Sampling Variability Research Articles

The utilisation of digital droplet PCR to enhance the diagnosis of bladder and pancreaticobiliary tumours in cytology specimens.

Digital droplet PCR (ddPCR) is a relatively new technique used to detect molecular alterations with unprecedented precision and accuracy. It is particularly useful for detecting point mutations and copy number variation (CNV) in samples with small amounts of target DNA. This proof of principle study was conducted to see if ddPCR technology could be applied to cytology specimens to detect molecular alterations which may influence diagnostic decision making. A range of cytological specimens derived from bladder or pancreaticobiliary origin, with varying diagnoses but with an emphasis on abnormality, underwent ddPCR testing. DNA was manually extracted from Thinprep vials, cell blocks or direct fine needle aspiration smears. ddPCR was performed using two somatic point mutations TP53 R248W and TP53 R273H assays for both urine and pancreaticobiliary cytology specimens. Three CNV assays; CDKN2A, E2F3 and YWHAZ were applied to urine samples. SMAD4 and CDKN2A CNVs were applied to the pancreaticobiliary samples. 16 of 21 urine specimens showed molecular alterations using ddPCR testing. 12 of those 16 cases were associated with malignant outcomes. The pancreaticobiliary specimens showed 14 of 37 specimens with molecular alterations, all of which were associated with carcinoma. We demonstrated an increasing percentage of molecular aberrations associated with increasing severity of cytological results. Our results have shown that ddPCR can identify both mutations and CNVs in urine and pancreaticobiliary cytology derived samples. Being able to detect these molecular alterations may reduce the number of equivocal results leading to more timely and informed patient management decisions.

Laser surface polishing of 3D printed polylactic acid (PLA) with different levels of absorption

Fused deposition modeling (FDM) based 3D printed polymer parts have received extensive attention in the industries. However, their high surface roughness due to the intrinsic layer deposition method limits the applicability, necessitating the printed parts' post-processing. Herein, we used colored (white, blue, and gray) 3D-printed polylactic acid (PLA) parts and investigated the color influence on the laser polishing process in detail. Interestingly, the level of laser absorption at an irradiated wavelength of 1060 nm differed in the order of PLA-gray > PLA-blue > PLA-white. Laser-polished PLA-white samples showed a negligible difference in the arithmetic average surface roughness (Ra) compared to the printed sample, corresponding to the low absorption level and melting behavior. On the other hand, the laser-polished PLA-blue sample exhibited a 96.4 % reduction in Ra value at a laser power of 15 W. The PLA-gray sample showed a 98.6 % reduction at 3 W. The Ra variation of the laser-polished samples confirmed a dramatic surface roughness improvement that could be made by controlling laser processing parameters and varying light absorption levels of the colored PLA substrates. Besides, PLA-blue and PLA-gray samples had different polishing conditions; Scanning electron microscope (SEM) images, thermal studies, and finite element model simulation results confirmed the polishing and melting behavior of the PLA samples. The comparative experimental results followed by statistical analysis also showed the significant effect of PLA color and laser parameters such as the power and scan speed. Through the advantages of the highly improved laser finishing results with optimal process parameters considering the different light absorption, this approach will broaden the application of efficient laser polishing of 3D printed materials.

On the Short-Term Creep and Recovery Behaviors of Injection Molded and Additive-Manufactured Tough Polylactic Acid Polymer

