bluuebunny/crossref_metadata_2025_split huggingface dataset:
A multi-centre observational study of HIV, tuberculosis and risk of chronic lung disease in urban West Africa
Authors: Fink Douglas L. , Oladele David A. , Slack Abigail J. , Odubela Oluwatosin , Musari-Martins Tomilola , Okechukwu Adaobi , Adetayo Kemi , Opaneye Sola , Abubakar Rufai , David Agatha , Cai James , Quaderi Shumonta , Abubakar Ibrahim , Ezechi Oliver , Hurst John R. , Lipman Marc , Salako Babatunde 
Published: August 2022

Objective:
HIV and tuberculosis (TB) are risk factors for non-communicable chronic lung disease (CLD). Despite the high prevalence of these infections in West Africa, there are no studies that compare CLD between people with HIV and HIV-negative populations in this setting. This study sought to quantify the contribution of HIV and TB infection in addition to conventional CLD risk factors, such as tobacco and biofuel exposure, to CLD in urban West Africa.

Design:
A multi-centre cross-sectional study was conducted in three community clinics in Lagos, Nigeria between 2018 and 2019.

Methods:
Spirometry, questionnaires and clinical records were used to estimate prevalence of CLD and association with risk factors.

Results:
In total, 148 HIV-negative individuals and 170 HIV-positive individuals completed the study. Current cigarette (11 of 318, 3.5%) and lifetime domestic biofuel (6 of 318, 1.8%) exposures were low. Airway obstruction (33 of 170, 19.4% vs. 12 of 148, 8.1%, P = 0.004) and CLD (73 of 170, 42.9% vs. 34 of 148, 23%, P < 0.0001) were more prevalent in people with HIV compared with the HIV-negative group. HIV infection [odds ratio 2.35 (1.33, 4.17), P = 0.003] and history of TB [odds ratio 2.09 (1.04, 4.20), P = 0.038] were independently associated with increased risk of CLD.

Conclusion:
HIV and TB far outweigh conventional risk factors, including tobacco and domestic biofuel exposure, as drivers of non-communicable CLD in urban West Africa. Current global policy for CLD may have limited impact on CLD in this setting. Enhanced prevention, diagnosis and management strategies for incident HIV and TB infections are likely to have a significant impact on long-term lung health in sub-Saharan Africa.
Accurate 3D Positron Range Correction Method for Heterogeneous Material Densities in PET
Authors: Li Chong , Scheins Jürgen , Tellmann Lutz , Issa Ahlam , Wei Long , Shah N. Jon , Lerche Christoph 
Published: August 2022

AbstractObjectiveThe positron range is a fundamental, detector-independent physical limitation to special resolution in positron emission tomography (PET) as it causes a significant blurring of the reconstructed PET images. A major challenge for positron range correction methods is to provide accurate range kernels that inherently incorporate the generally inhomogeneous stopping power, especially at tissue boundaries. In this work, we propose a novel approach to generate accurate three-dimensional (3-D) blurring kernels both in homogenous and heterogeneous media to improve PET spatial resolution.ApproachIn the proposed approach, positron energy deposition was approximately tracked along straight paths, depending on the positron stopping power of the underlying material. The positron stopping power was derived from the attenuation coefficient of 511keV gamma photons according to the available PET attenuation maps. Thus, the history of energy deposition is taken into account within the range of kernels. Special emphasis was placed on facilitating the very fast computation of the positron annihilation probability in each voxel.ResultsPositron path distributions of 18F in low-density polyurethane were in high agreement with Geant4 simulation at an annihilation probability larger than 10−2∼10−3 of the maximum annihilation probability. The Geant4 simulation was further validated with measured 18F depth profiles in these polyurethane phantoms. The tissue boundary of water with cortical bone and lung was correctly modeled. Residual artifacts from the numerical computations were in the range of 1%. The calculated annihilation probability in voxels shows an overall difference of less than 20% compared to the Geant4 simulation.SignificanceThe proposed method significantly improves spatial resolution for non-standard isotopes by providing accurate range kernels, even in the case of significant tissue inhomogeneities.
Attention Deficit Hyperactivity Disorder and the gut microbiome: An ecological perspective
Authors: Cickovski Trevor , Mathee Kalai , Aguirre Gloria , Tatke Gorakh , Hermida Alejandro , Narasimhan Giri , Stollstorff Melanie 
Published: August 2022

