bluuebunny/crossref_metadata_2025_split huggingface dataset:
Supporting siblings during the critical illness hospitalization of a child: learning from experience
Authors: Dryden-Palmer Karen , Shinewald Alexis , O'Leary Kimberly 
Published: August 2024

IntroductionChildhood critical illness impacts the entire family of the critically ill patient. Disruptions to usual family rhythms and routines, established relationships, physical relocations or shifts in caregivers, and the uncertainty about the patient's well-being can have significant impacts on siblings and other connected children in the family. Promoting and facilitating family interactions and engaging younger family members in the hospital experience have been shown to reduce patient and family anxiety, enhance family adaptation, and improve child and family outcomes. The critical care team can implement evidence-informed approaches to address and mitigate challenges for families and provide developmentally aligned support to impacted siblings.AimThis conceptual paper describes the potential impacts of a critical illness hospitalization on siblings, approaches to supporting siblings, and practical interventions drawn from a synthesis of the current literature and the author's practice experience caring for critically ill children and their families.Data sourcesA traditional review and narrative analysis moderated by the authors and supported by lived experience.ConclusionsThere is a range of impacts of a critical illness hospitalization on siblings and young family members of the patient. Providing consistent, transparent, and supportive child, sibling, and whole family-centered care can improve the experience and outcomes for the child and family.
Preclinical pharmacokinetic studies and prediction of human PK profiles for Deg-AZM, a clinical-stage new transgelin agonist
Authors: Gu Xiaoting , Li Xiaohe , Tian Weixue , Zheng Chaoyue , Cai Yutian , Xu Xiang , Zhao Conglu , Liu Hongting , Sun Yao , Luo Zhilin , Zhu Shuwen , zhou Honggang , Ai Xiaoyu , Yang Cheng 
Published: August 2024

IntroductionDeglycosylated azithromycin (Deg-AZM), a newly developed Class I drug with good therapeutic effects on slow transit constipation, is a small-molecule transgelin agonist that has been approved for clinical trials in 2024. The preclinical pharmacokinetic profile of Deg-AZM was investigated to support further development.MethodsA LC-MS/MS method was established and validated to detected the concentration of Deg-AZM in various biological samples. In vivo tests such as pharmacokinetic studies in rats and dogs, tissue distribution studies in rats, and extraction studies in rats were conducted to investigated the preclinical pharmacokinetic behaviors of Deg-AZM comprehensively. The plasma protein rate of Deg-AZM was determined by rapid equilibrium dialysis method in vitro. The metabolic stability and metabolite profile of Deg-AZM was assessed using pooled mice, rats, dogs, monkeys and humans microsomes in vitro. The PK profiles of Deg-AZM in human was predicted based on physiologically based pharmacokinetic (PBPK) models.ResultsThe plasma protein binding rates of Deg-AZM were lower in mice and rats, higher in dogs, and moderate in humans. The metabolic process of Deg-AZM was similar in rat and human liver microsomes. From Pharmacokinetic studies in rats and dogs, Deg-AZM was rapidly absorbed into the blood and then quickly eliminated. Plasma exposure of Deg-AZM was dose dependent with no accumulation after continuous gavage administration. In addition, there is no significant gender difference in the pharmacokinetic behavior of Deg-AZM. Deg-AZM was widely distributed in the tissues without obvious accumulation, and mainly excreted from the urinary excretion pathway. Furthermore, the pharmacokinetic profiles of Deg-AZM in humans showed dose dependency.ConclusionThe pharmacokinetic profiles of Deg-AZM was fully explored, these results could provide valuable information to support the first-in-human dosage prediction and phase I clinical design.
In vitro mechanistic study on mycophenolate mofetil drug interactions: effect of prednisone, cyclosporine, and others
Authors: Mao Junjun , Yu Feifei , Qin Weiwei , She Guixian , Rong Yi , Hu Zhuohan , Zhong Mingkang 
Published: August 2024

