bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mapping Climate Change’s Impact on Cholera Infection Risk in Bangladesh
Authors: Kruger Sophia E. , Lorah Paul A. , Okamoto Kenichi W. 
Published: June 2022

AbstractSeveral studies have investigated howVibrio choleraeinfection risk changes with increased rainfall, temperature, and water pH levels for coastal Bangladesh, which experiences seasonal surges in cholera infections associated with heavy rainfall events. While coastal environmental conditions are understood to influenceV. choleraepropagation within brackish waters and transmission to and within human populations, it remains unknown how changing climate regimes impact the risk for cholera infection throughout Bangladesh. To address this, we developed a random forest species distribution model to predict the occurrence probability of cholera incidence within Bangladesh for 2015 and 2050. Using R, our random forest model was trained on cholera incidence data and spatial environmental raster data at a resolution of 250 square meters. This model was then predicted to environmental data for the training data year (2015) and for 2050. We interfaced R with ArcGIS to develop risk maps for cholera infection for the years 2015 and 2050, proxying infection risk with cholera occurrence probability predicted by the model. The best-fitting model predicted cholera occurrence given elevation and distance to water. We find that although cells of high risk cluster along the coastline predominantly in 2015, by 2050 high-risk areas expand from the coast to inland Bangladesh with all but the northwestern district of Rangpur seeing increased clusters around surface water. Mapping the geographic distribution of cholera infections given projected environmental conditions provides a valuable tool for guiding proactive public health policy tailored to areas most at risk of future disease outbreaks.
Structure-based discovery of a novel small-molecule inhibitor of TEAD palmitoylation with anticancer activity
Authors: Gridnev Artem , Maity Subhajit , Misra Jyoti R. 
Published: June 2022

ABSTRACTThe paralogous oncogenic transcriptional coactivators YAP and TAZ are the distal effectors of the Hippo signaling pathway, which play a critical role in cell proliferation, survival and cell fate specification. The core kinase cascade of the Hippo signaling pathway phosphorylates YAP/TAZ and restrict its activity by promoting cytoplasmic sequestration and degradation. Unphosphorylated YAP/TAZ translocates into the nucleus and associates with the TEA domain (TEAD1-4) transcription factors to regulate their target genes. They are frequently misregulated in most human cancers, where they contribute to multiple aspects of tumorigenesis including growth, metabolism, metastasis and chemo/immunotherapy resistance. Thus, they provide a critical point for therapeutic intervention. However, due to their intrinsically disordered structure, they are challenging to target directly. Since YAP/TAZ exerts oncogenic activity by associating with the TEAD1-4 transcription factors, to regulate target gene expression, YAP activity can be controlled indirectly by regulating TEAD1-4. Interestingly, TEADs undergo autopalmitoylation, which is essential for their stability and function. The palmitic acid occupies a hydrophobic pocket in TEAD1-4, and small-molecule inhibitors that bind to this site can render them unstable, and allosterically inhibit their interaction with YAP/TAZ and chromatin. Here we combined structure-based virtual ligand screening with biochemical and cell biological studies and identified a novel small-molecule that inhibits TEAD palmitoylation and stability. Further, it affects YAP-TEAD interaction and inhibits YAP transcriptional activity and impairs proliferation, colony formation and migration of breast and ovarian cancer cells.
Performance estimation of two in-house ELISA assays for COVID-19 surveillance through the combined detection of anti-SARS-CoV-2 IgA, IgM, and IgG immunoglobulin isotypes
Authors: Ramírez-Reveco Alfredo , Velázquez Gerardo , Aros Christopher , Navarrete Gabriela , Villarroel-Espindola Franz , Navarrete Maritza , Fica Alberto , Plaza Anita , Castro Natalia , Verdugo Claudio , Acosta-Jamett Gerardo , Verdugo Cristóbal 
Published: June 2022

