bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identifying Optimal Neuroinflammation Treatment Using Nanoligomer™ Discovery Engine
Authors: Sharma Sadhana , Borski Curtis , Hanson Jessica , Garcia Micklaus A. , Link Christopher D. , Hoeffer Charles , Chatterjee Anushree , Nagpal Prashant 
Published: August 2022

ABSTRACTAcute activation of innate immune response in the brain, or neuroinflammation, protects this vital organ from a range of external pathogens and promotes healing after traumatic brain injury. However, chronic neuroinflammation leads to the activation of immune cells like microglia and astrocytes causes damage to the nervous tissue, and is causally linked to a range of neurodegenerative diseases such as Alzheimer’s diseases (AD), Multiple Sclerosis (MS), Parkinson’s diseases (PD), and many others. While neuroinflammation is a key target for a range of neuropathological diseases, there is a lack of effective countermeasures to tackle it, and existing experimental therapies require fairly invasive intracerebral and intrathecal delivery due to difficulty associated with the therapeutic crossover between the blood-brain barrier (BBB), making such treatments impractical to treat neuroinflammation long-term. Here, we present the development of an optimal neurotherapeutic using our Nanoligomer™ discovery engine, by screening downregulation of several proinflammatory cytokines (e.g., Interleukin-1β or IL-1β, tumor necrosis factor-alpha or TNF-α, TNF receptor 1 or TNFR1, Interleukin 6 or IL-6), inflammasomes (e.g., NLRP1), key transcription factors (e.g., nuclear factor kappa-B or NF-κβ) and their combinations, as upstream regulators and canonical pathway targets, to identify and validate the best-in-class treatment. Using our high-throughput drug discovery, target validation, and lead molecule identification via a bioinformatics and AI-based ranking method to design sequence-specific peptide molecules to up-or down-regulate gene expression of the targeted gene at will, we used our discovery engine to perturb and identify most effective upstream regulators and canonical pathways for therapeutic intervention to reverse neuroinflammation. The lead neurotherapeutic was a combination of Nanoligomers™ targeted to NF-κβ (SB.201.17D.8_ NF-κβ1) and TNFR1 (SB.201.18D.6_TNFR1), which were identified usingin vitrocell-based screening in donor-derived human astrocytes, and further validatedin vivousing a mouse model of lipopolysaccharide (LPS)-induced neuroinflammation. The combination treatment SB_NI_111 was delivered without any special formulation using a simple intraperitoneal injection of low-dose (5mg/kg) and was found to significantly suppress the expression of LPS-induced neuroinflammation in mouse hippocampus. These results point to the broader applicability of this approach towards the development of therapies for chronic neuroinflammation-linked neurodegenerative diseases, sleep countermeasures, and others, and the potential for further investigation of the lead neurotherapeutic molecule as reversible gene therapy.
Spiders as surrogates of biodiversity in a geothermal area of northern Puebla, México
Authors: Hernández-Salgado Luis Carlos , Romero Guillermo , Rodriguez-Canseco Jesus , Gonzalez-Estupiñan Krystal 
Published: August 2022

AbstractThe word biodiversity has gained popularity for more than 30 years; and we used this term for all aspects of biological diversity, from the richness of taxa, genetic variation, and ecosystem complexity. Thoroughly measuring biodiversity would be impractical due to many existing species and the effort that their identification would represent. Therefore, we need to find suitable surrogates or substitute taxa, which we can monitor because they represent broader biodiversity, helping us in ecological monitoring or conservation program planning. We tested the richness of spiders to measure their ability to estimate total spider richness at a site with geothermal influence. We use data from six locations with geothermal effect in the northern highlands of Puebla, Mexico. The genera richness of spiders was a good substitute for the total species richness, and the opposite happened with the family richness. Therefore, we recommend using this taxonomic level as a substitute to predict spider species richness or to evaluate and classify sites according to their importance for conservation. Here, we present the first spiders biodiversity data of a geothermal area and the use of spiders as surrogates in sites with geothermal condition.
SlowMoMan: A web app for discovery of important features along user-drawn trajectories in 2D embeddings
Authors: Deol Kiran , Weber Griffin M. , Yu Yun William 
Published: August 2022

