Prediction of Degraded Infrastructure Conditions for Railway Operation.

In the railway sector, rolling stock and infrastructure must be maintained in perfect condition to ensure reliable and safe operation for passengers. Climate change is affecting the urban and regional infrastructure through sea level rise, water accumulations, river flooding, and other increased-frequency extreme natural situations (heavy rains or snows) which pose a challenge to maintenance. In this paper, the use of artificial intelligence based on predictive maintenance implementation is proposed for the early detection of degraded conditions of a bridge due to extreme climatic conditions. For this prediction, continuous monitoring is proposed, with the aim of establishing alarm thresholds to detect dangerous situations, so restrictions could be determined to mitigate the risk. However, one of the main challenges for railway infrastructure managers nowadays is the high cost of monitoring large infrastructures. In this work, a methodology for monitoring railway infrastructures to define the optimal number of transductors that are economically viable and the thresholds according to which infrastructure managers can make decisions concerning traffic safety is proposed. The methodology consists of three phases that use the application of machine learning (Random Forest) and artificial cognitive systems (LSTM recurrent neural networks).

Objective hand eczema severity assessment with automated lesion anatomical stratification.

Hand eczema (HE) is one of the most frequent dermatoses, known to be both relapsing and remitting. Regular and precise evaluation of the disease severity is key for treatment management. Current scoring systems such as the hand eczema severity index (HECSI) suffer from intra- and inter-observer variance. We propose an automated system based on deep learning models (DLM) to quantify HE lesions' surface and determine their anatomical stratification. In this retrospective study, a team of 11 experienced dermatologists annotated eczema lesions in 312 HE pictures, and a medical student created anatomical maps of 215 hands pictures based on 37 anatomical subregions. Each data set was split into training and test pictures and used to train and evaluate two DLMs, one for anatomical mapping, the other for HE lesions segmentation. On the respective test sets, the anatomy DLM achieved average precision and sensitivity of 83% (95% confidence interval [CI] 80-85) and 85% (CI 82-88), while the HE DLM achieved precision and sensitivity of 75% (CI 64-82) and 69% (CI 55-81). The intraclass correlation of the predicted HE surface with dermatologists' estimated surface was 0.94 (CI 0.90-0.96). The proposed method automatically predicts the anatomical stratification of HE lesions' surface and can serve as support to evaluate hand eczema severity, improving reliability, precision and efficiency over manual assessment. Furthermore, the anatomical DLM is not limited to HE and can be applied to any other skin disease occurring on the hands such as lentigo or psoriasis.

In planta vs viral expression of HCPro affects its binding of nonplant 21-22 nucleotide small RNAs, but not its preference for 5'-terminal adenines, or its effects on small RNA methylation.

Previous studies have found a correlation between the abilities of PVX vector-expressed HCPro variants to bind small RNAs (sRNAs), and to suppress silencing. Moreover, HCPro preferred to bind viral sRNAs of 21-22 nucleotides (nt) containing 5'-terminal adenines. This would require such viral sRNAs to have either different access to the suppressor than those of plant sequences, or different molecular properties. To investigate this preference further, we have used suppressor-competent or suppressor-deficient HCPro variants, expressed from either T-DNAs or potyvirus constructs. Then, the sRNAs generated in plants and associated with the purified HCPro variants were characterized. Marked differences were observed in the ratios of sRNAs of plant vs nonplant origin that bound to suppressor-competent HCPro, depending on the mode of its expression. Regardless of the means of expression, HCPro retained the same preference among the nonplant sRNAs of 21-22 nt for those with 5'-terminal adenines. Relative methylation levels of individual sRNAs were assessed, and the nonplant sRNAs were found to be significantly less methylated in the presence of the suppressor. Targeted binding of sRNAs based on size, 5'-terminal sequence and origin, together with affecting their methylation, could explain how HCPro counteracts silencing.

