Reliable Differentiation Research Articles

Primary hyperparathyroidism with intrathyroidal location of parathyroid adenoma

Primary hyperparathyroidism is a common endocrine disease with high morbidity and mortality from all causes. The disease can be asymptomatic and for a long time remain undiagnosed, which leads to untimely surgical treatment, increases the risks of development and progression of severe disabling complications and worsens patients prognosis. In clinical practice there are certain difficulties in diagnosing this pathology. One of the urgent problems is the search for the source of parathyroid hormone hyperproduction, especially in case of atypical location of paraаdenoma. The most common atypical locations of altered parathyroid glands are thymus, retroor paraesophageal space, retropharyngeal space, mediastinum and thyroid gland. The frequency of intrathyroidal masses of parathyroid glands, in the thyroid parenchyma or under its capsule, ranges on average from 2 to 3%, but according to some authors can reach 18–22%. With such localization of paraadenomas there is a need for their differential diagnosis, first of all, with nodular formations of the thyroid gland. In addition, the absence of additional laboratory studies parathormone and calcium blood levels does not allow timely suspicion of the disease, and cytologic examination of the material obtained by fine-needle aspiration puncture biopsy does not allow reliable differentiation of the altered parathyroid gland. This article presents a clinical case of a patient with primary hyperparathyroidism with intrathyroidally located parathyroid adenoma, for a long time long identified as a “nodular goiter,” and provides a brief review of the methods that identify an intrathyroidally located parathyroma. Despite the abundance of diagnostic methods in visualization of intrathyroidal parathyroid glands, today the most appropriate seems to be expert ultrasound examination with assessment of the parathyroid hormone level in a washout after fine-needle aspiration, supplemented, if necessary, by scintigraphy and single-photon emission computed tomography combined with computed tomography or multispiral computed tomography.

Evaluation of Selected MRI Parameters in the Differentiation of Mucinous Ovarian Carcinomas and Metastatic Ovarian Tumors

Introduction: Analysis of selected MRI parameters in initial MRI for the characterization of ovarian masses enables differentiation between mucinous ovarian carcinoma and metastatic ovarian tumors. Material and Methods: A prospective analysis of contrast-enhanced MRI of patients with suspected ovarian masses diagnosed in ultrasound and CT examination. Morphological criteria, such as the size of lesion, bilateral location, presence of “mille-feuille sign”, so-called Seidman criteria, as well as the diffusion weighted imaging and dynamic contrast enhancement of each lesion, were evaluated. Patients were allocated into two groups; the first group contained patients with mucinous ovarian cancer, and the second group contained patients with metastatic ovarian tumors. Results: A total of 35 patients were enrolled into the study. Median age was 49 in the first group and 59 in the second group of patients (p = 0.04). In the first group, all patients (100%) had unilateral lesions, and in the second group, 94% had bilateral tumors (p < 0.000001). In the first group, a tumor size equal or greater than 10 cm was present in 80% of patients, and the same was true for 21% of patients in the second group. The mille-feuille sign was present in 30% of patients from the first group and in 64% of patients from the second group. In the first group of patients, TTP was 410 and Perf.Max Enhancement was 141; in the second group, they were, respectively, 154 and 167 (p = 0.0001 and p = 0.5). Median ADC values in the first group were significantly higher in the first group than in the second group (p < 0.01). Conclusions: Significant differences in TTP and ADC values as well as in Seidman criteria enable reliable differentiation between the analyzed groups of tumors.

E-waste driven eco-friendly highly sensitive wearable capacitive sensors for physical activity monitoring and sign language recognition

Owing to the continual and rapid advancement in technology, there has been a significant surge in electronic waste (e-waste) in recent decades, resulting in a harmful impact on our environment. Due to the growing demand for battery-powered devices, non-rechargeable batteries are a significant source of e-waste. This study describes fabricating a paper-based graphite strain sensor that is eco-friendly, inexpensive, biodegradable, and sensitive to the applied strain. Readily accessible materials are employed to design and fabricate MIDC strain sensors. The Modified Interdigital Capacitor (MIDC) structure is formed on basic printing paper, and the conductive substance made with the ink of a gel pen and graphite from a drained dry cell is painted on the paper and used as electrode material. The suggested sensor has a high gauge factor value of 1998.578 and fast response and recovery time of 112 ms and 100 ms, respectively. The proposed prototype has also been utilized to inspect fitness exercises and physical activities on the human body, inspiring the potential for its integration into wearable systems for various applications. Reliable detection and differentiation of finger positions are achieved, highlighting the sensor's potential for more advanced sign language applications. It’s a good option to integrate the suggested strain sensor in wearable systems, such as telemedicine systems, electromechanical detection, healthcare, and physical activity monitoring of humans.

