Chromatin immunoprecipitation experiments and transactivation ass

Chromatin immunoprecipitation experiments and transactivation assays revealed that high throughput screening assay p63 controls these genes at the transcriptional level. Consistent with reduced desmosome function, AEC mutant and p63-deficient keratinocytes had an impaired ability to withstand mechanical stress, which was alleviated by epidermal growth factor receptor inhibitors known to stabilize desmosomes. Our study reveals that p63 is

a crucial regulator of a subset of desmosomal genes and that this function is impaired in AEC syndrome. Reduced mechanical strength resulting from p63 mutations can be alleviated pharmacologically by increasing desmosome adhesion with possible therapeutic implications.”
“MicroRNAs (miRNAs) show differential expression

across breast cancer subtypes, and have both oncogenic and tumour-suppressive roles(1-6). Here we report the miRNA expression profiles of 1,302 breast tumours with matching detailed clinical annotation, long-term follow-up and genomic and messenger RNA expression data(7). This provides WH-4-023 mw a comprehensive overview of the quantity, distribution and variation of the miRNA population and provides information on the extent to which genomic, transcriptional and post-transcriptional events contribute to miRNA expression architecture, suggesting an important role for post-transcriptional regulation. The key clinical parameters and cellular pathways related to the miRNA landscape are characterized, revealing context-dependent interactions, for example with regards to cell adhesion and Wnt signalling. Notably, only prognostic miRNA signatures derived from breast tumours devoid of somatic copy-number aberrations (CNA-devoid) are consistently prognostic across several other subtypes and can be validated in external cohorts. We then use a data-driven approach(8) to seek the effects of miRNAs associated with differential co-expression of mRNAs, and find that

miRNAs act as modulators of mRNA-mRNA interactions rather than as on-off molecular switches. We demonstrate such an important modulatory role for miRNAs in the biology of CNA-devoid breast cancers, a common subtype in which the immune response is prominent. These findings represent a new framework for studying the biology of miRNAs in human breast cancer.”
“Background: Many investigators have conducted BI-D1870 supplier Studies to determine the biomechanics, causes, complications and treatment of unilateral facet joint dislocation in the cervical pine However, there is no quantitative data available on morphological changes in the intervertebral foramen of the cervical spine following unilateral facet joint dislocation These data are important to understand the cause of neurological compromise following unilateral facet joint dislocation.\n\nMethods Eight embalmed human cadaver cervical spine specimens ranging from level C1-T1 were used The nerve roots of these specimens at C5-C6 level were marked by wrapping a 0 12 mm diameter wire around them.

To investigate the potential impact of exercise training in this

To investigate the potential impact of exercise training in this patient group, a larger randomized trial is warranted.”
“Hybrid procedure (HP) involves epicardial isolation of pulmonary vein and posterior wall of left atrium, and endocardial checking of lesions and touchups (if needed). We aimed at observing the effect of hybrid procedure on P wave duration (PWD), calculated automatically from surface ECG leads at start and end of HP, and also for relationship to atrial fibrillation buy Liproxstatin-1 (AF) recurrence

at 9 months. Forty-one patients (32 male; mean age, 58.4 +/- 9.5 years) underwent HP, as first ever ablation. A new automated method was used for P wave segmentation and PWD estimation from recognizable P waves in ECG lead I or II before and after HP, based on fitting of each P wave by means of two Gaussian functions. Overall, PWD was significantly decreased after procedure (104.4 +/- 25.1 ms vs. 84.7 +/- 23.8 ms, p = 0.0151), especially in persistent AF patients (122.4 +/- 32.2 ms vs. 85.6 +/- 24.5 ms, p = 0.02). PWD preprocedure was significantly higher in persistent than in paroxysmal patients (122.4 +/- 32.2 ms vs. 92.5 Proteases inhibitor +/- 17.9 ms, p = 0.0383). PWD was significantly decreased after procedure in prior electrical cardioverted patients (106.7

