Purpose
The paraspinal muscles (PSM) are a key feature potentially related to low back pain (LBP), and their structure and composition can be quantified using MRI. Most commonly, quantifying PSM ...measures across individual muscles and individual spinal levels renders numerous separate metrics that are analyzed in isolation. However, comprehensive multivariate approaches would be more appropriate for analyzing the PSM within an individual. To establish and test these methods, we hypothesized that multivariate summaries of PSM MRI measures would associate with the presence of LBP symptoms (i.e., pain intensity).
Methods
We applied hierarchical multiple factor analysis (hMFA), an unsupervised integrative method, to clinical PSM MRI data from unique cohort datasets including a longitudinal cohort of astronauts with pre- and post-spaceflight data and a cohort of chronic LBP subjects and asymptomatic controls. Three specific use cases were investigated: (1) predicting longitudinal changes in pain using combinations of baseline PSM measures; (2) integrating baseline and post-spaceflight MRI to assess longitudinal change in PSM and how it relates to pain; and (3) integrating PSM quality and adjacent spinal pathology between LBP patients and controls.
Results
Overall, we found distinct complex relationships with pain intensity between particular muscles and spinal levels. Subjects with high asymmetry between left and right lean muscle composition and differences between spinal segments PSM quality and structure are more likely to increase in pain reported outcome after prolonged time in microgravity. Moreover, changes in PSM quality and structure between pre and post-spaceflight relate to increase in pain after prolonged microgravity. Finally, we show how unsupervised hMFA recapitulates previous research on the association of CEP damage and LBP diagnostic.
Conclusion
Our analysis considers the spine as a multi-segmental unit as opposed to a series of discrete and isolated spine segments. Integrative and multivariate approaches can be used to distill large and complex imaging datasets thereby improving the clinical utility of MRI-based biomarkers, and providing metrics for further analytical goals, including phenotyping.
•DODAB liposomes were coated with the xanthan and galactomannan biopolymers by LbL.•The non-ionic interaction between xanthan and galactomannan stabilize the LbL.•Stable LbL coating of liposomes ...extend the release of EGF up to 5 times.
A three-dimensional layer-by-layer (LbL) structure composed by xanthan and galactomannan biopolymers over dioctadecyldimethylammonium bromide (DODAB) liposome template was proposed and characterized for protein drug delivery. The polymers and the surfactant interaction were sufficiently strong to create a LbL structure up to 8 layers, evaluated using quartz crystal microbalance (QCM) and zeta potential analysis. The polymer–liposome binding enthalpy was determined by isothermal titration calorimetry (ITC). The bilayer of biopolymer-coated liposomes with diameters of 165 (±15)nm, measured by dynamic light scattering (DLS), and ζ-potential of −4 (±13)mV. These bilayer-coated nanoparticles increased up to 5 times the sustained release of epidermal growth factor (EGF) at a first order rate of 0.005min−1. This system could be useful for improving the release profile of low-stability drugs like EGF.
Patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer who have disease progression after therapy with multiple HER2-targeted agents have limited treatment ...options. Tucatinib is an investigational, oral, highly selective inhibitor of the HER2 tyrosine kinase.
We randomly assigned patients with HER2-positive metastatic breast cancer previously treated with trastuzumab, pertuzumab, and trastuzumab emtansine, who had or did not have brain metastases, to receive either tucatinib or placebo, in combination with trastuzumab and capecitabine. The primary end point was progression-free survival among the first 480 patients who underwent randomization. Secondary end points, assessed in the total population (612 patients), included overall survival, progression-free survival among patients with brain metastases, confirmed objective response rate, and safety.
