric pattern of reduced grey and white matter intensity in the language-dominant left hemisphere, including a significant portion of the lateral and medial temporal lobe. LvPPA+ patients demonstrated reduced grey and white matter in the left temporal lobe extending subcortically, anteriorly and posteriorly, as well as right temporal involvement. Our findings could aid diagnostic subtyping of PPA by adopting semantic control features and offer improved clinical characterisation of lvPPA in the trajectory of semantic decline.
Autoantibodies in maternal serum predict spontaneous preterm delivery
Authors: Rackaityte Elze , Borges Beltran , Shao Shirley J. , Creery Joseph S. , Kortbawi Hannah M. , Miller Haleigh S. , Mayer Margareta , Kouame Elaine , Mann Sabrina A. , McCarthy Frank , Oltman Scott , Zorn Kelsey C. , Kung Andrew F. , Mitchell Anthea , Rizzuto Gabrielle , Baer Rebecca J. , Mandel-Brehm Caleigh , Ryckman Kelli K. , Gaw Stephanie L. , Hillman Sara L. , Jelliffe-Pawlowski Laura L. , Halkias Joanna , Sobhani Nasim C. , Elias Joshua E. , MacKenzie Tippi C. , DeRisi Joseph L. 
Published: October 2024

SUMMARYComplications from preterm birth are the leading cause of global mortality in children under age five1,2. Spontaneous preterm labor is the most common cause of preterm delivery and is associated with a breakdown of maternal-fetal tolerance3–5. However, the current understanding of the role of autoantibodies in this process has been limited to a handful of examples of pathogenic antibodies that occur with pregnancy complications6–14. Here, we employ proteome-wide autoantibody profiling via phage display immunoprecipitation and sequencing (PhIP-seq) to identify autoreactivities associated with imminent preterm delivery in maternal sera across four cohorts of human pregnancy (n=1,023). We find that spontaneous preterm pregnancies exhibit greater proteome-wide autoreactivity, validated by placental proteome immunoprecipitation mass spectrometry analysis using patient sera. Within the preterm birth associated autoreactive signature, we find enrichment for pathways known to be critical for normal pregnancy outcomes, including vascular development, reproductive hormones, and regulators of inflammation. Further analysis of autoreactive targets revealed involvement of the IL1β inflammatory cytokine cascade. IL1β is one of the few inflammatory cytokines sufficient to rapidly induce labor in animals15–24and it is also elevated in preterm human pregnancies25–29. Across these four cohorts, antibodies to cytokine IL1 receptor antagonist (IL1RA), a natural antagonist to IL1β are significantly enriched in roughly 10% of preterm pregnancies and yet are completely absent in term pregnancies. Sera from these patients functionally neutralizes IL1RA activityin vitroand anti-IL1RA induces greater resorption, inflammation, and vascular malperfusion in timed-pregnant micein vivo. These findings suggest utility for serologic diagnostics as one approach to stratify risk of spontaneous preterm delivery in addition to interventional strategies for management of IL1β during pregnancy.
Estimating the seroprevalence of tuberculosis (Mycobacterium bovis) infection in a wild deer population in southwest England
Authors: Jinks Rachel , Hollingdale Alison , Avigad Rachelle , Velarde Juan , Pugsley Chris , de la Rua-Domenech Ricardo , Pritchard Charlotte , Roberts Tony , Clark Julia , Robinson Nick , Maynes Ruth , Withenshaw Susan , Smith Graham 
Published: October 2024

ABSTRACTBovine tuberculosis (bTB) is a major disease of cattle that is subject to an eradication strategy in England. To inform control policies and manage the epidemic, all potential sources of infection for cattle must be identified and understood. The causative agent of bTB,Mycobacterium bovis, has a wide host range including several deer species. While transmission between cattle and deer has been implicated in some localised endemic regions, the role of deer in the epidemiology of bTB in England is poorly understood. This paper presents the results of a serological survey to estimate the prevalence ofM. bovisin a large wild deer population in the High bTB Risk Area of southwest England.Blood samples were collected post-mortem over a 12-month period from wild deer during annual deer management controls in the Exmoor area and tested forM. bovisserum antibodies. Overall, 432 samples were collected and 69 (16.0%) were seropositive. The true seroprevalence in our sample was estimated to be 29.2% (95% CrI 21.1-38.6%), using Bayesian Latent Class Analysis to account for imperfect diagnostic test accuracy. Prevalence did not appear to differ between sexes nor between species, although the sample was predominantly red deer. The lowest prevalence was observed in animals aged under 1-year.Whilst these results provide valuable insights intoM. bovisseroprevalence in this wild deer population, they should be interpreted alongside other relevant information such as ecology, species-specific epidemiology and disease pathology, deer density and cattle management to inform potential transmission risks between cattle and wild deer.
Nuclear Histone 3 Post-translational Modification Profiling in Whole Cells using Spectral Flow Cytometry Histone H3 modification profiling using spectral flow
Authors: Golden Carly S , Williams Saylor , Blankevoort Sophia , Belkina Anna , Yost H. Joseph , Serrano Maria A 
Published: October 2024