Induced ligno-suberin vascular coating and tyramine-derived hydroxycinnamic acid amides restrict Ralstonia solanacearum colonization in resistant tomato.

Tomato varieties resistant to the bacterial wilt pathogen Ralstonia solanacearum have the ability to restrict bacterial movement in the plant. Inducible vascular cell wall reinforcements seem to play a key role in confining R. solanacearum into the xylem vasculature of resistant tomato. However, the type of compounds involved in such vascular physico-chemical barriers remain understudied, while being a key component of resistance. Here we use a combination of histological and live-imaging techniques, together with spectroscopy and gene expression analysis to understand the nature of R. solanacearum-induced formation of vascular coatings in resistant tomato. We describe that resistant tomato specifically responds to infection by assembling a vascular structural barrier formed by a ligno-suberin coating and tyramine-derived hydroxycinnamic acid amides. Further, we show that overexpressing genes of the ligno-suberin pathway in a commercial susceptible variety of tomato restricts R. solanacearum movement inside the plant and slows disease progression, enhancing resistance to the pathogen. We propose that the induced barrier in resistant plants does not only restrict the movement of the pathogen, but may also prevent cell wall degradation by the pathogen and confer anti-microbial properties, effectively contributing to resistance.

Strand-specific CpG hemimethylation, a novel epigenetic modification functional for genomic imprinting.

Imprinted genes are regulated by allele-specific differentially DNA-methylated regions (DMRs). Epigenetic methylation of the CpGs constituting these DMRs is established in the germline, resulting in a 5-methylcytosine-specific pattern that is tightly maintained in somatic tissues. Here, we show a novel epigenetic mark, characterized by strand-specific hemimethylation of contiguous CpG sites affecting the germline DMR of the murine Peg3, but not Snrpn, imprinted domain. This modification is enriched in tetraploid cortical neurons, a cell type where evidence for a small proportion of formylmethylated CpG sites within the Peg3-controlling DMR is also provided. Single nucleotide polymorphism (SNP)-based transcriptional analysis indicated that these epigenetic modifications participate in the maintainance of the monoallelic expression pattern of the Peg3 imprinted gene. Our results unexpectedly demonstrate that the methylation pattern observed in DMRs controlling defined imprinting regions can be modified in somatic cells, resulting in a novel epigenetic modification that gives rise to strand-specific hemimethylated domains functional for genomic imprinting. We anticipate the existence of a novel molecular mechanism regulating the transition from fully methylated CpGs to strand-specific hemimethylated CpGs.

Single mode GaSb diode lasers for sensor applications in a long wavelength regime.

The wavelength, λ, range of 1.8 µm≤λ≤3.5 µm contains strong spectral absorption lines of many gases used in health, industry, safety, and medicine and whose sensitive and quantitative detection is desirable. However, the performance of InP diode lasers markedly deteriorates beyond λ∼2 µm. In this paper we present new results on developing tunable high power single mode laser diodes based on the GaSb material system with emission in the wavelength range of 1.8 µm≤λ≤2.2 µm.

Arteriovenous fistulae after renal biopsy: diagnosis and outcomes using Doppler ultrasound assessment.

