bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantifying the effect of isolation and negative certification on COVID-19 transmission
Authors: Takeshita Jun-ichi , Murakami Michio , Kamo Masashi , Naito Wataru , Yasutaka Tetsuo , Imoto Seiya 
Published: February 2022

AbstractIsolation of close contact people and negative test certification are used to manage the spread of new coronavirus infections worldwide. These effectively prevent the spread of infection in advance, but they can lead to a decline in socio-economic activity. Thus, the present study quantified the extent to which isolation and negative test certification respectively reduce the risk of infection. To this end, a discrete-time SEIR model was used as the infectious disease model, and equations for calculating the conditional probability of non-infection status given negative test results on two different days were derived. Then the respective non-infection probabilities with two negative PCR test results, and with one negative PCR test result and one antigen test result, were quantified. By substituting initial parameters of the SEIR model into these probabilities, the present study revealed the following: (1) isolating close contact individuals can reduce by 80% the risk of infection during the first five days, but five more days are needed to reduce the risk 10% more, and seven more days to reduce the risk 20% more; and (2) if an individual with a negative PCR test result has a negative antigen test result the next day, then his or her infection probability is between 0.6% and 0.7%. Our results show that five-day isolation has a proportionally greater effect on risk reduction, compared to longer isolation; and thus, if an isolation period of longer than five days is contemplated, both the risk reduction and the negative effects from such increased isolation should be considered. Regarding negative test certification, our results provide those in managerial positions, who must decide whether to accept the risk and hold mass-gathering events, with quantitative information that may be useful in their decision-making.
An approach to quantify parameter uncertainty in early assessment of novel health technologies
Authors: Iskandar Rowan , Federici Carlo , Berns Cassandra , Blankart Carl Rudolf 
Published: February 2022

AbstractHealth economic modeling of novel technology at the early stages of a product lifecycle has been used to identify technologies that are likely to be cost-effective. Such early assessments are challenging due to the potentially limited amount of data. Modelers typically conduct uncertainty analyses to evaluate their effect on decision-relevant outcomes. Current approaches, however, are limited in their scope of application and imposes an unverifiable assumption, i.e., uncertainty can be precisely represented by a probability distribution. In the absence of reliable data, an approach that uses the fewest number of assumptions is desirable. This study introduces a generalized approach for quantifying parameter uncertainty, i.e., probability bound analysis (PBA), that does not require a precise specification of a probability distribution in the context of early-stage health economic modeling. We introduce the concept of a probability box (p-box) as a measure of uncertainty without necessitating a precise probability distribution. We provide formulas for a p-box given data on summary statistics of a parameter. We describe an approach to propagate p-boxes into a model and provide step-by-step guidance on how to implement PBA. We conduct a case and examine the differences between the status-quo and PBA approaches and their potential implications on decision-making.
Identifying the midline thalamus in humans in vivo
Authors: Reeders Puck C. , Rivera N. M. Vanessa , Vertes Robert P. , Mattfeld Aaron T. , Allen Timothy A. 
Published: February 2022

