bluuebunny/crossref_metadata_2025_split huggingface dataset:
Serum fibrinogen level and fibrinogen administration in patients with traumatic brain injury: a systematic review and meta-analysis protocol
Authors: Igoli Joanne , Daniel Jeremiah Oluwatomi Itodo , Oludele Halleluyah , Alao Adedoyin Esther , Ogedegbe Idemudia Stephen , Olaniyan Adewale , Adebayo Michael Adeshola , Matthew Damilola , Oyepitan Temidayo Elizabeth , Brabi Daniel , Olukoya Olatomiwa , Osunronbi Temidayo 
Published: August 2024

ABSTRACTIntroductionTraumatic Brain Injury (TBI) is a leading cause of disability and death globally. It has a significant economic burden. Coagulopathy has been identified as one of the key factors contributing to the poor outcomes observed in TBI patients, and it has been theorised that the management of coagulopathy will improve patient outcomes. Low serum fibrinogen levels denote a coagulopathic state, and the therapeutic administration of fibrinogen has been proposed to correct this state. However, there is no consensus on its efficacy in patients with TBI.This systematic review and meta-analysis seeks to ascertain the prognostic value of serum fibrinogen levels in patients with TBI and assess the effect of fibrinogen administration on these patients.MethodsUsing the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) guidelines, we will perform a comprehensive search of Scopus, Medline, Embase and Cochrane Library to retrieve all original articles that investigate the prognostic value of fibrinogen levels and/or the effect of fibrinogen administration in TBI patients. Primary outcomes include functional outcome and mortality assessments such as the Glasgow Outcome Score and modified Rankin Score. Secondary outcomes include progressive intracranial haemorrhage/contusion and need for surgical intervention. Data collected will encompass participant demographics, measured fibrinogen levels, dose of fibrinogen administered and specified outcome measures.ConclusionFindings from this study on if fibrinogen level has prognostic value and if fibrinogen administration improves patient outcomes, will help inform future TBI management and shared decision-making. Thus, TBI patient outcomes can be optimised accordingly.PROSPERO Registration NumberCRD42024556497. Available from:https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024556497
Odor source localization behavior of an insect enhanced by intermittent intake strategy
Authors: Shigaki Shunsuke , Matsushita Takumi , Ohashi Hirono , Ando Noriyasu , Hosoda Koh 
Published: August 2024

ABSTRACTThis study investigated odor acquisition strategies to enhance odor plume tracking performance. Efficient odor plume tracking is a crucial ability for organisms, affecting their survival, including for insects with relatively simple nervous systems. Insects can use odor cues to locate food sources or potential mates. Odors released from a source disperse in complex patterns owing to air currents and collisions with objects, making their spread unpredictable. Organisms must therefore engage in active odor acquisition behaviors to effectively gather spatial information from this highly uncertain odor environment. This study focused on odor acquisition via wing flapping in a male silk moth and its relationship with female localization. Given the difficulty of directly intervening in wing flapping, we employed an insect-mounted robotic system to engineer interventions and investigate the relationship between wing-flapping-induced odor acquisition and localization. We found that the difference between air inflow and stoppage in odor attraction was large, and that the odor plume tracking performance was highest at 10 Hz, where odor attraction can be performed at high frequencies. Although constant strong odor acquisition improves localization performance, it increases the likelihood of movement in directions other than that of the odor source. This suggests that periodic wing flapping helps to suppress undesired movements.
Investigating microscopic angioarchitecture in the human visual cortex in 3D with angioMASH tissue clearing and labelling
Authors: Hildebrand Sven , Franz Johannes , Hoogen Hanna , Capalbo Michael , Bethge Philipp , Herrler Andreas , Helmchen Fritjof , Roebroeck Alard 
Published: August 2024

