Preclinical Diagnosis Research Articles

The role of decellularized cell derived extracellular matrix in the establishment and culture of in vitro breast cancer tumor model

Decades of research have shown that two-dimensional cell culture studies are insufficient for preclinical cancer diagnosis and treatment, and that cancer cells in three-dimensional (3D) culture systems have better cell–cell and cell–matrix interactions, gene expression, heterogeneity, and structural complexity that more closely resemble in vivo tumors. Researchers are still optimizing 3D culturing settings for different cancers. Despite promising tumor spheroid research, tumor cell-only aggregates lack the tumor microenvironment and cannot model tumors. Here, MCF-7 breast cancer cell derived decellularized extracellular matrix (CD-dECMs) were obtained and converted into autologous, biologically active, biocompatible, and non-immunogenic hydrogels to be used as micro-environment in both organoid formation and culture. For the production of organoids, CD-dECM doping concentrations ranging from 0.1 mg ml−1 to 1.5 mg ml−1 were evaluated, and the lowest concentration was found to be the most effective. For organoid culture, 8 mg ml−1 CD-dECM, 4 mg ml−1 rat tendon collagen type I (Col I) (4 mg ml−1) and a 1:1 (v/v) mixture of these two were used and the most viable and the biggest organoids were discovered in CD-dECM/Col I (1:1) group. The results show that autologous CD-dECM can replace hydrogels in tumor organoid generation and culture at low and high concentrations, respectively.

AIEgen-deep: Deep learning of single AIEgen-imaging pattern for cancer cell discrimination and preclinical diagnosis

This study introduces AIEgen-Deep, an innovative classification program combining AIEgen fluorescent dyes, deep learning algorithms, and the Segment Anything Model (SAM) for accurate cancer cell identification. Our approach significantly reduces manual annotation efforts by 80%–90%. AIEgen-Deep demonstrates remarkable accuracy in recognizing cancer cell morphology, achieving a 75.9% accuracy rate across 26,693 images of eight different cell types. In binary classifications of healthy versus cancerous cells, it shows enhanced performance with an accuracy of 88.3% and a recall rate of 79.9%. The model effectively distinguishes between healthy cells (fibroblast and WBC) and various cancer cells (breast, bladder, and mesothelial), with accuracies of 89.0%, 88.6%, and 83.1%, respectively. Our method's broad applicability across different cancer types is anticipated to significantly contribute to early cancer detection and improve patient survival rates.

Importance in the determination of serum uric acid, cholesterol and triglyceride levels in pregnant women

The fundamental importance of the analytes lies in their role as primary biomarkers to identify possible conditions that may arise during the gestation process. Objective: To analytes the importance of determining uric acid, cholesterol and triglycerides in pregnant women. Methodology: The article was a literature review that focused on the synthesis and analysis of scientific articles related to the topic in question. The PRISMA method was used to search for information, which consisted of an exhaustive and systematic search for relevant data using appropriate search terms and strategies. Results: Thirteen articles were screened and selected for analysis, of which six were excluded because they focused on pregnant women, but with different analytes. From the standards, 7 articles were identified that met the methodology and were included in the article development analysis. Conclusions: The research evidenced that the evaluation of uric acid, cholesterol and triglyceride levels are a first source in preclinical diagnosis, however, among the most common pathologies such as preeclampsia there are approximately 66 predictive parameters being this an important part of prenatal care to promote a healthy pregnancy

Construction of built-in correction photoelectrochemical sensing platform for diagnosis of Alzheimer's disease