AbstractNonlinear low-dimensional embeddings allow humans to visualize high-dimensional data, as is often seen in bioinformatics, where data sets may have tens of thousands of dimensions. However, relating the axes of a nonlinear embedding to the original dimensions is a nontrivial problem. In particular, humans may identify patterns or interesting subsections in the embedding, but cannot easily identify what those patterns correspond to in the original data. Thus, we present SlowMoMan (SLOW Motions on MANifolds), a web application which allows the user to draw a 1-dimensional path onto a 2-dimensional embedding. Then, by back-projecting the manifold to the original, high-dimensional space, we sort the original features such that those most discriminative along the manifold are ranked highly. We show a number of pertinent use cases for our tool, including trajectory inference, spatial transcriptomics, and automatic cell classification.Software availabilityhttps://yunwilliamyu.github.io/SlowMoMan/Code availabilityhttps://github.com/yunwilliamyu/SlowMoMan
Exploring masses and internal mass distributions of single carboxysomes in free solution using fluorescence and interferometric scattering in an anti-Brownian trap
Authors: Lavania Abhijit A. , Carpenter William B. , Oltrogge Luke M. , Perez Davis , Borden Julia S. , Savage David F. , Moerner W. E. 
Published: August 2022

AbstractCarboxysomes are self-assembled bacterial microcompartments that facilitate carbon assimilation by co-localizing the enzymes of CO2 fixation within a protein shell. These microcompartments can be highly heterogeneous in their composition and filling, so measuring the mass and loading of an individual carboxysome would allow for better characterization of its assembly and function. To enable detailed and extended characterizations of single nanoparticles in solution, we recently demonstrated an improved Interferometric Scattering Anti-Brownian ELectrokinetic (ISABEL) trap, which tracks the position of a single nanoparticle via its scattering of a near-infrared beam and applies feedback to counteract its Brownian motion. Importantly, the scattering signal can be related to the mass of nanoscale proteinaceous objects, whose refractive indices are well-characterized. We calibrate single-particle scattering cross-section measurements in the ISABEL trap and determine individual carboxysome masses in the 50-400 MDa range by analyzing their scattering cross-sections with a core-shell model. We further investigate carboxysome loading by combining mass measurements with simultaneous fluorescence reporting from labeled internal components. This method may be extended to other biological objects, such as viruses or extracellular vesicles, and can be combined with orthogonal fluorescence reporters to achieve precise physical and chemical characterization of individual nanoscale biological objects.TOC Graphic
New Insights into How JUUL™ Electronic Cigarette Aerosols and Aerosol Constituents Affect SARS-CoV-2 Infection of Human Bronchial Epithelial Cells
Authors: Phandthong Rattapol , Wong Man , Song Ann , Martinez Teresa , Talbot Prue 
Published: August 2022

AbstractBackgroundThe relationship between the use of tobacco products and SARS-CoV-2 infection is poorly understood and controversial. Most studies have been done with tobacco cigarettes, while few have examined the effect of electronic cigarettes (ECs) on SARS-CoV-2 infection. We tested the hypothesis that EC fluids and aerosols with high concentrations of nicotine promote SARS-COV-2 infection by increasing viral entry into human respiratory epithelial cells.MethodsResponses of BEAS-2B cells to authentic JUUL™ aerosols or their individual constituents (propylene glycol (PG)/vegetable glycerin (VG) and nicotine) were compared using three exposure platforms: submerged culture, air-liquid-interface (ALI) exposure in a cloud chamber, and ALI exposure in a Cultex® system, which produces authentic heated EC aerosols. SARS-CoV-2 infection machinery was assessed using immunohistochemistry and Western blotting. Specifically, the levels of the SARS-CoV-2 receptor ACE2 (angiotensin converting enzyme 2) and a spike modifying enzyme, TMPRSS2 (transmembrane serine protease 2), were evaluated. Following each exposure, lentivirus pseudoparticles with spike protein and a green-fluorescent reporter were used to test viral penetration and the susceptibility of BEAS-2B cells to infection.ResultsNicotine, EC fluids, and authentic JUUL™ aerosols increased both ACE2 levels and TMPRSS2 activity, which in turn increased viral particle entry into cells. While most data were in good agreement across the three exposure platforms, cells were more responsive to treatments when exposed at the ALI in the Cultex system, even though the exposures were brief and intermittent. In the Cultex system, PG/VG, PG/VG/nicotine, and JUUL™ aerosols significantly increased infection above clean air controls. However, both the PG/VG and JUUL™ treatments were significantly lower than nicotine/PG/VG. PG/VG increased infection only in the Cultex® system, which produces heated aerosol.ConclusionOur data are consistent with the conclusion that authentic JUUL™ aerosols or their individual constituents (nicotine or PG/VG) increase SARS-CoV-2 infection. The strong effect produced by nicotine was modulated in authentic JUUL aerosols, demonstrating the importance of studying mixtures and aerosols from actual EC products. These data support the idea that vaping increases the likelihood of contracting COVID-19.
Downregulated NPAS4 in multiple brain regions is associated with Major Depressive Disorder
Authors: Selçuk Berkay , Aksu Tuana , Dereli Onur , Adebali Ogun 
Published: August 2022

