bluuebunny/crossref_metadata_2025_split huggingface dataset:
Timely sleep coupling: spindle-slow wave synchrony is linked to early amyloid-β burden and predicts memory decline
Authors: Chylinski Daphne , Van Egroo Maxime , Narbutas Justinas , Muto Vincenzo , Bahri Mohamed A. , Berthomier Christian , Salmon Eric , Bastin Christine , Phillips Christophe , Collette Fabienne , Maquet Pierre , Carrier Julie , Lina Jean Marc , Vandewalle Gilles 
Published: March 2022

ABSTRACTSleep alteration is a hallmark of ageing and emerges as a risk factor for Alzheimer’s disease (AD). While the fine-tuned coalescence of sleep microstructure elements may influence age-related cognitive trajectories, its association with AD processes is not fully established. Here, we investigated whether the coupling of spindles and slow waves is associated with early amyloid-beta (Aβ) brain burden, a hallmark of AD neuropathology, and cognitive change over 2 years in 100 healthy individuals in late-midlife (50-70y; 68 women). We found that, in contrast to other sleep metrics, earlier occurrence of spindles on slow-depolarisation slow waves is associated with higher medial prefrontal cortex Aβ burden (p=0.014, r2β*=0.06), and is predictive of greater longitudinal memory decline (p=0.032, r2β*=0.07). These findings unravel early links between sleep, AD-related processes and cognition and suggest that altered coupling of sleep microstructure elements, key to its mnesic function, contributes to poorer brain and cognitive trajectories in ageing.
Combining quadrat, rake and echosounding to estimate submerged aquatic vegetation biomass at the ecosystem scale
Authors: Botrel Morgan , Hudon Christiane , Biron Pascale M. , Maranger Roxane 
Published: March 2022

AbstractMeasuring freshwater submerged aquatic (SAV) biomass at large spatial scales is challenging and no single technique can cost effectively accomplish this while maintaining accuracy. We propose to combine and intercalibrate accurate quadrat-scuba diver technique, fast rake sampling and large scale echosounding. We found that the relationship between quadrat and rake biomass is moderately strong (R2 = 0.62, RMSECV = 2.19 g/m2) and varies with substrate type and SAV growth form. Rake biomass was also successfully estimated from biovolume10 and its error (R2 = 0.53, RMSECV = 5.95 g/m2), a biomass proxy derived from echosounding, at a resolution of 10 m radius from rake sampling point. However, the relationship was affected by SAV growth form, depth, acoustic data quality and wind conditions. Sequential application of calibrations yielded predictions in agreement with quadrat observations, but echosounding predictions underestimated biomass in shallow areas (< 1.5 m) while outperforming point estimation in deep areas (> 3 m). Whole-system biomass was more accurately estimated by calibrated echosounding than rake point surveys, owing to the large sample size and better representation of spatial heterogeneity of echosounding. We recommend developing as a one-time event a series of quadrat and rake calibration equations for each growth form and substrate type. Because the relationship between biovolume and biomass depends on SAV growth form, rake and echosounding calibration needs to be conducted frequently. With the two calibrations, rake can thus be used as a rapid ground truthing or in shallow areas where echosounding is inadequate.
Hospital length of stay in a mixed Omicron and Delta epidemic in New South Wales, Australia
Authors: Tobin Ruarai J , Wood James G , Jayasundara Duleepa , Sara Grant , Walker James , Martin Genevieve E , McCaw James M , Shearer Freya M , Price David J 
Published: March 2022