Molecular identification of Mycobacterium bovis in patients with tuberculosis attending a tertiary care hospital in South India

Background: Mycobacterium (M.) bovis is a member of Mycobacterium tuberculosis complex (MTBC). Clinical infection caused by M. bovis is indistinguishable from other MTBC and could pose a potential challenge for control of TB epidemic due to its zoonotic nature. Availability of reliable molecular diagnostic methods such as Genotype MTBC based on line probe assay (LPA) paves way for reliable differentiation of M. bovis from other MTBC. Objective: To determine the proportion of Mycobacterium bovis among the Mycobacterium tuberculosis complex isolates from patients with tuberculosis. Methods: In our study, we analysed MGIT positive cultures and performed Line probe assay (LPA) for identification of MTBC isolates. Total of 206 patient samples were taken, 104 pulmonary and 102 from extrapulmonary sites. Results: M.tuberculosis/ M.canettii was isolated in all pulmonary specimens (100%). Among 102 extrapulmonary samples, 99 % was identified as M.tuberculosis/ M.canettii, and 1 % as M. bovis BCG. Conclusion: Our study suggests that zoonotic TB by M. bovis may not be as prevalent in India and hence may not constitute a significant risk to public health in India. Keywords: TB; M. bovis; line probe assay.

Significance of apparent diffusion coefficient in diagnosis of rectal carcinoma.

The apparent diffusion coefficient (ADC) is a quantitative parameter that facilitates the detection and reliable differentiation of rectal cancer. MR differentiation between rectal carcinoma, post-radiation proctitis, and normal rectal wall with the ADC values and their comparison depending onthe level of tumor markers and pathohistological characteristics of rectal carcinoma. The retrospective study performed at the Oncology Institute of Vojvodina included 300 patients, 100 each with rectal cancer, post-radiation proctitis, and normal rectum. Mean ADC values were obtained by measuring the region of interest (ROI) of the rectal wall. Rectal cancer showed lower ADC values (0.665 ± 0.086 x 10-3mm2/s) compared to both post-radiation proctitis (1.648 ± 0.268 x 10-3mm2/s) and normal rectum (1.180 ± 0.110 x 10-3mm2/s) (p<0.001). No significant differences in ADC values were observed between different grades of rectal cancer (p=0.874; p>0.05), depending on the presence of metastases in the lymph nodes (p=0.357; p>0.05), different TN stage (p=0.196; p>0.05), local spread of the tumor (p=0.312; p>0.05), the presence of RAS mutation (p=0.829; p>0.05) and the value of tumor markers (p=0.923; p>0.05). ADC values below 1.013 x 10-3mm2/s with 100% sensitivity and 96% specificity indicate the presence of rectal cancer in relation to normal wall, with a positive predictive value of 96.1% and a negative of 100%. ADC values below 1.255 x 10-3mm2/s with 100% sensitivity and 95% specificity indicate rectal cancer in relation to post-radiation proctitis. ADC values above 1.339 x 10-3mm2/s with 87% sensitivity and 89% specificity indicate post-radiation proctitis in relation to normal wall. The ADC is a useful marker in differentiating between rectal cancer, post-radiation proctitis, and normal rectal wall with high sensitivity and specificity, but it cannot be used to distinguish the histological grades of rectal cancer, nor other pathohistological parameters.

