Background
The aim of this study was to investigate the prevalence of epidemiologic and physician‐diagnosed pollen‐induced AR (PiAR) in the grasslands of northern China and to study the impact of the ...intensity and time of pollen exposure on PiAR prevalence.
Methods
A multistage, clustered and proportionately stratified random sampling with a field interviewer‐administered survey study was performed together with skin prick tests (SPT) and measurements of the daily pollen count.
Results
A total of 6043 subjects completed the study, with a proportion of 32.4% epidemiologic AR and 18.5% PiAR. The prevalence was higher in males than females (19.6% vs 17.4%, P = .024), but no difference between the two major residential and ethnic groups (Han and Mongolian) was observed. Subjects from urban areas showed higher prevalence of PiAR than rural areas (23.1% vs 14.0%, P < .001). Most PiAR patients were sensitized to two or more pollens (79.4%) with artemisia, chenopodium, and humulus scandens being the most common pollen types, which were similarly found as the top three sensitizing pollen allergens by SPT. There were significant regional differences in the prevalence of epidemiologic AR (from 18.6% to 52.9%) and PiAR (from 10.5% to 31.4%) among the six areas investigated. PiAR symptoms were positively associated with pollen counts, temperature, and precipitation (P < .05), but negatively with wind speed and pressure P < .05).
Conclusion
Pollen‐induced AR (PiAR) prevalence in the investigated region is extremely high due to high seasonal pollen exposure, which was influenced by local environmental and climate conditions.
The protein compositions, or the proteomes, found in human salivary and plasma fluids are compared. From recent experimental work by many laboratories, a catalogue of 2290 proteins found in whole ...saliva has been compiled. This list of salivary proteins is compared with the 2698 proteins found in plasma. Approximately 27% of the whole-saliva proteins are found in plasma. However, despite this apparent low degree of overlap, the distribution found across Gene Ontological categories, such as molecular function, biological processes, and cellular components, shows significant similarities. Moreover, nearly 40% of the proteins that have been suggested to be candidate markers for diseases such as cancer, cardiovascular disease, and stroke can be found in whole saliva. These comparisons and correlations should encourage researchers to consider the use of saliva to discover new protein markers of disease and as a diagnostic non-proximal fluid to detect early signs of disease throughout the body.
We discover a new contribution to the pressure (or stress) exerted by a suspension of self-propelled bodies. Through their self-motion, all active matter systems generate a unique swim pressure that ...is entirely athermal in origin. The origin of the swim pressure is based upon the notion that an active body would swim away in space unless confined by boundaries-this confinement pressure is precisely the swim pressure. Here we give the micromechanical basis for the swim stress and use this new perspective to study self-assembly and phase separation in active soft matter. The swim pressure gives rise to a nonequilibrium equation of state for active matter with pressure-volume phase diagrams that resemble a van der Waals loop from equilibrium gas-liquid coexistence. Theoretical predictions are corroborated by Brownian dynamics simulations. Our new swim stress perspective can help analyze and exploit a wide class of active soft matter, from swimming bacteria to catalytic nanobots to molecular motors that activate the cellular cytoskeleton.
Evidence suggests interplay among the three major risk factors for Alzheimer’s disease (AD): age, APOE genotype, and sex. Here, we present comprehensive datasets and analyses of brain transcriptomes ...and blood metabolomes from human apoE2-, apoE3-, and apoE4-targeted replacement mice across young, middle, and old ages with both sexes. We found that age had the greatest impact on brain transcriptomes highlighted by an immune module led by Trem2 and Tyrobp, whereas APOE4 was associated with upregulation of multiple Serpina3 genes. Importantly, these networks and gene expression changes were mostly conserved in human brains. Finally, we observed a significant interaction between age, APOE genotype, and sex on unfolded protein response pathway. In the periphery, APOE2 drove distinct blood metabolome profile highlighted by the upregulation of lipid metabolites. Our work identifies unique and interactive molecular pathways underlying AD risk factors providing valuable resources for discovery and validation research in model systems and humans.
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•Aging leads to the most profound changes in brain gene expression networks•Immune module led by Alzheimer’s risk genes Trem2/Tyrobp is upregulated with aging•Alzheimer’s risk allele APOE4 increases the expression of Serpina3 family genes•Alzheimer’s protective allele APOE2 drives unique serum metabolome profiles
Zhao et al. present comprehensive datasets and analyses of brain transcriptomes and blood metabolomes from human apoE2-, apoE3-, and apoE4-targeted replacement mice across young, middle, and old ages with both sexes. The study provides critical insight on the molecular pathways underlying three major Alzheimer’s risk factors age, APOE, and sex.
APOE4 is the strongest genetic risk factor associated with late-onset Alzheimer's disease (AD). To address the underlying mechanism, we develop cerebral organoid models using induced pluripotent stem ...cells (iPSCs) with APOE ε3/ε3 or ε4/ε4 genotype from individuals with either normal cognition or AD dementia. Cerebral organoids from AD patients carrying APOE ε4/ε4 show greater apoptosis and decreased synaptic integrity. While AD patient-derived cerebral organoids have increased levels of Aβ and phosphorylated tau compared to healthy subject-derived cerebral organoids, APOE4 exacerbates tau pathology in both healthy subject-derived and AD patient-derived organoids. Transcriptomics analysis by RNA-sequencing reveals that cerebral organoids from AD patients are associated with an enhancement of stress granules and disrupted RNA metabolism. Importantly, isogenic conversion of APOE4 to APOE3 attenuates the APOE4-related phenotypes in cerebral organoids from AD patients. Together, our study using human iPSC-organoids recapitulates APOE4-related phenotypes and suggests APOE4-related degenerative pathways contributing to AD pathogenesis.