The creep and recovery behaviors of a tough polylactic acid polymer are investigated experimentally and theoretically. We studied the influence of manufacturing methods and parameters on the viscoelastic responses. Experimental comparisons were carried out on 13 different samples manufactured using fused deposition modeling (FDM) and injection molding methods. The sample variations in the FDM were based on four infill densities (70-100%) and 3 infill directions (0^circ ,45^circ ,90^circ ). Theoretically, the Burgers and Weibull’s models are used to predict the creep and recovery responses of the samples. Our experimental findings suggest that the injection-molded samples perform better in creep for most of the cases. However, at higher stress loadings, the 90 and 100% infill density samples showed excellent creep resistance behaviors at the 90^circ infill direction. On the other hand, the theoretical creep and recovery predictions were based on the nonlinear least-squares regression method. The Burgers model predicted the creep responses with reasonable accuracies. A maximum of 5.83% mean absolute percentage error (MAPE) was found for the 0° infill direction and 80% infill density sample. On the contrary, the model lacks accuracy in recovery strain predictions, showing an average of 173.15% MAPE for all studied samples. Introducing Weibull’s distribution improved the accuracies showing a 3.44% average MAPE for all samples.

Effects of container type and size on thermal processing characteristics and B-vitamin retention of canned cat food.

Rigid cans were the traditional container for canned cat foods, but semi-rigid trays/tubs and flexible pouches are popular options as well. Despite this, little is published on the effects of canned cat food container characteristics on thermal processing and retention of B-vitamins. Therefore, the objective was to evaluate the effects of container size and type on thermal processing and B-vitamin retention. Treatments were arranged in a factorial with two container sizes [small (85-99 g) and medium (156-198 g)] and three container types (flexible, semi-rigid, and rigid). A canned cat food formula was prepared, filled, and sealed into containers before retort processing to a heating cycle target lethality of 8 min. Internal retort and container temperatures were used to calculate accumulated lethality. Thiamin, riboflavin, niacin, pantothenic acid, pyridoxine, biotin, folic acid, cobalamin, and moisture contents were analyzed in pre- and post-retort samples by commercial laboratories. Thermal processing metrics were analyzed (SAS v. 9.4; SAS Institute, Cary, NC) with the fixed effects of container size, container type, and their interaction. Dry matter basis B-vitamin contents were analyzed with container size, container type, processing stage, and all two-way and three-way interactions as fixed effects. Means were separated using Fisher's LSD at a P-value < 0.05. Total accumulated lethality was greater (P < 0.05) for semi-rigid and flexible containers (average 14.99 min) than for rigid containers (12.86 min). The greater processing of semi-rigid and flexible containers was likely influenced by required retort settings. Thiamin and riboflavin contents decreased (P < 0.05) by 30.4 and 18.3%, respectively, due to retort processing. Niacin, biotin, and cobalamin were not affected (P > 0.05) by processing. Processing increased (P < 0.05) pantothenic acid (9.1%), pyridoxine (22.6%), and folic acid (22.6%). This was likely caused by sampling or analytical variation. No interaction involving processing stage was significant for any B-vitamin (P > 0.05). B-vitamin retention was not influenced by differences in thermal processing caused by the packaging treatments. Thiamin and riboflavin were the only B-vitamins meaningfully impacted by processing and retention was not improved by any container characteristic.

Discovering informative biomarkers in psychiatry.

Discovering informative biomarkers in psychiatry.

Comparative studies of fermented coffee fruits post-treatments on chemical and sensory properties of roasted beans in Yunnan, China

In this study, medium roasted coffee with four different fermented coffee fruits post-treatments (dry, wet, semi-dry and hot air dry) was used as the material. Chemical profile and sensorial analysis were used to comprehensively analyze the effects of post-treatments on coffee flavor characteristics from multiple dimensions. A total of 31 water-soluble chemical components and 39 volatile compounds were identified in roasted coffee, and distinct post-treatments based on chemical orientation make coffee highly differentiated. In addition, the principal component analysis (PCA) of the chemical composition integrated data set showed that the first two principal components could explain 54.9% of the sample variability. All four post-treatments can be classified as “specialty coffees” according to the Specialty Coffee Association (SCA) protocol, with various organoleptic characteristics and flavor attributes. As a result, the fermented coffee fruits post-treatment method further determines the quality characteristics of coffee, thus meeting the needs of different niche markets.

A Multi-Laboratory Evaluation of Commercial Monkeypox Virus Molecular Tests.

