bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ecosystems of Professionalism
Authors: Edgar Laura , Selden Nathan R. , Brigham Timothy P. , Inui Thomas S. 
Published: January 2025

Abstract
Objective: This chapter focuses on the way that professionalism can develop during graduate medical education and how it can be measured through milestones. Methods: Through use of the Accreditation Council for Graduate Medical Education’s milestones for professionalism (professional behavior, ethical principles, and accountability), the literature has been explored and vignettes have been developed to further demonstrate a developmental trajectory of attaining advanced levels of professionalism in these three areas. Results: Milestones data demonstrates the growth of professionalism during graduate medical education at both the residency and fellowship levels. Development and demonstration of these skills and attributes happen at different junctures in training. Conclusion: Professionalism is a competency that develops over time and through various experiences. As an individual moves from medical school to residency to fellowship and into practice, professionalism skills will continue to develop.
Special Considerations for Military and Veterans
Authors: Place Ronald , Sugden Steven G. 
Published: January 2025

Abstract
Military medicine serves the specific purpose of working to maintain the high-functioning capacity of the U.S. military complex, with the unique role to preserve the health of its Soldiers. This makes the provision of care in military medicine different from the care provided only to civilian populations and results in important differences in how medical professionalism is thought about and addressed within the provision of military medicine. This chapter addresses some of the historical aspects of military medicine, as well as how military medicine has helped advance medical care, while also addressing some of the specific differences in education and development of military medical professionals.
Health Law and Organizational Professionalism
Authors: Agris Julie L. 
Published: January 2025

Abstract
Fractions of the health sector continue to grapple with public skepticism about professionalism, on individual and organizational levels. This uncertainty has led to questions related to the ability to trust healthcare personnel at every level of the system. To foster healthcare organizations that prioritize organizational professionalism (OP), leaders, in addition to all stakeholders, within the entity must understand and consider the framework for realizing OP. One approach to purposefully incorporating OP principles into an organization’s culture may be to identify ongoing organizational behaviors and actions that promote professionalism. One area that is regularly implicated as an obstacle to achieving professionalism is the laws and associated policy requirements. To delve more deeply into the ways in which the law does or does not act as an impediment to prioritizing professionalism and OP, this chapter reviews the relevant domains of OP, identifies many of the areas on which they intersect with health law (HL), then concludes with a case study of the way in which the OP domains could be applied to an important aspect of HL: privacy and confidentiality of protected health information. The chapter identifies several of the commonly perceived areas of concern related to HL and its potential to impede the achievement of OP. The chapter concludes by suggesting preliminary strategies and recommendations for improving identified obstacles and ways in which the law can serve to support efforts to prioritize OP and bolster trust and trust building in the health sector.
Isopropyl Alcohol Nasal Inhalation for Nausea in the Emergency Department
Authors: Choi Alex , Morrison Laura 
Published: January 2025

Abstract
This randomized, double-blinded, placebo-controlled trial investigated whether inhaled isopropyl alcohol reduces nausea compared to inhaled normal saline. Eighty adults who presented to the emergency department with the chief complaint of nausea/vomiting were randomized to either inhaled isopropyl alcohol or inhaled normal saline. Investigators measured verbal scores of nausea and pain at fixed intervals, overall satisfaction, and coadministration of rescue antiemetics. The intervention group had a lower median nausea score at 10 minutes compared to the placebo group (P &lt; .01) and higher overall satisfaction. These findings suggest inhaled isopropyl alcohol as a potential effective treatment for acute nausea.
Methadone Versus Morphine as a First-Line Strong Opioid for Cancer Pain
Authors: Allen Jennifer , Gans Brian 
Published: January 2025

Abstract
This chapter reviews a study that compares the effectiveness and side effects of methadone and morphine as first-line opioid treatment for cancer pain. Patients in multiple international palliative care clinics with cancer pain were randomly assigned to receive methadone or morphine over the duration of a 4-week study. Methadone did not produce superior analgesic efficiency or overall tolerability at 4 weeks compared to morphine. This is the first double-blind study that uses methadone as a first-line strong opioid for patients with advanced cancer pain.
Octreotide in Malignant Bowel Obstruction
Authors: Latuga Natalie M. , Luczkiewicz Debra L. , Davis Mellar P. 
Published: January 2025

