Intervertebral Disc Degeneration is a pathophysiological condition that primarily affects the spinal discs, causing back pain and neurological deficits. It is caused by the contribution of several factors such as genetic predisposition, age-related degeneration, and lifestyle choices like obesity and physical activity. Even though there are medications to treat pain, there is a lack of medicines for a complete cure. The main difficulty lies in poor diagnosis of the morphological and functional changes in the disc. With the ever-increasing research on bioimaging techniques, new techniques are being developed and repurposed to evaluate disc shape and composition, and their defects like thinning or deformities on the disc, leading to the proper diagnostic intervention in intervertebral disc degeneration. In this review, we aim to present a comprehensive overview of the imaging techniques used in the pre-clinical and clinical stages for the diagnosis of intervertebral disc degeneration. First, we will discuss about patho-anatomy and the pathophysiology of degenerative disc disease with the significance and a brief description of various dyes and tracers utilized for bioimaging. Then we will shed light on the latest advancements in diagnostic modalities in intervertebral disc degeneration; concluded by an analysis of the repercussions of the methodologies and experimental systems employed in identifying mechanisms and developing therapeutic strategies in intervertebral disc degeneration.

Riverbed sediments have been identified as temporary and long-term accumulation sites for microplastic particles (MPs), but the relocation and retention mechanisms in riverbeds still need to be better understood. In this study, we investigated the depth-specific occurrence and distribution (abundance, type, and size) of MPs in river sediments down to a depth of 100 cm, which had not been previously investigated in riverbeds. In four sediment freeze cores taken for the Main River (Germany), MPs (≥ 100 µm) were detected using two complementary analytical approaches (spectroscopy and thermoanalytical) over the entire depth with an average of 21.7 ± 21.4 MP/kg or 31.5 ± 28.0 mg/kg. Three vertical trends for MP abundance could be derived, fairly constant in top layers (0-‍30 cm), a decrease in middle layers (30-60 cm), and a strong increase in deep layers (60-100 cm). The dominant polymer types were polyethylene (PE), polypropylene (PP), and polystyrene (PS). Polyethylene terephthalate (PET) and PP were also found in deep layers, albeit with the youngest age of earliest possible occurrence (EPO age of 1973 and 1954). The fraction of smaller-sized MPs (100-500 µm) increased with depth in shallow layers, but the largest MPs (> 1 mm) were detected in deep layers. Based on these findings, we elucidate the relationship between the depth-specific MP distribution and the prevailing processes of MP retention and sediment dynamics in the riverbed. We propose some implications and offer an initial conceptual approach, suggesting the use of microplastics as a potential environmental process tracer for driving riverbed sediment dynamics.

Immunotherapy targeted to immune checkpoint inhibitors, such as the program cell death receptor (PD-1) and its ligand (PD-L1), has revolutionized cancer treatment. However, it is now well-known that PD-1/PD-L1 immunotherapy response is inconsistent among patients. The current challenge is to customize treatment regimens per patient, which could be possible if the PD-1/PD-L1 expression and dynamic landscape are known. With positron emission tomography (PET) imaging, it is possible to image these immune targets non-invasively and system-wide during therapy. A successful PET imaging tracer should meet specific criteria concerning target affinity, specificity, clearance rate and target-specific uptake, to name a few. The structural profile of such a tracer will define its properties and can be used to optimize tracers in development and design new ones. Currently, a range of PD-1/PD-L1-targeting PET tracers are available from different molecular categories that have shown impressive preclinical and clinical results, each with its own advantages and disadvantages. This review will provide an overview of current PET tracers targeting the PD-1/PD-L1 axis. Antibody, peptide, and antibody fragment tracers will be discussed with respect to their molecular characteristics and binding properties and ways to optimize them.

Radon, a natural radioactive gas, serves as a valuable tracer in geophysical research and atmospheric science such as detecting stress induced signal in bedrock. However, the conventional radon monitoring methods often lack the sensitivity required to accurately capture such signals. This limitation, coupled with interference from meteorological effects, poses challenges in distinguishing genuine stress-induced signals. In this study, we propose a novel approach utilizing radon concentration gradients at the soil-air interface to enhance sensitivity and detect stress induced radon signals more effectively. Drawing from pressure diffusion models, we demonstrate how seismic stress accumulation in bedrock alters radon profiles in the sub-soil, providing insights into the mechanisms underlying stress-induced radon variations. Building upon this theoretical framework, we introduce the \"Bhabha Radon Observatory for Seismic Application (BhaROSA),\" a remote sensing, solar-powered radon observatory designed for widespread deployment and continuous unattended monitoring for big database generation. Field experiments comparing BhaROSA\'s performance to conventional soil probe techniques validate and confirm the superior sensitivity in line with theoretical predictions. This innovative approach holds promise for improving our understanding of stress dynamics in bedrock and has potential applications in various geophysical and atmospheric science such as earthquake precursory research, geo-genic radon potential and risk assessment. To progress, we propose international alliance and application of deep learning to a big database of precursor signals, which may lead to more informed conclusions on earthquake predictability-an enduring and unsolved challenge for humanity.