ABSTRACTThe main objective of this study was to estimate the performance, under local epidemiological conditions, of two in-house ELISA assays for the combined detection of anti-SARS-CoV-2 IgA, IgM, and IgG immunoglobulins. A total of 94 serum samples were used for the assessment, where 44 corresponded to sera collected before the pandemic (free SARS-CoV-2 antibodies), and 50 sera were collected from confirmed COVID-19 patients admitted to the main public hospital in the city of Valdivia, southern Chile. The Np and RBD proteins were separately used as antigens (Np and RBD ELISA, respectively) to assess their diagnostic performance. A receiver operating characteristic (ROC) analysis was performed to estimate the optical density (OD) cut-off that maximized the sensitivity (Se) and specificity (Sp) of the ELISA assays. Np ELISA had a mean Se of 94% (95% CI = 83.5 – 98.8%) and a mean Sp of 100% (95% CI = 92.0 – 100%), with an OD 450 nm positive cut-off value of 0.88. On the other hand, RBD ELISA presented a mean Se of 96% (95% CI = 86.3 – 99.5%) and a mean Sp of 90% (95% CI = 78.3 – 97.5%), with an OD 450 nm positive cut off value of 0.996. Non-significant differences were observed between the Se distributions of Np and RBD ELISAs, but the latter presented a significant lower Sp than Np ELISA. In parallel, collected sera were also analyzed using a commercial lateral flow chromatographic immunoassay (LFCI), to compare the performance of the in-house ELISA assays against a commercial test. The LFCI had a mean sensitivity of 94% (95% CI = 87.4 – 100%) and a mean specificity of 100% (95% CI = 100 – 100%). When compared to Np ELISA, non-significant differences were observed on the performance distributions. Conversely, RBD ELISA had a significant lower Sp than the LFCI. Although, Np ELISA presented a similar performance than the commercial test, this was 2.5 times cheaper than the LFCI assay. Thus, the in-house Np ELISA could be a suitable alternative tool, in resource limited environments, for the surveillance of SARS-CoV-2 infection, supporting further epidemiological studies.
Genome wide association neural networks (GWANN) identify genes linked to family history of Alzheimer’s disease
Authors: Ghose Upamanyu , Sproviero William , Winchester Laura , Amin Najaf , Zhu Taiyu , Newby Danielle , Ulm Brittany S. , Papathanasiou Angeliki , Shi Liu , Liu Qiang , Fernandes Marco , Adams Cassandra , Albukhari Ashwag , Almansouri Majid , Choudhry Hani , van Duijn Cornelia , Nevado-Holgado Alejo 
Published: June 2022

SummaryAugmenting traditional genome wide association studies (GWAS) with advanced machine learning algorithms can allow the detection of novel signals in available cohorts. We introduce “Genome wide association neural networks (GWANN)”, a novel approach that uses neural networks (NNs) to perform a gene-level association study with family history of Alzheimer’s disease (AD). In UK Biobank, we defined cases (n=42,110) as those with AD or family history of AD and sampled an equal number of controls. The data was split into an 80:20 ratio of training and testing samples, and GWANN was trained on the former followed by identifying associated genes using its performance on the latter. Our method identified 18 genes to be associated with family history of AD.APOE,BIN1, SORL1, ADAM10, APH1B,andSPI1have also been identified by previous AD GWAS.PCDH9, NGR3, ROR1, LINGO2, SMYD3,andLRRC7were among the new genes that have been previously associated with neurofibrillary tangles or phosphorylated tau. Furthermore, there is evidence for differential transcriptomic or proteomic expression between AD and healthy brains for 11 of the 12 new genes. A series of post-hoc analyses resulted in a significantly enriched protein-protein interaction network (P-value<1×10−16), and enrichment of relevant disease and biological pathways such as focal adhesion (P-value=1×10−4), extracellular matrix organisation (P-value=1×10−4), Hippo signalling (P-value=7×10−4), Alzheimer’s disease (P-value=3×10−4), impaired cognition (P-value=4×10−3), and autism spectrum disorders (P-value=1×10−2). Applying NNs for GWAS illustrates their potential to complement existing algorithms and methods and enable the discovery of new associations without the need to expand existing cohorts.
Evaluation of immunological responses to third COVID-19 vaccine among people treated with sphingosine receptor-1 modulators and anti-CD20 therapy
Authors: Sand Ilana Katz , Gnjatic Sacha , Krammer Florian , Tuballes Kevin , Carreño Juan Manuel , Satyanarayan Sammita , Filomena Susan , Staker Erin , Tcheou Johnstone , Miller Aaron , Fabian Michelle , Safi Neha , Nichols Jamie , Patel Jasmin , Krieger Stephen , Tankou Stephanie , Horng Sam , Klineova Sylvia , Beck Erin , Merad Miriam , Lublin Fred 
Published: June 2022

