bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of Vancomycin Dose Needed to Achieve 24-Hour Area Under the Concentration-Time Curve to Minimum Inhibitory Concentration Ratio Greater Than or Equal to 400 Using Pharmacometric Approaches in Pediatric Intensive Care Patients
Authors: Jung Dawoon , Kishk Omayma A. , Bhutta Adnan T. , Cummings Ginny E. , El Sahly Hana M. , Virk Manpreet K. , Moffett Brady S. , Morris Daniel Jennifer L. , Watanabe Amy , Fishbane Nicholas , Kotloff Karen L. , Gu Kenan , Ghazaryan Varduhi , Gobburu Jogarao V. S. , Akcan-Arikan Ayse , Campbell James D. 
Published: October 2024

OBJECTIVES:
To investigate which independent factor(s) have an impact on the pharmacokinetics of vancomycin in critically ill children, develop an equation to predict the 24-hour area under the concentration-time curve from a trough concentration, and evaluate dosing regimens likely to achieve a 24-hour area under the concentration-time curve to minimum inhibitory concentration ratio (AUC24/MIC) greater than or equal to 400.

DESIGN:
Prospective population pharmacokinetic study of vancomycin.

SETTING:
Critically ill patients in quaternary care PICUs.

PATIENTS:
Children 90 days old or older to younger than 18 years who received IV vancomycin treatment, irrespective of the indication for use, in the ICUs at the University of Maryland Children’s Hospital and Texas Children’s Hospital were enrolled.

INTERVENTIONS:
Vancomycin was prescribed at doses and intervals chosen by the treating clinicians.

MEASUREMENTS AND MAIN RESULTS:
A median of four serum levels of vancomycin per patient were collected along with other variables for up to 7 days following the first administration. These data were used to characterize vancomycin pharmacokinetics and evaluate the factors affecting the variability in achieving AUC24/MIC ratio greater than or equal to 400 in PICU patients who are not on extracorporeal therapy. A total of 302 children with a median age of 6.0 years were enrolled. A two-compartment model described the pharmacokinetics of vancomycin with the clearance of 2.76 L/hr for a typical patient weighing 20 kg. The glomerular filtration rate estimated using either the bedside Schwartz equation or the chronic kidney disease in children equation was the only statistically significant predictor of clearance among the variables evaluated, exhibiting equal predictive performance. The trough levels achieving AUC24/MIC = 400 were 5.6–10.0 μg/mL when MIC = 1 μg/mL. The target of AUC24/MIC greater than or equal to 400 was achieved in 60.4% and 36.5% with the typical dosing regimens of 15 mg/kg every 6 and 8 hours (q6h and q8h), respectively.

CONCLUSIONS:
The pharmacokinetics of vancomycin in critically ill children were dependent on the estimated glomerular filtration rate only. Trough concentrations accurately predict AUC24. Typical pediatric vancomycin dosing regimens of 15 mg/kg q6h and q8h will often lead to AUC24/MIC under 400.
Causes, Diagnostic Testing, and Treatments Related to Clinical Deterioration Events Among High-Risk Ward Patients
Authors: Churpek Matthew M. , Ingebritsen Ryan , Carey Kyle A. , Rao Saieesh A. , Murnin Emily , Qyli Tonela , Oguss Madeline K. , Picart Jamila , Penumalee Leena , Follman Benjamin D. , Nezirova Lily K. , Tully Sean T. , Benjamin Charis , Nye Christopher , Gilbert Emily R. , Shah Nirav S. , Winslow Christopher J. , Afshar Majid , Edelson Dana P. 
Published: October 2024

IMPORTANCE:
Timely intervention for clinically deteriorating ward patients requires that care teams accurately diagnose and treat their underlying medical conditions. However, the most common diagnoses leading to deterioration and the relevant therapies provided are poorly characterized.

OBJECTIVES:
We aimed to determine the diagnoses responsible for clinical deterioration, the relevant diagnostic tests ordered, and the treatments administered among high-risk ward patients using manual chart review.

DESIGN, SETTING, AND PARTICIPANTS:
This was a multicenter retrospective observational study in inpatient medical-surgical wards at four health systems from 2006 to 2020. Randomly selected patients (1000 from each health system) with clinical deterioration, defined by reaching the 95th percentile of a validated early warning score, electronic Cardiac Arrest Risk Triage, were included.