Our purpose was to determine how age affects metabolic flexibility and underlying glucose kinetics in healthy young and older adults. Therefore, glucose and lactate tracers along with pulmonary gas exchange data were used to determine glucose kinetics and respiratory exchange ratios [RER = carbon dioxide production (V̇co2)/oxygen consumption (V̇o2)] during a 2-h 75-g oral glucose tolerance test (OGTT). After an 12-h overnight fast, 28 participants, 15 young (21-35 yr; 7 men and 8 women) and 13 older (60-80 yr; 7 men and 6 women), received venous primed-continuous infusions of [6,6-2H]glucose and [3-13C]lactate with a [Formula: see text] bolus. After a 90-min metabolic stabilization and tracer equilibration period, volunteers underwent an OGTT. Arterialized glucose concentrations ([glucose]) started to rise 15 min post glucose consumption, peaked at 60 min, and remained elevated. As assessed by rates of appearance (Ra) and disposal (Rd) and metabolic clearance rate (MCR), glucose kinetics were suppressed in older compared to young individuals. As well, unlike in young individuals, fractional gluconeogenesis (fGNG) remained elevated in the older population after the oral glucose challenge. Finally, there were no differences in 12-h fasting baseline or peak RER values following an oral glucose challenge in older compared to young men and women, making RER an incomplete measure of metabolic flexibility in the volunteers we evaluated. Our study revealed that glucose kinetics are significantly altered in a healthy aged population after a glucose challenge. Furthermore, those physiological deficits are not detected from changes in RER during an OGTT.NEW & NOTEWORTHY To determine metabolic flexibility in response to an OGTT, we studied healthy young and older men and women to determine glucose kinetics and changes in RER. Compared to young subjects, glucose kinetics were suppressed in older healthy individuals during an OGTT. Surprisingly, the age-related changes in glucose flux were not reflected in RER measurements; thus, RER measurements do not give a complete view of metabolic flexibility in healthy individuals.

Effectively managing water resources in karst systems requires a thorough understanding of their general conduit network along with their seasonal dynamics. Their investigation has involved well construction or several advanced natural tracer data, most of which are not always available. Hence, this work showcases a pragmatic approach that makes use of basic hydrochemical variables of springs with coarse temporal resolution in characterising a karst system. In this study\'s example, physicochemical variables like major ion concentrations/ratios, Electrical Conductivity (EC), pH and water temperature (Tw) were measured on 20-day basis for a hydrological year at the Louros Catchment, Greece. We further performed the frequency distribution and variation analysis of EC and Tw, principal component analysis (PCA), scatter plots of carbonate ions vs sulphate and hydrochemographs to determine relevant hydrochemical processes and hydrogeological features. PCA and the scatter plots showed that the simple-type upper karst level is entirely dominated by carbonate dissolution, whereas the complex-type middle and lower levels also involve gypsum and dolomite dissolution. Presence of mixing between karst units was also detected. EC and Tw analyses revealed the degree of karstification of different units and relative depths of flow systems. Hydrochemographs reflected the seasonality of limestone and gypsum dissolution\'s contributions linked to the dominant flow type (conduit vs diffuse). This study thus was able to demonstrate the usefulness of such holistic hydrochemical analyses to better understand karst systems. Given their cost-effectiveness, they can be easily applied to any understudied karst system worldwide.

Few studies have examined the N kinetics of individual feeds with stable isotope tracing. We hypothesized that N partitioning to milk and excreta pools as well as the rates of the processes that drive this partitioning would differ for alfalfa silage, corn silage, corn grain, and soybean meal. Feed ingredients were endogenously labeled with 15N and included in 4 diets to create treatments with the same dietary composition and different labeled feed. Diets were fed to 12 late-lactation dairy cows for 4 d (96 h) and feces, urine, and milk collection proceeded during the 4 d of 15N enrichment and for 3 d (80 h) after cessation of label feeding. Nonlinear models of 15N enrichment and decay were fit to milk (MN), urine (UN), and fecal N (FN) in R with the nlme package and feed-specific parameter estimates were compared. The estimated proportions of feed N that were excreted in feces supported our understanding that N from soybean meal and corn grain is more digestible than N from alfalfa and corn silage. Estimates for the N partitioning between milk (MN) and urine (UN) from the 2 concentrate feeds (soybean meal and corn grain) indicated that UN:MN ratios were less than or equal to 1:1 indicating either more or equal nitrogen partitioning to milk compared with urine. It is important to maintain factual accuracy in representing the results rather than implying a desired outcome unsupported by the data. In contrast, UN:MN ratios for forage feeds (corn and alfalfa silage) were > 1:1, indicating more N partitioning to urine than milk. The modeled proportion of total FN that originated from feed N was 82.2% which is in line with previous research using a similar 15N measurement timeframe. However, the proportion of urinary and MN originating from feed N was much lower (60.5% for urine, 57.9% for milk), suggesting that approximately 40% of urinary and MN directly originate from body N sources related to protein turnover.