In this report, we describe the first national scale multi-laboratory evaluation of monkeypox virus (MPXV) DNA commercial PCR kits. The objective of this study was to evaluate 2 kits by different diagnostic laboratories across Israel. Ten standardized samples were tested simultaneously using the Novaplex (15 laboratories) and Bio-Speedy (seven laboratories) kits. An in-house assay based on previously published reactions was used as reference. Comparison of the results showed high intra-assay agreement between laboratories, with small variations for most samples. The in-house assay had an analytical detection limit of less than 10 copies per reaction. While the 2 commercial kits were able to detect specimens with low viral loads similarly to the in-house assay, significant differences were observed, in the Cq values and relative fluorescence (RF), between the assays. The RF signal of the in-house and Bio-Speedy assays ranged between 5,000 and 10,000 RFU, while the signal in the Novaplex assay was less than 600 RFU. Due to the kit measurement protocol, the Cq values of the Bio-Speedy kit were 5 to 7.5 cycles lower than those of the in-house assay. On the contrary, the Cq values of the Novaplex kit were significantly higher than those of the in-house assay, with differences of 3 to 5 cycles per sample. Our results suggest that while all assays were similar in their overall sensitivity, direct comparison of Cq values between them may be misleading. To our knowledge, this is the first methodical evaluation of commercial MPX test kits. We therefore anticipate that this study would help diagnostic laboratories in choosing a specific MPX detection assay. IMPORTANCE To the best of our knowledge, this study is the first methodical evaluation of commercial kits designed for Monkeypox virus detection. This was done by performing the same tests using the same sample set in multiple laboratories, simultaneously, on a national scale. It therefore provides important and unique information on the performance of such kits and provides a guideline for choosing the assay of choice for monkeypox virus diagnosis in a standard diagnostic laboratory. It also demonstrates potential complications when trying to compare the results of different assays, even when testing exactly the same samples, under identical conditions.

Bacteria separation and enrichment using viscoelastic flows in a straight microchannel

Bacteria occupy a large domain of prokaryotic microorganisms on earth and play a significant role in public health. In this study, we achieve continuous size-based bacteria separation using viscoelastic flows in a microchannel. Three types of bacteria that differ in size, including Lactobacillus rhamnosus (L. rhamnosus), Staphylococcus epidermidis (S. epidermidis) and Escherichia coli (E. coli) are employed. First, the separation of L. rhamnosus and S. epidermidis is investigated. Under the combined effects of inertial lift and elastic forces, the larger L. rhamnosus cells are driven toward the channel centre while the smaller S. epidermidis cells flow in narrow streams along the channel sidewalls. The results show that the separation performance of the viscoelastic microfluidic device is affected by four main factors: channel length, total flow rate (TFR), sheath-to-sample flow rate ratio (FRR) and polyethylene oxide (PEO) concentration. Furthermore, the separation of L. rhamnosus and E. coli is demonstrated. This work overcomes the issues like shape irregularity and size variation in bacterial samples and achieves the separation of two types of bacteria in a size-dependent manner. We expect that this work will facilitate the future studies of bacterial interspecies communication and interactions as well as the development of biology, biomedicine and biotechnology.

Mobile Measurement of a Dynamic Field via Compressed Sensing

In this paper, measuring dynamic signals at points of interest (POIs) using a mobile agent is considered, where the agent is required to repeatedly measure at and transit between the POIs. Dynamic field sensing is needed in areas ranging from nanomechanical mapping of live sample to crop monitoring. Existing work on mobile sensing, however, has been focused on cooperatively tracking one or few known or unknown POIs, whereas the dynamics of the signals is ignored. Challenges arises from capturing and recovering the dynamics at each POI by using data intermittently measured, resulting in temporal-spatial coupling in the mobile sensing. Moreover, trade off between the sensing cost and the performance needs to be addressed. We propose a compressed-sensing based approach to tackle this problem. First, a check-and-removal process based on random permutation and partition of the measurement periods is developed to avoid the temporal-spatial coupling under agent speed constraint. Then a shuffle-and-pair process based on the simulate-annealing is proposed to minimize the transition distance while preserving the performance. It is shown that the distribution of the measurement periods between the POIs converges. The proposed approach is illustrated through a simulation study of measuring the temperature-dependent nanomechanical variations of a polymer sample.

