bluuebunny/crossref_metadata_2025_split huggingface dataset:
Non-glycosylated G protein with CpG ODN provides robust protection against respiratory syncytial virus without inducing eosinophilia
Authors: Kawahara Eigo , Shibata Takehiko , Hirai Toshiro , Yoshioka Yasuo 
Published: December 2023

IntroductionRespiratory syncytial virus (RSV) vaccines targeting the fusion glycoprotein (F protein) are highly effective clinically in preventing RSV challenges. The attachment glycoprotein (G protein) is a potentially effective vaccine antigen candidate, as it is important for cell adhesion during infection. However, vaccine-associated enhanced diseases in mice, such as eosinophilic lung inflammation following RSV challenge, are a concern with G protein vaccines. This study aimed to design an effective G protein vaccine with enhanced safety and efficacy by evaluating the efficacy and adverse reactions of vaccines composed of different recombinant G proteins and adjuvants in mice.MethodsMice were subcutaneously immunized with glycosylated G protein expressed in mammalian cells (mG), non-glycosylated G protein expressed in Escherichia coli (eG), or F protein with or without aluminum salts (alum), CpG oligodeoxynucleotide (CpG ODN), or AddaVax. After vaccination, the levels of G-specific antibody and T-cell responses were measured. The immunized mice were challenged with RSV and examined for the viral load in the lungs and nasal turbinates, lung-infiltrating cells, and lung pathology.ResultsmG with any adjuvant was ineffective at inducing G-specific antibodies and had difficulty achieving both protection against RSV challenge and eosinophilia suppression. In particular, mG+CpG ODN induced G-specific T helper 1 (Th1) cells but only a few G-specific antibodies and did not protect against RSV challenge. However, eG+CpG ODN induced high levels of G-specific antibodies and Th1 cells and protected against RSV challenge without inducing pulmonary inflammation. Moreover, the combination vaccine of eG+F+CpG ODN showed greater protection against upper respiratory tract RSV challenge than using each single antigen vaccine alone.DiscussionThese results indicate that the efficacy of recombinant G protein vaccines can be enhanced without inducing adverse reactions by using appropriate antigens and adjuvants, and their efficacy is further enhanced in the combination vaccine with F protein. These data provide valuable information for the clinical application of G protein vaccines.
Machine learning to identify risk factors associated with the development of ventilated hospital-acquired pneumonia and mortality: implications for antibiotic therapy selection
Authors: Sophonsri Anthony , Lou Mimi , Ny Pamela , Minejima Emi , Nieberg Paul , Wong-Beringer Annie 
Published: December 2023

BackgroundAmong patients with nosocomial bacterial pneumonia, those who decompensated to requiring mechanical ventilation (vHABP) faced the highest mortality followed by ventilator-associated pneumonia (VABP) and non-ventilated hospital-acquired pneumonia (nvHABP). The objectives of this study were to identify risk factors associated with the development and mortality of vHABP and to evaluate antibiotic management.MethodsA multicenter retrospective cohort study of adult inpatients with nosocomial pneumonia during 2014–2019 was performed. Groups were stratified by vHABP, nvHABP, and VABP and compared on demographics, clinical characteristics, treatment, and outcomes. Multivariable models were generated via machine learning to identify risk factors for progression to vHABP as well as pneumonia-associated mortality for each cohort.Results457 patients (32% nvHABP, 37% vHABP, and 31% VABP) were evaluated. The vHABP and nvHABP groups were similar in age (median age 66.4 years) with 77% having multiple comorbidities but more vHABP patients had liver disease (18.2% vs. 7.7% p = 0.005), alcohol use disorder (27% vs. 7.1%, p &lt; 0.0001), and were hospitalized within the past 30  days (30.4% vs. 19.5%, p = 0.02). An immediate need for ventilatory support occurred in 70% of vHABP patients on the day of diagnosis. Mortality was the highest in vHABP followed by VABP and nvHABP groups (44.6% vs. 36% vs. 14.3%, p &lt; 0.0001). Nearly all (96%) vHABP patients had positive cultures, with Gram-negative pathogens accounting for 58.8% whereby 33.0% were resistant to extended-spectrum β-lactams (ESBLs), ceftriaxone (17.5%), fluoroquinolones (20.6%), and carbapenems (12.4%). Up to half of the vHABP patients with ESBL-Enterobacterales or P. aeruginosa did not receive an effective empiric regimen; over 50% increase in mortality rate was observed among patients whom effective therapy was initiated past the day of pneumonia diagnosis. Risk factors associated with vHABP development were alcohol use disorder, APACHE II score, vasopressor therapy prior to infection, and culture positive for ESBL-Enterobacterales whereas history of hospitalization in the past 30  days, active malignancy, isolation of ceftriaxone-resistant pathogens or Pseudomonas aeruginosa, and vasopressor therapy were risk factors for vHABP-associated mortality.ConclusionPatients with vHABP experienced an acute and severe decompensation upon diagnosis. The risk factors identified in this study could provide actionable data for clinicians to identify those at risk for vHABP at the onset of pneumonia and to target antimicrobial stewardship efforts to improve treatment success.
Do neutrophil extracellular traps implicate in atheromatous plaques from carotid endarterectomy? Re-analyzes of cDNA microarray data by surgeons
Authors: Takahira Ryotaro , Ujifuku Kenta , Izumo Tsuyoshi , Xie Ang , Okamura Kazuaki , Morofuji Yoichi , Matsuo Takayuki 
Published: December 2023