AbstractAimTo estimate the length of stay distributions of hospitalised COVID-19 cases during a mixed Omicron-Delta epidemic in New South Wales, Australia (16 Dec 2021 – 7 Feb 2022), and compare these to estimates produced over a Delta-only epidemic in the same population (1 Jul 2021 – 15 Dec 2022).BackgroundThe distribution of the duration that clinical cases of COVID-19 occupy hospital beds (the ‘length of stay’) is a key factor in determining how incident caseloads translate into health system burden as measured through ward and ICU occupancy.ResultsUsing data on the hospital stays of 19,574 individuals, we performed a competing-risk survival analysis of COVID-19 clinical progression. During the mixed Omicron-Delta epidemic, we found that the mean length of stay for individuals who were discharged directly from ward without an ICU stay was, for age groups 0-39, 40-69 and 70+ respectively, 2.16 (95% CI: 2.12–2.21), 3.93 (95% CI: 3.78–4.07) and 7.61 days (95% CI: 7.31–8.01), compared to 3.60 (95% CI: 3.48–3.81), 5.78 (95% CI: 5.59–5.99) and 12.31 days (95% CI: 11.75–12.95) across the preceding Delta epidemic (15 Jul 2021 – 15 Dec 2021). We also considered data on the stays of individuals within the Hunter New England Local Health District, where it was reported that Omicron was the only circulating variant, and found mean ward-to-discharge length of stays of 2.05 (95% CI: 1.80–2.30), 2.92 (95% CI: 2.50–3.67) and 6.02 days (95% CI: 4.91–7.01) for the same age groups.ConclusionsHospital length of stay was substantially reduced across all clinical pathways during a mixed Omicron-Delta epidemic compared to a prior Delta epidemic. These changes in length of stay have contributed to lessened health system burden despite greatly increased infection burden and should be considered in future planning of response to the COVID-19 pandemic in Australia and internationally.
A log-odds system for waning and boosting of COVID-19 vaccine effectiveness
Authors: Blakely Tony , Szanyi Joshua , Wilson Tim , Scott Nick 
Published: March 2022

AbstractImmunity to SARS-CoV-2 following vaccination wanes over time in a non-linear fashion, making modelling of likely population impacts of COVID-19 policy options challenging. We observed that it was possible to mathematize non-linear waning of vaccine effectiveness (VE) on the percentage scale as linear waning on the log-odds scale, and developed a random effects logistic regression equation based on UK Health Security Agency data to model VE against Omicron following two and three doses of a COVID-19 vaccine. VE on the odds scale reduced by 47% per month for symptomatic infection after two vaccine doses, lessening to 35% per month for hospitalisation. Waning on the odds scale after triple dose vaccines was 35% per month for symptomatic disease and 19% for hospitalisation. This log-odds system for estimating waning and boosting of COVID-19 VE provides a simple solution that may be used to parametrize SARS-CoV-2 immunity over time parsimoniously in epidemiological models.
Gene expression signature of castrate resistant prostate cancer
Authors: Dixcy Jaba Sheeba JM , Hegde Shraddha , Tamboli Ninad , Nadig Namratha , Keshavamurthy Ramaiah , Ranganathan Prathibha 
Published: March 2022

AbstractProstate gland is a highly androgen dependent gland and hence the first line of treatment for metastatic prostate cancer happens to be androgen ablation. This is achieved by multiple non-surgical methods. However, most of these cancers although respond well initially, become resistant to androgen ablation sooner or later. These cancers then become extremely aggressive and difficult to treat, thereby drastically affect the patient prognosis. The purpose of this project was to identify a gene expression signature for castrate resistant prostate cancer which may aid in identification of mechanisms responsible for castrate resistance. For this purpose, we have collected patient samples belonging to a. Control group; b. Castrate Sensitive group and c. Castrate resistant group. Gene expression profiling has been done on these samples using RNA-seq and several differentially expressed genes identified between the castrate sensitive and resistant groups. We have also identified some genes which are expressed in the castrate resistant group alone, which is of interest since these may have an implication in evolution of castrate resistance and also prognosis.We have compared this with data from The Cancer Genome Atlas (TCGA). Using criteria such as overall survival, disease free survival, progression free survival and biochemical recurrence, we have identified genes which may have relevance in progression to castrate resistance and in prognosis. Functional annotation of these genes may give an insight into the mechanism of development of castrate resistance.
Engineering Principles and Algorithmic Design Synthesis for Ultracompact Bio-Hybrid Perfusion Chip
Authors: Erben Amelie , Kellerer Thomas , Lissner Josefine , Eulenkamp Constanze , Hellerer Thomas , Hauke-Clausen-Schaumann  , Sudhop Stefanie , Heymann Michael 
Published: March 2022