AbstractDiscerning the dynamic nature of nuclear histone 3 post-translational modifications (H3-PTMs) is crucial for understanding gene regulatory mechanisms. Although conventional nuclear H3-PTM flow cytometry protocols currently offer acceptable sensitivity, they typically involve isolating nuclei prior to running the assay, leading to significant sample loss and limited throughput. To address these challenges, we present a high-throughput nuclear H3-PTM spectral flow cytometry protocol conducted directly in whole cells. By performing fixation, permeabilization, and antibody incubations in a 96-well plate format, we eliminate the need for nuclei isolation, thereby preserving sample integrity and increasing throughput. Notably, this protocol allows for the simultaneous assessment of histone PTMs, cytoplasmic proteins, plasma membrane receptors, and cell cycle analysis within the same cell, providing comprehensive insights into the status and functional utility of a cell. This approach not only streamlines experimental procedures but also enhances the efficiency and reproducibility of nuclear flow cytometry assays, allowing for a deeper exploration of epigenetic regulation across diverse biological samples.Summary StatementWe present a protocol for multi-parameter analysis of cell cycle, histone modifications, and caspase 3 in NPCs, utilizing spectral flow cytometry for improved sensitivity and sample integrity without nuclear enrichment.
Meta2DB: Curated Shotgun Metagenomic Feature Sets and Metadata for Health State Prediction
Authors: Kok Car Reen , Mulakken Nisha J. , Thissen James B. , Martí Jose Manuel , Lee Ryan , Trainer Jacob B. , Goncalves Andre R. , Ranganathan Hiranmayi , Avila-Herrera Aram , Jaing Crystal J. , Be Nicholas A. 
Published: October 2024

ABSTRACTMeta2DB is a curated metagenomic and metadata database that provides structurally consistent microbiome taxonomy feature count tables for 13,897 samples across 84 studies, 23 disease states, and 34 geographical locations. All samples were uniformly processed using a streamlined metagenomic classification pipeline that employs a reference database indexed to contain all sequences across all kingdoms of life that were present in the NCBI Nucleotide (nt) database retrieved on Jan 04, 2023. This pipeline leverages high-performance computing (HPC) resources at Lawrence Livermore National Laboratory and was used to process 50TB of publicly available raw metagenomic sequence data. Extensive metadata curation was carried out through a combination of manual curation and automated parsing, producing a consistent inter-study metadata table specifically structured to facilitate training of ML models for prediction of human health.
UBR4 regulates a MetAP2-dependent Arg/N-degron pathway
Authors: Morrison Evan J. , Horton Emma , Rissland Olivia S. 
Published: October 2024

ABSTRACTThe open reading frame does more than merely encode a linear peptide sequence; it is a reservoir of regulatory information. Here, as part of investigations into how the N-terminal amino acids regulate translation, we serendipitously uncovered a new N-degron that revealed an additional layer of regulation in these pathways. Using reporter assays, we discovered that peptides bearing position 3 arginine or lysine residues at the N-terminus were rapidly degraded in mammalian cells. We found this pathway requires MetAP2, which co-translationally cleaves the N-terminal methionine preceding second position threonine and valines to initiate protein decay. We used CRISPR-Cas9 to knockout key N-recognins and found that these N-degrons are exclusively targeted by the E3 ligase UBR4, but not by UBR1 or UBR2. Together, our results characterize a new N-degron pathway that reveals a unique role for MetAP2 and UBR4 in mediating protein decay.SIGNIFICANCEThe Arg/N-degron pathway targets position 1 or 2 N-terminal Lys and Arg residues via UBR Box E3 ligases to trigger protein decay. Here we show that UBR4 can specifically recognize position 3 Lys and Arg N-termini upon methionine removal by the methionine amino peptidase MetAP2. Accordingly, proteins that bear N-terminal residues that are processed by MetAP1 are unaffected by the loss or inhibition of MetAP2. Using a combination of reporter assays, and bioinformatic approaches were identified endogenous proteins whose N-termini are recognized by this MetAP2-dependent Arg/N-degron pathway. Thus, our results expand the number of Arg/N-degron substrates and describe a new mechanism through which they are targeted.