BACKGROUND: Percutaneous renal biopsy (PRB) is an important technique providing relevant information to guide diagnosis and treatment in renal disease. As an invasive procedure it has complications. Most studies up to date have analysed complications related to bleeding. We report the largest single-center experience on routine Doppler ultrasound (US) assessment post PRB, showing incidence and natural history of arteriovenous fistulae (AVF) post PRB. METHODS: We retrospectively analysed 327 consecutive adult PRB performed at Ramon Cajal University Hospital between January 2011 and December 2014. All biopsies were done under real-time US guidance by a trained nephrologist. Routine Doppler mapping and kidney US was done within 24 h post biopsy regardless of symptoms. Comorbidities, full blood count, clotting, bleeding time and blood pressure were recorded at the time of biopsy. Post biopsy protocol included vitals and urine void checked visually for haematuria. Logistic regression was used to investigate links between AVF, needle size, correcting for potential confounding variables. RESULTS: 46,5% were kidney transplants and 53,5% were native biopsies. Diagnostic material was obtained in 90,5% (142 grafts and 154 native). Forty-seven AVF's (14.37%) were identified with routine kidney Doppler mapping, 95% asymptomatic (n = 45), 28 in grafts (18.4%) and 17 natives (9.7%) (p-value 0.7). Both groups were comparable in terms of comorbidities, passes, cylinders or biopsy yield (p-value NS). 80% were <1 cm in size and 46.6% closed spontaneously in less than 30 days (range 3-151). Larger AVF's (1-2 cm) took a mean of 52 days to closure (range 13-151). Needle size was not statistically significant factor for AVF (p-value 0.71). CONCLUSIONS: Contrary to historical data published, AVF's are a common complication post PRB that can be easily missed. Routine US Doppler mapping performed by trained staff is a cost-effective, non-invasive tool to diagnose and follow up AVF's, helping to assess management.

Integrated electrically driven surface plasmon resonance device for biosensing applications.

Compact and portable surface plasmon resonance (SPR) biosensors of high sensitivities can be made through integration of discrete components in a single device. We report on a device comprising a vertical cavity light emitting diode (VLED) integrated with gold-based biosensing nanostructures fabricated atop its surface. Coupling of surface plasmon waves was achieved by the introduction of a spacer SiO2 layer located between the light source and the functionalized Au thin film. The SPR signal was extracted in far field with a Au-based nanograting and detected using a custom designed hyperspectral imager. We discuss the performance of a VLED-based SPR device employed for detection of different concentration saltwater solutions.

Carving versus Stitching: The Concept of Psychic Function and the Continuity/Discontinuity Debate.

BACKGROUND: The current debate on the continuity or discontinuity of psychotic symptoms and common psychic experiences has mainly dealt with methodological, epidemiological and clinical issues, but it has neglected epistemological research on the main concepts of the field. METHODS: The implicit epistemic structure of continuity models of psychotic symptoms and its effect on research are addressed. RESULTS: We explain how the seemingly commonsense, unproblematic concept of psychic function may explain the contradictions and paradoxes of research. CONCLUSIONS: A new model of symptom individuation and symptom eliciting is proposed - based on the concepts of 'schemas', 'embodied affordances' and 'thick/thin descriptions'.

A comparative analysis of Spanish Clinical encoder-based models on NER and classification tasks.

OBJECTIVES: This comparative analysis aims to assess the efficacy of encoder Language Models for clinical tasks in the Spanish language. The primary goal is to identify the most effective resources within this context. IMPORTANCE: This study highlights a critical gap in NLP resources for the Spanish language, particularly in the clinical sector. Given the vast number of Spanish speakers globally and the increasing reliance on electronic health records, developing effective Spanish language models is crucial for both clinical research and healthcare delivery. Our work underscores the urgent need for specialized encoder models in Spanish that can handle clinical data with high accuracy, thus paving the way for advancements in healthcare services and biomedical research for Spanish-speaking populations. MATERIALS AND METHODS: We examined 17 distinct corpora with a focus on clinical tasks. Our evaluation centered on Spanish Language Models and Spanish Clinical Language models (both encoder-based). To ascertain performance, we meticulously benchmarked these models across a curated subset of the corpora. This extensive study involved fine-tuning over 3000 models. RESULTS: Our analysis revealed that the best models are not clinical models, but general-purpose models. Also, the biggest models are not always the best ones. The best-performing model, RigoBERTa 2, obtained an average F1 score of 0.880 across all tasks. DISCUSSION: Our study demonstrates the advantages of dedicated encoder-based Spanish Clinical Language models over generative models. However, the scarcity of diverse corpora, mostly focused on NER tasks, underscores the need for further research. The limited availability of high-performing models emphasizes the urgency for development in this area. CONCLUSION: Through systematic evaluation, we identified the current landscape of encoder Language Models for clinical tasks in the Spanish language. While challenges remain, the availability of curated corpora and models offers a foundation for advancing Spanish Clinical Language models. Future efforts in refining these models are essential to elevate their effectiveness in clinical NLP.