The occurrence of Alzheimer's disease (AD) is strongly associated with the progressive aggregation of a 42-amino-acid fragment derived from the amyloid-β precursor protein (Aβ1-42). Therefore, it is crucial to establish a versatile platform that can effectively detect Aβ1-42 to aid in the early-stage preclinical diagnosis of AD. Herein, we introduce a specialized split-type analytical platform that enables sensitive and accurate monitoring of Aβ1-42 based on a self-corrected photoelectrochemical (PEC) sensing system. To realize this design, gelatinized Ti3C2@Bi2WO6 Schottky heterojunctions were prepared and served as photoelectrodes for tackling the photoinduced charge carriers. Functionalized CaCO3@CuO2 nanocomposites were used as signal converters to detect Aβ1-42 and amplify the signal further. Benefiting from the glucose oxidation induced acid microenvironment and H2O2 output, the nanocomposites are able to rapidly decompose, producing Ca2+ and Fenton-like catalyst Cu2+. The Cu2+-driven Fenton-like reaction generated ·OH, which accelerated the 3,3′,5,5′-tetramethylbenzidine (TMB) oxidation. Additionally, Ca2+ was cross-linked with alginate inducing gelation on the surface of Ti3C2@Bi2WO6 Schottky heterojunctions, influencing mass transfer and light absorption. Eventually results in the shift of photocurrent, allowing for precise quantification with a detection limit of 0.06 pg mL−1. The combination of colorimetric variation and the photoelectric effect provide a more accurate and reliable result. This research opens up new possibilities for constructing PEC platforms and beyond.

Modification of nanodiamonds for fluorescence bioimaging.

Non-invasive bioimaging is essential in enhancing pre-clinical diagnosis and therapy. Developing efficient imaging probes with high stability, low toxicity, and the potential of offering high resolution images is a very important aspect of developing non-invasive bioimaging techniques. Fluorescent nanodiamonds, which are produced by high energy beam irradiation and high temperature/pressure treatment, have been extensively investigated. In this study, we report the chemical modification of common nanodiamonds (prepared by detonation and high-pressure high-temperature milling) using a stable fluorophore (perylene diimide derivative) via carbodiimide coupling. The resulting nanodiamonds show good biocompatibility, cellular uptake and fluorescent imaging potential with mesenchymal stromal cells. This method provides an efficient alternative approach to the preparation and the use of fluorescent nanodiamonds for bioimaging, with the potential benefit of chemically adjusting the structure of perylene diimide for optimized emission/absorbance wavelength.

Towards the preclinical diagnosis of diabetic retinopathy and diabetic macular oedema using tear samples

Aims/Purpose: A wide spectrum of molecular‐genetic events, including inflammation (INF), angiogenesis (ANG), apoptosis (AP) and the concurrence of miRNAs and target genes, are involved in diabetic retinopathy (DR) and diabetic macular oedema (DMO). To unravel the complex pathogenesis of DR and DMO, we focus on the microvascular endothelial dysfunction (MVED) pathophysiologic pathways.Methods: Volunteers of both sexes, aged 35–80 years were enrolled and distributed into type 2 diabetics (T2DM), with DR (+DRG; n = 35), without DR (−DRG; n = 35), with DMO (DMOG; n = 28), and controls (CG; n = 40). Sociodemographic and comorbid data, ophthalmologic parameters, and molecular‐genetic variables related to INF, ANG, and AP, assayed in tear samples, were recorded. Statistics were performed by the R Core Team (2022) program.Results: Most of our participants were middle‐aged (mean age was 58 ± 11 years). Differential expression profile in tears was found statistically significant for SOCS6 gene (involved in INF) target of hsa‐miR‐155‐5p, VEGF‐A gene (implicated in ANG) target of hsa‐miR‐15b‐5p, and the BCL2L2 gene (AP effector) target of hsa‐miR‐10a‐5p, in both the +DRG and DMOG, as compared to the −DRG and CG.Conclusions: We confirm that INF, ANG, and AP, regulated by the hsa‐miR‐155‐5p, hsa‐miR‐15b‐5p and hsa‐miR‐10a‐5p, and its respective target genes SOCS6, VEGF‐A, and BCL2L2, expressed in tears, are key players in the development of structural and functional chorioretinal changes associated with MVED in DR/DMO patients. We may propose the above insights as potential diagnostic‐prognostic biomarkers for better managing the diabetic eyes and vision.