AbstractImportancePeople living with multiple sclerosis (MS) and other disorders treated with immunomodulatory therapies remain concerned about suboptimal responses to coronavirus disease 2019 (COVID-19) vaccines. Important questions persist regarding immunological response to third vaccines, particularly with respect to newer virus variants.ObjectiveEvaluate humoral and cellular immune responses to third COVID-19 vaccine dose in people on anti-CD20 therapy and sphingosine 1-phosphate receptor (S1PR) modulators, including Omicron-specific assays.DesignObservational study evaluating immunological response to third COVID-19 vaccine dose in volunteers treated with anti-CD20 agents, S1PR modulators, and healthy controls. Neutralizing antibodies against USA-WA1/2020 (WA1) and B.1.1.529 (BA.1) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were measured before and after third vaccine. Cellular responses to spike peptide pools generated from WA1 and BA.1 were evaluated.SettingMount Sinai HospitalParticipantsPeople treated with anti-CD20 therapy or S1PR modulators and healthy volunteersExposureTreatment with anti-CD20 therapy, S1PR modulator, or neitherMain outcomes and measuresSerum neutralizing antibodies and ex vivo T cell responses against SARS-CoV-2 antigens.ResultsThis cohort includes 25 participants on anti-CD20 therapy, 12 on S1PR modulators, and 14 healthy controls. Among those on anti-CD20 therapy, neutralizing antibodies to WA1 were significantly reduced compared to healthy controls (ID50% GM post-vaccination of 8.1 ± 2.8 in anti-CD20 therapy group vs 452.6 ± 8.442 healthy controls, P<0.0001) and neutralizing antibodies to BA.1 were below the threshold of detection nearly universally. However, cellular responses, including to Omicron-specific peptides, were not significantly different from controls. Among those on S1PR modulators, neutralizing antibodies to WA1 were detected in a minority, and only 3/12 had neutralizing antibodies just at the limit of detection to BA.1. Cellular responses to Spike antigen in those on S1PR modulators were reduced by a factor of 100 compared to controls (median 0.0008% vs. 0.08%, p<0.001) and were not significantly “boosted” by a third injection.Conclusions and RelevanceParticipants on immunomodulators had impaired antibody neutralization capacity, particularly to BA.1, even after a third vaccine. T cell responses were not affected by anti-CD20 therapies, but were nearly abrogated by S1PR modulators. These results have clinical implications warranting further study.
Platelet findings in 22q11.2 Deletion Syndrome correlate with disease manifestations but do not correlate with GP1b surface expression
Authors: Campbell Ian M. , Crowley T. Blaine , Jobaliya Chintan , Bailey Alice , McGinn Daniel E. , Gaiser Kimberly , Bassett Anne , Gur Raquel E. , Morrow Bernice , Emanuel Beverly S. , Franco Aime T. , French Deborah , Zackai Elaine H. , McDonald-McGinn Donna M. , Lambert Michele P. 
Published: June 2022

AbstractPrior studies have demonstrated that patients with chromosome 22q11.2 deletion syndrome (22q11.2DS) have lower platelet counts (PC) compared to non-deleted populations. They also have an increased mean platelet volume. The mechanism for this has been postulated to be haploinsufficiency of the GPIBB gene. We examined platelet parameters, deletion size and factors known to influence counts, including status of thyroid hormone and CHD, in a population of 825 patients with 22q11.2DS. We also measured surface expression of GPIB-IX complex by flow cytometry. The major determinant of PC was deletion status of GP1BB, regardless of surface expression or other factors. Patients with nested distal chromosome 22q11.2 deletions (those with GP1BB present) had higher PCs than those with proximal deletions where GP1BB is deleted. Patients with 22q11.2DS also demonstrated an accelerated PC decrease with age, occurring in childhood. These data demonstrate that genes within the proximal deletion segment drive PC differences in 22q11.2DS and suggest that PC reference ranges may need to be adjusted for age and deletion size in 22q11.2DS populations. Bleeding did not correlate with either platelet count or GP1b expression. Further studies into drivers of expression of GP1b and associations with severe thrombocytopenia and immune thrombocytopenia are needed to inform clinical care.
Microfluidics-free single-cell genomics with templated emulsification
Authors: Clark Iain C. , Fontanez Kristina M. , Meltzer Robert H. , Xue Yi , Hayford Corey , May-Zhang Aaron , D’Amato Chris , Osman Ahmad , Zhang Jesse Q. , Hettige Pabodha , Ishibashi Jacob S.A. , Delley Cyrille L. , Weisgerber Daniel W. , Replogle Joseph M. , Jost Marco , Phong Kiet T. , Kennedy Vanessa E. , Peretz Cheryl A. C. , Kim Esther A. , Song Siyou , Karlon William , Weissman Jonathan S. , Smith Catherine C. , Gartner Zev J. , Abate Adam R. 
Published: June 2022