MAIN OUTCOMES AND MEASURES:
Clinical deterioration was confirmed by a trained reviewer or marked as a false alarm if no deterioration occurred for each patient. For true deterioration events, the condition causing deterioration, relevant diagnostic tests ordered, and treatments provided were collected.

RESULTS:
Of the 4000 included patients, 2484 (62%) had clinical deterioration confirmed by chart review. Sepsis was the most common cause of deterioration (41%; n = 1021), followed by arrhythmia (19%; n = 473), while liver failure had the highest in-hospital mortality (41%). The most common diagnostic tests ordered were complete blood counts (47% of events), followed by chest radiographs (42%) and cultures (40%), while the most common medication orders were antimicrobials (46%), followed by fluid boluses (34%) and antiarrhythmics (19%).

CONCLUSIONS AND RELEVANCE:
We found that sepsis was the most common cause of deterioration, while liver failure had the highest mortality. Complete blood counts and chest radiographs were the most common diagnostic tests ordered, and antimicrobials and fluid boluses were the most common medication interventions. These results provide important insights for clinical decision-making at the bedside, training of rapid response teams, and the development of institutional treatment pathways for clinical deterioration.
Perioperative immunotherapy for nonsmall cell lung cancer
Authors: Huang Jingya , Li Wenyuan , Guo Hui 
Published: October 2024

Purpose of review
Recent years have witnessed significant advancements in the treatment of lung cancer with immunotherapy, primarily centered on immune checkpoint inhibitors (ICIs). Numerous clinical studies have evaluated or are currently evaluating the clinical benefits of neoadjuvant, adjuvant, and perioperative use of ICIs. These findings have notably reshaped the landscape of perioperative treatment for nonsmall cell lung carcinoma (NSCLC).

Recent findings
Comparing different treatment modes, adding ICIs in the adjuvant phase to neoadjuvant treatment with ICIs and chemotherapy may not improve survival outcomes for patients with resectable NSCLC and may be associated with increased adverse events. For prognostic factors, ctDNA minimal residual disease (MRD) status might serve as an early predictor of achieving pathological remission. For study endpoints, a positive result with PFS as the primary endpoint may not necessarily translate into overall survival benefits.

Summary
For perioperative immunotherapy, challenges persist, including the current lack of sensitive and reliable biomarkers, the effect of neoadjuvant therapy on surgical risk as well as the selection of the appropriate study endpoint. In this review, we discuss recent and ongoing trials investigating strategies of neoadjuvant, adjuvant and perioperative immunotherapy in NSCLC, while also proposing considerations for future directions in this continuously evolving field.
Thymic malignancies: role of immunotherapy and novel approaches
Authors: Kiesewetter Barbara , Melhorn Philipp , Fuereder Thorsten 
Published: October 2024

Purpose of review
Thymic epithelial tumors (TETs) are a diverse group of malignancies that include thymomas (T), thymic carcinomas (TC), and thymic neuroendocrine tumors. Given the rarity of this disease, evidence defining the optimal treatment approach in the advanced/metastatic setting is limited. This article reviews the latest advances in systemic therapy for TETs, with a special focus on immunotherapy and targeted therapy strategies.

Recent findings
Multiple recent efforts have been made to integrate novel immunotherapies and targeted therapy approaches into the current treatment algorithm for T and TC. In addition to trials of checkpoint inhibitor monotherapy, combinatorial approaches with novel immunotherapies or targeted therapies are being explored. Molecular profiling may help identify druggable targets, further optimizing outcomes in this population.

Summary
Immune checkpoint inhibitor therapy has shown promising activity in TETs patients. However, toxicity in an unselected cohort, particularly in T patients, can be substantial, and therefore it is not recommended outside of clinical trials. Until additional research validates biomarkers to safely select patients for immunotherapy, targeted therapies remain a reasonable second-line option. Contemporary next-generation sequencing panels may be applied to identify druggable targets in the absence of standard treatment.
Risk Perceptions of Health Care Workers and Occupational Health Experts on Psychological Distress
Authors: Emal Lima M. , Tamminga Sietske J. , Beumer Annechien , Kezic Sanja , Timmermans Danielle R. , Schaafsma Frederieke G. , van der Molen Henk F. 
Published: October 2024

Background
The objectives of this study are to explore healthcare workers’ (HCWs’) mental models regarding psychological distress and to compare these with that of experts.