Campylobacter fetus subspecies specific PCR assays inferred from comparative genomic analysis for accurate subspecies identification

Bovine Genital Campylobacteriosis (BGC) is caused by Campylobacter fetus subsp. venerealis and is a notifiable disease to the WOAH (World Organisation for Animal Health). For an effective BGC control program, the reliable differentiation of Campylobacter fetus subsp. venerealis (Cfv) from the closely related Campylobacter fetus subsp. fetus (Cff) is required. However, the available molecular C. fetus subspecies identification assays lack sensitivity and specificity to differentiate C. fetus isolates based on their phenotypic or genotypic differences. Furthermore, the current biochemical subspecies identification is not fully congruent with the genomic differentiation of C. fetus strains.In this study, the genome sequences of 41C. fetus strains with well identified subspecies, were analyzed with the large-scale BLAST score ratio (LS-BSR) pipeline to identify Cff and Cfv specific sequences. With this analysis, the asd gene encoding an aspartate-semialdehyde dehydrogenase was identified, which contained a 6-bp Cff-specific sequence, and this 6-bp sequence was absent in the asd gene of Cfv strains. This sequence was used for the development of PCR assays to differentiate Cff and Cfv strains. The C. fetus subspecies identification of the developed asd PCR assays was in full congruence with the genomic classification of strains and are recommended for molecular identification of C. fetus subspecies in BGC control programs.The asd PCR can be assessed on sequenced genomes using a web interface containing the Cfvcatch tool, which includes placement of the tested genome in a phylogenetic tree with reference C. fetus genomes to distinguish the two subspecies and to detect antimicrobial resistance genes.

Differentiating extradural head and neck arterial fenestrations from other intraluminal abnormalities

Background and PurposeArterial fenestrations are a benign entity arising from a failure of fetal fusion. However, fenestrations in the head and neck may be misinterpreted as carotid webs or dissections. Given differences in clinical management, the differentiation of these entities is imperative. We aim to document the prevalence of these entities on CTA imaging and highlight imaging features for confident differentiation. Materials and MethodsWe retrospectively reviewed head and neck CTA studies performed at our institution over an 18-month period. The extradural common carotid, internal carotid, external carotid, and vertebral arteries were inspected for intraluminal abnormalities. These abnormalities were classified as fenestration, web, or dissection. Location and associated non-atherosclerotic calcification, pseudoaneurysm, or thrombosis were also documented. ResultsA total of 1800 head and neck CTAs were examined. Normal extradural arteries were seen in 1731 patients (1731/1800; 96.2 %). An intraluminal abnormality was evident in the remaining 69 patients (69/1800; 3.8 %). There were 16 carotid webs (16/1800; 0.9 %), 46 dissections (46/1800; 2.6 %), and 7 fenestrations (7/1800; 0.4 %). An associated non-atherosclerotic pattern of calcification was only identified in a single fenestration case (1/7; 14.3 %). Thrombosis was not identified in any fenestration case. ConclusionArterial fenestrations of the extradural head and neck arterial vasculature are evident on 0.4 % of CTAs. It is important to differentiate these benign entities from carotid webs and arterial dissections. With the appropriate knowledge and interpretive tools, characteristic imaging findings on CTA can be used for reliable differentiation.

Diagnostic mistakes in assessing MRI semiotics of primary extra-axial brain tumors tumors.

Primary extra-axial brain tumors (PExT) are represented by benign and malignant tumors of the meninges and cranial nerves. Their preoperative differential diagnosis based on an analysis of the semiotics of magnetic resonance imaging. The critically important points that make it possible to classify tumors of this group are the following characteristics: tumors structure, contrast enhancements, invasion and relationship tumors with the meninges or cranial nerves. Differential diagnostic typical PExT is not difficult, because most of they heave typical MRI visual signs. With atypical MRI manifestations, reliable differentiation of tumors can be difficult. The greatest difficulty in this case is the differentiation of benign and malignant meningiomas, the distinction between solitary fibrous tumors and meningiomas, and the tumors when they localized in the cerebellopontine angles. The case series presented containing the most typical situations leading to errors in the differential diagnosis of PexT, all tumors had untypical signs. All presented tumors were histological verified. Analysis of the given clinical examples shows that consideration of the entire set of semiotic signs can reduce the number of diagnostic errors.

Utility of Ultrasound-Guided Attenuation Parameter (UGAP) in Renal Angiomyolipoma (AML): First Results.