Abstract
This chapter reviews a large, double-blind, placebo-controlled, randomized trial examining the effects of adding octreotide to standardized supportive therapy in the setting of malignant bowel obstruction. The study was rigorously designed and adequately powered for the primary endpoints and found no significant difference between octreotide and placebo, which is contrary to current practice and other reports of efficacy. This chapter describes the basics of the study and briefly reviews the study limitations and criticisms. The implications of this study are illustrated by a short clinical case.
Safety and Benefit of Discontinuing Statin Therapy in Advanced Life-Limiting Illness
Authors: Nymeyer Jessica 
Published: January 2025

Abstract
This multicenter, unblinded, randomized clinical trial evaluated the impact of discontinuation of statin therapy for individuals with a life expectancy of less than 1 year without active cardiovascular disease and found no significant difference in survival or cardiovascular events. The study found that statin discontinuation may be associated with improved quality of life, decreased use of nonstatin medications, and reduced medication cost.
Safety of Morphine Delivered via Patient-Controlled Analgesia Devices in the Pediatric Population
Authors: Urban Sophia S. , Higgins Elizabeth A. 
Published: January 2025

Abstract
Although the use of patient-controlled analgesia (PCA) in the pediatric population is widely accepted as an effective and preferable method of pain control, there have been no large-scale studies conducted to examine the safety of these devices in children. This study compared the delivery of morphine either via PCA device or intravenous (IV) administration in a retrospective cohort and assessed the short-term risk of cardiopulmonary resuscitation (CPR) or need for mechanical ventilation (MV). Results showed that patients who received morphine via PCA were not at increased risk of requiring CPR or MV, leading to the conclusion that PCA usage in pediatric patients is at least as safe as conventional IV analgesia.
Headache and sleep
Authors: Nesbitt Alex 
Published: January 2025

Abstract
A strong bidirectional relationship exists between sleep and headache disorders. This relationship exists at many levels, including neuroanatomical, physiological, pharmacological, homeostatic, and therapeutic. Disturbances in sleep, and sleep disorders, impact many of the primary headache disorders.
This chapter provides an overview of these relationships, and a practical approach to modifying and optimizing sleep to aid in the management of headache.
Headache in children
Authors: Abu-Arafeh Ishaq 
Published: January 2025

Abstract
Headache is one of the most common complaints in children. Recurrent headache can negatively impact a child’s life in a number of ways, including school absences, decreased academic performance, social stigma, and impaired ability to establish and maintain peer relationships.
Headache in young people is associated with a high risk of comorbidities, particularly anxiety and depression, sleep disorders, and attention deficit hyperactivity disorder. It invariably persists into adulthood, so timely diagnosis is an opportunity for early understanding and control of headache and its associated problems. This chapter offers an overview of the management of headache in children.
Psychological approaches to headache conditions
Authors: White Sophie 
Published: January 2025

Abstract
The psychological needs of people with headache conditions are frequently defined in terms of high rates of mental health comorbidities, such as anxiety, depression, and suicidality. Psychological factors may also maintain illness behaviour that leads to higher levels of disability. This chapter describes a range of assessment and screening tools and an overview of current approaches to the psychological management of the person with headache.
Cryo-EM structure of AAV2 Rep68 bound to integration site AAVS1: insights into the mechanism of DNA melting
Authors: Jaiswal Rahul , Braud Brandon , Hernandez-Ramirez Karen C , Santosh Vishaka , Washington Alexander , Escalante Carlos R 
Published: January 2025

