bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of RGD-binding Integrins in ovarian cancer progression, metastasis and response to therapy
Authors: Ranga Vipin , Dakal Tikam Chand , Maurya Pawan Kumar , Johnson Mark S , Sharma Narendra Kumar , Kumar Abhishek
Published: January 2025

Integrins are transmembrane receptors that play a crucial role in cell adhesion and signaling by connecting the extracellular environment to the intracellular cytoskeleton. After binding with specific ligands in the extracellular matrix (ECM), integrins undergo conformational changes that transmit signals across the cell membrane. The integrin-mediated bidirectional signaling triggers various cellular responses, such as changes in cell shape, migration and proliferation. Irregular integrin expression and activity are closely linked to tumor initiation, angiogenesis, cell motility, invasion, and metastasis. Thus, understanding the intricate regulatory mechanism is essential for slowing cancer progression and preventing carcinogenesis. Among the four classes of integrins, the arginine-glycine-aspartic acid (RGD)-binding integrins stand out as the most crucial integrin receptor subfamily in cancer and its metastasis. Dysregulation of almost all RGD-binding integrins promotes ECM degradation in ovarian cancer, resulting in ovarian carcinoma progression and resistance to therapy. Preclinical studies have demonstrated that targeting these integrins with therapeutic antibodies and ligands, such as RGD-containing peptides and their derivatives, can enhance the precision of these therapeutic agents in treating ovarian cancer. Therefore, the development of novel therapeutic agents is essential for treating ovarian cancer. This review mainly discusses genes and their importance across different ovarian cancer subtypes, the involvement of RGD motif-containing ECM proteins in integrin-mediated signaling in ovarian carcinoma, ongoing, completed, partially completed, and unsuccessful clinical trials of therapeutic agents, as well as existing limitations and challenges, advancements made so far, potential strategies, and directions for future research in the field.

Insight Box Integrin-mediated signaling regulates cell migration, proliferation and differentiation. Dysregulated integrin expression and activity promote tumor growth and dissemination. Thus, a proper understanding of this complex regulatory mechanism is essential to delay cancer progression and prevent carcinogenesis. Notably, integrins binding to RGD motifs play an important role in tumor initiation, evolution, and metastasis. Preclinical studies have demonstrated that therapeutic agents, such as antibodies and small molecules with RGD motifs, target RGD-binding integrins and disrupt their interactions with the ECM, thereby inhibiting ovarian cancer proliferation and migration. Altogether, this review highlights the potential of RGD-binding integrins in providing new insights into the progression and metastasis of ovarian cancer and how these integrins have been utilized to develop effective treatment plans.
Unraveling the influence of microbial necromass on subsurface microbiomes: metabolite utilization and community dynamics
Authors: Finley Brianna K , Enalls Brandon C , de Raad Markus , Al Said Mariam , Chen Mingfei , Joyner Dominique C , Hazen Terry C , Northen Trent R , Chakraborty Romy
Published: January 2025

The role of microbial necromass (nonliving microbial biomass), a significant component of belowground organic carbon, in nutrient cycling and its impact on the dynamics of microbial communities in subsurface systems remains poorly understood. It is currently unclear whether necromass metabolites from various microbes are different, whether certain groups of metabolites are preferentially utilized over others, or whether different microbial species respond to various necromass metabolites. In this study, we aimed to fill these knowledge gaps by designing enrichments with necromass as the sole nutrient source for subsurface microbial communities. We used the soluble fraction of necromass from bacterial isolates belonging to Arthrobacter, Agrobacterium, and Pseudomonas genera, and our results indicate that metabolite composition of necromass varied slightly across different strains but generally included amino acids, organic acids, and nucleic acid constituents. Arthrobacter-derived necromass appeared more recalcitrant. Necromass metabolites enriched diverse microbial genera, particularly Massilia sp. responded quickly regardless of the necromass source. Despite differences in necromass utilization, microbial community composition converged rapidly over time across the three different necromass amendments. Uracil, xanthine, valine, and phosphate-containing isomers were generally depleted over time, indicating microbial assimilation for maintenance and growth. However, numerous easily assimilable metabolites were not significantly depleted, suggesting efficient necromass recycling and the potential for necromass stabilization in systems. This study highlights the dynamic interactions between microbial necromass metabolites and subsurface microbial communities, revealing both selective utilization and rapid community and necromass convergence regardless of the necromass source.
Effects of multienzyme supplementation on energy and nutrient digestibility in various feed ingredients for pregnant gilts
Authors: Shipman Garrin L , Perez-Palencia Jorge Y , Hong Jinsu , Niu Yanxing , Rogiewicz Anna , Patterson Rob , Levesque Crystal L
Published: January 2025

