bluuebunny/crossref_metadata_2025_split huggingface dataset:
Therapeutic drug monitoring of linezolid in Chinese premature neonates: a population pharmacokinetic analysis and dosage optimization
Authors: Duan Lu-fen , Li Jing-jing , Shen Li-rong , Chen Xiang-long , Yu Yan-xia , Yang Zu-ming , Zhang Qian , Cai Yan , Li Jia-hui , Wu Juan , Zhao Han-zhen , Xu Jin-hui , Feng Zong-tai , Tang Lian 
Published: October 2024

ABSTRACT

This study aimed to develop a pharmacokinetic model of linezolid in premature neonates and evaluate and optimize the administration regimen. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to detect the blood concentration data of 54 premature neonates after intravenous administration of linezolid, and the relevant clinical data were collected. The population pharmacokinetic (PPK) model was established by nonlinear mixed effects modeling. Based on the final model parameters, the optimal administration regimen of linezolid in premature neonates with different body surface areas (BSA) was simulated and evaluated. The pharmacokinetic properties of linezolid in premature neonates are best described by a single-compartment model with primary elimination. The population typical values for apparent volume of distribution and clearance were 0.783 L and 0.154 L/h, respectively. BSA was a statistically significant covariate with clearance (CL) and volume of distribution (V
d
). Monte Carlo simulations showed that the optimal administration regimen for linezolid in premature neonates was 6 mg/kg q8h for BSA 0.11 m
2
, 7 mg/kg q8h for BSA 0.13 m
2
, and 9 mg/kg q8h for BSA 0.15 m
2
with minimum inhibitory concentration (MIC) ≤1 mg/L, 7 mg/kg q8h for BSA 0.11 m
2
, 8 mg/kg q8h for BSA 0.13 m
2
, and 10 mg/kg q8h for BSA 0.15 m
2
with MIC = 2 mg/L. A pharmacokinetic model was developed to predict the blood concentration on linezolid in premature neonates. Based on this model, the optimal administration regimen of linezolid in premature neonates needs to be individualized according to different BSA levels.
Clinical performance evaluation of the BioFire Joint Infection Panel
Authors: Lee Rose A. 
Published: October 2024

ABSTRACT

The BioFire Joint Infection (JI) Panel offers a significant advancement in the rapid diagnosis of joint infections by facilitating the simultaneous detection of multiple bacterial and fungal pathogens, as well as resistance markers, directly from synovial fluid samples. An article published in the
Journal of Clinical Microbiology
by Moran et al. (J Clin Microbiol 62:e00182-24, 2024,
https://doi.org/10.1128/jcm.00182-24
) presents both prospective and retrospective analyses of the panel’s real-world clinical application. The study highlights the panel’s benefits, such as its rapid turnaround time and ability to identify challenging pathogens, while also discussing its limitations, particularly in detecting certain off-panel organisms.
Retinoic acid-induced differentiation and oxidative stress inhibitors increase resistance of human neuroblastoma cells to La Crosse virus-induced cell death
Authors: Policastro Paul F. , Schneider Christine A. , Winkler Clayton W. , Leung Jacqueline M. , Peterson Karin E. 
Published: October 2024

ABSTRACT

La Crosse Virus (LACV) encephalitis patients are at risk for long-term deficits in cognitive function due to neuronal apoptosis following virus infection. However, the specific etiology underlying neuronal damage remains elusive. In this study, we examined how differentiation and mitotic inhibition of neuroblastoma cells influence their susceptibility to LACV infection and cell death. Treatment of SH-SY5Y cells with retinoic acid induced a neuronal cell phenotype which was similarly susceptible to LACV infection as untreated cells but had significantly delayed virus-induced cell death. Protein and RNA transcript analysis showed that retinoic acid-treated cells had decreased oxidative stress responses to LACV infection compared to untreated cells. Modulation of oxidative stress in untreated cells with specific compounds also delayed cell death, without substantially impacting virus production. Thus, the oxidative stress response of neurons to virus infection may be a key component of neuronal susceptibility to virus-induced cell death.