ObjectiveThe metabolism- and transporter-based drug-drug interactions (DDIs) between mycophenolate mofetil (MMF) and co-administered medications may be key factors for the high individual variability in MMF exposure. This study systematically assessed the influence of co-medications on the mycophenolic acid (MPA) pharmacokinetic (PK) process in vitro, particularly to provide mechanistic evidence of the metabolic interaction among steroids, cyclosporine (CsA), and MMF.MethodsBased on a previous study, we hypothesized that there are three main DDI pathways affecting MMF PK in vivo. A human hepatocyte induction study, transporter substrate/inhibition study using human embryonic kidney 293 cells, and multidrug resistance-associated protein 2 (MRP2) substrate/inhibition study using vesicle membrane were conducted to assess the mechanistic evidence of the metabolic interaction in triple therapies. The potential DDI risks associated with seven medications commonly co-administered with MMF in clinical practice were further evaluated.ResultsThe in vitro results suggested that prednisolone, the active metabolite of prednisone, induces the enzymatic activity of uridine 5′-diphospho-glucuronosyltransferase (UGT), particularly the UGT1A9 and UGT2B7 isoforms, resulting in increased metabolism of MPA to MPA glucuronide (MPAG). This induction potential was not observed in CsA-treated human hepatocytes. CsA inhibits organic anion-transporting polypeptide (OATP) 1B1- and OATP1B3-mediated MPAG. Prednisolone and CsA showed no inhibitory effect on MRP2-mediated MPAG efflux. Salvia miltiorrhiza significantly inhibited organic anion-transporting polypeptide and OAT 3 activities, suggesting that it affects the hepatic uptake and renal excretion of MPAG, causing increased MPAG exposure in vivo.ConclusionThese identified factors may contribute to the high inter-individual variability in MMF exposure and facilitate further development of mechanistic MMF PK models and individualized therapies.
The deuterated pyrazoloquinolinone targeting α6 subunit-containing GABAA receptor as novel candidate for inhibition of trigeminovascular system activation: implication for migraine therapy
Authors: Fan Pi-Chuan , Chiou Lih-Chu , Lai Tzu-Hsuan , Sharmin Dishary , Cook James , Lee Ming Tatt 
Published: August 2024

IntroductionThe α6 subunit-containing GABAA receptors (α6GABAARs) are highly expressed in the trigeminal ganglia (TG), the sensory hub of the trigeminovascular system (TGVS). Hypo-GABAergic transmission in the TG was reported to contribute to migraine-related behavioral and histopathological phenotypes. Previously, we found that Compound 6, an α6GABAAR-selective positive allosteric modulator (PAM), significantly alleviated TGVS activation-induced peripheral and central sensitization in a capsaicin-induced migraine-mimicking model.MethodsHere, we tested whether the deuterated analogues of Compound 6, namely DK-1-56-1 and RV-I-29, known to have longer half-lives than the parent compound, can exert a similar therapeutic effect in the same model. The activation of TGVS was triggered by intra-cisternal (i.c.) instillation of capsaicin in male Wistar rats. Centrally, i.c. capsaicin increased the quantity of c-Fos-immunoreactive (c-Fos-ir) neurons in the trigeminal cervical complex (TCC). Peripherally, it increased the calcitonin gene-related peptide immunoreactivity (CGRP-ir) in TG, and caused CGRP release, leading to CGRP depletion in the dura mater.ResultsDK-I-56-1 and RV-I-29, administered intraperitoneally (i.p.), significantly ameliorated the TCC neuronal activation, TG CGRP-ir elevation, and dural CGRP depletion induced by capsaicin, with DK-I-56-1 demonstrating better efficacy. The therapeutic effects of 3 mg/kg DK-I-56-1 are comparable to that of 30 mg/kg topiramate. Notably, i.p. administered furosemide, a blood-brain-barrier impermeable α6GABAAR-selective antagonist, prevented the effects of DK-I-56-1 and RV-I-29. Lastly, orally administered DK-I-56-1 has a similar pharmacological effect.DiscussionThese results suggest that DK-I-56-1 is a promising candidate for novel migraine pharmacotherapy, through positively modulating TG α6GABAARs to inhibit TGVS activation, with relatively favourable pharmacokinetic properties.
The effects of a 12-week combined motor control exercise and isolated lumbar extension intervention on lumbar multifidus muscle stiffness in individuals with chronic low back pain
Authors: Tornblom Audrey , Naghdi Neda , Rye Meaghan , Montpetit Chanelle , Fortin Maryse 
Published: August 2024