AbstractBioinspired 3D microfluidic systems that combine vascularization with extracellular matrix architectures of organotypic geometry, composition and biophysical traits can help advance our understanding of microorgan physiology. Here, two-photon stereolithography is adopted to fabricate freestanding perfusable 3D cell scaffolds with micrometer resolution from gelatin methacryloyl hydrogel derived from extracellular matrix protein. As a proof of concept, we introduce an ultracompact bio-hybrid chip layout to demonstrate perfusion and cell seeding of double-digit μm proteinaceous channels. This perfusion chip consists of a standardized microfluidic interface fabricated from standard resin and a GM10 bioink channel printed atop of this interface. In addition, we demonstrate that algorithmic design synthesis can recapitulate intact alveoli and capillary networks with tunable design parameters to implement vascularized alveolar tissue models. This approach will allow for a systematic investigation of cell-cell and tissue dynamics in response to defined structural, mechanical and bio-molecular cues and is ultimately scalable to fabricate organ-on-a-chip systems.
Projective LDDMM: Spatially Reconstructing a Story of Rostrally-Dominant Tau in Alzheimer’s Disease
Authors: Stouffer Kaitlin , Witter Menno , Chen Claire , Xu Eileen , Albert Marilyn , Mori Susumu , Troncoso Juan , Tward Daniel , Miller Michael 
Published: March 2022

AbstractSince Braak’s initial histological observations, it has been recognized that Alzheimer’s disease (AD) neurofibrillary tangles (NFTs) appear in the medial temporal lobe (MTL) of the brain very early in the disease course. MRI-based shape diffeomorphometry markers have demonstrated pre-clinical AD changes in the MTL but it has not been possible to confirm that these MRI changes correspond to the presence of NFTs. Here, we present a method termed Projective LDDMM for aligning sparse measurement profiles of AD pathology (i.e., 2D digital histology images) with 3D MRI. We reconstruct measures of 2D NFT density in the dense metric of 3D MRI, using the Mai Paxinos Atlas coordinates for two cases of advanced AD. Analyses reveal the highest levels of NFT density in the rostral third (10-15 mm) of the hippocampus and the adjoining regions of the entorhinal cortex and amygdala. These findings emphasize the selective vulnerability of MTL subregions in AD, and suggest that high resolution MRI methods might benefit from focusing on the rostral MTL to more closely link these MRI images to AD neuropathology.
WNK1-dependent water influx is required for CD4+T cell activation and T cell-dependent antibody responses
Authors: O’May Joshua Biggs , Vanes Lesley , de Boer Leonard L. , Hartweger Harald , Kunzelmann Simone , Hayward Darryl , Llorian Miriam , Lewis David A. , Köchl Robert , Tybulewicz Victor L. J. 
Published: March 2022

AbstractSignaling from the T cell antigen receptor (TCR) on CD4+T cells plays a critical role in adaptive immune responses by inducing T cell activation, proliferation, and differentiation. We demonstrate that WNK1, a kinase implicated in osmoregulation in the kidney, is required in T cells to support T-dependent antibody responses. WNK1-deficient CD4+T cells are severely impaired in their ability to proliferate and to generate antigen-specific T follicular helper cells in response to immunization with a T-dependent antigen. We show that WNK1 and its downstream OXSR1 and STK39 kinases are required for TCR signaling in CD4+T cells and for entry into cell cycle. Additionally, by preventing ATR activation, this pathway is required for T cells to progress from G2 into M phase of the cell cycle. Unexpectedly, we show that this WNK1 pathway regulates water influx, most likely through AQP3, which is required for TCR-induced signaling and cell cycle entry. Thus, TCR signaling via WNK1, OXSR1, STK39 and AQP3 leads to water entry that is essential for CD4+T cell proliferation and hence T cell-dependent antibody responses. Given the broad expression of WNK1, WNK1-dependent water influx may be a common feature of mitogenic pathways in many cell types, both within the immune system and beyond.One Sentence SummaryT cell antigen receptor signaling via the WNK1 kinase causes water entry which is essential for CD4+T cell proliferation.
Extracellular matrix guidance determines proteolytic and non-proteolytic cancer cell patterning
Authors: Beunk Lianne , van Helvert Sjoerd , Bekker Bram , Ran Lars , Kang Ross , Paulat Tom , Syga Simon , Deutsch Andreas , Friedl Peter , Wolf Katarina 
Published: March 2022