+/- 30.5 ms vs. 84.7 +/- 23.1 ms, p = 0.0353). After 9-month follow-up of 40 patients, HP-induced PWD decrease was significant for the 12 persistent patients without recurrence (122.4.1 +/- 35.3 ms vs. 85.6 +/- 22.0 ms, p = 0.0210). Preprocedure PWD was higher for persistent than paroxysmal patients. HP reduced PWD significantly. Nine-month follow-up suggests that HP is successful in restoring

and maintaining sinus rhythm. To individualize AF therapy, AF type-based Rabusertib selection of patients may be possible before procedure. Automated analysis of PWD from surface ECG is possible.”
“Rationale: Cross-sectional studies demonstrate an association between metabolic syndrome and impaired lung function.\n\nObjectives: To define if metabolic syndrome biomarkers are risk factors for loss of lung function after irritant exposure.\n\nMethods: A nested case-control study of Fire Department of New York personnel with normal pre-September 11th FEV1 and who presented for subspecialty pulmonary evaluation before March 10, 2008. We correlated metabolic syndrome biomarkers obtained within 6 months of World Trade Center dust exposure with subsequent FEV1. FEV1 at subspecialty pulmonary evaluation within 6.5 years defined disease status; cases had FEV1 less than lower limit of normal, whereas control subjects had FEV1 greater than or equal to lower limit of normal.

Leaf samples of six plant species (Radermachera sinica, Sapium ro

Leaf samples of six plant species (Radermachera sinica, Sapium rotundifolium, Sterculia euosma, Schefflera octophylla, Alchornea trewioides, and Vitex negundo, in different life-forms and leaf phenologies)

were collected for carbon isotope measurements in the wet and dry seasons, respectively. Contrary to the expectation, the evergreen big shrub species, S. octophylla, which always relied on deep water sources, exhibited the most positive delta C-13 values (high water-use efficiency, WUE), indicating more conservative water-use strategies. While the two deciduous small shrubs, A. trewioides and V. negundo, which always relied on shallow water sources, exhibited the most negative delta C-13 values (low Alvocidib purchase WUE). This result was associated with their short life spans, indicating an opportunistic water-use strategy. Leaf delta C-13 values of almost all (except for S. octophylla)

the selected www.selleckchem.com/products/mln-4924.html species were significantly (P smaller than 0.05) higher in the dry season than in the wet season. This indicated that it was a common strategy for species in rocky karst habitat to improve their WUE in dry season. Despite the similar water sources utilized by the selected three tree species, the widespread one (R. sinica) exhibited greater improvement in leaf delta C-13 values than the narrow endemic ones (S. rotundifolium and S. euosma). This suggested that the widespread tree species had more flexible water-use strategies. It was further speculated that broad spatial distribution of widespread species may contribute to their highly plastic responses to changes in environmental conditions rather than always maintaining high WUE.”
“Objectives In the brain, the PCI32765 mechanisms of attention to the left and the right are known to be different. It is possible that brain activity when driving also differs with different horizontal road alignments (left or right curves), but little is known about this. We found driver

brain activity to be different when driving on left and right curves, in an experiment using a large-scale driving simulator and functional near-infrared spectroscopy (fNIRS). Research Design and Methods The participants were fifteen healthy adults. We created a course simulating an expressway, comprising straight line driving and gentle left and right curves, and monitored the participants under driving conditions, in which they drove at a constant speed of 100 km/h, and under non-driving conditions, in which they simply watched the screen (visual task). Changes in hemoglobin concentrations were monitored at 48 channels including the prefrontal cortex, the premotor cortex, the primary motor cortex and the parietal cortex.

In contrast to soluble alpha-galactosylceramide, which caused NKT

In contrast to soluble alpha-galactosylceramide, which caused NKT anergy after single stimulation, nanoparticle

formulated alpha-galactosylceramide repeatedly stimulates NKT cells without inducing anergy. Mechanistic studies showed that nanoparticle formulated alpha-galactosylceramide is efficiently presented by Mouse CD11c + population containing dendritic cells, and CD11b + population containing macrophages, but very poorly by B220 + Population containing B cells. Hence, nanoparticle formulated alpha-galactosylceramide is an attractive immunomodulator for immunotherapy and vaccine development. Future studies will be focused on its application as adjuvant for protein and/or peptide antigens. (c) 2009 Elsevier Ltd. SNX-5422 supplier All rights reserved.”
“Background: De-escalating natalizumab (NTZ) to interferon beta 1b (IFN B 1B) is a possible treatment option in multiple sclerosis (MS) patients interrupting NTZ because of increased risk of progressive multifocal leukoencephalopathy (PML). The aim of this study was