AbstractAttention Deficit Hyperactivity Disorder (ADHD) is an increasingly prevalent neuropsychiatric disorder characterized by hyperactivity, inattention, and impulsivity. Symptoms emerge from underlying deficiencies in neurocircuitry, and recent research has suggested a role played by the gut microbiome. The gut microbiome is a complex ecosystem of interdependent taxa with an exponentially complex web of interactions involving these taxa, plus host gene and reaction pathways, some of which involve neurotransmitters with roles in ADHD neurocircuitry. Studies have analyzed the ADHD gut microbiome using macroscale metrics such as diversity and composition, and have proposed several biomarkers. Few studies have delved into the complex underlying dynamics ultimately responsible for the emergence of such metrics, leaving a largely incomplete, sometimes contradictory, and ultimately inconclusive picture.We aim to help complete this picture by venturing beyond taxa abundances and into taxa relationships (i.e. cooperation and competition), using a publicly available gut microbiome dataset from 30 Control (15 female, 15 male) and 28 ADHD (15 female, 13 male) undergraduate students. We conduct our study in two parts. We first perform the same macroscale analyses prevalent in ADHD gut microbiome literature (diversity, differential, biomarker, and composition) to observe the degree of correspondence, or any new trends. We then estimate two-way ecological relationships by producing Control and ADHD Microbial Co-occurrence Networks (MCNs), using SparCC correlations (p < 0.01). We perform community detection to find clusters of taxa estimated to mutually cooperate along with their centroids, and centrality calculations to estimate taxa most vital to overall gut ecology. We conclude by summarizing our results, and provide conjectures on how they can guide future experiments, some methods for improving our experiments, and general implications for the field.
Maximizing the impact of limited vaccine supply under different epidemic conditions: a two-city monkeypox modelling analysis
Authors: Knight Jesse , Tan Darrell H.S. , Mishra Sharmistha 
Published: August 2022

AbstractbackgroundIn the current global monkeypox outbreak, many jurisdictions have been faced with limited vaccine supply, motivating interest in efficient allocation. We sought to explore optimal vaccine allocation between two linked transmission networks over a short-term time horizon, across a range of epidemic conditions.methodsWe constructed a deterministic compartmentalsveirmodel of monkeypox transmission. We parameterized the model to reflect two representative, weakly connectedgbmsmsexual networks (cities) in Ontario. We simulated roll-out of 5000 vaccine doses over 15 days, starting 60 days after epidemic seeding with 10 imported cases. Within this model, we varied: the relative city (network) sizes, epidemic potentials (R0), between-city mixing, and distribution of imported/seed cases between cities. In each context (combination of varied factors), we then identified the “optimal” allocation of doses between cities — resulting in the fewest cumulative infections by day 120.resultsUnder our modelling assumptions, we found that a fixed supply of vaccines could generally avert more infections over short-term time horizons when prioritized to: a larger transmission network, a network with more initial infections, and/or a network with greaterR0. Greater between-city mixing decreased the influence of initial seed cases, and increased the influence of cityR0on optimal allocation. Under mixed conditions (e.g. fewer seed cases but greaterR0), optimal allocation saw doses shared between cities, suggesting that proximity-based and risk-based vaccine prioritization can work in combination to minimize transmission.interpretationPrioritization of limited vaccine supply based on network-level risk factors can help minimize transmission during an emerging epidemic. Such prioritization should be grounded in an understanding of context-specific drivers of risk, and should acknowledge the potential connectedness of multiple transmission networks.
Cell-associated Transcriptional Alterations in the Retinal of Alzheimer’s Disease
Authors: Ngolab Jennifer , Mark Adam , Buchanan Justin , Korouri Shaina , Priessl Sebastian , Rosenthal Sara Brin , Wang Allen , Fisch Kathleen M. , Rissman Robert A. 
Published: August 2022