IntroductionExercise therapy is the primary endorsed form of conservative treatment for chronic low back pain (LBP). However, there is still conflicting evidence on which exercise intervention is best. While motor control exercise can lead to morphological and functional improvements of lumbar multifidus muscle in individuals with chronic LBP, the effects of exercise prescription on multifidus stiffness assessed via shear wave elastography are still unknown. The primary aim of this study is to determine the effects of a combined motor control and isolated lumbar extension (MC + ILEX) intervention on lumbar multifidus muscle stiffness.MethodsA total of 25 participants aged 18 to 65 were recruited from local orthopedic clinics and the university community with moderate to severe non-specific chronic LBP. Participants performed a 12-week MC + ILEX intervention program. Stiffness of the lumbar multifidus muscle (primary outcome) at L4 and L5 was obtained at baseline, 6-week, and 12-week using shear wave elastography. Changes in stiffness ratio (e.g., ratio of lumbar multifidus muscle stiffness from rest to contracted) were also assessed at both time points. Pre to post-intervention changes in lumbar multifidus muscle stiffness were assessed using a one-way repeated measure ANOVA.ResultsFollowing the 12-week intervention, there were no statistically significant changes in lumbar multifidus muscle stiffness at rest on the right side at L4 (p = 0.628) and the left side at L4 and L5 (p = 0.093, p = 0.203), but a statistically significant decrease was observed on the right side at L5 (p = 0.036). There was no change in lumbar multifidus muscle stiffness ratio.ConclusionThis study provides preliminary evidence to suggest that a 12-week MC + ILEX intervention had minimal effect on lumbar multifidus muscle stiffness in individuals with chronic LBP. Further investigations are needed to confirm our findings and clarify the relationship between muscle stiffness and functional outcomes.
Passive sensing data predicts stress in university students: a supervised machine learning method for digital phenotyping
Authors: Shvetcov Artur , Funke Kupper Joost , Zheng Wu-Yi , Slade Aimy , Han Jin , Whitton Alexis , Spoelma Michael , Hoon Leonard , Mouzakis Kon , Vasa Rajesh , Gupta Sunil , Venkatesh Svetha , Newby Jill , Christensen Helen 
Published: August 2024

IntroductionUniversity students are particularly susceptible to developing high levels of stress, which occur when environmental demands outweigh an individual’s ability to cope. The growing advent of mental health smartphone apps has led to a surge in use by university students seeking ways to help them cope with stress. Use of these apps has afforded researchers the unique ability to collect extensive amounts of passive sensing data including GPS and step detection. Despite this, little is known about the relationship between passive sensing data and stress. Further, there are no established methodologies or tools to predict stress from passive sensing data in this group.MethodsIn this study, we establish a clear machine learning-based methodological pipeline for processing passive sensing data and extracting features that may be relevant in the context of mental health.ResultsWe then use this methodology to determine the relationship between passive sensing data and stress in university students.DiscussionIn doing so, we offer the first proof-of-principle data for the utility of our methodological pipeline and highlight that passive sensing data can indeed digitally phenotype stress in university students.Clinical trial registrationAustralia New Zealand Clinical Trials Registry (ANZCTR), identifier ACTRN12621001223820.
Abnormal activation patterns in MT+ during visual motion perception in major depressive disorder
Authors: Liu Dong-Yu , Hu Xi-Wen , Han Jin-Fang , Tan Zhong-Lin , Song Xue Mei 
Published: August 2024

ObjectivePrevious studies have found that patients with Major Depressive Disorder (MDD) exhibit impaired visual motion perception capabilities, and multi-level abnormalities in the human middle temporal complex (MT+), a key brain area for processing visual motion information. However, the brain activity pattern of MDD patients during the perception of visual motion information is currently unclear. In order to study the effect of depression on the activity and functional connectivity (FC) of MT+ during the perception of visual motion information, we conducted a study combining task-state fMRI and psychophysical paradigm to compare MDD patients and healthy control (HC).MethodsDuration threshold was examined through a visual motion perception psychophysical experiment. In addition, a classic block-design grating motion task was utilized for fMRI scanning of 24 MDD patients and 25 HC. The grating moved randomly in one of eight directions. We examined the neural activation under visual stimulation conditions compared to the baseline and FC.ResultsCompared to HC group, MDD patients exhibited increased duration threshold. During the task, MDD patients showed decreased beta value and percent signal change in left and right MT+. In the sample comprising MDD and HC, there was a significant negative correlation between beta value in right MT+ and duration threshold. And in MDD group, activation in MT+ were significantly correlated with retardation score. Notably, no such differences in activation were observed in primary visual cortex (V1). Furthermore, when left MT+ served as the seed region, compared to the HC, MDD group showed increased FC with right calcarine fissure and surrounding cortex and decreased FC with left precuneus.ConclusionOverall, the findings of this study highlight that the visual motion perception function impairment in MDD patients relates to abnormal activation patterns in MT+, and task-related activity are significantly connected to the retardation symptoms of the disease. This not only provides insights into the potential neurobiological mechanisms behind visual motion perception disorder in MDD patients from the aspect of task-related brain activity, but also supports the importance of MT+ as a candidate biomarker region for MDD.
ICF-based hearing and functioning assessment: validation and research outcomes of utilizing the HEAR-COMMAND tool for patients with mild to moderately severe hearing loss and individuals with normal hearing
Authors: Afghah Tahereh , Alfakir Razan , Meis Markus , Hammady Mahmoud , Youssif Mostafa , Abd Al-Ghaffar Mohamed , Kramer Sophia E. , Wagener Kirsten C. 
Published: August 2024