The utilization of exogenous fiber-degrading enzymes in commercial swine diets is a strategy to increase the nutrient and energy density of poorly digestible ingredients. In a prior set of studies, dietary multienzyme blend (MEblend) supplementation increased the apparent total tract digestibility (ATTD) of nutrients, non-starch polysaccharides, and energy in complete high-fibrous gestation diets by 6% when fed to gestating sows. The current study aimed to determine the effects of MEblend (containing xylanase, β-glucanase, cellulase, amylase, protease, pectinase, and invertase activities) supplementation on ATTD of energy and nutrients of individual feedstuffs commonly used in gestating sow diets across major pork-producing regions worldwide, which differ in their fibrous components. Twenty-seven gilts (initial body weight 176 ± 6.6 kg), in a crossover design with four periods (periods 1, 2, 3, and 4 from d 41 to 55, 56 to 70, 71 to 85, and 86 to 100 of gestation, respectively), were allocated to one of 7 diets (with or without MEblend supplementation at 0.1% inclusion; 7-8 observations per treatment) to determine the ATTD of energy and neutral detergent fiber (NDF). Three diets contained corn, wheat, and sorghum as the sole source of energy. In the other diets, soybean meal (SBM), field peas (FP), canola meal (CM), and sugar beet pulp (SBP) each replaced 25% of the corn in the corn diet to determine the energy value of individual feedstuffs. Data were analyzed using a Student’s t-test to evaluate the effect of enzyme supplementation on these feedstuffs. The MEblend increased the metabolizable and net energy of corn (P = 0.10) and wheat (P < 0.01) by 2% and 3%, respectively. The energy content of sorghum was not impacted by MEblend. Furthermore, a 6%, 4%, and 25% increase was observed in metabolizable and net energy of SBM, FP, and CM, respectively (P ≤ 0.05). The energy value in SBP was not affected by MEblend supplementation. In conclusion, supplementing diets with a multienzyme blend increased the energy content of corn, wheat, soybean meal, field peas, and canola meal fed to gestating sows by approximately 2% to 25%, depending on the feedstuffs. The energy value of sorghum and sugar beet pulp was not affected by the multienzyme blend. This should be considered when formulating fibrous diets for gestating sows to increase nutrient utilization of feedstuffs.
The price of remoteness: product availability and local cost of living in Ethiopia
Authors: Martin Julien , Mayneris Florian , Theophile Ewane
Published: January 2025

We use the microdata underlying the Ethiopian consumer price index to examine the spatial dispersion in local prices and availability of 401 items across 106 cities. Remote cities face higher prices and have access to fewer products. Large cities also face higher individual prices but enjoy access to a wider set of products. To assess the welfare implications of these patterns, we aggregate the data and build spatial cost-of-living indexes that account for both the price of available products and product availability. The cost of living is higher in remote and large cities. Moving from the first to the ninth decile in terms of remoteness (holding population size constant) results in an 8.3 per cent increase in the cost of living. A comparable move in terms of population size (holding remoteness constant) leads to a 3.7 per cent increase in the cost of living.
What every neuropathologist needs to know: Update on neuro infectious disease workups and consultation resources
Authors: Kenyon Alicia L , Solomon Isaac H
Published: January 2025

Efficient histopathological diagnosis of central nervous system infections can be challenging but is critical for therapeutic decision making in cases for which less invasive blood or cerebrospinal fluid testing has been unrevealing. A wide variety of bacteria, fungi, viruses, and parasites can cause infections, particularly in immunocompromised individuals. Histological findings may be nonspecific or overlap with noninfectious inflammatory conditions. To minimize wasted tissue and time, a systematic approach is recommended in which: (1) relevant patient history (eg, comorbidities, travel and other exposures, and immune status) and radiological findings are reviewed, (2) a preliminary differential diagnosis based on this information and on inflammatory patterns and visualization of potential microorganisms on hematoxylin and eosin stains is generated, (3) special stains, immunohistochemistry, in situ hybridization, or molecular testing (pathogen-specific or broad-spectrum) are used for confirmation and further classification, and (4) correlation with culture results and other laboratory testing is performed to arrive at a final integrated diagnosis. Discrepancies between molecular and histological findings are often due to contamination and require careful evaluation to avoid treatment of false positives. Consultation with infectious disease pathologists or public health reference laboratories may be needed to confirm diagnoses of unusual organisms or when specialized testing is required.
Retrospective Investigation of Pediatric Histoplasmosis Diagnosed at a Tertiary Children’s Hospital in an Endemic Area over 11 years
Authors: Al-Tahhan Lina , Harrison Christopher J , Lee Brian R , El Feghaly Rana E
Published: January 2025

Background

Most histoplasmosis data are from adults. We describe pediatric histoplasmosis diagnosed at a tertiary pediatric care center in an endemic area.

Methods

We performed a retrospective chart review of patients birth-18 years seen in our institution (January 1, 2010 – August 15, 2022) with histoplasmosis identified by International Classification of Disease (ICD) codes. We performed descriptive and univariate analyses of demographic, historical, clinical, laboratory, and treatment data.

Results

Of 122 patients, 26 had disseminated DH, 71 pulmonary/thoracic (P/T) disease, 21 had histoplasmosis as an incidental finding, and 4 were classified as other. Median age was 14 years (range 0.3-18.7 y); most were non-Hispanic White (70.5%) and city dwellers (77.1%). We noted neither seasonality nor disease category differences for age, race and ethnicity, residence, or environmental factors. Compared to P/T, DH more frequently had complex chronic conditions (73.1% vs 12.7%, p<0.001), fever (88.5% vs 52.1%, p<0.001), fatigue (76.9% vs 46.5%, p=0.01), vomiting (53.8% vs 25.3%, p=0.01), anemia (hemoglobin median 10.05 g/dL vs 12.5 g/dL, p<0.001), elevated sedimentation rate values (median 31 mm/h vs 29 mm/h, p=0.02), blood and urine Histoplasma antigen detection (63.6/84.6% vs 20.0/14.8%, p<0.001), and antifungal treatment (100% vs 70.4%, p<0.001). Patients with DH had longer antifungal treatment courses (399d vs 84d, p<0.001). Exposures were rarely recorded, but the most common was chickens. Chest radiographs were less likely to show adenopathy in DH compared to P/T (8.7% vs 55%, p<0.001).