Unveiling MRI markers for Parkinson’s Disease: GABAergic dysfunction and cortical changes

ObjectiveThe study aimed to investigate changes in basal levels of the inhibitory γ-aminobutyric acid (GABA) neurotransmitter in the sensorimotor cortex (SMC) and cortical gyrification in patients with Parkinson’s disease (PD), which could further identify potential imaging biomarkers for PD, particularly in patients with early-onset Parkinson’s disease (EOPD). MethodFifty patients with PD (EOPD: 10, late-onset Parkinson’s disease [LOPD]: 40) and fifty-two age- and gender-matched healthy controls (HC) underwent GABA-edited 1H MRS of the SMC and high-resolution 3D T1-weighted brain imaging. GABA levels and local gyrification index (LGI) were calculated to assess GABAergic and cortical gyrification deficits in PD. ResultThe Pearson correlation coefficients revealed significant negative associations between eight indicators, including GABA/Cr level and local gyrification index (LGI) of specific cortical regions (precentral, postcentral, entorhinal, superiortemporal, posteriorcingulate, cuneus, and transversetemporal cortex), and the likelihood of Parkinson’s disease (r < -0.4, p < 0.001). Additionally, GABA levels were significantly lower in the SMC region of both EOPD and LOPD patients compared to healthy controls (mean ± SD [u.i.]: EOPD=0.081 ± 0.022 vs. Young-HC=0.112 ± 0.021, p = 0.003; LOPD=0.054 ± 0.024 vs. Old-HC=0.099 ± 0.021, p < 0.001). The logistic regression model was established by using multivariate analysis, identifying two statistically significant indicators: GABA/Cr and LGI of the transversetemporal. The combined model exhibited the highest AUC values in both younger and older populations. ConclusionGABAergic dysfunction may play an important role in the pathogenesis of PD patients. Changes in neurotransmitter and morphological may serve as potential markers for the preclinical diagnosis and progression of PD, including EOPD.

Synthesis and Application of a Near-Infrared Light-Emitting Fluorescent Probe for Specific Imaging of Cancer Cells with High Sensitivity and Selectivity.

The preclinical diagnosis of tumors is of great significance to cancer treatment. Near-infrared fluorescence imaging technology is promising for the in-situ detection of tumors with high sensitivity. Here, a fluorescent probe was synthesized on the basis of Au nanoclusters with near-infrared light emission and applied to fluorescent cancer cell labeling. Near-infrared methionine-N-Hydroxy succinimide Au nanoclusters (Met-NHs-AuNCs) were prepared successfully by one-pot synthesis using Au nanoclusters, methionine, and N-Hydroxy succinimide as frameworks, reductants, and stabilizers, respectively. The specific fluorescence imaging of tumor cells or tissues by fluorescent probe was studied on the basis of SYBYL Surflex-DOCK simulation model of LAT1 active site of overexpressed receptor on cancer cell surface. The results showed that Met-NHs-AuNCs interacted with the surface of LAT1, and C_Score scored the conformation of the probe and LAT1 as five. Characterization and in vitro experiments were conducted to explore the Met-NHs-AuNCs targeted uptake of cancer cells. The prepared near-infrared fluorescent probe (Met-NHs-AuNCs) can specifically recognize the overexpression of L-type amino acid transporter 1 (LAT1) in cancer cells so that it can show red fluorescence in cancer cells. Meanwhile, normal cells (H9c2) have no fluorescence. The fluorescent probe demonstrates the power of targeting and imaging cancer cells.

UBE3A: The Role in Autism Spectrum Disorders (ASDs) and a Potential Candidate for Biomarker Studies and Designing Therapeutic Strategies.