Prospective secondary school teachers’ knowledge of sampling distribution properties

The aim of the work was to assess prospective Spanish secondary school mathematics teachers’ knowledge of sampling representativeness and variability. To achieve this goal, a questionnaire with four items taken from our previous research with secondary education and high school students was proposed to 66 prospective teachers. In each item, participants were asked to provide four values of a binomial distribution, varying the parameters of the distribution in each item. The analysis of the mean and range of the sample of four values provided by the participants, and its comparison with the theoretically normative and acceptable values of the sampling distribution suggests a good knowledge of the sample representativeness, except for one item and an overestimation of the variability for large values of the number of trials in the binomial distribution. The study of the participants’ arguments serves to identify some reasoning biases related to sampling distribution. The results are better than those obtained with students in our previous studies.

Stress-Dependent Shear Strength of Resedimented Nile Silty Clay

The variation of clay undrained shear strength with consolidation stresses is of paramount importance to geotechnical engineers. For several decades, the normalized shear strength of clays has been the cornerstone of geotechnical design in many applications, such as staged construction of embankments. Recently, different trends of shear strength dependency on consolidation stresses have emerged indicating nonlinear variation. Resedimentation has been a useful and reliable method to investigate stress dependency by generating lab test specimens of fine-grained soils with a minimum sample to sample variation for benchmark studies. Previous work on resedimented Nile silty clay (RNSC) has shown unique features, such as high sand fraction and contradicting index properties used for soil classification. The shear strength of Nile silty clay (NSC) and the effects of the consolidation stresses are explored through a laboratory program on resedimented samples from material excavated within the Nile River flood plains. A portion of the material was processed using mechanical energy, which exhibited a significant increase in the liquid limit and a larger clay-sized fraction of particles from grain-size distribution tests. The measured engineering parameters are compared with comparable studied soils and established empirical correlations to provide insights on mechanical behaviors of the NSC. NSC is found to have a rapid decrease in the undrained shear strength ratio and a rapid increase in the lateral stress ratio with increasing consolidation stress.

To be or not to be Unionized: A Case Study

This study aimed to shed light on how union activities should be conducted based on the views of teachers and administrators, what expectations teachers and administrators have of the union, whether these expectations are related to the core objectives of union activities or are simply intended to address personal issues or fulfill their desires, and reveal the strength or weakness of education workers’ ability to act in an organized manner in Turkey. The research was planned as a holistic single case study using qualitative research methods. The study group consists of 12 participants, and among the purposive sampling methods, criterion sampling and maximum variation sampling methods were used. The interview form used in the study was designed by the researchers as a result of the literature review. The data were analyzed through content analysis. The codes and categories obtained from the interviews on union activities were grouped under four themes; the reasons for being or not being a member of a union, views on unions, positive benefits and negative practices of union activities, and suggestions on union activities. According to the collected data, recommendations have been made, including that unions should unite under a single roof and make a division within themselves at the branch level; they should exert pressure on the formation of a just, merit-based system for appointment and relocation.