BackgroundCarotid artery stenosis is the cause of 15% of strokes. Neutrophil extracellular traps (NETs) and peptidyl arginine deiminase 4 (PAD4) are believed to be involved in thrombosis. This pilot study described the differential expression profile of NETs between atheromatous plaques and surrounding tissues.MethodsMicroarray datasets of carotid plaques were obtained from Gene Expression Omnibus. The normalized data were processed into comma-separated value matrix files using spreadsheet software. Analyzes of microarray data were conducted using integrated differential expression and pathway analysis.ResultThe clustering results illustrated that the classifications of plaque and control had reasonable biological validity. Pathway analysis revealed the relevance of immune response, cell signaling, and other pathways. Differentially expressed genes were detected between carotid plaques and control specimens. However, enrichment analyzes did not reveal a difference in PAD4 expression between the groups and that NET implication was only found in one cDNA microarray dataset.DiscussionThis pilot study does not necessarily dismiss the possibility of a relationship between NETs and atherothrombotic stroke. Gene expression could differ between endothelial cells and atheromas, and further studies are needed.
Pattern of neurological recovery in persons with an acute cervical spinal cord injury over the first 14 days post injury
Authors: Fallah Nader , Noonan Vanessa K. , Waheed Zeina , Charest-Morin Raphaele , Dandurand Charlotte , Cheng Christiana , Ailon Tamir , Dea Nicolas , Paquette Scott , Street John T. , Fisher Charles , Dvorak Marcel F. , Kwon Brian K. 
Published: December 2023

IntroductionFollowing a traumatic spinal cord injury (SCI) it is critical to document the level and severity of injury. Neurological recovery occurs dynamically after injury and a baseline neurological exam offers a snapshot of the patient's impairment at that time. Understanding when this exam occurs in the recovery process is crucial for discussing prognosis and acute clinical trial enrollment. The objectives of this study were to: (1) describe the trajectory of motor recovery in persons with acute cervical SCI in the first 14 days post-injury; and (2) evaluate if the timing of the baseline neurological assessment in the first 14 days impacts the amount of motor recovery observed.MethodsData were obtained from the Rick Hansen Spinal Cord Injury Registry (RHSCIR) site in Vancouver and additional neurological data was extracted from medical charts. Participants with a cervical injury (C1–T1) who had a minimum of three exams (including a baseline and discharge exam) were included. Data on the upper-extremity motor score (UEMS), total motor score (TMS) and American Spinal Injury Association (ASIA) Impairment Scale (AIS) were included. A linear mixed-effect model with additional variables (AIS, level of injury, UEMS, time, time2, and TMS) was used to explore the pattern and amount of motor recovery over time.ResultsTrajectories of motor recovery in the first 14 days post-injury showed significant improvements in both TMS and UEMS for participants with AIS B, C, and D injuries, but was not different for high (C1–4) vs. low (C5–T1) cervical injuries or AIS A injuries. The timing of the baseline neurological examination significantly impacted the amount of motor recovery in participants with AIS B, C, and D injuries.DiscussionTiming of baseline neurological exams was significantly associated with the amount of motor recovery in cervical AIS B, C, and D injuries. Studies examining changes in neurological recovery should consider stratifying by severity and timing of the baseline exam to reduce bias amongst study cohorts. Future studies should validate these estimates for cervical AIS B, C, and D injuries to see if they can serve as an “adjustment factor” to control for differences in the timing of the baseline neurological exam.
Luxembourg Parkinson’s study -comprehensive baseline analysis of Parkinson’s disease and atypical parkinsonism
Authors: Pavelka Lukas , Rawal Rajesh , Ghosh Soumyabrata , Pauly Claire , Pauly Laure , Hanff Anne-Marie , Kolber Pierre Luc , Jónsdóttir Sonja R. , Mcintyre Deborah , Azaiz Kheira , Thiry Elodie , Vilasboas Liliana , Soboleva Ekaterina , Giraitis Marijus , Tsurkalenko Olena , Sapienza Stefano , Diederich Nico , Klucken Jochen , Glaab Enrico , Aguayo Gloria A. , Jubal Eduardo Rosales , Perquin Magali , Vaillant Michel , May Patrick , Gantenbein Manon , Satagopam Venkata P. , Krüger Rejko ,   on behalf of the NCER-PD Consortium
Published: December 2023