Conclusion

Presentations, risk factors, diagnostics use/results, and therapy for pediatric histoplasmosis most often parallel those in adults.
A changepoint approach to modelling nonstationary soil moisture dynamics
Authors: Gong Mengyi , Killick Rebecca , Nemeth Christopher , Quinton John
Published: January 2025

Soil moisture dynamics provide an indicator of soil health that scientists model via drydown curves. The typical modelling process requires the soil moisture time series to be manually separated into drydown segments and then exponential decay models are fitted to them independently. Sensor development in recent years means that experiments that were previously conducted over a few field campaigns can now be scaled to months or years at a higher sampling rate. To better meet the challenge of increasing data size, this paper proposes a novel changepoint-based approach to automatically identify structural changes in the soil drying process and simultaneously estimate the drydown parameters that are of interest to soil scientists. A simulation study is carried out to demonstrate the performance of the method in detecting changes and retrieving model parameters. Practical aspects of the method such as adding covariates and penalty learning are discussed. The method is applied to hourly soil moisture time series from the National Ecological Observatory Network data portal to investigate the temporal dynamics of soil moisture drydown. We recover known relationships previously identified manually, alongside delivering new insights into the temporal variability across soil types and locations.
Vaccine-Induced Annular Atrophic Lichen Planus
Authors: Perz Curtis , Chittoor Jay , Grenier Liesel
Published: January 2025

Annular atrophic lichen planus (AALP) is a chronic subtype of lichen planus that classically does not respond to treatment with topical steroids. An inflammatory reaction in the dermal infiltrate may play a role in the development of AALP, but the exact pathogenesis remains unclear. We present the case of a 54-year-old-female with lesions on her trunk and extremities that developed following vaccination. Her failed treatment response warranted further workup for AALP, which was confirmed around 1 year after initiation. Although vaccine-induced lichen planus is not common, it has been reported in various cases. We present a rare case of AALP following vaccination and then provide an in-depth discussion of factors associated with the condition and current treatment response.
Hemispheric asymmetry of coronal bright point’s number and area over solar cycles 23–24
Authors: Karachik Nina V , Minenko Ekaterina P
Published: January 2025

Temporal variations in the number and area of coronal bright points (CBPs) were studied separately in the Northern and Southern hemispheres over more than two solar cycles (years 1996–2022). Hemispheric asymmetry was identified in both the total number and area of CBPs, with differences reaching up to 15 per cent. Statistical analysis using Student’s t-test confirms that these differences are statistically significant. The observed asymmetry arises from the asynchronous formation of CBPs in the hemispheres, rather than from the asymmetry of active regions. These variations in asymmetry are explained by the existence of two different types of CBP: ‘bright’ and ‘dim’. Differences in the asymmetry and overall number variations between these two types during solar cycles suggest distinct physical mechanisms underlying their formation. Bright CBPs closely follow the patterns of active regions, supporting the hypothesis that they are miniature active regions formed through similar mechanisms. In contrast, dim CBPs, predominantly located in quiet Sun regions, often display behaviour opposite to sunspots, partially attributable to the visibility effect and influence of active regions. However, the temporal variations in the normalized asymmetry index indicate that the visibility effect alone cannot fully explain the observed patterns. The relatively uniform asymmetry of dim CBPs across 11-yr solar cycles supports the hypothesis of a cycle-independent (or dependent on a longer period) component of the solar dynamo, potentially linked to a small-scale turbulent dynamo.
On the 3D transport of galactic cosmic rays in a selection of exoplanet-hosting astrospheres: the influence of stellar rotation
Authors: Light Juandrè , Engelbrecht N Eugene , Herbst Konstantin , Scherer K D
Published: January 2025

Galactic cosmic rays (GCRs) may influence the habitability of exoplanets. The recently proposed relationship between GCR intensities at exoplanetary locations and the rotation periods of their host stars is here investigated for several M-dwarf astrospheres, namely Proxima Centauri, TRAPPIST-1, GJ 436, and LHS1140, using a three-dimensional GCR modulation code. This relation, where higher GCR intensities result from enhanced particle transport along astrospheric magnetic fields that are underwound due to longer stellar rotation periods, is found to hold for the astrospheres considered here. The influence of the stellar rotation period on GCR intensities in a Sun-like astrosphere on Earth and Mars-like atmospheres is also investigated and found to directly influence atmospheric ionization and radiation exposure.
Two almost planetary mass survivors of common envelope evolution
Authors: Parsons S G , Brown A J , Casewell S L , Littlefair S P , van Roestel J , Rebassa-Mansergas A , Murillo-Ojeda R , Hollands M A , Zorotovic M , Castro Segura N , Dhillon V S , Dyer M J , Garbutt J A , Green M J , Jarvis D , Kennedy M R , Kerry P , McCormac J , Munday J , Pelisoli I , Pike E , Sahman D I
Published: January 2025