OBJECTIVE: Regional lymph node (LN) volume decreases after neoadjuvant therapy, requiring a tracer for more accurate detection. Nano-carbon tracer is a third-generation tracer with several advantages, but its use for LN detection after neoadjuvant chemoradiotherapy for middle and low rectal cancer remains unclear. Therefore, this study investigated the effects and safety of anoscope-guided subrectal injections of nano-carbon suspension in this patient population.
METHODS: This study retrospectively reviewed the medical records of 45 patients with middle and low rectal cancer admitted to our institution from March 2019 to March 2022. All patients received preoperative neoadjuvant chemotherapy and radiotherapy and were divided into nano-carbon injection (n = 23; anoscope-guided injections of nano-carbon suspension in the rectal submucosa 2 cm above the dentate line 24 h preoperatively) and control (n = 22; directly underwent surgery) groups. The LN detection and complication rates were compared between the groups.
RESULTS: The total and mean numbers of LNs and small LNs and the number of patients with > 12 LNs were significantly higher in the nano-carbon injection group than in the control group. The total number of positive LNs and LN metastasis did not differ between the groups, nor did the anastomotic leakage, bleeding, stenosis, and abscess occurrence rates.
CONCLUSIONS: Anoscope-guided nano-carbon lymphatic tracing increased the LN detection rate, caused less trauma, and resulted in fewer postoperative complications than the direct surgical procedure. Thus, it is an effective, safe, and practical method that may improve dissections and the postoperative pathological staging accuracy.

Nitric oxide (NO) plays a pivotal role as a biological signaling molecule, presenting challenges in its specific detection and differentiation from other reactive nitrogen and oxygen species within living organisms. Herein, a 18F-labeled (fluorine-18, t1/2 = 109.7 min) small-molecule tracer dimethyl 4-(4-(4-[18F]fluorobutoxy)benzyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate ([18F]BDHP) is developed based on the dihydropyridine scaffold for positron emission tomography (PET) imaging of NO in vivo. [18F]BDHP exhibits a highly sensitive and efficient C-C cleavage reaction specifically triggered by NO under physiological conditions, leading to the production of a 18F-labeled radical that is readily retained within the cells. High uptakes of [18F]BDHP are found within and around NO-generating cells, such as macrophages treated with lipopolysaccharide or benzo(a)pyrene. MicroPET/CT imaging of arthritic animal model mice reveals distinct tracer accumulation in the arthritic legs, showcasing a higher distribution of NO compared with the control legs. In summary, a specific radical-generating dihydropyridine tracer with a unique radical retention strategy has been established for the marking of NO in real-time in vivo.

Sentinel lymph node (SLN) detection with superparamagnetic iron oxide (SPIO) nanoparticles has been widely studied and standardized for breast and prostate cancer, but there is scarce evidence concerning its use in vulvar cancer. The objective of this study was to compare SLN detection using a SPIO tracer injected at the time of the surgery detected by a magnetometer, with the standard procedure of using a technetium 99 radioisotope (Tc99) detected by a gamma probe, in patients with vulvar cancer.
The SPIO vulvar cancer study was a single-center prospective interventional non-inferiority study of SPIO compared to Tc99, conducted between 2016 and 2021 in patients who met the GROINSS-V study inclusion criteria for selective sentinel lymph node dissection in vulvar cancer.
We included 18 patients and a total of 41 SLNs. The level of agreement between tracers was 92.7% (80.6%-97.4%), corresponding to 38 out of 41 SLNs, which confirms the non-inferiority of SPIO compared to Tc99. The SLN detection rate per groin was 96.3 (81.7%-99.3) using Tc99 and 100% (87.5%-100%) using SPIO. Both tracers had a detection rate of 100% for positive lymph nodes.
The use of SPIO as a tracer for detecting SLNs in patients with vulvar cancer has shown to be non-inferior to that of the standard radiotracer, with the advantages of not requiring nuclear medicine and being able to inject it at the time of surgery after induction of anesthesia.