ObjectiveCurrent clinical assessments for Hearing Loss (HL) are often limited to controlled laboratory settings in which a narrow spectrum of hearing difficulties can be assessed. A majority of the daily life challenges caused by HL cannot be measured in clinical methodologies. To screen the individuals' needs and limitations, a questionnaire named the HEAR-COMMAND tool was developed and qualitatively validated through an international collaboration, aligning with the World Health Organization's International Classification of Functioning, Disability, and Health Framework (ICF) Core Sets for Hearing Loss. The tool empowers healthcare professionals (HCPs) to integrate the ICF framework into patient assessments and patient-reported outcomes (PRO) in clinical and non-clinical settings. The aim is to provide a general foundation and starting point for future applications in various areas including ENT and hearing acoustics. The outcome can be employed to define and support rehabilitation in an evidence-based manner. This article presents the validation and research outcomes of using the tool for individuals with mild to moderately severe HL in contrast to normal-hearing individuals.DesignUsing a cross-sectional multicenter study, the tool was distributed among 215 participants in Germany, the USA, and Egypt, filled in German, English, or Arabic. Three outcome scores and the corresponding disability degree were defined: hearing-related, non-hearing-related, and speech-perception scores. The content and construct validation were conducted, and the tool's internal consistency was assessed.ResultsThe extracted constructs included “Auditory processing functionality”, “Sound quality compatibility”, “Listening and communication functionality”, “Interpersonal interaction functionality and infrastructure accessibility”, “Social determinants and infrastructure compatibility”, “Other sensory integration functionality”, and “Cognitive functionality”. Regarding content validity, it was demonstrated that normal-hearing participants differed significantly from individuals with HL in the hearing-related and speech-perception scores. The reliability assessment showed a high internal consistency (Cronbach's alpha = 0.9).ConclusionThe outcome demonstrated the HEAR-COMMAND tool's high content and construct validity. The tool can effectively represent the patient's perspective of HL and hearing-related functioning and enhance the effectiveness of the treatment plans and rehabilitation. The broad range of targeted concepts provides a unique overview of daily life hearing difficulties and their impact on the patient's functioning and quality of life.
Hepatitis B Virus, Hepatitis C Virus, and Human Immunodeficiency Virus Infection Among Premarital Screening Individuals in Saudi Arabia
Authors: Alfadhli Deemah S. , Sulimani Suha M. , Fadl Sahar M. , Bin Jumah Ibtihal M. , Alanazi Abdullah F. , Alangari Abdulaziz S. 
Published: August 2024

ObjectivePremarital screening is one of the most important strategies for preventing infectious diseases such as hepatitis B virus, hepatitis C virus, and human immunodeficiency virus in populations. This study aims to explore the prevalence of these viruses and their association with potential demographic factors among individuals undergoing premarital screening in Saudi Arabia.MethodsA cross-sectional study design using the National Healthy Marriage Program electronic registry in the Saudi Ministry of Health. Patients were selected from the premarital screening tests for the three blood-borne viruses. Data were obtained from January to August 2021 among 114,740 individuals.ResultsHepatitis B virus infection showed the highest prevalence followed by hepatitis C and human immunodeficiency viruses. Among those who were infected, men had higher infectious disease prevalence than women. The central and western regions had the highest percentages of infection.ConclusionThe studied infections pose a continuous public health issue among premarital screening individuals in Saudi Arabia. This study identified important demographic risk factors for these diseases and highlighted the need for future strategies and long-term plans at the national level.
Clinical Impacts of Pseudomonas aeruginosa Isolation in Patients with Bronchiectasis: Findings from KMBARC Registry
Authors: Song Jinhwa , Sin Sooim , Kang Hye-Rin , Oh Yeon-Mok , Jeong Ina 
Published: August 2024