AbstractMajor Depressive Disorder (MDD) is a commonly observed psychiatric disorder that affects more than 2% of the world population with a rising trend. However, disease-associated pathways and biomarkers are yet to be fully comprehended. In this study, we analyzed previously generated RNA-seq data across seven different brain regions from three distinct studies to identify differentially and co-expressed genes for patients with MDD. Differential gene expression (DGE) analysis revealed that NPAS4 is the only gene downregulated in three different brain regions. Furthermore, co-expressing gene modules responsible for glutamatergic signaling are negatively enriched in these regions. We used the results of both DGE and co-expression analyses to construct a novel MDD-associated pathway. In our model, we propose that disruption in glutamatergic signaling-related pathways might be associated with the downregulation of NPAS4 and many other immediate-early genes (IEGs) that control synaptic plasticity. In addition to DGE analysis, we identified the relative importance of KEGG pathways in discriminating MDD phenotype using a machine learning-based approach. We anticipate that our study will open doors to developing better therapeutic approaches targeting glutamatergic receptors in the treatment of MDD.
Primary postpartum haemorrhage and longer-term physical, psychological, and psychosocial health outcomes for women and their partners: a mixed-methods systematic review
Authors: Latt Su Mon , Alderdice Fiona , Elkington Madeline , Shar Mahkawnghta Awng , Kurinczuk Jennifer J , Rowe Rachel 
Published: August 2022

AbstractObjectivesMost research about outcomes following postpartum haemorrhage (PPH) has focused on immediate outcomes. There are fewer studies investigating longer-term maternal morbidity following PPH, resulting in a significant knowledge gap. This review aimed to synthesize the evidence about the longer-term physical and psychological consequences of primary PPH for women and their partners from high income settings.MethodsThe review was registered with PROSPERO and five electronic databases were searched. Studies were independently screened against the eligibility criteria by two reviewers and data were extracted from both quantitative and qualitative studies that reported non-immediate health outcomes of primary PPH.ResultsData were included from 24 studies, of which 16 were quantitative, five were qualitative and three used mixed-methods. The included studies were of mixed methodological quality. Of the nine studies reporting outcomes beyond five years after birth, only two quantitative studies and one qualitative study had a follow-up period longer than ten years. Seven studies reported outcomes or experiences for partners. The evidence indicated that women with PPH were more likely to have persistent physical and psychological health problems after birth compared with women who did not have a PPH. These problems, including PTSD symptoms and cardiovascular disease, may be severe and extend for many years after birth and were more pronounced after a severe PPH, as indicated by a blood transfusion or hysterectomy. There was limited evidence about outcomes for partners after PPH, but conflicting evidence of association between PTSD and PPH among partners who witnessed PPH.ConclusionThis review explored existing evidence about longer-term physical and psychological health outcomes among women who had a primary PPH in high income countries, and their partners. While the evidence about health outcomes beyond five years after PPH is limited, our findings indicate that women can experience long lasting negative impacts after primary PPH, including PTSD symptoms and cardiovascular disease, extending for many years after birth.PROSPERO registration numberCRD42020161144
Optimal Respiratory Syncytial Virus intervention programmes using Nirsevimab in England and Wales
Authors: Hodgson David , Koltai Mihaly , Krauer Fabienne , Flasche Stefan , Jit Mark , Atkins Katherine E. 
Published: August 2022