Angiomyolipoma (AML) are the most common benign solid renal mass. Differentiation from malignant tumours is essential. Imaging features in ultrasound may overlap between malignant lesions, especially between renal cell carcinoma (RCC) and AML. So far, sectional imaging has been necessary for reliable differentiation. The aim of this study is to evaluate the use of the ultrasound-guided attenuation parameter (UGAP), a recently established tool for assessing hepatic steatosis, in the differentiation of AMLs from other renal masses. Therefore, 27 patients with unknown solid renal masses were examined by ultrasound including UGAP. The attenuation was assessed qualitatively by attenuation map and quantitatively in comparison to the surrounding renal tissue. UGAP was applicable in 26/27 patients. Findings were compared with CT/MRI as the current imaging standard. A total of 18 AML and 9 other renal tumours were found. The diagnostic performance of B-Mode (hyperechogenic lesion) ultrasound was 77.8% in identifying AML. The diagnostic performance of the attenuation map showed a diagnostic performance of 92.6%, whereby UGAP measurements were successful in 76.9% of cases. Quantitatively, we found a significant difference (p < 0.034) in mean measured attenuation between AML (0.764 ± 0.162 dB/cm/MHz) vs. other renal tumours (0.658 ± 0.155 dB/cm/MHz). The best performance was found by a combined parameter of a hyperechogenic lesion with a positive attenuation map with an accuracy of 95.0%. In conclusion, UGAP may represent a possibility for differentiating solid renal lesions more accurately by ultrasound, especially classic hyperechoic AMLs from other renal lesions. Further studies are needed to increase the diagnostic reliability further.

A Microbial Phenomics Approach to Determine Metabolic Signatures to Enhance Seabream Sparus aurata Traceability, Differentiating between Wild-Caught and Farmed.

The need for efficient and simplified techniques for seafood traceability is growing. This study proposes the Biolog EcoPlate assay as an innovative method for assessing wild and farmed Sparus aurata traceability, offering advantages over other molecular techniques in terms of technical simplicity. The Biolog EcoPlate assay, known for its high-throughput capabilities in microbial ecology, was utilized to evaluate the functional diversity of microbial communities from various organs of S. aurata (seabream) from the Mediterranean area. Samples were taken from the anterior and posterior gut, cloaca swabs and gills to distinguish between farmed and wild-caught individuals. The analysis focused on color development in OmniLog Units for specific carbon sources at 48 h. Gills provided the most accurate clusterization of sample origin. The assay monitored the development of color for carbon sources such as α-cyclodextrin, D-cellobiose, glycogen, α-D-lactose, L-threonine and L-phenylalanine. A mock experiment using principal component analysis (PCA) successfully identified the origin of a blind sample. Shannon and Simpson indexes were used to statistically assess the diversity, reflecting the clusterization of different organ samples; Conclusions: The Biolog EcoPlate assay proves to be a quick, cost-effective method for discriminate S. aurata traceability (wild vs. farmed), demonstrating reliable reproducibility and effective differentiation between farmed and wild-caught seabream.

Differentiation of Spiral Ganglion Neurons from Human Dental Pulp Stem Cells: A Further Step towards Autologous Auditory Nerve Recovery.

The degeneration of spiral ganglion neurons (SGNs), which convey auditory signals from hair cells to the brain, can be a primary cause of sensorineural hearing loss (SNHL) or can occur secondary to hair cell loss. Emerging therapies for SNHL include the replacement of damaged SGNs using stem cell-derived otic neuronal progenitors (ONPs). However, the availability of renewable, accessible, and patient-matched sources of human stem cells is a prerequisite for successful replacement of the auditory nerve. In this study, we derived ONP and SGN-like cells by a reliable and reproducible stepwise guidance differentiation procedure of self-renewing human dental pulp stem cells (hDPSCs). This in vitro differentiation protocol relies on the modulation of BMP and TGFβ pathways using a free-floating 3D neurosphere method, followed by differentiation on a Geltrex-coated surface using two culture paradigms to modulate the major factors and pathways involved in early otic neurogenesis. Gene and protein expression analyses revealed efficient induction of a comprehensive panel of known ONP and SGN-like cell markers during the time course of hDPSCs differentiation. Atomic force microscopy revealed that hDPSC-derived SGN-like cells exhibit similar nanomechanical properties as their in vivo SGN counterparts. Furthermore, spiral ganglion neurons from newborn rats come in close contact with hDPSC-derived ONPs 5 days after co-culturing. Our data demonstrate the capability of hDPSCs to generate SGN-like neurons with specific lineage marker expression, bipolar morphology, and the nanomechanical characteristics of SGNs, suggesting that the neurons could be used for next-generation cochlear implants and/or inner ear cell-based strategies for SNHL.