White dwarfs are often found in close binaries with stellar or even substellar companions. It is generally thought that these compact binaries form via common envelope evolution, triggered by the progenitor of the white dwarf expanding after it evolved off the main sequence and engulfing its companion. To date, a handful of white dwarfs in compact binaries with substellar companions have been found, typically with masses greater than around 50 MJup. Here, we report the discovery of two eclipsing white dwarf plus brown dwarf binaries containing very low mass brown dwarfs. ZTF J1828+2308 consists of a hot ($15900\pm 75$ K) $0.610\pm 0.004$ ${\rm M}_{\odot }$ white dwarf in a 2.7 h binary with a $0.0186\pm 0.0008$ ${\rm M}_{\odot }$ ($19.5\pm 0.8$ MJup) brown dwarf. ZTF J1230−2655 contains a cool ($10000\pm 110$ K) $0.65\pm 0.02$ ${\rm M}_{\odot }$ white dwarf in a 5.7 h binary with a companion that has a mass of less than 0.0211 ${\rm M}_{\odot }$ (22.1 MJup). While the brown dwarf in ZTF J1828+2308 has a radius consistent with its mass and age, ZTF J1230−2655 contains a roughly 20 per cent overinflated brown dwarf for its age. We are only able to reconstruct the common envelope phase for either system if it occurred after the first thermal pulse, when the white dwarf progenitor had already lost a significant fraction of its original mass. This is true even for very high common envelope ejection efficiencies ($\alpha _\mathrm{CE}\sim 1$), unless both systems have extremely low metallicities. It may be that the lowest mass companions can only survive a common envelope phase if it occurs at this very late stage.
A novel ADP-directed chaperone function facilitates the ATP-driven motor activity of SARS-CoV helicase
Authors: Yu Jeongmin , Im Hyeryeon , Cho HyeokJin , Jeon Yongmoon , Lee Jong-Bong , Lee Gwangrog
Published: January 2025

Helicase is a nucleic acid motor that catalyses the unwinding of double-stranded (ds) RNA and DNA via ATP hydrolysis. Helicases can act either as a nucleic acid motor that unwinds its ds substrates or as a chaperone that alters the stability of its substrates, but the two activities have not yet been reported to act simultaneously. Here, we used single-molecule techniques to unravel the synergistic coordination of helicase and chaperone activities, and found that the severe acute respiratory syndrome coronavirus helicase (nsp13) is capable of two modes of action: (i) binding of nsp13 in tandem with the fork junction of the substrate mechanically unwinds the substrate by an ATP-driven synchronous power stroke; and (ii) free nsp13, which is not bound to the substrate but complexed with ADP in solution, destabilizes the substrate through collisions between transient binding and unbinding events with unprecedented melting capability. Our findings provide new insights into how the same enzyme works via two modes on different parts of the substrate and synergistically catalyses the unwinding reaction, utilizing ATP and recycling its by-product ADP as an energy source.
Nanoparticle encapsulation enables systemic IGF-Trap delivery to inhibit intracerebral glioma growth
Authors: Chen Yinhsuan Michely , Chambon Julien , Moquin Alexandre , Hashimoto Masakazu , Perrino Stephanie , Leibovitch Matthew , Benslimane Yasmine , Haçariz Orçun , Yang Qin , Nakano Ichiro , Meehan Brian , Rak Janusz , Gagné Stéphane , Brodt Pnina
Published: January 2025

Background

Glioblastoma is an aggressive brain cancer with a 5-year survival rate of 5–10%. Current therapeutic options are limited, due in part to drug exclusion by the blood–brain barrier, restricting access of targeted drugs to the tumor. The receptor for the type 1 insulin-like growth factor (IGF-1R) was identified as a therapeutic target in glioblastoma. We previously reported that the intracerebral growth of glioma cells with reduced IGF-1R levels was inhibited. The objectives of this study were to evaluate the sensitivity of glioma cells to a novel IGF-axis inhibitor, the IGF-Trap, and optimize its delivery to the brain.

Methods

We tested the effect of the IGF-Trap on the growth of the human glioma stem cells MES-1123 and U87 MG cells, and of murine GL261 cells in vivo, using subcutaneous and orthotopic implantation.

Results

We show that the growth of glioma cells implanted subcutaneously or orthotopically in the brain was inhibited by systemic and direct intracerebral administration of IGF-Trap, respectively, resulting in increased survival. To increase the efficiency of systemic delivery to the brain, we encapsulated the IGF-Trap in trimethyl chitosan (TRIOZAN™) nanoparticles prior to intravenous injection. We found that nanoparticle encapsulation increased the uptake and retention of the IGF-Trap in the brain and resulted in an improved therapeutic effect against intra-cerebrally growing tumors.

Conclusion

Our results identify the IGF-Trap as a potent inhibitor of intracerebral glioma growth and show that encapsulation in nanoparticles can improve delivery of biologics such as the IGF-Trap to the brain, thereby enhancing the therapeutic response.
222. Effectiveness of the Original BNT162b2 Messenger RNA Vaccine Against COVID-19 Omicron Infection in Children Aged 6 Months to 4 Years in Japan
Authors: Aizawa Yuta , Shobugawa Yugo , Tachikawa Jun , Ikuse Tatsuki , Shin Chansu , Ikarashi Takao , Okugawa Takayoshi , Otsuka Taketo , Sasagawa Fujio , Sakauchi Masako , Sato Masahisa , Ino Haruyoshi , Ota Masaya , Kon Miyako , Saitoh Akihiko
Published: January 2025

Background

The coronavirus disease 2019 (COVID-19) messenger RNA (mRNA) vaccines were confirmed to be safe and effective, and the original BNT162b2 mRNA vaccine for children aged 6 months to 4 years was introduced in October 2022. However, COVID-19 vaccination coverage has been low in children, especially among those aged 6 months to 4 years. Few studies have evaluated vaccine effectiveness (VE) in this age group, and no data are available from Japan.