AbstractCurrent approaches for studying pathologic changes in the retina associated with Alzheimer’s Disease (AD) remain heterogeneous, limiting the use of retinal amyloid-beta as a viable biomarker for AD. Transcriptomic profiling of the retina has provided cell-specific insight into AD progression in the brain yet is lacking in the retina. In this study, we implemented a non-biased approach through next generation sequencing to profile frozen archived retinal tissues from autopsy/pathologically confirmed AD and non-diagnosed cases (NonAD). A total of 37,211 nuclei were isolated from frozen retinal tissue punches originating from AD, and 31,326 were isolated from non-diagnosed cases. Gene expression patterns specific to the retinal region and major retinal cell types were represented in both tissue groups. AD-associated genes were differentially expressed in AD retinal glial cells, including microglia. A greater percentage of microglial nuclei from AD retinal nuclei expressed TYRO protein tyrosine kinase-binding protein (TYROBP) compared to nonAD retinal nuclei. However, compared to microglia from single retinal cell datasets from elderly non-diseased individuals, TYROBP expression is highly expressed in the single cell data set, indicating TYROBP transcripts reside within the cytoplasm. However, other AD-associated genes were differentially expressed in AD nuclei such as DOCK2, PICALM, and PLCG2 compared to non-diseased single-cell microglia, implicating a role of these genes in the AD retina. To summarize, we extracted a high number of nuclei from frozen retinal tissue that retain specific gene markers for cell classification and highlighted candidate AD-associated genes in retinal microglia that may be viable in future AD retinal studies.
Single-cell RNA sequencing highlights a reduced function of natural killer and cytotoxic T cell in recovered COVID-19 pregnant women
Authors: Aziz Nor Haslinda Abd , Salker Madhuri S. , Lankapalli Aditya Kumar , Shafiee Mohammed Nasir , Kocak Ersoy , Pal Surya Sekhar , Khalid Omer , Kasim Norhana Mohd , Kalok Aida , Fuad Norashikin Abdul , Ossowski Stephan , Casadei Nicolas ,   Deutsche COVID-19 OMICS Initiative (DeCOI), Brucker Sara Y , Riess Olaf , Singh Yogesh 
Published: August 2022

AbstractPregnancy is a complex phenomenon during which women undergo immense immunological change throughout this period. Having an infection with the SARS-CoV-2 virus leads to an additional burden on the highly stretched immune response. Some studies suggest that age-matched pregnant women are more prone to SARS-CoV-2 infection compared with normal healthy (non-pregnant) women, while alternative evidence proposed that pregnant women are neither susceptible nor develop severe symptoms. This discrepancy in different findings regarding the immune responses of pregnant women infected with SARS-CoV-2 virus is not well understood. In this study, we investigated how SARS-CoV-2 viral infection could modulate the immune landscape during the active infection phase and recovery in pregnant females. Using flow cytometry, we identified that intermediate effector CD8+ T cells were increased in pregnant women who had recovered from COVID-19 as opposed to those currently infected. Similarly, an increase in CD4+ T helper cells (early or late) during the recovered phase was observed during the recovery phase compared with infected pregnant women or healthy pregnant women, whilst infected pregnant women had a reduced number of late effector CD4+ T cells. CD3+CD4- CD8-NKT cells that diminished during active infection in contrast to healthy pregnant women were significant increase in recovered COVID-19 recovered pregnant women. Further, our single-cell RNA sequencing data revealed that infection of SARS-CoV-2 had changed the gene expression profile of monocytes, CD4+ effector cells and antibody producing B cells in convalescent as opposed to healthy pregnant women. Additionally, several genes with cytotoxic function, interferon signalling type I & II, and pro- and anti-inflammatory functions in natural killer cells and CD8+ cytotoxic T cells were compromised in recovered patients compared with healthy pregnant women. Overall, our study highlights that SARS-CoV-2 infection deranged the adaptive immune response in pregnant women and could be implicated in pregnancy complications in ongoing pregnancies.
A syntenin inhibitor blocks endosomal entry of SARS-CoV-2 and a panel of RNA viruses
Authors: Lindqvist Richard , Benz Caroline , Sereikaite Vita , Maassen Lars , Laursen Louise , Jemth Per , Strømgaard Kristian , Ivarsson Ylva , Överby Anna K. 
Published: August 2022