Abstract
The Rep68 protein from Adeno-Associated Virus (AAV) is a multifunctional SF3 helicase that performs most of the DNA transactions necessary for the viral life cycle. During AAV DNA replication, Rep68 assembles at the origin of replication, catalyzing the DNA melting and nicking reactions during the hairpin rolling replication process to complete the second-strand synthesis of the AAV genome. We report the cryo-electron microscopy structures of Rep68 bound to the adeno-associated virus integration site 1 in different nucleotide-bound states. In the nucleotide-free state, Rep68 forms a heptameric complex around DNA, with three origin-binding domains (OBDs) bound to the Rep-binding element sequence, while three remaining OBDs form transient dimers with them. The AAA+ domains form an open ring without interactions between subunits and DNA. We hypothesize that the heptameric structure is crucial for loading Rep68 onto double-stranded DNA. The ATPγS complex shows that only three subunits associate with the nucleotide, leading to a conformational change that promotes the formation of both intersubunit and DNA interactions. Moreover, three phenylalanine residues in the AAA+ domain induce a steric distortion in the DNA. Our study provides insights into how an SF3 helicase assembles on DNA and provides insights into the DNA melting process.
RNA G-quadruplex structure-based PROTACs for targeted DHX36 protein degradation and gene activity modulation in mammalian cells
Authors: Zhang Kun , Nie Qichang , Li Maolin , Chen Xiaona , Zhong Liting , Dai Tianle , Guo Xiaofan , Zhao Haizhou , Lau Terrence Chi-Kong , Wang Huating , Chen Shuo-Bin , Kwok Chun Kit 
Published: January 2025

Abstract
RNA G-quadruplexes (rG4s) are non-canonical secondary nucleic acid structures found in the transcriptome. They play crucial roles in gene regulation by interacting with G4-binding proteins (G4BPs) in cells. rG4-G4BP complexes have been associated with human diseases, making them important targets for drug development. Generating innovative tools to disrupt rG4-G4BP interactions will provide a unique opportunity to explore new biological mechanisms and potentially treat related diseases. Here, we have rationally designed and developed a series of rG4-based proteolytic targeting chimeras (rG4-PROTACs) aimed at degrading G4BPs, such as DHX36, a specific G4BP that regulates gene expression by binding to and unraveling rG4 structures in messenger RNAs (mRNAs). Our comprehensive data and systematic analysis reveals that rG4-PROTACs predominantly and selectively degrade DHX36 through a proteosome-dependent mechanism, which promotes the formation of the rG4 structure in mRNA, leading to the translation inhibition of rG4-containing transcripts. Notably, rG4-PROTACs inhibit rG4-mediated APP protein expression, and impact the proliferative capacity of skeletal muscle stem cells by negatively regulating Gnai2 protein expression. In summary, rG4-PROTACs provide a new avenue to understand rG4-G4BP interactions and the biological implications of dysregulated G4BPs, promoting the development of PROTACs technology based on the non-canonical structure of nucleic acids.
Job-exposure matrix (JEM) validity on crystalline silica among systemic sclerosis patients
Authors: Touchard M , Bourgeois A , Thoreau B , Fadel M , Zavarsky B , Diot E , Lescoat A , Le Roux G , Descatha A 
Published: January 2025

ABSTRACT

Background
Systemic sclerosis (SSc) is the connective tissue disease with the highest individual mortality. Crystalline silica is known to be an occupational risk factor for SSc. To assess past crystalline silica exposure, we aimed to study the validity of a job exposure matrix (JEM) to assess occupational exposure to crystalline silica compared to specific occupational interviews in two populations of SSc patients.

Aims
To demonstrate the reliability of JEM for the assessment of occupational exposure to hazards such as silica, in severe rare disorders like SSc.

Methods
Patients from two university hospital centres underwent standardized assessment of occupational silica exposure and collected job histories through face-to-face interviews. A JEM from the French program Matgéné was used to assess silica exposure and compared to the standardized interview results. Standard metrics were computed for evaluate the accuracy of JEM.

Results
67 participants from Rennes, and 119 from Tours were included, with respectively 10.5% and 18.0% of patients with silica exposure based on the results of the interview. The JEM with 50% probability cut-off had a good performance when compared with the classic assessment method. A cumulative exposure index from JEM over 250 had an area under the curve between 0.76 and 0.79 and also a very high positive likelihood ratio (17.14 and 10.29).