IMPORTANCE
Encephalitic viruses like La Crosse Virus (LACV) infect and kill neurons. Disease onset and progression is rapid meaning the time frame to treat patients before significant and long-lasting damage occurs is limited. Examining how neurons, the primary cells infected by LACV in the brain, resist virus-induced cell death can provide avenues for determining which pathways to target for effective treatments. In the current study, we studied how changing neuroblastoma growth and metabolism with retinoic acid treatment impacted their susceptibility to LACV-induced cell death. We utilized this information to test compounds for preventing death in these cells.
The multifaceted roles of phosphoethanolamine-modified lipopolysaccharides: from stress response and virulence to cationic antimicrobial resistance
Authors: Schumann Anna , Gaballa Ahmed , Wiedmann Martin 
Published: October 2024

SUMMARY

Lipopolysaccharides (LPS) are an integral part of the outer membrane of Gram-negative bacteria and play essential structural and functional roles in maintaining membrane integrity as well as in stress response and virulence. LPS comprises a membrane-anchored lipid A group, a sugar-based core region, and an O-antigen formed by repeating oligosaccharide units. 3-Deoxy-D-
manno
-octulosonic acid-lipid A (Kdo
2
-lipid A) is the minimum LPS component required for bacterial survival. While LPS modifications are not essential, they play multifaceted roles in stress response and host-pathogen interactions. Gram-negative bacteria encode several distinct LPS-modifying phosphoethanolamine transferases (PET) that add phosphoethanolamine (pEtN) to lipid A or the core region of LPS. The
pet
genes differ in their genomic locations, regulation mechanisms, and modification targets of the encoded enzyme, consistent with their various roles in different growth niches and under varied stress conditions. The discovery of mobile colistin resistance genes, which represent lipid A-modifying
pet
genes that are encoded on mobile elements and associated with resistance to the last-resort antibiotic colistin, has led to substantial interest in PETs and pEtN-modified LPS over the last decade. Here, we will review the current knowledge of the functional diversity of pEtN-based LPS modifications, including possible roles in niche-specific fitness advantages and resistance to host-produced antimicrobial peptides, and discuss how the genetic and structural diversities of PETs may impact their function. An improved understanding of the PET group will further enhance our comprehension of the stress response and virulence of Gram-negative bacteria and help contextualize host-pathogen interactions.
Correlation of patient symptoms with SARS-CoV-2 Omicron variant viral loads in nasopharyngeal and saliva samples and their influence on the performance of rapid antigen testing
Authors: Shiraishi Kenichiro , Chong Yong , Goto Takeyuki , Ishimaru Toshiyuki , Shimono Nobuyuki , Ikematsu Hideyuki , Akashi Koichi 
Published: October 2024

ABSTRACT

Evaluating SARS-CoV-2 viral loads in nasopharyngeal (NP) and saliva samples, factors affecting viral loads, and the performance of rapid antigen testing (RAT) have not been comprehensively conducted during SARS-CoV-2 Omicron epidemic. This prospective study included outpatients enrolled during Omicron variant period in Japan. Paired NP swab and saliva samples were collected to measure viral loads by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The correlation between viral loads and clinical symptoms was examined. The performance of an immunochromatography-based RAT kit was also assessed. A total of 153 patients tested within 3 days of symptom onset were included. The mean viral load was 5.60 log
10
copies/test and 3.65 log
10
copies/test in NP and saliva samples, respectively, resulting in a significant difference (
P
< 0.0001). Fever over 37°C (axillary temperature) and total number of symptoms other than fever were identified as independent factors positively correlated with the viral loads in both NP and saliva samples. RAT sensitivity using NP and saliva samples was 92% and 68%, respectively, using positive RT-qPCR results as the reference. The sensitivity of RAT using NP and saliva samples was significantly higher in patients with fever ≥37°C and/or at least one symptom than in those with fever <37°C and/or no symptoms (97% vs 83% in NP swabs; 80% vs 50% in saliva). Distinct symptoms, including fever ≥37°C, may reflect high Omicron variant viral loads. Rapid antigen testing, not only using nasopharyngeal swabs but also using saliva, would be useful for COVID-19 diagnosis as point-of-care testing, particularly for symptomatic patients.