AbstractViruses are dependent on interactions with host factors in order to efficiently establish an infection and replicate. Targeting such interactions provides an attractive strategy to develop novel antivirals. Syntenin is a protein known to regulate the architecture of cellular membranes by its involvement in protein trafficking, and has previously been shown to be important for HPV infection. Here we show that a highly potent and metabolically stable peptide inhibitor that binds to the PDZ1 domain of syntenin inhibits SARS-CoV-2 infection by blocking the endosomal entry of the virus. Furthermore, we found that the inhibitor also hampered chikungunya infection, and strongly reduced flavivirus infection, which are completely dependent on receptor mediated endocytosis for their entry. In conclusion, we have identified a novel pan-viral inhibitor that efficiently target a broad range of RNA viruses.
First-sight recognition of touched objects shows that chicks can solve the Molyneux’s problem
Authors: Versace Elisabetta , Freeland Laura , Wang Shuge , Emmerson Michael G. 
Published: August 2022

AbstractIf a congenitally blind person learns to distinguish between a cube and a sphere by touch, would they immediately recognise these objects by sight if their vision is restored? This question, posed by Molyneux in 1688, has puzzled philosophers and scientists. We overcame ethical and practical difficulties in the study of cross-modal recognition by using inexperienced chicks. We hatched chicks in darkness, exposed them to tactile smooth vs. bumpy stimuli in darkness and then tested them in a visual recognition task. At first sight, chicks previously exposed to smooth stimuli approached the smooth stimulus significantly more than those exposed to the bumpy stimuli. This shows that cross-modal recognition does not require multimodal experience. At least in precocial species, supra-modal brain areas already function at birth.
Muscle-derived Cues are Required to Specify Proprioceptor Pool Identity
Authors: Norovich Amy L. , Brenner-Morton Susan , Jessell Thomas M. 
Published: August 2022

SummaryThe formation of spinal sensory-motor circuits requires the diversification of proprioceptive sensory neurons (pSNs). During embryonic development, pSNs acquire molecular identities aligned with the limb muscle that they supply, but the extent of pSN “pool” diversity and how it is established are poorly understood. We find that the gene v-set transmembrane domain-2b (vstm2b) is preferentially expressed in pSN pools supplying dorsal limb muscle targets along the proximodistal extent of the limb. Genetic removal of muscle precursor cells from the developing limb greatly reduces the number of pSNs expressing vstm2b, demonstrating a requirement for limb muscle in specifying pSN pool identity. Comparison of dorsal and ventral muscle precursors identifies spatially restricted expression of the genes lumican (lum), decorin (dcn), and BMP binding endothelial regulator (bmper), demonstrating that dorsal and ventral muscle groups possess distinct molecular identities early in embryonic development. Together, these findings show that limb muscle is required for the specification of pSN pool identity and define early molecular correlates of dorsoventral muscle identity that are positioned to drive neuronal diversity.
Dauer fate in aCaenorhabditis elegansBoolean network model
Authors: Kandoor Alekhya Abhiram , Fierst Janna L. 
Published: August 2022

AbstractCellular fates are determined by genes interacting across large, complex biological networks. A critical question is how to identify causal relationships spanning distinct signaling pathways and underlying organismal phenotypes. Here, we address this question by constructing a Boolean model of a well-studied developmental network and analyzing information flows through the system. Depending on environmental signalsCaenorhabditis elegansdevelop normally to sexual maturity or enter a reproductively delayed, developmentally quiescent ‘dauer’ state, progressing to maturity when the environment changes. The developmental network that starts with environmental signal and ends in the dauer/no dauer fate involves genes across 4 signaling pathways including cyclic GMP, Insulin/IGF-1, TGF-β and steroid hormone synthesis. We identified three stable motifs leading to normal development, each composed of genes interacting across the Insulin/IGF-1, TGF-Beta and steroid hormone synthesis pathways. Three genes known to influence dauer fate,daf-2, daf-7andhsf-1, acted as driver nodes in the system. Using causal logic analysis, we identified a five gene cyclic subgraph integrating the information flow from environmental signal to dauer fate. Perturbation analysis showed that a multifactorial insulin profile determined the stable motifs the system entered and interacted withdaf-12as the switchpoint driving the dauer/no dauer fate. Our results show that complex organismal systems can be distilled into abstract representations that permit full characterization of the causal relationships driving developmental fates. Analyzing organismal systems from this perspective of logic and function has important implications for studies examining the evolution and conservation of signaling pathways.
Identification of transcriptional landscapes and functions of the inhibition of ARHGEF2 in hepatocellular carcinoma cells
Authors: Zhang Min , He David C , Chung Andrew 
Published: August 2022