to evaluate satisfaction and adherence to treatment, behavioral and fatigue changes in patients switched to IFN B 1B compared to continued NTZ treatment.\n\nMethods: A 1 year, prospective, randomized, rater-blinded, parallel-group study. Nineteen selleck products relapsing remitting (RR) MS patients, randomly assigned to undergo either NTZ (n = 10) or IFN B 1B (n = 9) treatment, who had previously received NTZ for at least 12 months

with Linsitinib chemical structure disease stability and fearing or at risk for PML were included. Patients underwent behavioral and treatment assessments at baseline, after 24-week and 1 year follow-up. Behavioral assessment included measures of cognition, fatigue and quality of life. Treatment assessment included measures of satisfaction, persistence and adherence to treatment. Clinical-radiological disease activity and safety were also assessed.\n\nResults: Baseline characteristics of patients were similar between groups except for Euro Quality Visual Analogue Scale, being higher in the NTZ group (p = 0.04). Within-group comparisons at the three time points, as well as interaction analysis of treatment effect over time did not show any statistically significant differences in behavioral or treatment assessments, but a coherent trend favoring NTZ over IFN B 1B.\n\nConclusions: De-escalating NTZ to IFN B 1B is feasible and associated with overall good patient related outcome and persistently stable behavioral measures.”
“This review will cover the recent advances in label-free approaches to isolate and manipulate circulating tumor cells (CTCs).

Further study indicated that sialidase failed to affect Cx43 at e

Further study indicated that sialidase failed to affect Cx43 at either protein or phosphorylation level, instead, it induced a considerable fraction of Triton X-100 insoluble, as compared with the untreated cells. We also found that sialidase treatment reduced the N-cadherin glycosylation and enhanced both Cx43-ZO-1 interaction and N-cadherin-ZO-1 association. Moreover, sialidase promoted the cell-cell adhesion with elevating N-cadherin binding to

beta-catenin, accompanied by increasing colocalization of Cx43 with microtubules at the cell periphery. Based on live cell microscopy, with the FARP technology in the Cx43-EGFP-Hela cells, we found that Cx43 in the plague recovered more quickly in sialidase treatment group, indicating that sialidase could promote the Cx43 traffic to the plague. Overall, Apoptosis inhibitor these studies indicate cell surface sialic acid on cancer cells may suppress Cx43 gap junction functions via inhibiting Cx43 traffic to the plague involving in sialylated N-cadherin, a process that likely underlies the intimate association between abnormal GJIC and glycosylation on cancer development.”
“Coherent and reversible mapping of quantum information between

light and matter is an important experimental challenge in quantum information science. In particular, it is an essential requirement for the implementation of quantum networks and quantum repeaters(1-3). So far, quantum interfaces between light and atoms have been demonstrated with atomic gases(4-9), and with single trapped atoms in cavities(10). Here we demonstrate the coherent and reversible mapping selleck kinase inhibitor of a light field with less than one photon per pulse onto an ensemble of similar to 10(7) atoms naturally trapped in a solid. This Torin 2 is achieved

by coherently absorbing the light field in a suitably prepared solid- state atomic medium(11). The state of the light is mapped onto collective atomic excitations at an optical transition and stored for a pre- determined time of up to 1 mu s before being released in a well- defined spatio- temporal mode as a result of a collective interference. The coherence of the process is verified by performing an interference experiment with two stored weak pulses with a variable phase relation. Visibilities of more than 95 per cent are obtained, demonstrating the high coherence of the mapping process at the single- photon level. In addition, we show experimentally that our interface makes it possible to store and retrieve light fields in multiple temporal modes. Our results open the way to multimode solid- state quantum memories as a promising alternative to atomic gases.”
“The nature of excess body weight may be changing over time to one of greater central adiposity. The aim of this study is to determine whether BMI and waist circumference (WC) are increasing proportionately among population subgroups and the range of bodyweight, and to examine the public health implications of the findings.