Progression-free survival at 1 year was 33.1% in the tucatinib-combination group and 12.3% in the placebo-combination group (hazard ratio for disease progression or death, 0.54; 95% confidence interval CI, 0.42 to 0.71; P<0.001), and the median duration of progression-free survival was 7.8 months and 5.6 months, respectively. Overall survival at 2 years was 44.9% in the tucatinib-combination group and 26.6% in the placebo-combination group (hazard ratio for death, 0.66; 95% CI, 0.50 to 0.88; P = 0.005), and the median overall survival was 21.9 months and 17.4 months, respectively. Among the patients with brain metastases, progression-free survival at 1 year was 24.9% in the tucatinib-combination group and 0% in the placebo-combination group (hazard ratio, 0.48; 95% CI, 0.34 to 0.69; P<0.001), and the median progression-free survival was 7.6 months and 5.4 months, respectively. Common adverse events in the tucatinib group included diarrhea, palmar-plantar erythrodysesthesia syndrome, nausea, fatigue, and vomiting. Diarrhea and elevated aminotransferase levels of grade 3 or higher were more common in the tucatinib-combination group than in the placebo-combination group.
In heavily pretreated patients with HER2-positive metastatic breast cancer, including those with brain metastases, adding tucatinib to trastuzumab and capecitabine resulted in better progression-free survival and overall survival outcomes than adding placebo; the risks of diarrhea and elevated aminotransferase levels were higher with tucatinib. (Funded by Seattle Genetics; HER2CLIMB ClinicalTrials.gov number, NCT02614794.).
Beneficial interactions between plant roots and rhizosphere microorganisms are pivotal for plant fitness. Nevertheless, the molecular mechanisms controlling the feedback between root architecture and ...microbial community structure remain elusive in maize. Here, we demonstrate that transcriptomic gradients along the longitudinal root axis associate with specific shifts in rhizosphere microbial diversity. Moreover, we have established that root-derived flavones predominantly promote the enrichment of bacteria of the taxa Oxalobacteraceae in the rhizosphere, which in turn promote maize growth and nitrogen acquisition. Genetic experiments demonstrate that LRT1-mediated lateral root development coordinates the interactions of the root system with flavone-dependent Oxalobacteraceae under nitrogen deprivation. In summary, these experiments reveal the genetic basis of the reciprocal interactions between root architecture and the composition and diversity of specific microbial taxa in the rhizosphere resulting in improved plant performance. These findings may open new avenues towards the breeding of high-yielding and nutrient-efficient crops by exploiting their interaction with beneficial soil microorganisms.
The spread of protein aggregates during disease progression is a common theme underlying many neurodegenerative diseases. The microtubule-associated protein tau has a central role in the pathogenesis ...of several forms of dementia known as tauopathies-including Alzheimer's disease, frontotemporal dementia and chronic traumatic encephalopathy
. Progression of these diseases is characterized by the sequential spread and deposition of protein aggregates in a predictable pattern that correlates with clinical severity
. This observation and complementary experimental studies
have suggested that tau can spread in a prion-like manner, by passing to naive cells in which it templates misfolding and aggregation. However, although the propagation of tau has been extensively studied, the underlying cellular mechanisms remain poorly understood. Here we show that the low-density lipoprotein receptor-related protein 1 (LRP1) controls the endocytosis of tau and its subsequent spread. Knockdown of LRP1 significantly reduced tau uptake in H4 neuroglioma cells and in induced pluripotent stem cell-derived neurons. The interaction between tau and LRP1 is mediated by lysine residues in the microtubule-binding repeat region of tau. Furthermore, downregulation of LRP1 in an in vivo mouse model of tau spread was found to effectively reduce the propagation of tau between neurons. Our results identify LRP1 as a key regulator of tau spread in the brain, and therefore a potential target for the treatment of diseases that involve tau spread and aggregation.
We compared fine-scale recombination rates at orthologous loci in humans and chimpanzees by analyzing polymorphism data in both species. Strong statistical evidence for hotspots of recombination was ...obtained in both species. Despite ~99% identity at the level of DNA sequence, however, recombination hotspots were found rarely (if at all) at the same positions in the two species, and no correlation was observed in estimates of fine-scale recombination rates. Thus, local patterns of recombination rate have evolved rapidly, in a manner disproportionate to the change in DNA sequence.
Although the Unruh effect can be rigorously considered as well tested as free quantum field theory itself, it would be nice to provide experimental evidence of its existence. This is not easy because ...the linear acceleration needed to reach a temperature 1 K is of order 10^{20} m/s^{2}. Here, we propose a simple experiment reachable under present technology whose result may be directly interpreted in terms of the Unruh thermal bath. Instead of waiting for experimentalists to perform it, we use standard classical electrodynamics to anticipate its output and fulfill our goal.