AbstractNon-invasive imaging techniques, such as ultra-high field fMRI, are intricately connected to the underlying vasculature and are approaching ever higher resolutions. For the analysis of fMRI signals over cortical depth at such high resolutions, microvascular differences might have to be taken into account. Therefore, a better understanding of the laminar distribution and interareal differences in the cortical vasculature is becoming more important. However, in comparison to cyto- and myeloarchitecture, the study of angioarchitecture has received far less attention and relatively few methods have been described to visualise the vascular network in the human brain. Here we present angioMASH, a method for double labelling angioarchitecture and cytoarchitecture in archival human brain tissue, based on the recently published MASH protocol. The double labelling and optical clearing of thick human brain slices can be accomplished within 16 days. We use this method to acquire multi-resolution 3D datasets of combined cyto- and angioarchitecture in large (∼30 mm x 10 mm x 3 mm) volumes of human samples covering visual areas V1 and V2. We demonstrate for the first time, that classical angioarchitectonic features can be visualised in the human cortex and in 3D using tissue clearing and light-sheet microscopy. Lastly, we show differences in the vessel density and orientation over cortical depth within and between the two areas. Especially in V1, the vascular density is not homogeneous over cortical depth but shows distinct layering. These layers are also determined by changes in the orientation of the blood vessels from a predominantly radial to a more tangential distribution. In V2, differences in vascular density are less pronounced, but orientation profiles follow a similar trend over cortical depth. We discuss potential consequences of these differences for the interpretation of non-invasive functional imaging modalities such as fMRI or fNIRS.Graphical Abstract
Near-infrared spectroscopy discriminates mass-reared sterile and wild tsetse flies
Authors: Pagabeleguem Soumaïla , Da Dari F. , Somé Bernard M. , Avelessi Marx S.P. , Djègbè Nicaise D. C. , Yoda Rebecca L. , Bagayogo Abdramane , Maïga Hamidou , Churcher Thomas S. , Dabiré Roch K. 
Published: August 2024

AbstractIn the frame of the Pan African Tsetse and Trypanosomosis Eradication Campaign, an integrated pest management approach has been adopted to manage tsetse fly populations using a sterile insect technique (SIT).. Monitoring the efficacy of the SIT programs requires the discrimination between wild and sterile males collected in monitoring traps. The discrimination between sterile and wild males relies mainly on marking of sterile males with a fluorescent dye powder (before the releases) and their identification using a fluorescence camera and /or a fluorescence microscope. However, the accuracy of this method remains limited with defective marking and wild flies contaminated with a few dye particles in the monitoring traps. The molecular techniques developed to discriminate doubtful flies are costly for endemic countries. Here, we investigate the ability of a new generation monitoring tool, the near-infrared spectroscopy (NIRS) to discriminate between lab-rearedGlossina palpalis gambiensisand their counterparts in the field. NIRS technique discriminates wild flies males with 86% accuracy toGlossina palpalis gambiensismales reared in an insectarium. Interestingly, the prediction accuracy between wild and laboratory-reared flies improved to 88% when theGlossinalab colony flies were irradiated. In light of these results, NIRS can discriminate tsetse flies even when identification with the UV camera is doubtful. However, more investigations integrating some natural variables are required before the validation of the technical as a complementary method for potential future tsetse eradication programs.
Highjacked by a pseudoenzyme: How eudicot plants make indole
Authors: Florean Matilde , Schultz Hedwig , Grabe Veit , Luck Katrin , O’Connor Sarah E. , Köllner Tobias G. 
Published: August 2024

AbstractIndole is crucial for plant defense, where it is released as a signaling volatile upon herbivore attack and also serves as a starting precursor for defensive specialized metabolites. Indole is known to be synthesized in plants from indole-3-glycerol phosphate by the enzyme indole-3-glycerol phosphate lyase. Here we report that in core eudicots, indole production for plant defense occurs via an alternative pathway. The α subunit of tryptophan synthase (TSA), an enzyme of core metabolism, normally binds to tryptophan synthase β subunit (TSB) to produce tryptophan. However, we show that a non-catalytic TSB paralogue (TSB-like) can highjack TSA to produce indole. The widespread occurrence ofTSB-likegenes in eudicots suggests that this alternative mechanism for indole formation is widespread throughout the plant kingdom.
De novo design of potent inhibitors of Clostridioides difficile toxin B
Authors: Ragotte Robert J. , Tam John , Miletic Sean , Palou Roger , Weidle Connor , Li Zhijie , Glögl Matthias , Beilhartz Greg L. , Liang Huazhu , Carr Kenneth D. , Borst Andrew J. , Coventry Brian , Wang Xinru , Rubinstein John L. , Tyers Mike , Melnyk Roman A. , Baker David 
Published: August 2024