Reliable delineation of Bacillus cytotoxicus from other members of the Bacillus cereus group by MALDI-TOF MS – An extensive validation study

Bacillus cytotoxicus is classified as a thermotolerant member of the Bacillus cereus group, producing the diarrhoea causing cytotoxin K1. This species came into the focus of food microbiologists when the type strain was isolated as the cause of a fatal food-borne outbreak. However, knowledge of the role of B. cytotoxicus as a food-borne microbe and data on its prevalence in food is still limited today. One reason for this is the lack of an easy to perform method of identification at the species level other than PCR, due to the highly similar phenotype of many B. cereus group representatives. Matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF MS) is widely used for the identification of microorganism species. This study describes the formal validation of a MALDI-TOF MS system for a reliable differentiation between B. cytotoxicus and other members of the B. cereus group. An extensive number of well-supported individual spectra from B. cytotoxicus, several other species of the B. cereus group, and 652 other microorganism species in a taxonomically wide range served as data sets. These were used to perform the validation for two database compilations: the commercial MALDI-Biotyper version K, and an extended compilation, including reference spectra from an open collection of spectra created by several users. Using both database combinations, the obtained values fulfil the formal criteria for the targeted identification of B. cytotoxicus in accordance with a national guideline for the validation of MALDI-TOF MS parameters in food analysis, with significant improvements due to the expanded database. By using 183 single spectra from 170 isolates, created in eleven different laboratories, the number of samples significantly exceeded the sample sizes for validation currently specified for ISO 16140–4:2020 for the validation of identification methods in food microbiology by single laboratories. Therefore, the method is suitable for routine application in an accredited laboratory context.

SMIAltmetric: A comprehensive metric for evaluating social media impact of scientific papers on Twitter (X)

The rise of social media has significantly influenced scholarly communication, knowledge dissemination, and research evaluation, leading to the enrichment of alternative metrics (altmetrics) for evaluating academic papers’ social impact, which assesses the social impact of academic papers through online activities, including reading, bookmarking, downloading, and commenting. However, these altmetrics often focus on the number of mentions on social media rather than thoroughly evaluating the source, content, and dissemination of these mentions. To address this gap, this study introduces the social media impact altmetric (SMIAltmetric), which is based on 44,087 publications and 860,680 tweets (now “posts”), a comprehensive scoring system for evaluating scientific papers on Twitter (now “X”), using diverse features, including literature-related, social media engagement-related, user-related, and content-related features. Employing Altmetric Attention Acores (AAS) as labels, we tested eight machine learning algorithms, with XGBoost demonstrating the highest accuracy at 0.8672. Crucial factors influencing SMIAltmetric, as identified by the SHAP value, were followers, retweets, mentions, and citation. Furthermore, consistency analysis and convergent validation between the proposed SMIAltmetric and AAS confirm the reliability and finer differentiation of SMIAltmetric. The proposed SMIAltmetric provides a more comprehensive understanding of a paper’s social media impact, enhancing the evaluation of scientific discourse and its engagement with society.