AbstractIntroductionRespiratory Syncytial Virus (RSV) is a major cause of acute lower respiratory tract infections (ALRI) in infants. There are no licensed vaccines and only one monoclonal antibody available to protect infants from disease. A new and potentially longer-lasting monoclonal antibody, Nirsevimab, showed promising results in phase IIb/III trials. We evaluate the cost-effectiveness of Nirsevimab intervention programmes in England and WalesMethodsWe used a dynamic model for RSV transmission, calibrated to data from England and Wales. We considered a suite of potential Nirsevimab programmes, including administration to all neonates (year-round); only neonates born during the RSV season (seasonal); or neonates born during the RSV season plus infants less than six months old before the start of the RSV season (seasonal + catch-up).ResultsIf administered seasonally to all infants at birth, we found that Nirsevimab would have to be priced less than £63 per dose for at least 50% certainty that it could cost-effectively replace the current Palivizumab programme, using an ICER threshold of £20,000/QALY. An extended seasonal programme which includes a pre-season catch-up becomes the optimal strategy below a £34/dose purchasing price for at least 50% certainty. At a purchasing price per dose of £5-32, the annual implementation costs of a seasonal programme could be as high as £2 million before a switch to a year-round strategy would be optimal.DiscussionNirsevimab has the potential to be cost-effective in England and Wales not only for use in high-risk infants.
Dynamics of anti-S IgG antibodies titers after the second dose of COVID 19 mRNA and non-mRNA vaccines in the manual and craft worker population of Qatar
Authors: Bansal Devendra , Atia Hassan , Badr Mashael Al , Nour Mohamed , Abdulmajeed Jazeel , Hasan Amal , Al-Hajri Noora , Ahmed Lina , Ibrahim Rumissa , Zamel Reham , Mohamed Almuthana , Pattalaparambil Hamad , Daraan Faisal , Chaudhry Adil , Oraby Sahar , El-Saleh Sahar , El-Shafie Sittana S , Al-Farsi Affra Faiz , Paul Jiji , Ismail Ahmed , Al-Romaihi Hamad E. , Al-Thani Mohammed H , Doi Suhail A.R. , Zughaier Susu M , Cyprian Farhan , Farag Elmobashar , Farooqui Habib Hasan 
Published: August 2022

AbstractBackgroundThere is limited seroepidemiological evidence on the magnitude and long-term durability of antibody titers of mRNA and non-mRNA vaccines in the Qatari population. This study was conducted to generate evidence on long-term anti-S IgG antibodies titers and their dynamics in individuals who have completed a primary COVID-19 vaccination schedule.MethodsA total of 300 participants who received any of the following vaccines BNT162b2/Comirnaty or mRNA-1273 or ChAdOx1-S/Covishield or COVID-19 Vaccine Janssen/Johnson or BBIBP-CorV or Covaxin were enrolled in our study. All sera samples were tested by chemiluminescent microparticle immunoassay (CMIA) for the quantitative determination of IgG antibodies to SARS-CoV-2, receptor-binding domain (RBD) of the S1 subunit of the spike protein of SARS-CoV-2. Antibodies against SARS-CoV-2 nucleocapsid (SARS-CoV-2 N-protein IgG) were also determined. Kaplan–Meier survival curves were used to compare the time from the last dose of the primary vaccination schedule to the time by which anti-S IgG antibodies titers fell into the lowest quartile (range of values collected) for the mRNA and non-mRNA vaccines.ResultsParticipants vaccinated with mRNA vaccines had higher median anti-S IgG antibody titers. Participants vaccinated with the mRNA-1273 vaccine had the highest median anti-S-antibody level of 13720.9 AU/mL (IQR 6426.5 to 30185.6 AU/mL) followed by BNT162b2 (median, 7570.9 AU/ml; IQR, 3757.9 to 16577.4 AU/mL); while the median anti-S antibody titer for non-mRNA vaccinated participants was 3759.7 AU/mL (IQR, 2059.7-5693.5 AU/mL). The median time to reach the lowest quartile was 3.53 months (IQR, 2.2-4.5 months) and 7.63 months (IQR, 6.3-8.4 months) for the non-mRNA vaccine recipients and Pfizer vaccine recipients, respectively. However, more than 50% of the Moderna vaccine recipients did not reach the lowest quartile by the end of the follow-up period.ConclusionsThis evidence on anti-S IgG antibody titers, their durability and decay over time should be considered for the utility of these assays in transmission dynamics after the full course of primary vaccination.
An idiosyncratic, zonated stroma encapsulates desmoplastic liver metastases and originates from injured liver
Authors: Fernández Moro Carlos , Harrizi Sara , Hamidi Yousra , Geyer Natalie , Kuznyecov Danyil , Tidholm-Qvist Evelina , Salmonson Schaad Media , del Valle Andrea C. , Söderqvist Sara , Bozóky Lorand , Sparrelid Ernesto , Dirix Luc , Vermeulen Peter B , Bozóky Béla , Engstrand Jennie , Gerling Marco 
Published: August 2022