AbstractClostridioides difficileis a major cause of secondary disease in hospitals. During infection,C. difficiletoxin B drives disease pathology. Here we use deep learning and Rosetta-based approaches to de novo design small proteins that block the entry of TcdB into cells. These molecules have binding affinities and neutralization IC50’s in the pM range and are compelling candidates for further clinical development. By directly targeting the toxin rather than the pathogen, these molecules have the advantage of immediate cessation of disease and lower selective pressure for escape compared to conventional antibiotics. AsC. difficileinfects the colon, the protease and pH resistance of the designed proteins opens the door to oral delivery of engineered biologics.Significance statementC. difficileinfection (CDI) is a major public health concern with over half a million cases in the United States annually resulting in 30,000 deaths. Current therapies are inadequate and frequently result in cycles of recurrent infection (rCDI). Progress has been made in the development of anti-toxin mAb therapies that can reduce the rate of rCDI, but these remain unaffordable and out of reach for many patients. Using de novo protein design, we developed small protein inhibitors targeting two independent receptor binding sites on the toxin that drives pathology during CDI. These molecules are high affinity, potently neutralizing and stable in simulated intestinal fluid, making them strong candidates for the clinical development of new CDI therapies.
Modulation of blood-tumor barrier transcriptional programs improves intra-tumoral drug delivery and potentiates chemotherapy in GBM
Authors: Jimenez-Macias Jorge L. , Vaughn-Beaucaire Philippa , Bharati Ayush , Xu Zheyun , Forrest Megan , Hong Jason , Sun Michael , Schmidt Andrea , Clark Jasmine , Hawkins William , Mercado Noe , Real Jacqueline , Huntington Kelsey , Zdioruk Mykola , Nowicki Michal O. , Cho Choi-Fong , Wu Bin , Li Weiyi , Logan Theresa , Manz Katherine E. , Pennell Kurt D. , Fedeles Bogdan I. , Brodsky Alexander S. , Lawler Sean E. 
Published: August 2024

AbstractGlioblastoma (GBM) is the most common malignant primary brain tumor. GBM has an extremely poor prognosis and new treatments are badly needed. Efficient drug delivery to GBM is a major obstacle as the blood-brain barrier (BBB) prevents passage of the majority of cancer drugs into the brain. It is also recognized that the blood-brain tumor barrier (BTB) in the growing tumor represents a challenge. The BTB is heterogeneous and poorly characterized, but similar to the BBB it can prevent therapeutics from reaching effective intra-tumoral doses, dramatically hindering their potential. Here, we identified a 12-gene signature associated with the BTB, with functions related to vasculature development, morphogenesis and cell migration. We identified CDH5 as a core molecule in this set and confirmed its over-expression in GBM vasculature using spatial transcriptomics of GBM patient specimens. We found that the indirubin-derivative, 6-bromoindirubin acetoxime (BIA), could downregulate CDH5 and other BTB signature genes, causing endothelial barrier disruption in endothelial monolayers and BBB 3D spheroidsin vitro. Treatment of tumor-bearing mice with BIA enabled increased intra-tumoral accumulation of the BBB non-penetrant chemotherapeutic drug cisplatin and potentiated cisplatin-mediated DNA damage by targeting DNA repair pathways. Finally, using an injectable BIA nanoparticle formulation, PPRX-1701, we significantly improved the efficacy of cisplatin in patient-derived GBM xenografts and prolonged their survival. Overall, our work reveals potential targets at the BTB for improved chemotherapy delivery and the bifunctional properties of BIA as a BTB modulator and potentiator of chemotherapy, supporting its further development.
Blood immunomap for prediction of responses to aPD1 immunotherapy in metastatic non-small cell lung cancer
Authors: Semitekolou Maria , Paschalidis Nikolaos , Lo Tartaro Domenico , Tsitsopoulou Aikaterini , Stamou Panagiota , Mavroudis Alexandros , Markaki Effrosyni , Varveri Athina , Morianos Ioannis , Lavigne Matthieu , Fotsitzoudis Charalampos , Magkouta Sophia , Dede Konstantina , Kalomenidis Ioannis , Samitas Konstantinos , Potaris Konstantinos , Cossarizza Andrea , Mavroudis Dimitrios , De Biasi Sara , Verginis Panayiotis 
Published: August 2024