Reliability of Kudo’s Glandular Pit Pattern in Predicting Colorectal Lesion Histology at Routine Colonoscopy with Digital Chromoendoscopy

Background. The large number of lesions detected via high-definition (HD) imaging during colonoscopy calls for the reliable real-time histological characterization of polyps, especially diminutive and small ones, to permit tailored management based on the neoplastic risk, such as a “resect-and-discard” or a “diagnose-and-leave” strategy for low-risk adenomas and hyperplastic polyps (HPs). The Kudo classification of glandular pit pattern is currently used for predicting polyp histology. Aim. The aim in this study was to assess whether Kudo’s glandular pit pattern, assessed via HD digital chromoendoscopy (i-Scan) without magnification and optical enhancement, reliably predicts polyp histology and differentiates neoplastic lesions (NLs) from non-neoplastic lesions (non-NLs) during routine colonoscopy. Methods. Consecutive colorectal lesions recorded in a database over 12 months, with Kudo’s glandular pit pattern classification, were retrospectively compared with histology. The diagnostic accuracy and negative predictive value (NPV) for adenomatous histology of Kudo’s pit patterns were assessed separately for diminutive (≤5 mm) and small (6–9 mm) polyps, accordingly to the American Society for Gastrointestinal Endoscopy (ASGE) Preservation and Incorporation of Valuable Endoscopic Innovations (PIVI), and in large (≥10 mm) lesions. Results. A total of 2230 lesions were recorded: 898 diminutive, 704 small, and 628 large. Kudo’s type II pit pattern was prevalent in diminutive polyps and recognized mostly in HPs (83.27%); it was also found in 38.8% of adenomas. In the right colon, Kudo’s type II pit pattern was prevalent in adenomas (70.04% vs. 20.74% in HPs); among the serrated lesions, it was evenly distributed between HPs and adenomas. Kudo’s type IIIL/IIIs/IV pit pattern was prevalent in NLs (61% vs. 8.37% of non-NLs) in diminutive polyps, evenly distributed between non-NLs and NLs in small polyps, and found only in NLs in large polyps. Kudo’s type Vi/Vn pit pattern correctly identified all but one adenocarcinoma. The NPV for adenomatous histology did not reach the recommended 90% PIVI threshold for differentiation between NLs and non-NLs in diminutive polyps showing Kudo’s type II pit pattern and in small polyps showing type IIIL/IIIs/IV pit pattern. Conclusions. Kudo’s pit pattern classification carried out with digital chromoendoscopy (i-Scan) during routine colonoscopy does not allow the reliable differentiation between non-NLs and NLs in diminutive and small polyps, so a “diagnose-and-leave” strategy for diminutive polyps may leave undetected adenomas, while a “resect-and-discard” strategy could miss lesions requiring closer follow-up.

Comparative profiling of serum biomarkers and ATR-FTIR spectroscopy for differential diagnosis of patients with rheumatoid and psoriatic arthritis − a pilot study

BackgroundRheumatoid arthritis (RA) and psoriatic arthritis (PsA) are chronic inflammatory diseases in which innate and adaptive responses of the immune system are induced. RA and PsA have complex signaling pathways. Despite the differences in their clinical presentation, there is a great demand for fast and accurate diagnosis of diseases to implement treatment and plan an individual therapeutic strategy quickly. In this report, we present the results of differential diagnosis of patients with RA and PsA and healthy subjects (C, control group), allowing for reliable differentiation of groups of rheumatoid patients based on biochemical parameters, attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectra, and combined data sets. Materials and methodsBiochemical analyses, ELISA (enzyme-linked immunosorbent assays), and multiplex assays were conducted for blood sera from patients with RA (n = 32), patients with PsA (n = 28), and the control group (n = 18). ATR-FTIR spectra were collected for lyophilized sera. ResultsThe combination of six biochemical parameters (WBC, ESR, RF, CRP, HCC-4/CCL16, and HMGB1/HMGB) allowed the development of the partial least squares discriminant analysis (PLS-DA) model with an overall accuracy (OA) of 80% for test samples. The best separation between RA, PsA, and the control group was obtained utilizing spectral data. Using the interval PLS algorithm (iPLS) specific spectral ranges were selected and a classifier characterized by OA value for test set equal to 88% was obtained. This parameter, for the hybrid PLS-DA model constructed using selected biochemical parameters and a significantly reduced number of spectral variables, reached the level of 84%. ConclusionsPLS-DA models developed on the basis of spectral data enable effective differentiation of patients with RA, patients with PsA, and healthy subjects. They appeared to be insensitive to existing inflammation processes which opens interesting perspectives for new diagnostic tests and algorithms for identification of patients with RA and PsA.

