bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prophylactic management of cerebral vasospasm with clazosentan in real clinical practice: a single-center retrospective cohort study
Authors: Sakata Hiroyuki , Kanoke Atsushi , Uchida Hiroki , Haryu Shinya , Omodaka Shunsuke , Kimura Naoto , Yoshida Masahiro , Niizuma Kuniyasu , Tominaga Teiji , Endo Hidenori 
Published: June 2024

IntroductionClazosentan, a selective endothelin receptor subtype A antagonist, reduces vasospasm-related morbidity and all-cause mortality following aneurysmal subarachnoid hemorrhage (SAH) in the Japanese population, as demonstrated by a recent randomized phase 3 trial. However, evidence to suggest clazosentan should be prioritized over the current standard of care to prevent cerebral vasospasm is still lacking. Therefore, we investigated the efficacy and safety of clazosentan in comparison with conventional postoperative management in real-world clinical practice.MethodsWe conducted a single-center, retrospective, observational cohort study using prospectively collected data from consecutive patients with aneurysmal SAH. After clazosentan was approved for use in Japan, the conventional postoperative management protocol, composed of intravenous fasudil chloride and oral cilostazol (control group, April 2021 to March 2022), was changed to the clazosentan protocol (clazosentan group, April 2022 to March 2023). The primary endpoint was the incidence of vasospasm-related symptomatic infarction. The secondary endpoints were favorable functional outcomes (modified Rankin scale score &lt; 3) at discharge, angiographic vasospasm, and the need for rescue therapy for delayed cerebral ischemia.ResultsThe analysis included 100 and 81 patients in the control and clazosentan groups, respectively. The incidence of vasospasm-related symptomatic infarction was significantly lower in the clazosentan group than in the control group (6.2% vs. 16%, p = 0.032). Multiple logistic analyses demonstrated that the use of clazosentan was independently associated with fewer incidence of vasospasm-related symptomatic infarct (23.8% vs. 47.5%, odds ratio 0.34 [0.12–0.97], p = 0.032). Clazosentan was significantly associated with favorable outcomes at discharge (79% vs. 66%, p = 0.037). Moreover, both the incidence of angiographic vasospasm (25.9% vs. 44%, p = 0.013) and the need for rescue therapy (16.1% vs. 34%, p = 0.006) was lower in the clazosentan group. The occurrence of pulmonary edema was significantly higher with clazosentan use (19.8% vs. 5%, p = 0.002), which did not result in morbidity.ConclusionA postoperative management protocol centering on clazosentan was associated with the reduced vasospasm-related symptomatic infarction and improved clinical outcomes compared to the conventional management protocol in Japanese clinical practice. Clazosentan might be a promising treatment option for counteracting cerebral vasospasm after aneurysmal SAH.
Proteomics and lipidomic analysis reveal dysregulated pathways associated with loss of sacsin
Authors: Galatolo Daniele , Rocchiccioli Silvia , Di Giorgi Nicoletta , Dal Canto Flavio , Signore Giovanni , Morani Federica , Ceccherini Elisa , Doccini Stefano , Santorelli Filippo Maria 
Published: June 2024

IntroductionAutosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a rare incurable neurodegenerative disease caused by mutations in the SACS gene, which codes for sacsin, a large protein involved in protein homeostasis, mitochondrial function, cytoskeletal dynamics, autophagy, cell adhesion and vesicle trafficking. However, the pathogenic mechanisms underlying sacsin dysfunction are still largely uncharacterized, and so attempts to develop therapies are still in the early stages.MethodsTo achieve further understanding of how processes are altered by loss of sacsin, we used untargeted proteomics to compare protein profiles in ARSACS fibroblasts versus controls.ResultsOur analyses confirmed the involvement of known biological pathways and also implicated calcium and lipid homeostasis in ARSACS skin fibroblasts, a finding further verified in SH-SY5Y SACS–/– cells. Validation through mass spectrometry-based analysis and comparative quantification of lipids by LC-MS in fibroblasts revealed increased levels of ceramides coupled with a reduction of diacylglycerols.DiscussionIn addition to confirming aberrant Ca2+ homeostasis in ARSACS, this study described abnormal lipid levels associated with loss of sacsin.
Mapping intracellular NAD content in entire human brain using phosphorus-31 MR spectroscopic imaging at 7 Tesla
Authors: Guo Rong , Yang Shaolin , Wiesner Hannes M. , Li Yudu , Zhao Yibo , Liang Zhi-Pei , Chen Wei , Zhu Xiao-Hong 
Published: June 2024