BackgroundDeep phenotyping of Parkinson’s disease (PD) is essential to investigate this fastest-growing neurodegenerative disorder. Since 2015, over 800 individuals with PD and atypical parkinsonism along with more than 800 control subjects have been recruited in the frame of the observational, monocentric, nation-wide, longitudinal-prospective Luxembourg Parkinson’s study.ObjectiveTo profile the baseline dataset and to explore risk factors, comorbidities and clinical profiles associated with PD, atypical parkinsonism and controls.MethodsEpidemiological and clinical characteristics of all 1,648 participants divided in disease and control groups were investigated. Then, a cross-sectional group comparison was performed between the three largest groups: PD, progressive supranuclear palsy (PSP) and controls. Subsequently, multiple linear and logistic regression models were fitted adjusting for confounders.ResultsThe mean (SD) age at onset (AAO) of PD was 62.3 (11.8) years with 15% early onset (AAO &lt; 50 years), mean disease duration 4.90 (5.16) years, male sex 66.5% and mean MDS-UPDRS III 35.2 (16.3). For PSP, the respective values were: 67.6 (8.2) years, all PSP with AAO &gt; 50 years, 2.80 (2.62) years, 62.7% and 53.3 (19.5). The highest frequency of hyposmia was detected in PD followed by PSP and controls (72.9%; 53.2%; 14.7%), challenging the use of hyposmia as discriminating feature in PD vs. PSP. Alcohol abstinence was significantly higher in PD than controls (17.6 vs. 12.9%, p = 0.003).ConclusionLuxembourg Parkinson’s study constitutes a valuable resource to strengthen the understanding of complex traits in the aforementioned neurodegenerative disorders. It corroborated several previously observed clinical profiles, and provided insight on frequency of hyposmia in PSP and dietary habits, such as alcohol abstinence in PD.Clinical trial registration: clinicaltrials.gov, NCT05266872.
Case report: Parsonage-turner syndrome in a melanoma patient treated by BRAF/MEK inhibitors after immune checkpoint inhibitors
Authors: Bonnefin Charlotte , Duval Fanny , Rouanet Marie , Kostine Marie , Gerard Emilie 
Published: December 2023