#1004 Single-nucleus RNA sequencing identifies upregulated antigen presentation, apoptosis, mTORC1 signaling and EMT in primary FSGS podocytes

Abstract Background and Aims Primary focal segmental glomerulosclerosis (FSGS) is associated with irreversible podocyte damage, but the underlying cause and pathophysiology are incompletely understood. Furthermore, diagnostic markers that allow reliable differentiation between primary and secondary FSGS subtypes are lacking. We applied single-nucleus RNA-sequencing (snRNA-seq) on podocytes of patients with primary or secondary (maladaptive) FSGS, to identify subtype-specific differentially expressed genes and pathways. Method We used droplet-based snRNA-seq (10X Genomics Chromium) on cryopreserved kidney biopsy cores from human patients with newly diagnosed primary FSGS (n = 9, all nephrotic), maladaptive FSGS (n = 9, not nephrotic), proteinuric controls (PLA2R-positive membranous nephropathy (PLA2R+ MN), n = 3), and healthy controls (pre-perfusion biopsies, n = 4). Differential gene expression (DGE) analysis was done with a pseudobulk method provided by the EdgeR R-package to reduce bias and false discoveries. The fGSEA R-package was used for subsequent gene set enrichment analysis. Results We identified a total of 120 751 high-quality nuclei, of which 2 471 were podocytes (Fig. 1A). DGE analysis identified the top 20 differentially expressed genes (DEGs) per diagnosis (Fig. 1B). Remarkably, primary FSGS podocytes showed more transcriptional similarity to PLA2R+ MN podocytes, compared to maladaptive FSGS podocytes. This underscores the heterogeneity of patients with FSGS and shows that heavy proteinuria, regardless of the underlying diagnosis, may be associated with a distinct transcriptional profile in podocytes. Upregulated genes in primary FSGS podocytes included TIMP1, BTG2, ZNF44, EHD4, ZNF250, ECM1, SEMA4G, PHLDB1, and HDAC5. Upregulation of the matrix metalloproteinase inhibitor TIMP1 may possibly contribute to the development of glomerulosclerosis. Upregulation of BTG2 has previously been found to be pathogenic in FSGS by promoting epithelial-mesenchymal transition (EMT)-induced podocyte injury [1]. Next, gene set enrichment analysis on the identified DEGs in primary FSGS podocytes showed upregulation of pathways involved in antigen presentation (driven by upregulation of HLA-A, HLA-B, HLA-C, HLA-E and B2M), mTORC1 signaling, apoptosis and EMT (Fig. 1C). In maladaptive FSGS, upregulated pathways were mainly involved in extracellular matrix interaction. This may correlate with the significantly higher degree of chronic damage on kidney biopsy in the maladaptive FSGS patients (median Mayo Clinic Chronicity Score of 6.0, IQR [4.0-7.0]) vs. primary FSGS (2.0, [1.0-4.0]) and PLA2R+ MN (1, IQR [1.0-1.5]) (Kruskal-Wallis test, P = 0.007). Conclusion Our results corroborate previous studies that implicate apoptosis, mTORC1 signaling, EMT and auto-immunity in primary FSGS. Our future work will focus on cell-cell interactions within the glomerular niche and validation studies of candidate podocyte-specific genes.

Colour fusion effect on deep learning classification of uveal melanoma.

Reliable differentiation of uveal melanoma and choroidal nevi is crucial to guide appropriate treatment, preventing unnecessary procedures for benign lesions and ensuring timely treatment for potentially malignant cases. The purpose of this study is to validate deep learning classification of uveal melanoma and choroidal nevi, and to evaluate the effect of colour fusion options on the classification performance. A total of 798 ultra-widefield retinal images of 438 patients were included in this retrospective study, comprising 157 patients diagnosed with UM and 281 patients diagnosed with choroidal naevus. Colour fusion options, including early fusion, intermediate fusion and late fusion, were tested for deep learning image classification with a convolutional neural network (CNN). F1-score, accuracy and the area under the curve (AUC) of a receiver operating characteristic (ROC) were used to evaluate the classification performance. Colour fusion options were observed to affect the deep learning performance significantly. For single-colour learning, the red colour image was observed to have superior performance compared to green and blue channels. For multi-colour learning, the intermediate fusion is better than early and late fusion options. Deep learning is a promising approach for automated classification of uveal melanoma and choroidal nevi. Colour fusion options can significantly affect the classification performance.