IntroductionNicotinamide adenine dinucleotide (NAD) is a crucial molecule in cellular metabolism and signaling. Mapping intracellular NAD content of human brain has long been of interest. However, the sub-millimolar level of cerebral NAD concentration poses significant challenges for in vivo measurement and imaging.MethodsIn this study, we demonstrated the feasibility of non-invasively mapping NAD contents in entire human brain by employing a phosphorus-31 magnetic resonance spectroscopic imaging (31P-MRSI)-based NAD assay at ultrahigh field (7 Tesla), in combination with a probabilistic subspace-based processing method.ResultsThe processing method achieved about a 10-fold reduction in noise over raw measurements, resulting in remarkably reduced estimation errors of NAD. Quantified NAD levels, observed at approximately 0.4 mM, exhibited good reproducibility within repeated scans on the same subject and good consistency across subjects in group data (2.3 cc nominal resolution). One set of higher-resolution data (1.0 cc nominal resolution) unveiled potential for assessing tissue metabolic heterogeneity, showing similar NAD distributions in white and gray matter. Preliminary analysis of age dependence suggested that the NAD level decreases with age.DiscussionThese results illustrate favorable outcomes of our first attempt to use ultrahigh field 31P-MRSI and advanced processing techniques to generate a whole-brain map of low-concentration intracellular NAD content in the human brain.
Characterization of antiseizure medications effects on the EEG neurodynamic by fractal dimension
Authors: Porcaro Camillo , Seppi Dario , Pellegrino Giovanni , Dainese Filippo , Kassabian Benedetta , Pellegrino Luciano , De Nardi Gianluigi , Grego Alberto , Corbetta Maurizio , Ferreri Florinda 
Published: June 2024

ObjectivesAn important challenge in epilepsy is to define biomarkers of response to treatment. Many electroencephalography (EEG) methods and indices have been developed mainly using linear methods, e.g., spectral power and individual alpha frequency peak (IAF). However, brain activity is complex and non-linear, hence there is a need to explore EEG neurodynamics using nonlinear approaches. Here, we use the Fractal Dimension (FD), a measure of whole brain signal complexity, to measure the response to anti-seizure therapy in patients with Focal Epilepsy (FE) and compare it with linear methods.MaterialsTwenty-five drug-responder (DR) patients with focal epilepsy were studied before (t1, named DR-t1) and after (t2, named DR-t2) the introduction of the anti-seizure medications (ASMs). DR-t1 and DR-t2 EEG results were compared against 40 age-matched healthy controls (HC).MethodsEEG data were investigated from two different angles: frequency domain—spectral properties in δ, θ, α, β, and γ bands and the IAF peak, and time-domain—FD as a signature of the nonlinear complexity of the EEG signals. Those features were compared among the three groups.ResultsThe δ power differed between DR patients pre and post-ASM and HC (DR-t1 vs. HC, p &lt; 0.01 and DR-t2 vs. HC, p &lt; 0.01). The θ power differed between DR-t1 and DR-t2 (p = 0.015) and between DR-t1 and HC (p = 0.01). The α power, similar to the δ, differed between DR patients pre and post-ASM and HC (DR-t1 vs. HC, p &lt; 0.01 and DR-t2 vs. HC, p &lt; 0.01). The IAF value was lower for DR-t1 than DR-t2 (p = 0.048) and HC (p = 0.042). The FD value was lower in DR-t1 than in DR-t2 (p = 0.015) and HC (p = 0.011). Finally, Bayes Factor analysis showed that FD was 195 times more likely to separate DR-t1 from DR-t2 than IAF and 231 times than θ.DiscussionFD measured in baseline EEG signals is a non-linear brain measure of complexity more sensitive than EEG power or IAF in detecting a response to ASMs. This likely reflects the non-oscillatory nature of neural activity, which FD better describes.ConclusionOur work suggests that FD is a promising measure to monitor the response to ASMs in FE.
Vitamin D status, vitamin D receptor, CYP2R1, and CYP24A1 profiles in children
Authors: Iriani Anggraini , Rachman Andhika , Fatina Marsya Kaila , Gemilang Rizka Kurnia , Trisnandi Andi , Muskananfola Fiona Valerie , Nugraha Media Fitri Isma 
Published: June 2024