Published reports from the CDC's Autism and Development Disabilities Monitoring Networks have shown that an average of 1 in every 44 (2.3%) 8-year-old children were estimated to have ASD in 2018. Many of the ASDs exhibiting varying degrees of autism-like phenotypes have chromosomal anomalies in the Chr15q11-q13 region. Numerous potential candidate genes linked with ASD reside in this chromosomal segment. However, several clinical, in vivo, and in vitro studies selected one gene more frequently than others randomly and unbiasedly. This gene codes for UBE3A or Ubiquitin protein ligase E3A [also known as E6AP ubiquitin-protein ligase (E6AP)], an enzyme involved in the cellular degradation of proteins. This gene has been listed as one of the several genes with a high potential of causing ASD in the Autism Database. The gain of function mutations, triplication, or duplication in the UBE3A gene is also associated with ASDs like Angelman Syndrome (AS) and Dup15q Syndrome. The genetic imprinting of UBE3A in the brain and a preference for neuronal maternal-specific expression are the key features of various ASDs. Since the UBE3A gene is involved in two main important diseases associated with autism-like symptoms, there has been widespread research going on in understanding the link between this gene and autism. Additionally, since no universal methodology or mechanism exists for identifying UBE3A-mediated ASD, it continues to be challenging for neurobiologists, neuroscientists, and clinicians to design therapies or diagnostic tools. In this review, we focus on the structure and functional aspects of the UBE3A protein, discuss the primary relevance of the 15q11-q13 region in the cause of ASDs, and highlight the link between UBE3A and ASD. We try to broaden the knowledge of our readers by elaborating on the possible mechanisms underlying UBE3A-mediated ASDs, emphasizing the usage of UBE3A as a prospective biomarker in the preclinical diagnosis of ASDs and discuss the positive outcomes, advanced developments, and the hurdles in the field of therapeutic strategies against UBE3A-mediated ASDs. This review is novel as it lays a very detailed and comprehensive platform for one of the most important genes associated with diseases showing autistic-like symptoms. Additionally, this review also attempts to lay optimistic feedback on the possible steps for the diagnosis, prevention, and therapy of these UBE3A-mediated ASDs in the upcoming years.

EFFECTS OF DISCLOSING DIAGNOSES AND BIOMARKER RESULTS FOR ALZHEIMER’S DISEASE AND RELATED DISORDERS

Abstract Early diagnosis of mild cognitive impairment (MCI) and Alzheimer’s disease and related dementias (ADRD) has been recognized as a key strategy to improve health-related outcomes. However, given that these conditions are highly stigmatized, receiving a diagnostic label or knowing about biomarkers related to MCI or ADRD may have a profound impact on the person’s life. As the impacts of disclosure of diagnostic information related to MCI and ADRD on the well-being of people living with these conditions are not well understood, this symposium attempts to address this knowledge gap. The first presenter will describe a study that examined racial/ethnic variations in the effects of diagnostic labeling of ADRD on social aspects of the person’s life. The second presenter will discuss findings from a systematic review of the effects of ADRD and cognitive impairment on social engagement. The third presenter will present the findings of the study on the effect of amyloid PET results disclosure on health-related behaviors of people with MCI. The fourth presenter will describe the results of an online vignette study on the outcomes of a preclinical Alzheimer disease diagnosis. The fifth presenter will discuss the use of blood biomarkers to aid in the diagnosis of ADRD in primary care (PC). At the end of the presentation, the discussant will highlight implications for future research and policy development to alleviate negative impacts and maximize the positive impacts of a diagnostic label of MCI and ADRD.

Within-person changes in the aging white matter microstructure and their modifiers: A meta-analysis and systematic review of longitudinal diffusion tensor imaging studies

Abstract This meta-analysis and systematic review synthesized data from 30 longitudinal diffusion tensor imaging (DTI) studies on the magnitude, direction, spatial patterns, and modifiers of naturally occurring within-person changes in healthy adult white matter (WM) microstructure. Results revealed: (1) significant within-person declines in fractional anisotropy (FA) in the whole WM (d = -0.12), genu (d = -0.16), and splenium (d = -0.13); (2) greater declines in FA associated with older age, longer follow-up times, and female sex; (3) a possible yet inconclusive vulnerability of late-myelinating WM (the “development-to-degeneration” gradient); and (4) factors decelerating (e.g., physical activity and social activities) and accelerating (e.g., vascular risk factors, biomarkers for Alzheimer’s disease, and alcohol consumption) age-related FA changes. Our findings encourage the consideration of WM as a new target for treatments and interventions against cognitive decline and lay the foundation for studying the plastic and regenerative potential of adult WM in clinical trials. Individual differences in WM changes could aid in the preclinical diagnosis of dementia, opening a window for earlier, more effective treatments.