Methods

A test-negative, case-control study was conducted between April and October in 2023 at 10 pediatric clinics in Niigata, Japan. We included patients aged 6 months to 4 years with upper respiratory tract symptoms who were tested for severe acute respiratory syndrome coronavirus 2 by rapid antigen testing or PCR assay. Cases and controls were defined as those with positive and negative test results, respectively. The recommended original BNT162b2 mRNA COVID-19 vaccine primary series comprised 3 doses, and a vaccine dose was recorded if at least 2 weeks had passed since the last vaccination. Odds ratios (OR) were calculated using a multivariable logistic regression model adjusted for sex, age, underlying disease, history of COVID-19, and outbreak period. VE was calculated as (1 − adjusted OR) × 100% and is presented with the 95% confidence interval (95% CI).

Results

During the study period an outbreak of omicron subvariants XBB and EG.5 occurred between July and September. In total, 2253 patients were included—262 (11.6%) patients were the cases and the remaining 1991 patients were the controls; 181 (8.0%) patients received ≥3 vaccine doses, and 938 (41.6%) patients had a history of COVID-19. VE against COVID-19 was 62% (95% CI, 26–81%) after ≥3 doses. Three months after the last vaccine dose, VE against COVID-19 was 59% (95% CI, 13–81%) among patients who received ≥3 doses of COVID-19 mRNA vaccine.

Conclusion

Among children aged 6 months to 4 years in Japan who received ≥3 doses of the original BNT162b2 mRNA COVID-19 vaccine, the vaccine was effective against COVID-19 infection by omicron subvariants for at least 3 months after the last dose. To ensure protection against COVID-19 in this vulnerable population, further follow-up study is necessary.

Disclosures

All Authors: No reported disclosures
P-901. Clinical Characteristics and Outcomes of CNS Nocardiosis Differ by Nocardia Species: A Review of Published Cases
Authors: Abers Michael S
Published: January 2025

Background

Nocardiosis is an opportunistic infection with a predilection for central nervous system (CNS) involvement. A large number of Nocardia species ( >50) have been associated with human infection. Efforts to compare the clinical characteristics of nocardiosis across Nocardia species have been limited by insufficient sample size.

Distribution of Nocardia species/species complex among all patients with CNS nocardiosis.

Methods

A literature search of multiple databases (PubMed, Scopus, Google Scholar, Google) was conducted to identify potential cases of CNS nocardiosis published from 1/2000-3/2024. CNS nocardiosis was defined as either identification of Nocardia in a CNS specimen or identification of Nocardia at any site combined with clinical, laboratory, radiographic, or histopathologic evidence of CNS infection. Cases of CNS nocardiosis were included if Nocardia species was reported to at least the species complex level. Duplicate cases were excluded. Categorical variables were compared by chi-squared test with statistical significance defined as P< 0.05.

Frequency of each Nocardia species/species complex stratified by risk factor group.

Results

In total, 826 cases of CNS nocardiosis were included; one-third were derived from the grey literature (sources not included in PubMed). Cases were reported in 54 countries with 81.1% from North America, Europe, or East Asia. Half of all cases were caused by N. farcinica (Figure 1). Brain abscess +/- meningitis was the most common manifestation of CNS nocardiosis (96.4%). The frequency of various characteristics differed across species (Table 1, Figure 2). N. paucivorans/brevicatena cases were disproportionately reported in Oceania. N. abscessus and N. paucivorans/brevicatena were overrepresented in immunocompetent individuals and among patients with pulmonary alveolar proteinosis (PAP). These species were associated with a lower mortality rate. N. nova was particularly among recipients of solid organ (SOT) or hematopoietic stem cell transplantation (HSCT). Skin and musculoskeletal involvement were more common in patients with N. brasiliensis.

Frequency of clinical characteristics for each Nocardia species/species complex.

Conclusion

Patient population, clinical manifestations, and outcome of CNS nocardiosis varies according to the species of Nocardia responsible for infection. Knowledge of the causative species has important implications for clinical practice.

Disclosures

All Authors: No reported disclosures
P-968. Academic - Practice Partnership to Advance Infection Prevention Education and Practice
Authors: Manning Mary Lou , Zabriskie Kelly , Renzi John , Hou Cindy M
Published: January 2025

Background

Nurses entering the workforce must have the requisite knowledge, skills, and abilities to recognize, prevent, and manage infection in individuals and populations, and be prepared to respond collaboratively to local, regional, and global infection prevention and control (IPC) challenges. Studies indicate that IPC content is lacking in US baccalaureate nursing (BSN) programs and graduates feel ill-prepared to implement infection risk mitigation strategies to protect patients and health care workers. Establishing academic- practice partnerships between colleges of nursing and health system IPC programs could close this gap.

Methods

Our urban college of nursing, enrolling over 600 BSN students annually, convened a one-day invitational workshop focused on establishing an academic- practice partnership with our 18-hospital University-Health System IPC program. The workshop included presentations and small group work among expert inter-professional participants from IPC, nursing faculty and students, health system nursing, public health, and research.