AbstractThe midline thalamus is essential to flexible cognition, memory, and stress regulation and its dysfunction is associated with several neurological and mental health disorders including Alzheimer’s disease, schizophrenia, and depression. Despite the pervasive role of the midline thalamus in cognition and disease, almost nothing is known about it in humans due to the lack of a rigorous methodology for finding this brain region using noninvasive imaging technologies. Here, we introduce a new method for identifying the midline thalamus in vivo using probabilistic tractography and k-means clustering with diffusion weighted imaging data. This method clusters thalamic voxels based on data-driven cortical and subcortical connectivity profiles, and then segments midline thalamic nuclei based on connectivity profiles established in rodent and macaque tracer studies. Results from two different diffusion weighted imaging sets, including adult data (22-35yrs) from the Human Connectome Project (n=127) and adolescent data (9-14yrs) collected at Florida International University (n=34) showed that this approach reliably classifies midline thalamic clusters. As expected, these clusters were most evident along the dorsal/ventral extent of the third ventricle and primarily connected to the agranular medial prefrontal cortex (e.g., anterior cingulate cortex), nucleus accumbens, and medial temporal lobe regions. The midline thalamic clusters were then bisected based on a human brain atlas (Ding et al., 2016) into a dorsal midline thalamic cluster (paraventricular and paratenial nuclei) and a ventral midline thalamic cluster (rhomboid and reuniens nuclei). This anatomical connectivity-based identification procedure for the midline thalamus offers new opportunities to study this region in vivo in healthy populations and in those with psychiatric and neurological disorders.Significance StatementThe midline thalamus is essential for flexible cognition, decision making, and stress regulation. Abnormal development, dysfunction, and neurodegeneration of the midline thalamus is thought to be a critical pathology in several psychiatric and neurological disorders. Yet, little is known about the role of the human midline thalamus. Here we solve the problem of localization in vivo by using probabilistic tractography and data driven clustering (k-means), a method capable of capitalizing on known connectivity in non-human animal tracer studies. Localizing the midline thalamus based on its connectivity patterns provides a useful tool for future functional and structural human MRI studies to investigate clinical implications of the midline thalamus in diseases such as Alzheimer’s and schizophrenia.
Public volume electron microscopy data: An essential resource to study the brain microvasculature
Authors: Bonney Stephanie K. , Coelho-Santos Vanessa , Huang Sheng-Fu , Takeno Marc , Kornfeld Joergen , Keller Annika , Shih Andy Y. 
Published: February 2022

ABSTRACTElectron microscopy is the primary approach to study ultrastructural features of the cerebrovasculature. However, 2D snapshots of a vascular bed capture only a small fraction of its complexity. Recent efforts to synaptically map neuronal circuitry using volume electron microscopy have also sampled the brain microvasculature in 3D. Here, we perform a meta-analysis of 6 data sets spanning different species and brain regions, including 2 data sets from the MICrONS consortium that have made efforts to segment vasculature in addition to all parenchymal cell types in mouse visual cortex. Exploration of these data have revealed rich information for detailed investigation of the cerebrovasculature. Neurovascular unit cell types (including, but not limited to, endothelial cells, mural cells, perivascular fibroblasts, microglia, and astrocytes) could be discerned across broad microvascular zones. Image contrast was sufficient to identify subcellular details, including endothelial junctions, caveolae, peg-and-socket interactions, mitochondria, Golgi cisternae, microvilli and other cellular protrusions of potential significance to vascular signaling. Additionally, noncellular structures including the basement membrane and perivascular spaces were visible and could be traced between arterio-venous zones along the vascular wall. These explorations revealed structural features that may be important for vascular functions, such as blood-brain barrier integrity, blood flow control, brain clearance, and bioenergetics. They also identified limitations where accuracy and consistency of segmentation could be further honed by future efforts. The purpose of this article is to introduce these valuable community resources within the framework of cerebrovascular research by providing an assessment of their vascular contents, identifying features of significance for further study, and discussing next step ideas for refining vascular segmentation and analysis.
Profiling skeletal muscle-derived secretome with differentiation and acute contractile activity
Authors: Bydak Benjamin , Pierdoná Taiana M. , Seif Samira , Sidhom Karim , Obi Patience O. , Labouta Hagar I. , Gordon Joseph W. , Saleem Ayesha 
Published: February 2022

