bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

Abstract

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

Abstract

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

Abstract

Background
Nocardiosis is an opportunistic infection with a predilection for central nervous system (CNS) involvement. A large number of Nocardia species ( &gt;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&lt; 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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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 &gt;1 mo and &lt; 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