The CdS/CdSe/CdS nanoplatelets represent a new example of colloid

The CdS/CdSe/CdS nanoplatelets represent a new example of colloidal nanoheterostructures with mixed confinement regimes for electrons and holes. In these materials holes are confined to a thin (similar

to 1.8 nm) two dimensional CdSe quantum well, while the electron confinement can be gradually relaxed in all three dimensions by growing epitaxial CdS layers on both Sides of the quantum well VX-689 The relaxation of the election confinement energy caused a shift of the emission band from 510 to 665 nm with unusually small inhomogeneous broadening of the emission spectra.”
“As researchers continue to understand non-clinical psychosis (NCP-brief psychotic-like experiences occurring in 5-7% of the general population; van Os et al., 2009), it is becoming evident that functioning deficits and facial emotion recognition (FER) impairment characterize this phenomenon. However, the extent to which these domains are related remains unclear. Social/role functioning and FER were assessed in 65 adolescents/young adults exhibiting low and high-NCP. Results indicate that

FER and social/role functioning deficits were present in the High-NCP group, and that the domains were associated in this group alone. Taken together, findings suggest that a core emotive deficit is tied to broader social/role dysfunction in NCP. (C) 2012 Elsevier B.V. All rights reserved.”
“Ellagic acid has been ACY-241 purchase shown to inhibit tumor cell growth. However, the underlying molecular mechanisms remain elusive. In this study, our aim was to investigate whether ellagic acid inhibits the proliferation of MCF-7 human breast cancer cells via regulation of the TGF-beta/Smad3 signaling pathway. MCF-7 breast cancer cells were transfected with pEGFP-C3 or pEGFP-C3/Smad3 plasmids, and treated with ellagic acid alone or in combination with SIS3, a specific inhibitor of Smad3 phosphorylation.

Cell proliferation was assessed by MTT assay and the cell cycle was detected by flow cytometry. Moreover, gene expression was detected by RT-PCR, real-time PCR and Western blot analysis. The PFTα chemical structure MTT assay showed that SIS3 attenuated the inhibitory activity of ellagic acid on the proliferation of MCF-7 cells. Flow cytometry revealed that ellagic acid induced G0/G1 cell cycle arrest which was mitigated by SIS3. Moreover, SIS3 reversed the effects of ellagic acid on the expression of downstream targets of the TGF-beta/Smad3 pathway. In conclusion, ellagic acid leads to decreased phosphorylation of RB proteins mainly through modulation of the TGF-beta/Smad3 pathway, and thereby inhibits the proliferation of MCF-7 breast cancer cells.”
“Objectives: The aim of this study was to elucidate the prognostic significance of mitral regurgitation (MR) after primary percutaneous coronary intervention (PCI) for acute ST-elevation myocardial infarction (STEMI).

BH(4) is formed de novo from GTP via

BH(4) is formed de novo from GTP via Elafibranor a sequence of three enzymatic steps carried out by GTP cyclohydrolase I, 6-pyruvoyltetrahydropterin synthase and sepiapterin reductase. An alternative or salvage pathway involves dihydrofolate reductase and may play an essential role in peripheral tissues. Cofactor regeneration requires pterin-4a-carbinolamine dehydratase and dihydropteridine reductase, except for NOSs, in

which the BH(4), cofactor undergoes a one-electron redox cycle without the need for additional regeneration enzymes. With regard to the regulation of cofactor biosynthesis, the major controlling point is GTP cyclohydrolase I. BH(4), biosynthesis is controlled in mammals by hormones and cytokines. BH(4) deficiency due to autosomal recessive mutations in all enzymes, except for sepiapterin reductase, has been described as a

cause of hyperphenylalaninaemia. A major contributor to vascular dysfunction associated with hypertension, ischaemic reperfusion injury, diabetes and others, appears to be an effect of oxidized BH(4), which leads to an increased formation of oxygen-derived radicals instead of NO by decoupled NOS. Furthermore, several neurological diseases have been suggested to be a consequence of restricted cofactor availability, and oral cofactor ACY-738 price replacement therapy to stabilize mutant phenylalanine hydroxylase in the BH(4)-responsive type of hyperphenylalaninaemia has an advantageous effect on pathological phenylalanine levels in patients.”
“Objective: Numerous population-based studies have found an association between major depression and CVD, though these studies did not assess anxiety disorders. Patient samples have shown associations https://www.selleckchem.com/products/p5091-p005091.html between anxiety disorders and cardiovascular disease (CVD), but without consideration of depressive disorders. Therefore,

it remains unclear whether: (a) both anxiety and depressive disorder are associated with CVD; (b) these associations are generalizable to adults in the community.\n\nMaterials and Methods: Data were drawn from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), a nationally representative sample of 43,093 civilian non-institutionalized participants aged 18 and older.\n\nResults: CVD (total prevalence 3.3%) was associated with increased likelihood of any anxiety disorder (OR = 1.43, (1.20, 1.71)), after adjusting for depressive disorders, as well as Generalized Anxiety Disorder (OR = 1.48 (1.09, 2.01)), Panic disorder (OR = 1.46 (1.12, 1.91)), and specific phobia (OR = 1.29 (1.04, 1.59)). CVD was significantly associated with any mood disorder (OR = 1.34 (1.13, 1.58)) after adjusting for anxiety disorders, though neither the link with major depression, nor other specific mood disorders remained significant after adjustment.