IntroductionVitamin D plays a major role in the musculoskeletal and immune system. Understanding the comprehensive mechanism of vitamin D receptors and the enzyme of vitamin D induction (CYP2R1) and inhibition (CYP24A1) in its metabolism is interesting. This study aims to understand vitamin D metabolism in Indonesian pediatrics, specifically in Jakarta, which has abundant sun exposure.MethodologyA cross-sectional study with comparative, correlative, and multivariate analysis on vitamin D, vitamin D receptor, CYP2R1, and CYP24A1 levels was conducted on 46 children with no known morbidity.ResultSubjects were mostly male (52.2%), age group of 2–6 years (34.8%), and had sufficient vitamin D status (43.5%, median 27.55 ng/mL). Age was found to have a negative correlation with vitamin D levels (p &lt; 0.001; r = −0.625) and CYP2R1 (p = 0.035; r = −0.311). Significant positive associations were found between CYP24A1 and CYP2R1 (p = 0.046; r = 0.296). Participants aged 0–2 are more likely to have a higher level of vitamin D status compared to those aged &gt;2 years (OR 42.092, 95% CI [4.532–390.914], p = 0.001). VDR levels were significantly lower in insufficient vitamin D levels than in the sufficient group (p = 0.018). VDR and vitamin D status had a positive relation (OR 7.023, 95% CI [1.864–26.453], p = 0.004).ConclusionVitamin D levels decrease with the increase in age. Vitamin D receptor level has an inline-level progression with vitamin D level. CYP2R1 and CYP24A1 suggest a directly proportional relationship. Vitamin D screening and supplementation in children older than 2 years old are suggested.
Effect of frozen gloves on chemotherapy-induced neurotoxicity in breast cancer patients: a systematic review and meta-analysis
Authors: Wu Hongting , Jin Ying , Song Jiaqing , Gao Xiufei 
Published: June 2024

BackgroundChemotherapy-induced peripheral neurotoxicity (CIPN) is a dose-limiting side effect observed in breast cancer patients. Its primary clinical manifestations include limb numbness, tingling sensations, hypoesthesia, or paresthesia. In severe instances, some patients may also encounter muscle cramps, weakness, and pain, leading to potential paralysis. The onset of CIPN significantly impacts the quality of life for cancer patients. Hence, it is imperative to explore preventive strategies for managing CIPN.MethodsWe searched for relevant randomized controlled trials (RCTs) and non-randomized controlled trials (non-RCTs) in several databases. The primary outcome measures encompassed the Patient Neurotoxicity Questionnaire (PNQ), the Functional Assessment of Cancer Therapy-Taxane (FACT-Taxane), and the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE). Secondary outcomes aimed to evaluate the quality of life and the tolerability of ice gloves. Meta-analysis was conducted using RevMan 5.3 software to determine the relative risk ratio (RR) and 95% confidence interval (CI).ResultsWe conducted an analysis involving 372 patients across seven trials. In our meta-analysis, the use of ice gloves demonstrated non-significant results in reducing the incidence of both motor and sensory neuropathy, as assessed through CTCAE (sensory: RR: 0.94; 95% CI: 0.85 to 1.02; P = 0.15; motor: RR: 1.04; 95% CI: 0.88 to 1.22; P = 0.64). Similarly, when evaluated using the PNQ, there was no significant reduction observed in the incidence of sensory and motor neuropathy (sensory: RR: 0.49; 95% CI: 0.20 to 1.20; P = 0.12; motor: RR: 0.71; 95% CI: 0.26 to 1.99; P = 0.52). Consistently, our conclusions remained unchanged when employing the FACT-Taxane assessment. Regarding the evaluation of the quality of life, our observations suggested a potential improvement with the use of ice gloves, and participants exhibited moderate tolerance towards them.ConclusionIce gloves are a reasonable option for the treatment of CIPN in patients undergoing chemotherapy for breast cancer. However, the effectiveness of ice gloves in combating CIPN remains inconclusive at this time due to the low quality and limited number of clinical trials on this topic.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023457045, identifier CRD42023457045.
Placental co-transcriptional activator Vestigial-like 1 (VGLL1) drives tumorigenesis via increasing transcription of proliferation and invasion genes
Authors: Sonnemann Heather M. , Pazdrak Barbara , Nassif Barbara , Sun Yimo , Elzohary Lama , Talukder Amjad H. , Katailiha Arjun S. , Bhat Krishna , Lizée Gregory 
Published: June 2024