AbstractExtracellular vesicles (EVs) released from all cells, are essential to cellular communication, and contain biomolecular cargo that can affect recipient cell function. Studies on the effects of contractile activity (exercise) on EVs usually rely on plasma/serum-based assessments, which contain EVs from many different cells. To specifically characterize skeletal muscle-derived vesicles and the effect of acute contractile activity, we used an in vitro model where C2C12 mouse myoblasts were differentiated to form myotubes. EVs were isolated from conditioned media from muscle cells, pre-differentiation (myoblasts) and post-differentiation (myotubes), as well as from acutely stimulated myotubes (1hr @ 14V, C-Pace EM, IonOptix) using total exosome isolation reagent (TEI, ThermoFisher, referred to as extracellular particles [EPs]) and differential ultracentrifugation (dUC; EVs). Myotube-EPs (~98 nm) were 41% smaller than myoblast-EPs (~167 nm, p<0.001, N=8-10). Two-way ANOVA showed a significant main effect for size distribution of myotube vs. myoblast-EPs (p<0.01, N=10-13). Myoblast-EPs displayed a bimodal size distribution profile with peaks at <200 nm and 400-600 nm, compared to myotube-EPs that were largely 50-300 nm in size. Total protein yield from myotube-EPs was nearly 15-fold higher than myoblast-EPs, (p<0.001 N=6-9). Similar biophysical characteristics were observed when EVs were isolated using dUC: myotube-EVs (~195 nm) remained 41% smaller in average size than myoblast-EVs (~330 nm, p=0.07, N=4-6) and had comparable size distribution profiles as EPs isolated via TEI. Myotube-EVs also had 4.7-fold higher protein yield vs. myoblast EVs (p<0.05, N=4-6). Myotube-EPs had significantly decreased expression of exosomal marker proteins TSG101, CD63, ALIX and CD81 compared to myoblast-EPs (p<0.05, N=7-12). Conversely, microvesicle marker ARF6, and lipoprotein marker APO-A1was only found in the myotube-EPs (p<0.05, N=4-12). There was no effect of acute stimulation on myotube-EP biophysical characteristics (N=7), nor on expression of TSG101, ARF6 or CD81 (N=5-6). Myoblasts treated with control or acute stimulation-derived EPs (13 μg/well) for 48hrs and 72hrs showed no changes in mitochondrial mass (MitoTracker Red), cell viability or cell count (N=3-4). Myoblasts treated with EP-depleted media (72hrs) had ~90% lower cell counts (p<0.01, N=3). Our data show that EVs differ in size, distribution, protein yield and expression of subtype markers pre- vs. post-skeletal muscle differentiation. There was no effect of acute stimulation on biophysical profile or protein markers in EPs. Acute stimulation-derived EPs did not alter mitochondrial mass nor cell count/viability. Further investigation into the effects of chronic contractile activity on the biophysical characteristics and cargo of skeletal muscle-specific EVs are warranted.
A mesoscale connectome-based model of conscious access in the macaque monkey
Authors: Klatzmann Ulysse , Froudist-Walsh Sean , Bliss Daniel P. , Theodoni Panagiota , Mejías Jorge , Niu Meiqi , Rapan Lucija , Margulies Daniel S. , Palomero-Gallagher Nicola , Sergent Claire , Dehaene Stanislas , Wang Xiao-Jing 
Published: February 2022

AbstractA growing body of evidence suggests that conscious perception of a sensory stimulus coincides with all-or-none activity across multiple cortical areas, a phenomenon called ‘ignition’. In contrast, the same stimulus, when undetected, induces only transient activity. In this work, we report a large-scale model of the macaque cortex based on recently quantified structural mesoscopic connectome data. We use this model to simulate a detection task, and demonstrate how a dynamical bifurcation mechanism produces ignition-like events in the model network. The model predicts that feedforward excitatory transmission is primarily mediated by the fast AMPA receptors to ensure rapid signal propagation from sensory to associative areas. In contrast, a greater proportion of the inter-areal feedback projections and local recurrent excitation depend on the slow NMDA receptors, to ensure ignition of distributed frontoparietal activity. Our model predicts, counterintuitively, that fast-responding sensory areas contain a higher ratio of NMDA to AMPA receptors compared to association cortical areas that show slow, sustained activity. We validate this prediction using cortex-widein-vitroreceptor autoradiography data. Finally, we show how this model can account for various behavioral and physiological effects linked to consciousness. Together, these findings clarify the neurophysiological mechanisms of conscious access in the primate cortex and support the concept that gradients of receptor densities along the cortical hierarchy contribute to distributed cognitive functions.
Estrogen receptor negative breast cancer incidence rates are similar in Ghanaian and Non-Hispanic Black women in the USA
Authors: Davis Lynn Brittny C , Figueroa Jonine , Awittor Fred Kwame , Ohene Oti Naomi O. , Edusei Lawrence , Titiloye Nicolas , Adjei Ernest , Addai Beatrice Wiafe , Adjei Robertson , Afriyie Lucy T. , Yarney Joel , Ansong Daniel , Wiafe Seth , Ahearn Thomas , Vanderpuye Verna , Dedey Florence , Brinton Louise A. , Awuah Baffour , Clegg-Lamptey Joe Nat , Abubakar Mustapha , Garcia-Closas Montserrat , Biritwum Richard , Graubard Barry I 
Published: February 2022