Performance of Anti-Carbamylated Protein Antibody Testing in the Routine Evaluation of Rheumatoid Arthritis from a Single Center.

Detection of anticyclic citrullinated peptide antibodies (anti-CCP) and rheumatoid factors (RF) in sera support the diagnosis of rheumatoid arthritis (RA); however, these markers are not detected in about 20% of RA patients. More recently, antibodies against carbamylated proteins (anti-CarP) have emerged with implications for preclinical RA diagnosis. The objective of this study was to assess the clinical performance of anti-CarP and correlate with disease severity in routine clinical practice. Retrospective chart review of 331 subjects submitted for RA panel serology: 136 clinically defined RA-positive and 195 RA-negative patients. Fifty additional individuals were recruited for healthy controls. Patients' sera were tested for anti-CCP, anti-CarP, and RF antibodies. Clinical performance characteristics were evaluated for anti-CarP individually and in combination with anti-CCP and RF. Documented erosions and synovitis were correlated with anti-CarP positivity. Anti-CarP had a clinical sensitivity and specificity of 27% and 94%, respectively, for established RA. This sensitivity was lower than anti-CCP (79%) and RF (85%). The specificity of anti-CarP was similar to anti-CCP (93%) and higher than RF (69%). Anti-CarP in combination with anti-CCP and RF increased specificity (100%) but decreased sensitivity (21%). There was no correlation of anti-CarP positivity with presence of bone erosions; however, there was an increase in anti-CarP positivity among patients with synovitis. Anti-CarP demonstrates high specificity in diagnosis of established RA but lacks clinical sensitivity. In combination, anti-CarP does not improve clinical performance of anti-CCP and RF but may be useful in anti-CCP negative patients and in identifying patients with more active disease.

Subjective cognitive decline domain improves accuracy of plasma Aβ 42 /Aβ 40 for preclinical Alzheimer's disease diagnosis: The SILCODE study.

Subjective cognitive decline domain improves accuracy of plasma Aβ 42 /Aβ 40 for preclinical Alzheimer's disease diagnosis: The SILCODE study.

Vitamin D level and indicators of bone tissue metabolism in kazakh infants

BACKGROUND: Insufficiency and deficiency of vitamin D are recorded in a significant part of the population. Vitamin D, along with the formation of bone tissue, is included in all types of metabolism, determining the growth and development of the body, immunity, and the normal development of the nervous system. The consequences of deficiency can be long-term and in some cases irreversible. The problem of deficiency in infants is not well understood.&#x0D; AIM: To determine the content of vitamin D and indicators of bone metabolism in children of the first year of life of the Kazakh population.&#x0D; MATERIALS AND METHODS: 250 infants of the Kazakh population were examined. The content of vitamin D in the blood was determined. The state of bone metabolism was assessed by the results of a blood test to determine the serum concentration of calcium, phosphorus, parathyroid hormone, osteocalcin, calcitonin, and in the urine deoxypyridinoline.&#x0D; RESULTS: There is a wide prevalence (77.8%) of vitamin D insufficiency/deficiency in children under one year old in the Kazakh population. The greatest decrease in vitamin D was found in newborns. Statistically significant differences were found in the levels of bone metabolism indicators, such as total calcium, phosphorus, calcitonin and osteocalcin in different age groups. Indicators of bone metabolism, such as total calcium, phosphorus, parathyroid hormone, osteocalcin, depend on the degree of decrease in vitamin D levels. The most sensitive indicator that responds to changes in vitamin D levels is osteocalcin. The level of serum vitamin D can be used as a marker for the preclinical diagnosis of metabolic disorders of bone homeostasis in children.&#x0D; CONCLUSIONS: The study confirms the effect of vitamin D on metabolic processes in the skeletal system. The most sensitive indicator that responds to changes in vitamin D levels is osteocalcin. Research in this direction may be the basis for discussing the feasibility of vitamin D substitution and clarifying prenatal care schemes.