Results

A strategy and research agenda was developed to advance BSN student IPC education and practice, including opportunities for infection preventionists to inform academic content and provide IPC student clinical practice experiences. As an immediate outcome, we conducted a survey of our graduating BSN seniors (n=345) to gauge perceived value of a clinical IPC rotation, and a survey of student’s clinical preceptors (n=345) to elicit perceived ability of students to transfer their classroom knowledge into clinical practice. A quarter of the 86 student respondents (25%) expressed value in doing a clinical rotation in the IPC department. Almost 100% of the 160 preceptor respondents (46%) indicated that students successfully adapt classroom knowledge to various clinical practice situations.

Conclusion

The workshop provided a forum to explore and begin to establish an academic- practice partnership between our college of nursing and the University-Health System IPC program. The survey results provide informative stakeholder data. The aim of this abstract is to report on the workshop proceedings, including short and long-term strategies, results of student and clinical preceptor surveys and next steps.

Disclosures

All Authors: No reported disclosures
P-1037. Prevalence and antifungal susceptibility of Candida species isolated from Korean infants and children with candidemia, 2011-2023
Authors: Moon Hye Jeong , Kang Da Yun , Cho Youngmin , Lee Hyunju , Choi Eun Hwa , Yun Ki Wook
Published: January 2025

Background

Candida is the most common cause of fungal infections, and candidemia is the most common form of invasive fungal infection. The widespread use of antifungal agents has led to a global increase in non-albicans Candida infections and antifungal resistance. This study aims to investigate the clinical characteristics, treatment outcomes, fungal species, and antifungal susceptibility results of candidemia cases in Korean children.

Trend of annual candidemia prevalence and distribution of Candida species

Methods

This study retrospectively collected and analyzed clinical data from Korean children at two referring hospitals from 2011 to 2023. A case of candidemia was defined as a positive confirmation of any Candida species on at least one blood culture. Information on the Candida species and antifungal susceptibility was obtained from the results of the VITEK II automated equipment. The annual incidence of candidemia was adjusted to the combined number of hospitalized children in the two hospitals, and statistical analysis was performed on 30-day mortality as risk factors.

Distribution of Candida species according to the age groups

Results

A total of 144 cases of candidemia were diagnosed in 139 children. The prevalence rate of candidemia per 1,000 actual hospitalized children was 0.6-2.4 (median 1.6). The age distribution showed 46.0% of individuals were younger than three months. All patients had an underlying medical condition, with prematurity (93.2%) most common in those under three months and hemato-oncology (HO) disease (44.0%) in those three months and older. In the younger age group, Candida glabrata was the most prevalent (31.8%), followed by Candida albicans (27.3%) and Candida parapsilosis (24.2%). In the older age group, C. albicans was the most prevalent (34.9%), followed by C. parapsilosis (26.5%). Non-susceptibility were 0.9% for amphotericin, 15.6% for fluconazole, 0% for voriconazole, 2.9% for caspofungin, and 7.7% for micafungin. The 30-day mortality rate for candidemia was 28%. The distribution of the Candida species was comparable between the mortality and survival groups. Age of 5-9 years and HO underlying disease were significantly associated with 30-day mortality.

Antifungal non-susceptibility according to Candida species

Conclusion

The proportion of candidemia caused by non-albicans Candida species remained high in Korean children, requiring individualized strategies for initial treatment based on age group and underlying medical conditions.

Risk factors for 30-mortality in Korean children with candidemia

Disclosures

All Authors: No reported disclosures
P-1038. Clinical Analysis of Nosocomial Candidemia: Species Profile, Resistance Patterns and Mortality Determinants
Authors: Kumar Deepak , Chaudhary Monika , Midha Naresh Kumar , Meena Durga Shankar , Bohra Gopal Krishna , Garg M K , Kothari Nikhil , Bhatia Pradeep
Published: January 2025

Background

Candidemia has become one of the commonest nosocomial blood stream infection (BSI) secondary to infected central venous catheters or surgical site infections. Prompt diagnosis followed by early treatment is needed to reduce the high mortality associated with it. Hence this study was conducted to analyse the epidemiology, clinical characteristics, species distribution, resistance profile, outcome and factors related to outcome in nosocomial candidemia.

Methods

It was a retrospective observational analysis done for the period of 1 year in a tertiary health care centre of western Rajasthan from 1st July 2022 to 30th June 2023. All adult patients admitted in multispeciality intensive care unit (ICU) for more than 48 hours and developing candidemia were included and those patients with a single blood fungal culture positive from the sample obtained from indwelling central venous catheter were excluded as colonisers. Data was collected by regular AMS rounds and was analysed using SPSS version 20.

Results

Out of total 76 cases of candidemia,61 were included in the study. As shown in figure 1, the most common species isolated was Candida tropicalis followed by Candida parapsilosis.both were associated with high mortality. Clinicoepidemiological characters are described in table1. Overall, all cause 28th day mortality was 63.9 %. Highest resistance was found for the azoles. As depicted in table 2, on univariate and multivariate analysis infection with Candida tropicalis, use of inotropes, ventilator use, and high SOFA scores were the independent factors affecting mortality in candidemia.

Conclusion

Candidemia is a nosocomial infection with very high mortality which needs to be diagnosed early. Candida tropicalis being the most frequent species isolated in our ICU setup with a significantly high mortality.

