Project description:Despite the vast amounts of information gathered about gliomas, the overall survival of glioma patients has not improved in the last four decades. This could partially be due to an apparent failure to include basic concepts of glioma biology into clinical trials. Specifically, attempts to overcome the limitations of the blood brain barrier (BBB) and the chemoresistance of glioma stem cells (GSCs) were seldom included (a phenomenon known as the translational gap, TG) in a study involving 29 Phase I/II clinical trials (P2CT) published in 2011. The aim of this study was to re-evaluate this finding with a new series of 100 ongoing, but still unpublished, P2CT in order to determine if there is a TG reduction. As indicators, we evaluated in each P2CT the number of drugs tested, concomitant radiotherapy, and the ability of drugs to pass the BBB and to target GSCs. Compared to clinical trials published in 2011, we found that while in OCT there is an increase in the number of P2CT using two drugs (from 24.1% to 44.9%), and an increase in the number of drugs able to pass the BBB (7.14% versus 64.29%) and target GSCs (0% versus 16.3%), there was a decrease in the number of P2CT using concomitant radiotherapy (34.5% versus 18.37%). Overall our results suggest that there is only a modest improvement regarding reducing the TG because the vast majority of ongoing P2CT are still not including well known concepts of glioma biology important for a successful treatment.
Project description:BackgroundThe objective of the study is to analyse the regions, age and sex differences in the incidence of knee osteoarthritis (KOA).MethodsData were extracted from the global burden of diseases (GBD) 2019 study, including incidence, years lived with disability (YLD), disability-adjusted life-years (DALYs) and risk factors. Estimated annual percentage changes (EAPCs) were calculated to quantify the temporal trends in age standardized rate (ASR) of KOA. Paired t-test, paired Wilcoxon signed-rank test and spearman correlation were performed to analyze the association of sex disparity in KOA and socio-demographic index (SDI).ResultsThere were significant regional differences in the incidence of knee osteoarthritis. In 2019, South Korea had the highest incidence of knee osteoarthritis (474.85,95%UI:413.34-539.64) and Thailand had the highest increase in incidence of knee osteoarthritis (EAPC = 0.56, 95%CI = 0.54-0.58). Notably, higher incidence, YLD and DALYs of knee osteoarthritis were associated with areas with a high socio-demographic index (r = 0.336, p < 0.001; r = 0.324, p < 0.001; r = 0.324, p < 0.001). In terms of age differences, the greatest increase in the incidence of knee osteoarthritis was between the 35-39 and 40-44 age groups. (EAPC = 0.52, 95%CI = 0.40-0.63; 0.47, 95%CI = 0.36-0.58). In addition, there were significant sex differences in the disease burden of knee osteoarthritis (P < 0.001).ConclusionsThe incidence of knee osteoarthritis is significantly different with regions, age and sex.
Project description:Despite continuous updates of the human reference genome, there are still hundreds of unresolved gaps which account for about 5% of the total sequence length. Given the availability of whole genome de novo assemblies, especially those derived from long-read sequencing data, gap-closing sequences can be determined. By comparing 17 de novo long-read sequencing assemblies with the human reference genome, we identified a total of 1,125 gap-closing sequences for 132 (16.9% of 783) gaps and added up to 2.2 Mb novel sequences to the human reference genome. More than 90% of the non-redundant sequences could be verified by unmapped reads from the Simons Genome Diversity Project dataset. In addition, 15.6% of the non-reference sequences were found in at least one of four non-human primate genomes. We further demonstrated that the non-redundant sequences had high content of simple repeats and satellite sequences. Moreover, 43 (32.6%) of the 132 closed gaps were shown to be polymorphic; such sequences may play an important biological role and can be useful in the investigation of human genetic diversity.
Project description:BackgroundThe fast reduction of prices of DNA sequencing allowed rapid accumulation of genome data. However, the process of obtaining complete genome sequences is still very time consuming and labor demanding. In addition, data produced from various sequencing technologies or alternative assemblies remain underexplored to improve assembly of incomplete genome sequences.FindingsWe have developed FGAP, a tool for closing gaps of draft genome sequences that takes advantage of different datasets. FGAP uses BLAST to align multiple contigs against a draft genome assembly aiming to find sequences that overlap gaps. The algorithm selects the best sequence to fill and eliminate the gap.ConclusionsFGAP reduced the number of gaps by 78% in an E. coli draft genome assembly using two different sequencing technologies, Illumina and 454. Using PacBio long reads, 98% of gaps were solved. In human chromosome 14 assemblies, FGAP reduced the number of gaps by 35%. All the inserted sequences were validated with a reference genome using QUAST. The source code and a web tool are available at http://www.bioinfo.ufpr.br/fgap/.