Conclusions
Despite limitations inherent to JEMs and associated validation methods, the JEM used in this setting provided accurate results to assess occupational exposure to crystalline silica for clinical purposes such as in SSc patients, especially to detect positive cases.
579. Safety and Immunogenicity of Mpox Vaccination in Adolescents
Authors: Healy C Mary , Creech C Buddy , Frey Sharon E , Lerner Andrea , Tomashek Kay , Beigel John H 
Published: January 2025

Abstract

Background
Monkeypox (Mpox) is a global public health threat. In the current Democratic Republic of Congo (DRC) mpox outbreak, children &lt; 15 years of age comprise 70% of cases and 88% of deaths. Modified Vaccinia Ankara-Bavarian Nordic (MVA-BN) vaccine is a live attenuated, non-replicating orthopoxvirus vaccine licensed in the US to prevent smallpox and mpox. MVA-BN is not approved in persons &lt; 18 years of age (though is available in some countries under emergency use authorization).
Geometric Mean Titers of Vaccinia-Specific PRNT by Time Point and Age Group

Methods
We conducted a Phase 2, open-label, multisite clinical trial to evaluate the safety and immunogenicity of two 1x108 TCID50 doses of MVA-BN vaccine administered subcutaneously 28 days apart in adolescents aged 12-17 years compared to adults aged 18-50 years (NCT05740982). A planned interim analysis evaluated safety through Day 210 (180 days post dose 2) and immunogenicity through Day 43 (14 days post dose 2).

Results
Three hundred fifteen adolescents (161 [51%] aged 12-14 years, 160 [51%] male, 216 [69%] white, 251 [80%] not Hispanic or Latino) were compared to 211 adults (94 [45%] male, 145 [69%] white, 149 [71%] not Hispanic or Latino). Solicited systemic and local events, and unsolicited adverse events (AEs), were similar in both groups. Dizziness was more common in adolescents (9 events in 8/315 (3%) versus none in adults) but similar to rates reported after other adolescent vaccines. Overall, MVA-BN was well tolerated. Day 43 antibody responses, based on vaccinia virus (Western Reserve strain) plaque-reduction neutralization titer (PRNT) assay geometric mean titer (GMT), elicited by MVA-BN in adolescents (470.3 [95% CI: 422.3, 523.8]) were non-inferior to the response in adults (293.2 [95% CI: 249.8, 344.2]); GMT ratio: 1.60 [95% CI: 1.32, 1.95]) (Figure).

Conclusion
The interim data demonstrate MVA-BN vaccine is well-tolerated and the peak GMT met prespecified non-inferiority criteria for adolescents as compared to adults. These findings are relevant to adolescents in the US and in areas where Mpox is endemic. Evaluations in younger children are urgently needed to extend protection to those who are most vulnerable.

Disclosures
C. Mary Healy, MD, FIDSA, Dexcom Inc: Stocks/Bonds (Public Company)|Hillevax, Inc: Member of Advisory board|Intuitive Surgical Inc: Stocks/Bonds (Public Company)|Quidel Corporation: Stocks/Bonds (Public Company)|Vapotherm: Stocks/Bonds (Public Company) C. Buddy Creech, MD, MPH, CommenseBio: Advisor/Consultant|GSK: Advisor/Consultant|Moderna: Advisor/Consultant|Moderna: Grant/Research Support|TDCowen: Advisor/Consultant|UpToDate: Honoraria|Vedanta: Grant/Research Support Sharon E. Frey, MD, Bavarian Nordic: Grant/Research Support|Saint Louis University (SLU): Grant/Research Support
170. Intrapartum Antibiotic Exposure and Infectious Diseases in Childhood - A Population-based Cohort Study
Authors: Hakkola Mikael , Ainonen Sofia , Ronkainen Eveliina , Honkila Minna , Paalanne Marika , Pokka Tytti , Kajantie Eero , Paalanne Niko , Ruuska Terhi 
Published: January 2025

Abstract

Background
Universal maternal screening for group B streptococcus (GBS) colonization and subsequent use of intrapartum antibiotics is currently recommended practice in many high-income countries. This strategy has reduced the occurrence of early-onset GBS diseases in infants significantly. However, this practice exposes up to 30% of infants to antibiotics at birth. Intrapartum antibiotics have been shown to alter the gut microbiome composition in the offspring, which may be associated with long-term clinical outcomes. We hypothesized that maternal use of intrapartum antibiotics increases the risk of infectious diseases in the offspring.Table 1.Baseline characteristics of the study cohort

Methods
In a cohort study of 45 575 vaginally delivered newborn infants in Finland, there were 9733 children exposed to intrapartum antibiotics and 35 842 unexposed children. Intrapartum antibiotic exposure was defined as antibiotics administered to mother 24 hours or less before birth of the child. The data used in the study were retrieved from high quality national registers and electronic medical records. Primary outcome was the annual number of infectious disease episodes leading to hospitalization, emergency department visit, or other outpatient visit in specialized health care during the first five years of life.Table 2.Number of infectious disease episodes during the first five years of life.