AbstractThe RHO guanine exchange factor ARHGEF2 has exchange activity toward RHOA, which is essential for the development of cancers such as liver cancer. However, the potential functions and mechanisms of ARHGEF2 in the progression of liver cancer are largely unknown. In this study, we identified the transcriptional landscapes of hepatocellular carcinoma cells treated with ARHGEF2 shRNAs. The gene enrichment assays such as KEGG and GO were used to further analyze the potential signaling pathways. Moreover, the PPI network and Reactome map were used to further identify the biological processes. The results showed that Alzheimer’s disease disease (AD) and Cushing syndrome (CS) are the major signaling pathways involved in the ARHGEF2-shRNAs treated hepatocellular carcinoma cells. We identified the top ten interactive genes including ICAM1, APOE, LDLR, NAT10, HSPA1A, EDN1, CACNA1C, KCNMA1, SNAI1, and ELN. Our study may provide novel mechanisms for the treatment of liver cancer by inhibiting ARHGEF2.
A touchscreen device for behavioral testing in pigs
Authors: Ao Will , Grace Megan , Floyd Candace L. , Vonder Haar Cole 
Published: August 2022

AbstractPigs are becoming more common research models due to their utility in studying neurological conditions such as traumatic brain injury, Alzheimer’s disease, and Huntington’s Disease. However, behavioral tasks often require a large apparatus and are not automated, which may disinterest researchers in using important functional measures. To address this, we developed a touchscreen that pigs could be trained on for behavioral testing. A rack-mounted touchscreen monitor was placed in an enclosed, weighted audio rack. A pellet dispenser was operated by a radio frequency transceiver to deliver fruit-flavored sugar pellets from across the testing room. Programs were custom written in Python and executed by a Raspberry Pi. A behavioral shaping program was designed to train pigs to interact with the screen and setup responses for future tasks. Pigs rapidly learned to interact with the screen. To demonstrate efficacy in more complex behavior, two pigs were trained on a delay discounting tasks and two pigs on a color discrimination task. The device held up to repeated testing of large pigs and could be adjusted to the height of minipigs. The device can be easily recreated and constructed at a relatively low cost. Research topics ranging from brain injury to pharmacology to vision could benefit from behavioral tasks designed to specifically interrogate relevant function. More work will be needed to develop tests which are of specific relevance to these disciplines.
The neighborhood of interaction in human crowds is neither metric nor topological, but visual
Authors: Wirth Trenton D. , Dachner Gregory C. , Rio Kevin W. , Warren William H. 
Published: August 2022

AbstractGlobal patterns of collective motion in bird flocks, fish schools, and human crowds are thought to emerge from local interactions within a neighborhood of interaction, the zone in which an individual is influenced by their neighbors. Both topological and metric neighborhoods have been reported in birds, but this question has not been addressed in humans. With a topological neighborhood, an individual is influenced by a fixed number of nearest neighbors, regardless of their physical distance; whereas with a metric neighborhood, an individual is influenced by all neighbors within a fixed radius. We test these hypotheses experimentally with participants walking in real and virtual crowds, by manipulating the crowd’s density. Our results rule out a strictly topological neighborhood, are approximated by a metric neighborhood, but are best explained by a visual neighborhood with aspects of both. This finding has practical implications for modeling crowd behavior and understanding crowd disasters.