AbstractColorectal cancer liver metastases (CRLM) grow in two major patterns defined by the histomorphology of the invasion front, replacement or desmoplastic. The desmoplastic pattern, in which a stromal rim separates tumor cells and liver parenchyma is a strong positive prognostic factor, implying favorable biological features. However, the origin of the perimetastatic stroma is unknown and the underlying biological mechanisms are unclear. Here, we created spatial growth pattern maps of resected CRLM at cell-level resolution using digital pathology and quantified growth pattern heterogeneity at unprecedented resolution. We manually generated > 60’ 000 individual digital annotations on 543 metastases from 263 consecutive patients. We found that, in contrast to standard growth pattern assessments, high-resolution scoring revealed the prognostic outcome to be dependent on growth pattern proportions, such that survival improved with increasing fractions of desmoplastic encapsulation. The desmoplastic pattern was coupled to decreased tumor viability and to preoperative chemotherapy, hinting at a potentially causative connection of tumor viability and fibrotic encapsulation. Analyses of the cellular constituents of the rim revealed previously unrecognized liver parenchymal remnants. Spatial quantitation of liver remnants in the rim uncovered its gradual zonation from benign-like fibrosis at the liver side to tumor-associated stroma at the metastasis edge. Together, our data suggest that the perimetatstic “desmoplastic” capsule primarily results from a reparative hepatic process in conjunction with inefficient tumor cell colonization of liver plates, rather than from actively induced desmoplasia. We posit a model in which efficient replacement-type growth that precludes a mature hepatic injury reaction determines prognosis. Our results underscore tumor-cell replacement of hepatocytes as key for liver metastatic progression and suggest that the spatial heterogeneity of tumor invasion can be leveraged to understand fundamental mechanisms of metastatic growth.
Aberrant oscillatory activity in Neurofibromatosis Type 1: An EEG study of resting state and working memory
Authors: Booth Samantha J. , Garg Shruti , Brown Laura J. E. , Green Jonathan , Pobric Gorana , Taylor Jason R. 
Published: August 2022

AbstractBackgroundNeurofibromatosis Type 1 (NF1) is a genetic neurodevelopmental disorder commonly associated with impaired cognitive function. Despite the well-explored functional roles of neural oscillations in neurotypical populations, only a limited number of studies have investigated oscillatory activity in the NF1 population.MethodsWe compared oscillatory spectral power and theta phase coherence in a paediatric sample with NF1 (N=16; mean age: 13.03 years; female: n=7) to an age/sex-matched typically-developing control group (N=16; mean age: 13.34 years; female: n=7) using electroencephalography measured during rest and during working memory task performance.ResultsRelative to typically-developing children, the NF1 group displayed higher resting state slow wave power and a lower peak alpha frequency. Moreover, higher theta power and frontoparietal theta phase coherence were observed in the NF1 group during working memory task performance, but these differences disappeared when controlling for baseline (resting state) activity.ConclusionsOverall, results suggest that NF1 is characterised by aberrant resting state oscillatory activity that may contribute towards the cognitive impairments experienced in this population.Trial registrationClinicalTrials.gov identifier: NCT03310996 (first posted: October 16 2017).