This study was therefore carried out with the objective of estima

This study was therefore carried out with the objective of estimating the biogas production potential of typical Vietnamese biomasses such as animal manure, slaughterhouse waste and plant residues, and developing a model that relates methane (CH4) production to the chemical characteristics of the biomass. The biochemical methane potential (BMP) and biomass characteristics were measured. Results showed that piglet manure produced the highest CH4 yield of 443 normal litter (NL) CH4 kg(-1)

volatile solids (VS) compared to 222 from cows, 177 from sows, 172 from rabbits, 169 from goats and 153 from buffaloes. Methane production from duckweed selleck chemicals llc (Spirodela polyrrhiza) was higher than from lawn grass and water spinach at 340, 220, and 110.6 NL CH4 kg(-1) VS, respectively. The BMP experiment also demonstrated that the CH4 production was inhibited with chicken manure, slaughterhouse www.selleckchem.com/products/jq1.html waste, cassava residue

and shoe-making waste. Statistical analysis showed that lipid and lignin are the most significant predictors of BMP. The model was developed from knowledge that the BMP was related to biomass content of lipid, lignin and protein from manure and plant residues as a percentage of VS with coefficient of determination (R-square) at 0.95.This model was applied to calculate the CH4 yield for a household with 17 fattening pigs in the highlands and lowlands of northern Vietnam.”
“The tolerance to organophosphate pesticide, dichlorvos, is essential for the application of Trichoderma in bioremediation and integrated

pest management, although the molecular events associated with the tolerance process have not yet been elucidated. RNA-seq analysis of wild-type Trichoderma atroviride T23 and the hex1-deleted mutant under dichlorvos stress was designed to search for genes involved in the tolerance process. A total of 5382 differentially expressed genes were identified, highlighting the complex transcriptional changes of T. atroviride in response to dichlorvos stress. 137 genes were regulated by dichlorvos and hex1, encoding major facilitator superfamilies, cytochrome P450, glutathione-S-transferase, flavoprotein, IWR-1-endo Hsp70, Hsp90, etc. Pathway and expression analysis indicated that ABC transporters were affected by the disruption of hex1 gene and might play a vital role in the tolerance process. Expression patterns of seven selected ABC transporter genes were confirmed by qRT-PCR after exposure to dichlorvos for 2, 6 and 24 h. The present study provides insights into the genetic basis of dichlorvos tolerance in Trichoderma that may be exploited for further development of bioremediation or biocontrol agents.”
“Objective Systemic sclerosis (SSc) is characterized by fibrosis of the skin and visceral organs, vascular dysfunction, and immunologic dysregulation. Platelet-derived growth factors (PDGFs) have been implicated in the development of fibrosis and dysregulation of vascular function.

The IL-4-induced

The IL-4-induced find more downregulation of melanogenesis was inhibited by treating NHMs with a JAK2 inhibitor AG490 or STAT6 siRNA. In conclusion, the involvement of the IL-4-induced JAK2-STAT6 signaling and the IFN gamma- or IL-17A-dependent antimelanogenic IL-6 production should be considered as one of the mechanisms explaining the association with hypopigmention in skin diseases. Journal of Investigative Dermatology (2013) 133, 528-536; doi:10.1038/iid.2012.331;

published online 20 September 2012″
“Infectious diseases affecting livestock and human health that involve vector-borne pathogens are a global problem, unrestricted by borders or boundaries, which may be exacerbated by changing global climate. Thus, the availability of effective tools for control of pathogen vectors is of the utmost importance. The aim of this

article is to review, selectively, current knowledge of the chemical ecology of pathogen vectors that affect livestock and human health in the developed and developing world, based on key note lectures presented in a symposium on “The Chemical Ecology of Disease Vectors” at the 25th Annual ISCE meeting in Neuchatel, Switzerland. click here The focus is on the deployment of semiochemicals for monitoring and control strategies, and discusses briefly future directions that such research should proceed along, bearing in mind the environmental challenges associated with climate change that we will face during the 21st century.”
“Sulfanilamide reacted with acryloyl chloride to give 4-(N-acrylamido)benzenesulfonamide (ABA), which converted to the corresponding polymer (PABA) upon treatment with initiator at 75A degrees C. Various copolymers BI 2536 molecular weight formed from ABA with acrylamide (AA), acrylonitrile