Spatiotemporal description of African swine fever virus nucleic acid and antibodies detected in pigs sampled at abattoirs in the greater Kampala metropolitan area, Uganda from May 2021 through June 2022

BackgroundAfrican swine fever virus (ASFV) infections in Africa cause hemorrhagic disease in domestic pigs and is maintained by a sylvatic cycle in warthogs. It is endemic in Uganda, leading to significant economic losses. Previous studies performed in rural areas and in Kampala had differing diagnostic results. The purpose of this study was to provide a robust spatial, temporal, and diagnostic summary of pigs slaughtered in the greater Kampala metropolitan area over the course of one year. This study characterized 1208 to 1323 serum, blood, and tissue samples collected from pigs at six abattoirs in the greater Kampala metropolitan area of Uganda monthly from May 2021 through June 2022. Validated and standardized serologic and molecular diagnostics were used.ResultsOnly 0.15% of pigs had detectable antibodies against ASFV, suggesting low survival rates or pre-clinical diagnosis. Yet, 59.5% of pigs were positive for ASFV DNA. Blood had the lowest detection rate (15.3%) while tonsil and lymph nodes had the highest (38% and 37.5%, respectively), spleen samples (31.5%) were in between. Agreement between sample types was fair to moderate overall. A significant seasonality of ASFV infections emerged with infections found predominately in the dry seasons. Spatial assessments revealed that the greater Kampala metropolitan area abattoirs have a catchment area that overlaps with Uganda’s most pig dense regions.ConclusionsPigs at greater Kampala metropolitan area abattoirs can be sentinels for acute disease throughout the pig dense region of Uganda, particularly in the dry seasons. The high prevalence detected suggests that pigs are sold in response to local reports of ASFV infections (panic sales). Serological surveillance is not useful, as very few pigs seroconverted in this study prior to slaughter. In contrast, tissue samples of pigs can be used to detect disease using qPCR methods.

In Memoriam: Valerii Semenovych Ponomarchuk

In Memoriam: Valerii Semenovych Ponomarchuk

The role of multifocal electroretinography in the preclinical diagnosis of tumor-associated distant maculopathy in small melanoma of the choroid of extramacular localization

To assess the role of multifocal electroretinography (mf-ERG) in preclinical diagnosis of tumor-associated distant maculopathy in small choroidal melanoma (CM) of extramacular localization.Material and methods. 35 patients (35 affected and 35 fellow eyes) with small CM of extramacular localization and 23 healthy volunteers (46 eyes) aged 59.67 ± 14.2 years were given general ophthalmological examinations and mf-ERG. Density (nV/deg2), culmination time of the P1 component and amplitude (μV) of the N1 component were measured for 5 response rings (R1–R5) at different distances from the fixation point: central hexagon R1: 2.3° (fovea zone); R2: 2.3–6.9° (parafovea); R3: 6.9–14.3° (perifovea); R4: 14.3–20.8° and R5: 20.8–29.9° (middle periphery areas of the retina).Results. Eyes affected by CM showed a decrease in the density of the P1 component in the R1 hexagon by 25.7% of the normal values (p = 0.03). The fellow eyes showed an increase in the density of the P1 component in the R2 ring (p &lt; 0.05). The peak latency of the P1 component in the R1–R5 rings in the affected and fellow eye was found to elongate by 30–45% (p &lt; 0.05). The amplitude of the N1 component in the central hexagon of CM-affected eyes increased by 12.96%, whilst in the R4–R5 rings it decreased by 36–45% as compared with healthy individuals (p &lt; 0.05). The fellow eye showed supernormal values of the N1 amplitude in R1 and its suppression in R4 and R5 rings (p &lt; 0.05).Conclusion. The mf-ERG method is useful for preclinical diagnosis of tumor-associated distant maculopathy in small CM of extramacular localization. Changes in mf-ERG of the fellow eye in patients with small CM have been documented.