AbstractImmune checkpoint inhibitor immunotherapy has revolutionized the treatment of non-small cell lung cancer (NSCLC). Despite the immense success, still a significant proportion of patients do not develop durable responses, allowing disease progression accompanied by high mortality rates. Therefore, there is an imperative need for identification of reliable non-invasive predictive biomarkers to guide therapeutic decisions. Herein, we constructed a blood immunomap in NSCLC patients with metastatic disease, using a high-dimensional mass cytometry approach. Assessment of clinical responses to aPD1 immunotherapy revealed, among others, a significant expansion of CD8+PD-L1+T cells in individuals not responding to immunotherapy. Of interest, CD8+PD-L1+T cells were enriched in tumor biopsies and bronchoalveolar lavage of NSCLC individuals at early stages of disease as well as in pleural infusions of individuals with thoracic malignancies. Transcriptomic analysis revealed that CD8+PD-L1+T cells exhibited a regulatory/exhausted phenotype, while various transcripts associated with the overall survival of NSCLC individuals, were mapped. Overall, our findings define an immunomap in the early stage and advanced NSCLC patients and identify immune-related events which may benefit the quest for identification of predictive biomarkers of immunotherapy responses.
Long-Term Impact of Stressful Life Events on Breast Cancer Risk: A 36-Year Genetically Informed Prospective Study in the Finnish Twin Cohort
Authors: Azzi Elissar , Bode Hannes , Palviainen Teemu , Hukkanen Mikaela , Ollikainen Miina , Kaprio Jaakko 
Published: August 2024

ABSTRACTTo investigate potential interactions between stress, genetic predisposition, and breast cancer, we employed a multifaceted approach, analysing polygenic risk scores (PRS), DNA methylation (DNAm) patterns, stressful life events, and breast cancer risk using data from 10342 women in the Finnish Twin Cohort, including 719 breast cancer cases. Stressful life events data was gathered from a 1981 questionnaire while cancer and mortality data were obtained from Finnish Cancer Registry, Finnish Population Register and Statistics Finland. DNAm data from breast cancer discordant twin pairs was used to explore within-pair differences between 212 breast cancer associated CpG sites and stressful life events. A hazard ratio (HR) of 1.05 (95%CI 1.02-1.08) was observed for breast cancer per one-event increase in total stressful life events. Women exposed to over 10 stressful life events exhibited an almost two-fold increase in risk of breast cancer (HR=1.93, 95%CI 1.19-3.14). Stratifying by birth decade revealed a lower HR for those born after 1950 (HR 1.01; 95%CI 0.96-1.06) compared to those born between 1940-1949 (HR 1.07; 95%CI 1.01-1.12). In a subsample with genetic data, no association with breast cancer PRS was seen (HR = 1.03, 95%CI 0.92-1.15 per SD of PRS). Stressful life events exposure associated with breast cancer related DNAm in 42 of the 212 CpG sites. This 36-year genetically informed study highlights the long-term association between stressful life events and breast cancer risk. These findings suggest epigenetic changes, but not polygenic risk may mediate the impact the effects of stressful life events on breast cancer incidence.
Lesion distribution and network mapping in dyskinetic cerebral palsy
Authors: de Almeida Marcelino Ana Luísa , Al-Fatly Bassam , Tuncer Mehmet S. , Krägeloh-Mann Ingeborg , Koy Anne , Kühn Andrea A. 
Published: August 2024

AbstractObjectiveDyskinetic cerebral palsy (DCP) encompasses a group of predominantly perinatally acquired complex motor disorders that present with dystonia and/or choreoathetosis and are frequently associated with brain lesions in neuroimaging. Recently, lesion network mapping provided a tool to redefine neurological disorders as circuitopathies. In this study, we aim to assess lesion distribution in DCP and identify a DCP-related network derived from lesions.MethodsHere, we review the literature of MRI findings in DCP and perform literature-based lesion network mapping (LNM). Imaging findings and their anatomical distribution were extracted from literature and quantified according to an established MRI classification system for cerebral palsy. Whole-brain functional connectivity from lesions causing DCP was calculated using a pediatric resting-state functional MRI connectome. Results were contrasted with two control datasets for spatial specificity.ResultsReview of 48 selected articles revealed that grey matter injury predominated (51%), followed by white matter injury (28%). In 16% of cases MRI was normal. Subcortical lesions affected the thalamus, pallidum and putamen in >40% of reported patients, respectively. Figures available from 23 literature cases were used to calculate DCP-LNM. The LNM revealed functional connectivity to a wide network including the brainstem, cerebellum, basal ganglia, cingulate, and sensorimotor cortices. Strongest connectivity was found for the motor thalamus.InterpretationThe neural network of DCP identified with LNM includes areas previously implicated in hyperkinetic disorders and highlights the motor thalamus as a common network node. The effects of targeting motor thalamic networks with neuromodulation in DCP should be explored in future trials.
Cost-benefit of Influenza Vaccinations in Frontline Workers: A Dynamic Modelling Study
Authors: Mortensen Peter , Gilks William , Kim Selina , Bennett Richard , Linley Matthew 
Published: August 2024