IntroductionVestigial-like 1 (VGLL1) is a co-transcriptional activator that binds to TEA domain-containing transcription factors (TEADs). Its expression is upregulated in a variety of aggressive cancer types, including pancreatic and basal-like breast cancer, and increased transcription of VGLL1 is strongly correlated with poor prognosis and decreased overall patient survival. In normal tissues, VGLL1 is most highly expressed within placental trophoblast cells, which share the common attributes of rapid cellular proliferation and invasion with tumor cells. The impact of VGLL1 in cancer has not been fully elucidated and no VGLL1-targeted therapy currently exists.MethodsThe aim of this study was to evaluate the cellular function and downstream genomic targets of VGLL1 in placental, pancreatic, and breast cancer cells. Functional assays were employed to assess the role of VGLL1 in cellular invasion and proliferation, and ChIP-seq and RNAseq assays were performed to identify VGLL1 target genes and potential impact using pathway analysis.ResultsChIP-seq analysis identified eight transcription factors with a VGLL1-binding motif that were common between all three cell types, including TEAD1-4, AP-1, and GATA6, and revealed ~3,000 shared genes with which VGLL1 interacts. Furthermore, increased VGLL1 expression led to an enhancement of cell invasion and proliferation, which was supported by RNAseq analysis showing transcriptional changes in several genes known to be involved in these processes.DiscussionThis work expands our mechanistic understanding of VGLL1 function in tumor cells and provides a strong rationale for developing VGLL1-targeted therapies for treating cancer patients.
Evaluating the strengths and limitations of multimodal ChatGPT-4 in detecting glaucoma using fundus images
Authors: AlRyalat Saif Aldeen , Musleh Ayman Mohammed , Kahook Malik Y. 
Published: June 2024

OverviewThis study evaluates the diagnostic accuracy of a multimodal large language model (LLM), ChatGPT-4, in recognizing glaucoma using color fundus photographs (CFPs) with a benchmark dataset and without prior training or fine tuning.MethodsThe publicly accessible Retinal Fundus Glaucoma Challenge “REFUGE” dataset was utilized for analyses. The input data consisted of the entire 400 image testing set. The task involved classifying fundus images into either ‘Likely Glaucomatous’ or ‘Likely Non-Glaucomatous’. We constructed a confusion matrix to visualize the results of predictions from ChatGPT-4, focusing on accuracy of binary classifications (glaucoma vs non-glaucoma).ResultsChatGPT-4 demonstrated an accuracy of 90% with a 95% confidence interval (CI) of 87.06%-92.94%. The sensitivity was found to be 50% (95% CI: 34.51%-65.49%), while the specificity was 94.44% (95% CI: 92.08%-96.81%). The precision was recorded at 50% (95% CI: 34.51%-65.49%), and the F1 Score was 0.50.ConclusionChatGPT-4 achieved relatively high diagnostic accuracy without prior fine tuning on CFPs. Considering the scarcity of data in specialized medical fields, including ophthalmology, the use of advanced AI techniques, such as LLMs, might require less data for training compared to other forms of AI with potential savings in time and financial resources. It may also pave the way for the development of innovative tools to support specialized medical care, particularly those dependent on multimodal data for diagnosis and follow-up, irrespective of resource constraints.
Pathophysiological changes and injury markers for acute lung injury from blunt impact in infant rabbits
Authors: Wang Ke , Huang ZhenPeng , He JiaWei , Kong LingWang , Chen Mingwei 
Published: June 2024

BackgroundTraffic accidents, particularly blunt impacts, cause serious injuries in children. We aimed to assess inflammatory and injury responses in infant rabbits subjected to acute lung injury resulting from blunt impact, with the goal of identifying potential circulatory injury markers.MethodsForty 4-week-old infant rabbits were subjected to a right chest impact using a Hopkinson bar with 2,600 g. Computed tomography was employed to assess injury severity. Pathological changes were observed using hematoxylin and eosin staining in the control, 0, 24, and 72 h groups, post-injury. Immunohistochemistry was used to examine surfactant protein A (SP-A) changes in right lung tissues and upper main bronchi. Serum levels of interleukin-6 (IL-6), IL-8, and SP-A were measured using ELISA within 24 h post-injury in the control, 0 h, and 24 h groups.ResultsFollowing blunt injury, significant increases were observed in blood white blood cell count (F = 101.556, P &lt; 0.01) and neutrophil percentage (F = 104.228, P &lt; 0.01), which gradually decreased after 24 and 72 h. The lung wet/dry weight ratio indicated significant edema (F = 79.677, P &lt; 0.01), corroborated by hematoxylin and eosin staining showing edema, exudation, and marked granulocyte infiltration in the control, 0 h, 24 h and 72 h groups. SP-A levels decreased rapidly at 0 h, and recovered between 24 and 72 h in the right lung tissues (F = 6.7, P &lt; 0.05), left lung (F = 15.825, P &lt; 0.05) and upper main bronchi (F = 59.552, P &lt; 0.01). The ELISA results showed increasing trends for the control and 0 h groups, while decreasing trends were observed in 24 h group for IL-6 (F = 58.328, P &lt; 0.01) and IL-8 (F = 41.802, P &lt; 0.01). Conversely, SP-A exhibited a decreasing trend in the control and 0 h groups but increased in the serum of 24 h group (F = 52.629, P &lt; 0.01).DiscussionIn cases of direct chest trauma in infant rabbits, particularly mild injuries without rib fractures. SP-A levels correlated with pathological changes across all groups and may serve as biomarkers for pediatric blunt lung impact.
A computerized tool for the systematic visual quality assessment of infant multiple-breath washout measurements
Authors: Oestreich Marc-Alexander , Doswald Isabelle , Salem Yasmin , Künstle Noëmi , Wyler Florian , Frauchiger Bettina S. , Kentgens Anne-Christianne , Latzin Philipp , Yammine Sophie 
Published: June 2024