Disclosures

All Authors: No reported disclosures
P-1118. Clinician knowledge, attitudes, and practices around empiric vancomycin use in the pediatric intensive care unit
Authors: Chiotos Kathleen , Gerber Jeffrey S , Jaggi Preeti , Facer Evan E , Goldsmith Matthew I , Newland Jason G , Same Rebecca G , Tamma Pranita , Muller Brandi M , Meyahnwi Didien , Lautenbach Ebbing , Szymczak Julia E
Published: January 2025

Background

Overuse of empiric vancomycin is common in pediatric intensive care units (PICU) despite a low prevalence of infections requiring vancomycin. Determinants of excess vancomycin prescribing are unknown. Our objective was to evaluate PICU clinician knowledge, attitudes, and practices regarding empiric vancomycin.Table 1.Demographic variables of survey respondents

Methods

We conducted a cross-sectional survey of PICU attendings, fellows, residents, and advanced practice providers in five tertiary care PICUs. The survey was distributed by email in August-September 2023. Survey items included Likert scale (1-5), ranking, and multiple-choice responses. Agree/Strongly Agree and Disagree/Strongly Disagree were collapsed to Agree and Disagree for analysis. Data were analyzed using descriptive statistics.Figure 1.Clinician attitudes about vancomycin use

Results

A total of 134 of 297 eligible clinicians (45%) answered the survey (Table 1). Knowledge of the spectrum of activity of vancomycin was low with only 14 of 117 (12%) respondents answering all questions correctly. Just over half of clinicians agreed that vancomycin overuse was a significant problem (72/134, 54%); this proportion varied from 0% to 65% across sites. Most clinicians (105/133, 79%) agreed that reducing vancomycin overuse would reduce antibiotic-associated adverse events. Clinicians had greater confidence in determining when vancomycin should be given to a patient with sepsis as compared to a hemodynamically stable patient with a fever (107/134, 80% vs 80/131, 61%). Respondents were most confident in determining when vancomycin could be stopped (113/134, 84% agreed) (Figure 1). Illness severity was the factor influencing the decision to start vancomycin ranked highest by the most respondents (55%), followed by suspected source of infection (19%), followed by patient history of methicillin-resistant Staphylococcus aureus (MRSA) (18%); local prevalence of MRSA was ranked highest least often (4%) (Figure 2).Figure 2.Factors influencing clinician decisions to administer empiric vancomycin

Respondents ranked each possible factor 1-7 with 1 being the most influential factor in choosing to give vancomycin and 7 being the least influential. The blue shading reflects more influential factors and the gray shading reflects less influential factors.

Conclusion

Most PICU clinicians in this multi-site study felt confident about when to stop or start vancomycin, though many misunderstood the spectrum of vancomycin activity. Focusing stewardship efforts on improving clinician knowledge and supporting decision making, particularly for patients without sepsis, may address these barriers.

Disclosures

Jason G. Newland, MD, MEd, Moderna: Grant/Research Support|Pfizer: Grant/Research Support
P-1131. Comparison of Vancomycin Use Before and After the Implementation of an Antimicrobial Stewardship Program in a Pediatric Reference Hospital in Mexico
Authors: Concha-Mora Lindsay A , Ayala Villegas Gloria R , Rodriguez-Chong Jose Guillermo , Treviño-Valdez Pablo D , Tamez-Rivera Oscar
Published: January 2025

Background

The growing threat of antimicrobial resistance is associated with the overprescription of broad-spectrum antibiotics. Antimicrobial stewardship programs (ASP) promote the responsible use of antibiotics. Their successful implementation requires adequate infrastructure and interdisciplinary efforts. ASPs in Mexico (Mx) are still scarce, particularly in pediatric centers.

Table 1. Diagnostics that justified use of Vancomycin

Total of diagnostics founded on 71 Stewardship Interventions

Methods

Ambispective study to compare Vancomycin (VA) use before-after implementing a pilot 9-month handshake (HS) ASP at the pediatric reference hospital in NL, Mx. Stewardship interventions were applied from Jan to Oct 2022 among patients >1 mo and < 16 yr hospitalized with clinical suspicion/confirmation of Gram-positive infection, candidates to receive or currently receiving VA. PID specialists performed morning HS rounds. Prescription was labeled as correct/incorrect according to IDSA guidelines. Interventions were stratified as VA prevention and early discontinuation. VA use (DOT/1000 PD) from Jan to Oct 2021 was compared with t-Student test and ANOVA.Table 2.DOT/1000 PD Pre and Post the 9-month Pilot Hand-Shake Stewardship Program

Analysis of the DOT/1000 PD Compared of the Same Population at the Pediatric Reference Hospital in NL, Mx on a 9-month Period.

Results

A total of 92 stewardship interventions were applied. Of these, the incorrect use of VA was prevented before its prescription in 21 cases. VA prescription was incorrect in 46% of the cases, in which early discontinuation was ordered. Correct use of VA (54%) occurred in patients with meningitis (31.5%), CLABSI (21%), septic shock (13%), among others (Table 1). SA was isolated in 14 patients. MRSA prevalence was 35.7% (5/14). Both prevention and early discontinuation of VA led to a decrease of 5.2 DOT/1000 PD (8.2 vs 3.6 DOT/1000 PD) (p=0.06) (Table 2).