Macroscopic mechanical properties of granular materials are closely related to particle morphology. For practical reasons, the morphological features are commonly examined from projected ...two-dimensional (2D) images of the three-dimensional (3D) particles. This brings forward the need for quantifying the correlations between the 2D and 3D particle descriptors. This paper addresses these correlations for irregular granular particles. Three-dimensional images of sand particles were acquired through microfocus X-ray computed tomography, based on which 3D surfaces of the particles were reconstructed using spherical harmonic analyses. The 3D particle size and shape descriptors were subsequently evaluated. All-around projection and random projection of the particles onto 2D planes were undertaken numerically to obtain the projected 2D images and thus the corresponding 2D size and shape descriptors. The results indicate that there are close correlations between 3D and 2D size descriptors averaged from the all-around projections. 2D and 3D shape descriptors can be approximately fitted with a linear relationship. The mean value of 2D descriptors of the tested sands obtained from a series of independent random-projection tests is essentially identical to that from the all-around projections; except that the data from the random-projection tests show a larger scatter. In light of the relationships among the descriptors, a novel and promising approach to predict the cumulative distribution of 3D descriptors from that of 2D descriptors evaluated from a random-projection test is proposed.
The COVID pandemic disrupted health care spending and utilization, and the Medicare Shared Savings Program (MSSP), Medicare’s largest value-based payment model with 11.2 million assigned ...beneficiaries, was no exception. Despite COVID, the 513 accountable care organizations (ACO) in MSSP returned a program record $1.9 billion in net savings to Medicare in 2020. To understand the extent of COVID’s impact on MSSP cost and quality, we describe how ACO spending changed in 2020 and further analyze changes in measured quality and utilization. We found that non-COVID per capita spending in MSSP fell by 8.3 percent from $11,496 to $10,537 (95% confidence interval(CI),-1,223.8 to-695.4, p<0.001), driven by 14.6% and 7.5% reductions in per capita acute inpatient and outpatient spending, respectively. Utilization fell across inpatient, emergency, and outpatient settings. On quality metrics, preventive screening rates remained stable or improved, while control of diabetes and blood pressure worsened. Large reductions in non-COVID utilization helped ACOs succeed financially in 2020, but worsening chronic disease measures are concerning. The appropriateness of the benchmark methodology and exclusion of COVID-related spending, especially as the virus approaches endemicity, should be revisited to ensure bonus payments reflect advances in care delivery and health outcomes rather than COVID-related shifts in spending and utilization patterns.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
OBJECTIVE:The ε4 allele of the APOE gene (APOE4) is the strongest genetic risk factor for Alzheimer disease when compared with the common ε3 allele. Although there has been significant progress in ...understanding how apoE4 (apolipoprotein E4) drives amyloid pathology, its effects on amyloid-independent pathways, in particular cerebrovascular integrity and function, are less clear.
APPROACH AND RESULTS:Here, we show that brain pericytes, the mural cells of the capillary walls, differentially modulate endothelial cell phenotype in an apoE isoform-dependent manner. Extracellular matrix protein induction, tube-like structure formation, and barrier formation were lower with endothelial cells cocultured with pericytes isolated from apoE4-targeted replacement (TR) mice compared with those from apoE3-TR mice. Importantly, aged apoE4-targeted replacement mice had decreased extracellular matrix protein expression and increased plasma protein leakages compared with apoE3-TR mice.
CONCLUSIONS:ApoE4 impairs pericyte-mediated basement membrane formation, potentially contributing to the cerebrovascular effects of apoE4.
Zoonotic and pandemic influenza continue to pose threats to global public health. Pandemics arise when novel influenza A viruses, derived in whole or in part from animal or avian influenza viruses, ...adapt to transmit efficiently in a human population that has little population immunity to contain its onward transmission. Viruses of previous pandemic concern, such as influenza A(H7N9), arose from influenza A(H9N2) viruses established in domestic poultry acquiring a hemagglutinin and neuraminidase from influenza A viruses of aquatic waterfowl. We report a novel influenza A(H3N8) virus in chicken that has emerged in a similar manner and that has been recently reported to cause zoonotic disease. Although they are H3 subtype, these avian viruses are antigenically distant from contemporary human influenza A(H3N2) viruses, and there is little cross-reactive immunity in the human population. It is essential to heighten surveillance for these avian A(H3N8) viruses in poultry and in humans.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The human genome contains "dark" gene regions that cannot be adequately assembled or aligned using standard short-read sequencing technologies, preventing researchers from identifying mutations ...within these gene regions that may be relevant to human disease. Here, we identify regions with few mappable reads that we call dark by depth, and others that have ambiguous alignment, called camouflaged. We assess how well long-read or linked-read technologies resolve these regions.
Based on standard whole-genome Illumina sequencing data, we identify 36,794 dark regions in 6054 gene bodies from pathways important to human health, development, and reproduction. Of these gene bodies, 8.7% are completely dark and 35.2% are ≥ 5% dark. We identify dark regions that are present in protein-coding exons across 748 genes. Linked-read or long-read sequencing technologies from 10x Genomics, PacBio, and Oxford Nanopore Technologies reduce dark protein-coding regions to approximately 50.5%, 35.6%, and 9.6%, respectively. We present an algorithm to resolve most camouflaged regions and apply it to the Alzheimer's Disease Sequencing Project. We rescue a rare ten-nucleotide frameshift deletion in CR1, a top Alzheimer's disease gene, found in disease cases but not in controls.
While we could not formally assess the association of the CR1 frameshift mutation with Alzheimer's disease due to insufficient sample-size, we believe it merits investigating in a larger cohort. There remain thousands of potentially important genomic regions overlooked by short-read sequencing that are largely resolved by long-read technologies.
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