Methods
Semistructured interviews were conducted (n = 28 HCWs, n = 13 experts). The topic list encompassed risk perception, early stress symptoms, causes, consequences, and preventive measures of psychological distress. Interviews were transcribed verbatim and thematically analyzed using MAXQDA (VERBI Software, Berlin).

Results
Similarities were found in risk perception, symptoms, causes, and consequences. Differences arose in HCWs’ reliance on personal experiences and values versus experts’ scientific perspective. Preventive measures also showed discrepancies. Variation within HCWs was found on all aspects of their mental model.

Conclusion
For effective preventive interventions regarding psychological distress, experts should consider HCWs’ personal values and experiences, acknowledging the variation in their mental models. This approach may enhance HCWs’ engagement in preventive behaviors.
In-depth cerebrovascular lipidomics profiling for discovering novel biomarkers and mechanisms in moyamoya and intracranial atherosclerotic disease
Authors: He Kangmin , Wang Xinmei , Gu Yu , Tong Xiao , Qin Xuanfeng , Liao Yujun , Huang Li-Hao , Wang Jiaxi , Xu Bin 
Published: October 2024

Background:
Despite considerable research efforts, the precise etiology and underlying pathways contributing to moyamoya disease (MMD) remain poorly understood. Moreover, the overlapping vascular pathologies shared between MMD and intracranial atherosclerotic disease (ICAD) pose challenges in clinical differentiation, even with gold-standard cerebral angiography. An in-depth exploration of lipidomic alterations in cerebral intracranial MMD vessels could offer valuable insights into the pathogenesis of MMD-related mechanisms, encompassing MMD and ICAD, and unveil novel biomarkers and potential therapeutic targets. However, to date, comprehensive lipidomic profiling has been lacking.

Materials and methods:
To discover novel biomarkers and unravel the pathophysiological mechanisms underlying MMD, we conducted a lipidomics analysis to characterize various lipid species in matched human extracranial and intracranial artery tissues from patients diagnosed with MMD (n=99) and ICAD (n=12).

Results:
Our analysis identified 569 lipid species and delineated a robust panel of lipidomic biomarkers capable of effectively distinguishing MMD from ICAD (area under curve=0.98), as determined by receiver operating characteristic curve analysis. Notably, we observed a significantly more pronounced positive correlation of diacylglycerols and a negative association of triglycerides in intracranial artery tissues of MMD patients compared to those with ICAD, suggesting a potential role of dysregulated diacylglycerol-induced signaling in MMD pathogenesis. Furthermore, our investigation into the correlations of critical differential intracranial artery vessel lipid species between MMD and ICAD and clinical parameters revealed negative associations with plasma iron levels, implying a potential link between plasma iron metabolism and artery lipid homeostasis during MMD pathogenesis.

Conclusion:
These findings offer promising prospects for advancing clinical diagnosis for enhanced differentiation between the two disease conditions. Additionally, they shed light on the fundamental mechanisms implicated in MMD pathogenesis and suggest potential therapeutic avenues through targeting artery vessel lipids or plasma iron levels.
RRFERV stabilizes TEAD1 expression to mediate nasopharyngeal cancer radiation resistance rendering tumor cells vulnerable to ferroptosis
Authors: Xu Qingqing , Wen Xin , Huang Chenglong , Lin Zaishan , Xu Zhen , Sun Ciming , Li Li , Zhang Suixian , Song Shuanghong , Lou Jiahao , Hou Zan , Chen Yuanyuan , Li Xuan , Chen Lei 
Published: October 2024

Background:
Long noncoding RNAs (lncRNAs) regulate various essential biological processes, including cell proliferation, differentiation, apoptosis, migration, and invasion. However, in nasopharyngeal carcinoma (NPC), the clinical significance and mechanisms of lncRNAs in malignant progression are unknown.