IntroductionCombination molecular BRAF/MEK inhibitors targeted therapy has been shown to improve overall survival in patients with BRAF V600 mutated unresectable or metastatic melanoma. Most patients treated with BRAF/MEK inhibitors will experience adverse events but neurological adverse events (nAEs) remain rare.Case reportA 42-year-old woman diagnosed with metastatic melanoma presented with an intense pain in the left shoulder 7 days after the beginning of encorafenib/binimetinib after immune checkpoint inhibitors (ICI) combination. No other triggering factors were identified. Electromyogram performed one month after the pain onset revealed a left brachial plexopathy suggestive of a Parsonage-Turner syndrome. The weakness slowly improved with intensive rehabilitation and targeted therapies were continued.ConclusionWe report the first case of Parsonage-Turner syndrome in a melanoma patient treated with encorafenib/binimetinib following checkpoint inhibitors combination.We cannot rule out the implication of ICI in the development of this syndrome but the rapid onset of the symptoms after the beginning of targeted therapies makes their involvment more likely.Given the increased use of BRAF/MEK inhibitors in managing of stage III and IV melanoma, as well as the development in stage II, clinicians should be aware of this potential side effect.
Oral FXIIa inhibitor KV998086 suppresses FXIIa and single chain FXII mediated kallikrein kinin system activation
Authors: Clermont Allen C. , Murugesan Nivetha , Edwards Hannah J. , Lee Daniel K. , Bayliss Natasha P. , Duckworth Edward J. , Pethen Stephen J. , Hampton Sally L. , Gailani David , Feener Edward P. 
Published: December 2023

Background: The kallikrein kinin system (KKS) is an established pharmacological target for the treatment and prevention of attacks in hereditary angioedema (HAE). Proteolytic activities of FXIIa and single-chain Factor XII (FXII) zymogen contribute to KKS activation and thereby may play roles in both initiating and propagating HAE attacks. In this report, we investigated the effects of potent small molecule FXIIa inhibitors on FXIIa and single chain FXII enzymatic activities, KKS activation, and angioedema in mice.Methods: We examined the effects of 29 structurally distinct FXIIa inhibitors on enzymatic activities of FXIIa and a mutant single chain FXII with R334A, R343A and R353A substitutions (rFXII-T), that does not undergo zymogen conversion to FXIIa, using kinetic fluorogenic substrate assays. We examined the effects of a representative FXIIa inhibitor, KV998086, on KKS activation and both carrageenan- and captopril-induced angioedema in mice.Results: FXIIa inhibitors designed to target its catalytic domain also potently inhibited the enzymatic activity of rFXII-T and the pIC50s of these compounds linearly correlated for rFXIIa and rFXII-T (R2 = 0.93). KV998086, a potent oral FXIIa inhibitor (IC50 = 7.2 nM) inhibited dextran sulfate (DXS)-stimulated generation of plasma kallikrein and FXIIa, and the cleavage of high molecular weight kininogen (HK) in human plasma. KV998086 also inhibited rFXII-T mediated HK cleavage (p &lt; 0.005) in plasma from FXII knockout mice supplemented with rFXII-T and stimulated with polyphosphate or DXS. Orally administered KV998086 protected mice from 1) captopril-induced Evans blue leakage in colon and laryngotracheal tissues and 2) blocked carrageenan-induced plasma HK consumption and paw edema.Conclusion: These findings show that small molecule FXIIa inhibitors, designed to target its active site, also inhibit the enzymatic activity of FXII zymogen. Combined inhibition of FXII zymogen and FXIIa may thereby suppress both the initiation and amplification of KKS activation that contribute to hereditary angioedema attacks and other FXII-mediated diseases.
Cytokinin Response of the Streptophyte Alga Coleochaete scutata provides a clue to the evolution of cytokinin signaling
Authors: Pinto Sandra , Tajeshwar Navindra , Gordon Kyana , Borrero Paloma , Novák Ondřej , Strnad Miroslav , Foellmer Matthias , Heyl Alexander 
Published: December 2023

IntroductionCytokinins, a group of adenine derivatives, are phytohormones that regulate many aspects of the plant's reaction to changes in the abiotic and biotic environment and ensure the correct execution of developmental programs. While the signaling pathway and its effects are very well established for Angiosperms, its origin, and evolution are less well understood. MethodsThe first step in the analysis of the cytokinin signaling pathway is to test if the organism can react to the hormone. Thus, an assay was established, that uses differences in the growth pattern of the Streptophyte alga, Coleochaete scutata, to determine if this algal species reacts to different cytokinins.ResultsSurprisingly not only classical cytokinins, such as trans-zeatin and kinetin, led to a change in the pattern of growth, but also adenine, which is usually used as a negative control. DiscussionThis raises questions about the origin and the functioning of the cytokinin signaling in C. scutata and also in algae in general.
Study on detection of intracerebral hemorrhage based on frequency difference of permittivity
Authors: Peng Shixin , Wang Xiaoshu , Jin Gui , Wang Feng , Zhu Ji , Zhang Xiaodong , Liu Nan , Xu Rui 
Published: December 2023