Elevated levels of cell-free NKG2D-ligands modulate NKG2D surface expression and compromise NK cell function in severe COVID-19 disease.

Introduction: It is now clear that coronavirus disease 19 (COVID-19) severity is associated with a dysregulated immune response, but the relative contributions of different immune cells is still not fully understood. SARS CoV-2 infection triggers marked changes in NK cell populations, but there are contradictory reports as to whether these effector lymphocytes play a protective or pathogenic role in immunity to SARS-CoV-2. Methods: To address this question we have analysed differences in the phenotype and function of NK cells in SARS-CoV-2 infected individuals who developed either very mild, or life-threatening COVID-19 disease. Results: Although NK cells from patients with severe disease appeared more activated and the frequency of adaptive NK cells was increased, they were less potent mediators of ADCC than NK cells from patients with mild disease. Further analysis of peripheral blood NK cells in these patients revealed that a population of NK cells that had lost expression of the activating receptor NKG2D were a feature of patients with severe disease and this correlated with elevated levels of cell free NKG2D ligands, especially ULBP2 and ULBP3 in the plasma of critically ill patients. In vitro, culture in NKG2DL containing patient sera reduced the ADCC function of healthy donor NK cells and this could be blocked by NKG2DL-specific antibodies. Discussion: These observations of reduced NK function in severe disease are consistent with the hypothesis that defects in immune surveillance by NK cells permit higher levels of viral replication, rather than that aberrant NK cell function contributes to immune system dysregulation and immunopathogenicity.

Determination of De Novo Suberin-Lignin Ferulate Deposition in Xylem Tissue Upon Vascular Pathogen Attack.

Plant vascular pathogens use different ways to reach the xylem vessels and cause devastating diseases in plants. Resistant and tolerant plants have evolved various defense mechanisms against vascular pathogens. Inducible physico-chemical structures, such as the formation of tyloses and wall reinforcements with phenolic polymers, are very effective barriers that confine the pathogen and prevent colonization. Here, we use a combination of classical histochemistry along with bright-field and fluorescence microscopy and two-dimensional nuclear magnetic resonance (2D-NMR) spectroscopy to visualize and characterize wall reinforcements containing phenolic wall polymers, namely, lignin, ferulates, and suberin, which occur in different xylem vasculature in response to pathogen attack.

BCG priming followed by a novel interleukin combination activates Natural Killer cells to selectively proliferate and become anti-tumour long-lived effectors.

The short-lived nature and heterogeneity of Natural Killer (NK) cells limit the development of NK cell-based therapies, despite their proven safety and efficacy against cancer. Here, we describe the biological basis, detailed phenotype and function of long-lived anti-tumour human NK cells (CD56highCD16+), obtained without cell sorting or feeder cells, after priming of peripheral blood cells with Bacillus Calmette-Guérin (BCG). Further, we demonstrate that survival doses of a cytokine combination, excluding IL18, administered just weekly to BCG-primed NK cells avoids innate lymphocyte exhaustion and leads to specific long-term proliferation of innate cells that exert potent cytotoxic function against a broad range of solid tumours, mainly through NKG2D. Strikingly, a NKG2C+CD57-FcεRIγ+ NK cell population expands after BCG and cytokine stimulation, independently of HCMV serology. This strategy was exploited to rescue anti-tumour NK cells even from the suppressor environment of cancer patients' bone marrow, demonstrating that BCG confers durable anti-tumour features to NK cells.

The Tomato Feruloyl Transferase FHT Promoter Is an Accurate Identifier of Early Development and Stress-Induced Suberization.