AbstractAge-standardized incidence rates of estrogen receptor negative (ERN) breast cancers in the US are higher among Non-Hispanic Black (NHB) compared to Non-Hispanic White (NHW) women. We aimed to determine if incidence rates were similar between NHB and Ghanaians, given that a high proportion of NHB share West African genetic ancestry. We compared US rates (per 100,000 women) to those in Ghana, using data from US SEER, the Ghanaian census, and the Ghana Breast Health Study (GBHS), a population-based case-control study conducted between 2013-2015 in Accra and Kumasi. ERN age-standardized rates were similar among Ghanaian (40.7) and US NHB women (43.1), and both were higher compared to US NHW (24.0). Estrogen receptor-positive (ERP) rates were lower in Ghanaian (43.7) than US NHB (84.4), and highest in US NHW (128.5). Our data support higher ERN rates among women in Ghana similar to US NHB suggesting shared putative risk factors that require investigation.
Understanding the immunological landscape of England during SARS-CoV2 Omicron variant wave
Authors: Shingleton Joseph , Dyke Steven , Herrick Archie , Finnie Thomas 
Published: February 2022

AbstractUnderstanding the scale of the threat posed by SARS-CoV2 B.1.1.529, or Omicron, variant formed a key problem in public health in the early part of 2022. Early evidence indicated that the variant was more transmissible and less severe than previous variants. As the virus was expected to spread quickly through the population of England, it was important that some understanding of the immunological landscape of the country was developed. This paper attempts to estimate the number of people with good immunity to the Omicron variant, defined as either recent infection with two doses of vaccine, or two doses of vaccine with a recent booster dose. To achieve this, we use a process of iterative proportional fitting to estimate the cell values of a contingency table, using national immunisation records and real-time model infection estimates as marginal values. Our results indicate that, despite the increased risk of immune evasion with the Omicron variant, a high proportion of England’s population had good immunity to the virus, particularly in older age groups. However, low rates of immunity in younger populations may allow endemic infection to persist for some time.
Seasonal dynamics and polyphenism of butterfly communities in the coastal plains of central Western Ghats, India
Authors: Naik Deepak , Rao R. Shyama Prasad , Kunte Krushnamegh , Mustak Mohammed S. 
Published: February 2022

AbstractLong-term socioeconomic progress requires a healthy environment/ecosystem, but anthropogenic activities cause environmental degradation and biodiversity loss. Constant ecological monitoring is therefore necessary to assess the state of biodiversity and ecological health. However, baseline data is lacking even for ecologically sensitive regions such as the Western Ghats. We looked at the seasonality and polyphenism of butterflies of the central Western Ghats to get baseline population patterns on these charismatic taxa. We recorded 43118 individuals (175 species) using fortnightly time-constrained counts for two consecutive years, and found the peak abundance (49% of the total individuals) in post-monsoon period (Oct to Jan). The seasonal abundance was correlated with the overall increase in species richness. Habitat differences were stronger than seasonality as samples clustered based on sites. Several species also displayed polyphenism with distinct distributions of wet and dry season forms. Seasonal equitability and indicator species analysis showed distinct inter-species differences in seasonality patterns. This work provides key baseline data on the seasonal dynamics of butterflies of the Western Ghats in the context of climate change and conservation, and will help in future monitoring of this ecologically sensitive region using butterflies.
Intravesical BCG in patients with non-muscle invasive bladder cancer induces trained immunity and decreases respiratory infections
Authors: van Puffelen Jelmer H. , Novakovic Boris , van Emst Liesbeth , Kooper Denise , Zuiverloon Tahlita C.M. , Oldenhof Ursula T.H. , Witjes J. Alfred , Galesloot Tessel E. , Vrieling Alina , Aben Katja K.H. , Kiemeney Lambertus A.L.M. , Oosterwijk Egbert , Netea Mihai G. , Boormans Joost L. , van der Heijden Antoine G. , Joosten Leo A.B. , Vermeulen Sita H. 
Published: February 2022