Project description:Topological phase transition is accompanied with a change of topological numbers. According to the bulk-edge correspondence, the gap closing and the breakdown of the adiabaticity are necessary at the phase transition point to make the topological number ill-defined. However, the gap closing is not always needed. In this paper, we show that two topological distinct phases can be continuously connected without gap closing, provided the symmetry of the system changes during the process. Here we propose the generic principles how this is possible by demonstrating various examples such as 1D polyacetylene with the charge-density-wave order, 2D silicene with the antiferromagnetic order, 2D silicene or quantum well made of HgTe with superconducting proximity effects and 3D superconductor Cu doped Bi2Se3. It is argued that such an unusual phenomenon can occur when we detour around the gap closing point provided the connection of the topological numbers is lost along the detour path.
Project description:Bone strength in human cortical bone is determined by the composition and structure of both the mineral and collagen matrices and influenced by factors such as age, gender, health, lifestyle and genetic factors. Age-related changes in the bone matrix are known to result in loss of mechanical strength and increased fragility. In this study we show how Raman spectroscopy, with its exquisite sensitivity to the molecular structure of bone, reveals new insights into age- and sex-related differences. Raman analysis of 18 samples of cortical hip bone obtained from people aged between 47-82 years with osteoarthritis (OA) found subtle changes in the lipid and collagen secondary structure, and the carbonate (CO32-) and phosphate (PO43-) mineral ratios in the bone matrix. Significant differences were observed between older and younger bones, and between older female and older male bones; no significant differences were observed between younger male and female bones. Older female bones presented the lowest mineral to matrix ratios (MMR) and highest CO32-/PO43- ratios, and relative to lipid/collagen -CH2 deformation modes at 1450 cm-1 they had lowest overall mineral content, higher collagen cross linking and lipid content but lower levels of α-helix collagen structures than older male and younger male and female bones. These observations provided further insight on bone composition changes observed in the bone volume fraction (BV/TV) for the older female bones from microCT measurements on the same samples, while tissue mineral density (TMD) measurements had shown no significant differences between the samples.
Project description:China accounts for 1/5 of the global population and China faces a particularly heavy dementia burden due to its rapidly ageing population. Unique historical events, genetic background, sociocultural factors, lifestyle, and the COVID-19 pandemic further influence cognitive outcomes in the Chinese population. We searched PubMed, Web of Science, and Embase for community-based cohort studies related to dementia in the Chinese population, and summarized the characteristics, methodologies, and major findings published over the last 25 years from 39 cohorts. We identified critical research gaps and propose future directions, including enhancing sample representativeness, investigating China-specific risk factors, expanding exposure measurements to the whole life-span, collecting objective data, conducting administer-friendly domain-specific cognitive assessments, adopting pathological diagnostic criteria, standardizing biobank construction, verifying multi-modal biomarkers, examining social and genetic-environmental aspects, and monitoring post-COVID cognitive health, to approach high quality of dementia studies that can provide solid evidence to policy making and promote global brain health research.
Project description:Individualized outcome prediction classifiers were successfully constructed through expression profiling of a total of 779 genes in microglial cells from 36 mice, which had been consecutively operated on within a defined short period of time
Project description:The fibromyalgia syndrome (FMS) is characterized by chronic widespread pain, sleep disturbances, fatigue, and cognitive alterations. A limited efficacy of targeted treatment and a high FMS prevalence (2-5% of the adult population) sums up to high morbidity. Although, altered nociception has been explained with the central sensitization hypothesis, which may occur after neuropathy, its molecular mechanism is not understood. The marked female predominance among FMS patients is often attributed to a psychosocial predisposition of the female gender, but here we will focus on sex differences in neurobiological processes, specifically those of the immune system, as various immunological biomarkers are altered in FMS. The activation of innate immune sensors is compatible with a neuropathy or virus-induced autoimmune diseases. Considering sex differences in the immune system and the clustering of FMS with autoimmune diseases, we hypothesize that the female predominance in FMS is due to a neuropathy-induced autoimmune pathophysiology. We invite the scientific community to verify the autoimmune hypothesis for FMS.