Introduction: Current detection of intracerebral hemorrhage (ICH), whether employing Electrical Capacitance Tomography (ECT) or other electrical imaging techniques, rely on time-difference measurements. The time-difference methods necessitate baseline measurements from the patient in a non-hemorrhagic state, which is impractical to obtain, rendering rapid detection of ICH unfeasible.Methods: This study introduces a novel approach that capitalizes on the distinct dispersion characteristics of the permittivity in brain tissue and the spectral variance of the permittivity between blood and other brain components. Specifically, the frequency-dependent variations in the permittivity are employed to achieve absolute detection of ICH, thereby eliminating the need for non-hemorrhagic baseline data. The methodology entails identification of two frequency points that the frequency-dependent variation in the permittivity at these two frequency points manifest the maximal difference between blood and other brain tissues. Subsequently, this permittivity differential at the two identified frequency points is utilized for hemorrhage detection. Experimental measurements were conducted using an impedance analyzer and a parallel plate capacitor to capture the capacitance in four single-component substances—distilled water, sheep blood, isolated pig fat, and isolated pig brain—as well as three mixed blood compounds—distilled water enveloping sheep blood, pig fat encapsulating sheep blood, and pig brain surrounding sheep blood—across a frequency range of 10 kHz to 20 MHz.Results: The results show that in different frequency bands, it is indeed possible to distinguish single-component substances from mixed substances by the frequency difference of capacitance variation. Comparative analysis reveals that the 1 MHz to 5 MHz frequency range is most effective for detecting blood in distilled water. For blood detection in pig fat, a 10 kHz to 1 MHz frequency range is identified as optimal, while a 10 kHz to 0.5 MHz frequency range is advantageous for blood detection in pig brain tissue.Discussion: The findings confirm that absolute detection of ICH is achievable through frequency-dependent variations in the permittivity. However, this necessitates the identification of the frequency band manifesting the largest difference of frequency-dependent variation between single-component and mixed substances. The study acknowledges limitations primarily due to the use of anticoagulant-altered sheep blood, which exhibits permittivity divergent from those of natural blood. Additionally, the in vitro pig fat and pig brain samples, having been subjected to freeze-thaw cycles, also demonstrate permittivity unrepresentative of in vivo tissue.
Meta-analysis of Arabidopsis thaliana microarray data in relation to heat stress response
Authors: Chaddad Zohra , Kaddouri Kaoutar , Smouni Abdelaziz , Missbah El Idrissi Mustapha , Taha Kaoutar , Hayah Ichrak , Badaoui Bouabid 
Published: December 2023

IntroductionIncreasing global warming has made heat stress a serious threat to crop productivity and global food security in recent years. One of the most promising solutions to address this issue is developing heat-stress-tolerant plants. Hence, a thorough understanding of heat stress response mechanisms, particularly molecular ones, is crucial.MethodsAlthough numerous studies have used microarray expression profiling technology to explore this area, these experiments often face limitations, leading to inconsistent results. To overcome these limitations, a random effects meta-analysis was employed using advanced statistical methods. A meta-analysis of 16 microarray datasets related to heat stress response in Arabidopsis thaliana was conducted.ResultsThe analysis revealed 1,972 significant differentially expressed genes between control and heat-stressed plants (826 over-expressed and 1,146 down-expressed), including 128 differentially expressed transcription factors from different families. The most significantly enriched biological processes, molecular functions, and KEGG pathways for over-expressed genes included heat response, mRNA splicing via spliceosome pathways, unfolded protein binding, and heat shock protein binding. Conversely, for down-expressed genes, the most significantly enriched categories included cell wall organization or biogenesis, protein phosphorylation, transmembrane transporter activity, ion transmembrane transporter, biosynthesis of secondary metabolites, and metabolic pathways.DiscussionThrough our comprehensive meta-analysis of heat stress transcriptomics, we have identified pivotal genes integral to the heat stress response, offering profound insights into the molecular mechanisms by which plants counteract such stressors. Our findings elucidate that heat stress influences gene expression both at the transcriptional phase and post-transcriptionally, thereby substantially augmenting our comprehension of plant adaptive strategies to heat stress.