AbstractSingle-cell RNA sequencing is now a standard method used to reveal the molecular details of cellular heterogeneity, but current approaches have limitations on speed, scale, and ease of use that stem from the complex microfluidic devices or fluid handling steps required for sample processing. We, therefore, developed a method that does not require specialized microfluidic devices, expertise, or hardware. Our approach is based on particle-templated emulsification, which allows single-cell encapsulation and barcoding of cDNA in uniform droplet emulsions with only a vortexer. PIP-seq accommodates a wide range of emulsification formats, including microwell plates and large-volume conical tubes, enabling thousands of samples or millions of cells to be processed in minutes. We demonstrate that PIP-seq produces high-purity transcriptomes in mouse-human mixing studies, is compatible with multi-omics measurements, and can accurately characterize cell types in human breast tissue when compared to a commercial microfluidic platform. Single-cell transcriptional profiling of mixed phenotype acute leukemia using PIP-seq revealed the emergence of heterogeneity within chemotherapy-resistant cell subsets that were hidden by standard immunophenotyping. PIP-seq is a simple, flexible, and scalable next-generation workflow that extends single-cell sequencing to new applications, including screening, diagnostics, and disease monitoring.
Aberrant MNX1 Expression Associated with t(7;12)(q36;p13) Pediatric Acute Myeloid Leukemia Induces the Disease Through Altering Histone Methylation
Authors: Waraky Ahmed , Östlund Anders , Nilsson Tina , Weichenhan Dieter , Lutsik Pavlo , Bähr Marion , Hey Joschka , Adamsson Jenni , Abdelrazak Morsy Mohammad Hamdy , Li Susann , Fogelstrand Linda , Plass Christoph , Palmqvist Lars 
Published: June 2022

ABSTRACTCertain subtypes of acute myeloid leukemia (AML) in children have inferior outcome. One of these has a translocation t(7;12)(q36;p13) leading to aMNX1::ETV6fusion along with high expression of MNX1. Here we identified the transforming event in this AML and possible ways of treatment. Only MNX1 was able to induce AML in mice, with similar gene expression and pathway enrichment to t(7;12) AML patient data. Importantly, this leukemia was only induced in immune incompetent mice using fetal but not adult hematopoietic stem and progenitor cells. The restriction in transforming capacity to cells from fetal liver is in alignment with t(7;12)(q36;p13) AML being mostly seen in infants. Expression of MNX1 led to increased histone 3 lysine 4 mono-, di- and trimethylation, reduction in H3K27me3, accompanied with changes in genome-wide chromatin accessibility and genome expression, likely mediated through MNX1 interaction with the methionine cycle and methyltransferases. MNX1 expression increased DNA damage, depletion of the Lin-/Sca1+/c-Kit+ population and skewing toward the myeloid lineage. These effects, together with leukemia development, was prevented by pretreatment with the S-adenosylmethionine analog Sinefungin. In conclusion, we have shown the importance of MNX1 in development of AML with t(7;12), supporting a rationale for targeting MNX1 and downstream pathways.
Assessing COVID-19 vaccination strategies in varied demographics using an individual-based model
Authors: Ben-Zuk Noam , Daon Yair , Sasson Amit , Ben-Adi Dror , Huppert Amit , Nevo Daniel , Obolski Uri 
Published: June 2022

AbstractBackgroundNew variants of SARS-CoV-2 are constantly discovered. Administration of COVID-19 vaccines and booster doses, combined with applications of non-pharmaceutical interventions (NPIs), is often used to prevent outbreaks of emerging variants. Such outbreak dynamics are further complicated by the population’s behavior and demographic composition. Hence, realistic simulations are needed to estimate the efficiency of proposed vaccination strategies in conjunction with NPIs.MethodsWe developed an individual-based model of COVID-19 dynamics that considers age-dependent parameters such as contact matrices, probabilities of symptomatic and severe disease, and households’ age distribution. As a case study, we simulate outbreak dynamics under the demographic compositions of two Israeli cities with different household sizes and age distributions. We compare two vaccination strategies: vaccinate individuals in a currently prioritized age group, or dynamically prioritize neighborhoods with a high estimated reproductive number. Total infections and hospitalizations are used to compare the efficiency of the vaccination strategies under the two demographic structures, in conjunction with different NPIs.ResultsWe demonstrate the effectiveness of vaccination strategies targeting highly infected localities and of NPIs actively detecting asymptomatic infections. We further show that there are different optimal vaccination strategies for each demographic composition of sub-populations, and that their application is superior to a uniformly applied strategy.ConclusionOur study emphasizes the importance of tailoring vaccination strategies to subpopulations’ infection rates and to the unique characteristics of their demographics (e.g., household size and age distributions). The presented simulation framework and our findings can help better design future responses against the following emerging variants.
Association between perinatal mental health and reproductive and neonatal complications: a retrospective birth cohort study
Authors: Runkle Jennifer D. , Risley Kendra , Roy Manan , Sugg Maggie M. 
Published: June 2022