IMPORTANCE
We examined nasopharyngeal and salivary viral loads using samples collected from outpatients with SARS-CoV-2 infection during the Omicron epidemic in Japan and explored the outpatient factors correlated with viral loads. In addition, we evaluated the performance of an authorized rapid antigen testing (RAT) kit using nasopharyngeal and saliva samples with RT-PCR testing as the reference. Intriguingly, a correlation between fever and other symptoms and SARS-CoV-2 viral loads in nasopharyngeal and saliva samples was observed based on one COVID-19 outpatient visit. RAT sensitivity was influenced by viral loads. Nevertheless, nasopharyngeal RAT is considered useful for SARS-CoV-2 point-of-care diagnosis. In patients with distinct symptoms, including high-grade fever, salivary RAT could be a practical diagnostic tool because of the higher estimated viral loads. After the Omicron epidemic, outpatients with mild COVID-19 have become the main focus of diagnosis and treatment. Our study provides valuable information regarding the point-of-care diagnosis of these patients.
Comparison of a hepatitis C core antigen assay to nucleic acid amplification testing for detection of hepatitis C viremia in a US population
Authors: Gunsolus Ian L. , Prostko John , Pearce Sandra , Degaga Biniam , Eickstead Scott , Taylor Russ , Grieshaber Jessica , Richard Kyle , Hoffman Anne , Pekalska Aneta , Daghfal David 
Published: October 2024

ABSTRACT

The prevalence of hepatitis C virus (HCV) infection in the United States has increased over the past decade despite the development of effective direct-acting antiviral treatments. To meet the World Health Organization’s (WHO) goal of eliminating HCV infection by 2030, transmission events must be reduced. Currently, infection screening relies on detection of HCV antibodies, with nucleic acid amplification testing (NAAT) used to confirm HCV viremia and monitor changes in viral load. However, the seroconversion window for detection of HCV antibodies is long, averaging 6 weeks, with delayed seroconversion common in co-infected and immunosuppressed populations. Testing for HCV core antigen, which is present approximately 5 weeks before HCV antibodies, holds promise for earlier detection of HCV infection. It may also hold promise as a cheaper, more accessible, and more rapid alternative to NAAT for infection confirmation. Here, we evaluated the agreement between a research-use HCV Core Antigen Assay and NAAT among US patients receiving clinically indicated NAAT. Among 412 specimens, the overall concordance was 97.1%, with a positive percent agreement of 95.5%. Discrepancies primarily occurred among patients with chronic HCV and low viral loads; 11/12 discrepancies showed viral loads <4,000 IU/mL. Among patients being screened for HCV infection (i.e., excluding those undergoing NAAT for serial monitoring of a previously diagnosed infection), the positive percent agreement was 97.0%. Among patients undergoing serial testing, changes in HCV Core Antigen Assay signal-to-cut-off values were generally correlated with changes in the viral load. Results suggest that the research-use HCV Core Antigen Assay studied here may reliably detect and/or confirm HCV infection.

IMPORTANCE
A research-use HCV Core Antigen Assay showed high concordance with nucleic acid amplification testing for the detection of current hepatitis C infection. The assay may enable more rapid and lower-cost detection and/or confirmation of hepatitis C infection.
Exploring the causes of variability in quality of oropharyngeal swab sampling for SARS-CoV-2 nucleic acid testing and proposed improvement measures: a multicenter, double-blind study
Authors: Zhu Jie , Xing Fanfan , Li Yunzhu , Wu Chunchen , Li Shasha , Wang Qin , Huang Jinyue , Zhang Yafei , Zheng Xiaowei , Liu Zhenjun , Rao Jianguo , Hong Rui , Tian Shuilin , Xiong Shuangyun , Tan Lin , Chen Xinlei , Li Yanwu , He Wei , Hong Xiaodan , Xia Jianbo , Zhou Qiang , Zhang Zhenhua 
Published: October 2024