Glucose level in amniotic fluid as a preclinical marker of chorioamnionitis

The article presents the results of a study amniotic glucose concentration as a potential early indicator of the inflammatory process in the fetal membranes. The main focus was on the analysis of the features of pregnancy and labor in women with premature rupture of membranes (PROM) during full-term and preterm labor according to amniotic fluid glucose levels. Currently, the expectant approach in cases of PROM is widely practiced throughout the world. The objective: to estimate the glucose level in the amniotic fluid as a preclinical marker of chorioamnionitis. Materials and methods. Depending on the glucose concentration in the amniotic fluid at the time of rupture of membranes and the term of rupture of membranes, 97 pregnant women were divided into 4 groups. I and II groups consisted of women with PROM between 24 and 36 weeks and 6 days. In the I group there were 34 pregnant women with a glucose concentration in the amniotic fluid of more than 0.5 mmol/l, and in the II group – 15 pregnant women with the indicator of less than 0.5 mmol/l. III and IV groups included pregnant women with PROM at full-term pregnancy (after 37 weeks). In the III group there were 34 patients with an amniotic glucose concentration of more than 0.5 mmol/l, and in the IV – 14 pregnant women with the indicator of less than 0.5 mmol/l. In all groups, the further course of pregnancy, the time period from the rupture of membranes to the beginning of labor, the need for induction of labor, hyperthermia before the beginning of labor, deviations from the normal course of labor were analyzed (hyperthermia, fetal distress in labor, uterine weakness) and the frequency of operative delivery. Results. The study determined that women with an amniotic glucose concentration below 0.5 mmol/l at the time of hospitalization were more likely to have hyperthermia before and during childbirth. Hyperthermia was most often observed during the first 12 hours after membrane rupture. In addition, these women were more prone to serious birth complications, such as fetal distress, weak labor, and a greater likelihood of needing an operative delivery. Conclusions. 1. A decreased amniotic glucose level less than 0.5 mmol/l is associated with more frequent clinical manifestations of amniotic infection (20% in preterm pregnancies and 14.8% – in full-term pregnancies) than in groups with a glucose content of more than 0.5 mmol/l (8.8% in preterm pregnancies and 5.9% – in full-term pregnancies, p≤0.05). 2. Among patients with a glucose content in amniotic fluid less than 0.5 mmol/l, laboratory manifestations of intra-amniotic infection were detected more often (40% in preterm pregnancies and 42.5% in full-term pregnancies) than among pregnant women with a glucose content of more than 0.5 mmol/l (20% in both full-term and preterm pregnancies, p≤0.05). 3. Determination of the glucose level in amniotic fluid can be considered as an available method of preclinical diagnosis of chorioamnionitis for the individual choice of management tactics in case of premature rupture of the amniotic membranes, which is especially important in premature pregnancy.

B-103 A Single Centre Experience of Anti-carbamylated Protein Antibody Testing in the Routine Evaluation of Rheumatoid Arthritis