AbstractMetastatic tumor cell invasion into interstitial tissue is a mechanochemical process that responds to tissue cues and further involves proteolytic remodeling of the tumor stroma. How matrix density, tissue guidance and the ability of proteolytic tissue remodeling cooperate and determine decision-making of invading tumor cells in complex-structured three-dimensional (3D) tissue remains unclear. We here developed a collagen-based invasion assay containing a guiding interface of low collagen density adjacent to randomly organized 3D fibrillar lattice and examined the invasion of melanoma cells from multicellular spheroids in response to matrix density, guidance cues and collagenolysis. After 48 hours of culture, two invasion niches developed, (i) sheet-like collective migration along the interface and (ii) single cell- and strand-like invasion into randomly organized 3D matrix. High collagen density impeded migration into the random matrix, whereas migration along a high-density collagen interface was increased compared to the low-density matrix assay. In silico analysis predicted that facilitated interface migration in high-density matrix depended on physical guidance without collagen degradation, whereas migration into randomly organized matrix was strongly dependent on collagenolysis. When tested in 3D culture, inhibition of matrix metalloprotease (MMP)-mediated collagen degradation compromised migration into random matrix in dependence of density, whereas interface-guided migration remained effective. In conclusion, with increasing tissue density, matrix cues bordered by dense matrix, but not randomly organized matrix, support effective MMP-independent migration. This identifies the topology of interstitial tissue a primary determinant of switch behaviors between MMP-dependent and MMP-independent cancer cell invasion.
Transcriptomic analysis of the C3-CAM transition in Cistanthe longiscapa, a drought tolerant plant in the Atacama Desert
Authors: Ossa P. G. , Moreno A. A. , Orellana D. , Toro M. , Carrasco-Valenzuela T. , Riveros A. , Meneses C. C. , Nilo-Poyanco R. , Orellana A. 
Published: March 2022

AbstractOne of the most outstanding plant species during the blooming of the Atacama Desert is the annual plantCistanthe longiscapa. This plant can perform CAM photosynthesis, but the ecophysiological and molecular mechanisms that this plant uses to withstand the extreme conditions it inhabits in the field are unknown.Morphological and ecophysiological traits were studied and leaf samples at dawn/dusk times were collected from three sites distributed across an increasing south to north arid gradient, to evaluate CAM expression and transcriptomic differences, and search for links between photosynthetic path and abiotic response.Plants from the different sites presented significant differences in nocturnal leaf acid accumulation, isotopic carbon ratio (δ13C), succulence and other four traits that clearly indicated a spectrum of CAM photosynthesis intensity that correlated with aridity intensity. The differential gene expression analysis among Dawn vs Dusk between sampling sites showed higher gene expression in the arid northern site (3991 v/s 2293) with activation of regulatory processes associated with abscisic acid and circadian rhythm.The analysis highlights clear ecophysiological differences and the requirement of a strong rewiring of the gene expression to allow a transition from a weak into a strong CAM inC. longiscapa.
GPCR-IFP: A Web Server for Analyzing G-Protein Coupled Receptor-Ligand Fingerprint Interaction from Experimental Structures
Authors: Xu Marc , li Yi , Dong Junlin , Yuan Shuguang 
Published: March 2022