As a wall polymer, suberin has a multifaceted role in plant development and stress responses. It is deposited between the plasma membrane and the primary cell wall in specialized tissues such as root exodermis, endodermis, phellem, and seed coats. It is formed de novo in response to stresses such as wounding, salt injury, drought, and pathogen attack and is a complex polyester mainly consisting of fatty acids, glycerol, and minor amounts of ferulic acid that are associated to a lignin-like polymer predominantly composed of ferulates. Metabolomic and transcriptomic studies have revealed that cell wall lignification precedes suberin deposition. The ferulic acid esterified to ω-hydroxy fatty acids, synthetized by the feruloyl transferase FHT (or ASFT), presumably plays a role in coupling both polymers, although the precise mechanism is not understood. Here, we use the promoter of tomato suberin feruloyl transferase (FHT/ASFT) fused to GUS (ß-glucuronidase) to demonstrate that ferulate deposition agrees with the site of promoter FHT activation by using a combination of histochemical staining and UV microscopy. Hence, FHT promoter activation and alkali UV microscopy can be used to identify the precise localization of early suberizing cells rich in ferulic acid and can additionally be used as an efficient marker of early suberization events during plant development and stress responses. This line can be used in the future as a tool to identify emerging suberization sites via ferulate deposition in tomato plants, which may contribute to germplasm screening in varietal improvement programs.

BCG-activation of leukocytes is sufficient for the generation of donor-independent innate anti-tumor NK and γδ T-cells that can be further expanded in vitro.

Bacillus Calmette-Guérin (BCG), the nonpathogenic Mycobacterium bovis strain used as tuberculosis vaccine, has been successfully used as treatment for non-muscle invasive bladder cancer for decades, and suggested to potentiate cellular and humoral immune responses. However, the exact mechanism of action is not fully understood. We previously described that BCG mainly activated anti-tumor cytotoxic NK cells with upregulation of CD56 and a CD16+ phenotype. Now, we show that stimulation of human peripheral blood mononuclear cells with iBCG, a preparation based on BCG-Moreau, expands oligoclonal γδ T-cells, with a cytotoxic phenotype, together with anti-tumor CD56high CD16+ NK cells. We have used scRNA-seq, flow cytometry, and functional assays to characterize these BCG-activated γδ T-cells in detail. They had a high IFNγ secretion signature with expression of CD27+ and formed conjugates with bladder cancer cells. BCG-activated γδ T-cells proliferated strongly in response to minimal doses of cytokines and had anti-tumor functions, although not fully based on degranulation. BCG was sufficient to stimulate proliferation of γδ T-cells when cultured with other PBMC; however, BCG alone did not stimulate expansion of purified γδ T-cells. The characterization of these non-donor restricted lymphocyte populations, which can be expanded in vitro, could provide a new approach to prepare cell-based immunotherapy tools.

Renal Transplant Artery Stenosis and Kinking: An Unusual Association.

Renal artery stenosis of the kidney allograft associated with kinking is not a frequent finding. As a correctable cause of graft dysfunction, it is important to diagnose it as soon as possible to avoid further graft damage and improve graft and patient survival. As pulsed wave Doppler ultrasound mapping of the graft's renal arteries is essential to diagnose possible alterations, point of care ultrasound (POCUS) is a highly useful tool for early diagnosis. We present a case in which nephrologists performed this examination promptly allowing a timely diagnosis and treatment plan.

[Evaluation of the sentinel lymph node in T1-T2 papillary thyroid cancer: a preliminary study]. / Valoración del ganglio centinela en el cáncer papilar de tiroides T1-T2. Estudio preliminar.