Abstract Background Rheumatoid arthritis (RA) early diagnosis and treatment can slow disease progression and potentially prevent bone erosion. Anticyclic citrullinated peptide (CCP) IgG and rheumatoid factors (RF) serological testing supports the diagnosis of RA; however, these markers are not detected in about 20% of RA patients. Recently, IgG antibodies against carbamylated proteins (CarP) emerged with implications on preclinical RA diagnosis and disease severity. CarP testing is offered as part of RA panel (CarP, RF and CCP) and as a standalone test in our institution. In this study, we evaluated the contribution of CarP testing for RA diagnosis in our routine clinical practice. Our objectives were 1) to assess the clinical performance of CarP in combination with CCP and/or RF antibodies 2) to understand the association of CarP with disease severity. Methods Our cohort included 331 subjects submitted for RA panel serology. Retrospective chart-review revealed 136 clinically defined RA-positive and 195 RA-negative patients. Patients’ sera were tested for CCP, CarP (Inova Diagnostics, San Diego, US) and RF (Roche Diagnostics, Indianapolis, US) antibodies. Clinical performance characteristics were evaluated for CarP individually and in combination with CCP and RF. Disease manifestations (bone damage and synovitis), were correlated with CarP testing. Results Single antibody testing for CarP differentiated RA patients from disease-controls with a 27.2% sensitivity, 93.3% specificity, 74.0% positive predictive value and 64.8% negative predictive value. When CarP testing was combined with RF, specificity increased to 95.4%, in combination with CCP it increased to 98.5% and in a triple combination with CCP and RF, specificity increased to 99.5%. The specificity observed in CCP and RF combination (98.5%) was equivalent to CCP and CarP combination or CCP, CarP and RF triple combination. Amongst the RA patients, frequency of bone erosions was slightly greater (P = 0.76) in the presence of CarP positivity (19/37, 51.4%) compared to the presence of CCP (51/107, 47.7%) or RF (50/112, 44.6%) positivity in isolation and/or in combination. Frequency of synovitis was higher in RA patients that tested positive for CarP (20/37, 54.1%) compared to patients who tested positive for CCP (44/107, 41.1%) or RF (43/112, 38.4%). In the seronegative subgroup, 17.2% (5/29) of CCP negative and 14.3% (3/21) of RF negative patients were positive for CarP. Six out of 8 patients in this subgroup displayed bone erosions and/or synovitis. Of the early RA- diagnosed patients (&amp;lt; 6 months of symptom onset), 22.2% (2/9) were CarP positive, of which one patient (11.1%) was seronegative for CCP but positive for RF. Conclusion Despite low sensitivity, individual CarP testing offered a specificity comparable to CCP. In combination with CCP and/or RF, CarP displayed a superior specificity compared to any individual testing, however, was inferior to the CCP and RF combination. CarP positivity independently and/or in combination was associated with a severe disease course. These data support the use of CarP in combination with CCP and RF for assessing disease severity but may not be advantageous for initial diagnosis. In CCP or RF seronegative patients, CarP testing may be beneficial in establishing a diagnosis of RA.

Regularized reconstruction based on joint smoothly clipped absolute deviation regularization and graph manifold learning for fluorescence molecular tomography

Objective. Fluorescence molecular tomography (FMT) is an optical imaging modality that provides high sensitivity and low cost, which can offer the three-dimensional distribution of biomarkers by detecting the fluorescently labeled probe noninvasively. In the field of preclinical cancer diagnosis and treatment, FMT has gained significant traction. Nonetheless, the current FMT reconstruction results suffer from unsatisfactory morphology and location accuracy of the fluorescence distribution, primarily due to the light scattering effect and the ill-posed nature of the inverse problem. Approach. To address these challenges, a regularized reconstruction method based on joint smoothly clipped absolute deviation regularization and graph manifold learning (SCAD-GML) for FMT is presented in this paper. The SCAD-GML approach combines the sparsity of the fluorescent sources with the latent manifold structure of fluorescent source distribution to achieve more accurate and sparse reconstruction results. To obtain the reconstruction results efficiently, the non-convex gradient descent iterative method is employed to solve the established objective function. To assess the performance of the proposed SCAD-GML method, a comprehensive evaluation is conducted through numerical simulation experiments as well as in vivo experiments. Main results. The results demonstrate that the SCAD-GML method outperforms other methods in terms of both location and shape recovery of fluorescence biomarkers distribution. Siginificance. These findings indicate that the SCAD-GML method has the potential to advance the application of FMT in in vivo biological research.