Evaluating the Use of UV Absorbance for the Differentiation of Humified From Non-Humified Materials.

Products containing humic acids (HA) and fulvic acids (FA) have significant commercial potential; however, unknown to the consumer, some products may be mislabeled or contain adulterants. The prevalence of mislabeling and adulterants is found primarily in FA products. Using UV-Vis spectroscopy to differentiate between real and fake FA products is practical and desirable. The objective of this study was to expand the dataset generated using a UV-Vis-based method proposed by Mayhew et al., 2023. In total, 30 test samples were used to generate 90 test portions (three replicates per test sample) for analysis using the UV-Vis methodology outlined in Mayhew et al., 2023, which in this study is referred to as the UVAC (UV absorbance confirmation) method. None of the 13 FA test samples investigated were determined as humified using the UVAC method. The FA samples studied consisted of two IHSS standards, five commercial FA products (CFAP), and six full FA fractions (SFA), which were isolated from six known solid humic material sources (SHMS). There was a leonardite, a humalite, and four peat sources used as the SHMS. Analysis of the neutralized extract of the SHMS found only 3/6 SHMS were determined as humified. Six HA (SHA) test samples were also generated by isolating the HA from the SHMS, and only 3/6 SHA were determined as humified. Given the high prevalence of false determinations, more work is needed to improve the method so that it can be used by industry or regulators. The proposed method failed to determine IHSS FA standards as humified. Although the method is practical, it needs improvement and further study before it can be used for reliable differentiation of real from fake FA.

Event identification in acoustic emission from wire breaks in pre-stressing/post-tensioning cables

Steel tendons commonly used in pre-stressed/post-tensioned concrete structural systems can lose cross-section due to corrosion, eventually leading to acoustic emission (AE) events when the stress exceeds the breaking strength of the wires that make up the tendons. Reliable differentiation of wire break AE events from traffic or grout crack events is critical for monitoring large structures, even where the distance between sensors may produce highly attenuated signals. In this paper, the Fuzzy c-means clustering algorithm was employed to differentiate AEs released from breaking wires of steel tendons from a database of 13464 AEs, including wire breaks, environmental and grout crack AEs. Wire breaks and grout crack AEs were collected from axial loading tests of grouted tendons in which the load increased until a wire broke. Environmental acoustic signals were collected from a bridge. Then all the collected AEs were gathered in a database and post-processed to simulate attenuation of up to 20 m from source to sensor. To optimize the speed and reliability of the Fuzzy c-means clustering algorithm, a non-dominated sorting genetic algorithm-II (NSGA-II) was used to find the minimum number of acoustic features needed. The NSGA-II algorithm started with 201 possible acoustic features and found 12 combinations of features that resulted in more than 80% wire break detection accuracy. In contrast, less than 3% of grout cracks and 0% of environmental signals were detected as wire breaks. The proposed method is suitable for deployment in a large sensor network and has sufficiently low-computational requirements for at-the-sensor processing, eliminating the need to send high-frequency sampled data outside the sensor node.

A Dual-Mode Surface Acoustic Wave Delay Line for the Detection of Ice on 64°-Rotated Y-Cut Lithium Niobate.

Ice accumulation on infrastructure poses severe safety risks and economic losses, necessitating effective detection and monitoring solutions. This study introduces a novel approach employing surface acoustic wave (SAW) sensors, known for their small size, wireless operation, energy self-sufficiency, and retrofit capability. Utilizing a SAW dual-mode delay line device on a 64°-rotated Y-cut lithium niobate substrate, we demonstrate a solution for combined ice detection and temperature measurement. In addition to the shear-horizontal polarized leaky SAW, our findings reveal an electrically excitable Rayleigh-type wave in the X+90° direction on the same cut. Experimental results in a temperature chamber confirm capability for reliable differentiation between liquid water and ice loading and simultaneous temperature measurements. This research presents a promising advancement in addressing safety concerns and economic losses associated with ice accretion.