AbstractBacillus Calmette-Guérin (BCG) is recommended as intravesical immunotherapy to reduce the risk of tumor recurrence in patients with non-muscle invasive bladder cancer (NMIBC). Currently, it is unknown whether intravesical BCG application induces trained immunity. Here, we found that intravesical BCG does induce trained immunity based on an increased production of TNF and IL-1β after heterologous ex-vivo stimulation of circulating monocytes 6- 12 weeks after intravesical BCG treatment; and a 37% decreased risk (OR 0.63 (95% CI 0.40- 1.01)) for respiratory infections in BCG-treated versus non-BCG-treated NMIBC patients. An epigenomics approach combining ChIP-sequencing and RNA-sequencing with in-vitro trained immunity experiments identified enhanced inflammasome activity in BCG-treated individuals. Finally, germline variation in genes that affect trained immunity was associated with recurrence and progression after BCG therapy in NMIBC, suggesting a link between trained immunity and oncological outcome.
Integrating phylogenetic and functional data in microbiome studies
Authors: Douglas Gavin M. , Hayes Molly G. , Langille Morgan G. I. , Borenstein Elhanan 
Published: February 2022

AbstractMicrobiome functional data are frequently analyzed to identify associations between microbial gene families and sample groups of interest. This is most often performed with approaches focused on the metagenome-wide relative abundance of microbial functions. Although such approaches can provide valuable insights, it is challenging to distinguish between different possible explanations for variation in community-wide functional profiles by considering functions alone. To help address this problem, we have developed a novel, phylogeny-aware framework to expand taxonomic balance tree-based approaches to identify enriched functions more robustly. The key focus of our approach, termed POMS, is on identifying functions that are consistently enriched in sample groups across independent taxonomic lineages. Based on simulated data we demonstrate that POMS can more accurately identify gene families that confer a selective advantage compared with commonly used differential abundance approaches. We also show that POMS can identify enriched functions in real-world metagenomics datasets that are potential targets of strong selection on multiple members of the microbiome. While this framework may not be able to identify all potential functional enrichments, the enrichments it does identify are more interpretable and conservative compared with those identified by existing differential abundance approaches. More generally, POMS is a novel approach for exploring microbiome functional data, which could be used to complement standard analyses. POMS is freely available as an R package at:https://github.com/gavinmdouglas/POMS.
Transcriptional response of a target plant to benzoxazinoid and diterpene allelochemicals highlights commonalities in detoxification
Authors: Knoch Eva , Kovács Judit , Deiber Sebastian , Shanmuganathan Reshi , Serra Núria Serra , Becker Claude , Schandry Niklas 
Published: February 2022

AbstractPlants growing in proximity to other plants are exposed to a variety of metabolites that these neighbors release into the environment. Some species produce allelochemicals to inhibit growth of neighboring plants, which in turn have evolved ways to detoxify these compounds. In order to understand how the allelochemical-receiving target plants respond to chemically diverse compounds, we performed whole-genome transcriptome analysis ofArabidopsis thalianaexposed to either the benzoxazinoid derivative 2-amino-3H-phenoxazin-3-one (APO) or momilactone B. These two allelochemicals belong to two very different compound classes, benzoxazinoids and diterpenes, respectively, produced by different cereal crop species. Despite their distinct chemical nature, we observed similar molecular responses ofA. thalianato these allelochemicals. In particular, many of the same or closely related genes belonging to the three-phase detoxification pathway were upregulated in both treatments. Further, we observed an overlap between genes upregulated by allelochemicals and those involved in herbicide detoxification. Our findings highlight the overlap in the transcriptional response of a target plant to natural and synthetic phytotoxic compounds and illustrate how herbicide resistance could arise via pathways involved in plant-plant interaction.