ABSTRACT

Although coronavirus disease 2019 (COVID-19) has not been considered a public health emergency of international concern since last year, intermittent regional impacts still persist, and accurate testing remains crucial. Ribonuclease
P
protein subunit P30 (
RPP30
) RNA, known for its broad and stable expression in tissue cells, was used to evaluate samples from 10 hospitals with over 3,000 negative nucleic acid tests. The results revealed that the overall pass rate for the collected samples was consistently low and exhibited significant heterogeneity. After reassessing the evaluative effectiveness of
RPP30
RNA Ct values from the samples of 132 positive individuals under quarantine observation, it was used to identify factors affecting sampling quality. These factors included different stages ranging from sample collection to PCR processing, various characteristics of both samplers and individuals being sampled, as well as sampling season and location. The results indicated that post-sampling handling had minimal impact, winter and fever clinic samples showed higher quality, whereas children’s samples had lower quality. The key finding was that the characteristics of samplers were closely related to sampling quality, emphasizing the role of subjectivity. Quality control warnings led to substantial improvements, confirming this finding. Consequently, although there are various factors during the testing process, the most critical aspect is to improve, supervise, and maintain standardized practices among sampling staff.

IMPORTANCE

This study further confirmed the reliability of internal references (IRs) in assessing sample quality, and utilized a large sample IR data to comprehensively and multidimensionally identify significant interference factors in nucleic acid test results. By further reminding and intervening in the subjective practices of specimen collectors, good results could be achieved.
Costs and resource distribution of direct services for HIV in Uganda
Authors: Ekirapa Elizabeth , Jordan Monica , Nong Thuong , Marton Tozoe Elaine , Balidawa Hudson , Ssempala Richard , Ssebagereka Anthony , Kagaayi Joseph , Nandakumar Allyala , McBain Ryan K 
Published: October 2024

ObjectiveIn high HIV-burden countries like Uganda, financing and resource allocation for HIV services have rapidly evolved. This study aimed to employ time-driven activity-based costing (TDABC) to examine the allocation of resources and associated costs for HIV care throughout the country.DesignA cross-sectional study.SettingThis study was conducted at 31 health facilities throughout Uganda: 16 level III health centres, 10 level IV health centres and 5 district hospitals.Participants1119 persons receiving HIV services in 2020.MethodsWe conducted TDABC to quantify costs, resource consumption and duration of service provision associated with antiretroviral therapy, prevention of mother-to-child transmission, HIV counselling and testing (HCT), voluntary medical male circumcision (VMMC) and pre-exposure prophylaxis. We also quantified disparities in resource consumption according to client-level and facility-level characteristics to examine equity. Fixed-effects multivariable regression analyses were employed to inspect factors associated with service costs and provider-client interaction time.ResultsThe mean cost of services ranged from US$8.18 per visit for HCT to US$32.28 for VMMC. In terms of disparities, those in the Western region received more provider time during visits compared with other regions (35 more minutes, p<0.001); and those receiving care at private facilities received more provider time compared with public facilities (13 more minutes, p=0.02); and those at level IV health centres received more time compared with those at level III (12 more minutes, p=0.01). Absent consumables, services for older adults (US$2.28 higher, p=0.02), those with comorbidities (US$1.44 higher, p<0.001) and those living in the Western region (US$2.88 higher, p<0.001) were more expensive compared with younger adults, those without comorbidities and those in other regions, respectively. Inclusive of consumables, services were higher-cost for individuals in wealthier households (US$0.83 higher, p=0.03) and those visiting level IV health centres (US$3.41 higher, p=0.006) compared with level III.ConclusionsCosts and resources for HIV care vary widely throughout Uganda. This variation requires careful consideration: some sources of variation may be indicative of vertical and horizontal equity within the health system, while others may be suggestive of inequities.
ECO-MIND: enhancing pro-environmental behaviours and mental health through nature contact for urban youth – a research protocol for a multi-country study using geographic ecological momentary assessment and mental models
Authors: Bubalo Martina , van den Broek Karlijn , Helbich Marco , Labib S M 
Published: October 2024