AbstractBackgroundMaternal mental health as an important precursor to reproductive and neonatal complications remains understudied in the US, particularly in the Southeastern region, despite high medical costs and maternal morbidity, and infant burden.ObjectiveThis study sought to estimate the incidence of perinatal mental health disorders and the associated increased risk of leading pregnancy and infant complications.MethodsA population-based retrospective birth cohort of delivery hospitalizations and readmissions was constructed for birthing populations in South Carolina, 1999 to 2017. Prevalence rates were calculated for perinatal mood and anxiety disorders (PMAD), severe mental illness (SMI), and maternal mental disorders of pregnancy (MDP). Poisson regression models using generalized estimating equations were used to estimate adjusted relative risks for the association between mental health conditions and severe maternal morbidity (SMM), hypertensive disorders of pregnancy (HDP), gestational diabetes (GD), cesarean delivery (CD), preterm birth (PTB), and low-birth weight (LBW).ResultsThe most prevalent maternal mental condition was MDP (3.9%), followed by PMAD (2.7%) and SMI (0.13%). PMAD was associated with a higher risk of SMM, HDP, and CD, as well as a higher risk of PTB and LBW infants. SMI was associated with LBW, HDP, and CD. Pregnant populations with MDP were more at risk for SMM, PTB, HDP, LBW, and CD. Each maternal mental health outcome was associated with an elevated risk for hospital readmissions up to 45 days after delivery.DiscussionResults demonstrated the escalating burden of PMAD and MDP for pregnant populations over time with important consequences related to maternal and infant morbidity.
Experimental and In Silico interaction studies of Alpha Amylase-Silver nanoparticle: a nano-bio-conjugate
Authors: Verma Awadhesh Kumar , Mishra Abhijeet , Dhiman Tarun Kumar , Sardar Meryam , Solanki Pratima R. 
Published: June 2022

AbstractIn the current work, biosynthesis of silver nanoparticle (Ag NPs) and interaction study between alpha amylase and Ag NPs/nanocluster has been performed via wet-lab as well as in silico approach. We have synthesized Ag NPs using alpha amylase enzyme which reduces the silver nitrate precursor forming the stable Ag NPs. UV-Visible spectroscopy and fluorescence spectroscopies were performed for optical characterization of Ag NPs. UV-Vis spectra showed the wide absorption band centered around 475 nm due to surface plasmon resonance. We have also observed gradual decrease in fluorescence intensity with the increase in incubation time. Also, shift in λmax of the emission spectra was recorded which clearly suggested the formation of nano-bio-conjugate. Circular dichroism spectra show the initial decrease in the ellipticity, when we added the silver nitrate, but after incubating for different time, there are no major changes in secondary structure of protein. In computational study we have modelled ground state configuration of (Ag)24 nanocluster using in silico approach. Further docking of the modelled optimized nanocluster with alpha amylase was performed and found that Ag-nanocluster showing non-covalent interaction with alpha amylase and forming stable docking complex.
A Conservative Approach for Describing Cancer Progression
Authors: Rossi Nicolò , Gigante Nicola , Vitacolonna Nicola , Piazza Carla 
Published: June 2022

AbstractThe field of tumor phylogenetics focuses on studying the differences within cancer cell populations and many efforts are done within the scientific community to build cancer progression models trying to understand the heterogeneity of such diseases. These models are highly dependent on the kind of data used for their construction and, as the experimental technologies evolve, it is of major importance to exploit their peculiarities. In this work we describe a cancer progression model based on Single Cell DNA Sequencing data. When constructing the model, we focus on tailoring the formalism on the specificity of the data, by defining a minimal set of assumptions to reconstruct a flexible DAG structured model, capable of identifying progression beyond the limitation of the infinite site assumption. We provide simulations and analytical results to show the features of our model, test it on real data, show how it can be integrated with other approaches to cope with input noise. Moreover, our framework can be exploited to produce simulated data that follows our theoretical assumptions. Finally, we provide an open source R implementation of our approach that is publicly available on BioConductor.