OBJECTIVE: Sentinel lymph node biopsy in differentiated thyroid cancer may benefit patients with no clinically affected lymph nodes and can avoid a prophylactic or staging lymphadenectomy. METHODS: A prospective study was conducted on 23 consecutive patients with papillary thyroid carcinoma with no clinical or radiological suspicion of lymph involvement. After injecting methylene blue around the tumour during the biopsy of the identified sentinel lymph node, a total thyroidectomy and a via-b ipsilateral lymphadenectomy was performed for the later study with cytokeratin. If the sentinel lymph node was positive, a modified ipsilateral radical lymphadenectomy was perfumed (groups ii to v). RESULTS: The sentinel lymph node was clearly identified in 21 of the 23 patients (91.3%). Seven (33%) of the 21 lymph nodes identified were positive in the intra-operative study, of which 3 (42.8%) demonstrated involvement with the lateral compartment. All together, 9 patients (39.1%) showed lymph node involvement group vi, with two more patients being identified with micro-metastases in the later study. Biopsy of the sentinel lymph node had a sensitivity of 87.5%, a specificity of 100%, a positive predictive value of 100% and a negative predictive value of 93.7%, with 7.1% false negatives. Five patients (21.7%) had transient hypocalcaemia. CONCLUSIONS: The identification of the sentinel lymph node in patients with T1-T2 tumours with no suspicion of lymph node involvement helps in the selection of patients who should be treated with selective lymphadenectomies.

Quantification of Efflorescences in Pustular Psoriasis Using Deep Learning.

OBJECTIVES: Pustular psoriasis (PP) is one of the most severe and chronic skin conditions. Its treatment is difficult, and measurements of its severity are highly dependent on clinicians' experience. Pustules and brown spots are the main efflorescences of the disease and directly correlate with its activity. We propose an automated deep learning model (DLM) to quantify lesions in terms of count and surface percentage from patient photographs. METHODS: In this retrospective study, two dermatologists and a student labeled 151 photographs of PP patients for pustules and brown spots. The DLM was trained and validated with 121 photographs, keeping 30 photographs as a test set to assess the DLM performance on unseen data. We also evaluated our DLM on 213 unstandardized, out-of-distribution photographs of various pustular disorders (referred to as the pustular set), which were ranked from 0 (no disease) to 4 (very severe) by one dermatologist for disease severity. The agreement between the DLM predictions and experts' labels was evaluated with the intraclass correlation coefficient (ICC) for the test set and Spearman correlation (SC) coefficient for the pustular set. RESULTS: On the test set, the DLM achieved an ICC of 0.97 (95% confidence interval [CI], 0.97-0.98) for count and 0.93 (95% CI, 0.92-0.94) for surface percentage. On the pustular set, the DLM reached a SC coefficient of 0.66 (95% CI, 0.60-0.74) for count and 0.80 (95% CI, 0.75-0.83) for surface percentage. CONCLUSIONS: The proposed method quantifies efflorescences from PP photographs reliably and automatically, enabling a precise and objective evaluation of disease activity.

High-throughput RNA sequencing transcriptome analysis of ABC-DLBCL reveals several tumor evasion strategies.

Activated B-cell (ABC) lymphoma, a distinct molecular entity within diffuse large B-cell lymphoma (DLBCL), remains highly incurable, showing a worse response to standard immunochemotherapy. The discouraging results obtained in several clinical trials using proteasome inhibitors, tyrosine kinase inhibitors, or immunomodulators, lead to an intense search for new, potentially druggable biomarkers in DLBCL. In this study, we designed an experimental strategy for DLBCL to discover high- and low-abundance RNA-seq-derived transcripts involved in the oncogenic phenotype in patients diagnosed with ABC-DLBCL. Based on the results of a comparative analysis, 79 DE genes and two enriched gene sets related to metabolism and immunity were selected. Genes related to drug resistance, anti-inflammatory response, and tumor-cell dissemination were found to be up-regulated, while tumor suppressor genes were down-regulated. Then, we searched for the perturbagens most suitable for gene expression profiling (GEP) by iLINCS-CMap. Herein, we present a novel experimental approach that connects the omics signature of DLBCL with potential drugs for more accurate treatments.