ACT-Discover: identifying karyotype heterogeneity in pancreatic cancer evolution using ctDNA

BackgroundLiquid biopsies and the dynamic tracking of somatic mutations within circulating tumour DNA (ctDNA) can provide insight into the dynamics of cancer evolution and the intra-tumour heterogeneity that fuels treatment resistance. However, identifying and tracking dynamic changes in somatic copy number alterations (SCNAs), which have been associated with poor outcome and metastasis, using ctDNA is challenging. Pancreatic adenocarcinoma is a disease which has been considered to harbour early punctuated events in its evolution, leading to an early fitness peak, with minimal further subclonal evolution.MethodsTo interrogate the role of SCNAs in pancreatic adenocarcinoma cancer evolution, we applied whole-exome sequencing of 55 longitudinal cell-free DNA (cfDNA) samples taken from 24 patients (including 8 from whom a patient-derived xenograft (PDX) was derived) with metastatic disease prospectively recruited into a clinical trial. We developed a method, Aneuploidy in Circulating Tumour DNA (ACT-Discover), that leverages haplotype phasing of paired tumour biopsies or PDXs to identify SCNAs in cfDNA with greater sensitivity.ResultsSCNAs were observed within 28 of 47 evaluable cfDNA samples. Of these events, 30% could only be identified by harnessing the haplotype-aware approach leveraged in ACT-Discover. The exceptional purity of PDX tumours enabled near-complete phasing of genomic regions in allelic imbalance, highlighting an important auxiliary function of PDXs. Finally, although the classical model of pancreatic cancer evolution emphasises the importance of early, homogenous somatic events as a key requirement for cancer development, ACT-Discover identified substantial heterogeneity of SCNAs, including parallel focal and arm-level events, affecting different parental alleles within individual tumours. Indeed, ongoing acquisition of SCNAs was identified within tumours throughout the disease course, including within an untreated metastatic tumour.ConclusionsThis work demonstrates the power of haplotype phasing to study genomic variation in cfDNA samples and reveals undiscovered intra-tumour heterogeneity with important scientific and clinical implications. Implementation of ACT-Discover could lead to important insights from existing cohorts or underpin future prospective studies seeking to characterise the landscape of tumour evolution through liquid biopsy.

Guaranteed performance of individual control chart used in gamma passing rate-based patient-specific quality assurance

PurposeTo assess the effect of sampling variability on the performance of individual charts (I-charts) for PSQA and provide a robust and reliable method for unknown PSQA processes. Materials and methodsA total of 1327 pretreatment PSQAs were analyzed. Different datasets with samples in the range of 20–1000 were used to estimate the lower control limit (LCL). Based on the iterative “Identify-Eliminate-Recalculate” and direct calculation without any outlier filtering procedures, five I-charts methods, namely the Shewhart, quantile, scaled weighted variance (SWV), weighted standard deviation (WSD), and skewness correction (SC) method, were used to compute the LCL. The average run length (ARL0) and false alarm rate (FAR0) were calculated to evaluate the performance of LCL. ResultsThe ground truth of the values of LCL, FAR0, and ARL0 obtained via in-control PSQAs were 92.31%, 0.135%, and 740.7, respectively. Further, for in-control PSQAs, the width of the 95% confidence interval of LCL values for all methods tended to decrease with the increase in sample size. In all sample ranges of in-control PSQAs, only the median LCL and ARL0 values obtained via WSD and SWV methods were close to the ground truth. For the actual unknown PSQAs, based on the “Identify-Eliminate-Recalculate” procedure, only the median LCL values obtained by the WSD method were closest to the ground truth. ConclusionsSampling variability seriously affected the I-chart performance in PSQA processes, particularly for small samples. For unknown PSQAs, the WSD method based on the implementation of the iterative “Identify-Eliminate-Recalculate” procedure exhibited sufficient robustness and reliability.

Assessment of WHO 07/202 reference material and human serum pools for commutability and for the potential to reduce variability among soluble transferrin receptor assays.