Methods:
RNA sequencing and bioinformatic analysis were used to determine the potential function of RRFERV (radiation-resistant but ferroptosis-vulnerable), and its biological effects were investigated using in vitro and in vivo experiments. Western blotting, quantitative real-time reverse transcription PCR, RNA immunoprecipitation (RIP) assays, and flow cytometry detected RRFERV expression. Ferroptosis and lipid peroxidation were added to evaluate the relationship between it and radiotherapy resistance.

Results:
LncRNA–RRFERV was both highly expressed in NPC tissues and radiation-resistant cells. RRFERV is associated with poor clinical outcomes of NPC patients and stabilizes TEAD1 by competitive binding with microRNA-615-5p and microRNA-1293. RRFERV–TEAD1 signaling axis leads to malignant progression and radiotherapy resistance of NPC. Furthermore, we observed that NPC radiotherapy-resistance cells exist in a fragile oxidative stress equilibrium, which makes them more sensitive to ferroptosis inducers. Surprisingly, we found that RRFERV–TEAD1 signaling axis also plays a key role in mediating the lipid peroxidation levels of NPC radiotherapy-resistance cells through transcriptional activation of ACSL4/TFRC.

Conclusions:
RRFERV serves as an independent prognostic factor in NPC. During the malignant progression of NPC caused by high expression of RRFERV, ferroptosis can be induced to effectively kill cancer cells and reverse the radiotherapy resistance of NPC cells, suggesting a potential treatment approach for recurrent and refractory NPC.
Analysis of Burnout and Self-Efficacy of Teachers of Physical Education During Online Learning
Authors: Ran Xu 
Published: October 2024

Abstract
The research is based on interpretive phenomenological analysis and the interview method. The sample involved 100 secondary school students from five to nine grades and eight physical education teachers. All participants studied the proposed physical education program in-person for one academic semester, as well as studied the program online for one academic semester. It was found that online learning was viewed unfavorably by 87% of teachers. However, 65% of participants admitted that learning opportunities were limited, and they experienced difficulties with appropriate lesson content, equipment, and space to foster a positive learning environment and a productive working context. In addition, marginalization occurred as parents and students paid more attention to other subject areas except for physical education. The research suggested that the majority of teachers (89%) were looking forward to full-time and face-to-face physical education training because they lacked personal relationships and interaction with their students.
Nurse-led self-management support to improve symptom management and self-reported outcomes in people with irritable bowel syndrome
Authors: Barandouzi Zahra A. , Chen Jie , Henderson Wendy A. , Starkweather Angela R. , Cong Xiaomei S. 
Published: October 2024

Abstract

Objectives:
Irritable bowel syndrome (IBS) is a disorder of gut-brain interaction with an unknown precise etiology. Intricate mechanisms underlying the disruption of bidirectional communication between the brain and the gut may influence the severity of symptoms as well as the response to self-management interventions. Management of IBS can be particularly challenging due to recurrent and resistant symptoms to therapeutic approaches. The present study aimed to evaluate the role of nurse-led self-management support on symptom management and self-reported outcomes in people with IBS.

Methods:
In the current study, which was part of a parent randomized controlled trial, participants with IBS received one-on-one self-management intervention either by phone or in-person by Registered Nurses (RNs) in 3 sessions over 12 weeks. Each intervention was between 15 and 30 minutes. During the first intervention, the RN asked open-ended questions on symptom episodes, stress, physical activity, Quality of Life (QOL), and diet to provide recommendations for improved self-management. At the second and the third nurse-led self-management sessions, the RN helped in problem-identification and solving throughout the intervention. Quantitative content analysis was performed using the coding system developed by 2 authors for analyzing the participants’ responses.

Results:
In total, 24 participants with IBS completed the 3 nurse-led self-management sessions. Participants’ mean age was 21.37 (±2.55) years old, and 83.33% were female. At the first nurse-led self-management session, 79% of participants reported pain, 62.5% reported bloating, 50% reported diarrhea, 37.5% reported constipation, 100% reported stress, and 95.6% had physical activity as part of their routines, while only 33.3% of the participants reported having a “high” QOL. After 3 nurse-led self-management sessions, participants reported improved IBS symptoms in pain 73%, bloating 73.7%, diarrhea 76.8%, constipation 50%, stress 42.1%, and physical activity 45%, as well as 66.7% of the participants experienced a “high” QOL. Dairy, fast/processed foods, and high-fat foods were the most frequent triggers of the symptoms, with a frequency of 40%, 24.5%, and 12%, respectively. After receiving nurse-led support, 69.20% of the participants reported improved dietary habits.