Haemogregarines are a group of intracellular blood parasites reported in reptiles, other vertebrate taxa including mammals and fish, and haematophagous invertebrates. Information on prevalence, ...biodiversity, and host-specificity of haemogregarines of tortoises in Nigeria are scarce. A total of 120 African hinge-back tortoises (Kinixys belliana, n=70, and K. homeana, n=50) were bought from the Wildlife and Herbal Market in Ibadan, Nigeria. Blood was withdrawn via the subcarapacial sinuses of each tortoise. The prevalence and parasite intensity of haemogregarine infection was determined using a light microscope, and parasite species were determined by PCR using HepF300 and HepR900 primers. A sequence of 654 base pairs (bp; Hepatozoon cf. fitzsimonsi) from the study aligned with published 18SrRNA and closely related with a similarity of 97.38% to Hepatozoon fitzsimonsi sequenced from Kinixys zobensis in South Africa. Overall prevalence of haemogregarines was 53.33% from light microcopy and 75.83% from PCR, which is considered very high. Higher prevalence and mean±SD parasite intensity were recorded for K. belliana (82.89%, 0.29%) than for K. homeana (66.00%, 0.26%). Prevalence rates and parasite intensities of haemogregarines were significantly higher in wet than in dry seasons. The differences in prevalence and intensity between and within species may be due to habitat characteristics, feeding habits of vectors and hosts, seasons, and vector abundance.
En este trabajo se recopila y analiza información sobre la iconografía de personajes antropomorfos de brazos alzados, registrada en diversos espacios y sociedades andinas (Perú, Bolivia, norte de ...Chile y Noroeste Argentino) y representada en distintos soportes entre 4000 y 500 años AP. A partir de un estudio comparativo de este tipo de motivos en el arte rupestre del sitio Cueva Inca Viejo, en la puna de Salta, se rastrea la diversidad de estas figuras antropomorfas y sus asociaciones con determinados atributos o variantes, estableciendo así una cronología relativa o aproximada, desde el primer milenio DC hasta la expansión incaica. Los resultados reflejan rasgos compartidos entre las representaciones de la cueva y las figuras andinas analizadas, como los brazos flexionados y elevados, la posición frontal o atributos felínicos. En relación con la variabilidad macrorregional de estos personajes, se reconocen diversos objetos o elementos asociados, como cetros, cabezas cercenadas, propulsores y hachas. Junto con estas variaciones, sobresale una tradición cultural de antigua data, cuya iconografía muestra patrones comunes a lo largo de los Andes.
Graphene-Based Micro-Rectenna Resende, Ursula C.; Mello, Thiago H. G.; Almeida, Gabriel A. T. ...
IEEE transactions on magnetics,
03/2024, Letnik:
60, Številka:
3
Journal Article
Odprti dostop
The increasing demand for sustainable energy generation has often pointed to solar energy as an exceedingly promising alternative. A new procedure to harvest solar energy is using solar rectennas, ...which are composed of micro-sized antennas and nanodiodes. This configuration allows the capture and conversion of electromagnetic (EM) energy into direct current. The challenges in developing this technology arise as the wave frequency increases to terahertz spectrum, causing metals to no longer exhibit perfect electrical conductivity (PEC) behavior, and diodes deviate from classical modeling, approaching more toward quantum model. Within this context, this work presents an investigative study on a novel solar rectenna designed to operate at 30 THz. It consists of a micro-bowtie antenna and a geometric diode, both constructed using graphene as conducting material. The antenna is designed using classical EM theory employing CST software. For the diode, a parametric study is conducted to seek the optimal <inline-formula> <tex-math notation="LaTeX">I </tex-math></inline-formula>-<inline-formula> <tex-math notation="LaTeX">V </tex-math></inline-formula> relationship. Given the complexity and time demands of quantum analysis, an approach utilizing the Monte Carlo (MC) method is proposed. The novelty of this approach lies in the time discretization process, triggered only when a collision occurs between the electrons and the rectifier boundaries.
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