The clinical use of soluble transferrin receptor (sTfR) as an iron status indicator is hindered by a lack of assay standardization and common reference ranges and decision thresholds. In 2009, the WHO and National Institute for Biological Standards and Controls (NIBSC) released a sTfR reference material (RM), 07/202, for assay standardization; however, a comprehensive, formal commutability study was not conducted. This study evaluated the commutability of WHO 07/202 sTfR RM and human serum pools and the impacts of their use as common calibrators. Commutability was assessed for six different measurement procedures (MPs). Serum pools were prepared according to updated CLSI C37-A procedures (C37) or non-C37 procedures. The study design and analyses were based on Parts 2 and 3 of the 2018 IFCC Commutability in Metrological Traceability Working Group's Recommendations for Commutability Assessment. WHO 07/202 and serum pools were used for instrument/assay and mathematical recalibration, respectively, to determine if their use decreases inter-assay measurement variability for clinical samples. The WHO 07/202 RM dilutions were commutable for all 6MPs assessed and, when used for instrument calibration, decreased inter-assay variability from 208 to 55.7 %. Non-C37 and C37 serum pools were commutable for all 6MPs assessed and decreased inter-assay variability from 208 to 13.8 % and 4.6 %, respectively, when used for mathematical recalibration. All materials evaluated, when used as common calibrators, substantially decreased inter-assay sTfR measurement variability. MP calibration to non-C37 and C37 serum pools may reduce the sTfR IMPBR to a greater extent than WHO 07/202 RM.

Synchronously Enhanced strength-ductility of L-DEDed GH4169 with Varying Energy Input

The energy input highly determines the microstructure, texture and tensile properties of the laser directed energy deposited (L-DEDed) Ni-based superalloy. This study adopted three levels of energy input from low, medium to high evaluated by the areal energy density to fabricate GH4169 alloy. Results show that a synchronously enhanced strength-ductility of L-DEDed GH4169 Ni-based superalloy with the the high energy input, although the microstructure exhibits the largest grain size and most significant Laves phase size and fraction. This synchronously enhance strength-ductility of L-DEDed GH4169 with high energy input can be mainly attributed to the combined effect of texture variation and residual stress. The crystallographic characterization depicted a texture variation from the {001} <100> cube texture with low energy input to the {111} <110> Goss texture with high energy input, which can be quantitatively analyzed by the average Schmid factor for slip and twinning derived from the “Texture parameters (TP)”. In this case, the average Schmid factor for slip and twinning of the tensile specimen with high energy input are both the smallest, which enhances the yield strength and deformation twinning of the specimen. The microstructure observations showed that the texture variation of the L-DEDed samples from low to high energy input was dominated by the “maximum deviation angel θd” of dendrites determined by the melt-pool shape and related heat-dissipation direction. Besides, the residual stress decreases as the energy input increases, which also contributes to the enhanced strength-ductility with high energy input.

Stability and Antioxidant Activity of Pouteria macrophylla Fruit Extract, a Natural Source of Gallic Acid.

Pouteria macrophylla (cutite) fruits are rich in phenolic acids, resulting in antioxidant and skin depigmenting activity. The aim of this study, then, is to evaluate the cutite extract stability under three variations of light, time, and temperature using a Box-Behnken experimental design to analyze through the surface response the variations of the total phenolic content (TPC), antioxidant activity (AA), and gallic acid content (GA). A colorimetric assay was also performed, and a decrease in the darkening index was noticed due to the high phenolic coloration in the presence of light, indicating less degradation to extract stability. The experimental planning showed variations in all responses, and second-order polynomial models were calculated and considered predictable, as well as the effects were significant. The TPC exhibited a variation in less concentrated samples (0.5% p/v) at higher temperatures (90 °C). In contrast, the temperature was the only influential variable for AA, where only higher temperatures (60-90 °C) were able to destabilize the fruit extract. Differently, GA showed only the concentration as the influential variable, exhibiting that neither temperature nor time of exposure could affect the gallic acid content stability of P. macrophylla extract. For this, P. macrophylla extract was shown to be highly stable, providing a great perspective on cosmetic application.