Results
Intrapartum antibiotic exposure was associated with increased risk of any infectious disease episode at ages 7-28 days (adjusted incidence rate [aIR)] 1.32, 95% CI 1.12−1.57), 1−2 years (aIR 1.09, 95% CI 1.03−1.15), and 2−3 years (aIR 1.08, 95% CI 1.00−1.17). Intrapartum antibiotic exposure was also associated with an increased cumulative incidence of at least one infectious disease episode, increased number of urinary tract infection episodes, and increased number of antibiotic courses received. We found no association with severe infections. Intrapartum antibiotics protected offspring from severe infections caused by pathogens susceptible to penicillin beyond neonatal period.Table 3.Number of severe infection episodes, number of antibiotics courses used and number of infection related surgical operations performed during the first five years of life.,

Conclusion
Intrapartum antibiotics were associated with a long-term altered risk of infectious diseases in childhood. The observed associations appeared to depend on the causative pathogens and their susceptibility to penicillin. Previously observed changes in gut microbiome might explain the findings.Figure 1.Cumulative incidence of at least one infectious disease episode during the first five years of life.

Disclosures
All Authors: No reported disclosures
174. Implementation of Methicillin Resistant Staphylococcus Aureus (MRSA) Nasal Polymerase Chain Reaction (PCR) Swabs in Pediatric Patients
Authors: Bischoff Hannah , Hughes Heather , Addington Beth , Withers Sarah , Richardson Katherine , Faulkner-Fennell Carmen 
Published: January 2025

Abstract

Background
Current society guidelines for community-, hospital-, and ventilator-acquired pneumonia in adult patients mention use of polymerase chain reaction (PCR) nasal screening for methicillin-resistant Staphylococcus aureus (MRSA) colonization to aid de-escalation of anti-MRSA antibiotics. MRSA nasal PCR has a 96% negative predictive value when utilized for pneumonia. Most available data is in the adult population with limited application in the pediatric patient population. In a single-center retrospective analysis of 95 pediatric patients, MRSA nasal PCR showed a negative predictive value of 95.5% in multiple types of infections. The objective of this study is to expand on the limited pediatric data, encouraging the use of MRSA nasal PCR as a tool to guide de-escalation of anti-MRSA antibiotics.

Methods
This single-center, pre- and post-interventional, retrospective cohort study compared antibiotic regimens in pediatric patients who were treated empirically with anti-MRSA antibiotics and had a MRSA nasal PCR collected compared to those who did not have a MRSA nasal PCR collected. Use of MRSA nasal PCR in the pediatric hospital was encouraged following an antimicrobial stewardship provider-lead continuing education presentation. The primary outcome was duration of therapy of anti-MRSA antibiotics in days. Secondary outcomes include positive predictive values (PPV) and negative predictive values (NPV) for all infections, pneumonia, and skin and soft tissue infections.

Results
A total of 319 patients were included in the study, 252 in the pre-intervention group and 67 in the post-intervention group. The duration of anti-MRSA antibiotics in the pre-intervention group was 6.66 days compared to the post-intervention group at 2.00 days (p-value = 0.027). Using data from 38 patients with appropriate culture results for the diagnosis, negative predictive value was calculated as 92.1%. Skin and soft tissue infections and pneumonia were found to have negative predictive values of 90.1% (22 patients) and 100% (5 patients), respectively.

Conclusion
Implementation of MRSA nasal PCRs swab in pediatric patients significantly reduced the number of days patients received anti-MRSA coverage promoting their use for antimicrobial stewardship.

Disclosures
All Authors: No reported disclosures