Conclusions:
Nurse-led self-management can support participants to manage various IBS symptoms and improve their QOL. The unique strength of this study was evaluating participant needs and offering individualized solutions. A further study utilizing novel nurse-led self-management approaches may provide a valuable platform for empowering IBS patients’ self-management.
Self-management of multimorbidity in sub-Saharan Africa: a systematic review and meta-synthesis with focus on diabetes, hypertension, chronic kidney disease and HIV infection
Authors: Salimu Sangwani Nkhana , Taylor Melissa , Spencer Stephen A , Nyirenda Deborah , Desmond Nicola , Morton Ben 
Published: October 2024

AbstractBackgroundThe increasing prevalence of multimorbidity in sub-Saharan Africa (SSA) is an urgent concern for health systems delivery. It is uncertain how best to promote self-management approaches or the actions that patients and carers take to maintain physical and mental health, in this context. This review aims to identify, critically appraise, and synthesize qualitative evidence that describes self-management of multimorbidity among patients and their carers in SSA.MethodsWe systematically searched PubMed, MEDLINE, CINAHL Global Health, Google Scholar and grey literature for studies on self-management of multimorbidity or common individual chronic diseases (HIV, diabetes, hypertension or chronic kidney disease) in SSA published between 1 January 2000 and 28 to 15thSeptember 2024. Using qualitative meta-synthesis techniques to formulate the questions and synthesize findings. We used a 10-point Critical Appraisal Skills Program (CASP)-Qualitative-Checklist to assess the quality of the studies and NVivo 12 software to facilitate a thematic analysis approach.ResultsWe screened 2010 articles for inclusion and 20 studies met inclusion criteria. We identified themes related to medical, diet, emotional and physical self-management activities. Patients negotiate self-management based on immediacy of needs and available family support. Patients are motivated to apply biomedical management but are limited by factors such as drug stock-outs and out-of-pocket expenditure. Limited knowledge and low self-efficacy toward self-management of multimorbidity impact decision making and problem solving. We found that diabetes mellitus presents the biggest stressor in terms of burden of treatment; temporal discontinuation of medications is more prevalent amongst patients with hypertension; and patients with multimorbidity are frequently hypervigilant about their health, more likely to suffer from stress and to seek healthcare.ConclusionsWe found that there is relative lack of data on self-management of multimorbidity among patients and their carers in SSA. Where data exists, we observed significant health literacy gaps, low health literacy support and limited self-efficacy as barriers to implementation of self-management. Context sensitive programmes are required to improve health literacy to increase patient autonomy and their toolkit of options to manage chronic disease.
Inversed association of locus coeruleus MRI integrity with structural volume and its impact on individual’s inattentiveness
Authors: Neal Joshua , Kim Sun Hyung , Katz Benjamin , Kim Il Hwan , Lee Tae-Ho 
Published: October 2024

AbstractThe locus coeruleus (LC) is a nucleus within the brainstem associated with physiological arousal and altered structure and function in the context of neurodegenerative disorders. Pathologies related to difficulties with attention have previously been associated with abnormalities in neurotransmitter production and sensitivity, suggesting the possibility of abnormality in neurotransmitter producing neural regions. One such region is the LC, associated with norepinephrine production. To examine the possibility that LC alteration is associated with inattentive symptom reporting, a set of analyses have been performed with 141 individuals age-ranged from 8 to 54. We found that the structural integrity value of the LC, especially on the right hemisphere, showed a significant negative association with the level of individual’s inattentiveness score. Furthermore, LC volume size was significantly positively associated with inattention, and this finding was also lateralized to the right LC. Interestingly, an inverse association was found between structural integrity and volume size. These findings support the relationship between LC and attention-related behavior through both neuromelanin-sensitive and structural imaging, with important implications for the association between regional structure and function.