Abstract LB081: Concurrent characterization of somatic nucleotide mutations, 5mC, and 5hmC methylation in clinical research samples using a single nanopore sequencing assay

Abstract Genomic and epigenomic variants accumulate during cancer progression, resulting in a tumor consisting of heterogeneous collections of cells, or clones, with distinct profiles of genomic and/or epigenomic alterations. The ability to characterize a broad set of somatic (epi)genomic variations simultaneously, using a single sequencing assay, facilitates cancer research and can help inform treatment. Here we describe a comprehensive approach to analyze native tumor DNA with long nanopore reads. First, we demonstrate that shallow (&amp;lt;1x) whole genome nanopore sequencing provides sufficient information to observe large-scale copy number aberrations. This enables rapid and affordable screening of samples with an aim of selecting those that contain variation(s) of potential interest; such samples can then be sequenced to higher coverages for a higher resolution picture of specific structural variants. We further demonstrate an analysis workflow vimba for high coverage (&amp;gt;30x) nanopore sequencing of tumor/normal datasets that detects clone- and haplotype-resolved structural variations in patient-derived research samples. We provide an example of haplotype- and breakpoint-resolved compounded amplification and loss of heterozygosity (LOH) of a region containing the EGFR gene in an admixed kidney tumor sample. Finally, we describe the suitability of this assay to gather genome-wide (epi)genomic variations (e.g., SNPs, indels, SVs, microsatellite instability) across tumor samples of different cancer types. For the first time with native long nanopore reads we are able to capture 5mC and 5hmC methylation information and map it over some of the most challenging repetitive regions of the genome. This information can empower a better understanding of cancer-type-specific (epi)genomic alterations, which in turn can help map out the landscape for further research. Our approach demonstrates how nanopore sequencing can be used as a single comprehensive platform to better understand and resolve the complexity of (epi)genomic somatic alterations in tumor samples. Citation Format: Sergey Aganezov, Philipp Rescheneder, John Beaulaurier, Phillip James, Sissel Juul. Concurrent characterization of somatic nucleotide mutations, 5mC, and 5hmC methylation in clinical research samples using a single nanopore sequencing assay [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB081.

A Sensitive Colorimetric and Near-Infrared Fluorescent Probe for Tracing Slight pH Variation in Food Samples

A Sensitive Colorimetric and Near-Infrared Fluorescent Probe for Tracing Slight pH Variation in Food Samples

A SYSTEMATIC REVIEW OF THE POTENTIAL VALUE OF SYNOVIAL FLUID BIOMARKERS TO PREDICT CLINICAL OUTCOMES IN CARTILAGE REPAIR TREATMENTS

Multiple biochemical biomarkers have been previously investigated for the diagnosis, prognosis and response to treatment of articular cartilage damage, including osteoarthritis (OA). Synovial fluid (SF) biomarker measurement is a potential method to predict treatment response and effectiveness. However, the significance of different biomarkers and their correlation to clinical outcomes remains unclear. This systematic review evaluated current SF biomarkers used in investigation of cartilage degeneration or regeneration in the knee joint and correlated these biomarkers with clinical outcomes following cartilage repair or regeneration interventions.PubMed, Institute of Science Index, Scopus, Cochrane Central Register of Controlled Trials, and Embase databases were searched. Studies evaluating SF biomarkers and clinical outcomes following cartilage repair intervention were included. Two researchers independently performed data extraction and QUADAS-2 analysis. Biomarker inclusion, change following intervention and correlation with clinical outcome was compared.9 studies were included. Study heterogeneity precluded meta-analysis. There was significant variation in sampling and analysis. 33 biomarkers were evaluated in addition to microRNA and catabolic/anabolic ratios. Five studies reported on correlation of biomarkers with six biomarkers significantly correlated with clinical outcomes following intervention. However, correlation was only demonstrated in isolated studies.This review demonstrates significant difficulties in drawing conclusions regarding the importance of SF biomarkers based on the available literature. Improved standardisation for collection and analysis of SF samples is required. Future publications should also focus on clinical outcome scores and seek to correlate biomarkers with progression to further understand the significance of identified markers in a clinical context.