(AN), and N-(thiazol-2-yl)acrylamide (TA) at different ratios (50 : 50, 70 : 30 and 30 : 70) were prepared. The polymer and copolymers were characterized using IR, H-1 NMR, C-13 NMR and mass spectroscopy, thermogravimetry, and scanning electron microscopy. The drug release from polymeric chain and copolymers was studied at 37A degrees C and pH 8.4. The drug release was highly increased upon adding sodium chloride at various concentrations, 0.1%, 0.5% and 0.9%. The drug release from the polymer and copolymer chains was measured using a UV-visible spectroscopy technique. Antimicrobial activity of the polymer and copolymers was studied. It is established that the ABA copolymer with TA is more effective as compared to other copolymers.”
“The potential energy surfaces of the initial reactions of ethylene insertion for the Ziegler-Natta catalysis with bridging groups of Cp ligands were studied by ab initio MO and density functional methods. Three metals (Ti, Zr, and Hf) in the Zeigler-Natta catalysis and eight bridging groups (BH, CH2, NH, O, AlH, SiH2, PH, and S) were treated. For the complex formation between ethylene and metallocenes, two type structures (vertical and horizon) were found.

Darkening effects

could not be observed for these systems

Darkening effects

could not be observed for these systems, and partially light brightening of the tissue was observed. Advantageous colors were suggested to be pink and yellow.”
“Introduction: Extracellular matrix changes occur in many heart valve pathologies. For example, Selleckchem CDK inhibitor myxomatous mitral valves are reported to contain excess proteoglycans and hyaluronan. However, it is unknown which specific proteoglycans are altered in myxomatous valves. Because proteoglycans perform varied functions in connective tissues, this study was designed to identify and localize three matrix-associated proteoglycans, as well as hyaluronan and the hyaluronan receptor for endocytosis, within myxomatous and normal mitral valves. Methods: Human mitral posterior leaflets PR-171 clinical trial (control, n=6-9;

myxomatous, n=14-21; mean age, 61 years for all groups) were histochemically stained for proteoglycan core proteins, hyaluronan, and the hyaluronan receptor for endocytosis. Stain intensity was semiquantitatively graded to determine differences in marker abundance between normal and myxomatous valves. The proteoglycans were localized to different regions of the leaflet by correspondence to parallel Movat-stained sections. Results: The proteoglycans decorin, biglycan, and versican were more abundant in myxomatous valves than in normal controls (P<.03). There was a gender effect on proteoglycan presence, but no age-related trends were observed. Hyaluronan and the hyaluronan GSK126 molecular weight receptor for endocytosis were distributed throughout all valves. There was no significant difference in hyaluronan between groups, but expression of the hyaluronan receptor for endocytosis was reduced in myxomatous valves compared to normal controls (P<.002). Conclusion:

Excess decorin, biglycan, and versican may be associated with the remodeling of other matrix components in myxomatous mitral valves. Decreased expression of the hyaluronan receptor for endocytosis in myxomatous valves suggests that hyaluronan metabolism could be altered in myxomatous mitral valve disease. These findings contribute towards elucidating the pathogenesis of myxomatous mural valve disease and developing potential new therapies. (C) 2009 Elsevier Inc. All rights reserved.”
“Comprehensive management of rheumatoid arthritis (RA) requires regular monitoring of disease activity, functional status, and structural damage to facilitate optimal patient outcomes. Tight control strategies have been successfully used in other diseases including diabetes and hypertension. Tight control requires frequent disease activity measurements in order to tailor treatment for individual patients, resulting in improved patient outcomes. Current monitoring measures used in clinical practice are largely driven by subjective evaluation of signs and symptoms, which are critical but limited by assessor variability and may not reflect true biological change in a timely manner.