Background: Pseudomonas aeruginosa isolation in bronchiectasis is associated with a poor prognosis, including increased hospital admissions, exacerbation, and mortality. In this study, we aimed to evaluate the clinical characteristics and outcomes of P. aeruginosa isolation from patients with bronchiectasis in South Korea. Methods: This multicenter prospective cohort study analyzed 936 patients with bronchiectasis. We examined the prevalence of P. aeruginosa isolates and other microbiological characteristics. Additionally, the clinical characteristics related to disease severity and 1-year prognosis were compared between patients with and without P. aeruginosa isolation. Propensity score matching was used to mitigate confounding biases. Results: Of the 936 patients with bronchiectasis, P. aeruginosa was isolated from 89. A total of 445 matched patients—356 patients without (non-Pseudomonas group) and 89 with (Pseudomonas group) P. aeruginosa isolation—were analyzed. The Pseudomonas group showed poorer lung function, greater involvement of radiographic bronchiectasis, and a higher proportion of cystic bronchiectasis than the non-Pseudomonas group. After one year, more patients in the Pseudomonas group were admitted for bronchiectasis than in the non-Pseudomonas group. Moreover, the Bronchiectasis Health Questionnaire scores were significantly lower in the Pseudomonas group than in the non-Pseudomonas group. Conclusions: The isolation of P. aeruginosa was independently associated with increased disease severity and poor clinical outcomes in Korean patients with bronchiectasis.
Anaphylaxis after SonoVue: A Case Report and a Literature Review
Authors: Longhino David , Buonomo Alessandro , Zocco Maria Assunta , Ainora Maria Elena , Esposto Giorgio , Mignini Irene , Cerrito Lucia , Ponziani Francesca Romana , Gasbarrini Antonio , Nucera Eleonora , Aruanno Arianna 
Published: August 2024

SonoVue (Bracco, Milan, Italy) is a drug used in ultrasonography for the purpose of increasing the echogenicity of blood or fluids by improving the signal-to-noise ratio. Background/Objectives/Methods: We described a case of anaphylaxis due to SonoVue and performed a literature review. Results and Conclusions: We reported a case of anaphylaxis secondary to the administration of SonoVue and described all the 13 literature cases. Given its widespread use and the potentially dangerous nature of the reactions it can cause, it is advisable to know how to promptly recognize fatal reactions.
Impact of Graphene Layers on Genetic Expression and Regulation within Sulfate-Reducing Biofilms
Authors: Gopalakrishnan Vinoj , Saxena Priya , Thakur Payal , Lipatov Alexey , Sani Rajesh K. 
Published: August 2024

Bacterial adhesion and biofilm maturation is significantly influenced by surface properties, encompassing both bare surfaces and single or multi-layered coatings. Hence, there is an utmost interest in exploring the intricacies of gene regulation in sulfate-reducing bacteria (SRB) on copper and graphene-coated copper surfaces. In this study, Oleidesulfovibrio alaskensis G20 was used as the model SRB to elucidate the pathways that govern pivotal roles during biofilm formation on the graphene layers. Employing a potent reporter green fluorescent protein (GFP) tagged to O. alaskensis G20, the spatial structure of O. alaskensis G20 biofilm on copper foil (CuF), single-layer graphene-coated copper (Cu-GrI), and double-layer graphene-coated copper (Cu-GrII) surfaces was investigated. Biofilm formation on CuF, Cu-GrI, and Cu-GrII surfaces was quantified using CLSM z-stack images within COMSTAT v2 software. The results revealed that CuF, Cu-GrI, and Cu-GrII did not affect the formation of the GFP-tagged O. alaskensis G20 biofilm architecture. qPCR expression showed insignificant fold changes for outer membrane components regulating the quorum-sensing system, and global regulatory proteins between the uncoated and coated surfaces. Notably, a significant expression was observed within the sulfate reduction pathway confined to dissimilatory sulfite reductases on the Cu-GrII surface compared to the CuF and Cu-GrI surfaces.