AbstractG-protein coupled receptors (GPCRs) are interesting targets for a broad range of drugs. The comprehensions of the interaction’s mode between GPCRs and their ligands remains to be resolved. Here, we present GPCR-IFP, a web server which drives to gather experimental information supports a better understanding of ligand-receptor interaction and the chemical space. Despite the vast chemical library used for drug discovery, the structures of ligands for a particular receptor share some common molecular features. Thus, we foraged to collect all experimental structures of GPCRs and analyzed protein-ligand interactions which resulted in important unique patterns for both agonist and antagonist. All those results can be analyzed and visualized in GPCR-IFP, a friendly-used webserver.
Development of visual cortex in human neonates are selectively modified by postnatal experience
Authors: Li Mingyang , Liu Tingting , Xu Xinyi , Wen Qingqing , Zhao Zhiyong , Dang Xixi , Zhang Yi , Wu Dan 
Published: March 2022

AbstractExperience-dependent cortical plasticity is a pivotal process of human brain development and essential for the formation of most cognitive functions. Although studies found that early visual experience could influence the endogenous development of visual cortex in animals, little is known about such impact on human infants. Using the multi-modal MRI data from developing human connectome project, we revealed the early structural and functional maps in the ventral visual cortex and their development across the first month of age. Particularly, we found the postnatal experience could modulate both the cortical morphology in ventral visual cortex and the functional circuit between bilateral primary visual cortices. But the cortical myelination and overall functional circuits of ventral cortex, particularly that of the high-order visual cortex, developed without significant influence of postnatal experience in such early period. These experience-dependent cortical properties were further validated in the preterm-born infants who have longer postnatal time but immature cortical development at birth. The results confirmed that the development of cortical thickness was dominated by the postnatal experience but the functional circuit might be determined by the overall maturity of visual cortex. These data suggest in human newborns that early postnatal experience shapes the structural and functional development of the visual cortex in selective and organized pattern.
Enhanced envelope coding following acoustic trauma is detrimental to neural coding of speech in noise
Authors: Parida Satyabrata , Heinz Michael G. 
Published: March 2022

AbstractPeople with hearing loss struggle understanding speech in noisy backgrounds. Speech-intelligibility models highlight the importance of slow-varying envelopes of speech and noise; however, the physiological basis of impaired perception remains unclear. We provide neurophysiological evidence that, although acoustic trauma enhances both speech and noise envelopes, disruptions in cochlear tonotopicity preferentially enhance neural responses to noise in noisy speech. These results provide mechanistic insights into everyday-communication challenges created by hearing loss.
Extracting physical characteristics of higher-order chromatin structures from 3D image data
Authors: Lamberti William Franz , Zang Chongzhi 
Published: March 2022

AbstractHigher-order chromatin structures have functional impacts on gene regulation and cell identity determination. Using high-throughput sequencing (HTS)-based methods like Hi-C, active or inactive compartments and open or closed topologically associating domain (TAD) structures can be identified on a cell population level. Recently developed high-resolution three-dimensional (3D) molecular imaging techniques such as 3D electron microscopy with in situ hybridization (3D-EMSIH) and 3D structured illumination microscopy (3D-SIM) enable direct detection of physical representations of chromatin structures in a single cell. However, computational analysis of 3D image data with explainability and interpretability on functional characteristics of chromatin structures is still challenging. We developed Extracting Physical-Characteristics from Images of Chromatin Structures (EPICS), a machine-learning based computational method for processing high-resolution chromatin 3D image data. Using EPICS on images produced by 3D-EMISH or 3D-SIM techniques, we generated more direct 3D representations of higher-order chromatin structures, identified major chromatin domains, and determined the open or closed status of each domain. We identified several high-contributing features from the model as the major physical characteristics that define the open or closed chromatin domains, demonstrating the explainability and interpretability of EPICS. EPICS can be applied to the analysis of other high-resolution 3D molecular imaging data for spatial genomics studies. The R and Python codes of EPICS are available athttps://github.com/zang-lab/epics.