AbstractInfluenza significantly impacts public health, particularly among the elderly and those with underlying health conditions, but it also imposes substantial economic and operational burdens on the working-age population. This study introduces a novel machine learning-based Susceptible-Infected-Recovered (SIR) model solved as an agent-based model (ABM), designed to dynamically simulate influenza spread and assess the cost-benefit of vaccination programs specifically for frontline workers. Unlike traditional models, our approach accounts for the diverse contact rates and risk profiles across different job types, offering a more granular and accurate prediction of influenza’s impact on workforce productivity. We utilised historical influenza data from the CDC and WHO/FluMart to model the effects of varying vaccination coverage levels on infections, sick days, and associated costs within a typical workplace. The results demonstrate that higher vaccination coverage significantly reduces both the total number of infections and the peak sickness levels, leading to substantial cost savings. Additionally, higher vaccination coverage was associated with a significantly lower peak in sickness, mitigating periods of high absenteeism and operational disruptions. The model highlights the economic advantages of vaccination programs, particularly for sectors with higher salaries and absenteeism rates. It also underscores the importance of targeting frontline workers, who have higher contact rates and contribute more significantly to influenza transmission. This model’s ability to capture the dynamic nature of influenza transmission and its differential effects on various work types represents a significant advancement over previous static models. It provides a robust tool for organisations to optimise vaccination strategies, ensuring business continuity and enhancing productivity during influenza seasons.
Developmental origins of the Autism Spectrum Disorder in the Middle East and North Africa Region: A Systematic Review and Meta-Analysis of adjusted risk factors
Authors: Akomolafe Aishat F. , Mahmood Fathima R. , Abdallah Bushra M. , Elshoeibi Amgad M. , Mahmoud Elhassan , Al-Khulaifi Aisha Abdulla , Darwish Nour , Dweidri Yara , Yousif Duaa , Khalid Hafsa , Al-Theyab Majed , Azeem Muhammad Waqar , Shahwar Durre , Kamal Madeeha , Alabdulla Majid , Khaled Salma M. , Chivese Tawanda 
Published: August 2024

AbstractBackground and ObjectivesThe etiology of autism spectrum disorder (ASD) is poorly understood, with sparse data from the Middle East and North Africa (MENA) region, which has a unique climate and socio-epidemiological setting. This research investigated the developmental (early life) risk factors associated with ASD in the MENA region.MethodsIn this systematic review and meta-analysis, we searched for observational studies, which carried out adjusted analyses for ASD risk factors in the MENA region, in PubMed, Embase, Scopus, and CINAHL databases. We analyzed associations between ASD and factors related to conception, inheritance, maternal morbidity during pregnancy and adverse pregnancy outcomes. After study quality assessment, meta-analyses for each risk factor were carried out using the bias-adjusted inverse variance heterogeneity model. Heterogeneity was assessed using I2and publication bias using Doi and funnel plots.ResultsThe systematic review included 19 case control studies from eight countries within the MENA region. In overall synthesis, male sex (OR=3.27, 95% CI: 2.39-4.48, I2 = 40.9%), family history of ASD (OR=2.98, 95% CI: 0.51-17.31, I2 = 85.0%), and consanguinity (OR= 1.77, 95% CI: 1.38-2.28, I2 = 57.1%) were associated with ASD. Although with limited studies, a review of the literature showed some possible associations between ASD and gestational diabetes, gestational hypertension, macrosomia, NICU admission, respiratory distress syndrome, cesarean delivery, gestational age, and older maternal age.ConclusionThese findings confirm the association between male sex, family history of ASD and consanguinity with ASD, potentially suggesting some inherited mechanism in the etiology of ASD in the MENA region. Some maternal co-morbidities during pregnancy and adverse pregnancy outcomes may contribute to ASD risk in the MENA region, although more studies are needed in the region.RegistrationThe protocol for this systematic review and meta-analysis is registered on the International Prospective Register of Systematic Reviews (PROSPERO) with registration ID CRD42024499837.