Conclusion

Implementing a HS ASP for 9 months in a pediatric reference hospital in Mx decreased the use of VA by 5.2 DOT/1000 PD. Although this was a short pilot program, implementing ASP reduced the use of broad-spectrum antibiotics. Extending the ASP duration may achieve lower VA use and statistical significance. The number of PID specialists in Mx is limited, which highlights the importance of ASP. Multidisciplinary efforts are required to reduce antimicrobial overuse.

Disclosures

All Authors: No reported disclosures
P-1155. Acute Osteomyelitis and Septic Arthritis in Children in Israel: Epidemiology, Microbiology, Clinics and Outcomes
Authors: Grisaru Galia , Lerner Reut Kassif , Elmaleh Yael , Michaan Nadav , Paret Gideon
Published: January 2025

Background

The goal of this study was to characterize the clinical, microbiologic epidemiological characteristics and outcome associated with osteoarticular infections ( OAIs) in hospitalized children in Israel.Figure 1:Annual incidence for each disease per 100,000 hospitalizations during the years of study. SA-septic arthritis, OM-osteomyelitis

Methods

Patients < 18 years old admitted with a diagnosis of acute osteomyelitis (AOM) or septic arthritis ( SA), between January 2007 and December 2019 were included if they had a microbiological and/or radiological findings supporting the diagnosis. Clinical and laboratory data were retrieved from the medical records.

Results

305 children with OAIs were included. The annual incidence among osteomyelitis patients increased by 10.25 cases per 100,000 hospitalizations every year (P=0.019) during the study period. Tibia and knee were the most frequently involved bones and joints. About one-half (47.5%) of the patients were febrile upon admission. Laboratory data analyses showed that 36 (26%) AOM and 74 (48%) SA patients had leukocytosis at presentation. C-reactive protein (CRP) levels ( >5 mg\dL) were elevated in 87% and 71% of patients with SA, and AOM, respectively. The most common isolated pathogens were methicillin susceptible Staphylococcus aureus followed by Kingella Kingae. About 5% of the hospitalized patients due to septic arthritis and 6% of the osteomyelitis patients had complications and underwent a surgical intervention. There were no long term sequelae.

Conclusion

The admission rate for acute osteomyelitis in children increased significantly during the last decade. Fever and WBC, were not sufficiently reliable to diagnose or rule out OAIs. The most common isolated pathogens are methicillin susceptible Staphylococcus aureus followed by Kingella Kingae. Through accurate diagnosis and treatment with appropriate antibiotics and surgical intervention when indicated osteoarticular infections have a favorable outcome and no long term sequelae.

Disclosures

All Authors: No reported disclosures
427. Underlying Medical Conditions and Vaccination Status among U.S. Children Aged ≤17 Years Hospitalized for COVID-19 in COVID-19-Associated Hospitalization Surveillance Network (COVID-NET), January–December 2023
Authors: Free Rebecca J , Patel Kadam , Sachdev Darpun , Alden Nisha B , Meek James , Ryan Patricia A , Falkowski Anna , D’Heilly Paige , Smelser Chad , Engesser Kerianne , Bushey Sophrena , Moran Nancy E , Sutton Melissa , Talbot H Keipp , Swain Ashley , Campbell Angela P , Havers Fiona , Openo Kyle P
Published: January 2025

Background

SARS-CoV-2 infection can result in serious illness in children. We used COVID-19-Associated Hospitalization Surveillance Network (COVID-NET) data to assess characteristics associated with pediatric COVID-19 hospitalizations, including underlying medical conditions and vaccination status.

Percent of COVID-19-Associated Hospitalizations† with Specific Underlying Medical Conditions among U.S. Children Aged ≤17 Years by Age Group — COVID-NET, January–December 2023

Methods

U.S. children aged ≤ 17 years with COVID-19 as the likely primary reason for hospitalization during January–December 2023 were identified in the population-based COVID-NET active surveillance system, which includes patients residing in a catchment area of > 300 acute care hospitals in 13 states with a positive SARS-CoV-2 test result during or ≤ 14 days before admission. Medical records of a random sample of children stratified by age-group and site were abstracted; reported percentages were weighted to account for probability of selection. We assessed patient age, underlying medical conditions, and receipt of vaccine dose within 12 months before illness.

Results

Of 2016 children hospitalized for COVID-19, 1232 (61%) were aged < 2 years (611 aged < 6 months; 621 aged 6–23 months). Overall, 51% had no underlying condition, including 73% of infants aged < 6 months, 58% of children aged 6–23 months, and 24% of children aged 12–17 years (Figure). Among children aged < 2 years, prematurity was the most common underlying condition (17–20%). Neurologic disorders (27–31%) and asthma (21–33%) were most prevalent among children aged ≥ 2 years. Among 1379 children aged ≥ 6 months eligible for vaccination with vaccine data available, only 14% had received ≥ 1 vaccine dose within 12 months before illness, with the lowest frequency (9%) among children aged 6–23 months (Table). Among age-eligible children with neurologic disorders and asthma, only 18% and 16% were vaccinated, respectively.

Conclusion

Most children aged < 2 years hospitalized for COVID-19 during 2023 had no underlying conditions; underlying conditions were more prevalent among older children. More than 85% of age-eligible children had not received a vaccine dose within 12 months, including among children with underlying conditions. Increasing pediatric COVID-19 vaccination, especially among children with underlying medical conditions, could help reduce COVID-19 hospitalizations.

Disclosures

Anna Falkowski, Master of Science, Council of State and Territorial Epidemiologists (CSTE): Grant/Research Support