BackgroundMultiple-breath washout (MBW) is a sensitive method for assessing lung volumes and ventilation inhomogeneity in infants, but remains prone to artefacts (e.g., sighs). There is a lack of tools for systematic retrospective analysis of existing datasets, and unlike N2-MBW in older children, there are few specific quality control (QC) criteria for artefacts in infant SF6-MBW.AimWe aimed to develop a computer-based tool for systematic evaluation of visual QC criteria of SF6-MBW measurements and to investigate interrater agreement and effects on MBW outcomes among three independent examiners.MethodsWe developed a software package for visualization of raw Spiroware (Eco Medics AG, Switzerland) and signal processed WBreath (ndd Medizintechnik AG, Switzerland) SF6-MBW signal traces. Interrater agreement among three independent examiners (two experienced, one novice) who systematically reviewed 400 MBW trials for visual artefacts and the decision to accept/reject the washin and washout were assessed.ResultsOur tool visualizes MBW signals and provides the user with (i) display options (e.g., zoom), (ii) options for a systematic QC assessment [e.g., decision to accept or reject, identification of artefacts (leak, sigh, irregular breathing pattern, breath hold), and comments], and (iii) additional information (e.g., automatic identification of sighs). Reviewer agreement was good using pre-defined QC criteria (κ 0.637–0.725). Differences in the decision to accept/reject had no substantial effect on MBW outcomes.ConclusionOur visual quality control tool supports a systematic retrospective analysis of existing data sets. Based on predefined QC criteria, even inexperienced users can achieve comparable MBW results.
Efficacy of an online lung ultrasound module on skill acquisition by clinician: a new paradigm
Authors: Sharma Alok , Kumar Gunjana , Nagpal Rema , Naranje Kirti , Sengupta Arnab , Jagannath Vanitha , Suryawanshi Sonali , Suryawanshi Pradeep 
Published: June 2024

IntroductionLung ultrasound (LUS) as an assessment tool has seen significant expansion in adult, paediatric, and neonatal populations due to advancements in point-of-care ultrasound over the past two decades. However, with fewer experts and learning platforms available in low- and middle-income countries and the lack of a standardised supervised training programme, LUS is not currently effectively used to the best of its potential in neonatal units.MethodologyA cross-sectional survey assessed the efficacy of learning LUS via a mentor-based online teaching module (NEOPOCUS). The questionnaire comprised the clinicians’ demographic profile, pre-course skills, and self-assessment of skill acquisition after course completion with ongoing hands-on practice.ResultsA total of 175 clinicians responded to the survey, with the majority (87.9%) working in level 3 and 4 neonatal intensive care units. Clinicians had variable clinical experience. Of them, 53.2% were consultant paediatricians/neonatologists with over 10 years of experience. After the course, there was a significant increase in clinician confidence levels in diagnosing and assessing all LUS pathology, as evidenced by the increase in median cumulative scores [from baseline 6 (interquartile range, IQR, 6–9) to 20 (IQR 16–24), p &lt; 0.001] with half of them gaining confidence within 3 months of the course.ConclusionAn online curriculum-based neonatal lung ultrasound training programme with clinician image demonstration and peer review of images for image optimisation increases self-reported confidence in diagnosing and managing neonatal lung pathology. Web-based online training in neonatal lung ultrasound has merits that can help with the delivery of training globally, and especially in low- and middle-income countries.