IntroductionUrban youth are experiencing increasing mental health problems due to diverse personal, social and environmental concerns. Youths’ detachment from natural environments, including green and blue spaces, may intensify such issues further. Contact with nature can benefit mental health and promote pro-environmental behaviour (PEB). Yet, only a few studies assess these relationships among the youth usually ignoring effects of living in diverse urban contexts, and everyday nature experiences. ECO-MIND will investigate whether urban youth’s dynamic greenspace exposure and their mental models about nature connectedness explain the associations between greenspace exposure, mental health and PEB in multiple urban contexts.Methods and analysisWe will collect data from university students from the Global South (ie, Dhaka, Kampala) and Global North cities (ie, Utrecht). Participants aged 18–24 will be recruited through stratified random sampling. We will use geographic ecological momentary assessment to assess respondents’ everyday experiences and exposure to greenspaces. Our definition of greenspace exposure will be based on the availability, accessibility and visibility of greenspaces extracted from satellite and street view images. We will administer a baseline questionnaire to participants about mental health, nature connectedness and PEB characteristics. Further, we will ask participants to build mental models to show their perception of nature connectedness. Finally, we will fit partial least square structural equation models and multi-level models to our longitudinal geographic momentary assessment data.Ethics and disseminationThe study was approved by the Ethical Review Board of the Utrecht University (Geo S-23221). Informed consent must be given freely, without coercion and based on a clear understanding of the participation in the study. Findings will be disseminated in peer-reviewed journals and at conferences. Furthermore, we will implement public engagement activities (eg, panel discussion) to share results among local stakeholders and policymakers and cocreate policy briefs.
Deep brain stimulation versus vagus nerve stimulation for the motor function of poststroke hemiplegia: study protocol for a multicentre randomised controlled trial
Authors: Xu Junpeng , Liu Bin , Shang Guosong , Liu Shuzhen , Feng Zhebin , Zhang Yanyang , Yang Haonan , Liu Di , Chang Qing , Yuhan Chen , Yu Xinguang , Mao Zhiqi 
Published: October 2024

IntroductionDeep brain stimulation (DBS) and vagus nerve stimulation (VNS) can improve motor function in patients with poststroke hemiplegia. No comparison study exists.Methods and analysisThis is a randomised, double-blind, controlled clinical trial involving 64 patients who had their first stroke at least 6 months ago and are experiencing poststroke limb dysfunction. These patients must receive necessary support at home and consent to participate. The aim is to evaluate the effectiveness and safety of DBS and VNS therapies. Patients are excluded if they have implantable devices that are sensitive to electrical currents, severe abnormalities in their lower limbs or are unable to comply with the trial procedures. The study has two parallel, distinct treatment arms: the Stimulation Group and the Sham Group. Initially, the Stimulation Group will undergo immediate electrical stimulation postsurgery, while the Sham Group will receive non-stimulation 1 month later. After 3 months, these groups will swap treatments, with the Stimulation Group discontinuing stimulation and the Sham Group initiating stimulation. Six months later, both groups will resume active stimulation. Our primary outcomes will meticulously assess motor function improvements, using the Fugl-Meyer Assessment, and safety, monitored by tracking adverse reaction rates. Furthermore, we will gain a comprehensive view of patient outcomes by evaluating secondary measures, including clinical improvement (National Institutes of Health Stroke Scale), surgical complications/side effects, quality of life (36-item Short Form Questionnaire) and mental health status (Hamilton Anxiety Rating Scale/Hamilton Depression Rating Scale). To ensure a thorough understanding of the long-term effects, we will conduct follow-ups at 9 and 12 months postsurgery, with additional long-term assessments at 15 and 18 months. These follow-ups will assess the sustained performance and durability of the treatment effects. The statistical analysis will uncover the optimal treatment strategy for poststroke hemiplegia, providing valuable insights for clinicians and patients alike.Ethics and disseminationThis study was reviewed and approved by the Ethical Committee of Chinese PLA General Hospital (S2022-789-01). The findings will be submitted for publication in peer-reviewed journals with online accessibility, ensuring adherence to the conventional scientific publishing process while clarifying how the research outcomes will be disseminated and accessed.Trial registration numberNCT06121947.